{ "Contributors": [ "BIOASQ" ], "Source": [ "BIOASQ" ], "URL": [ "http://participants-area.bioasq.org/datasets/" ], "Categories": [ "Question Answering" ], "Definition": [ "Given a question, answer it with comprehensive details." ], "Reasoning": [], "Input_language": [ "English" ], "Output_language": [ "English" ], "Instruction_language": [ "English" ], "Domains": [ "Medical Knowledge" ], "Positive Examples": [], "Negative Examples": [], "Instances": [ { "input": "Is Hirschsprung disease a mendelian or a multifactorial disorder?", "output": "Coding sequence mutations in RET, GDNF, EDNRB, EDN3, and SOX10 are involved in the development of Hirschsprung disease. The majority of these genes was shown to be related to Mendelian syndromic forms of Hirschsprung's disease, whereas the non-Mendelian inheritance of sporadic non-syndromic Hirschsprung disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model." }, { "input": "List signaling molecules (ligands) that interact with the receptor EGFR?", "output": "The 7 known EGFR ligands are: epidermal growth factor (EGF), betacellulin (BTC), epiregulin (EPR), heparin-binding EGF (HB-EGF), transforming growth factor-\u03b1 [TGF-\u03b1], amphiregulin (AREG) and epigen (EPG)." }, { "input": "Is the protein Papilin secreted?", "output": "Yes, papilin is a secreted protein" }, { "input": "Are long non coding RNAs spliced?", "output": "Long non coding RNAs appear to be spliced through the same pathway as the mRNAs" }, { "input": "Is RANKL secreted from the cells?", "output": "Receptor activator of nuclear factor \u03baB ligand (RANKL) is a cytokine predominantly secreted by osteoblasts." }, { "input": "Does metformin interfere thyroxine absorption?", "output": "No. There are not reported data indicating that metformin reduce with thyroxine absorption." }, { "input": "Which miRNAs could be used as potential biomarkers for epithelial ovarian cancer?", "output": "miR-200a, miR-100, miR-141, miR-200b, miR-200c, miR-203, miR-510, miR-509-5p, miR-132, miR-26a, let-7b, miR-145, miR-182, miR-152, miR-148a, let-7a, let-7i, miR-21, miR-92 and miR-93 could be used as potential biomarkers for epithelial ovarian cancer." }, { "input": "Which acetylcholinesterase inhibitors are used for treatment of myasthenia gravis?", "output": "Pyridostigmine and neostygmine are acetylcholinesterase inhibitors that are used as first-line therapy for symptomatic treatment of myasthenia gravis. Pyridostigmine is the most widely used acetylcholinesterase inhibitor. Extended release pyridotsygmine and novel acetylcholinesterase inhibitors inhibitors with oral antisense oligonucleotides are being studied." }, { "input": "Has Denosumab (Prolia) been approved by FDA?", "output": "Yes, Denosumab was approved by the FDA in 2010." }, { "input": "List the human genes encoding for the dishevelled proteins?", "output": "DVL-1\nDVL-2\nDVL-3" }, { "input": "Name synonym of Acrokeratosis paraneoplastica.", "output": "Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive paraneoplastic dermatosis characterized by erythematosquamous lesions located at the acral sites and is most commonly associated with carcinomas of the upper aerodigestive tract." }, { "input": "Which are the classes of anti-arrhythmic drugs according to Vaughan-Williams classification?", "output": "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV). Class I antiarrhythmic agents have as a common action, blockade of the sodium channels. Class II agents are antisympathetic drugs, particularly the beta-adrenoceptor blockers. Class-III antiarrhythmics have as a common action the potassium-channel blockade. Class IV antiarrhythmic drugs are calcium channel blockers." }, { "input": "Which are the different isoforms of the mammalian Notch receptor?", "output": "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Four Notch receptors have been identified in man: Notch-1, Notch-2, Notch-3 and Notch-4." }, { "input": "Which are the major characteristics of cellular senescence?", "output": "The defining characteristics of cellular senescence are altered morphology, arrested cell-cycle progression, development of aberrant gene expression with proinflammatory behavior, and telomere shortening." }, { "input": "Orteronel was developed for treatment of which cancer?", "output": "Orteronel was developed for treatment of castration-resistant prostate cancer." }, { "input": "Is the monoclonal antibody Trastuzumab (Herceptin) of potential use in the treatment of prostate cancer?", "output": "Although is still controversial, Trastuzumab (Herceptin) can be of potential use in the treatment of prostate cancer overexpressing HER2, either alone or in combination with other drugs." }, { "input": "Which are the Yamanaka factors?", "output": "The Yamanaka factors are the OCT4, SOX2, MYC, and KLF4 transcription factors" }, { "input": "What is the aim of the Human Chromosome-centric Proteome Project (C-HPP)?", "output": "The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams" }, { "input": "What is the aim of the Human Chromosome-centric Proteome Project (C-HPP)?", "output": "The Chromosome-Centric Human Proteome Project (C-HPP) is an international effort for creating an annotated proteomic catalog for each chromosome. (PMID: 23312004) The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams. (PMID: 23308364) The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. (PMID: 23253012)" }, { "input": "Where is the protein Pannexin1 located?", "output": "The protein Pannexin1 is localized to the plasma membranes." }, { "input": "Which currently known mitochondrial diseases have been attributed to POLG mutations?", "output": "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO)." }, { "input": "Which currently known mitochondrial diseases have been attributed to POLG mutations?", "output": "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO)" }, { "input": "What is the effect of ivabradine in heart failure after myocardial infarction?", "output": "\u0399vabradine decreases heart rate and reduces myocardial oxygen demand, increases diastolic perfusion time and improves energetics in ischemic myocardium. Ivabradine protects the myocardium during ischemia, improves left ventricular function in heart failure and reduces remodeling following myocardial infarction. It improves prognosis in patients with coronary artery disease, left ventricular dysfunction and heart rate \u226570 beats per minute, as well as in patients with heart failure and left ventricular dysfunction. The beneficial effects of ivabradine may be due to the reversal of electrophysiological cardiac remodelling in post-MI rats by reduction of functional overexpression of HCN channels. Furthermore, the improvement of cardiac function is related not only to the HR reduction per se but also to modifications in the extracellular matrix." }, { "input": "What is the mode of inheritance of Wilson's disease?", "output": "Wilson's disease (WD) is an autosomal recessive disorder." }, { "input": "Are transcription and splicing connected?", "output": "Yes. There is strong evidence that splicing and transcription are intimately coupled in metazoans, with genome wide surveys show that most splicing occurs during transcription. Chromatin structure, RNA polymerase dynamics, and recruitment of splicing factors through the transcriptional machinery are factors that explain a role for transcription in the regulation of splicing." }, { "input": "What is the mode of inheritance of Facioscapulohumeral muscular dystrophy (FSHD)?", "output": "Facioscapulohumeral muscular dystrophy has an autosomal dominant inheritance pattern." }, { "input": "Is Alu hypomethylation associated with breast cancer?", "output": "Yes, Alu elements were found to be hypomethylated in breast cancer, especially in the HER2-enriched subtype. Furthermore, Alu hypomethylation was identified as a late event during breast cancer progression, and in invasive breast cancer, tended to be associated with negative estrogen receptor status and poor disease-free survival of the patients." }, { "input": "Is Alu hypomethylation associated with breast cancer?", "output": "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer " }, { "input": "Which proteins participate in the formation of the ryanodine receptor quaternary macromolecular complex?", "output": "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin. " }, { "input": "Which proteins participate in the formation of the ryanodine receptor quaternary macromolecular complex?", "output": "Calsequestrin (CSQ) is a Ca(2+) storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca(2+) signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). Junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release." }, { "input": "What kind of chromatography is HILIC?", "output": "Hydrophilic Interaction Chromatography (HILIC)" }, { "input": "What is the effect of TRH on myocardial contractility?", "output": "TRH improves myocardial contractility" }, { "input": "Proteomic analyses need prior knowledge of the organism complete genome. Is the complete genome of the bacteria of the genus Arthrobacter available?", "output": "Yes, the complete genome sequence of Arthrobacter (two strains) is deposited in GenBank." }, { "input": "What is the structural fold of bromodomain proteins?", "output": "The structure fold of the bromodomains is an all-alpha-helical fold, which includes a left-handed four-helix bundle topology, with two short additional helices in a long connecting loop." }, { "input": "List the endoscopic diagnoses that have been reported in children with autism", "output": "Endoscopic examinations in autistic children have been reported to show : I or II reflux esophagitis, Achalasia, chronic gastritis and chronic duodenitis, mild acute and chronic inflammation of the small bowel and colorectum and Ileo-colonic lymphoid nodular hyperplasia (LNH). \nThe number of Paneth's cells in the duodenal crypts was found to be significantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was reported although there was no abnormality found in pancreatic function. Autistic children have ben reported to have an increased pancreatico-biliary fluid output after intravenous secretin administration." }, { "input": "What are the outcomes of Renal sympathetic denervation?", "output": "Significant decreases and progressively higher reductions of systolic and diastolic blood pressure were observed after RSD. The complication rate was minimal.\nRenal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk." }, { "input": "Which MAP kinase phosphorylates the transcription factor c-jun?", "output": "c-Jun is phosphorylated by c-Jun NH2-terminal kinase (JNK)." }, { "input": "Which MAP kinase phosphorylates the transcription factor c-jun?", "output": "An in vitro kinase assay revealed that c-Jun phosphorylation is primarily mediated via activated c-Jun N-terminal protein kinase (JNK)." }, { "input": "What is the meaning of the acronym \"TAILS\" used in protein N-terminomics?", "output": "TAILS stands for \"Terminal Amine Isotopic Labeling of Substrates\"" }, { "input": "Do mutations of AKT1 occur in meningiomas?", "output": "Yes, AKT1 mutation occurs in meningiomas." }, { "input": "What are the main indications of lacosamide?", "output": "Lacosamide is an anti-epileptic drug, licensed for refractory partial-onset seizures. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety." }, { "input": "Which fusion protein is involved in the development of Ewing sarcoma?", "output": "Ewing sarcoma is the second most common bone malignancy in children and young adults. In almost 95% of the cases, it is driven by oncogenic fusion protein EWS/FLI1, which acts as an aberrant transcription factor, that upregulates or downregulates target genes, leading to cellular transformation." }, { "input": "List Hemolytic Uremic Syndrome Triad.", "output": "Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of anaemia, thrombocytopenia, renal failure." }, { "input": "Does physical activity influence gut hormones?", "output": "Yes." }, { "input": "What are the effects of depleting protein km23-1 (DYNLRB1) in a cell?", "output": "The knockdown of km23-1 results in numerous effects at the cellular level, such as decreased cell migration. Additionaly, km23-1 is involved in signalling pathways and its knockdown results in decreased RhoA activation, inhibition of TGF\u03b2-mediated activation of ERK and JNK, phosphorylation of c-Jun, transactivation of the c-Jun promoter and decreased TGFbeta responses." }, { "input": "Treatment of which disease was investigated in the MR CLEAN study?", "output": "Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study investigated endovascular treatment for acute ischemic stroke." }, { "input": "Which factors activate zygotic gene expression during the maternal-to-zygotic transition in zebrafish?", "output": "Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression." }, { "input": "Is irritable bowel syndrome more common in women with endometriosis?", "output": "Yes, irritable bowel syndrome (IBS) is more common in women with endometriosis. It has been shown that 15% of the patients with endometriosis also had IBS. Women with endometriosis are more likely to have received a diagnosis of IBS. Endometriosis may coexist with or be misdiagnosed as IBS." }, { "input": "What is evaluated using the EORTC QLQ \u2013 INFO25 questionnaire?", "output": "The European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25) evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects together with satisfaction with information." }, { "input": "Does BNP increase after intensive exercise in athletes?", "output": "BNP and NTproBNP increase early after exercise in healthy athletes performing different types of sports. It is unknown the reason of this increase. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage." }, { "input": "What is the association of estrogen replacement therapy and intracranial meningioma risk?", "output": "The association between hormone replacement therapy and meningioma risk is controversial. Increased risk of meningioma was demonstrated in estrogen-only hormonal replacement therapy. However, other studies did not find an association between hormonal replacement therapy and meningioma risk." }, { "input": "Are there web based self management strategies for chronic pain ?", "output": "Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. " }, { "input": "Are there web based self management strategies for chronic pain ?", "output": "Yes, there are successful web based self management strategies for chronic pain." }, { "input": "Is Weaver syndrome similar to Sotos?", "output": "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes" }, { "input": "Is Weaver syndrome similar to Sotos?", "output": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling." }, { "input": "Which enzyme is targeted by Evolocumab?", "output": "Evolocumab (AMG145) is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that demonstrated marked reductions in plasma low-density lipoprotein cholesterol concentrations in statin-intolerant patients." }, { "input": "Are ultraconserved elements often transcribed?", "output": "Yes. Especially, a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand." }, { "input": "What is the methyl donor of DNA (cytosine-5)-methyltransferases?", "output": "S-adenosyl-L-methionine (AdoMet, SAM) is the methyl donor of DNA (cytosine-5)-methyltransferases. DNA (cytosine-5)-methyltransferases catalyze the transfer of a methyl group from S-adenosyl-L-methionine to the C-5 position of cytosine residues in DNA." }, { "input": "Is peripheral neuroepithelioma related to Ewing sarcoma?", "output": "Experimental data support the concept that Ewing sarcoma and peripheral neuroepithelioma are both peripheral primitive neuroectodermal neoplasms, differing only in the extent of neuroectodermal phenotype and morphological differentiation." }, { "input": "Which signaling pathway does sonidegib inhibit?", "output": "Sonidegib is a Hedghog signalling pathway inhibitor." }, { "input": "In which phase of the cell cycle arrest is impaired in Fanconi anemia?", "output": "In response to damage induced by DNA cross-linking agents, the S-phase checkpoint is inefficient in Fanconi anemia (FA) cells, leading to accumulation of secondary lesions, such as single- and double-strand breaks and gaps. The prolonged time in G2 phase seen in FA cells therefore exists in order to allow the cells to remove lesions which accumulated during the preceding abnormal S phase." }, { "input": "Which DNA sequences are more prone for the formation of R-loops?", "output": "R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes. R-loops are particularly enriched over G-rich terminator elements." }, { "input": "Mutation of which gene is implicated in the familial isolated pituitary adenoma?", "output": "Mutation of aryl hydrocarbon receptor interacting protein (AIP) gene was implicated in the familial isolated pituitary adenoma (FIPA) syndrome. About 20% of the families with FIPA harbor inactivating mutation in AIP gene." }, { "input": "which mutations of troponin C gene have been found to cause hypertrophic cardiomyopathy?", "output": "The following mutations of troponin C gene have been found to cause hypertrophic cardiomyopathy: L29Q; A8V; A31S; E134D; c.363dupG; A23Q; D145E and C84Y" }, { "input": "What is known about the effect of acupuncture in smoking cessation ?", "output": "Ear acupressure (EAP) and ear acupuncture have been used for smoking cessation, and some positive results have been reported.\nAuricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant.\nThe combined acupuncture-education group showing the greatest effect from treatment." }, { "input": "Which post-translational histone modifications are characteristic of constitutive heterochromatin?", "output": "H3K9me3 is the major marker of constitutive heterochromatin. Other histone methylation marks usually found in constitutive heterochromatin, are H4K20me3 and H3K79me3. Classical histone modifications associated with heterochromatin include H3K9me2, H3K27me1 and H3K27me2. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin. H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage" }, { "input": "GV1001 vaccine targets which enzyme?", "output": "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. It has been developed as a vaccine against various cancers." }, { "input": "Which is the E3 ubiquitin ligase which ubiquitinates IkB leading to its proteasomal degradation?", "output": "I\u03baB degradation involves ubiquitination mediated by a specific E3 ubiquitin ligase SCF(\u03b2-TrCP). SCF(\u03b2-TrCP) -mediated I\u03baB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor I\u03baB\u03b1 within a few minutes of cell stimulation." }, { "input": "Which is the E3 ubiquitin ligase which ubiquitinates IkB leading to its proteasomal degradation?", "output": "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation." }, { "input": "Which is the E3 ubiquitin ligase which ubiquitinates IkB leading to its proteasomal degradation?", "output": "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. SCF(\u03b2-TrCP) -mediated I\u03baB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor I\u03baB\u03b1 within a few minutes of cell stimulation." }, { "input": "Is c-met involved in the activation of the Akt pathway?", "output": "HGF-induced activation of c-Met is playing a pivotal role in the stimulation of c-Src activation, resulting in induction of phosphatidylinositol 3-kinase complexes p85\u03b1/p110\u03b1 and p85\u03b1/p110\u03b4, which is required for Akt-mediated activation of mammalian target of rapamycin, with consequent inhibition of I\u03baB kinase and nuclear factor-\u03baB activation, resulting in enhanced cell survival." }, { "input": "Is pregnancy an additional risk during during H1N1 infection?", "output": "Pregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. Pregnancy, particularly during the third trimester, increases the risk of complications and early antiviral treatment is associated with improved outcomes." }, { "input": "Are long non coding RNAs as conserved in sequence as protein coding genes?", "output": "No. Most long non coding RNAs (lncRNAs) are under lower sequence constraints than protein-coding genes." }, { "input": "Mutation of which gene is implicated in the Brain-lung-thyroid syndrome?", "output": "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations." }, { "input": "What is clathrin?", "output": "Clathrin helps build small vesicles in order to safely transport molecules within and between cells." }, { "input": "What are the main results of PRKAR1A Knockdown?", "output": "Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis. Also, Knockdown of the cAMP-dependent protein kinase (PKA) Type Ialpha regulatory subunit in mouse oocytes disrupts meiotic arrest and results in meiotic spindle defects." }, { "input": "Is TENS machine effective in pain?", "output": "Transcutaneous electrical nerve stimulation is widely used in pain management" }, { "input": "Is there any algorithm for enhancer identification from chromatin state?", "output": "yes" }, { "input": "Is there any algorithm for enhancer identification from chromatin state?", "output": "Yes. RFECS is a random-forest based algorithm for enhancer identification from chromatin state. It integrates histone modification profiles for the identification of enhancers, and can be used to identify enhancers in a number of cell-types. RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction." }, { "input": "Which enzyme is targeted by the drug Imetelstat?", "output": "Imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'\u2192P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA subunit. In preclinical trials, this compound has been found to inhibit telomerase activity in multiple cancer cell lines, as well as in vivo xenograft mouse models." }, { "input": "Which interleukins are inhibited by Dupilumab?", "output": "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels." }, { "input": "Which human genes are more commonly related to craniosynostosis?", "output": "The genes that are most commonly linked to craniosynostoses are the members of the Fibroblast Growth Factor Receptor family FGFR3 and to a lesser extent FGFR1 and FGFR2. Some variants of the disease have been associated with the triplication of the MSX2 gene and mutations in NELL-1. NELL-1 is being regulated bu RUNX2, which has also been associated to cases of craniosynostosis. Other genes reported to have a role in the development of the disease are RECQL4, TWIST, SOX6 and GNAS." }, { "input": "Are transcribed ultraconserved regions involved in cancer?", "output": "Yes, it appears that there is widespread T-UCR (Transcribed - UltraConserved Region) involvement in diverse cellular processes that are deregulated in the process of tumourigenesis. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells." }, { "input": "In which breast cancer patients can palbociclib be used?", "output": "Palbociclib is useful for women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer." }, { "input": "Do patients with Pendred syndrome present congenital deafness?", "output": "Congenital deafness is one of the characteristics of Pendred syndrome patients." }, { "input": "List side effects of SGLT2 inhibitors?", "output": "SGLT2 inhibitors can be associated with urogenital infections related to the enhanced glycosuria, and low blood pressure." }, { "input": "Is CD56 useful in Ewing sarcoma prognosis?", "output": "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometryIn patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)" }, { "input": "Is CD56 useful in Ewing sarcoma prognosis?", "output": "CD56 expression could be used to reveal Ewing sarcoma patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy." }, { "input": "What is the method FASP used for?", "output": "Filter Aided Sample Preparation (FASP), a type of proteomic reactor, in which samples dissolved in sodium dodecyl sulfate (SDS) are digested in an ultrafiltration unit." }, { "input": "What is the role of extracellular signal-related kinases 1 and 2 (ERK1/2) proteins in craniosynostosis?", "output": "Reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1/2 causes complex craniosynostosis (premature fusion of the cranial sutures) in humans and mice. Features of this newly recognized clinical disorder include multiple-suture synostosis, craniofacial dysmorphism, Chiari malformation and language delay." }, { "input": "Are there any urine biomarkers for chronic kidney disease?", "output": "Chronic kidney disease (CKD), is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or pericarditis. It is differentiated from acute kidney disease in that the reduction in kidney function must be present for over 3 months." }, { "input": "Are there any urine biomarkers for chronic kidney disease?", "output": "Yes, there is a number of urine biomarkers used for early detection of chronic kidney disease." }, { "input": "What is being measured with an accelerometer in back pain patients", "output": "Accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)...\nThe following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count." }, { "input": "List the releases of JASPAR database", "output": "JASPAR, JASPAR CORE, JASPAR FAM, JASPAR phyloFACTS, JASPAR 2008 update, JASPAR 2010, JASPAR 2014." }, { "input": "List symptoms of the IFAP syndrome.", "output": "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia." }, { "input": "Which gene is required for the efficient function of clopidogrel?", "output": "The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 CYP2C19), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients" }, { "input": "Is valproic acid effective for glioblastoma treatment?", "output": "Yes, valproic acid prolong survival of glioblastoma patients. Valproic acid is an antiepileptic agent with histone deacetylase inhibitor activity shown to sensitize glioblastoma cells to radiation in preclinical models." }, { "input": "Which transcription factor is considered as a master regulator of lysosomal genes?", "output": "Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy, driving lysosome adaptation to environmental cues, such as starvation, and therefore targeting of TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease." }, { "input": "Which antibiotics target peptidoglycan biosynthesis?", "output": "Under some conditions, both ramoplanin and vancomycin probes produce helicoid staining patterns along the cylindrical walls of B. subtilis cells. This work has implications for the design of ramoplanin derivatives and may influence how other proposed substrate binding antibiotics are studied. This was confirmed by in vitro studies involving a wall-membrane particulate fraction from Gaffkya homari in which peptidoglycan synthesis from UDP-MurNAc-tetrapeptide was inhibited by ramoplanin but not by vancomycin. New results support a two-state model for septal and peripheral PG synthesis at mid-cell, involvement of essential cell division proteins in PG remodeling, and mid-cell localization of proteins that organize PG biosynthesis and that form the protein translocation apparatus." }, { "input": "Which antibiotics target peptidoglycan biosynthesis?", "output": "Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice. Cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division. The antibiotics bacitracin and vancomycin showed no obvious effect. Colchicine inhibits Closterium cell elongation after division. Surprisingly, also cinnamycin of Streptomyces cinnamoneus cinnamoneus), previously known to bind specifically to phosphatidylethanolamin of biological membranes, provoked strong cell wall biosynthetic stress. Other substances include fluorescent derivatives of two PG-binding antibiotics, vancomycin and ramoplanin. The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety. The muraymycins inhibited peptidoglycan biosynthesis. Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis. The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation. Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria." }, { "input": "Can Levoxyl (levothyroxine sodium) cause insomnia?", "output": "Levoxyl monotherapy is associated with increased insomnia compared to a combination of levothyroxine and liothyronine." }, { "input": "Is fatigue prevalent in patients receiving treatment for glioblastoma?", "output": "Yes, fatigue is a common complication of glioblastoma patients receiving chemotherapy or radiotherapy." }, { "input": "List two common features of Tay syndrome.", "output": "Tay syndrome is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and trichothiodystrophy (abnormal brittle hair). Other less common features of this syndrome are photosensitivity, low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections." }, { "input": "Which cell types are known to be driving Rheumatoid Arthritis?", "output": "Macrophages, T cells and their respective cytokines play a pivotal role in RA. Rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. Activated synovial fibroblasts (SFs) have the ability to invade joint cartilage, actively contributing to joint destruction in RA." }, { "input": "What is the association between personality trait of neuroticism and risk for Alzheimer's disease?", "output": "High neuroticism is associated with increased risk to develop Alzheimer's disease. Greater neuroticism is also associated more advanced Alzheimer's disease neuropathology and younger age of dementia onset. Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety. Neuroticism moderates the relationship between APOE-4 genotype and cognitive outcomes in elderly. Neuroticism also predicts Mild Cognitive Impairment, Aging-Associated Cognitive Decline and cognitive decline among elderly. Alzheimer's disease patients have greater neuroticism relative to controls." }, { "input": "What is the mode of action of everolimus?", "output": "Everolimus is a drug that binds to mTORC1 and inhibits activation of the mTOR signalling pathway. It is used in targeted cancer therapy protocols or after transplantation for maintenance immunosuppression, against allograft rejection." }, { "input": "Have Quantitative Trait Loci affecting splicing (splicing QTLs) been linked to disease?", "output": "Yes, mutations in the DNA that affect the splicing pattern of genes have been linked in transcriptome population studies to a number of diseases." }, { "input": "Which technique is used for detection of EWS/FLI1 fusion transcripts?", "output": "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors is carried out by reverse transcription-polymerase chain reaction (RT-PCR)." }, { "input": "Does the CTCF protein co-localize with cohesin?", "output": "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin." }, { "input": "Does the CTCF protein co-localize with cohesin?", "output": "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin " }, { "input": "What is the application of the Bimolecular Fluorescence Complementation (BiFC) assay in Drosophila embryos?", "output": "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms. This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context." }, { "input": "Which pathological condition of the heart is known as hypertrophic cardiomyopathy (HCM)?", "output": "Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young particularly among athletes. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins. HCM is the most prevalent genetic disorder affecting the heart and is typically inherited in an autosomal dominant pattern. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM." }, { "input": "What is the genetic basis of Rubinstein-Taybi syndrome?", "output": "Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are a microdeletion at 16p13.3 or mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) at 22q13 (5%). Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots. Thus about 55% of patients have cytogenetic or molecular abnormalities in the Crebbp or E1A binding protein p300 (Ep300) gene, leaving the diagnosis in 45% of patients to rest on clinical features only." }, { "input": "What is the function of the viral KP4 protein?", "output": "The virally encoded fungal toxin KP4 specifically blocks L-type voltage-gated calcium channels." }, { "input": "What is the function of the AIRE gene at the embryonic stage?", "output": "Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells. Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance. Knockdown of Aire in mouse ESCs resulted in significantly decreased clone-forming efficiency as well as attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells." }, { "input": "What is the function of the AIRE gene at the embryonic stage?", "output": "Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells." }, { "input": "What is the function of the AIRE gene at the embryonic stage?", "output": "The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. Monitoring Aire expression in MSCs may thus be a critical parameter for clinical use." }, { "input": "What is the principle of the PAR-CLIP methodology?", "output": "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. " }, { "input": "What is the principle of the PAR-CLIP methodology?", "output": "A powerful cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs was termed PAR-CliP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation). PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions. It relies on the intracellular incorporation of photoactivatable ribonucleoside analogs into nascent transcripts, and yields characteristic sequence changes upon crosslinking that facilitate the separation of signal from noise." }, { "input": "What is the principle of the PAR-CLIP methodology?", "output": "AR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteinsOne characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. " }, { "input": "What is the principle of the PAR-CLIP methodology?", "output": "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. " }, { "input": "What is the principle of the PAR-CLIP methodology?", "output": "In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. A recent method, PAR-CLIP, uses photoreactive nucleosides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins. PAR-CLIP shows high efficiency of RNA co-immunoprecipitation, but it also lead to T to C conversion in miRNA-RNA-protein crosslinking regions " }, { "input": "Which drugs are utilized to treat amiodarone-induced thyroitoxicosis?", "output": "Amiodarone-induced thyrotoxicosis treatment includes anti-thyroid drugs and steroid therapy\nRadio Iodine Treatment (RIT) may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.\nLithium is a useful and safe medication for treatment of iodine-induced thyrotoxicosis caused by amiodarone.\nThyrodectomy may be necessary in presence of unresponsiveness to standard medical treatments" }, { "input": "How is spastic diplegia diagnosed?", "output": "Diagnosis of spastic diplegia is mainly carried out with through clinical gait analysis (CGA), with variations such as 1-minute walk, LSU, and 10-meter walk tests, or Gross Motor Function Measure-88 (GMFM-88). Other methods used for evaluation of patients include brain magnetic resonance imaging (MRI) and motor function, presence of epileptic episodes, and IQ or developmental quotient." }, { "input": "How is spastic diplegia diagnosed?", "output": "Clinical gait analysis (CGA) has been highlighted as a possible tool to support the differential diagnosis of Hereditary Spastic Paraplegia (HSP) and Spastic Diplegia (SD). Argininaimia should be considered more frequently in the differential diagnosis of a patient with slowly progressive neurologic manifestations, especially progressive spastic diplegia. Gait Analysis (GA) complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns." }, { "input": "Which is the genetic defect causing Neurofibromatosis type 1?", "output": "Neurofibromatosis type 1 (NF1) is due to all types of mutations in the neurofibromin (NF1) gene." }, { "input": "Which is the human selenoprotein that contains several Se-Cys residues?", "output": "Selenoprotein P, that contains 10 selenocysteines." }, { "input": "Which package is available for analysing genomic interactions in R/Bioconductor?", "output": "r3Cseq is an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results." }, { "input": "How many clinical trials for off-label drugs in neonates are cited in the literature.", "output": "There are no reports on clinical trials of off-label drugs in neonates. An analysis of Pediatric Investigation Plans submitted between 2007 and 2010 shows that neonates were included in the study of 4 products, but it is unknown if the trial drugs are off-label and if the trials are being conducted at all." }, { "input": "Are stress granules involved in the pathogenesis of Amyotrophic Lateral Sclerosis?", "output": "Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis. ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism." }, { "input": "Are stress granules involved in the pathogenesis of Amyotrophic Lateral Sclerosis?", "output": "Yes, stress granules (SGs) have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)." }, { "input": "Does TGF-beta play a role in cardiac regeneration after myocardial infarction?", "output": "TGF\u03b2 signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration." }, { "input": "Is there a genetic component for happiness?", "output": "Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. The MAOA gene predicts happiness in women. The heritability of happiness was estimated at 22% for males and 41% in females." }, { "input": "What enzyme is inhibied by Opicapone?", "output": "Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease" }, { "input": "What kind of affinity purification would you use in order to isolate soluble lysosomal proteins?", "output": "The rationale for purification of the soluble lysosomal proteins resides in their characteristic sugar, the mannose-6-phosphate (M6P), which allows an easy purification by affinity chromatography on immobilized M6P receptors." }, { "input": "Which are the genes thought to be regulated by EWS/FLI?", "output": "The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of a significant number of genes are affected in Ewing sarcoma, some of which are known to be directly or indirectly regulated by EWS/FLI. Such genes are BCL11B, NRoB1, GSTM4, NKX2.2 and p53." }, { "input": "Do archaeal genomes contain one or multiple origins of replication?", "output": "Some archaea replicate from single origins but most archaea and all eukaryotes replicate using multiple origins." }, { "input": "Do archaeal genomes contain one or multiple origins of replication?", "output": "Multiple functional sites of origin of replication may exist in the genomes of most archaea. This has only been demonstrated recently. Two studies have shown that multiple origins of replication function in two archaeal species." }, { "input": "Which pathological conditions are caused by mutations in the CYLD gene?", "output": "Since loss of CYLD expression can be observed in different types of human cancer, it is now well established that CYLD acts as a tumor suppressor gene. Pathogenic mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma. CYLD expression has also been reported to be dramatically downregulated in basal cell carcinoma (BCC), the most common cancer in humans." }, { "input": "Which is the genetic basis of Spinal Muscular Atrophy (SMA)?", "output": "The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1). Mutations of the SMN1 gene are responsible for SMA. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA). H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.\nThe molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1)." }, { "input": "Which are the common symptoms of Cushing's syndrome?", "output": "Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension." }, { "input": "Which is the third subunit of the TSC1-TSC2 complex upstream of mTORC1?", "output": "TBC1D7 was identified as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. It was demonstrated that TSC1-TSC2-TBC1D7 (TSC-TBC) is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity to negatively regulate mTORC1 activity. In agreement with this, TBC1D7 knockdown was shown to result in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions." }, { "input": "Which kinase is inhibited by the small molecule KN-93?", "output": "The calcium/calmodulin-dependent protein kinase-II (CaMK-II) is inhibited by the small molecule KN-93. KN-93 is a membrane-permeant calcium/calmodulin- dependent kinase II (CaMK-II)-selective inhibitor" }, { "input": "What is the effect of Chk2 splice variants on wild-type Chk2 kinase activity?", "output": "Chk2 splice variants have been demonstrated to exert a dominant-negative effect on wild-type Chk2 kinase activity." }, { "input": "List genes that have been found mutated in CMT1A (Charcot-Marie-Tooth disease type 1 A).", "output": "PMP22 is the common gene found mutated through a duplication in CMT1A. Other genes are\nMPZ and SH3TC2" }, { "input": "Which viruses are best known to cause myocarditis?", "output": "The most frequent viruses causing myocarditis are Enterovirus, Adenovirus and Coxsackie B viruses." }, { "input": "Which genes have been associated with Cerebral Cavernous Malformation?", "output": "Loss-of-function mutations in genes encoding CCM1 (also known as KRIT1), CCM2 (also known as OSM and malcavernin) or CCM3 (also known as PDCD10) cause cerebral cavernous malformations (CCMs)." }, { "input": "Is DITPA a thyroid hormone analog utilized in experimental and clinical studies", "output": "There is very large body of evidence that DITPA is a true thyroid hormone analog, largely utilized in experimental and clinical studies." }, { "input": "What is Tarlov Cyst?", "output": "Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic." }, { "input": "What are 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin'?", "output": "\"Sitagliptin,\" \"vildagliptin,\" \"saxagliptin,\" \"alogliptin,\" \"linagliptin,\" and \"dutogliptin\" are dipeptidyl peptidase-4 (DPP-4) inhibitors." }, { "input": "Which is the most important prognosis sub-classification in Chronic Lymphocytic Leukemia?", "output": "The mutational status of the immunoglobulin heavy variable (IGHV) genes, defines two subsets: mutated and unmutated CLL. Unmutated CLL patients show a shorter progression-free and overall survival than mutated CLL patients." }, { "input": "Is MammaPrint cleared by the United States Food and Drug Administration? ", "output": "Yes. MammaPrint is cleared by the FDA for breast cancer recurrence." }, { "input": "Is amantadine effective for treatment of disorders conciousness?", "output": "Amantadine, a dopaminergic agent, has been shown to be effective for induction of recovery from disorders of consciousness. Amantadine is a commonly prescribed medication for patients with prolonged disorders of consciousness after traumatic brain injury. Amantadine accelerates the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. Higher dosing of amantadine may be considered in the setting of brain injury." }, { "input": "What is needed for MMP proteins to be functional?", "output": "Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases." }, { "input": "What is hyperosmia", "output": "Hyperosmia is increased olfactory acuity " }, { "input": "What is hyperosmia", "output": "increased olfactory acuity" }, { "input": "What is the number of long non coding RNAs in the human genome", "output": "Different estimates put currently the number of human long non coding RNAs between 10,000 and 20,000" }, { "input": "Which is the most known bacterium responsible for botulism (sausage-poisoning)?", "output": "Botulism is a severe neuroparalytic disease caused by botulinum neurotoxin (BoNT), and affects humans, all warm-blooded animals, birds, and some fishes. Botulinum toxin is produced under anaerobic conditions by the bacterium Clostridium botulinum, which is the most known etiological agent of the disease, and some other clostridia, and is one of the most dangerous toxin in the world." }, { "input": "What is the association of spermidine with \u03b1-synuclein neurotoxicity?", "output": "Spermidine protects against \u03b1-synuclein neurotoxicity. In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human \u03b1-synuclein, which is thought to be the principal toxic trigger of Parkinson's Disease (PD). In this line, administration of spermidine rescued \u03b1-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes. Alleviation of PD-related neurodegeneration by spermidine was accompanied by induction of autophagy, suggesting that this cytoprotective process may be responsible for the beneficial effects of spermidine administration." }, { "input": "List symptoms of 4H leukodystrophy.", "output": "Hypomyelination, hypodontia, and hypogonadotropic hypogonadism are major symptoms of 4H leukodystrophy." }, { "input": "What is the extracellular core \"matrisome\"?", "output": "The \"matrisome\" is defined as the ensemble of extracellular matrix proteins (ECM) proteins and associated factors. The core matrisome have been defined in mammals through the analysis of whole genome sequences and comprises of ~ 300 proteins." }, { "input": "Is GAGA associated with nucleosome-free regions (NFR)?", "output": "The GAGA factor is a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin. The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions. While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization." }, { "input": "Is GAGA associated with nucleosome-free regions (NFR)?", "output": "The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. To study the contribution of transcription factors to the establishment of this specific chromatin configuration we assembled nucleosomes on the hsp26 promoter using a cell-free reconstitution system derived from fly embryos. This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) sites (Q. Lu, L.L. Wallrath, B.D. Allan, R.L. Glaser, J.T. Lis, and S.C.R. Elgin, J. Mol. Biol. Both DH sites were readily reconstituted from extract components." }, { "input": "Is GAGA associated with nucleosome-free regions (NFR)?", "output": "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin." }, { "input": "Which are the plant DNA (cytosine-5) methyltransferase families?", "output": "The plant DNA (cytosine-5)methyltransferases are classified into the families: MET, CMT, and the de novo DRM." }, { "input": "Where is the histone variant CENPA preferentially localized?", "output": "Centromere protein A (Cenpa for mouse, CENP-A for other species) is an essential histone H3-like protein that localizes to the centromeric region of eukaryotic chromosomes, where it replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores." }, { "input": "Where is the histone variant CENPA preferentially localized?", "output": "THe histone variant CENPA is preferentially located at Centromeric chromatin" }, { "input": "In which proteins is the chromodomain present?", "output": "The chromodomain (chromatin organizer modifier domain) is a highly conserved motif, 40-50 amino acids in length, present in a wide range of animal and plant proteins involved in chromatin organization. Chromodomain-containing proteins can be classified into boader families based, particularly, on the presence of other types of domains. Chromodomain is present in: the heterochromatin proteins HP1 alpha and HP1 beta, chromointgrases (e.g. Tf1 integrase) the chromodomain helicase DNA-binding proteins (CHD) and CHD 1-like (CHD1L), CReMM (chromatin-related mesenchymal modulator), dna methyltransferase 3 (cmt3), the chromointegrase of the LTR-retrotransposons, the Polycomb group (PcG) proteins, the mouse Polycomb homologs (Cbx2, Cbx4, Cbx6, Cbx7, Cbx8), the chromodomain Y chromosome (CDY) family of proteins and the CDY-like protein (CDYL), the histone acetyltransferases TgMYST-A and \u2013B, MRG-1 and -15 (MORF4-Related Gene on chromosome 15), ADP/ATP translocase 1, MPP8, MSL3, NlMof, Chp1, Chriz, dMi-2, Corto, cpSRP43, KISMET, PICKLE (PKL), ScoHET1 and ScoHET2.\n" }, { "input": "What is Genomicus?", "output": "Genomicus had been developed as a database and a browser to study gene synteny in modern and ancestral genomes. It allows easy comparative genomic visualization in >150 eukaryote genomes and in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. The graphical modules of Genomicus show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and facilitate the study of the evolution of a locus through homology relationships. The Genomicus server provides access to ancestral gene orders, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets." }, { "input": "Is amiodarone a class I anti-arrhythmic drug?", "output": "Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile" }, { "input": "Is amiodarone a class I anti-arrhythmic drug?", "output": "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone." }, { "input": "Is amiodarone a class I anti-arrhythmic drug?", "output": "Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile." }, { "input": "Is amiodarone a class I anti-arrhythmic drug?", "output": "No. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile." }, { "input": "Is amiodarone a class I anti-arrhythmic drug?", "output": "Amiodarone, an iodinated benzofuran derivative, introduced in 1960 s as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970 s and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent. " }, { "input": "Which is the prognostic meaning of delayed enhancement documented in patients hypertrophic cardiomyopathy?", "output": "Delayed enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients, and is associated with cardiovascular mortality, heart failure death, and all-cause mortality in HCM." }, { "input": "What is the COUGER tool?", "output": "COUGER takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. " }, { "input": "What is the COUGER tool?", "output": "COUGER is a classification-based framework for identifying protein co-factors that might provide specificity to paralogous TFs. It takes as input two sets of genomic regions bound by paralogous TFs, and it identifies a small set of putative co-factors that best distinguish the two sets of sequences. To achieve this task, COUGER uses a classification approach, with features that reflect the DNA-binding specificities of the putative co-factors. The identified co-factors are presented in a user-friendly output page, together with information that allows the user to understand and to explore the contributions of individual co-factor features." }, { "input": "Are there drugs for Tick-borne Encephalitis?", "output": "No drug therapy available today" }, { "input": "Is SLC22A3 expressed in the brain?", "output": "Yes, SLC22A3 (organic cation transporter (OCT3)) is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission." }, { "input": "Has the protein TIEG1 been associated with apoptosis?", "output": "Yes, TIEG1 (also known as KLF10) seems to play a role in regulating apoptosis." }, { "input": "Which is the cellular localization of the protein Opa1?", "output": "The Opa1 protein localizes to the mitochondria." }, { "input": "Which is the cellular localization of the protein Opa1?", "output": "Opa1 is found normally in the mitochondrial intermembrane space." }, { "input": "Which are the drugs utilized for the burning mouth syndrome?", "output": "Dopaminergic drugs should be given in patients with BMS. \nCatuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease.\nCapsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS.\nTreatment with placebos produced a response that was 72% as large as the response to active drugs" }, { "input": "Is PTEN involved in follicular thyroid carcinoma?", "output": "The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%." }, { "input": "Which genome browser database for DNA shape annotations is available?", "output": "The Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution." }, { "input": "What is known about clinical efficacy of ceftriaxone for treatment of amyotrophic lateral sclerosis?", "output": "There have been a few case reports to suggest that ceftriaxone can be effective for treatment of amyotrophic lateral sclerosis. However, other case reports did not report clinical benefit of ceftriaxone therapy for ALS. Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis a through increased expression and activity of the glutamate transporter, GLT1. Clinical trials investigating potential clinical benefits of ceftriaxone in ALS are ongoing." }, { "input": "What is the relationship between TailorX and Oncotype?", "output": "The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone." }, { "input": "Does strenuous physical activity affect thyroid hormone metabolism?", "output": "YES" }, { "input": "Which is the main function of \"RNA sponges\"?", "output": "Natural RNA circles function as efficient microRNA sponges. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants." }, { "input": "Which is the main function of \"RNA sponges\"?", "output": "Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. Natural RNA sponges sequestering cellular noncoding RNA molecules have been found in diverse organisms. In this issue, Lalaouna et al. (2015) report another type of RNA sponge, showing that stable intermediates of bacterial tRNA processing control endogenous small RNAs. Furthermore, survival analysis suggests that high OCT4-pg4 level is significantly correlated with poor prognosis of HCC patients." }, { "input": "Is the gene MAOA epigenetically modified by methylation?", "output": "In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus.\nWe conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order." }, { "input": "Which mutations of phopspholamban have been found in patients with cardiomyopathy?", "output": "PLN mutation R14del [or c.40_42delAGA(p.Arg14del)] was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. Another PLN mutation is a T116G point mutation, substituting a termination codon for Leu-39 (L39stop), and it was identified in two families with hereditary heart failure. Hereditary mutants of phospholamban, such as Arg(9) to Cys, Arg(9) to Leu, Arg(9) to His, cause lethal, hereditary dilated cardiomyopathy.in specific, two patients presented a G-T missense mutation at the G26 nucleotide, which encodes an Arg-Leu substitution at codon 9 (R9L).One patient presented a G-A missense mutation at the same nucleotide, which encodes an Arg-His substitution at codon 9 (R9H). A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death." }, { "input": "Which are the supplemental antioxidant in athletes?", "output": "There are several antioxidant supplements belonging to different families, i.e. Vitamins, Polyphenols, alpha-lipoic acid, ubiquinones, n-3- polyunsaturated acids (PUFAs), minerals and others. Nonetheless the widespread use of these supplements, it is still debated their true usefulness, and it is not unanimously advised their use in athletes." }, { "input": "Is glycyl-tRNA synthetase gene involved in the development of Charcot-Marie-Tooth disease?", "output": "Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration." }, { "input": "Is glycyl-tRNA synthetase gene involved in the development of Charcot-Marie-Tooth disease?", "output": "Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D" }, { "input": "Is there any software for automated analysis of FISH images?", "output": "FISH is a popular molecular cytogenetic method. The output of a single FISH analysis is a set of several tens or hundreds microscopic images \u2014 a single evaluated sample is of roughly 20mm diameter. The goal of an automated evaluation is to replace the subjective evaluation of images by the laboratory technician to achieve higher uniformity of results. Following explanation of the principle of the method and the typical contents of images, the processing flow of image segmentation is outlined and the results are presented on several example images. Based on results there are software for automated analysis of FISH images." }, { "input": "How do histone methyltransferases cause histone modification?", "output": "Histone methyltransferases (HMTs) are responsible for the site-specific addition of covalent modifications on the histone tails, which serve as markers for the recruitment of chromatin organization complexes. There are two major types of HMTs: histone-lysine N-Methyltransferases and histone-arginine N-methyltransferases. The former methylate specific lysine (K) residues such as 4, 9, 27, 36, and 79 on histone H3 and residue 20 on histone H4. The latter methylate arginine (R) residues such as 2, 8, 17, and 26 on histone H3 and residue 3 on histone H4. Depending on what residue is modified and the degree of methylation (mono-, di- and tri-methylation), lysine methylation of histones is linked to either transcriptionally active or silent chromatin." }, { "input": "Is there an increased risk for cancer in Dyskeratosis Congenita?", "output": "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis " }, { "input": "Is there an increased risk for cancer in Dyskeratosis Congenita?", "output": "Yes. Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer. Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST)" }, { "input": "Is there an increased risk for cancer in Dyskeratosis Congenita?", "output": "People with Dyskeratosis Congenita are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis." }, { "input": "Does MicroRNA-21 (miR-21) contribute to cardiovascular disease?", "output": "MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches" }, { "input": "What is the enzymatic activity of the breast cancer associated gene BRCA1?", "output": "E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain.BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways." }, { "input": "What is the enzymatic activity of the breast cancer associated gene BRCA1?", "output": "Discovering the precise function of the breast and ovarian specific tumor suppressor, BRCA1, has proven to be quite complicated. The protein encoded by BRCA1 interacts in vivo with the related BARD1 protein to form a heterodimeric complex that acts as a ubiquitin E3 ligase. E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain." }, { "input": "List markers for autophagy.", "output": "Expression of LC3-II and BECN1 as well as SQSTM1 are used as markers of autophagy activity." }, { "input": "Are there any statistical methods for normalizing and identifying differential regions in histone modification ChIP-seq data?", "output": "Yes. ChIPnorm is a two-stage statistical method to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types." }, { "input": "Is CD84 genetically associated with arthritis?", "output": "Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations. Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with Rheumatoid Arthritis disease activity." }, { "input": "What is the function of Neu5Gc (N-Glycolylneuraminic acid)?", "output": "N-glycolylneuraminic acid (Neu5Gc) is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. N-Glycolylneuraminic acid (Neu5Gc) can be incorporated in human cells and can trigger immune response, a response that is diverse and polyclonal. As dietary Neu5Gc is primarily found in red meat and milk products, it is suggested that this ongoing antigen-antibody reaction may generate chronic inflammation, possibly contributing to the high frequency of diet-related carcinomas and other diseases in humans." }, { "input": "Are there any specific antidotes for rivaroxaban?", "output": "Currently, there is no specific antidote for rivaroxaban" }, { "input": "Which metabolite activates AtxA?", "output": "Upon infection of a mammalian host, Bacillus anthracis responds to host cues, and particularly to elevated temperature (37\u00b0C) and bicarbonate/CO2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer. Cultures grown with elevated CO(2) /bicarbonate exhibited increased AtxA dimer/monomer ratios and increased AtxA activity, relative to cultures grown without added CO(2) /bicarbonate, suggesting that this host-associated signal enhances AtxA function by shifting the dimer/monomer equilibrium towards the dimeric state. CO2-enhanced toxin gene transcription is not observed in atx4-null mutants. Overall data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins." }, { "input": "Which metabolite activates AtxA?", "output": "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2. However, the steady-state level of atxA mRNA in cells grown in elevated CO2/bicarbonate at 37 degrees C is five- to sixfold higher than that observed in cells grown in the same conditions at 28 degrees C. A corresponding difference in AtxA protein was also seen at the different growth temperatures. All mutants multimerized, but one mutation, C402S, prevented cross-linking." }, { "input": "What is the function of 6SRNA in bacteria?", "output": "6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. The carboxy terminus containing the Arg-Gly-Gly (RGG) repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain." }, { "input": "What is the function of 6SRNA in bacteria?", "output": "Escherichia coli 6S RNA represents a non-coding RNA (ncRNA), which, based on the conserved secondary structure and previous functional studies, had been suggested to interfere with transcription. 6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription. 6S RNA regulation of both sigma(70) and sigma(S) activities contributes to increased cell persistence during nutrient deprivation. 6S RNA acts as a template for the transcription of defined RNA molecules in the absence of DNA. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase." }, { "input": "What is the function of 6SRNA in bacteria?", "output": "6S RNA function enhances long-term cell survival. " }, { "input": "Is cytisine superior to nicotine replacement therapy for smoking cessation?", "output": "Yes, one clinical trial that directly compared smoking cessation rates with cytisine versus nicotine replacement therapy reported that cytisine was superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events." }, { "input": "Which amino acid residue appears mutated in most of the cases reported with cadasil syndrome?", "output": "CADASIL is caused mostly by missense mutations in the NOTCH3 gene, invariably involving a cysteine residue." }, { "input": "Which syndromes are associated with mutations in the EZH2 gene?", "output": "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined. Recent studies have shown that EZH2 mutations are often associated with RUNX1 mutations in MDS patients, although its pathological function remains to be addressed. These data show that mutations in EZH2 cause Weaver syndrome. The EZH2 gene is a homolog of the Drosophila Polycomb group (PcG) gene enhancer of zest, a crucial regulator of homeotic gene expression." }, { "input": "Which syndromes are associated with mutations in the EZH2 gene?", "output": "Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML). Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL). The EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukaemia." }, { "input": "Which databases exist for experimentally determined topologies of \u03b1-helical transmembrane proteins ?", "output": "ExTopoDB and TMPDB." }, { "input": "Which disease is characterized by congenital absence of intrinsic ganglion cells of the gastrointestinal tract?", "output": "Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. " }, { "input": "Which disease is characterized by congenital absence of intrinsic ganglion cells of the gastrointestinal tract?", "output": "The medical condition characterized by the congenital absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract is called aganlionic megacolon or Hirschsprung disease." }, { "input": "Which disease is characterized by congenital absence of intrinsic ganglion cells of the gastrointestinal tract?", "output": "Hirschsprung disease (HSCR) is a congenital disorder associated with the absence of intrinsic ganglion cells in the distal gastrointestinal tract.This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells." }, { "input": "Which disease is characterized by congenital absence of intrinsic ganglion cells of the gastrointestinal tract?", "output": "Hirschsprungs disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells." }, { "input": "What is the disease in which patients are sensitive to DNA crosslinking agents, presenting with a high frequency of chromosomal aberrations?", "output": "Fanconi anemia (FA) is an autosomal disorder that causes genome instability and manifests by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations." }, { "input": "What is the disease in which patients are sensitive to DNA crosslinking agents, presenting with a high frequency of chromosomal aberrations?", "output": "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations. " }, { "input": "What is the disease in which patients are sensitive to DNA crosslinking agents, presenting with a high frequency of chromosomal aberrations?", "output": "Fanconi anemia (FA) is an autosomal disorder that causes genome instability. FA patients suffer developmental abnormalities, early-onset bone marrow failure, and a predisposition to cancer. The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations." }, { "input": "How is oprozomib administered?", "output": "Oprozomib is administered orally." }, { "input": "What is a Caveolae?", "output": "Caveolae, plasma membrane invaginations of 60-80nm in diameter, are a subset of lipid rafts enriched in cholesterol and sphingolipids." }, { "input": "Which are the roles of chromatin compartments in the eukaryotic nucleus?", "output": "The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments. Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements. Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Therefore, concentrating proteins needed to perform different steps of RNA synthesis within specialized nuclear compartments is important in orchestrating events required for efficient gene expression." }, { "input": "Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?", "output": "No. Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells." }, { "input": "Does thyroid hormone regulate calcium transient in the myocardium? ", "output": "YES" }, { "input": "What are the biological roles proposed for proteins containing the SPRY domain?", "output": "defence against retroviral infection\ninnate and adaptative immunity\nvesicular trafficking\nneural differentiation\nembryonic development" }, { "input": "How could we infer functional associations from gene fusion events?", "output": "The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, based on the observation that related proteins in one organism (including physically interacting proteins/members of complexes, proteins involved in the same pathway) tend to be found in other species as a fused composite gene encoding a single multifunctional protein. For this purpose, gene fusion events may be used as the sole evidence or as independent information combined with other 'genome-aware' or similarity-based methods, and functional association may be predicted at different levels. An advantage of this approach is that it is not necessary to know the function of the composite/components to infer association." }, { "input": "The protein NONO forms heterodimers. With which proteins?", "output": "The protein NONO forms heterodimers with PSPC1, SFPQ." }, { "input": "Which syndrome is associated with mutant DVL1?", "output": "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome." }, { "input": "Are proteasome inhibitors good candidates for treatment of leukemia and solid tumors?", "output": "Yes, several compounds that inhibit different members of the proteasome pathway (for example Bortezomib) are on trial for treatment of leukemia and solid tumors. It seems that a combination with other drugs may be a useful therapy for solid tumors." }, { "input": "Is there any link between CTF4 and CTF18 during sister chromatid cohesion?", "output": "Yes. CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. Absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion." }, { "input": "What is the Genomic Regions Enrichment of Annotations Tool (GREAT)?", "output": "Genomic Regions Enrichment of Annotations Tool (GREAT) is a tool to analyse the functional significance of cis-regulatory regions identified by localised measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, many functions of these factors are recovered that are missed by existing gene-based tools, and testable hypotheses are generated. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets." }, { "input": "What is the target of the drug Olaparib?", "output": "The drug Olaparib target the protein poly(ADP-ribose) polymerase." }, { "input": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "output": "The lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH" }, { "input": "What is the role of RhoA in bladder cancer?", "output": "In urinary bladder cancer, RhoA was more commonly found to be activated in the later stages of the disease. This activation was related to poor tumor differentiation, muscle invasion, lymph node metastasis, and shortened disease-free and overall survival." }, { "input": "List human proteins that are subject to a dimer-to-tetramer transition.", "output": "GAC\nSHMT2\nAMPAR\nOrai1\nOrai3" }, { "input": "Inhibition of which transporter is the mechanism of action of drug Canagliflozin?", "output": "Inhibition of sodium glucose co-transporter 2 (SGLT2) is the major mechanism of action of canagliflozin. Canagliflozin is the first SGLT2 inhibitor to be approved in the USA for the treatment of type 2 diabetes and is under regulatory review in the EU. Other SGLT2 inhibitors include dapagliflozin and empagliflozin." }, { "input": "What is the prognostic role of thyroid hormone in patients with heart failure?", "output": "Altered thyroid profile, particularly sick euthyroid syndrome, is an independent predictor of mortality in patients with chronic heart failure, adding prognostic information to conventional clinical and functional cardiac parameters." }, { "input": "which mutations of phospholamban gene have been found to cause hypertrophic cardiomyopathy?", "output": "The following mutations of the phospholamban gene have been found to be associated with hypertrophic cardiomyopathy: PLN L39X nonsense mutation; PLN Leu39Ter; PLN -42 C>G and PLN -77A-->G" }, { "input": "Which gene strand is targeted by transcription-coupled repair (TCR)?", "output": "Nucleotide Excision Repair (NER) removes a variety of helix-distorting lesions from DNA. It has two sub-pathways, the global genome (gg) NER and the transcription-coupled repair (TCR). TCR is triggered when a RNA polymerase, translocating along the transcribed strand, is arrested at a lesion or unusual structure in the DNA. TCR is dedicated to target and repair the transcribed strand of an active gene." }, { "input": "Abnormalities in which chromosomes were linked to the Moyamoya disease?", "output": "chromosomes 3, 6, 8, 12, 15, 17, 21, X and Y were implicated in the Moyamoya disease." }, { "input": "Which is the branch site consensus sequence in U12-dependent introns?", "output": "The branch site consensus sequence in U12-dependent introns is UUCCUUAAC." }, { "input": "For what is Protein A from Staphylococcus aureus used in biochemistry?", "output": "Protein A from the bacterium Staphylococcus aureus (SpA) is used as an affinity ligand for purification of immunoglobulin G (IgG)." }, { "input": "What is the suggested therapy for Mycobacterium avium infection?", "output": "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection. TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex. Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. In vivo phage treatment may also be used in some cases." }, { "input": "What is the suggested therapy for Mycobacterium avium infection?", "output": "Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks" }, { "input": "What is the suggested therapy for Mycobacterium avium infection?", "output": "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection" }, { "input": "What is the treatment of acute pericarditis?", "output": "A multidisciplinary approach is frequently necessary to treat acute pericarditis; the most frequent treatments are: antiinflammatory steroid and non-steroid drugs, antibiotic therapy, pericardial drainage and, less frequently ,intrapericardial irrigation of fibrinolytics; antituberculous chemotherapy in presence of Tuberculous Agent" }, { "input": "What is the genetic basis of tuberous sclerosis?", "output": "The genetic basis of tuberous sclerosis has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2. The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently. Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors." }, { "input": "What is the genetic basis of tuberous sclerosis?", "output": "The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2." }, { "input": "What is the genetic basis of tuberous sclerosis?", "output": "We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease. The study of hereditary tumor syndromes has laid a solid foundation toward understanding the genetic basis of cancer." }, { "input": "What is the molecular function of the Chd1 protein?", "output": "The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. One of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity. Human CHD1 is an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4." }, { "input": "Which drugs are included in the FEC-75 regimen?", "output": "Fluorouracil, epirubicin, and cyclophosphamide are included in the FEC-75 regimen. This chemotherapy regiment is used for breast cancer treatment." }, { "input": "Between which probes does the recurrent translocation breakpoint on chromosome 22 of neuroepithelioma lie?", "output": "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids" }, { "input": "Between which probes does the recurrent translocation breakpoint on chromosome 22 of neuroepithelioma lie?", "output": "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids. " }, { "input": "Between which probes does the recurrent translocation breakpoint on chromosome 22 of neuroepithelioma lie?", "output": "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids." }, { "input": "Between which probes does the recurrent translocation breakpoint on chromosome 22 of neuroepithelioma lie?", "output": "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids " }, { "input": "Does administration of triiodothyronine improve outcome following coronary artery bypass grafting?", "output": "Perioperative administration of synthetic thyroid hormone therapy have positive hemodynamic effects (consisting of increases cardiac output, lowered systemic vascular resistance) determining improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, in the absence of relevant effects on outcome ad exception of lower incidence of atrial fibrillation." }, { "input": "Which are the most widely used computational methods for the identification of CRMs (cis-regulatory modules)?", "output": "Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specific interactions involved remains limited. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs." }, { "input": "Which are the most widely used computational methods for the identification of CRMs (cis-regulatory modules)?", "output": "The optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. A statistical model to describe the underlying cluster structure as well as individual motif conservation has also been proposed, accompanied with a Monte Carlo motif screening strategy for predicting novel regulatory modules in upstream sequences of coregulated genes." }, { "input": "Which enzyme does MLN4924 inhibit?", "output": "MLN4924 is an investigational small molecule inhibitor of NEDD8-activating enzyme (NAE)." }, { "input": "Which protein has been found to interact with phospholamban (PLN) and is also an anti-apoptotic protein?", "output": "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential." }, { "input": "Which protein has been found to interact with phospholamban (PLN) and is also an anti-apoptotic protein?", "output": "The HS-1 associated protein X-1 (HAX-1) is a mitochondrial protein with anti-apoptotic function and presents with numerous similarities to Bcl-2. and was identified as a phospholamban-binding partner. Using the yeast-two-hybrid system, HS-1 associated protein X-1 (HAX-1) was identified as a PLN-binding partner." }, { "input": "Which protein has been found to interact with phospholamban (PLN) and is also an anti-apoptotic protein?", "output": "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. Recently, the antiapoptotic HS-1-associated protein X-1 (HAX-1) was identified as a binding partner of PLN, and this interaction was postulated to regulate cell apoptosis.Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function." }, { "input": "Is long QT syndrome a cause for sudden cardiac death in athletes?", "output": "One of several causes of sudden cardiac death in athletes is long QT syndrome" }, { "input": "What is the clinical value of MammaPrint?", "output": "MammaPrint has a prognostic value for distant metastasis and death, as well as predictive value for response to adjuvant chemotherapy in patients with breast cancer. However, the EGAPP Working Group found no evidence regarding the clinical utility of the MammaPrint." }, { "input": "Is protein M3/6 a dual specificity phosphatase?", "output": "M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs." }, { "input": "Is protein M3/6 a dual specificity phosphatase?", "output": "Yes. Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins." }, { "input": "Is protein M3/6 a dual specificity phosphatase?", "output": "The protein M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK" }, { "input": "Are there focused databases from which you can retrieve gene expression data on renal disease?", "output": "Biological databases are used to store and edit large amount of data, created from genomics data. In the most of the cases the data are stored according to their type but there are cases of focused databases that store database on a specific disease. In the case of renal disease there are plenty of databases, for example KUPKB a collection of omics datasets, Nephromine a renal genome-wide gene expression dataset based in transcriptomics, CDKD and Proteomics Database in Chronic Kidney Disease." }, { "input": "What systems have been developed for the numbering of antibody residues?", "output": "The most prevalent antibody numbering systems are the Kabat system, the Chothia system as well as the IMGT numbering system." }, { "input": "Are there any DNMT3 proteins present in plants?", "output": "Yes. The plant DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) is a homolog of the mammalian de novo methyltransferase DNMT3. DRM2 contains a novel arrangement of the motifs required for DNA methyltransferase catalytic activity." }, { "input": "What is the number of protein coding genes in the human genome?", "output": "The number of protein coding genes in the human genome is currently estimated between 20,000 and 25,000" }, { "input": "Has vitamin D has been shown to reduce incidence of falls in older people in clinical trials?", "output": "The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke.\nTwo studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling.\nOverall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.\nWe found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96)" }, { "input": "What is the indication for prophylactic use of antibiotics in COPD?", "output": "In a subset of patients with severe disease and prone to developing infections prophylactic use of antibiotics may reduce number of exacerbations and improve social and health care costs." }, { "input": "Has depression been shown to be a predictor of frailty?", "output": "Yes" }, { "input": "What is the generic name of Gliolan?", "output": "5-aminolevulinic acid (or 5-ALA) is the generic name of Gliolan. It is approved for fluorescence-guided resections of adult malignant gliomas." }, { "input": "Is there any association between Jarid2 and miR-155 in Th17 cells?", "output": "Yes. Activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells." }, { "input": "What is enCHIP?", "output": "Engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) is a novel method for purification of specific genomic regions retaining molecular interactions. EnChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest." }, { "input": "How many genes does the human hoxD cluster contain?", "output": "The human HOXD complex contains nine genes: HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12 and HOXD13, which are clustered from 3\u2032 to 5\u2032 in an approximately 100-kb stretch on chromosome 2q31.1 with HOXD1 at the 3' end and HOXD13 the 5\u2032 end." }, { "input": "Is it safe to take isotretinoin during pregnancy?", "output": "No. The isotretinoin has severe teratogenic effects and it is not safe to use during pregnancy." }, { "input": "Which protein is the E3-ubiquitin ligase that targets the tumor suppressor p53 for proteasomal degradation?", "output": "The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2). The RING domain E3 ubiquitin ligase Mdm2 is the master regulator of the tumor suppressor p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation." }, { "input": "Which protein is the E3-ubiquitin ligase that targets the tumor suppressor p53 for proteasomal degradation?", "output": "This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development., p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation., Mdm2 has been thought to regulate the tumor suppressor p53 in two ways: by masking p53's access to transcriptional machinery, and by ubiquitinating p53, targeting it for proteasomal degradation" }, { "input": "Can DNA intercalators function as topoisomerase inhibitors?", "output": "The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II. Among its many properties, amiloride is a DNA intercalator and topoisomerase II inhibitor. Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent. AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator. Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases." }, { "input": "Which diseases is microRNA 132 (miR-132) implicated in?", "output": "Several targets for for miR-132 have been described and it is implicated in many diseases such as:\nneurodegenerative disease, \nepilepsy,\nschizophrenia,\nHuntington's disease (HD),\nAlzheimer's disease (AD),\nneuroinflammation,\nosteosarcoma,\nchronic lymphocytic leukemia (CLL),\nangiogenesis,\neye disease,\nalcoholic liver disease,\nprogressive supranuclear palsy (PSP taupathy),\nmild cognitive impairment." }, { "input": "Which are the human glutamate transporters?", "output": "Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. Using immunofluorescence and postembedding immunogold labeling, we investigated the distributions of the glutamate-aspartate transporter (GLAST or excitatory amino acid transporter 1), vesicular glutamate transporter (VGLUT1), and the AMPA receptor glutamate receptor 4 (GluR4) along the spiral." }, { "input": "Which are the human glutamate transporters?", "output": "To date, five distinct mammalian glutamate transporters have been cloned. The extracellular levels of excitatory amino acids are kept low by the action of the glutamate transporters. Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. Expression of short interfering RNA-mediated knockdown of RTN2B decreases the EAAC1 protein level in neurons." }, { "input": "What are the functions of sorting nexin 27?", "output": "Sorting nexin 27 (SNX27) regulates endocytic sorting/recycling and intracellular trafficking of ion channels and receptors." }, { "input": "Do orphan and gene related CpG islands follow power-law-like distributions?", "output": "Yes. Orphan and gene related CpG Islands follow power-law-like distributions in several genomes. The observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow." }, { "input": "What is the proportion of non canonical splice sites in the human genome?", "output": "Between 1% and 2% of human splice sites do not contain the canonical GT-AG dinucleotides" }, { "input": "List protein gel staining methods visualizing the entire protein set.", "output": "Several staining protocols for the visualization of proteins separated by SDS-PAGE have been described in literature: \nfluorescence\nSypro Ruby\nColloidal Coomassie Blue\nCoomassie Blue\nSilver staining\nCoomassie Brilliant Blue" }, { "input": "What clinical use aptamers may have?", "output": "In the clinic, aptamers may be used to enhance the antigenicity of disseminated tumors, leading to their immune recognition and rejection; to target HPV16 E7 oncoprotein, inhibiting cell proliferation and activating apoptosis of infected cells; to act as inhibitors for targets such as VEGF, in age-related macular degeneration, and thrombin, or von Willebrand factor, in patients with acute coronary syndromes; to target the RNase H domain of the HIV-1 reverse transcriptase and inhibit viral replication; to transfect and activate B cells in human chronic lymphocytic leukemia (CLL); or finally, to be used as probes in CD4-cell phenotyping." }, { "input": "What is the causative agent of the \"Panama disease\" affecting bananas?", "output": "Panama disease of banana is caused by the fungus Fusarium oxysporum f. sp. cubense." }, { "input": "What is the mechanism of action of Nalmefene?", "output": "Nalmefene shows opioid receptor antagonism, binds the \u03bc-opioid receptor (MOR1) and modulates opioidergic transmission in the CNS." }, { "input": "Synostosis of which cranial structures are characteristic to the Mercedes Benz syndrome?", "output": "Synostosis of sagittal and lambdoid structures are characteristic to the Mercedes Benz syndrome." }, { "input": "Can valproic acid act as an activator of AMPK?", "output": "Yes, valproic acid canact as an activator of AMPK." }, { "input": "Can valproic acid act as an activator of AMPK?", "output": "VPA is a novel activator of AMP-activated protein kinase (AMPK)" }, { "input": "Which signaling pathways have been associated with medulloblastoma formation and growth?", "output": "Medulloblastoma comprises approximately 20% of all primary pediatric brain tumors. Multiple signaling pathways have been associated with disease formation and growth. These include the developmental pathways Hedgehog, Notch, and Wnt, as well as pathways in which the receptor tyrosine kinases (RTK) c-Met, erbB2, IGF-R and TrkC, and the oncoprotein Myc are involved." }, { "input": "What is the role of invadopodia in EMT?", "output": "In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. An important type of such membrane protrusions are the invadopodia, which have been increasingly recognized as important drivers of local invasion in metastasis. They are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix." }, { "input": "What are cancer driver genes?", "output": "Recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for 'driver' mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to 'passenger' mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation. Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression. A subset of these mutations contribute to tumor progression (known as \"driver\" mutations) whereas the majority of these mutations are effectively neutral (known as \"passenger\" mutations)." }, { "input": "What is a mitochondrial nucleoid?", "output": "A naked mtDNA molecule is longer than a typical mitochondrion and is therefore compacted in vivo to form a nucleoprotein complex, denoted the mitochondrial nucleoid." }, { "input": "What is the treatment of amiodarone-induced thyrotoxicosis?", "output": "Treatment of amiodarone-induced thyrotoxicosis is complex and may include drugs such as antithyroid drugs, beta-blockers, corticosteroids lithium as well as iopanoic acid in preparation of thyroidectomy. Total thyroidectomy and radioiodine represent alternative treatment options" }, { "input": "How does exercise affect thyroid hormone receptors expression in the heart?", "output": "Exercise has been shown to increase TR\u03b21 receptor expression in young rats. Exercise has been shown to increase both TR\u03b11 and TR\u03b21 receptor expression in aged rats." }, { "input": "Is the Drosophila Translational Control Element (TCE) involved in spermatogenesis?", "output": "Yes. The Drosophila Translational Control Element (TCE), a 12 nucleotide long sequence element, was demonstrated to be necessary for translational control of expression in the male germ line of Drosophila melanogaster." }, { "input": "What are the symptoms of abacavir hypersensitivity?", "output": "Patients receiving abacavir develop an idiosyncratic hypersensitivity reaction that can include a wide range of symptoms. The most common are: fever, enathema, skin rash, nausea, vomiting, diarrhoea, cough, gastrointestinal disorders, anaphylactic shock, respiratory symptoms." }, { "input": "What is the effect of ivabradine in heart failure with preserved ejection fraction?", "output": "I(f)-channel inhibition potentially exhibits beneficial effects in diastolic heart failure. In patients with heart failure with preserved ejection fraction (HFpEF), short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity. Ivabradine has demonstrated benefits in HFpEF without improving mortality.\tIn db/db, a model of HFpEF, ivabradine improved vascular stiffness, left ventricular contractility, and diastolic function. Furthermore, ivabradine reduces cardiac fibrosis in hypercholesterolemic rabbits." }, { "input": "Is low T3 syndrome a prognostic marker in patients with renal insufficiency?", "output": "Low fT3 is an independent predictor of death in chronic kidney disease, in particular in dialised patients at end-stage renal diseases." }, { "input": "Does burning mouth syndrome preferentially affect post-mepopausal women?", "output": "BMS is observed principally in middle-aged patients and postmenopausal women \nBMS mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%." }, { "input": "Which biomarker is widely used in the diagnosis of Ewing sarcoma?", "output": "CD99 is a hallmark marker for Ewing sarcoma and primitive neuroectodermal tumors." }, { "input": "Proteomic analyses have revealed proteins associated with the triple-negative breast cancers. List some proposed proteins.", "output": "Selected proteins of interest proposed from triple-negative cancer proteomic studies are CD44, PARP1, Mage-A4, LSR, RAB25, S100A14, MUC1, Hsp90, Actin, 14-3-3, vimentin, HSP70, CK18, moesin, IDH2, CRABP2, SEC14L2, beta-catenin, MUC18, Stat1 and CD74." }, { "input": "Which signalling pathway is involved in Tuberous Sclerosis?", "output": "Tuberous Sclerosis is a multisystem genetic disorder caused by mutation in TSC1 or TSC2 gene, that leads to hyperactivation of the mTOR signalling pathway, and subsequent dysregulation of cell growth control." }, { "input": "Can life style changes reduce oxidative stress", "output": "Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities." }, { "input": "Which is the relation between sweating and anaerobic threshold?", "output": "There is no clear evidence of the relationship between sweating and anaerobic threshold" }, { "input": "Name monoclonal antibody against SLAMF7.", "output": "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer cell-mediated antibody-dependent cellular cytotoxicity of SLAMF7-expressing myeloma cells." }, { "input": "What is the mode of action of bedaquiline?", "output": "Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents that is used for treatment of multi drug resistant tuberculosis." }, { "input": "Does helicobacter pylori infection increase risk for ischemic stroke?", "output": "Findings regarding association between helicobacter pylori infection and ischemic stroke risk are conflicting. There is evidence to suggest that helicobacter pylori infection is associated with increased risk for ischemic stroke and should be considered stroke risk factors. However, some studies reported no association between helicobacter pylori infection and stroke." }, { "input": "Which are the major types of the motor speech disorder dysarthria?", "output": "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility. There are six major types of dysarthria: \"flaccid dysarthria\" associated with lower motor neuron impairment, \"spastic dysarthria\" associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, \"ataxic dysarthria\" primarily caused by cerebellar dysfunction, and \"hyperkinetic dysarthria\" and \"hypokinetic dysarthria\", which are related to a disorder of the extrapyramidal system. The sixth is generally termed a \"mixed dysarthria\" and is associated with damage in more than one area, resulting in speech characteristics of at least two groups." }, { "input": "Is oxidative stress affected by FOXO expression?", "output": "Yes. In different cell types, induction of forkhead transcription factor FOXO1 was found to increase expression of the mitochondrial antioxidant manganese superoxide dismutase, and lead to suppression of oxidative stress." }, { "input": "Describe the mechanism of action of the LINX system for treatment of gastroesophageal reflux disease.", "output": "LINX Reflux Management System is a sphincter augmentation device designed to prevent gastroesophageal reflux due to abnormal opening of the lower esophageal sphincter (LES) by augmenting the sphincter barrier. It is implanted via laparoscopic procedure that does not alter gastric anatomy and is easily reversible." }, { "input": "Which enzyme deficiency can cause GM1 gangliosidoses?", "output": "GM1 gangliosidoses are associated with deficiency of \u03b2-galactosidase." }, { "input": "What is the characteristic feature of the Dyke-Davidoff-Masson syndrome.", "output": "Cerebral hemiatrophy (atrophy of one cerebral hemisphere) is the characteristic feature of the Dyke-Davidoff-Masson syndrome. It develops due to an insult to the brain in fetal or early childhood period. Calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures are also characteristic to the Dyke-Davidoff-Masson syndrome.\n." }, { "input": "Which gene is involved in the development of Barth syndrome?", "output": "Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS)" }, { "input": "Which gene is involved in the development of Barth syndrome?", "output": "Tafazzin, a mitochondrial acyltransferase encoded by a gene of the same name, plays an important role in cardiolipin side chain remodeling. Studies have shown that mutation-induced dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome (BTHS)." }, { "input": "What is the treatment of subacute thyroiditis?", "output": "Common treatment of subacute thyroiditis is with anti-inflammatory drug agents, namely corticosteroids" }, { "input": "What are the effects of BMAL1 deficiency?", "output": "BMAL1 deficiency is associated with premature aging and reduced lifespan and BMAL1 deficiency leads to development of stress induced senescence in vivo. Down-regulation of Bmal1 also accelerates the development of tumours, adipogenesis." }, { "input": "Which histone modifications are associated with Polycomb group (PcG) proteins?", "output": "A member of the polycomb repressive complex 2 (PRC2) directly mediates the addition of K27me3 to histone H3, a modification associated with heterochromatin, and it is believed that this activity mediates transcriptional repression. At the same time PRC2 activity results in a global increase in H3K27 acetylation. Some members of the PcG display affinity towards both histone H3 trimethylated at K9 and H3K27me3, and one CD prefers K9me3." }, { "input": "Where is the protein CLIC1 localized?", "output": "CLIC1 is an intracellular chloride ion channel that is localized both to the nucleus and to the cytolasm." }, { "input": "List phosphorylation consensus motifs for Casein Kinase 1 (CK1)?", "output": "The most common consensus motifs for CK1 are: pSer-Xaa-Xaa-Ser, K/R-X-K/R-X-X-S/T, SLS and acidic cluster motifs and SerP/ThrP-Xaa-Xaa-Ser/Thr." }, { "input": "What medication were compared in the ROCKET AF Trial?", "output": "ROCKET-AF trial compared rivaroxaban and warfarin for for prevention of stroke and embolism." }, { "input": "Describe the usefulness of the SPIKE database in human signaling pathways", "output": "The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator\u2019s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways." }, { "input": "Is the Dictyostelium discoideum proteome known?", "output": "Yes, The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. Consequently, this genomic sequence information can now be exploited to realize D. discoideum proteomics projects." }, { "input": "List proteins of lipids droplets", "output": "perilipins\nadipose differentiation-related protein\nlipid storage droplet protein 5 \ntail-interacting protein of 47 kilodaltons \nS3-12" }, { "input": "What is the Barr body?", "output": "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). Barr body is an inactivated X chromosome in the normal female somatic cell. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified. " }, { "input": "What is the Barr body?", "output": "The Barr body is the inactive X chromosome in a female somatic cell." }, { "input": "What is the Barr body?", "output": "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). " }, { "input": "What is the Barr body?", "output": "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified. " }, { "input": "What is the Barr body?", "output": "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. Despite being known for over 50 years, relatively few components of the Barr body have been identified. The Barr body, is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). However, numerous investigators have observed extreme variations in Barr body frequency in tumour cells." }, { "input": "Is single-cell analysis (SCA) possible in proteomics?", "output": "No, it is not yet feasible, although smaller pilot studies has been performed where a limited number of proteins has been analysed." }, { "input": "Is shotgun lipidomics the direct infusion of a lipid sample into a mass spectrometer?", "output": "Yes, shotgun lipidomics relies on direct infusion of total lipid extracts into a high-resolution tandem mass spectrometer." }, { "input": "How many genes are in the gene signature screened by MammaPrint?", "output": "Mammaprint has a 70 gene signature." }, { "input": "Is apixaban effective for treatment of acute venous thromboembolism?", "output": "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies." }, { "input": "Is apixaban effective for treatment of acute venous thromboembolism?", "output": "Yes, apixaban is effective for treatment of acute venous thromboembolismis. Apixiban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies." }, { "input": "Is the tricarboxylic acid (TCA) cycle affected in inflammation?", "output": "Metabolic reprogramming is implicated in macrophage activation. In many cases, intermediates of the TCA cycle are involved in the response to hypoxic conditions brought about by inflammation." }, { "input": "What are the indications for treatment with anti-hepcidin?", "output": "improving anemia control\nanemia management in hemodialysis\niron-restricted anemias" }, { "input": "How many genera comprise the Flaviviridae family?", "output": "The family Flaviviridae is comprised of three genera: Flavivirus, Pestivirus and Hepacivirus." }, { "input": "Are reduced-nicotine cigarettes effective for smoking cessation?", "output": "Yes, reduced-nicotine cigarettes are effective for smoking cessation." }, { "input": "Is the Wnt protein modified by notum?", "output": "Yes, \tNotum deacylates Wnt proteins to suppress signalling activity." }, { "input": "List functions that are evaluated with the Full Outline of Unresponsiveness score?", "output": "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration." }, { "input": "For the constructions of which organs has 3D printing been tested?", "output": "Nose, ear and meniscus prototypes/constructs have been produced with 3D (3-dimesional) printing." }, { "input": "Is ospemifene effective for treatment of dyspareunia?", "output": "Yes, ospamifene is effective for treatment of dyspareunia. Ospemifene is a selective estrogen receptor modulator, or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy." }, { "input": "Is pregabalin effective for treatment of patients with restless leg syndrome?", "output": "Yes, numerous evidence from clinical trials indicate that pregabalic is effective for treatment of patients diagnosed with restless leg syndrome." }, { "input": "What is the biological role of expansins in fungi?", "output": "Expansins are extracellular proteins that increase plant cell-wall extensibility. These wall-loosening proteins are involved in cell wall extension and polysaccharide degradation. In fungi expansins and expansin-like proteins have been found to localize in the conidial cell wall and are probably involved in cell wall remodeling during germination." }, { "input": "Can zinc finger nucleases be used to combat disease?", "output": "Yes, zinc finger nucleases are a useful tool for treating disease." }, { "input": "What is known about depression in acoustic neuroma patients?", "output": "From 10.2% to 38% acoustic neuroma patients report depression. Depression is predicted by the number of symptoms, prolonged postoperative headache, deterioration of hearing and female gender." }, { "input": "Mutation of which gene is associated with Achondroplasia?", "output": "Achondroplasia is due to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene." }, { "input": "What is the mode of action of Hsp90 inhibitors?", "output": "Pharmacologic inhibition of Hsp90 involves interaction with the ATP-binding site of the chaperone. This exerts antiproliferative effects resulting in a marked suppression of tumor growth. Following treatment with a Hsp90 inhibitor, expression of a number of proteins is affected, and most notably the Hsp90 clients, leading to dysregulation of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism, finally resulting in cancer cell death through activation of both intrinsic and extrinsic apoptotic pathways." }, { "input": "Is RET the major gene involved in Hirschsprung disease?", "output": "The RET proto-oncogene is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology." }, { "input": "Is RET the major gene involved in Hirschsprung disease?", "output": "RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology " }, { "input": "Which type of lung cancer is the most strongly associated with Lambert-Eaton syndrome?", "output": "Small-cell lung cancer is most commonly associated with Lambert-Eaton syndrome. Case reports suggest that other non-small-cell lung cancer types, such as large-cell neuroendocrine carcinoma and squamous cell carcinoma, can be also very rarely associated this syndrome." }, { "input": "What distinguishes lantibiotics from antibiotics?", "output": "Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials." }, { "input": "What distinguishes lantibiotics from antibiotics?", "output": "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. Low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it." }, { "input": "What distinguishes lantibiotics from antibiotics?", "output": "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides." }, { "input": "List three major features of the CCFDN syndrome.", "output": "Congenital cataracts, facial dysmorphism and peripheral neuropathy are three major features of the CCFDN syndrome. Other described signs and symptoms of the CCFDN syndrome include microcornea, microphthalmos, micropupil, floppy eyelid syndrome, pseudoptosis, nystagmus, congenital esotropia, impairment of distant visual acuity, ataxia, pyramidal signs, mild chorea, short stature, muscular atrophy, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, serious complications related to general anaesthesia and parainfectious rhabdomyolysis." }, { "input": "is intense physical activity associated with longevity ?", "output": "Several survival studies showed that professional athletes has higher longevity than general population. These epidemiological data matches the evidences that long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality, and also telomere length." }, { "input": "Are cyclophilins proteins that bind to prolines?", "output": "Cyclophilins are ubiquitously expressed proteins that bind to prolines." }, { "input": "Can a given genotype exhibit opposite fitness effects (beneficial and detrimental) within the same environment?", "output": "A given genotype can be either beneficial or detrimental, even deleterious, depending on the environment in which an organism lives. This is known as antagonistic pleiotropy. Antagonistic pleiotropy can operate even within the same environment. For example, in Escherichia coli, certain mutations can exhibit beneficial, deleterious or neutral fitness effects at different growth rates. Also, antagonistic pleiotropy is involved in the evolution of ageing, since a certain genotype may affect late- and early-life fitness in opposite directions." }, { "input": "Has the protein SETMAR (Metnase) a transposase domain?", "output": "Yes, the protein SETMAR (Metnase) has a transposase domain." }, { "input": "Is alternative splicing of apoptotic genes playing a role in the response to DNA or mitochondrial damage?", "output": "Yes, alternative splicing seem to play a key role in the response to DNA or mitocondrial damage as suggested by the number of apoptotic genes that are alternatively spliced, with often antagonistic roles of the isoforms generated." }, { "input": "Which oncogenes are able to induce cellular senescence?", "output": "Cellular senescence can be induced through activation or inactivation of a number of oncogenes, such as Ras, c-Abl, Raf, Myc, Skp2, BRAF, AKT, HDAC2, p38 MAPK, Caveolin-1 and Mek1." }, { "input": "What is HbVar?", "output": "HbVar (http://globin.cse.psu.edu) is a relational database of hemoglobin variants and thalassemia mutations. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\" This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci." }, { "input": "Can DMSO as an additive improve proteomic analysis results?", "output": "Quantitative precisions improved significantly when DMSO (dimethylsulfoxide) was added to the matrix solution.\nIntroducing to the 80% formic acid injection solution an organic solvent such as acetonitrile or acetonitrile-DMSO induced further retention selectivity, and increasing levels of organic solvents reduced on-column retention.\nLow percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold." }, { "input": "Can DMSO as an additive improve proteomic analysis results?", "output": "Llow percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold. Additionally, the presence of DMSO in the sample allow the retention time selectivity of the peptides." }, { "input": "The antibodies MK-3475 and CT-011 have shown promising results in treating malignancies. Which protein are they targeting?", "output": "Modulation of the immune system by targeting coinhibitory and costimulatory receptors has become a promising new approach of immunotherapy for cancer. OBJECTIVE: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. The median t1/2 of CT-011 ranged from 217 to 410 hours. The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. The recent approval of the CTLA-4-blocking antibody ipilimumab for the treatment of melanoma was a watershed event, opening up a new era in the field of immunotherapy. T-cell expression of programmed death receptor-1 down-regulates the immune response against malignancy by interacting with cognate ligands ( eg, PD-L1 ) on tumor cells; however, little is known regarding PD-1 and natural killer ( NK ) cells. " }, { "input": "The antibodies MK-3475 and CT-011 have shown promising results in treating malignancies. Which protein are they targeting?", "output": "PD-1" }, { "input": "Which are the different proteins/isoforms encoded but the ASPH (aspartate beta-hydroxylase) gene in humans?", "output": "Alternative splicing of the locus AbetaH-J-J (asparetyl-beta-hydroxylase) generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate). Aspartyl (asparaginyl)-beta-hydroxylase (AAH), has also two related transcripts, Humbug and Junctin, which lack catalytic domains. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. A human junctin isoform (isoform 1, 225 aa) was also identified and characterized. The isoform 1 has a 15 aa insertion at the amino acid residue 55 of the human junctin." }, { "input": "List processes which are under the control of the YAP protein.", "output": "Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control, cell poliferation and cancer development and tissue homeostasis and differentiation." }, { "input": "What family do mDia proteins belong in?", "output": "mDia proteins are members of the formin family." }, { "input": "Is nucleosome eviction ATP-dependent?", "output": "Yes, nucleosome eviction and chromatin remodelling depends on ATP" }, { "input": "Is TREM2 associated with Alzheimer's disease in humans?", "output": "TREM2 variants have been found to be associated with early as well as with late onset Alzheimer's disease." }, { "input": "Which is the most common measure of differences between dinucleotide relative abundance \"genomic signatures\"", "output": "The concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs). The set of dinucleotide odds ratios or 'general design' is a remarkably stable property of the DNA of an organism, and can be used to discriminate between sequences from different organisms. The average absolute dinucleotide relative abundance difference is termed delta-distance. Delta-distance is the most commonly used measure of differences bwetween \"genomic signatures\". Delta-distances between different genomic sequences in the same species are low, and are generally smaller than the between-species delta-distances." }, { "input": "Name a method for enrichment of arginine-methylated peptides.", "output": "Immunoaffinity purification using specific antibodies has been used in order to perform enrichment of methylated peptides." }, { "input": "Why do we use \"N-terminal proteomics\"?", "output": "N-terminal proteomics allows the systematic identification of protease/peptidase cleavage events revealing substrate cleavage specificities." }, { "input": "List omics technologies comprised in system biology.", "output": "System biology combines various omics technologies such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, glucomics, degradomics and fluxomics." }, { "input": "Rindopepimut is an analog of which growth factor?", "output": "Rindopepimut is an analog of EGFRvIII. It is being tested for treatment of glioblastoma multiforme" }, { "input": "Rindopepimut is an analog of which growth factor?", "output": "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. " }, { "input": "Which gene mutations are responsible for isolated Non-compaction cardiomyopathy?", "output": "The gene mutations that have been shown to be the causes of isolated non-compaction cardiomyopathy are alpha-tropomyosin, alpha-tropomyosin, troponin T and desmoplakin" }, { "input": "Which gene mutations are responsible for isolated Non-compaction cardiomyopathy?", "output": "cardiac \u03b2-myosin heavy chain gene (MYH7)\nc.349G>A (p.D117N) in the ZASP gene\nmutation in the isoform-1 specific region of the DSP C-terminus\npE96K mutation in the cardiac troponin T gene (TNNT2)" }, { "input": "From which tissue was the NCI-H520 cell-line derived?", "output": "Non-small cell lung cancer (NSCLC) cell line NCI-H520. \nSquamous cell carcinoma cell line NCI-H520." }, { "input": "From which tissue was the NCI-H520 cell-line derived?", "output": "The NCI-H520 cell-line is derived from human non-small cell lung cancer tissue." }, { "input": "Have mutations in the Polycomb group been found in human diseases?", "output": "Yes, different members of the Polycomb family have been found mutated in diseases such as primary microcephaly, nonsyndromic cleft lip and several cancers (including hemotopoietic malignancies, esophageal carcinoma, head and neck cancer or prostate cancer).\n\nExact anser:\nYes" }, { "input": "Describe the mechanism of action of drisapersen", "output": "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. It has potential for treatment of Duchenne muscular dystrophy." }, { "input": "Is microRNA(miRNA) 29 involved in post-ischemic cardiac remodeling?", "output": "miRNA 29 is involved in post-ischemic myocardial remodeling in particular in the peri-infarctual zone. miRNA 29 produces apoptosis and enhances fibrotic response." }, { "input": "What is the incidence of Edwards syndrom in the european population?", "output": "Between 0.125 and 39 in every 1000 live births. Most probably 1:5000 of live-born." }, { "input": "Is exonuclease Xrn1 a component of the P-bodies?", "output": "In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' \u2192 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place. Many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3." }, { "input": "Is exonuclease Xrn1 a component of the P-bodies?", "output": "In eukaryotic cells, degradation of bulk mRNA in the 5' to 3' direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5' to 3' exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies." }, { "input": "Is exonuclease Xrn1 a component of the P-bodies?", "output": "We show that the RNA-binding protein GW182 and the DCP1:DCP2 decapping complex are required for miRNA-mediated gene silencing, uncovering a crucial role for P-body components in the miRNA pathway. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs. Recent evidence suggests that the processing bodies may constitute specialized cellular compartments of mRNA turnover, which suggests that mRNA and protein localization may be integral to mRNA decay." }, { "input": "What is the substrate of the microbial enzyme inulinase?", "output": "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose." }, { "input": "What is the treatment of acute myocarditis?", "output": "Treatment of acute myocarditis includes antiinflammatory drugs like ibuoprofen and steroids, inotropic agents and mechanical support (intra-aortic ballon pump). TandemHeart percutaneous ventricular assist device may be used in some, more compromised, patients for few days." }, { "input": "List causative genes for autosomal recessive forms of monogenic Parkinson's disease", "output": "Causative genes for autosomal recessive forms of monogenic Parkinson's disease are:\nPARK2\nPARK7\nPINK1\nPARK9\nPARK14\nPARK15" }, { "input": "How does ranolazine affect calcium handling in the heart", "output": "Ranolazine has only a small effect on the basal calcium current, while it greatly affects whole cell calcium current when facilitated by beta-adrenoceptor or histamine receptor activation.\nRanolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload.\nRanolazine reduces Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion.\nranolazine decreases I(Na,L)-induced dysregulation of calcium cycling that contributes to the antiarrhythmic actions of this agent.\nranolazine desensitizes Ca(2+)-dependent RyR2 activation, and inhibits Ca(i) oscillations.\nranolazine ameliorates the Ca(2+) response and cross-bridge kinetics of cardiac myofilaments." }, { "input": "Which is the primary distinction between the Reverse Warburg effect and the conventional Warburg effect?", "output": "The conventional \"Warburg effect\" reffers to the metabolic shift of cancer cells towards aerobic glycolysis, due to mitochondrial dysfunction. The \"reverse Warburg effect\" or \"parasitic\" energy-transfer, is a model of \"two-compartment tumor metabolism\". In this model, cancer cells secrete hydrogen peroxide (H2O2), initiating oxidative stress and aerobic glycolysis in the tumor stroma. The cancer-associated fibroblasts of the stroma are glycolytic and lack detectable mitochondria. These glycolytic stromal cells produce mitochondrial fuels (L-lactate, ketone bodies and chemical building blocks, such as amino acids -glutamine-, and nucleotides) that are then transferred to oxidative epithelial cancer cells. Lactate and ketones drive cancer cell oxidative mitochondrial metabolism (OXPHOS), and building blocks sustain the anabolic needs of rapidly proliferating cancer cells. Therefore, according to the \"reverse Warburg effect\", stromal catabolism fuels anabolic tumor growth via energy transfer. Thus, in \"reverse Warburg effect\" the cancer-associated fibroblasts of the stroma undergo aerobic glycolysis, rather than epithelial cancer cells themselves, as proposed by the conventional \"Warburg effect\"." }, { "input": "What is the role of per genes in circadian rhythm control?", "output": "PER1 and PER2 genes are involved in cell cycle regulation and tumor suppression, controlling expression of genes such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha." }, { "input": "Can sorafenib activate AMPK?", "output": "Sorafenib induces persisten AMPK activation" }, { "input": "What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?", "output": "The fusion protein BCR-ABL" }, { "input": "When was empagliflozin FDA approved?", "output": "Empagliflozin was approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM)." }, { "input": "Which R/bioconductor package is used for integrative genomics visualizations?", "output": "Sushi.R is a flexible, quantitative and integrative genomic visualizations for publication-quality multi-panel figures using common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE). Sushi.R is open source and made publicly available through GitHub (https://github.com/dphansti/Sushi) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/Sushi.html)." }, { "input": "List symptoms of congenital toxoplasmosis triad.", "output": "Classic triad of toxoplasmosis include hydrocephalus, cerebral calcification and chorioretinitis." }, { "input": "How many genes are imprinted in the human genome?", "output": "Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. " }, { "input": "How many genes are imprinted in the human genome?", "output": "Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. To date, fewer than 100 imprinted genes have been identified in the human genome." }, { "input": "Is exome sequencing efficient for the detection of germline mutations?", "output": "Exome sequencing is an efficient, sensitive, rapid and relatively cheap method for detection of germline mutations." }, { "input": "Which cellular processes are regulated by Nanog?", "output": "The pluripotency sustaining factor Nanog, controls a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination. Elevated expression of Nanog has also been reported to result in clonal expansion of murine ESCs, but it also plays a role in tumor development. A positive regulator of cell proliferation, it is essential for G1 to S transition in human embryonic stem cells while it regulates primordial germ cell migration." }, { "input": "In which cells are A-type lamins expressed?", "output": "In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type. Human cells with reduced expression of the major B-type lamin protein, lamin B1, were generated using RNA interference. In addition, horizontal cells and a subpopulation of retinal ganglion cells expressed lamin A and C, while photoreceptor cells expressed neither lamin A nor C, and all other retinal neurons expressed lamin C only. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6." }, { "input": "In which cells are A-type lamins expressed?", "output": "Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present. Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B." }, { "input": "What is the definition of autophagy?", "output": "There are several definitions of autophagy. Among them, autophagy can be defined as a non- apoptotic programmed cell death that consists on a catabolic trafficking pathway for bulk destruction and turnover of long-lived proteins and organelles via regulated lysosomal degradation." }, { "input": "Gene silencing can be achieved by RNA interference (RNAi) in eukaryotic organisms. What is the name of the analogous process in prokaryotic organisms?", "output": "Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium." }, { "input": "Between which types of DNA bases are mutational biases introduced due to directional mutation pressure?", "output": "The rates of substitution mutations in two directions, v (from an AT-pair to a GC-pair) and u (from a GC-pair to an AT-pair), are usually not the same. Thereafter, the effect of mutation on a genome is not random but has a directionality toward higher or lower GC content of DNA. The net effect, v/(u + v), has previously been defined as directional mutation pressure. Thus, directional mutation pressure (GC/AT pressure) refers to mutational biases between alpha-bases (A or T) and gamma-bases (G or C)." }, { "input": "Is it feasible to determine the complete proteome of yeast?", "output": "Yes, since the complete genome of yeast is known." }, { "input": "Which mutations of alpha-myosin heavy chain gene are implicated in hypertrophic cardiomyopathy?", "output": "The following mutations of alpha-myosin heavy chain gene are implicated in hypertrophic cardiomyopathy: R403Q; Q1065H and Arg-249-->Gln" }, { "input": "Which are the cardiac manifestations of Marfan syndrome?", "output": "Cardiac manifestations of Marfan syndrome include aortic root dilation,aortic regurgitation, mitral valve prolapse and mitral valve regurgitation." }, { "input": "How is connected \"isolated Non-compaction cardiomyopathy\" with dilated cardiomyopathy?", "output": "Mutations in cardiac beta-myosin heavy chain and alpha-tropomyosin link isolated Non-compaction cardiomyopathy with dilated cardiomyopathy" }, { "input": "What is the role of AMPK in diabetic cardiomyopathy?", "output": "AMPK activation protects cardiac structure and function by increasing cardiac autophagy in the diabetic heart. Decreased AMPK activity and the subsequent reduction in cardiac autophagy are central to the development of diabetic cardiomyopathy. In fact, dissociation of Bcl-2 from Beclin1 may be an important mechanism for preventing diabetic cardiomyopathy via AMPK activation that restores autophagy and protects against cardiac apoptosis. In addition, genetic inhibition of AMPK in cardiomyocytes attenuates cardiac autophagy, exacerbates cardiac dysfunction and increases mortality in diabetic mice. The modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy. Stimulation of AMPK by metformin or trimetazidine administration may represent a novel approach to treat diabetic cardiomyopathy." }, { "input": "Are circRNAs associated with diseases and traits?", "output": "Yes. Circular RNAs (circRNAs) play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation." }, { "input": "Which is the most common cause of sudden cardiac death in young athletes?", "output": "the most common cause of sudden cardiac death in young athletes is hypertrophic cardiomyopathy" }, { "input": "Could the Menzerath-Altmann law be proved mathematically trivial in genomes?", "output": "Yes. The view of Menzerath-Altmann law in genomes, as inevitable, is seriously flawed." }, { "input": "What is the rate of survival after commotio cordis?", "output": "Survival rates for commotio cordis are low, even when resuscitation is performed. Survival rates vary between 10% and 28%." }, { "input": "What is the oldest human sample analysed by paleontology proteomics?", "output": "The Tyrolean Iceman's brain is the oldest (5300 years old) human sample that has been studied by paleoproteomics." }, { "input": "What are the results of loss of the protein Lon1 in the plant Arabidopsis?", "output": "Loss of Lon1 in Arabidopsis changes the mitochondrial proteome leading to altered metabolite profiles and growth retardation. Additionaly, seedling establishment is also impaired." }, { "input": "Which gene is involved in Giant Axonal Neuropathy?", "output": "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin" }, { "input": "Which gene is involved in Giant Axonal Neuropathy?", "output": "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene, resulting in a loss of a ubiquitously expressed protein, gigaxonin." }, { "input": "Are there studies representing the involvement of Notch mutations in neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome?", "output": "The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in organisms as diverse as insects, nematodes, echinoderms and mammals. Disruptions in conserved developmental pathways frequently result in inherited congenital anomalies in humans. Mutations in genes encoding Notch pathway components underlie human disease such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome." }, { "input": "Are there any functional differences between Mfd and its human Cocaine syndrome protein B (CSB) homolog?", "output": "Both Cockayne syndrome protein B (CSB) and Mfd are involved in transcription-coupled repair. CSB is the human TCR coupling factor and Mfd is the bacterial TCR coupling factor. However, unlike Mfd, CSB does not act as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. Moreover, Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage." }, { "input": "What is membrane scission?", "output": "Membrane scission is the final step in order to complete the budding process, pinching off of the vesicle. To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane. The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers." }, { "input": "How many TAp73 isoforms have been identified in humans?", "output": "The TP73 gene, due to the presence of two promoters (P1 and P2) in its 5' flanking region, encodes a fully transcriptionally active domain (TAp73) and the amino terminus deleted (\u0394Np73). TAp73 possesses pro-apoptotic properties, while deltaNp73 has anti-apoptotic functions. Alternative 3'-end splicing results in generation of at least seven TAp73 distinctive isoforms ( \u03b1, \u03b2, \u03b3, etc )." }, { "input": "How many TAp73 isoforms have been identified in humans?", "output": "The Trp73 gene belongs to the p53 family of transcription factors and, like the other members, is transcribed into different isoforms [1-4]. TP73 gene contains two promoters, encoding the transcriptional domain-containing (TAp73) and the amino deleted (DNp73) isoforms [5, 6]. Furthermore alternative splicing at the 3'-end (to generate a, b, g, etc isoforms) and 5'-end (to generate D2, D3 and D2-3 isoforms) results in generation of at least 14 different transcripts, with different abilities to promote or repress apoptosis [7, 8]. (PMID: 22388545)" }, { "input": "Is the yeast \u039cac1 transcription factor induced upon copper deficiency?", "output": "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions." }, { "input": "What is the mechanism of DNA replication termination in vertebrates?", "output": "Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly. DNA synthesis does not slow detectably as forks approach each other, and leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly." }, { "input": "Which are the different members/isoforms of the Ras oncogenes?", "output": "Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions." }, { "input": "Which are the different members/isoforms of the Ras oncogenes?", "output": "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)" }, { "input": "Which is the subcellular localization of ERAP2?", "output": "Endoplasmic reticulum aminopeptidase 2 (ERAP2) is localized to the luminal side of the endoplasmic reticulum." }, { "input": "Have thyronamines effects on fat tissue?", "output": "There is not clear evidence that thyronamines have direct effect on adipose tissue" }, { "input": "What are the names of anti-CD52 monoclonal antibody that is used for treatment of multiple sclerosis patients?", "output": "Alemtuzumab and Campath-1H are the names of anti-CD52 monoclonal antibody that is used for treatment of multiple sclerosis patients. It has been shown to be effective for treatment naive and treatment resistant multiple sclerosis patients." }, { "input": "Is there a package in R/bioconductor for classification of alternative splicing?", "output": "Yes. SpliceR is an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data." }, { "input": "Which brain structures have been investigated as potential targets for deep brain stimulation of patients suffering from major depression?", "output": "Subgenual cingulate gyrus, the anterior limb of the capsula interna, nucleus accumbens, medial forebrain bundle, habenula, and caudate nucleus have been investigated as potential targeted for the deep brain stimulation of patients suffering from major depression." }, { "input": "Is alemtuzumab effective for remission induction in patients diagnosed with T-cell prolymphocytic leukemia?", "output": "Yes, alemtuzumab (anti-CD52, Campath-1H) is effective for remission induction in patients diagnosed with T-cell prolymphocytic leukemia. Alemtuzumab can be administered in combination with other chemotherapeutic agents or as mono-therapy. Response rate to alemtuzumab is more than 90%. Alemtuzumab therapy is associated with improved survival of T-cell prolymphocytic leukemia patients." }, { "input": "What is the association between moon cycle and rupture risk of intracranial aneurysms?", "output": "It has been reported that moon phases correlate with the incidence of aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysms. However, other authors have found no correlation between incidence of aneurysmal SAH, location of the aneurysm, initial clinical presentation, or amount of subarachnoid blood and the lunar cycle." }, { "input": "Is there an association between TERT promoter mutation and survival of glioblastoma patients?", "output": "Telomerase reverse transcriptase (TERT) promoter are associated with shorter survival of glioblastoma patients. Prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations." }, { "input": "Is bapineuzumab effective for treatment of patients with Alzheimer's disease?", "output": "Clinical trials have demonstrated that bapineuzumab, a humanized monoclonal antibody against the end terminus of amyloid plaques, is not effective for treatment of patients with Alzheimer's disease. The burden of beta amyloid plaques was reduced in response to bapineuzumab therapy. However, bapineuzumab therapy did not improve cognitive functioning and was associated with significant adverse effects in Alzheimer's disease patients." }, { "input": "Which deiodinase polymorphisms are implicated in arterial hypertension?", "output": "Two deiodinase polymorphisms are implicated in arterial hypertension: Ala92 type 2 deiodinase allele and rs7140952 polymorphism of DIO2" }, { "input": "Which deiodinase polymorphisms are implicated in arterial hypertension?", "output": "At least two deiodinease polymorfisms are implicated in arterial hypertension:\nDIO 2 Thr92Ala\nrs7140952" }, { "input": "At which kind of individuals is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events?", "output": "Treatment of subclinical hypothyroidism is associated with fewer cardiovascular events in younger individuals, but this issue has not been resolved yet in elderly people." }, { "input": "Is intense physical activity associated with longevity?", "output": "YES:" }, { "input": "How homoplasy affects phylogenetic reconstruction?", "output": "Evolutionary processes create both newly derived characteristics shared by related descendant lineages (homology) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy). Homology arises by divergent evolution from a common ancestor and provides us with a phylogenetic signal, while homoplasy arises by convergent evolution or random coincidence. Homoplastic characters do not allows branch points and clade membership to be accurately estimated, as they may group unrelated taxa together. Such characters add \"noise\" in phylogenetic analysis and are not informative for the population genetics and the phylogenetic reconstruction of closely related taxa. In phylogenetic reconstruction, homoplasy leads to inaccurate conclusions about phylogenetic relationships among operational taxonomic units, and characters with high degree of homoplasy result in incongruences of cladistic relationships." }, { "input": "What is known about the association between the use of selective serotonin reuptake inhibitors during pregnancy and risk for autism in offspring?", "output": "Greater risk for autism spectrum disorders has been reported among mothers that have used selective serotonin reuptake inhibitors during pregnancy. However, others did not find an association between the use of selective serotonin reuptake inhibitors during pregnancy and risk for autism in offspring. Also, selective serotonin reuptake inhibitor use during pregnancy were associated with a greater number of gastrointestinal complaints in children with autism spectrum disorders." }, { "input": "Which transcription factors are involved in E-cadherin repression during EMT?", "output": "Downregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression. Overexpression of Snail1 (Snail), Snail2 (Slug), Zeb1, Twist, SIP1 and DeltaEF1 have been found to mediate E-cadherin repression, induce the mesenchymal markers vimentin and fibronectin, and finally promote the migratory and invasive capabilities in cancer cells." }, { "input": "Is desmin an intermediate filament protein involved in Dilated Cardiomyopathy (DCM)?", "output": "According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Desmin defects were also recently identified in 1 familial dilated cardiomyopathy." }, { "input": "Is lambrolizumab effective for treatment of patients with melanoma ?", "output": "Lambrolizumab, a programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibody, has been shown to be effective for treatment of patients with melanoma. High rate of sustained tumor regression with mainly minimal adverse effects in melanoma patients treated with lambrolizumab has been reported. Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year." }, { "input": "Is lambrolizumab effective for treatment of patients with melanoma ?", "output": "Yes. In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects." }, { "input": "List human diseases involving genomic imprinting.", "output": "Prader Willi Syndrome\nAngelman syndrome\nBeckwith-Wiedemann syndrome\nHydatidiform mole\nCancer\nSilver-Russell syndrome\nDiabetes" }, { "input": "Why are insulators necessary in gene therapy vectors?", "output": "a) They inhibit oncogene activation upon vector integration and b) They maximize the probability of vector expression upon integration in heterochromatinic regions" }, { "input": "Why are insulators necessary in gene therapy vectors?", "output": "The presence of insulators in gene therapy vectors is necessary because these elements have the ability to help overcome the problem of position effects, caused due to random integration of the therapeutic genes in the host cell genome." }, { "input": "Which deficiency is the cause of restless leg syndrome?", "output": "It has been well-documented that iron deficiency is the cause of restless leg syndrome. Magnesium and ferritin were also associated with restless leg syndrome." }, { "input": "What histone modification is recognized by the bromodomain?", "output": "Acetylated lysines in histones (generally H3 and H4)" }, { "input": "What memory problems are reported in the \" Gulf war syndrome\"?", "output": "Loss of memory and dysmnesia are memory problems reported in the \" Gulf war syndrome\". Patients suffering from this syndrome often have other\nnonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain and sexual dysfunction." }, { "input": "Is cadasil syndrome a hereditary disease?", "output": "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. CADASIL is the most common form of hereditary cerebral angiopathy." }, { "input": "Which neuroendocrine tumors are associated with specific tumor syndromes?", "output": "Neuroendocrine tumors are a heterogeneous group of benign and malignant neoplasias, detectable in the context of hereditary tumor syndromes in up to 30% of cases. Neuroendocrine tumors include medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma." }, { "input": "How many periods of regulatory innovation led to the evolution of vertebrates?", "output": "Investigators proposed that there have been three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers." }, { "input": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "output": "Yes, nintedanib is approved for Idiopathic Pulmonary Fibrosis treatment. Nintedanib was shown to slow the decline in lung function, decrease acute exacerbations, decrease the annual rate of decline in forced vital capacity and increase time to acute exacerbation." }, { "input": "What is the role of SERCA in diabetic cardiomyopathy?", "output": "Diabetic cardiomyopathy is accompanied by reduced SERCA levels and activity in later stages. The up-regulation of SERCA2a in the early phase of type 2 diabetes is an important physiological adaptation of the heart." }, { "input": "Is pesticide exposure associated with polyneuropathy?", "output": "Yes, it is associated with peripheral neuropathy." }, { "input": "Is pesticide exposure associated with polyneuropathy?", "output": "Yes, pesticide exposure is associated with delayed polyneuropathy. Electrophysiological studies have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Pesticide exposure was also implicated in Alzheimer's disease, suicide attempts and affective disorders." }, { "input": "What is the methodological principle of ChIA-PET?", "output": "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. To minimize non-specific noise and reduce complexity, as well as to increase the specificity of the chromatin interaction analysis, chromatin immunoprecipitation (ChIP) is used against specific protein factors to enrich chromatin fragments of interest before proximity ligation. Combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall." }, { "input": "What is the methodological principle of ChIA-PET?", "output": "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. It converts functional chromatin structure into millions of short tag sequences. By combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors." }, { "input": "Is there an association between borna virus and brain tumor?", "output": "There is no data to suggest an association between borna virus and brain tumor. Borna disease virus establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures causing cellular damage. Infected neural cells, include astrocytes, neurons, oligodendroglioma cell line. Borna disease virus replicates and can cause damage of brain cells." }, { "input": "List medication interfering with purine metabolism that are used for treatment of T-cell prolymphocytic leukemia?", "output": "Deoxycoformycin and pentostatin are purine analogs that interfere with purine metabolism and are used for treatment of T-cell prolymphocytic leukemia patients." }, { "input": "Does PU.1 (SPI1) affect NF-kB binding?", "output": "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs). Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified." }, { "input": "Does PU.1 (SPI1) affect NF-kB binding?", "output": "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs)." }, { "input": "Does the majority of the mitochondrial genomes abide to the second parity rule (PR2)?", "output": "A large number of mitochondrial genomes significantly deviate from the 2nd parity rule, in contrast to the eubacterial ones. This behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria." }, { "input": "What is the association between h-index and academic rank in academic neurosurgery?", "output": "Greater h-index is associated with greater academic rank in academic neurosurgery. The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors was shown to be 2, 5, 10, and 19, respectively. In addition, h-index was shown to be predictive of NIH funding, fellowship training, academic productivity and salary." }, { "input": "Is there an association between bruxism and reflux?", "output": "Yes, bruxism is associated with reflux. Sleep bruxism is prevalent in GERD patients." }, { "input": "What is known about the value of mindfulness interventions in prostate cancer patients?", "output": "In prostate cancer patients, mindfulness interventions were well accepted and were effective in reducing stress, anxiety, avoidance, fear of cancer recurrence, cortisol levels and blood pressure, and improving quality of life, sleep quality and immune system functioning. In addition, mindfulness interventions promoted initiation of healthy dietary changes and decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer." }, { "input": "What is known about prostate cancer screening in the UK ?", "output": "There is still no national screening programme established in the UK. Prostate cancer screening of asymptomatic men is not recommended by the National Screening Council at present and is not encouraged in the NHS. However, PSA tests are being performed for prostate cancer screening. The CAP and ProtecT trials are aimed to evaluate prostate cancer screening in the UK." }, { "input": "Which hormone abnormalities are common in Williams syndrome ?", "output": "Thyroid hormone abnormalities are common in Williams syndrome. Oxytocin and vasopressin, cortisol, growth hormone and calcitonin were also implicated in the Williams syndrome." }, { "input": "The secreted frizzled-related protein 3 (sFPR3) is altered in human cancers.\nAre its level found to increase or to decrease?", "output": "SFRPs are down-regulated in several cancers and this is often correlated with poor prognosis, as has been shown for breast, colorectal, and a number of other cancers. (PMID: 21494614) We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. (PMID: 20160027)" }, { "input": "The secreted frizzled-related protein 3 (sFPR3) is altered in human cancers.\nAre its level found to increase or to decrease?", "output": "Secreted frizzled-related protein 3 is potentially acting as a tumor suppressor gene, thus it is down-regulated (decreased) in some cancers." }, { "input": "Albumin depletion is a common first step for proteomic analysis of CSF fluid. What is the advantage and disadvantage of this procedure?", "output": "Depletion of the high abundant protein Albumin from CSF samples is improving the detection of lower abundant proteins but may also lead to the potential loss of non-target proteins." }, { "input": "How are lincRNA affecting the regulation of gene expression?", "output": "lincRNA may function either as modulators of epigenetic mark deposition or as endogenous antagonists for microRNA binding. A lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. Mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation. Observed biases in lincRNA genomic locations and expression profiles are consistent with some of these lincRNAs being involved in the regulation of neighboring protein-coding genes with developmental functions." }, { "input": "Which is the protein encoded by the human gene GRIK?", "output": "Glutamate Receptor Ionotropic Kainate" }, { "input": "Which residue of alpha-synuclein was found to be phosphorylated in Lewy bodies?", "output": "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson's disease patients where it mainly accumulates in the Lewy bodiesApproximately 90% of \u03b1-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129). In contrast, only 4% or less of total \u03b1-syn is phosphorylated at this residue in the normal brain. This suggests that the accumulation of Ser129-phosphorylated \u03b1-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease" }, { "input": "Which residue of alpha-synuclein was found to be phosphorylated in Lewy bodies?", "output": "Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies, which are characteristic pathologic lesions of Parkinson disease." }, { "input": "Which residue of alpha-synuclein was found to be phosphorylated in Lewy bodies?", "output": "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinsons disease patients where it mainly accumulates in the Lewy bodies" }, { "input": "Which residue of alpha-synuclein was found to be phosphorylated in Lewy bodies?", "output": "Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson s disease patients where it mainly accumulates in the Lewy bodies " }, { "input": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "output": "Yes, paroxetine is effective and FDA approved treatment of women with premenstrual dysphoric disorder. A number of well designed clinical trials have confirmed efficacy and safety of both continuous or intermittent regiments of paroxetine for treatment of premenstrual dysphoric disorder. A number of other antidepressants and hormaonal therapies were also shown to be effective and are FDA approved for treatment of women with premenstrual dysphoric disorder." }, { "input": "What is known about thalidomide therapy and survival of glioblastoma patients?", "output": "Findings regarding clinical value of thalidomide in terms of survival in patients with glioblastoma remain mixed. It has been shown that thalidomide can improve survival of recurrent glioblastoma patients. However, other authors have not confirmed these findings. Furthermore, thalidomide did not improve survival of newly diagnosed glioblastoma and pediatric glioblastoma patients." }, { "input": "Is endostatin a proangiogenic factor?", "output": "No, endostatin is an antiangiogenic factor" }, { "input": "List Genes associated with adolescent idiopathic scoliosis", "output": "Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis." }, { "input": "List Genes associated with adolescent idiopathic scoliosis", "output": "No genetic associations have yet been found to adolescent idiopathic scoliosis." }, { "input": "Can botulism poisoning of a pregnant woman harm her fetus?", "output": "Botulinum toxin, which causes botulism, is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, botulinum toxin has a high molecular weight, and does not appear to cross the placenta. Based on the study cases reported in the literature, botulism poisoning during pregnancy does not appear to increase the risk of adverse outcome in the fetus." }, { "input": "List the off-label use of SSRIs", "output": "depression during childhood and adolescence\nPremature ejaculation (PE)\nerectile dysfunction\nInsomnia\npostprostatectomy established stress urinary incontinence.\nmood and anxiety disorders during pregnancy and breast feeding\nsymptoms of vasomotor dysregulation (hot flashes) associated with the menopausal transition and sex hormone deprivation\n..off-label uses include the treatment of bulimia, benzodiazepine/alcohol dependence, fibromyalgia, central nervous system degenerative diseases (behavioral disorders in dementia and other organic disorders), schizophrenia, chronic pain disease and diabetic neuropathy, sexual dysfunction." }, { "input": "Which is the definition of pyknons in DNA?", "output": "Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA, which have additional nonoverlapping instances in the untranslated and protein-coding regions. They are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome." }, { "input": "Does a linker histone exist in the yeast genome?", "output": "Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. These results suggest that HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin. The binding was structure specific, since the use of double-stranded DNA, or a mutant Hho1p in which the second DNA binding site of globular domain 1 was abolished, resulted in a significant decrease in bridged binding." }, { "input": "Does a linker histone exist in the yeast genome?", "output": "Hho1p is a bona fide linker histone" }, { "input": "Does a linker histone exist in the yeast genome?", "output": "In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1. The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes." }, { "input": "What is the role of deadenylases in the cell?", "output": "The 3'-poly(A) tail, found on mRNAs, is enzymatically shortened by a process referred to as \"deadenylation\" which is carried out by deadenylases. Deadenylases are magnesium dependent exoribonucleases that specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'-->5' direction with the release of 5'-AMP as the product. They consist of three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain." }, { "input": "What molecule is targeted by brodalumab?", "output": "Interleukin-17. Brodalumab is anti interleukin-17 monoclonal antibody." }, { "input": "How long, in kb (kilobases), is a \"Long interspersed nuclear element\"?", "output": "The retrotransposon known as long interspersed nuclear element-1 (L1) is 6-7 kb long," }, { "input": "Which is the gene mutated in type 1 neurofibromatosis?", "output": "NF1 gene, encoding neurofibromin 1" }, { "input": "List receptors of the drug Cilengitide", "output": "Cilengitide binds \u03b1v\u03b23 and \u03b1v\u03b25 integrins. It inhibits attachment and invasion of malignant cells. Thus, cilengitide is being tested for treatment of cancer patients." }, { "input": "Can protein coding exons originate from ALU sequences?", "output": "Yes. Intronic ALUs can evolve into exons by the activation of splice signals residing within the ALU sequence. While most ALU exons do not add or modify the coding capacity of the resulting transcript, examples have been identified of ALU exons becoming protein coding." }, { "input": "How could U1 small nuclear RNA be used in therapeutics?", "output": "Until now, two main types of therapeutic strategies have been developed using U1 small nuclear RNA (snRNA): 1) Production of a defective, but partially functional protein, with the help of exon skipping, through modulation of pre-mRNA splicing, and 2) Correction of pathogenic effects of splice donor site mutations with the use of U1 snRNA adapted to the defective variant." }, { "input": "What is the influence of patent expiry on ACE inhibitor prescribing.", "output": "Patent expiry has different effects on prescribing in different systems. It leads to decreased cost but no decreased refill compliance in countries like Sweden, Germany etc. In countries like Taiwan, where doctors profit directly from dispensing, patients are switched to ARBs which are more costly." }, { "input": "Is there evidence that tomato juice lowers cholesterol levels?", "output": "Yes, there is evidence to suggest that tomato juice (and other tomato products) can decrease cholesterol concentrations. It was shown that tomatoes inhibit cholesterol biosynthesis." }, { "input": "Are there transposon-free regions in mammalian genomes?", "output": "Yes. Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation." }, { "input": "Are messenger RNA molecules epigenetically methylated?", "output": "Yes, methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts." }, { "input": "Which genes are more frequently affected by somatic mutations in Chronic Lymphocytic Leukemia", "output": "TP53, ATM, NOTCH1, XPO1, MYD88, KLHL6, SF3B1, ZMYM3, MAPK1, FBXW7 and DDX3X" }, { "input": "How effective is the dentritic cells treatment on cancer?", "output": "Another approach to cancer therapy takes advantage of the normal role of the dendritic cell as an immune educator. Dendritic cells grab antigens from viruses, bacteria, or other organisms and wave them at T cells to recruit their help in an initial T cell immune response. This works well against foreign cells that enter the body, but cancer cells often evade the self/non-self detection system. By modifying dendritic cells, researchers are able to trigger a special kind of autoimmune response that includes a T cell attack of the cancer cells. Because a cancer antigen alone is not enough to rally the immune troops, scientists first fuse a cytokine to a tumor antigen with the hope that this will send a strong antigenic signal. Next, they grow a patient's dendritic cells in the incubator and let them take up this fused cytokine-tumor antigen. This enables the dendritic cells to mature and eventually display the same tumor antigens as appear on the patient's cancer cells. When these special mature dendritic cells are given back to the patient, they wave their newly acquired tumor antigens at the patient's immune system, and those T cells that can respond mount an attack on the patient's cancer cells." }, { "input": "What is the mode of inheritance of nemaline myopathy?", "output": "Nemaline myopathy has a autosomal dominant or recessive mode of inheritance." }, { "input": "Which syndrome is NHE6 associated with?", "output": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal Na+/H+ exchanger 6 (NHE6) are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by microcephaly, severe global developmental delay, autistic behavior, early onset seizures and ataxia." }, { "input": "What is known about the reimbursement of Viagra", "output": "Coverage of Viagra/Sildenafil for erectile dysfunction by health insurance plans is a contentious issue in developed countries. There are data of the limitations (6 per month) and co-payments (26.6%) by patients in the US.\nThe costs for Viagra/Sildenafil for PAH (pulmonary artery hypertension) appear to be covered by health insurances in the US." }, { "input": "Why is lock mass used in Orbitrap measurements?", "output": "The lock mass is a compound of known mass and is used to compensate for drifts in instrument calibration." }, { "input": "Which virus is Cidofovir (Vistide) indicated for?", "output": "Cidofovir is commonly used in the treatment of cytomegalovirus (CMV) infection and disease." }, { "input": "Have gnotobiotic animal models been used for the study of bowel disease?", "output": "Yes, gnotobiotic animals (e.g. mice) have been used for the study of bowel disease (e.g. inflammatory bowel disease)." }, { "input": "List chromosomes that have been linked to Arnold Chiari syndrome in the literature.", "output": "Chromosomes 1, 3, 5, 6, 8, 9, 12, 13, 15, 16, 18, 22, X and Y have been reported in association with Arnold Chiari syndrome in genetic linkage studies and individual case reports." }, { "input": "Which translocation is the hallmark of Ewing sarcoma?", "output": "Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients" }, { "input": "Which translocation is the hallmark of Ewing sarcoma?", "output": "The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24;12), is detected in 95% of Ewing sarcoma patients." }, { "input": "Which translocation is the hallmark of Ewing sarcoma?", "output": "The hallmark of Ewing s sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene " }, { "input": "Is invasion and metastasis one of the hallmarks of cancer?", "output": "Yes, invasion and metastasis are one of the so-called hallmarks of cancer." }, { "input": "Is it possible to detect survivin protein expression in normal human adult tissues?", "output": "No. Survivin is an inhibitor of apoptosis that is undetectable in normal differentiated tissues of adult human." }, { "input": "Is it possible to detect survivin protein expression in normal human adult tissues?", "output": "Most normal adult tissues do not express survivin, thymus and testis are the only exceptions." }, { "input": "List symptoms of Meigs' Syndrome.", "output": "Meigs' syndrome is a benign ovarian tumor associated with ascites and pleural effusion." }, { "input": "What is the effect of CRD-BP on the stability of c-myc mRNA?", "output": "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack." }, { "input": "What is the effect of CRD-BP on the stability of c-myc mRNA?", "output": "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance " }, { "input": "What is the molecular function of psoralen photobinding on DNA?", "output": "The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix." }, { "input": "Is progesterone effective for treatment of patients with traumatic brain injury based on clinical trial data?", "output": "No. Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. However, a recent large clinical trial showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials." }, { "input": "Is there a role for the cylindromatosis tumor suppressor (CYLD) in lung cancer?", "output": "To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF - B activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF - B activity. Cyld encodes a 956-amino acid deubiquitinating enzyme, which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 mice ) using a conditional approach. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. " }, { "input": "Is there a role for the cylindromatosis tumor suppressor (CYLD) in lung cancer?", "output": "To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF - B activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B activity. Cyld encodes a 956-amino acid deubiquitinating enzyme, which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 mice ) using a conditional approach. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer. " }, { "input": "Is there a role for the cylindromatosis tumor suppressor (CYLD) in lung cancer?", "output": "Yes. Down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. Fibroblasts from Cyld(Delta 9/Delta 9) embryos had hyperactive nuclear factor kappaB and c-Jun kinase pathways compared with control fibroblasts. Cyld(Delta 9/Delta 9) newborn mice were smaller than wild-type littermates with a short and kinky tail and no major developmental defects. However, Cyld(Delta 9/Delta 9) mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld(Delta 9/Delta 9) lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle and endothelial structures. Thus, it is thought that CYLD has an important role in lung maturation, which may underlie the development of many cases of lung cancer." }, { "input": "Which medical diagnostic tests are used to test kidney function?", "output": "Most common tests used in diagnosing normal kidney function include blood tests such as serum creatinine levels, glomerular filtration rate (GFR) and blood urea nitrogen (BUN) levels, also medical imaging tests like ultrasound and CT Scan. Additionally kidney biopsy is used in more direct but invasive approach. Lastly, and probably the most relevant tests to kidney function are urine tests along the lines of urinalysis, urine protein levels and microalbuminuria creatinine clearance." }, { "input": "Against which protein is the antibody used for immonostaining of Lewy bodies raised?", "output": "alpha-Synuclein is a presynaptic protein, which was identified as a specific component of Lewy bodies (LB) and Lewy neurites. Therefore, immunostaining for detecting the presence of Lewy bodies is carried out using antibodies against alpha-synuclein." }, { "input": "Which are the main causes of fetal echogenic bowel?", "output": "Fetal echogenic bowel is mainly associated to feto-maternal, intramniotic bleeding but in several cases it is linked to cystic fibrosis, cytomegalovirus (CMV), herpes simplex virus and other viral infections and fetal aneuploidy." }, { "input": "Which are the main causes of fetal echogenic bowel?", "output": "Fetal echogenic bowel (FEB) is a soft marker found on second trimester sonography. (PMID: 22990134) A disorder was diagnosed in 32.2% of the fetuses, cystic fibrosis being the most commonly identified (7.6%). We also found digestive malformations (7.0%), chromosomal abnormalities (3.7%), and maternofetal infections (3.7%). (PMID: 20932506) Brightly echogenic bowel in the second trimester was found to be associated with a significant risk of fetal aneuploidy. (PMID: 1415421) echogenic bowel does not uniformly herald an abnormal outcome. Echogenic bowel coexistent with other abnormalities (such as growth deficiency or structural malformations) may be a comarker for aneuploidy. (PMID: 8142051) 112 cases (57%) had a known etiology, which included chromosomal abnormality (7%), infection (4%), cystic fibrosis (1.5%), bowel abnormality (3%), bleeding or stained amniotic fluid (11%), Doppler abnormality (14%), malformation (16%) and miscellaneous (0.5%) (PMID: 12835583)" }, { "input": "How does trimetazidine affect intracellular kinase signaling in the heart?", "output": "Trimetazidine activates AMPK in diabetic myocardium. Trimetazidine when administered before reperfusion results in activation of p38 mitogen-activated protein kinase and Akt signaling. Trimetazidine when administered during reperfusion does not affect p38MAPK and JNK activation." }, { "input": "Which is the enzymatic activity of the myotubularin family of proteins?", "output": "The myotubularin family of proteins are lipid inositol phosphatases" }, { "input": "Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?", "output": "The set of dinucleotide relative abundances can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome. Thus, dinucleotide relative abundance profiles are species-type specific. These profiles are computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). Dinucleotide relative abundance \"genomic signatures\" are strand-independent second-order DNA features. Thus, they cannot be used to detect DNA strand asymmetries." }, { "input": "What is the percentage of responders to tetrabenazine treatment for dystonia in children?", "output": "Tetrabenazine is used empirically in the treatment of dystonia in children with variable success. Observational studies report improvement of up to > 60% of the patients." }, { "input": "Is there any relationship between histone ubiquitylation and splicing?", "output": "Yes, in the case of histone H2B" }, { "input": "Which disease can be treated with Delamanid?", "output": "Delamanid is used in patients with multidrug-resistant tuberculosis." }, { "input": "What was the aim of the COSS (Carotid Occlusion Surgery Study) clinical trial?", "output": "The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion." }, { "input": "What are the advantages of the top down mass spectrometric analysis of histones?", "output": "Top down mass spectrometry is a way to analyze intact proteins thus enabling: isoform characteriztion and analysis of post-translational modifications." }, { "input": "What is situs inversus?", "output": "Situs inversus totalis is a rare congenital anomaly with a complete mirror image of the thoracic and abdominal organs." }, { "input": "Can SUMO affect calcium homeostasis?", "output": "Yes, SUMO proteins can affect calcium homeostasis." }, { "input": "What is the indication of Daonil (Glibenclamide)?", "output": "Glibenclamide is an antidiabetic and antiglycemic, used in severe NIDDM, and increasingly viewed as a rational alternative to insulin therapy." }, { "input": "Which is the most typical peptide sequence responsible for retrieval of endoplasmic reticulum (ER) lumenal proteins from the Golgi apparatus?", "output": "The lumenal endoplasmic reticulum (ER) proteins carry a specific sorting signal which enables their retrieval from multiple post-ER compartments (up to the TGN along the exocytotic pathway), back to the ER. The most typical such signal is the carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), which is bound by a KDEL receptor in the Golgi apparatus, as well as in the intermediate compartment. Thus KDEL functions as a retrieval signal of lumenal ER proteins from Golgi to ER." }, { "input": "What are the clinical trial outcomes of metformin use in polycystic ovary disease?", "output": "Metformin treatment vs placebo significantly but modestly improves ovulation frequency in women with abnormal ovarian function/oligomenorrhea and polycystic ovaries, the lower BMI women were more likely to become pregnant. While in naturally conceiving normal weight PCOS women pre-treatment with metformin tends to improve pregnancy rates, pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome.\nMetformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement.\nStudies on the effect of metformin on serum Anti-Mullerian Hormone levels /AMH concentrations bring conflicting results, from Metformin having no effect on AMH to Metformin treatment resulting in significant decrease of AMH levels, antral follicle numbers and ovarian volume. \nMetformin has been shown to cause significant weight loss (and leptin reduction) in PCOS." }, { "input": "List the main proteases used for sample digestion in proteomics.", "output": "Trypsin is the main protease used in proteomics followed by Asp-N, chymotrypsin, LysC, GluC and thermolysin." }, { "input": "Which proteins act as factors that promote transcription-coupled repair in bacteria?", "output": "Transcription coupled nucleotide excision repair (TC-NER or TCR) is a cellular process by which UV-induced damage and other road-blocks encountered in the transcribed strand are restored. Bacterial transcription-coupled repair is initiated when RNA polymerase stalled at a DNA lesion is removed by Mfd (Mutation frequency decline), an ATP-dependent DNA translocase. Mfd is the major transcription repair coupling factor in bacteria. Also, the transcription elongation factor NusA, in addition to its role in recruiting translesion synthesis (TLS) DNA polymerases to gaps encountered during transcription, promotes an alternative class of TCR involved in the identification and removal of a class of lesion, such as the N(2)-f-dG lesion." }, { "input": "What is the association between Generalized anxiety disorder and mortality risk?", "output": "Numerous studies have demonstrated that Generalized anxiety disorder is associated with increased mortality risk in different populations, including veterans and non demented elderly individuals. Anxiety disorders predict greater mortality, particularly when present with other psychiatric disorders. However, one study has found that generalized anxiety disorder was not associated with excess mortality in depressive elderly people." }, { "input": "Which molecule is targeted by a monoclonal antibody Mepolizumab?", "output": "Mepolizumab is a humanized monoclonal antibody that binds to and inactivates interleukin-5 that has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma." }, { "input": "Which is the major symptom of the Doose syndrome?", "output": "Myoclonic astatic epilepsy is the major symptom of the Doose syndrome, which is a difficult to treat idiopathic generalized epilepsy of early childhood." }, { "input": "Have mutations in the GARS gene been identified to cause Charcot-Marie-Tooth Disease Type 2D (CMT2D)?", "output": "Charcot-Marie-Tooth disease type 2D (CMT2D) is caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)." }, { "input": "Which treatment leads to an increase in neutrophil counts in severe congenital neutropenia?", "output": "In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections " }, { "input": "Which treatment leads to an increase in neutrophil counts in severe congenital neutropenia?", "output": "In patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections." }, { "input": "Which genes are affected in ROMANO-WARD syndrome?", "output": "The genes involved in ROMANO-WARD syndrome are KCNQ1, KCNE1, KCNE2, KCNH2, SCN5A, CAV3, SCN4B, AKAP9, SNTA1, KCNJ5 and Ankyrin-B." }, { "input": "Does melanoma occur in people of African origin ?", "output": "Yes. Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians. The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces." }, { "input": "What is the effect of resveratrol on mTOR activity?", "output": "Resveratrol (RSV) inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR." }, { "input": "What is the effect of resveratrol on mTOR activity?", "output": "Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human cells. It has been found that resveratrol targets multiple components of the phosphatidylinositol 3- kinase(PI3K)/Akt and mTOR signaling pathways, including PI3K, Akt, PTEN, and DEPTOR, suggesting that this natural compound and its derivatives may offer a promising new cancer treatment." }, { "input": "Are people with blood group O protected against severe Malaria?", "output": "It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection." }, { "input": "Which eye condition is managed by the athens protocol?", "output": "The athens protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking) was developed for the management of cornea blindness due to severe corneal scarring." }, { "input": "What is the role of AMPK kinase in myocardial remodeling after myocardial infarction", "output": "AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The activation of AMPK by metformin prevents cardiac remodeling after myocardial infarction (MI). \nAdiponectin protects the heart from ischemia-reperfusion injury through an AMPK-dependent mechanism.\nAMPK activation by metformin and the subsequent suppression of TLRs activity could be considered as a target in protecting the infarcted heart." }, { "input": "What is the mechanism of action of solanezumab?", "output": "Solanezumab is a monoclonal anti-amyloid beta peptide (A\u03b2) antibody. It has been tested for treatment of Alzheimer's disease patients." }, { "input": "What is the mechanism of action of solanezumab?", "output": "Solanezumab, a humanized anti-A\u03b2 monoclonal antibody directed against the midregion of the A\u03b2 peptide, was shown to neutralize soluble A\u03b2 species." }, { "input": "What are the major clinical Villefranche criteria for classic Ehlers-Danlos syndrome?", "output": "The major clinical Villefranche criteria for classic Ehlers-Danlos syndrome are skin hyperextensibility, dystrophic scarring, and joint hypermobility." }, { "input": "What is the treatment of neuropathic pain in children?", "output": "It is unclear if any treatment is registered for pediatric use. The reported treatments are:\nOxcarbazepine \nOpioids alone, in rotations or with Analgesics (e.g. Ketamine and Lidocaine infusion)\nOpioids and Benzodiazepines\nPregabalin - is one of the first drugs registered for the treatment of neuropathic pain. It is unclear if Pregabalin is registered for the treatment of neuropathic pain in children specifically but it is being used in practice.\nTricyclic Antidepressants\nLidocaine 5% patches for chronic localized neuropathic pain" }, { "input": "Which phenomenon is known as the \"calcium paradox\" in the isolated perfused heart?", "output": "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. " }, { "input": "Which phenomenon is known as the \"calcium paradox\" in the isolated perfused heart?", "output": "When hearts are reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity is observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the \"calcium paradox\". This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores. The Ca(2+) paradox represents a good model to study Ca(2+) overload injury in ischemic heart diseases. The Ca(2+) paradox can be elicited by perfusing isolated hearts with Ca(2+)-free media for 3 min or 5 min followed by 30 min of Ca(2+) repletion. A possible mechanism for the 'calcium paradox' is that exposure to a calcium-free medium removes extracellular calcium rendering the sarcolemma more permeable to calcium. On calcium repletion, cell injury is triggered by calcium influx. Cardiac dysfunction due to Ca2+ -paradox may be associated with apoptosis." }, { "input": "Which phenomenon is known as the \"calcium paradox\" in the isolated perfused heart?", "output": "\"Calcium paradox\" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption.Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney" }, { "input": "Which phenomenon is known as the \"calcium paradox\" in the isolated perfused heart?", "output": "Isolated perfusion of the heart with a Ca2+-free perfusate followed by a Ca2+-containing perfusate causes dramatic alterations in the physiology and biochemistry of the tissue, a phenomenon known as the calcium paradox. A similar paradoxical effect of Ca2+ has also been reported to occur in the kidney When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the calcium paradox . Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. " }, { "input": "Is there a crystal structure of the full-length of the flaviviridae NS5(Methyltransferase - RNA depended RNA Polymerase) ?", "output": "Yes, there is the crystal Structure of the full-length Japanese encephalitis virus (Flaviviridae) NS5 - PDB:4K6M" }, { "input": "How do Hsp70 and Hsp110 affect mRNA stability?", "output": "Hsp70 and Hsp110 act as RNA-binding entities in vivo to guide the appropriate folding of RNA substrates for subsequent regulatory processes such as mRNA degradation and/or translation." }, { "input": "What is Prudent Diet?", "output": "The Prudent dietary pattern is characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products, legumes, fish, poultry. Generally recommendations are to use saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake \u2265 25 g/day in women and \u2265 35 grams per day in men." }, { "input": "What is the role of necroptosis in cancer therapy?", "output": "Necroptosis, a novel form of programmed cell death (PCD), is caspase independent but RIPK and RIPK3 dependent. The apoptotic, autophagic and necroptotic pathways of PCD were shown to be interconnected, with molecules such as FLIP acting as a bridge between them. Therefore, simultaneous activation of the three PCD pathways would make cancer therapy more effective, whereas induction of necroptosis could be an alternative, in cases where apoptosis-inducing cancer chemotherapy is not effective. For example, inhibition of GSK3B was found to bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to 5-FU treatment." }, { "input": "Can venlafaxine block NET and SERT?", "output": "Yes, venlafaxine inhibits both the NET and SERT." }, { "input": "Is Rheumatoid Arthritis more common in men or women?", "output": "Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome." }, { "input": "What is FINDbase?", "output": "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Database access is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'." }, { "input": "What is FINDbase?", "output": "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'." }, { "input": "Can vitamin B1 deficiency cause encephalopathy?", "output": "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. It is commonly associated with heavy alcohol consumption. Other clinical associations are with hyperemesis gravidarum (HG), starvation, and prolonged intravenous feeding." }, { "input": "Can vitamin B1 deficiency cause encephalopathy?", "output": "Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia" }, { "input": "Which methyl-CpG-binding protein when mutant becomes the hallmark for Rett syndrome?", "output": "Rett syndrome (RTT) was shown to be caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, with molecular studies identifying MECP2 mutations in up to 80% of classic RTT patients. MECP2 protein was found to assist in the transcriptional silencing process via DNA methylation. We therefore hypothesize that disruption of this gene alters the normal developmental expression of various other genes, some of which must account for the peculiar neurologic phenotype of RTT." }, { "input": "Are epigenetic modifications implicated in cardiovascular development and disease?", "output": "Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD).Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease." }, { "input": "Which deiodinases are present in skeletal muscle?", "output": "Type 2 and Type 3 deiodinases are expressed in skeletal muscle and their expression is modulated by disease state and fasting." }, { "input": "Which genes are involved in patient response to warfarin?", "output": "The following genes have been associated with patient response to warfarin: CYP2C9, VKORC1, ORM1, CYP4F2, EPHX1, CYP2C18, CYP2C19, CYP3A5, protein S, clotting factor V, PROC, GGCX." }, { "input": "Which is the molecular weight of the protein angiogenin?", "output": "The molecular weight of angiogenin is 14,120 Da. The bovine angiogenin is 14,595 Da" }, { "input": "List sodium glucose co-transporter-2 (SGLT2) inhibitors that have been FDA approved for type 2 diabetes mellitus treatment.", "output": "Canagliflozin, along with dapagliflozin and empagliflozin, are SGLT2 inhibitors approved by the US FDA for use in the treatment of type 2 diabetes." }, { "input": "What is the gene mutated in the Gaucher disease?", "output": "The glucocerebrosidase gene (GBA)" }, { "input": "Why does the prodrug amifostine (ethyol) create hypoxia?", "output": "After the administration of Prodrug amifostine the cells of the tissue prefer anaerobic glycolysis rather than regular cellular aerobic respiration. By the beggining of anaerobic glycolysis the inducible by hypoxia proteins are induced and by all these molecules the hypoxic conditions consist of." }, { "input": "What is considered a reliable technique for the definitive cytogenetic diagnosis of Fanconi anemia homozygosity?", "output": "In vitro enhancement of chromosome breakage by diepoxybutane (DEB) and mitomycin C (MMC) are reliable techniques for the definitive cytogenetic diagnosis of Fanconi anemia homozygosity." }, { "input": "What is considered a reliable technique for the definitive cytogenetic diagnosis of Fanconi anemia homozygosity?", "output": "In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity" }, { "input": "Can exosomes be detected in urine?", "output": "Yes, urinary exosomes can be detected in urine." }, { "input": "What is the role of lysine-specific demethylase 1 (LSD1) in hematopoiesis?", "output": "LSD1 represents a central regulator of hematopoietic stem and progenitor cells. LSD1 knockdown (LSD1-kd) expanded progenitor numbers by enhancing their proliferative behavior. LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors. In contrast, terminal granulopoiesis, erythropoiesis and platelet production were severely inhibited. The only exception was monopoiesis, which was promoted by LSD1 deficiency. Importantly, we showed that peripheral blood granulocytopenia, monocytosis, anemia and thrombocytopenia were reversible after LSD1-kd termination. Extramedullary splenic hematopoiesis contributed to the phenotypic reversion, and progenitor populations remained expanded. LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, Hoxa9 and Meis1, which are known regulators of the HSC/progenitor compartment. We also demonstrated that LSD1-kd abrogated Gfi1b-negative autoregulation by crossing LSD1-kd with Gfi1b:GFP mice. There is also epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b that is mediated by the cofactors CoREST and LSD1. A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. The enzymatic domain of LSD1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a thymidine kniase minimal promoter. Furthermore, the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation. Consistent with the rapid changes of TAL1-corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells. ShRNA-mediated knockdown of LSD1 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at the promoter region. Thus, it appears that histone lysine demethylase LSD1 may negatively regulate TAL1-mediated transcription and that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs. Furthermore, RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 in erythroid cells. RUNX1 interacts with LSD1 and MYEF2 in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Finally, LSD1 also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei. Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF." }, { "input": "For the treatment of which conditions can atypical neuroleptic drugs be used?", "output": "Atypical neuroloeptic drugs are antipsychotics used in patients with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders, psychotic relapse in neuroleptic malignant syndrome and attention deficit hyperactivity disorder when presenting with negativism and conduct disorder." }, { "input": "Which are the characteristics of Andersen syndrome?", "output": "the characteristics of Andersen syndrome are abnormal QT-U complex, ventricular arrhythmia, periodic paralysis, and facial and skeletal dysmorphisms" }, { "input": "How are induced pluripotent stem cells used in the study and treatment of cardiovascular diseases?", "output": "The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. The production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study \"disease in a dish\" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. Long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia are two heart rhythm disorders that have been already successfully modeled by several groups using this approach, which will likely serve to model other mono- or polygenetic cardiovascular disorders in the future. The use of iPSC-derived cardiomyocytes to study genetic cardiovascular disorders will enable a deeper and more applicable understanding of the molecular mechanisms of human disease, as well as improving our ability to achieve successful cell-based therapies." }, { "input": "Which disease is included as an additional feature in the Goldberg-Shprintzen syndrome?", "output": "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus." }, { "input": "Which disease is included as an additional feature in the Goldberg-Shprintzen syndrome?", "output": "Hirschsprung disease is very often identified as an additional feature of the Goldberg-Shprintzen syndrome." }, { "input": "Which disease is included as an additional feature in the Goldberg-Shprintzen syndrome?", "output": "Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndromeMutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans." }, { "input": "Which disease is included as an additional feature in the Goldberg-Shprintzen syndrome?", "output": "Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.\nThe Shprintzen-Goldberg syndrome is an extremely rare syndrome with a characteristic face. This is one of a group of disorders characterized by craniosynostosis and marfanoid features." }, { "input": "Which protein is causing Netherton syndrome?", "output": "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor)" }, { "input": "Mutations in which gene and which protein are associated with Netherton syndrome?", "output": "NS is due to loss-of-function mutations in the SPINK5 gene and to the consequent lack of expression of its encoded protein LEKTI in the skin and all stratified epithelial tissues." }, { "input": "Which disease of the central nervous system is characterized by the presence of Lewy bodies?", "output": "Parkinson s disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar \u03b1-synuclein " }, { "input": "Which disease of the central nervous system is characterized by the presence of Lewy bodies?", "output": "Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar \u03b1-synuclein." }, { "input": "Which disease of the central nervous system is characterized by the presence of Lewy bodies?", "output": "Parkinsons disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The protein \u03b1-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites" }, { "input": "Which deiodinase is known to be present in liver?", "output": "High D1 and D3 activities are present in fetal human liver, and high D1 and mostly absent D3 activities are present in adult human liver." }, { "input": "Which proteins participate in the formation of the Notch transcriptional activation complex?", "output": "The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML). ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex." }, { "input": "Which proteins participate in the formation of the Notch transcriptional activation complex?", "output": "Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled. The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML)." }, { "input": "How is the sequence variability defined in antibodies?", "output": "The variability at each position of the polypeptide chain is defined as:\nVariability = number of different amino acids at a given position / frequency of the most common amino acid at given position." }, { "input": "Is the transcriptional regulator BACH1 an activator or a repressor?", "output": "BACH1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has antioxidant and anti-inflammatory activities. In the absence of elevated intracellular heme or oxidative stress, BACH1 functions as a repressor of the enhancers of heme oxygenase-1 (HO-1) gene (Hmox-1) by forming heterodimers with the small Maf proteins such as MafK. Bach1 is recruited to a subset of p53 target genes and contributes to impeding p53 action by promoting histone deacetylation." }, { "input": "Is the transcriptional regulator BACH1 an activator or a repressor?", "output": "BACH1 is, in most contexts, a transcriptional repressor" }, { "input": "Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase?", "output": "Yes, Kanzaki disease is attributable to a deficiency in alpha-N-acetylgalactosaminidase, which hydrolyzes GalNAcalpha1-O-Ser/Thr." }, { "input": "Is Mycobacterium avium less susceptible to antibiotics than Mycobacterium tuberculosis?", "output": "Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome. M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival. Patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated. Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare. The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5" }, { "input": "What molecule is targeted by suvorexant?", "output": "Suvorexant is a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia." }, { "input": "For which type of diabetes can empagliflozin be used?", "output": "The oral antidiabetes agent, empagliflozin, can be used as monotherapy or alongside other glucose-lowering treatments, including insulin, to treat T2DM." }, { "input": "Which are the main methods for pharmacophore modelling?", "output": "A pharmacophore describes the arrangement of molecular features a ligand must contain to efficaciously bind a receptor. Pharmacophore models are developed to improve molecular understanding of ligand\u2013protein interactions, and can be used as a tool to identify novel compounds that fulfil the pharmacophore requirements and have a high probability of being biologically active. Protein structure-based pharmacophores (SBPs) derive these molecular features by conversion of protein properties to reciprocal ligand space. Unlike ligand-based pharmacophore models, which require templates of ligands in their bioactive conformation, SBPs do not depend on ligand information." }, { "input": "Are there conserved noncoding elements identified between genomes of human and teleosts?", "output": "Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages " }, { "input": "Are there conserved noncoding elements identified between genomes of human and teleosts?", "output": "Yes. Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. CNEs have been identified, among others, in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu)." }, { "input": "How early during pregnancy does non-invasive cffDNA testing allow sex determination of the fetus?", "output": "Using cffDNA from maternal blood, the fetal gender can be determined as early as 6 to 10 weeks of gestation (during the first trimester of pregnancy)." }, { "input": "Does cortical spreading depression appear in ischemic penumbra following ischemic stroke?", "output": "Yes, cortical spreading depression appears in ischemic penumbra following ischemic stroke and is associated with expansion of ischemic injury. This has been shown in humans and in animal models." }, { "input": "Is phospholamban a regulatory/inhibitory protein of the Ca ATPase SERCA?", "output": "Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles.The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. \u03b2-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism." }, { "input": "Is phospholamban a regulatory/inhibitory protein of the Ca ATPase SERCA?", "output": "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban. When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance.Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy." }, { "input": "What is TFBSshape?", "output": "To utilize DNA shape information when analysing the DNA binding specificities of TFs, the TFBSshape database was developed for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone." }, { "input": "Is Alpers disease inherited in an autosomal recessive mode?", "output": "Alpers disease is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease." }, { "input": "Is Alpers disease inherited in an autosomal recessive mode?", "output": "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder" }, { "input": "Is vemurafenib effective for hairy-cell leukemia?", "output": "Yes, vemurafenib is highly effective in patients with relapsed or refractory hairy-cell leukemia." }, { "input": "Which are the inhibitors of histone methyltransferases?", "output": "In general, histone methyltransferases (HMTs) have no widely approved high-throughput screening assay format, and therefore reference inhibitors are not available for many of the HMTs. However, there are several selective HMT inhibitors: Trichostatin A (TSA), BIX-01294 and its derivative TM2-115, 2,4-pyridinedicarboxylic acid (2,4-PDCA), 3-deazaneplanocin A (DZNep), Psammaplin A (PsA) and Sulforaphane (SFN)." }, { "input": "What is the main characteristic of Amyotrophic Lateral Sclerosis?", "output": "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons. " }, { "input": "What is the main characteristic of Amyotrophic Lateral Sclerosis?", "output": "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons." }, { "input": "Which genes are regulated by MEF-2 in the heart?", "output": "COX-2, ANF, estrogen receptor (ER)alpha gene, calsequestrin gene, casq2, cTnT, MCK, alpha-cardiac actin, sarco(endo)plasmic reticulum Ca2+-ATPase, SERCA, MLC-2, alpha-cardiac myosin heavy chain gene, phosphoglycerate mutase and PGAM-M are regulated by MEF-2 in the heart" }, { "input": "Is there an association between TERT promoter mutation and survival of glioma patients?", "output": "Yes, TERT mutation is associated with survival of glioma patients and was suggested as a bio-marker of gliomas." }, { "input": "Which JAK (Janus kinase) inhibitor is approved for treatment of rheumatoid arthritis?", "output": "Tofacitinib (or CP690.550) is an oral JAK (Janus kinase) inhibitor that is approved for treatment of rheumatoid arthritis. Tofacitinib inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. Tofacitinib has also a proven efficacy as an immunosuppressive regimen after renal transplantation. \nGLPG-0634 and INCB18424 are other JAK kinase inhibitors that are being studied for treatment of rheumatoid arthritis." }, { "input": "Which is the mechanism used for synthesis of a highly functional N-truncated dystrophin isoform that attenuates dystrophinopathy?", "output": "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice" }, { "input": "Which is the mechanism used for synthesis of a highly functional N-truncated dystrophin isoform that attenuates dystrophinopathy?", "output": "Alternative translation initiation beginning in DMD exon 6 with the use of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible leads to expression of a highly functional N-truncated dystrophin isoform which is able to ameliorate disease severity." }, { "input": "Which is the mechanism used for synthesis of a highly functional N-truncated dystrophin isoform that attenuates dystrophinopathy?", "output": "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice " }, { "input": "Which are the newly identified DNA nucleases that can be used to treat thalassemia?", "output": "Thalassemia is genetic diseases of the blood caused by mutations in the globin gene. Main goal for thalassemia treatment is to develop homologous recombination based gene therapy in order to cure these diseases. Zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) are proper targets for the human globin gene. Genome editing using engineered nucleases such as ZFNs and TALENs has become a powerful technology for reverse genetics." }, { "input": "Which are the newly identified DNA nucleases that can be used to treat thalassemia?", "output": "The newly identified DNA nucleases that can be used to treat thalassemia are the transcription activator-like effector nucleases (TALEN). These are engineered proteins able to stimulate targeted integration of therapeutic wild-type beta-globin cDNAs to the endogenous beta-globin locus." }, { "input": "Does ziconotide bind to N-type calcium channels?", "output": "Yes, ziconotide/omega-conotoxin MVIIA blocks N-type calcium channels." }, { "input": "How is OCT3 associated with serotonin?", "output": "OCT3 plays a role in serotonin clearance" }, { "input": "What constitutes an increased risk for individuals with Fanconi anemia?", "output": "Fanconi anemia is a rare genetic disorder associated with an increased risk of leukemias and solid tumors." }, { "input": "Is stop codon bypass possible?", "output": "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC.\nAminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT).\nExpression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift)." }, { "input": "Is stop codon bypass possible?", "output": "Yes it is. The UGA stop codon was found to code for seleno-cysteine in a number of Saccharomyces cerevisiae genes, whereas the UAG stop codon was shown to code for pyrro-lysine in some archaean species. Moreover, in experimental and therapeutic settings, aminoglycoside-induced stop codon bypass has been used to restore protein translation by promoting readthrough of stop codons, generated by mutations causing premature termination of protein synthesis. Additionally, cytosine deamination to uracil in stop codons may result in stop codon bypass, whereas in a number of polycistronic genes or sequential ORFs, there is evidence for stop codon bypass, although their induction mechanisms are still unclear. Additional hypotheses for stop codon bypass involve the 3' context of the translated transcript, non-conventional anticodon-codon interactions or translational frameshifts." }, { "input": "Is the protein \u03b21-integrin recycled?", "output": "Yes, the \u03b21-integrin is recycled." }, { "input": "Are BBS mutations involved in syndromic Hirschsprung disease?", "output": "In 3 families with Bardet-Biedl syndrome (BBS) and Hirschsprung disease (HSCR), concomitant mutations in BBS genes and regulatory RET elements have been identified. Analysis of the data suggests that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease." }, { "input": "Which signaling pathway is activating the dishevelled proteins?", "output": "Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling" }, { "input": "Which is the defective protein causing the lysosomal storage disease Fabry?", "output": "Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme." }, { "input": "Is there any software for automated analysis of immuno-histochemistry images?", "output": "In some studies of breast cancer, quantitation of immunohistochemically highlighted microvessel \u2018hot spots\u2019 has been shown to be a powerful prognostic tool. However, the antibody used, the number and size of the \u2018hot spots\u2019 assessed, and the stratification of patients into high and low vascular groups vary between studies. Furthermore, little is known about the relationship between microvessel density and other vascular parameters. These uncertainties and the laborious nature of the technique make it unsuitable for diagnostic practice. Both manual and computerized image analysis techniques were used in this study to examine the relationship between microvessel density and the vascular parameters in different sized microscopic fields in a pilot series of 30 invasive breast carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley point counting, and observer subjective vascular grading were also assessed as more rapid methods of measuring tumour vascularity" }, { "input": "Is TALEN being used on stem cells?", "output": "Yes, TALEN is being used on stem cells for genome editing." }, { "input": "Is there an association between bruxism and reflux", "output": "There is an association between bruxism and reflux." }, { "input": "what is the role of IGF-1 in cardiac regeneration after myocardial infarction?", "output": "Ischemia-reperfusion injury is a strong stimulus for both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of IGF-1. Furthermore, in an animal model of myocardial infarction, intracoronary administration of IGF-1 is shown to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function. IGF-1 is a potent modulator of stem cell replication, commitment to the myocyte lineage, and myocyte differentiation. In another study, the dual delivery of IGF-1 and HGF from affinity-binding alginate biomaterial prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry and increased the incidence of GATA-4-positive cell clusters. The addition of nanofiber-mediated IGF-1 delivery to Cardiac Progenitor Cells therapy improved in part the recovery of myocardial structure and function after infarction. IGF-1 promotes proliferation and survival of CPCs. The strategy of IGF-1 transgene expression has shown to induce massive stem cell mobilization via SDF-1alpha signaling and culminated in extensive angiomyogenesis in the infarcted heart." }, { "input": "What is known about prostate cancer screening in the UK", "output": "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. Two systematic reviews have concluded that screening should not be carried out. In general, this recommendation has been accepted in the United Kingdom." }, { "input": "Can a peptide aptamer be used as protein inhibitor?", "output": "Yes, peptide aptamers can be used as inhibitors." }, { "input": "List inflammatory caspase proteins?", "output": "caspase-1\ncaspase-4\ncaspase-5" }, { "input": "List invertebrates where ultraconserved elements have been identified.", "output": "Ultraconserved elements have been identified in the following genomes of invertebrates: tunicates, diptera, worm and yeast." }, { "input": "Which gene is most commonly associated with severe congenital and cyclic neutropenia?", "output": "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (SCN) and cyclic neutropenia (CN)." }, { "input": "Which gene is most commonly associated with severe congenital and cyclic neutropenia?", "output": "Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other " }, { "input": "what is the role of TGFbeta in cardiac regeneration after myocardial injury?", "output": "TGF\u03b2 is activated in the myocardium in response to injury and plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. In fact, upregulation of TGF-beta signaling promotes the formation of a myofibroblast-like phenotype. TGF-beta interacts with bone morphogenic protein and Wnt pathways to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells, determining whether functional regeneration or the formation of scar tissue follows an injury. In addition, TGF-beta enhances the formation of cardiospheres and could potentially enhance the regenerative potential of adult cardiac progenitor cells." }, { "input": "List two chemotherapeutic agents that are used for treatment of Subependymal Giant Cell Astrocytoma", "output": "Everolimus and rapamycin are chemotherapeutic agents that are used for treatment of Subependymal Giant Cell Astrocytoma." }, { "input": "Are integrins part of the extracellular matrix?", "output": "Yes, \tintegrins are a central family of extracellular matrix receptors." }, { "input": "Is Calcium homeostasis important in cardiac physiology and pathophysiology?", "output": "Calcium homeostasis is very important in cardiac physiology and pathophysiology. Maintenance of cellular calcium homeostasis is critical to regulating cardiac contraction. Abnormalities in calcium homeostasis underlie cardiac arrhythmia, contractile dysfunction and cardiac remodelling." }, { "input": "List available databases containing information about conserved noncoding elements.", "output": "Ancora and TFCONES." }, { "input": "What was the purpose of the FANTOM5 project?", "output": "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome." }, { "input": "Is the gene DUX4 epigenetically regulated in somatic cells?", "output": "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Recent studies provide evidence that DUX4 is expressed in the human germline and then epigenetically silenced in somatic cells." }, { "input": "Is the gene DUX4 epigenetically regulated in somatic cells?", "output": "Yes, the human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues." }, { "input": "Is the gene DUX4 epigenetically regulated in somatic cells?", "output": "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. " }, { "input": "Is the gene DUX4 epigenetically regulated in somatic cells?", "output": "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells." }, { "input": "What is the function of the mammalian gene Irg1?", "output": "Human IRG1 and mouse Irg1 mediates antiviral and antimicrobial immune responses, without its exact role having been elucidated. Irg1 has been suggested to have a role in apoptosis and to play a significant role in embryonic implantation. Irg1 is reported as the mammalian ortholog of methylcitrate dehydratase." }, { "input": "Have hESC been tested for the treatment of age-related macular degeneration?", "output": "Yes, human embryonic stem cell (hESC) therapies are being assessed for age-related macular degeneration (AMD)." }, { "input": "What disease in Loxapine prominently used for?", "output": "The best indication of loxapine is paranoid schizophrenia." }, { "input": "What is the systemic nickel allergy syndrome?", "output": "A severe form of this allergy is the Systemic nickel allergy syndrome, clinically characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and systemic symptoms (headache, asthenia, itching, and gastrointestinal disorders related to histopathological alterations of gastrointestinal mucosa, borderline with celiac disease)." }, { "input": "Which antibodies cause Riedel thyroiditis?", "output": "Riedel thyroiditis (Immunoglobulin G4-related thyroid disease) is caused by IgG4 antibodies. It is part of the spectrum of Ig4-related sclerosing disease.\nIt is associated with fibrosis and inflammation of the thyroid gland." }, { "input": "What are the effects of ILK ablation?", "output": "Depending on the tissue or cell where ILK is ablated we see different effects:\nAblation of ILK in heart results in dilated cardiomyopathy and spontaneous heart failure\nAblation of ILK in fibroblasts leads to impaired healing due to a severe reduction in the number of myofibroblasts\nAblation of ILK in osteoclasts inhibits bone resorption\nAblation of ILK in liver results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration and in abnormal histology\nAblation of ILK in podocytes caused an aberrant distribution of nephrin and alpha-actinin-4" }, { "input": "Does d-tubocurarine (d-TC) induces irreversible inhibition of nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction?", "output": "The d-tubocurarine is a nondepolarizing neuromuscular blocking agent (nondepolarizing muscle relaxant - NDMR). The nondepolarizing muscle relaxants act by blocking the nicotinic acetylcholine receptors of the neuromuscular junction. The neuromuscular blocking action of tubocurarine is reversible and concentration-dependent. The inhibition of acetylcholine-induced currents by d-tubocurarine can be reversed by anticholinesterase agents, such as edrophonium and methamidophos." }, { "input": "Which receptors are bound by Tasimelteon?", "output": "Tasimelteon (HETLIOZ\u2122) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder." }, { "input": "Is zyxin a focal adhesion protein?", "output": "Yes, zyxin is a focal adhesion protein." }, { "input": "What is the role of ELMO1 gene in cell migration?", "output": "ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex. In mammalian cells, ELMO1 interacts with Dock180 as a component of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration. We also show that Hck and ELMO1 interact in intact cells and that ELMO1 is heavily tyrosine-phosphorylated in cells that co-express Hck, suggesting that it is a substrate of Hck.The ELMO1/DOCK180 complex then forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems. Rac activation by the ELMO.Dock180 complex at discrete intracellular locations is mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration." }, { "input": "What is the role of ELMO1 gene in cell migration?", "output": "Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac." }, { "input": "What is the biological role of K-48 linked protein ubiquitination?", "output": "The proteasome, which identifies and destroys unwanted proteins rapidly, plays a vital role in maintaining cellular protein homeostasis. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery. K(48)-linked polyubiquitinated proteins are degraded by the proteasomes to elevate cellular levels of amino acids needed for intracellular proliferation. NF-\u03baB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-\u03baB precursors and the degradation of inhibitor of kappa B (I\u03baB) proteins." }, { "input": "Could DNA (cytosine-5-)-methyltransferases serve as tumour markers?", "output": "Yes. It has been demonstrated in a number of experimental studies that DNA (Cytosine-5-)-methyltransferases (DNMT1, DNMT3A and DNMT3B) are deregulated in several types of cancer (invasive cervical cancer, colon cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer, embryonal carcinoma, cervical cancer, adenoma, adenoid cystic carcinoma, salivary gland neoplasms). Moreover, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region have been reported to be stratification markers that can predict an individual's susceptibility to cancers. Therefore, DNA (Cytosine-5-)-methyltransferases can serve as tumour markers." }, { "input": "Which RNA polymerase is used for the replication of viroids?", "output": "DNA-dependent RNA polymerase II of plant origin transcribes viroid RNA into full-length copies" }, { "input": "Which RNA polymerase is used for the replication of viroids?", "output": "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro. The RNA genome of potato spindle tuber viroid (PSTV) is transcribed in vitro into complementary DNA and RNA by DNA-dependent DNA polymerase I and RNA polymerase, respectively, from Escherichia coli. Host DNA-dependent RNA polymerase II (RNAP II) was proposed to be critical for its replication, but no interaction site for RNAP II on the PSTVd RNA genome was identified. Whereas maximum total activity was observed in 1 mM Mn(2+) with a pronounced reduction (80%) in 5 mM Mn(2+), CEV synthesis was maintained in 1-15 mM Mn(2+)." }, { "input": "Which RNA polymerase is used for the replication of viroids?", "output": "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro. Research results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV." }, { "input": "List Parkin binding partners", "output": "HSP90\nCDC37\nGRP75\nHSP60\nLRPPRC\nTUFM\nPICK1\nPSMA7\nPael receptor" }, { "input": "What is generic name of drug Adempas?", "output": "Riociguat is generic name of drug Adempas. It is a soluble guanylate cyclase stimulator that was approved for the treatment of patients with chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension." }, { "input": "What is known about Vancomycin dosing in neonates?", "output": "Staphylococcus epidermis, including methicillin-resistant strains, are inhibited by vancomycin concentrations of 1-4 \u00b5g/ml. \nStaphylococcus pyogenes, Streptococcus pneumonia, and Streptococcus viridans are susceptible to 2 \u00b5g/ml vancomycin. \nBacillus spp. are inhibited by 2 \u00b5g/ml, Corynebacterium spp. by 0.04-3.1 \u00b5g/ml and Clostridium spp. by 0.39-6 \u00b5g/ml vancomycin. \nPeak and trough concentrations of vancomycin should be 40 \u03bcg/ml and 10 \u03bcg/ml, respectively, to both be effective and avoid oto- or nephrotoxicity in adults. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. Because vancomycin activity is primarily time-dependent, the 24-h area under the curve (AUC0-24h) divided by the minimum inhibitor concentration (MIC) value (AUC0-24h/MIC) is a better predictor of efficacy. In adults with MIC values less than 1 \u03bcg/ml, trough concentrations greater than 10 \u00b5g/ml result in AUC0-24h/MIC values 400\nCompared with adults, neonates have a higher extracellular fluid volume and a limited renal elimination capacity resulting in different pharmacokinetics subject to maturation stage. Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants.\nVancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations 40 microg/mL. Vancomycin is associated with ototoxicity.\nThere is no consensus on vancomycin dosing in newborns and young infants, which leads to significant variation in vancomycin dosing regimens and TDM guidance across neonatal units. The development of standardized, evidence-based protocols should be prioritized." }, { "input": "Is single guide RNA part of the CRISPR/Cas9 tool or an inhibitor of its function?", "output": "Single guide RNA is part of the CRISPR/Cas9 system." }, { "input": "What is the target protein of the drug Idelalisib?", "output": "Idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform." }, { "input": "Which antiepileptic drug is most strongly associated with spina bifida? ", "output": "Phenytoin is not used in pregnancy as it is associated with a severe fetal deformation. From the other anticonvulsants most studies report the higher association between use during pregnancy and spin bifida to occur with Valproate." }, { "input": "Which bacteria caused plague?", "output": "Yersinia pestis is the causative bacteria of the plague." }, { "input": "The drug JTV519 is derivative of which group of chemical compounds?", "output": "The 1,4-benzothiazepine derivative JTV-519 is a new type of calcium ion channel modulator.JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998" }, { "input": "The drug JTV519 is derivative of which group of chemical compounds?", "output": "JTV519 (K201), is a 1,4-benzothiazepine derivative and multi-channel blocker, which has been found to stabilize RyR2s and decrease SR Ca\u00b2\u207a leak." }, { "input": "Is the long non- coding RNA malat-1 up or downregulated in cancer?", "output": "Malat-1 expression is upregulated in several tumor types" }, { "input": "Oxantel is used for periodontitis treatment. How does it work?", "output": "Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms." }, { "input": "What is apelin?", "output": "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor." }, { "input": "What is the function of the protein encoded by the gene PABPC4?", "output": "The main function of PABPC4 is in mRNA stability and translation initiation. PABPC4 may also play a role in chronic inflammation and in the pathogenesis of colorectal cancer." }, { "input": "What kind of enzyme is encoded by the proto-oncogene ABL1?", "output": "ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. " }, { "input": "What kind of enzyme is encoded by the proto-oncogene ABL1?", "output": "The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration and invasion. Constitutively activated mutants of the non-receptor tyrosine kinase (TK) ABL1 (Abelson murine leukemia viral (v-abl) homolog (1) protein) play a central role in the pathogenesis myeloproliferative disorders and in some cases of acute leukemia and lymphoma." }, { "input": "What is the mode of inheritance of Romano Ward long QT syndrome?", "output": "The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of inheritance." }, { "input": "Which histone modifications have been associated to alternative splicing?", "output": "H3K36m3 has been systematically associated to exon inclusion in almost all published studies. Other marks have been associated as well in specific studies to exon expression, but it can not be concluded that the effect of these marks in exon expression it is not a consequence of their effect in gene expression." }, { "input": "Is phospholamban phosphorylated by Protein kinase A?", "output": "Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that is phosphorylated at Ser16 by PKA. Phosphorylation of PLB by PKA reverses the inhibitory action of PLB." }, { "input": "Are there telemedicine applications for chronic pain management?", "output": "Yes, telemedicine is feasible and cost-effective for education and therapy of patients with chronic pain." }, { "input": "Are there telemedicine applications for chronic pain management?", "output": "Yes, there are." }, { "input": "What is a P-body (processing body)?", "output": "Processing bodies (P bodies, PB) are cytoplasmic protein complexes involved in degradation and translational arrest of mRNA." }, { "input": "What is the mechanism of action of decitabine?", "output": "Decitabine reactivates unmethylated p21WAF1 in some AML cell lines but the possible occurrence of p21WAF1 methylation in AML in vivo has not been studied in detail and decitabine effects on p21WAF1 chromatin remodeling have not been reported. We also discuss the following questions: What is the best administration schedule of decitabine in solid tumors? Is there tumor type specificity for decitabine-based epigenetic therapy? We found that p21WAF1 mRNA was undetectable in 6 of 24 AML patient samples and 4 of 5 AML cell lines but there was no evidence of p21WAF1 promoter methylation." }, { "input": "What is the mechanism of action of decitabine?", "output": "The use of the DNA methylation inhibitor decitabine (Dacogen\u00ae) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention." }, { "input": "What is the mechanism of action of decitabine?", "output": "Decitabine is a potent demethylating agent that exhibits clinical activity against myeloid malignancies. Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action." }, { "input": "Which gene is associated with the Mitchell-Riley syndrome?", "output": "Mutations in the gene coding for the transcription factor RFX6 (regulatory factor X,6) have been described as the cause of the Mitchell-Riley syndrome." }, { "input": "Is paramyxovirus involved in human subacute thyroiditis?", "output": "There is no evidence that paramyxovirus are involved in etiology of subacute thyroiditis." }, { "input": "What are the mobile applications fields of use for patients ?", "output": "Weight-loss mobile applications\npediatric obesity prevention and treatment, healthy eating, and physical activity promotion\nA total of 229 dermatology-related apps were identified in the following categories: general dermatology reference (61 [26.6%]), self-surveillance/diagnosis (41 [17.9%]), disease guide (39 [17.0%]), educational aid (20 [8.7%]), sunscreen/UV recommendation (19 [8.3%]), calculator (12 [5.2%]), teledermatology (8 [3.5%]), conference (6 [2.6%]), journal (6 [2.6%]), photograph storage/sharing (5 [2.2%]), dermoscopy (2 [0.9%]), pathology (2 [0.9%]), and other (8 [3.5%]). The most reviewed apps included Ultraviolet\u2009~\u2009UV Index (355 reviews), VisualDx (306), SPF (128), iSore (61), and SpotMole (50)\nmobile health and fitness app\nalcohol-use behavior change or recovery\nMore than 17,000 mHealth apps now are available for smart phones and other devices, and they do everything from monitoring urine flow for patients with enlarged prostates to reminding people prone to kidney stones to drink more water." }, { "input": "Is there any link between the aurora B kinase and the polycomb protein ring1B?", "output": "Yes. The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes." }, { "input": "Which are the genes responsible for Dyskeratosis Congenita?", "output": "To date, 8 genes have been associated with Dyskeratosis Congenita development. These are DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1. Seven of these are important in telomere maintenance, because either they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2)." }, { "input": "Which are the genes responsible for Dyskeratosis Congenita?", "output": "To date, CTC1, DKC1, TERC, TERT, TINF2, NHP2, NOP10, and WRAP53 are the genes in which mutations are known to cause DC and result in very short telomeres Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2) " }, { "input": "Is CD99 encoded by MIC2 gene?", "output": "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene " }, { "input": "Is CD99 encoded by MIC2 gene?", "output": "CD99 is a transmembrane protein encoded by MIC2 gene. It is involved in multiple cellular functions, including cell adhesion and migration, apoptosis, cell differentiation, and regulation of protein trafficking, in either physiological or pathological conditions." }, { "input": "Name five programs for transcript quantification from RNASeq experiments", "output": "Popular programs for transcript quantification from RNASeq experiments include: Cufflinks, RSEM, Flux Capacitor, Mitie, Miso, Tigar, Montebello, Drut, Traph, Pome, IsoformEx, Neuma," }, { "input": "What are the main characteristics/symptoms of the \"Brugada\" syndrome", "output": "In 1992, Brugada and Brugada first described a new entity, which became known as Brugada syndrome, that is associated with a high risk of ventricular arrhythmias and sudden cardiac death in patients without structural heart disease. This syndrome is characterized by a distinct electrocardiographic phenotype, type 1 Brugada pattern, consisting of a coved ST-segment elevation (\u22650.2 mV) followed by a negative T wave in more than one right precordial lead. The typical Brugada electrocardiogram (ECG) phenotype is often concealed in affected population. Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias. Brugada syndrome (BrS)is considered to be a primary inherited channelopathy often involving the inward sodium current and the diagnosis has traditionally required the exclusion of overt structural heart disease. Brugada syndrome (BrS) is an inherited cardiac disease characterized by ST segment elevation in V1-V3 ECG leads. Mutations SCN5A gene encoding for the cardiac voltage-gated Na(+) channel are found in some BrS patients, but also in family members with isolated conduction disturbances." }, { "input": "What is the main component of the Lewy bodies?", "output": "Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. Alpha-synuclein has been identified as the main component of the Lewy bodies." }, { "input": "What is the main component of the Lewy bodies?", "output": "The main component of Lewy bodies is alpha-synuclein." }, { "input": "What is the main component of the Lewy bodies?", "output": "Parkinson s disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis " }, { "input": "How does thyroid hormone regulate mitochondrial biogenesis in the myocardium?", "output": "T4 increases myocardial mitochondrial bioenergetic capacity, oxygen consumption and markers of mitochondrial biogenesis. The marked, parallel increases in PPARalpha levels suggest its potential involvement in mediating myocardial-specific remodeling of mitochondria in response to T4. T3 induces mitochondrial biogenesis. In fact, T3 treatment for 72h increases activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha). Furthermore, L-T3 increases the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1\u03b1, mitochondrial transcription factor A and peroxisome proliferator activated receptor \u03b3 coactivator-1\u03b1, in the LV peri-infarct zone.\nThe activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis by T3. Truncated forms of the nuclear receptor TR\u03b11, with molecular weights of 43 kDa (p43) and 28 Kda have been previously identified in mitochondria. P43 is a mitochondrial T3 receptor which stimulates mitochondrial transcription and protein synthesis in the presence of T3. p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity." }, { "input": "What is the link between HOT regions and RNA polymerase recruitment?", "output": "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance." }, { "input": "List variants of the MC1R gene.", "output": "V60L\nD84E\nV92M\nR151C\nR160W\nR163Q\nD294H" }, { "input": "Which is the enzyme that degrades decapped mRNAs?", "output": "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1" }, { "input": "Which is the enzyme that degrades decapped mRNAs?", "output": "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1." }, { "input": "Which phenotypes are associated with heterozygous mutations of the BSCL2 gene?", "output": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement." }, { "input": "Which phenotypes are associated with heterozygous mutations of the BSCL2 gene?", "output": "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement" }, { "input": "Which is the target protein of the drug nivolumab?", "output": "Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation." }, { "input": "The CXCR2 receptor is targeted in cancer. Name five antagonists.", "output": "There are numerous CXCR2 receptor antagonists, such as SB225002, G31P, SCH-527123, AZ10397767, SCH-479833." }, { "input": "What is the genomic structure of the FAA (FANCA) gene?", "output": "The FAA (FANCA) gene contains 43 exons spanning approximately 80 kb. Exons range from 34 to 188 bp, whereas sequence analysis of the 5' region upstream of the putative transcription start site showed no obvious TATA and CAAT boxes, but did show a GC-rich region, typical of housekeeping genes." }, { "input": "What is Snord116?", "output": "SNORD116 is a small nucleolar (sno) RNA gene cluster (HBII-85) implicated as a major contributor the Prader-Willi phenotype. \nSNORD116 genes appears to be responsible for the major features of PWS. \nSNORD116 is a paternally expressed box C/D snoRNA gene cluster.\nThe mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.\nSnord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally.\nSnord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation." }, { "input": "What is the functional role of the protein Drp1?", "output": "Drp1 is involved in the regulation of mitochondrial fission." }, { "input": "What is the functional role of the protein Drp1?", "output": "Dynamin-related protein 1 (Drp1) mediates mitochondrial fission." }, { "input": "Which is the genetic cause for the development of Fanconi anemia complementation group D1?", "output": "Fanconi anemia complementation group D1 (FANCD1) was shown to be induced by biallelic mutations in the BRCA2 breast-cancer-susceptibility gene." }, { "input": "Which diseases are caused by mutations in Calsequestrin 2 (CASQ2) gene?", "output": "CASQ2 mutations are associated with autosomal recessive catecholaminergic polymorphic ventricular tachycardia (CPVT) and familial hypertrophic cardiomyopathy." }, { "input": "Which diseases are caused by mutations in Calsequestrin 2 (CASQ2) gene?", "output": "Mutations in the gene encoding for cardiac calsequestrin, CASQ2, cause a rare but severe form of catecholaminergic polymorphic ventricular tachycardia (CPVT).\nThere is also a publication that links mutations in CASQ2 gene to the disease of hypertrophic cardiomyopathy (HCM)." }, { "input": "What are the most frequent non-canonical sequence motifs at the donor and acceptor splice sites in vertebrates?", "output": "There are two major exceptions to the canonical GT-AG dinucleotides at donor and acceptor sites: the GG-AG splice site pairs, recognized through the typical U2 splicing machinery, and the AT-AC splice pairs recognized by the U12 splicing machinery." }, { "input": "What does isradipine do to L-type channels?", "output": "Isradipine antagonizes/blocks the L-type channels." }, { "input": "Why does cranberry juice help combat urinary tract infections?", "output": "Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli." }, { "input": "In which diseases have electronic patient diaries been applied ?", "output": "Parkinson's disease\nCOPD\nFood hypersensitivity\nNiacin induced flushing\nHemophilia\nHeartburn\nHeadache" }, { "input": "Which type of myeloma is ixazomib being evaluated for?", "output": "The disease focus for the irreversible epoxyketone proteasome inhibitor ixazomib is multiple myeloma." }, { "input": "Which are the Atg8 homologs in human?", "output": "Autophagy (Autophagy-related protein 8 or Atg8p or APG8 or AUT7 or CVT5) is a yeast protein involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosomes formation. In yeast it is represented by a single gene, the ATG8 family in humans contains 6 members (microtubule-associated protein-1 light chain 3A (MAP1LC3A), MAP1LC3B, MAP1LC3C, GABA(A) receptor-associated protein (GABARAP), GABARAPL1, and GABARAPL2/GATE-16)." }, { "input": "To which family does the Zika virus belong?", "output": "The Zika virus belongs to the family Flaviviridae." }, { "input": "Has the fungus Ashbya gossypii got many nuclei that share cytoplasm?", "output": "Yes, Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae." }, { "input": "What is the functionality of the Triplex R/bioconductor package?", "output": "Triplex is an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences. The package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz." }, { "input": "Which is the molecular mechanism underlying K-ras alterations in carcinomas?", "output": "Activating point mutations most frequently in codon 12" }, { "input": "Is microRNA(miRNA) 30 involved in post-ischemic cardiac remodeling?", "output": "Myocardial remodeling after an ischemic insult involves extracellular matrix proteins with increased fibrosis\nInitial experimental data indicate that miRNA 30 decreases CTGF a key molecule in the process of fibrosis, by directly downregulating the production of CTGF" }, { "input": "List all clinical trials of the polypill.", "output": "'Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial, European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250.\n'IMProving Adherence using Combination Therapy (IMPACT)', Australian New Zealand Clinical Trial Registry (ACTRN12606000067572).\n'Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)'\nPhase II study of the Polycap, double-blind, randomised trial, registered with ClinicalTrials.gov, number NCT00443794\nSecond Indian Polycap Study, TIPS-2\nCluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial)\nGEMINI trial, 14-week, open-label trial conducted in 1220 patients from the USA\nGEMINI-Australia, Asia, Latin America, Africa/Middle East (AALA) study \nJEWEL study program, with JEWEL 1 conducted among 1138 patients from the UK and Canada and JEWEL 2 conducted in 1107 patients from Europe\nCAPABLE54, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points , in the USA\nCUSP (The Caduet\u00ae in an Untreated Subject Population trial)\nTOGETHER trial\nA randomised controlled trial in seven countries \u2013 Australia, Brazil, India, Netherlands , New Zealand , United Kingdom and United States. Australian New Zealand Clinical Trials Registry (ACTRN 12607000099426)" }, { "input": "List all clinical trials of the polypill.", "output": "A number of clinical trials evaluating polypill, mainly in cardiovascular patients, have been performed and include the Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial), Atorvastatin and Amlodipine in Patients with Elevated Lipids and Hypertension (AVALON) trial, Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), GEMINI trial, GEMINI-Australia, Asia, Latin America, Africa/Middle East (GEMINI-AALA) study, JEWEL 1 trial, JEWEL 2 trial, Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE54), The Caduet\u00ae in an Untreated Subject Population trial (CUSP), TOGETHER trial, TIPS trial, TIPS-2 trial and IMProving Adherence using Combination Therapy (IMPACT)." }, { "input": "What is transvection?", "output": "An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals." }, { "input": "What is transvection?", "output": "Pairing-dependent interallelic complementation was first described for the Ultrabithorax gene of the bithorax-complex in Drosophila by Lewis and cited as an example of a new phenomenon that Lewis called the trans-vection effect. Several different kinds of pairing-dependent gene expression have been observed in Drosophila, and it is now clear that a variety of different molecular mechanisms probably underlie the changes in gene expression that are observed after disrupting chromosome pairing. Transvection in the bithorax-complex appears to result from the ability of cis-regulatory elements to regulate transcription of the promoter on the homologous chromosome. The same phenomenon appears to be responsible for pairing-dependent interallelic complementation at numerous other genes in Drosophila. Some transvection effects are dependent on the presence of wild-type or specific mutant forms of the protein encoded by the zeste trans-regulatory gene, but other transvection effects are zeste-independent. The ease with which chromosome aberrations can disrupt transvection also varies widely among different genes " }, { "input": "What is the role of probiotics in gastrointestinal disease?", "output": "Probiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Across all 11 probiotic species and eight different gastrointestinal diseases - Irritable Bowel Syndrome (IBS), Helicobacter pylori infection (HPP), Necrotizing Enterocolitis (NEC), Pouchitis (Pouch), Antibiotic Associated diarrhea (AAD), Clostridium difficile Disease (CDD), Infectious diarrhea (ID), and Travellers diarrhea (TD) - probiotics have been shown to have effect on prevention and treatment of gastrointestinal disease through enhancing the immune response, protection against abnormal invasive bacteria. Probiotics have a role in all age groups, incl. infants." }, { "input": "What is the main symptom of Marfan syndrome patients?", "output": "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. Pathohistological alterations of the aorta in patients with Marfan syndrome consisted in pronounced restructuring of the wall with deep irreversible alternative changes. The risk of aortic dissection, which is the most serious manifestation of the Marfan syndrome, increases as the aorta enlarges. Surgical replacement of the aortic root with a composite graft does not end the disease process." }, { "input": "What is the main symptom of Marfan syndrome patients?", "output": "Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, which may involve the proximal and distal aorta, mitral valve prolapse, and mitral regurgitation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations." }, { "input": "What is the main symptom of Marfan syndrome patients?", "output": "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. It is of utmost importance to identify patients at risk for acute aortic events to establish the correct surgical timing and the appropriate surgical treatment" }, { "input": "What species is associated with Tetrodotoxin?", "output": "Tetrodotoxin (TTX) is a low molecular weight (approximately 319 Da) neurotoxin found in a number of animal species, including pufferfish. TTX is originally produced by marine bacteria, and pufferfish are intoxicated through the food chain that starts with the bacteria. TTX is found in warm waters, especially of the Indian and Pacific Oceans. TTX poisoning due to marine snails has recently spread through Japan, China, Taiwan, and Europe." }, { "input": "How is myotonic dystrophy inherited?", "output": "Myotonic dystrophy (DM) is a heterogeneous neuromuscular disease with an autosomal dominant pattern of inheritance." }, { "input": "How do HBS1L-MYB intergenic variants regulate fetal hemoglobin?", "output": "HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers. Several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. Several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels." }, { "input": "Which are the mammalian orthologs of Drosophila Yki?", "output": "There are two mammalian orthologs of Yki: YAP and TAZ" }, { "input": "Is statin use associated with improved outcomes after aneurysmal subarachnoid hemorrhage?", "output": "Statin use after subarachnoid hemorrhage has been shown be associated with improved outcomes by some prospective clinical trials. It has been reported that statin use after subarachnoid hemorrhage reduced rates of vasospasm, delayed cerebral ischemia, and mortality. However, other authors have failed to find beneficial effect of statin use in subarachnoid hemorrhage patients." }, { "input": "What is the typical outer diameter of microtubules (tubulin heterodimers)?", "output": "Microtubules are highly anisotropic structures built from tubulin heterodimers. They are hollow cylindrical shells with a \u223c 25 nm (24nm - 25nm) outer diameter." }, { "input": "Does molindone affect body weight?", "output": "Yes, molindone has a tendency to cause weight loss or limited weight gain." }, { "input": "What is the genetic basis of propionic acidemia?", "output": "Mutations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase." }, { "input": "Which protein phosphatase has been found to interact with the heat shock protein, HSP20?", "output": "Protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, revealed an association between Hsp20 and PP1. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling." }, { "input": "Which protein phosphatase has been found to interact with the heat shock protein, HSP20?", "output": "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling." }, { "input": "What is the risk in G-CSF treatment for severe congenital neutropenia?", "output": "Severe congenital neutropenia is a rare hematological condition causing severe chronic neutropenia. Treatment with the myeloid growth factor, granulocyte-colony stimulating factor (G-CSF) is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of the patients evolve to develop acute myeloid leukemia or myelodysplastic syndromes, necessitating careful clinical monitoring." }, { "input": "Neurostimulation of which nucleus is used for treatment of dystonia?", "output": "Neurostimulation of globus pallidus internus is effective for treatment of dystonia. Ventral intermediate thalamic nucleus has also been tested for neurostimulation in dystonia patients." }, { "input": "Which myosin isozymes are located within the pericuticular necklace of the hair cell?", "output": "The hair cell is located in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes. Within the pericuticular necklace, a domain of the hair cell, certain unconventional myosin isozymes are located, namely myosins-Ibeta, myosin-VI, and myosin-VIIa." }, { "input": "Which is the treatment strategy followed in spinocerebellar ataxia type 3 for CAG removal?", "output": "The novel treatment strategy proposed for treatment of Spinocerebellar ataxia type 3 is the removal of the toxic polyglutamine repeat from the ataxin-3 protein through antisense oligonucleotide-mediated exon skipping while maintaining important wild type functions of the protein." }, { "input": "Where is the angiogenin binding element located?", "output": "Angiogenin binds to CT repeats that are abundant in the nontranscribed region of the ribosomal RNA gene. An angiogenin-binding DNA sequence (CTCTCTCTCTCTCTCTCCCTC) has been identified and designated angiogenin-binding element (ABE)." }, { "input": "Which proteins cause cytoplasmic sequestration of NF-kB?", "output": "In unstimulated cells, NF-kB transcription factors are retained in the cytoplasm with the inhibitory activity of I-kBs, Sef, NF-kB1 (p105) and NF-kB2 (p100)." }, { "input": "What is the mode of inheritance of Marchesani syndrome?", "output": "Marchesani syndrome is transmitted either by an autosomal dominant (mutations in FBN1) or an autosomal recessive (mutations in ADAMTS10) mode of inheritance" }, { "input": "Tumor-treating fields are effective for treatment of which cancers?", "output": "Clinical trials have shown that Tumor-treating fields are effective for treatment of non-small cell lung cancer and glioblastoma. Ongoing and future trials will evaluate TTFields in solid tumor brain metastases, and ovarian, pancreatic cancers and multidrug resistance cancer cells." }, { "input": "Which event results in the acetylation of S6K1?", "output": "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation. We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling. Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300" }, { "input": "Which event results in the acetylation of S6K1?", "output": "Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin deacetylases in S6K deacetylationUsing acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation" }, { "input": "Which event results in the acetylation of S6K1?", "output": "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling" }, { "input": "Which event results in the acetylation of S6K1?", "output": "K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling, followed by interaction with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6K1 can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300." }, { "input": "List angiocrine factors", "output": "Angiocrine factors are: Ccl4, neurotensin, vascular endothelial growth factor, metalloproteinases-1, thrombospondin 3, Slit2, hepatocyte growth factor, Wnt2. " }, { "input": "What is protein carbamylation?", "output": "Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and carbamylation occurs when cyanate ions react with the amino groups of lysines, arginines, protein N-termini, as well as sulfhydryl groups of cysteines. Protein carbamylation is one of the important post-translational modifications, which plays a pivotal role in a number of biological conditions, such as diseases, chronic renal failure and atherosclerosis." }, { "input": "What is the cause of episodic ataxia type 6?", "output": "Episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. Reduced glutamate uptake by mutant excitatory amino acid transporter-1 (EAAT1) has been thought to be the main pathophysiological process in episodic ataxia type 6." }, { "input": "What is the main role of Ctf4 in dna replication?", "output": "coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this processAnd-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery" }, { "input": "What is the main role of Ctf4 in dna replication?", "output": "Ctf4 coordinates the progression of helicase and DNA polymerase alpha. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery." }, { "input": "Could Arimidex (anastrozole) cause hot flashes?", "output": "Yes. Hot flashes are one of the most common adverse effects of Arimidex." }, { "input": "What is the role of Inn1 in cytokinesis?", "output": "Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane during cytokinesis in budding yeast, whereas the remainder of the protein recruits Inn1 to the actomyosin ring" }, { "input": "Which hormone deficiency is implicated in the Costello syndrome ?", "output": "Growth hormone deficiency is implicated in Costello syndrome. Growth hormone therapy should be administered with caution due to possible severe side effects. Cortisol and sex hormone deficiencies were also implicated in Costello syndrome." }, { "input": "List the components of a Replisome Progression Complex (RPC).", "output": "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I." }, { "input": "List the components of a Replisome Progression Complex (RPC).", "output": "RPCs also interact with Mcm10 and topoisomerase I. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs. This interaction requires the RPC components Mrc1 and Ctf4, both of which associate with a tetratricopeptide repeat (TPR) domain located at the amino terminus of Dia2. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. " }, { "input": "What is the definition of minimal absent words?", "output": "An absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation also provides a fast alternative for measuring approximation in sequence comparison." }, { "input": "What is the common feature in congenital central hypoventilation and Mowat-Wilson syndromes?", "output": "About 30% of Hirschsprung disease (HSCR) cases are syndromic. Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)." }, { "input": "What is the common feature in congenital central hypoventilation and Mowat-Wilson syndromes?", "output": "In CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant." }, { "input": "Which is the most common CFTR mutation in Caucasians?", "output": "The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4)." }, { "input": "Which CDK targets control cytokinesis?", "output": "Aip1, Ede1 and Inn1 are CDK targets whose dephosphorylation is required for cytokinesis." }, { "input": "Are Alu elements transcribed?", "output": "A significant percentage of the more than 1 million copies of Alu elements was shown to be transrcribed. Free Alu RNAs are known to be transcribed by Pol III from their own promoter. On the other hand, embedded Alu RNAs are transcribed by Pol II as part of protein- and non-protein-coding RNAs. Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression." }, { "input": "In what type(s) of plant organelles we can detect prolamellar bodies?", "output": "Prolamellar body (PLB) is a highly organized lipid structure, which is the main site of accumulation of the ternary light-harvesting POR complex LHPP (light-harvesting NADPH:protochlorophyllide oxidoreductase:protochlorophyllide). Prolamellar bodies have been discovered in etioplasts with the use of thin section electron microscopy. Etioplasts develop in the place of chloroplasts in the dark. During skotomorphogenesis in angiosperms, NADPH:protochlorophyllide oxidoreductase (POR) forms the photolabile NADPH-POR-protochlorophyllide (Pchlide) ternary complexes. Prolamellar bodies (PLBs) efficiently capture the light energy for photo conversion in etioplasts. Upon illumination, the etioplasts transformed into regular chloroplasts. PLBs are formed not only in etioplasts but also in chloroplasts in young developing leaves during the night." }, { "input": "What do mepolizumab and reslizumab have in common?", "output": "Mepolizumab and reslizumab are monoclonal antibodies that target and neutralize interleukin 5. They have been shown to reduce eosinophil counts and they are used for the treatment of refractory asthma (associated with eosiniphilia) and other eosinophilic diseases." }, { "input": "When are itaconic acid levels elevated?", "output": "Itaconic acid levels are elevetad in immune defence." }, { "input": "Are chromomethylases present in animal genomes?", "output": "No. Multiple lines of experimental evidence suggest that chromomethylases (CMTs) have been hitherto identified in plant genomes(Arabidopsis, maize, tomato). CMTs maintain CpNpG (N = A, T, C, or G) methylation and they are unique to the plant kingdom. The lack of CMT homologs in animal genomes could be explained based on the fact that, in contrast to plants, animals maintain primarily CG methylation. Therefore, the presence of CMTs is not required in the animal genomes." }, { "input": "Which genes are associated with autosomal dominant Charcot-Marie-Tooth?", "output": "The genes associated with the X-linked and the autosomal dominant forms of Charcot-Marie-Tooth disease are GJB1, MPZ, INF2, DNM2, YARS, GNB4, NEFL, MFN2, LRSAM1, GDAP1, PMP22, LITAF, and EGR2. Identification of these genes has not only been important for patients and families, but also provided new information about disease pathogenesis." }, { "input": "Which transcription factors (TFs) participate in the formation of the interferon-beta (IFN-b) enhanceosome?", "output": "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y). Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. " }, { "input": "Which transcription factors (TFs) participate in the formation of the interferon-beta (IFN-b) enhanceosome?", "output": "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B. However, HMG I(Y) plays an essential role in the assembly and function of the IFN beta gene enhanceosome." }, { "input": "Is low T3 syndrome related with high BNP in cardiac patients?", "output": "BNP and fT3 are independently associated in severely compromised HF patients.\nNT-pro-BNP was significantly associated with low-T3 syndrome in cardiac patients.\nHigher NT-pro BNP concentrations are related to lower total T3 concentrations in cardiac patients" }, { "input": "List packages for transcription factor binding sites' (TFBS) analysis available in R/Bioconductor", "output": "Neighbourhood Consistent PC (NCPC) algorithms, MMDiff and cosmo." }, { "input": "Simpson grading is used to describe resection of which brain tumor?", "output": "The Simpson grading system was used to assess the extent of surgical resection of meningioma." }, { "input": "Where in the cell do we find the protein Cep135?", "output": "centrosome" }, { "input": "Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy?", "output": "Delayed enhancement is documented in almost 30% of patients with non-ischemic dilated cardiomyopathy and its pattern is characterized by mid-wall, patchy or diffuse location." }, { "input": "Which enzyme is inhibited by Varespladib?", "output": "Varespladib is a secretory phospholipase A2 (sPLA2) inhibitor. It was tested in patients with acute coronary syndrome." }, { "input": "Which protein does empagliflozin inhibit?", "output": "Empagliflozin (Jardiance) is a SGLT2 inhibitor." }, { "input": "What symptoms characterize the Muenke syndrome?", "output": "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition. Tarsal coalition is a distinct feature of Muenke syndrome and has been reported since the initial description of the disorder in the 1990s. " }, { "input": "What symptoms characterize the Muenke syndrome?", "output": "Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pansynostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (broad skull), although turribrachycephaly (a \"tower-shaped\" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: ocular hypertelorism, ptosis or proptosis (usually mild), midface hypoplasia, temporal bossing, and a highly arched palate. Strabismus is common. Extracranial findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family." }, { "input": "List all reported treatment options for anxiety in autism spectrum disorder.", "output": "The predominant approach is to use versions of cognitive behavioural therapies, such as:\nMindfulness Based Therapy (MBT)\nMultimodal Anxiety and Social Skills Intervention (MASSI) program\nmodified version of the Coping Cat program, (cognitive-behavioral therapy; CBT)\nFamily cognitive-behavioral therapy has been found to be more effective than Individual cognitive-behavioral therapy \nConflict management for couples, even when conflict and family distress is low\n\nDrugtherapy: \nSertraline" }, { "input": "List adenosine A2A receptor antagonists that are used for Parkinson's disease treatment.", "output": "Istradefylline and preladenant are adenosine A2A receptor antagonists that are used for Parkinson's disease treatment." }, { "input": "What is the clinical indication of cardiac T1 mapping magnetic resonance?", "output": "T1 mapping can quantitatively characterize myocardial tissue, in particular diffuse and interstitial fibrosis, edema in both overt and subclinical cardiophyopathies. However more research is required before a large-scale application for clinical decision-making can be recommended." }, { "input": "What is the clinical indication of cardiac T1 mapping magnetic resonance?", "output": "The clinical indication of cardiac T1 mapping magnetic resonance is the detection of diffuse myocardial fibrosis in nonischemic cardiomyopathies" }, { "input": "Which autophagy pathway is trigered by the KFERQ motif of cytosolic proteins?", "output": "Cytosolic proteins carrying the KFERQ motif (a specific lysosomal import consensus sequence) are directed to a selective form of lysosomal degradation, called chaperone-mediated autophagy (CMA), as chaperone protein Hsc73 and other chaperones are involved in this process." }, { "input": "Which are the clinical characteristics of TSC?", "output": "Tuberous sclerosis or tuberous sclerosis complex (TSC) is a rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease. TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation." }, { "input": "How does dabigatran therapy affect aPTT in patients with atrial fibrillation?", "output": "Dabigatran increases aPTT in patients with atrial fibrillation, although aPTT does not respond linearily to dabigatran therapy." }, { "input": "List fish anti-freeze proteins.", "output": "AFP-I\nAFP-II\nAFP-III\nAnti-freeze glycoprotein\nThermal hysteresis protein" }, { "input": "Which is the phosphorylated residue in the promoter paused form of RNA polymerase II?", "output": "The promoter paused form of RNA polymerase II is phosphorylated on serine 5 residues of the C-terminal heptapeptide repeat domain (CTD) of the largest subunit." }, { "input": "Has overexpression of sirtuins been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)?", "output": "Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)." }, { "input": "Name the major classes of small non coding RNAs in mammalians?", "output": "microRNAs (miRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs) are the major classes of small non coding RNAs. Recently, thanks mostly to massively parallel sequencing technologies, other classes of small RNAs have been discovered, such as piRNAs and scaRNAs." }, { "input": "Describe a diet that reduces the chance of kidney stones.", "output": "People can help prevent kidney stones by making changes in fluid intake and, depending on the type of kidney stone, changes in consumption of sodium, animal protein, calcium, and oxalate.\nDrinking enough fluids each day is the best way to help prevent most types of kidney stones. Health care providers recommend that a person drink 2 to 3 liters of fluid a day. People with cystine stones may need to drink even more. Though water is best, other fluids may also help prevent kidney stones, such as citrus drinks." }, { "input": "What pharmacological and non-pharmacological interventions can be considered as prophylactic therapies in Cluster Headache patients?", "output": "Verapamil, a calcium channel blocker, is considered the mainstay of prophylactic therapy of Cluster Headache patients. Lithium carbonate, topiramate, valproic acid, gabapentin, baclofen, methysergide, melatonin, ketoprofen and indomethacin can also be tried for prophylactic therapy of Cluster Headaches patients. Non-pharmacological prophylactic measures, such as peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation, ablative surgery, and botulinum toxin type-A (BTX-A) injection, can be also considered." }, { "input": "How does phospholamban affect the biological activity of the calcium ATPase SERCA?", "output": "SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum. Based on structural and dynamics data, a model in which PLN undergoes allosteric activation upon encountering SERCA has been proposed. The allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation of PLN shifts the populations toward the B state, increasing SERCA activity. Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure." }, { "input": "List the components of mTOR Complex 2 (mTORC2).", "output": "Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/G\u03b2L and PRR5." }, { "input": "What is known about the Digit Ratio (2D:4D) cancer?", "output": "Digit ratio (2D:4D) is associated with gastric cancer, prostate cancer, breast cancer, cervical intraepithelial neoplasia and oral squamous cell carcinoma. 2D:4D was found to be higher in patients diagnosed with gastric cancer and prostate cancer patients relative to controls. Among prostate cancer patients, 2D:4D shows strong differences between African-Americans and Caucasians; however, it does not correlate with disease severity in men already diagnosed with prostate cancer. However, other authors did not find an association between 2D:4D and prostate cancer risk.\n 2D:4D is not associated with testicular germ cell tumors." }, { "input": "Is TREM2 associated with Alzheimer's disease?", "output": "A rare variant of the TREM2 gene, which encodes the triggering receptor encoded in myeloid cells 2 (rs75932628-T) causing a R47H substitution has been associated with both early and late onset Alzheimer's disease in various populations. Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons. Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients which indicates that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis. Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment." }, { "input": "Does the protein mTOR regulate autophagy?", "output": "mammalian target of rapamycin (mTOR) is a major negative regulator of autophagy." }, { "input": "Which are the mains risk factors of metabolic syndrome?", "output": "Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes." }, { "input": "Which multiple kinase inhibitors are used in cancer therapy?", "output": "Multiple kinase inhibitors used in cancer therapy include ZD6474, SU11248, AEE 788, sorafenib, vatalanib, and AG-013736." }, { "input": "Has proteomics been used in the study of Pick's disease?", "output": "Yes, proteomics has been used in the study of Pick's disease." }, { "input": "Are there any urine biomarkers for bladder cancer diagnosis?", "output": "Bladder cancer is any of several types of malignancy arising from the epithelial lining of the urinary bladder. Rarely the bladder is involved by non-epithelial cancers, such as lymphoma or sarcoma. It is a disease in which abnormal cells multiply without control in the bladder.The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer recapitulates the normal histology of the urothelium and is known as transitional cell carcinoma or more properly urothelial cell carcinoma. It is estimated that there are 383,000 cases of bladder cancer worldwide" }, { "input": "Are there any urine biomarkers for bladder cancer diagnosis?", "output": "Yes, there are. Urine biomarkers for bladder cancer diagnosis range from voided urine cytology and the UroVysion\u00ae cytogenetic test, to fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22, Bladder Tumor Antigen, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, telomerase, IL-8, MMP-9 and 10, PAI-1, VEGF, ANG, CA9 and APOE." }, { "input": "List types of avoided words in bacterial genomes", "output": "Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in the complete genome of the archaeon Methanococcus jannaschii. Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly, suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages. Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes." }, { "input": "Which gene(s) should be genotyped in order to prescribe the drug Cetuximab (anti-EGFR)?", "output": "KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients.\nOther genes are such as EGFR, BRAF and T53 have also been suggested to be genotyped in order to evaluate the drug responsivness." }, { "input": "Is signal transducer and activator of transcription-3 (STAT3) critical for tumor angiogenesis progression?", "output": "(STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis" }, { "input": "Which is the physiological target for LeuRS translational quality control?", "output": "QUALITY CONTROL" }, { "input": "Which is the physiological target for LeuRS translational quality control?", "output": "The physiological target for LeuRS translational quality control is norvaline." }, { "input": "Which is the physiological target for LeuRS translational quality control?", "output": "The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNAs. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline." }, { "input": "Is sumoylation implicated in myogenesis?", "output": "Yes, sumoylation is implicated in myogenesis." }, { "input": "Is sumoylation implicated in myogenesis?", "output": "Yes, protein sumoylation present in myoblasts is regulated in myogenesis." }, { "input": "What do studies show about the effect of Induced hypothermia in premature babies?", "output": "Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities in term or late preterm infants. It remains unclear to what degree preterm infants were included in these studies.\nA prospective non-randomised pilot study reported that mild hypothermia for 48 hours in preterm neonates with severe NEC (necrotising enterocolitis) seems both feasible and safe." }, { "input": "Describe what is the advantage of using a stain free protein gel in a Western Blot experiment?", "output": "Stain-Free technology can be used as a normalization tool in Western blot analysis." }, { "input": "Which is the target of the drug Denosumab?", "output": "Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-\u03baB ligand (RANKL)." }, { "input": "Which enzyme is inhibited by a drug fostamatinib?", "output": "Fostamatinib (R788) acts by inhibiting spleen tyrosine kinase. Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase that is required for the expression of a number of proinflammatory cytokines. Fostamatinib has been shown to be effective in patients with rheumatoid arthritis, leukemia, lymphoma, bronchial asthma and thrombocytopenic purpura." }, { "input": "Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barr\u00e9?", "output": "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia" }, { "input": "Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barr\u00e9?", "output": "Miller-Fisher syndrome is a variant of Guillain-Barr\u00e9 syndrome, characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia." }, { "input": "Is Ctf4 involved in sister chromatid cohesion establishment?", "output": "Yes. Ctf4 is associated with the replisome and is required for proper establishment of cohesion by facilitating cohesin acetylation." }, { "input": "What states the second parity rule (PR2)?", "output": "The second parity rule (PR2), also known as Chargaff' s second parity rule, is an intra-strand rule which states that, when there are no biases between the two complementary strands of DNA in mutation and selection rates (substitution rates), complementary nucleotides are expected to have almost equal frequencies within single stranded DNA, namely A = T and G = C at equilibrium, without regard to the G + C content of the DNA." }, { "input": "Are retroviruses used for gene therapy?", "output": "Gene therapy is one of the most promising and active fields in therapeutic research. Gene therapy is a treatment option that introduces genetic material in vivo or ex vivo into the cells of an affected organism in order to: exchange a defective gene; manipulate a disease-related gene; or introduce an additional gene copy for overexpression of the encoded protein to generate a curative biological effect. Somatic gene therapy is gene transfer by a specific vector to a somatic cell; in contrast to germline gene therapy, the modification of the cell is restricted to the recipient and cannot be passed to her/his progeny. High efficiency of gene transfer, high specificity for the target cells, long-lasting expression of the transgene and safety without adverse reactions are the desired characteristics of an ideal vector for gene transfer.\nRetroviral (gretroviral and lentiviral) vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred transgene(s), and also because little effort is required for their cloning and production. Several monogenic inherited diseases, mostly immunodeficiencies, can now be successfully treated." }, { "input": "Do lincRNAs play a role in human cancer?", "output": "Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. The best-studied examples include HOTAIR, a negative prognostic factor that exhibits pro-oncogenic activity in a variety of human cancers, CRNDE the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression and ANRIL, a lincRNA that is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene." }, { "input": "Explain the concept proteostasis.", "output": "Protein homeostasis, or proteostasis, refers to a proper balance between synthesis, maturation, and degradation of cellular proteins. Disruption of proteostasis is implicated in aging and the pathogenesis of numerous degenerative diseases." }, { "input": "Which gene test can be used for the X-linked myotubular myopathy?", "output": "Genetic testing of the MTM1 gene can be used for the X-linked myotubular myopathy." }, { "input": "Is there a phylogenetic analysis for HIV?", "output": "In biology, phylogenetics is the study of evolutionary relationships among groups of organisms (e.g. species, populations), which are discovered through molecular sequencing data and morphological data matrices. The result of phylogenetic studies is a hypothesis about the evolutionary history of taxonomic groups: their phylogeny. \nPhylogenetic analysis examines small differences in HIV\u2019s genes using computational methods to calculate the genetic distance between strains. Unlike\nhuman DNA, which remains stable for a lifetime, HIV\u2019s RNA changes very rapidly, leading to a huge amount of genetic diversity. This diversity means that scientists, using phylogenetic analysis, have been able to ascertain where HIV comes from, as well as track the various strains of HIV that exist worldwide.\nBased on results, there are found many studies on HIV phylogenetic analysis." }, { "input": "What is the association between adiponectin and migraine?", "output": "There is evidence to suggest that adiponectin plays a role in migraine. Increase in body fat elevates adiponectin and leptin secretion which in turn impair inflammatory processes that could be contributing to migraine risk. In episodic migraine patients, adiponectin was associated with migraine severity and predictive of acute treatment response. Serum adiponectin levels are increased in women chronic daily headache sufferers." }, { "input": "Which phenomenon is described as oncogene addiction?", "output": " Oncogene addiction describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. We propose that addiction may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call oncogenic shock, prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death. " }, { "input": "Which phenomenon is described as oncogene addiction?", "output": "\"Oncogene addiction\" describes the curious acquired dependence of tumor cells on an activated oncogene for their survival and/or proliferation, a phenomenon that has important implications for the success of targeted cancer therapies. However, the mechanisms explaining oncogene addiction remain elusive. \"Addiction\" may be an illusion generated as a consequence of differential attenuation rates of prosurvival and proapoptotic signals emanating from an oncoprotein acutely following its inactivation. According to this model, which we call \"oncogenic shock,\" prosurvival signals dissipate quickly on oncoprotein inactivation whereas proapoptotic signals linger sufficiently long to commit the cell to an apoptotic death." }, { "input": "Are there randomised controlled trials on sevoflurane?", "output": "Yes. There are < 10 studies reported, answering questions like : how to improve speed of recovery, relationship to dreaming and anesthetic experience, effect on cardiac troponin release, effect on myocardial injury, postoperative delirium, haemodynamics & emergence and recovery characteristics of total intravenous anaesthesia, costs of postoperative nausea and vomiting, pediatric conscious sedation for dental procedures" }, { "input": "In which cells are gasdermins expressed?", "output": "Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract." }, { "input": "Where in a protein can a signal sequence be found?", "output": "Proteins have signal sequences typically resent at the most N-terminal end." }, { "input": "Can FOXOs modulate longevity?", "output": "FOXOs are reliable markers of longevity." }, { "input": "Which antibody is implicated in the Bickerstaff's brainstem encephalitis?", "output": "The syndrome defined by Bickerstaff of progressive, external ophthalmoplegia and ataxia, with disturbance of consciousness or hyperreflexia, has subsequently been associated with antiganglioside antibody, anti-GQ1b" }, { "input": "Which micro-RNAs have been associated in the pathogenesis of Rheumatoid Arthritis?", "output": "Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients." }, { "input": "Is there an association between FGFR3 mutation and plagiocephaly?", "output": "Yes, FGFR3 mutation is associated with plagiocephaly. It is the most common mutation in plagiocephaly. FGFR genes have important effects on bone development, and mutations in 4 \"hot spot\" exons of FGFR1-3 are found in many patients with craniosynostosis and some with synostotic plagiocephaly." }, { "input": "Are CD44 variants (CD44v) associated with poor prognosis of metastasis?", "output": "Yes, several isoforms (obtained by by usage of ten variant exons in various combinations) have been causally related to metastasis." }, { "input": "Is Bladder training an effective method to treat urge incontinence ?", "output": "Yes. Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy. Quoted results vary from 26 to 90% . Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency." }, { "input": "What is the scope of the OMIA database?", "output": "Online Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited disorders and other familial traits in animals. OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible." }, { "input": "What is the effect of methotrexate in treating uveitis due to juvenile idiopathic arthritis ?", "output": "The first-line standard therapy for uveitis is topical and systemic corticosteroids, often reinforced by methotrexate as a second-line disease-modifying antirheumatic drug (DMARD). MTX has a topical steroid sparing effect as well. Early treatment with MTX is advocated to prevent complications such as cataract. There are no trial data on the effect of MTX. Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study). Biologic DMARDs can be used with Methotrexate in refractory uveitis as well." }, { "input": "Which are the enzymes involved in the addition of 7-methylguanosine in mRNA?", "output": "The 7-methylguanosine cap added to the 5\u2032 end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. In the addition of 7-methylguanosine in mRNA involved the RNA polymerase II, RNA guanylyltransferase and RNA guanine-7 methyltransferase enzymes." }, { "input": "Which are the enzymes involved in the addition of 7-methylguanosine in mRNA?", "output": "The enzymes involved in the addition of 7-methylguanosine in mRNA are RNA guanylyltransferase and 5'-phosphatase (RNGTT), RNA guanine-7 methyltransferase (RNMT or hMTr1), RNMT-activating mini-protein (RAM), RNA polymerase II, S-adenosylhomocysteine hydrolase (SAHH), and Myc." }, { "input": "What is HOCOMOCO?", "output": "HOCOMOCO is a comprehensive collection of human transcription factor binding sites models constructed by integration of binding sequences obtained by both low- and high-throughput methods. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source." }, { "input": "In which condition was protein S100A7 originally identified?", "output": "Psoriasin (S100A7) was originally identified in psoriasis." }, { "input": "Do proton pump inhibitors affect thyroxine absorption?", "output": "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption.\nPatients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose." }, { "input": "Is PER3 required for CHK2 activation in human cells?", "output": "Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.Per3, a circadian gene, is required for Chk2 activation in human cells." }, { "input": "Is PER3 required for CHK2 activation in human cells?", "output": "Per3, a circadian gene, is required for Chk2 activation in human cells. " }, { "input": "Is PER3 required for CHK2 activation in human cells?", "output": "Per3, a circadian gene, is required for Chk2 activation in human cells.Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage," }, { "input": "Is PER3 required for CHK2 activation in human cells?", "output": "Per3 gene, involved in circadian rhythm control, is required for Chk2 activation in human cells." }, { "input": "What is the typical alteration of the thyroid profile metabolism early after coronary artery bypass graft surgery?", "output": "Low T3 Syndrome is the more frequent alteration of thyroid hormone profile early after coronary artery bypass graft surgery." }, { "input": "Which proteins are involved in actin bundling and filopodia formation and function?", "output": "A number of proteins have been found to regulate F-actin bundling and enhance filopodia formation and motility. Among these are Cysteine-rich protein 1 (CRP1), Fascin, Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2), Insulin receptor tyrosine kinase substrate p53 (IRSp53), Missing in metastasis protein (MIM), Eps8, Diaphanous-related formin (dDia2) and Vasodilator-stimulated phosphoprotein (VASP)." }, { "input": "What does the SAGA complex acronym stands for?", "output": "SAGA stands for Spt-Ada-Gcn5-acetyltransferase (SAGA)" }, { "input": "What is the result of the interaction between TSC1 and PLK1?", "output": "Phosphorylated TSC1 (hamartin) interacts with Plk1 independent of TSC2 (tuberin), with all three proteins present in a complex, and negatively regulates the protein levels of Plk1, to control centrosome duplication." }, { "input": "What are the characteristics of the \"Universal Proteomics Standard 2\" (UPS2)?", "output": "The UPS2 proteomic dynamic range standard was introduced by the Association of Biomolecular Resource Facilities Proteomics Standards Research Group in 2006 and it has a dynamic range of 5 orders of magnitude." }, { "input": "Which polyQ tract protein is linked to Spinocerebellar Ataxia type 2?", "output": "Ataxin-2 is an evolutionarily conserved protein first identified in humans as responsible for spinocerebellar ataxia type 2 (SCA2). The molecular basis of SCA2 is the expansion of a polyglutamine tract in Ataxin-2, encoding a Lsm domain that may bind RNA and a PAM2 motif that enables interaction with the poly (A) binding protein." }, { "input": "Which are the smallest known subviral pathogens of plants?", "output": "Contrary to earlier beliefs, viruses are not the smallest causative agents of infectious diseases. Single-stranded RNAs as small as 246 nucleotides exist in certain higher plants and cause more than a dozen crop diseases. These RNAs have been termed viroids. Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein." }, { "input": "Which are the smallest known subviral pathogens of plants?", "output": "Since the discovery of non-coding, small, highly structured, satellite RNAs (satRNAs) and viroids as subviral pathogens of plants , have been of great interest to molecular biologists as possible living fossils of pre-cellular evolution in an RNA world." }, { "input": "What causes Katayama Fever?", "output": "Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection." }, { "input": "List clinical trials for prevention of sarcopenia", "output": "Several clinical trials with androgen replacement therapy. \nStudy was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis. This trial was registered at clinical trials.gov as NCT00794079" }, { "input": "Which is the database of molecular recognition features in membrane proteins?", "output": "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins." }, { "input": "Which is the database of molecular recognition features in membrane proteins?", "output": "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins " }, { "input": "Which is the database of molecular recognition features in membrane proteins?", "output": "mpMoRFsDB provides valuable information related to disorder-based protein-protein interactions in membrane proteins" }, { "input": "Which database is available for the identification of chorion proteins in Lepidopteran proteomes?", "output": "LepChorionDB" }, { "input": "Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?", "output": "Yes" }, { "input": "Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant?", "output": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid \u03b1-glucosidase (GAA))" }, { "input": "Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant?", "output": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme acid \u03b1-glucosidase (GAA), responsible for degradation of lysosomal glycogen." }, { "input": "Which kinase is inhibited by Tripolin A?", "output": "Tripolin A reduced the localization of pAurora A on spindle microtubules (MTs), affected centrosome integrity, spindle formation and length, as well as MT dynamics in interphase, consistent with Aurora A inhibition by RNAi or other specific inhibitors, such as MLN8054 or MLN8237. Interestingly, Tripolin A affected the gradient distribution towards the chromosomes, but not the MT binding of HURP (Hepatoma Up-Regulated Protein), a MT-associated protein (MAP) and substrate of the Aurora A kinase. Therefore Tripolin A reveals a new way of regulating mitotic MT stabilizers through Aurora A phosphorylation. Mitotic regulators exhibiting gain of function in tumor cells are considered useful cancer therapeutic targets for the development of small-molecule inhibitors." }, { "input": "Which kinase is inhibited by Tripolin A?", "output": "Tripolin A inhibits Aurora A kinase activity both in vitro and in human cells." }, { "input": "Is the optogenetics tool ChR2 light-sensitive?", "output": "Channelrhodospin-2 (ChR2) is a light-sensitive ion channel that has emerged as new optogenetics tool." }, { "input": "Is the Prostate- Specific Antigen (PSA) test relevant only for prostate cancer?", "output": "No, although the PSA test can detect high levels of PSA that may indicate the presence of prostate cancer, many other conditions, such as an enlarged or inflamed prostate, can also increase PSA levels." }, { "input": "List symptoms of Hakim Triad.", "output": "Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence." }, { "input": "Which is the cellular target of gefitinib?", "output": "The specific cellular target of Gefitinib (Iressa) is the epidermal growth factor receptor (EGFR)." }, { "input": "What kind of bonds are connecting keratin molecules?", "output": "cystine disulfide bonds\namide bonds\nhydrogen bonds" }, { "input": "Is autism one of the characteristics of Moebius syndrome?", "output": "Moebius syndrome is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius syndrome with autism spectrum disorders (ASDs) has been suggested in early studies with heterogenous age groups." }, { "input": "Is Sarcolipin a regulatory/inhibitory protein of the Calcium ATPase SERCA?", "output": "Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR) and it is a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure. Sarcolipin is a key regulator of SERCA2a in atria." }, { "input": "Is Sarcolipin a regulatory/inhibitory protein of the Calcium ATPase SERCA?", "output": "Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport.Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure." }, { "input": "What is the risk of developing acute myelogenous leukemia in Fanconi anemia?", "output": "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia." }, { "input": "What is the risk of developing acute myelogenous leukemia in Fanconi anemia?", "output": "A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia " }, { "input": "How many different mutations have been associated with Muenke syndrome?", "output": "Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)." }, { "input": "How can the fetal Rhesus be determined with non-invasive testing?", "output": "The detection of fetal RhD status can be achieved with the non-invasive method of assessing free fetal DNA in the maternal blood." }, { "input": "Which genes have been proposed as potential candidates for gene therapy of heart failure?", "output": "There are at least 6 genes which have been proposed as potential candidates of gene therapy in heart failure.\n1. Cardiac Sarco-Endoplasmic Reticulum Calcium ATPase 2A (SERCA2A)\n2. Inhibitor 1 (I-1) of Protein Phosphatase 1B\n3. Protein Phosphatase 1B (PP1B)\n4. Yes Associated Protein (YAP)\n5. Survivin\n6. S100A1" }, { "input": "DX-88 is investigational name of which drug?", "output": "DX-88 is investigational name of a drug Ecallantide, a 60-amino acid recombinant protein discovered through phage display technology, that is a highly specific, potent inhibitor of human plasma kallikrein that has been used successfully in the treatment of patients experiencing acute hereditary angioedema attacks." }, { "input": "What type of arrhythmia is known as bidirectional ventricular tachycardia (BDVT)?", "output": "Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT). Based on similarity of electrocardiographic features, bidirectional ventricular tachycardia has been considered a variant of long QT syndrome. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His-Purkinje system in the left and/or right ventricle, respectively. This \"ping pong\" mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy." }, { "input": "Which genes have been found to be associated with restless leg syndrome", "output": "Human L-Ferritin\nThe genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes\nHomozygosity for the T-allele of BTBD9 rs9296249\nMEIS1\nIntragenic guanosine triphosphate cyclohydrolase-1 duplication\nLRRK2 gene mutation" }, { "input": "Is the circadian clock involved in ribosome biogenesis?", "output": "Yes. The circadian clock coordinates ribosome biogenesis. It influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation." }, { "input": "Can mutations in Calmodulin cause ventricular fibrillation?", "output": "Yes, mutations in CALM underly IVF manifesting in childhood and adolescence." }, { "input": "Do the Sleeping Beauty or the piggyBac transposons have higher transposition efficiency?", "output": "Compared with Sleeping Beauty, PiggyBac exhibits higher transposition efficiencies." }, { "input": "Where does TORC1 sequester during heat stress?", "output": "Upon heat stress, TORC1 is recruited to stress granules." }, { "input": "Is rivaroxaban metabolized in kidneys?", "output": "rivaroxaban undergoes renal metabolism" }, { "input": "What are the side effects of Nalmefene?", "output": "Side effects of nalmefene include nausea, dizziness / lightheadedness, insomina, fatigue, vomiting, reduced caloric intake / apetite, increased self-rated alertness and decreased tiredness. In horses some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation has been described. In some studies nalmefene was well tolerated by all subjects, and no clinically significant adverse effects were observed." }, { "input": "Is Hirschsprung disease one of the characteristics of the Mowat-Wilson syndrome?", "output": "Mowat-Wilson syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects." }, { "input": "Is Hirschsprung disease one of the characteristics of the Mowat-Wilson syndrome?", "output": "Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprung s disease, intellectual disability, and prominent facial features are present " }, { "input": "Is Hirschsprung disease one of the characteristics of the Mowat-Wilson syndrome?", "output": "Yes. Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprungs disease, intellectual disability, and prominent facial features are present" }, { "input": "Which are the most common methods for gene prioritization analysis?", "output": "Functional annotation-based approaches and literature-based approaches have been initially used. In recent years, network-based methods - which utilize a knowledge network derived from biological knowledge - have been utilized for gene prioritization. Currently network-based methods are the ones most widely used." }, { "input": "Which is the most common disease attributed to malfunction or absence of primary cilia?", "output": "When ciliary function is perturbed, photoreceptors may die, kidney tubules develop cysts, limb digits multiply and brains form improperly. Mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease. Malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD)." }, { "input": "What is the usefulness of ultraconserved elements in phylogeny?", "output": "Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales" }, { "input": "What is the usefulness of ultraconserved elements in phylogeny?", "output": "Ultraconserved elements and their flanking DNA are novel phylogenomic markers that resolve placental mammal phylogeny when combined with species-tree analysis. Because orthologous UCEs can be obtained from a wide array of taxa, are polymorphic at shallow evolutionary timescales, and can be generated rapidly at low cost, they are an effective genetic marker for studies investigating evolutionary patterns and processes at shallow timescales." }, { "input": "Treprostinil is an analogue for which prostaglandin?", "output": "Treprostinil is a prostaglandin I(2) (PGI(2)) analog." }, { "input": "Which are the characteristics of the Meier-Gorlin syndrome?", "output": "The Meier-Gorlin syndrome is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia or hypoplasia of the patellae, and severe pre- and postnatal growth retardation." }, { "input": "Which are the characteristics of the Meier-Gorlin syndrome?", "output": "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation " }, { "input": "Which are the characteristics of the Meier-Gorlin syndrome?", "output": "The Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder, characterized by bilateral microtia, aplasia or hypoplasia of the patellae, and severe intrauterine and post-natal growth retardation" }, { "input": "Which enzyme is deficient in Gaucher's disease?", "output": "Gaucher's disease is caused by deficient lysosomal glucocerebrosidase activity" }, { "input": "Which enzyme is deficient in Gaucher's disease?", "output": "Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia." }, { "input": "What is the role of Hsp90 inhibition in cancer therapy?", "output": "Hsp90 inhibition is followed by G1/S cell cycle arrest, downregulation of key signalling proteins such as IGF-IR, Akt, IKK-\u03b1, IKK-\u03b2, FOXO1, ERK1/2 and c-Met, and sequestration-mediated inactivation of NF-\u03baB, resulting in disruption of oncogenic signalling integrity, reduced cell proliferation, decline of cell motility, enhanced apoptotic cell death, and finally, sensitization of cancer cells to additional chemotherapy and/or radiotherapy." }, { "input": "Which is the most common type of pediatric cerebellar tumor?", "output": "Medulloblastoma is the most common malignant cerebellar tumor seen in the pediatric age group, which has a known ability to metastasize extraneurally." }, { "input": "Which is the most common type of pediatric cerebellar tumor?", "output": "Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally " }, { "input": "Which is the E3 ubiquitin ligase of Hsp90?", "output": "Carboxyl terminus of hsc70-interacting protein (CHIP) can mediate ubiquitination of the 90 kDa heat-shock protein (hsp90) in vitro, with subsequent proteasomal degradation of the chaperone." }, { "input": "Which are the major phycobiliproteins present in cyanobacteria?", "output": "Phycobiliproteins are derived from the photosynthetic apparatus of cyanobacteria and eukaryotic algae, and form their large extrinsic antenna complexes called phycobilisomes. Phycobilisomes have a core composed from allophycocyanin (APC) and rods, which are of variable phycobiliprotein composition. C-Phycocyanin (C-Pc) is one of the major light harvesting biliprotein pigments constitutively produced by many cyanobacteria, such as Spirulina platenesis (a blue-green alga). B-Phycoerythrin (B-PE) is an other major light-harvesting pigment found in red algae and cyanobacteria. R-phycoerythrin (R-PE) is the major light-harvesting pigment protein of most red algal phycobilisomes." }, { "input": "Is PLK2 involved in alpha-synuclein phosphorylation in the nervous system?", "output": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in the central nervous system." }, { "input": "Is PLK2 involved in alpha-synuclein phosphorylation in the nervous system?", "output": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system " }, { "input": "In which kingdom do microsporidia belong, according to their current classification scheme?", "output": "Traditionally, microsporidia were considered as protozoans, but recently they have been reclassified as the earliest-diverging clade of sequenced fungi. Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore-forming parasites; they are ubiquitous fungi, with genomes that have undergone a strong reduction." }, { "input": "What is the inheritance pattern of Emery-Dreifuss muscular dystrophy? ", "output": "The inheritance pattern of Emery-Dreifuss muscular dystrophy (EDMD) can be X-linked, autosomal dominant or autosomal recessive." }, { "input": "What is the mechanism of action of anticoagulant medication Dabigatran?", "output": "Dabigatran is orally administered, reverisble direct and competetive inhibitor of both free and bouded thrombin." }, { "input": "What is the effect of a defective CLN3 gene?", "output": "Mutations in the CLN3 gene, which encodes a lysosomal membrane protein, are responsible for the neurodegenerative disorder juvenile Batten disease." }, { "input": "Which genes are regulated by TRalpha2 in the heart?", "output": "ARB1, ARB2, TAK1, p38, TRalpha1" }, { "input": "Is insulin-like growth factor-I (IGF-I) able to affect tendon protein synthesis in classic Ehlers-Danlos syndrome patients?", "output": "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I " }, { "input": "Is insulin-like growth factor-I (IGF-I) able to affect tendon protein synthesis in classic Ehlers-Danlos syndrome patients?", "output": "In an experimental setting, baseline protein synthesis rates in connective tissue appeared normal in classic Ehlers-Danlos syndrome patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections." }, { "input": "List available methods for transmembrane protein topology prediction.", "output": "HMMpTM, MetaTM, Philius, HMM_RA, HMMTOP, MEMSAT3, HMM-TM, TMHMM, Phobius and SignalP." }, { "input": "Does GC content vary markedly within a given isochore?", "output": "Isochores are relatively long regions with a relatively homogeneous GC content, and with rather sharp boundaries with neighboring isochores. The base composition, and thus the GC content may differ between different isochores, but is more or less consistent within a given isochore." }, { "input": "Is tubulin acetylation involved in cell motility?", "output": "Yes, induction of alpha-tubulin acetylation correlates with inhibition of cell motility, while it is involved in additional cellular processes, e.g. cell cycle progression, differentiation, intracellular trafficking, and signalling. Dynamic microtubule (MT) acetylation/deacetylation mediating cell motility and adhesion is controlled by enzymes such as HDAC6, a major cytoplasmic \u03b1-tubulin deacetylase. While its overexpression and activation is capable to enhance cell motility, HDAC6 activity can also be negatively regulated by a number of cellular inhibitors, thus decreasing the ability of cells for migration." }, { "input": "List available genetic multicolor cell labeling techiniques in Drosophila", "output": "Flybow and Drosophila Brainbow." }, { "input": "Which growth factors are known to be involved in the induction of EMT?", "output": "EMT is characterized by acquisition of cell motility, modifications of cell morphology, and cell dissociation correlating with the loss of desmosomes from the cellular cortex. A number of growth factors have been shown to be involved in this process. These include fibroblast growth factors (FGFs), TGF-\u03b21, TGF-\u03b22, TNF-\u03b1, CCN family, Sonic Hedgehog (SHh), Notch1, GF-\u03b2, Wnt, EGF, bFGF, IGF-I and IGF-II." }, { "input": "What is the function of the yeast protein Aft1?", "output": "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions. Aft1 interacts with the FOB (ferrioxamine B) transporter Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment. Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability. Aft1 has also been shown to affect a diverse range of cellular processes, including the RIM101 pH pathway, cell-wall stability, DNA damage, protein transport, chromosome stability, mitochondrial function, while it was recently shown to interact with the kinetochore protein Iml3 and to promote pericentromeric cohesin." }, { "input": "Can PLN mutations lead to dilated cardiomyopathy?", "output": "Yes, PLN mutations can lead to dilated cardiomyopathy." }, { "input": "Which is the genetic lesion associated with Huntington\u2019s disease?", "output": "The genetic lesion associated with Huntington's disease is a CAG trinucleotide repeat expansion in the HD (or HTT) gene." }, { "input": "Is corpus callosum involved in the Mowat\u2013Wilson syndrome?", "output": "Yes, agenesis of the corpus callosum is common patients with Mowat\u2013Wilson syndrome. Other characteristic features of Mowat\u2013Wilson syndrome include typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, and eye defects." }, { "input": "Which histone modification discriminates between active and poised enhancers?", "output": "Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. " }, { "input": "What are the properties of super-enhancers?", "output": "Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation. In this respect, the super-enhancer definition is useful in identifying regulatory elements likely to control genes important for cell type specification. Super-enhancers thus play key roles in the control of mammalian cell identity." }, { "input": "What is the inheritance pattern of Li\u2013Fraumeni syndrome?", "output": "Li-Fraumeni syndrome shows autosomal dominant inheritance." }, { "input": "Which pituitary adenoma is common cause of infertility is women?", "output": "Prolactinoma is a pituitary adenoma that is strongly associated with infertility in women mainly due to increased prolactin secretion causing hyperprolactinemia. Other pituitary lesions can also be associated with infertility." }, { "input": "What is the role of mismatched uracil glycosylase (Mug) in DNA repair?", "output": "The mismatch-specific uracil DNA glycosylase (MUG) belongs to a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. The crystal structure of the Mug repair complex points to a preference of Mug for G:U over G:T mispairs. Nonetheless, Mug does not repair U:G or T:G mismatches in vivo. Mug possesses xanthine DNA glycosylase (XDG) activity in E.coli. The repair activity of Mug is more robust against xanthine than uracil. Furthermore, Mug excises the alkylated base, 3, N(4)-ethenocytosine (epsilonC) from epsilonC:G mismatches, and may be the only enzyme in E.coli that can remove this mutagenic adduct. Thus, the principal role of Mug may be the repair of DNA damages caused by exogenous chemical agents such as chloroacetaldehyde." }, { "input": "Which are the cardiac effects of thyronamines?", "output": "Thyronamines have negative chronotropy, negative inotropy; in particular thyronamines are considered negative inotropic agents" }, { "input": "Which are the cardiac effects of thyronamines?", "output": "In the heart, thyronamines cause negative chronotropy, negative inotropy,reduced cardiac output and resistance to ischemic injury." }, { "input": "Matuzumab has been tested for treatment of which cancers?", "output": "Matuzumab has been tested for treatment of non-small cell lung, gastric, esophageal, colorectal, primary peritoneal, pancreatic, ovarian and cervical cancers." }, { "input": "Which are the synonyms of prostate-specific antigen?", "output": "Prostate-specific antigen (PSA) is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases which is produced by epithelial cells of both normal and malignant prostate tissue. PSA is an important marker for the diagnosis of prostate cancer. PSA is also known as human kallikrein-related peptidase 3 (hK3)." }, { "input": "Which are the synonyms of prostate-specific antigen?", "output": "Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases. (PMID: 19079621)" }, { "input": "What is the lipid droplet used for in the cell?", "output": "Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands." }, { "input": "What is the function of circular RNA?", "output": "Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. The biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression." }, { "input": "What is the function of circular RNA?", "output": "Circular RNAs are new players in regulation of post transcriptional gene expression. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. This new type of transcript might represent a novel aspect of gene expression and hold some interesting clues about the splicing mechanism. Here we determine the structure of these novel transcripts, showing that they correspond to circular RNA molecules containing only exons in genomic order." }, { "input": "Can NXY-059 be used for treatment of acute ischemic stroke patients?", "output": "No. 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective." }, { "input": "Is flibanserin effetive for Hypoactive Sexual Desire Disorder? ", "output": "Yes, flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) antagonist, has been shown to increase sexual desire and reduce distress in women with Hypoactive Sexual Desire Disorder." }, { "input": "List available biomedical question answering systems.", "output": "We live in an age of access to more information than ever before. The exponential growth in the volume of publications in the biomedical domain has made it impossible for an individual to keep pace with the advances. Thus, there is a need for intelligent information retrieval systems that can summarize relevant and reliable textual sources to satisfy a user's query. Question answering is a specialized type of information retrieval with the aim of returning precise short answers to queries posed as natural language questions. This accentuates the need for fast and accurate biomedical question answering systems. In this paper we introduce INDOC -- a biomedical question answering system based on novel ideas of indexing and extracting the answer to the questions posed. Increased access to information allows for more informed and empowered researchers, while information overload becomes an increasingly serious risk. INDOC displays the results in clusters to help the user arrive the most relevant set of documents quickly. Evaluation was done against the standard OHSUMED test collection. We present a review and comparison of three biomedical question answering systems: askHERMES, EAGLi ( http://eagl.unige.ch/EAGLi/ ), and HONQA ( http://services.hon.ch/cgi-bin/QA10/qa.pl ). " }, { "input": "List available biomedical question answering systems.", "output": "askHERMES, EAGLi, HONQA and INDOC." }, { "input": "Which dediodinases are present in kidney?", "output": "Type 1 and Type 3 deiodinases are both present in liver" }, { "input": "What is the presumed key event in Fanconi anemia pathogenesis?", "output": "Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. Failure of FANCD2 monoubiquitination by the nuclear FA protein complex has a severe impact on the DNA repair functions of cells." }, { "input": "What is the effect of Allopurinol on asphyxia in neonates?", "output": "Allopurinol was shown in a number of clinical trial to be safe and effective for treatment of neonatal asphyxia. Allopurinol improves short-term and long-term clinical outcomes of neonatal asphyxia. Allopurinol should be administered as soon as possible. Postulated mechanism of allopurinol action in this setting is prevention of hypoxia-perfusion injury by reduction of free radical formation." }, { "input": "Is recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?", "output": "Currently there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting." }, { "input": "When is the protein NFL a biomarker?", "output": "Neurofilament light protein (NFL), may be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS).\nNeurofilament light chain is a prognostic biomarker in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, multiple sclerosis and head trauma." }, { "input": "Is protein CXCR4 used as a prognostic marker of cancer?", "output": "Yes, the chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer." }, { "input": "How does thyroid hormone regulate SR-Ca2+ ATPase (SERCA) protein in the heart?", "output": "The thyroid hormone (TH) induced regulation of SERCA is mediated both by non-genomic and genomic actions.\nGenomic actions are mediated by the binding of T(3) receptors (TRs) to the thyroid response elements in the SERCA promotor and result in increased gene expression. \nThyroid hormone increases the transcription of SERCA 2 through three thyroid hormone response elements. \nData show that the regulation of cardiac SERCA by thyroid hormone is made at the pretranslational and possibly transcriptional level \nTR\u03b21 is shown to be coupled to the expression of SERCA in the heart\nAn increase of TR expression in the hypertrophied heart has been show to result in increased SERCA expression.\nInhibition of TR\u03b11 by dronedarone does not change the expression of SERCA in the heart\nFindings show that SERCA 2 gene expression is regulated by TR isoform-specific interactions with transcription factor (MEF-2) \nHypothyroidism is accompanied by decreased expression of SERCA in the heart. T3 increases expression of the cardiac SERCA\nTH treatment can reverse the reduction in the ratio of SERCA to phospholamban expression which is found in postinfarcted hearts\nTH treatment results in increased expression of SERCA in hearts from banded rats" }, { "input": "Which trancription factor activates the betalain pathway?", "output": "The beet Y locus encodes an anthocyanin MYB-like protein that activates the betalain red pigment pathway." }, { "input": "List common symptoms of patients with the DOORS syndrome.", "output": "DOORS syndrome is a constellation of deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures. It is a rare autosomal recessive disorder of unknown cause." }, { "input": "Which is the most well-accepted method for Down syndrome non-invasive prenatal diagnosis?", "output": "Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR). This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21." }, { "input": "Which is the most well-accepted method for Down syndrome non-invasive prenatal diagnosis?", "output": "This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. Moreover, the differential methylation for each locus could be seen during the whole pregnant period." }, { "input": "Is the H3K4me3 histone mark related to transcriptional initiation or elongation?", "output": "H3K4me3 is associated with transcriptionally active genes, but its function in the transcription process is still unclear. It is well known to occur in the promoter region of genes for transcription activation but its levels correlate positively with the antisense expression levels of the associated sense genes implying that it may be also involved in the activation of antisense transcription. Although it is mostly associated with transcription initiation H3K4me3 levels determine the efficiency of transcription elongation." }, { "input": "What does polyadenylate-binding protein 4 (PABP4) bind to?", "output": "PABP4 binds mRNA poly(A) tails." }, { "input": "What is the average diameter of intermediate filaments?", "output": "Intermediate filaments have an average diameter of 10 nanometers (nm)." }, { "input": "Elaborate on the association between Genomic Regulatory Blocks (GRBs) and target genes", "output": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region." }, { "input": "Which therapeutic interventions for sarcopenia have been applied", "output": "The main bulk of experimental pharmacological interventions addressing the clinical problem of frailty have been focused on the use of hormones, as replacement therapy in subjects with low or normal circulating basal levels of the hormone. Results have been disappointing, except for the case of testosterone that have shown some benefits. The effectiveness of other potential therapeutic interventions (antioxidants, anti-inflammatory agents, nutritional supplements) appears to be limited or has not been explored in detail until now." }, { "input": "What is the genetic basis of progeria?", "output": "Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. \tThe genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription." }, { "input": "What is the function of cryptochrome-1 in mouse?", "output": "Cryptochrome-1 (Cry1) is an essential component of the central and peripheral circadian clocks for generation of circadian rhythms in mice." }, { "input": "Describe July Effect.", "output": "The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year (in July)." }, { "input": "Which intermediate filament (IF) protein can be used as a non-specific marker of the neuronal precursor cells of the subventricular zone?", "output": "Nestin can be used as a nonspecific marker protein for precursor cells in the subventricular zone (SVZ). Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's SVZ." }, { "input": "Which enzyme is involved in the maintenance of DNA (cytosine-5-)-methylation?", "output": "The mammalian DNA (cytosine-5) methyltransferase 1, DNMT1 is the major enzyme responsible for the maintenance of the DNA methylation patterns on the newly synthesized strand after DNA replication. DNMT1 prefers hemimethylated DNA and during DNA replication methylates hemimethylated CpG sites by copying methylation patterns from the parental DNA strand to the newly synthesized daughter strand. The equivalent of DNMT1 in plants is MET1." }, { "input": "Is transcapillary albumin escape altered in diabetic patients?", "output": "An altered TERalb is present in type 2 diabetic patients, both with normal and altered patterns of AER.\nTERalb is increased also in normo-albuminuric type 1 diabetic patients." }, { "input": "Which genes does thyroid hormone receptor beta1 regulate in the liver?", "output": "LDL receptor\"//\n\"ChREBP\"//\n\"ME\", \"malic enzyme\"//\n\"cytochrome P450 oxidoreductase\"//" }, { "input": "Are conserved noncoding elements associated with developmental genes?", "output": "Yes. Numerous studies suggest that conserved noncoding elements span developmental regulatory genes and define regulatory domains." }, { "input": "In what proportion of children with heart failure has Enalapril been shown to be safe and effective?", "output": "In children with heart failure evidence of the effect of enalapril is empirical. Enalapril was clinically safe and effective in 50% to 80% of for children with cardiac failure secondary to congenital heart malformations before and after cardiac surgery, impaired ventricular function , valvar regurgitation, congestive cardiomyopathy, , arterial hypertension, life-threatening arrhythmias coexisting with circulatory insufficiency. \nACE inhibitors have shown a transient beneficial effect on heart failure due to anticancer drugs and possibly a beneficial effect in muscular dystrophy-associated cardiomyopathy, which deserves further studies." }, { "input": "Is myasthenia gravis associated with osteoporosis?", "output": "Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased risk of glucocorticoid-induced osteoporosis. Thymectomy can also increase risk for osteoporosis. Appropriate osteoporosis preventive measures can reduce osteoporosis risk in MG patients." }, { "input": "Which cell type has the protein Chromogranin A as marker?", "output": "Chromogranin A is a marker for neuroendocrine cells" }, { "input": "Does a selective sweep increase genetic variation?", "output": "Selective sweep is a phenomenon in which the fixation of strongly beneficial alleles within a population reduces genetic diversity at partially linked neutral loci. Reduced variation or deviations from neutrality, along with an excess of fixed replacement sites, are indicative of selective sweep." }, { "input": "Which disease phenotypes are associated to PRPS1 mutations?", "output": "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1." }, { "input": "Is indicated the use of antioxidant supplements in patients at risk for coronary artery disease?", "output": "antioxidant supplementation \nHowever there are no clear evidencies on the clinical and prognostic benefit of this supplementation. \nCurrently there areno recommendation for the antioxidant therapy in patients with coronary artery disease.\nCurrently the American Heart Association recommends consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but does not recommend antioxidant supplementation for the general population." }, { "input": "Which are the main functions of the human HuR (ELAVL1) protein in fibroblasts?", "output": "HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3' untranslated regions and has been shown to shuttle between the nucleus and cytoplasm. HuR function was previously shown to be implicated in the maintenance of a \"young cell\" phenotype in models of replicative cellular senescence. Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence. Importantly, overexpression of HuR in senescent cells restored a \"younger\" phenotype, while a reduction in HuR expression accentuated the senescent phenotype. HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels. In mesenchymal cells HuR plays a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis. In fibroblasts knockdown of HuR decreased the endogenous expression of TGF\u03b21 under exogenous TGF\u03b21 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression. HuR (human antigen R), represses ARF mRNA translation, thereby maintaining the replicative life span of mouse embryonic fibroblasts (MEFs). HuR is considered a global regulator of cell-cycle progression and tumorigenesis. Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli." }, { "input": "Which kinases does baricitinib inhibit?", "output": "Baricitinib is an inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2." }, { "input": "Is there evidence to suggest that triiodothyronine has neuroprotective properties in traumatic brain injury?", "output": "Yes, it has been demonstrated that triiodothyronine exerts neuroprotective properties in traumatic brain injury setting." }, { "input": "What is the role played by mTOR in hypertrophic response and heart failure?", "output": "When subjected to pressure overload, mTOR-ablated mice demonstrated an impaired hypertrophic response and accelerated heart failure progression. Thus, mTOR complex 1 signaling plays an important role in myocardial response to stress, to regulate cardiomyocyte viability and heart failure." }, { "input": "Is Lysine-specific demethylase 1 (LSD1) a critical regulator of hematopoiesis?", "output": "Yes. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation of erythroid, granulomonocytic and megakaryocytic progenitors." }, { "input": "Is K-63 linked protein ubiquitination related to proteasomal degradation?", "output": "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor kappaB (NF-kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways.In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes." }, { "input": "Is K-63 linked protein ubiquitination related to proteasomal degradation?", "output": "In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes. Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism." }, { "input": "Is K-63 linked protein ubiquitination related to proteasomal degradation?", "output": "One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism" }, { "input": "Is K-63 linked protein ubiquitination related to proteasomal degradation?", "output": "Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes." }, { "input": "Could transcription factors act as cell-cell signalling molecules?", "output": "Yes. Recent data support the view that transcription factors - in particular, homeoproteins - can be transferred from cell to cell and have direct non-cell-autonomous (and therefore paracrine) activities." }, { "input": "Could transcription factors act as cell-cell signalling molecules?", "output": "Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short-range cell-cell signalling molecules, hormones and structural proteins" }, { "input": "Magnetic beads has been used in numerous applications. List some coatings used.", "output": "aptamers\nenzymes\nstreptavidin\nconcanavalin A\ncarboxylic-modified \nTiO2\nantibodies\nSELEX library\nsynthesized DNA\nC18\nC8\noligo(dT)" }, { "input": "is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events?", "output": "whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy." }, { "input": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)\ncause sudden cardiac death?", "output": "Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) can cause sudden cardiac death." }, { "input": "What is the mechanism of action of DNA topoisomerase II inhibitors?", "output": "DNA topoisomerase II inhibitors eliminate cancer cells by causing DNA double-strand breaks, finally leading to apoptotic cell death. Moreover, drug-induced histone eviction was also shown to be associated with attenuated DNA repair, epigenetic changes and transcpription deregulation." }, { "input": "Are histone deacetylase (HDAC) inhibitors good candidates to control metastasis of solid tumors?", "output": "Yes, some HDAC inhibitors, such as Vorinostat, are on trial for human treatment after proving successful in animal models. Combination with other drugs is likely to be needed to control metastasis." }, { "input": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "output": "The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function." }, { "input": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "output": "Yes, Muscle LIM protein is involved in cardiomyopathies. In specific, the skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy. MLP became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype." }, { "input": "Which gene harbors the mutation T790M?", "output": "The T790M mutation refers to the mutation in exon 20 of the EGFR gene" }, { "input": "what is the role of FGF-2 in cardiac regeneration after myocardial infarction?", "output": "Exogenous FGF-2 was shown to increase angiogenesis and myocardial perfusion, promote myocardial regeneration by activating the SDF-1\u03b1/CXCR4 axis, and thereby improve the cardiac function after myocardial infarction. Furthermore, prevascularization with basic FGF-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. In another study, transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) was shown to promote Cardiac Progenitor Cells proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following myocardial infarction and improving cardiac function." }, { "input": "Have 5q35 microdeletions been implicated in Sotos syndrome development?", "output": "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID)." }, { "input": "Have 5q35 microdeletions been implicated in Sotos syndrome development?", "output": "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID)" }, { "input": "Tumors of which three organs are classically associated with the multiple endocrine neoplasia type 1 syndrome?", "output": "Multiple endocrine neoplasia type 1 syndrome is an inherited cancer syndrome defined by occurrence of multiple neuro-endocrine tumors and is classically associated with the combined occurrence of two or more tumors involving parathyroid gland, pancreas and pituitary gland. Other tumors, including but not limited to adrenal cortical tumor, carcinoid tumors lipoma, leiomyoma, duodenal gastrinoma, hepatic focal nodular hyperplasia, and renal angiomyolipoma, angiofibroma, colagenoma, thyroid tumor and meningioma, may also be present." }, { "input": "Which is the protein implicated in Spinocerebellar ataxia type 3?", "output": "Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3)." }, { "input": "Which is the protein implicated in Spinocerebellar ataxia type 3?", "output": "Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem" }, { "input": "What is Tn-seq?", "output": "The transposon mutagenesis and high-throughput sequencing (Tn-seq) is a technique that allows for quantitative assessment of individual mutants within a transposon mutant library by sequencing the transposon-genome junctions and then compiling mutant presence by mapping to a base genome. Using Tn-seq, it is possible to quickly define all the insertional mutants in a library and thus identify nonessential genes under the conditions in which the library was produced. Identification of fitness of individual mutants under specific conditions can be performed by exposing the library to selective pressures." }, { "input": "Is metabolic syndrome related with cardiovascular disease?", "output": "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM)." }, { "input": "Is there any functional association during viral replication between flaviviridae viral RNA depended RNA polymerase and viral helicase?", "output": "Several labs have obtained evidence for a protein complex that involves many of the nonstructural (NS) proteins encoded by the virus. NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally. The interaction between the helicase, NS3, and the RNA polymerase, NS5B play a key role in viral replication. Pull-down experiments and surface plasmon resonance data indicate a direct interaction between NS3 and NS5B that is primarily mediated through the protease domain of NS3. This interaction reduces the basal ATPase activity of NS3. However, NS5B stimulates product formation in RNA unwinding experiments under conditions of excess nucleic acid substrate. When the concentrations of NS3 and NS5B are in excess of nucleic acid substrate, NS5B reduces the rate of NS3-catalyzed unwinding. Under pre-steady-state conditions, in which NS3 and substrate concentrations are similar, product formation increased in the presence of NS5B. The increase was consistent with 1:1 complex formed between the two proteins." }, { "input": "Are defects in recombination repair involved in carcinogenesis?", "output": "Yes. The breast cancer-associated BRCA1 and BRCA2 proteins are strongly implicated in recombination repair." }, { "input": "Are defects in recombination repair involved in carcinogenesis?", "output": "Carcinogenesis or oncogenesis or tumorigenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes at the cellular, genetic and epigenetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.\nCarcinogenesis is caused by mutation and epimutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. The uncontrolled and often rapid proliferation of cells can lead to benign tumors; some types of these may turn into malignant tumors (cancer). Based on studies, carcinogenesis also related with the defects in recombination repair." }, { "input": "Which is the prevalence of cystic fibrosis in the human population?", "output": "Prevalence of Cystic Fibrosis varies according to the population. A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, real data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants). Results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98." }, { "input": "Which is the prevalence of cystic fibrosis in the human population?", "output": "The results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98 (PMID: 18442953) The allelic frequency of this variant was calculated to be 0.7% for this population (PMID: 22627569) CF mutations were identified in 374 (4.0%) individuals. (PMID: 11336401)" }, { "input": "Are seizures among the neurological symptoms of incontinentia pigmenti?", "output": "Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth." }, { "input": "Which are the different homologs or family members of the hedgehog proteins in mammals?", "output": "Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic hedgehog (Shh), Indian hedgehog (Ihh) , and Desert hedgehog (Dhh), are present in mammals." }, { "input": "What does mTOR stands for?", "output": "mTOR stands for: mammalian target of rapamycin." }, { "input": "Which is the most common genetic lesion among patients with Joubert Syndrome and a cerebello-oculo-renal phenotype?", "output": "Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion." }, { "input": "Which is the most common genetic lesion among patients with Joubert Syndrome and a cerebello-oculo-renal phenotype?", "output": "Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion" }, { "input": "Which scales are recommended by the American Heart Association for depression screening in cardiovascular patients? ", "output": "Patient Health Questionnaire-2 (PHQ-2) and Patient Health Questionnaire-9 (PHQ-9) are recommended by the American Heart Association for depression screening in cardiovascular patients." }, { "input": "Is there a genome-wide technique for the detection of R-loop formation?", "output": "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops. Here we show that recombination factors are required for the survival of yeast FACT mutants, consistent with an accumulation of DNA breaks that we detected by Rad52 foci and transcription-dependent hyperrecombination. The latter pathway operates on nascent transcripts that are not simultaneously translated and requires factors Rho, NusG, and NusA, each of which is essential for viability of WT Escherichia coli. DNA replication in Escherichia coli is normally initiated at a single origin, oriC, dependent on initiation protein DnaA." }, { "input": "Is there a genome-wide technique for the detection of R-loop formation?", "output": "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops\nA bisulfite-sensitivity assay may demonstrate genome-wide increase in the occurrence of RNA-DNA hybrids (R-loops)." }, { "input": "How is CBX1/M31 related to position-effect variegation?", "output": "M31 is a heterochromatin component, that is concentrated in the XY body during spermatogenesis. M31 overexpression has two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric." }, { "input": "Can bioprinting use human cells?", "output": "Yes, human cells can be used for bioprinting" }, { "input": "Is transcription-associated mutagenesis (TAM) related to gene expression levels?", "output": "Spontaneous point mutation rate in a gene increases with its transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es). This phenomenon is termed transcription-associated mutation (TAM). Transcription-associated mutagenesis is directly proportional to the level of gene expression." }, { "input": "Is there a pharmacogenetic test for trastuzumab?", "output": "Yes. HER2 testing is performed in breast cancer patients to determine suitability for trastuzumab (Herceptin therapy)." }, { "input": "Which calcium channels does ethosuximide target?", "output": "Ethosuximide blocks the T-type calcium channels." }, { "input": "What is the sedimentation coefficient of the mammalian mitoribosome?", "output": "The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits." }, { "input": "Describe the mechanism of action of aliskiren. ", "output": "Aliskiren is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks renin and consequential angiotensin I generation. Renin inhibition interrupts the renin-angiotensin-aldosterone system (RAAS)." }, { "input": "Which proteins act as histone-like molecules in prokaryotes?", "output": "Prokaryotic histone-like proteins (Hlps) or nucleoid-associated proteins (NAPs) are abundant proteins found in bacterial and plastid nucleoids. HU protein is a small, basic, heat-stable DNA-binding protein that is well-conserved in prokaryotes and is associated with the bacterial nucleoid. HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF. In prokaryotes, IHF and HU are key architectural proteins present at high concentrations. Histone-like Nucleoid Structuring (H-NS) protein can facilitate correct recognition of a promoter by RNA polymerase in AT-rich gene regulatory regions" }, { "input": "Which proteins act as histone-like molecules in prokaryotes?", "output": "THe histone-like proteins HU, IHF, H-NS (Nucleoid Structuring) act as histones in prokaryotes" }, { "input": "Which receptor is targeted by telcagepant?", "output": "Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine." }, { "input": "What is the role of photodynamic therapy for meningioma treatment?", "output": "Photodynamic therapy was shown to have activity againt meningioma treatment. Gefitinib and ciprofloxacin enhance efficacy of photodynamic therapy." }, { "input": "Do carmustine wafers improve survival of glioblastoma patients?", "output": "Yes, it has been documented that implantation of carmustine wafers improves survival of newly diagnosed and recurrent glioblastoma patients." }, { "input": "Is Dicer part of the RISC loading complex?", "output": "Yes, Dicer is part of the RISC loading complex." }, { "input": "What is the Arnold-Chiari syndrome?", "output": "Arnold Chiari syndrome is a condition characterized by herniation of the cerebellar tonsils through the foramen magnum, manifesting usually with downbeat nystagmus, palsy of the caudal cerebral nerves, headache, and vertigo." }, { "input": "What is the biological role of SERCA2 SUMOylation in cardiac physiology and pathophysiology, such as in heart failure?", "output": "Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. SERCA2a is SUMOylated at lysines 480 and 585 and this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO-1 gene transfer improved cardiac function supporting the critical role of SUMO-1 in SERCA2a function and underlining the therapeutic potential of SUMO-1 for HF patients." }, { "input": "Which trinucleotide repeat disorders are affecting the nervous system?", "output": "At least six neudegenerative disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA)." }, { "input": "Is hypersensitivity to DNA crosslinking agents a hallmark of Fanconi anemia?", "output": "Yes, hypersensitivity to DNA crosslinking agents is one of the hallmarks of Fanconi anemia, the others being defective FANCD2 monoubiquitination, and genomic instability." }, { "input": "Which are the cellular targets of imatinib mesylate?", "output": "The cellular targets of imatinib mesylate are BCR-ABL, platelet-derived growth factor receptor (PDGFR) and c-kit kinases." }, { "input": "Which are the clinical characteristics of Tuberous Sclerosis?", "output": "The clinical characteristics of Tuberous Sclerosis include epilepsy, subependymal giant cell astrocytomas, lymphangioleiomyomatosis, rhabdomyoma, renal angiomyolipomas, cortical tubers, neurofibromas, angiofibromas, mental retardation, and behavioral disorders." }, { "input": "What is known about MER41 repeat sequences?", "output": "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu familyMER41 repeat sequences contain inducible STAT1 binding sites" }, { "input": "What is known about MER41 repeat sequences?", "output": "The sequences of five families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family. MER41 repeat sequences contain inducible STAT1 binding sites. The observation of the binding of activated STAT1 protein to a specific repetitive element bolsters similar reports concerning p53 and other TFs, and strengthens the notion of an involvement of repeats in gene regulation." }, { "input": "What is known about MER41 repeat sequences?", "output": "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family MER41 repeat sequences contain inducible STAT1 binding sites " }, { "input": "How functional connectivity of the default mode network changes in patients with disorders of consciousness?", "output": "Functional connectivity in the default mode network (DMN) is reduced in patients with different disorders of consciousness, and correlates with the level of consciousness. \nSpecifically, functional connectivity in the default mode network was shown to be absent in brain death patients, extremely low in vegetative state patients and slightly decreased in minimally conscious state patients when compared to healthy subjects. Therefore, functional connectivity in the default mode network was suggested to be valuable in differentiating patients with different disorders of consciousness. Clinically, functional connectivity in the default mode network was also shown to be an indicator of the extent of cortical disruption and predict reversible impairments in consciousness." }, { "input": "Have C12orf65 mutations been associated with axonal neuropathy and optic atrophy?", "output": "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy" }, { "input": "Have C12orf65 mutations been associated with axonal neuropathy and optic atrophy?", "output": "The association of neuropathy and optic atrophy (also known as Charcot-Marie-Tooth [CMT] disease type 6) has been described with autosomal dominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, whereas a protein-truncating mutation in the C12orf65 gene, which codes for a protein involved in mitochondrial translation, was found to be the cause of an autosomal recessive form of the disease, with childhood onset neuropathy and optic atrophy." }, { "input": "List drugs included in the DHAP-R chemotherapy regiment.", "output": "Dexamethasone (a steroid hormone), cytarabine (ara-C), cisplatin (platinum agent) and rituximab are included in the DHAP-R chemotherapy protocol." }, { "input": "Are psammoma bodies characteristic to meningiomas?", "output": "Yes, psammoma bodies are commonly seen and are characteristic to meningiomas. However, they can be also present in other types of tumors or non-neoplastic tissues." }, { "input": "Which are the most common symptoms in Lambert-Eaton Myasthenic Syndrome?", "output": "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome)" }, { "input": "Which are the most common symptoms in Lambert-Eaton Myasthenic Syndrome?", "output": "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms, that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer, and the other that is a pure autoimmune form." }, { "input": "What is the pyroptotic pathway?", "output": "Pyroptosis is an inflammasome-mediated programmed cell death pathway." }, { "input": "Which types of bacterial microflora are associated with the progression of peri-implantitis?", "output": "Bacteria such as A. actinomycetemcomitans, P. gingivalis, T. forsythensis, T. denticola, P. intermedia and F. nucleatum are associated with the progression of peri-implantitis." }, { "input": "What are the known families of deadenylases?", "output": "All known deadenylases belong to either the DEDD or the exonuclease\u2013endonuclease\u2013phosphatase (EEP) superfamily. Members of DEDD include the POP2, CAF1Z, PARN and PAN2 families. Members of EEP include the CCR4, Nocturnin, ANGEL and 2'-PDE families." }, { "input": "Which translocation is harbored in the Askin tumor cells?", "output": "The Askin tumor is a primitive malignant small-cell tumor of the chest wall mostly seen among children and adolescents. It is closely related to Ewing's sarcoma of the same location, with both tumors harboring reciprocal translocation t(11;22) (q24;q12)." }, { "input": "What is the function of the AtxA pleiotropic regulator?", "output": "AtxA is the gene encoding the trans-activator of anthrax toxin synthesis and is essential for virulence of B. anthracis. It is located on the resident 185-kb plasmid pXO1 and its activation is stimulated by bicarbonate. AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air. Dual promoters control expression of AtxA. Transcription of the atxA gene occurs from two independent promoters, P1 and P2, whose transcription start sites are separated by 650 bp." }, { "input": "What is the function of the AtxA pleiotropic regulator?", "output": "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The AtxA virulence regulator of Bacillus anthracis is required for toxin and capsule gene expression. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. We purified histidine-tagged AtxA [AtxA(His)] from Escherichia coli and used anti-AtxA(His) serum to detect AtxA in protein preparations from B. anthracis cells." }, { "input": "What is the function of the AtxA pleiotropic regulator?", "output": "The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence." }, { "input": "Is cystatin C or cystatin 3 used as a biomarker of kidney function?", "output": "Yes, cystatin C (CysC) is a novel biomarker of renal function." }, { "input": "Which R/bioconductor package utilizes the Hilbert curve in order to visualize genomic data?", "output": "The so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data. An open-source application, called HilbertVis, has been developed for R/bioconductor that allows the user to produce and interactively explore such plots." }, { "input": "Can fetal aneuploidy be detected with non-invasive prenatal testing?", "output": "Yes, the non-invasive preanatal test of cell-free fetal DNA is being used for fetal aneuploidy screening." }, { "input": "Which packages are used for performing overlap analysis of genomic regions in R/bioconductor?", "output": "IRanges, GenomicRanges, and GenomicFeatures provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization." }, { "input": "Which packages are used for performing overlap analysis of genomic regions in R/bioconductor?", "output": "At the core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization." }, { "input": "Is dichlorphenamide effective for periodic paralysis?", "output": "Yes, dichlorphenamide is effective for periodic paralysis. Dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis." }, { "input": "What is evaluated with the Hydrocephalus Outcome Questionnaire?", "output": "The Hydrocephalus Outcome Questionnaire (HOQ) is a simple, reliable, and valid measure of health status in children with hydrocephalus." }, { "input": "What is known about maternal smoking and brain tumor risk?", "output": "Findings regarding association of maternal smoking and brain tumor risk are mixed. It was shown that children of women who smoked during pregnancy had an increased incidence of brain tumors (hazard ratio = 1.24; 95% confidence interval: 1.01-1.53). The increase in risk was similar for benign and malignant tumors, and was most apparent for astrocytoma. However, other authors did not find association between maternal smoking and brain tumor risk." }, { "input": "Which pathway is activated by ficolin-3?", "output": "Ficolin-3 activates lectin complement pathway." }, { "input": "Is nivolumab used for treatment of Non\u2013Small-Cell Lung Cancer?", "output": "Yes, nivolumab used for treatment of Non\u2013Small-Cell Lung Cancer." }, { "input": "Global quantitative phosphoproteomic analyses are emerging. List the preferred technologies for the enrichment for phosphorylated peptides?", "output": "There are many different approaches to enrich for phosphorylated peptides: titanium dioxide, IMAC, simple derivatization through phosphoramidate chemistry and antibodies." }, { "input": "Which histone modifications are correlated with transcription elongation?", "output": "This is accompanied by reductions in the level of H3K36 trimethylation, a posttranslational histone modification associated with efficient transcriptional elongation, and the number of full-length transcripts from these genes. The 3' ZNF exons contain H3K36me3, a mark of transcriptional elongation." }, { "input": "Does thyroid hormone receptor beta1 affect insulin secretion?", "output": "No" }, { "input": "List disorders that have been associated to the polymorphism rs2535629.", "output": "schizophrenia and major depressive disorder. " }, { "input": "What is targeted by monoclonal antibody Pembrolizumab?", "output": "Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Pembrolizumab is approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways." }, { "input": "Does replication timing affect the rate of somatic mutations?", "output": "Mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome. In yeast the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. In humans DNA replication patterns help shape the mutational landscapes of normal and cancer genomes." }, { "input": "Does replication timing affect the rate of somatic mutations?", "output": "Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. The mutations were distributed randomly throughout the genome, independent of replication timing. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Interestingly, 5% of the single base pair substitutions might represent double-slippage events that occurred at the junction of immediately adjacent repeats, resulting in a shift in the repeat boundary." }, { "input": "Does replication timing affect the rate of somatic mutations?", "output": "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome" }, { "input": "Which metazaon species or taxa are known to lack selenoproteins", "output": "Some insect genomes have lost the capacity of synthesizing selenoproteins. Several insect species without selenoproteins have been identified." }, { "input": "What is the mode of inheritance of Facioscapulohumeral muscular\ndystrophy (FSHD)?", "output": "The mode of inheritance of Facioscapulohumeral muscular dystrophy is autosomal dominant." }, { "input": "Is NOD1 activated in inflammation?", "output": "Nod proteins fight off bacterial infections by stimulating proinflammatory signaling and cytokine networks and by inducing antimicrobial effectors, such as nitric oxide and antimicrobial peptides. NOD1 engagement generates an inflammatory response via activation of NF\u03baB and MAPK pathways and several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents. Together, Nod1 and Nod2 represent central players in the control of immune responses to bacterial infections and inflammation. Mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue" }, { "input": "Is NOD1 activated in inflammation?", "output": "Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions. The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice. However, the influence of Rip2 was strictly dependent on infection conditions that favored expression of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (TTSS), as Rip2 was dispensable for inflammation when mice were infected with bacteria grown under conditions that promoted expression of the SPI-1 TTSS." }, { "input": "Is NOD1 activated in inflammation?", "output": "Nod1 and Nod2 control bacterial infections and inflammation" }, { "input": "List diseases where protein citrullination plays an important role.", "output": "Rheumatoid arthritis, multiple sclerosis, prion diseases, cancer and Alzheimer's disease are examples of diseases where protein citrullination involvement has been demonstrated." }, { "input": "What is commotio cordis?", "output": "Commotio cordis is a term used to describe cases of blunt thoracic impact causing sudden death without structural damage of the heart" }, { "input": "What is the cause of Phthiriasis Palpebrarum?", "output": "Phthiriasis palpebrarum is a rare eyelid infestation caused by phthirus pubis." }, { "input": "Does the histidine-rich Ca-binding protein (HRC) interact with triadin?", "output": "Yes. HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart. A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported." }, { "input": "Does the histidine-rich Ca-binding protein (HRC) interact with triadin?", "output": "Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) and binds to triadin (TRN), a protein associated with the ryanodine receptor and thought to be involved in calcium release." }, { "input": "How are CpG island shores defined?", "output": "CpG island \"shores\" are defined as genomic regions up to 2kb distant to known CpG islands. Differential DNA methylation correlates with gene expression more strongly at CpG island shores than CpG islands." }, { "input": "Does magnesium sulfate improve outcomes of subarachnoid hemorrhage patients?", "output": "No. Although initial studies have provided with encouraging findings regarding administration of magnesium sulphate in aneurysmal subarachnoid haemorrhage patients, but subsequent larger studies have reported that intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended." }, { "input": "Which gene is mutated in a subtype of arrhythmogenic right ventricular cardiomyopathy known as Naxos disease?", "output": "Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmias and sudden death. A recessive mutation in the gene encoding plakoglobin has been shown to cause Naxos disease, a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin." }, { "input": "Which gene is mutated in a subtype of arrhythmogenic right ventricular cardiomyopathy known as Naxos disease?", "output": "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmias and sudden death. A recessive mutation in the gene encoding plakoglobin has been shown to cause Naxos disease, a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin. " }, { "input": "Which gene is mutated in a subtype of arrhythmogenic right ventricular cardiomyopathy known as Naxos disease?", "output": "A homozygous loss-of-function mutation of the Plakoglobin (Jup) gene, which encodes a major component of the desmosome and the adherens junction, had been identified in Naxos patients, although the underlying mechanism remained elusive." }, { "input": "Which gene is mutated in a subtype of arrhythmogenic right ventricular cardiomyopathy known as Naxos disease?", "output": "A homozygous loss-of-function mutation of the Plakoglobin (Jup) gene, had been identified in Naxos Disease patients, a subset of ARVC, which is characterized by cutaneous disorder." }, { "input": "What is the role of edaravone in traumatic brain injury?", "output": "Edaravone, a free radical scavenger, has been shown to have neuroprotective effects after traumatic brain injury. In animal models, edaravone has been shown to reduce neuronal damage by scavenging reactive oxygen species (ROS), maintain intact the autoregulation of the cerebral vasculature, decrease neuronal loss, reduce programmed cell death, the presence of inflammatory cytokines, cerebral edema, and blood-brain barrier (BBB) permeability. Edaravone also protects against neurological deficits and memory deficits following traumatic brain injury." }, { "input": "Are there plasma membrane receptors for thyroid hormones?", "output": "Receptors for thyroid hormones are present on plasma membrane of cells; in particular thyroid hormones bind integrin that is a heterodimeric component of plasma membrane" }, { "input": "Which disorder is rated by Palmini classification?", "output": "Palmini classification system is used for classification of focal cortical dysplasia." }, { "input": "what is the role of erythropoietin in cardiac regeneration after myocardial infarction?", "output": "In preclinical studies, erythropoietin improved cardiac function and perfusion by angiomyogenesis and protection of cardiomyocytes in myocardial infarction indicating that erythropoietin may play a role in the stimulation of cell regeneration under normal physiologic conditions and in patients with myocardial injury. Epo overexpression was found to enhance the cellular regenerative properties of MSCs by both autocrine and paracrine pathways. However, results from recent clinical trials did not support beneficial effects of cytokine therapy with erythropoietin in patients with myocardial infarction." }, { "input": "Does Rad9 interact with Aft1 in S.cerevisiae?", "output": "Yes. Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events." }, { "input": "Are there any desmins present in plants?", "output": "No. Desmins are type III intermediate filament (IF) proteins that have been identified to date only in metazoa (human, Danio rerio, bovine). Desmins are also associated with severe forms of skeletal, cardiac and myofibrillar myopathies." }, { "input": "Are viruses involved in the etiology of human subacute thyroiditis?", "output": "Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid caused probably by viruses\nThe principal classes of viruses involed in SAT include Epstein Barr and Retroviridae" }, { "input": "List core circadian clock genes.", "output": "The core circadian clock genes are CLOCK, BMAL1, Per, and Cry." }, { "input": "Which peripheral neuropathy has been associated with NDRG1 mutations?", "output": "Charcot-Marie-Tooth (CMT) 4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1)." }, { "input": "Which peripheral neuropathy has been associated with NDRG1 mutations?", "output": "CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1)" }, { "input": "Is miR-126 involved in heart failure?", "output": "Yes, miR-126 is associated with heart failure." }, { "input": "Does resveratrol reduce cardiac remodeling?", "output": "Resveratrol attenuates left ventricular remodeling.\nResveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart.\nResveratrol administration improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function.\nResveratrol can constitute an adjuvant therapeutic option in prevention of dilated cardiomyopathy." }, { "input": "Does resveratrol reduce cardiac remodeling?", "output": "Most of the evidence shows that Resveratrol supresses cardiac remodeling." }, { "input": "Which is the receptor for substrates of Chaperone Mediated Autophagy?", "output": "Chaperone-mediated autophagy (CMA) is a lysosomal pathway for selective removal of damaged cytosolic proteins. The LAMP2A (Lysosome-associated membrane protein 2 isoform A) functions as a receptor for cytosolic proteins and also as essential component of the CMA translocation complex [28]. Cytosolic substrate proteins bind to monomers of LAMP-2A, which then multimerizes to form the complex required for substrate transmembrane import." }, { "input": "What are the hallmarks of congestive heart failure?", "output": "Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid. Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation. Disturbed myocardial calcium handling is also one of the pathophysiologic hallmarks of congestive heart failure. One of the hallmarks of chronic congestive heart failure is an increase in sympathetic tone to the peripheral circulation and to the heart. It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure. Myocardial failure ultimately leads to exaggerated neurohumoral compensatory mechanisms and derangements of the peripheral circulation, which are the hallmarks of congestive heart failure. Two additional hallmarks of this syndrome are sodium and water retention. Accumulation of oxidized matrix between the endothelium and cardiac muscle, and endocardial endothelial dysfunction, are also hallmarks of congestive heart failure." }, { "input": "What is the mode of inheritance of short QT syndrome?", "output": "The short QT syndrome has an autosomal dominant mode of inheritance." }, { "input": "List clinical trials that have directly compared microsurgical clipping with endovascular coiling for treatment of ruptured brain aneurysms?", "output": "Barrow Ruptured Aneurysm Trial (BRAT) and international subarachnoid aneurysmal trial (ISAT) have directly compared microsurgical clipping with endovascular coiling for treatment of ruptured brain aneurysms. FIAT study, a clinical care trial aiming to compare angiographic and clinical outcomes following treatment with a Flow-Diverter or with the best conventional treatment option (including clipping) is underway." }, { "input": "What is the reason for the narcolepsy cases developed after H1N1 influenza vaccination?", "output": "The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility." }, { "input": "Which are the biotracers used for detection of Alzheimer's disease using PET?", "output": "Pittsburgh compound B (PIB) was the first radiotracer capable of highlighting deposits of beta-amyloid\u2014one pathological hallmark of Alzheimer's disease\u2014in living individuals during a PET scan. The Alzheimer's Association helped fund early PIB development. The Association in 2006 also awarded a $2.1 million grant to the Alzheimer's Disease Neuroimaging Initiative (ADNI) to expand this long-term, nationwide study to include PIB-PET imaging.\n\n18F flutemetamol (flute), another radiotracer that highlights beta-amyloid in a PET scan, is structurally identical to PIB except for one fluorine atom in place of a carbon atom. That small chemical change enables flutemetamol to remain stable significantly longer than does PIB, potentially increasing its usefulness outside research settings. In phase II study results reported in the Annals of Neurology, flutemetamol performed similarly to PIB. Additional testing is under way.\n\nFlorbetapir F 18 (18F-AV-45) is also a radiotracer that highlights brain beta-amyloid during a PET scan. At the 2010 Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD), florbetapir's developer first reported data, later published in the JAMA, showing nearly perfect correlation between brain amyloid levels detected by florbetapir PET scans in study volunteers and levels found in autopsies of the same individuals a few months later. The developer has sought Food and Drug Administration (FDA) approval to market florbetapir under the brand name Amyvid. The FDA has said it will withhold approval until the developer establishes a professional training program to ensure accuracy and consistency in reading and interpreting Amyvid scans.\n\nFlorbetaben (BAY 94-9172) is another radiotracer designed to detect beta-amyloid during a PET scan. Phase II study results and other florbetaben data were reported at the 2010 Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD). Phase II data were also later published in Lancet Neurology. Further studies are now under way." }, { "input": "What was the purpose of the FANTOM3 project?", "output": " The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species" }, { "input": "What was the purpose of the FANTOM3 project?", "output": "Functional Annotation Of Mouse 3 (FANTOM3), an international collaboration research project focusing on expanding the transcriptome and subsequent analyses. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species." }, { "input": "In which isochores are Alu elements enriched?", "output": "Alu elements are enriched in high GC% isochores due to reduced Alu loss by recombination in these regions. The frequency of Alu sequences increases with increasing GC, but attains a maximum in H2 isochores." }, { "input": "Is oxalate renal excretion increased after bariatric surgery?", "output": "Bariatric surgery is associated with a significant risk of nephrolithiasis.\nEnteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of bariatric surgery\nHyperoxaluria in patients treated with bariatric surgery was found to be a result of hyperabsorption of oxalate" }, { "input": "Is oxalate renal excretion increased after bariatric surgery?", "output": "Urinary oxalate increases after bariatric surgery" }, { "input": "Which are the mutational hotspots of the human KRAS oncogene?", "output": "The KRAS oncogene has four main mutational hotspots located at codons 12, 13, 61 and 146." }, { "input": "Which are the mutational hotspots of the human KRAS oncogene?", "output": "The mutational hotspots for the K-ras oncogene are codons 12 and 13" }, { "input": "Which intraflagellar transport (IFT) motor protein has been linked to human skeletal ciliopathies?", "output": "Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies" }, { "input": "Which intraflagellar transport (IFT) motor protein has been linked to human skeletal ciliopathies?", "output": "Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS)." }, { "input": "What is the mechanism of action of ocrelizumab for treatment of multiple sclerosis?", "output": "Ocrelizumab is a cytolytic monoclonal antibody that binds CD20 antigen present of B cells. It is approved for treatment of multiple sclerosis." }, { "input": "What is the link between Nonidet-40 (NP-40) and biotinylation?", "output": "0.5% of the non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is sufficient to practically eliminate contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins." }, { "input": "What is the link between Nonidet-40 (NP-40) and biotinylation?", "output": "NP-40 reduces contamination by endogenous biotinylated carboxylases during purification of biotin tagged nuclear proteins." }, { "input": "Which is the transcript responsible for X-chromosome inactivation?", "output": "The long non- coding RNA Xist (X inactive specific transcript)" }, { "input": "What are viral vectors used for in optogenetics?", "output": "Viral vectors are used to express optogenetic constructs in selected cells." }, { "input": "Which domain allowing self-association do exist in TDP-43 and FUS proteins?", "output": "PRION PROTEINS" }, { "input": "Which domain allowing self-association do exist in TDP-43 and FUS proteins?", "output": "Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. TDP-43, FUS and TAF15 share similar properties, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. For TDP-43, both the RRM1 and the C-terminal glycine-rich domain are required for SG localization. Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion protein" }, { "input": "Which domain allowing self-association do exist in TDP-43 and FUS proteins?", "output": "Scouring the human genome with this algorithm enriches a select group of RNA-binding proteins harboring a canonical RNA recognition motif (RRM) and a putative prion domain. Moreover, two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins. PrLDs are over-represented in human RNA-binding proteins and mediate phase transitions underpinning RNP granule assembly. For example, TDP-43 and FUS form cytoplasmic inclusions in amyotrophic lateral sclerosis (ALS) and mutations in TDP-43 and FUS can cause ALS." }, { "input": "Which domain allowing self-association do exist in TDP-43 and FUS proteins?", "output": "Two RNA-binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins." }, { "input": "Is there a role for transcription factories in genome organization?", "output": "The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer " }, { "input": "Is there a role for transcription factories in genome organization?", "output": "Yes. The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. Those active chromatin hubs and transcription factories also involve long-range interactions. Thus, it seems that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs." }, { "input": "Which are the Chompret criteria for Li-Fraumeni syndrome?", "output": "1) According to the Chompret criteria for LFS, any patient with adrenocortical cancer (ACC), irrespective of age and family history, is at high risk for a TP53 germline mutation.\n2) All families with a p53 mutation must have at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC)." }, { "input": "When ceritinib used instead of crizotinib?", "output": "Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC patients that are crizotinib-resistant and crizotinib-na\u00efve." }, { "input": "What type of enzyme is peroxiredoxin 2 (PRDX2)?", "output": "Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme that uses cysteine residues to decompose peroxides. \nPeroxiredoxin-2 (PRDX2), an enzyme reducing hydrogen peroxide and lipid peroxides \nPeroxiredoxin 2 (Prx2) is a thiol-dependent peroxidase." }, { "input": "Is the length of the poly(A) tail involved in human disease?", "output": "Yes. Severely truncated poly(A) tails of mitochondrial mRNAs were found to be involved in an autosomal recessive spastic ataxia with optic atrophy." }, { "input": "Why graphics processing units (GPU) are more suitable for biological tasks than central processing units (CPU)?", "output": "Traditional central processing unist (CPUs) are reaching their limit in processing power and are not designed primarily for multithreaded applications. Graphics processing units (GPUs) on the other hand are affordable, scalable computer powerhouses that, thanks to the ever increasing demand for higher quality graphics, have yet to reach their limit. Typically high-end CPUs have 8-16 cores, whereas GPUs can have more than 2,500 cores. GPUs are also, by design, highly parallel, multicore and multithreaded, able of handling thousands of threads doing the same calculation on different subsets of a large data set. This ability is what makes them perfectly suited for biological analysis tasks. Lately this potential has been realized by many bioinformatics researches and a huge variety of tools and algorithms have been ported to GPUs, or designed from the ground up to maximize the usage \nof available cores." }, { "input": "Which are the thyroid hormone analogs utilized in human studies?", "output": "TRIAC and TETRAC are two different thyroid hormone analogs utilized in human studies" }, { "input": "Are patients with marfan syndrome at increased risk of arrhythmias?", "output": "Patients with marfan syndrome carry increased risk for arrhythmias" }, { "input": "What are the treatments of choice for GIST (gastrointestinal stromal tumor)?", "output": "The surgical resection is a treatment of choice for gastrointestinal stromal tumors. It has been shown that adequate surgical resection correlates with high 5-years survival rates for patients with gastric GIST. When they are localized, the treatment of choice is surgical excision, but advanced tumors have a limited response to chemo or radiotherapy. Imatinib (STI571 or Glivec) is a selective inhibitor or tyrosine kinase proteins that has been used successfully in the treatment of advanced GIST. " }, { "input": "What are the treatments of choice for GIST (gastrointestinal stromal tumor)?", "output": "Approximately 80% of patients with metastatic GIST benefit from imatinib, although acquired resistance to the agent may develop. For patients with primary GIST, surgery remains the treatment of choice, and whether outcome is improved by adjuvant imatinib is currently under broad investigation." }, { "input": "List Kartagener Syndrome Triad.", "output": "The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome." }, { "input": "Which disease is associated with the ectopic expression of the protein encoded by the gene DUX4?", "output": "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat." }, { "input": "Which G protein is essential in the formation and function of lamellipodia?", "output": "Recruitment of the small G-protein Rac1 to the plasma membrane is essential in inducing the local formation of specialized cellular processes termed lamellipodia." }, { "input": "Which are the main functions of the APOBEC3 family of proteins?", "output": "The APOBEC3 family of cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1), and endogenous transposable elements, such as LINE-1 and Alu retrotransposons." }, { "input": "Which histone modifications are associated with constitutive heterochromatin?", "output": "Strong methylation at H3 lysine 9 occurred preferentially in heterochromatic chromocenters of Arabidopsis nuclei. In general, heterochromatin has been linked to trimethylation of H3 at lysine 9 and parsimony analysis reveal that histone H3K9 methylation is, next to histone deacetylation, the evolutionary most stable heterochromatic mark. Classical histone modifications associated with heterochromatin also include H3K27me1 and H3K27me2. H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin. Other histone methylation marks usually found in constitutive heterochromatin are H4K20me3, H3K9me3, and H3K79me3. H3S10P is a good marker of pericentromeric heterochromatin." }, { "input": "Which histone modifications are associated with constitutive heterochromatin?", "output": "H3K9 methylation\nH3S10 phosphorylation\nH3K79 and H4K20 methylation" }, { "input": "What is the main application of SWATH-MS in proteomics?", "output": "Using the method called SWATH-MS one might ask sample sets for the presence and quantity of essentially any protein of interest." }, { "input": "Do selenoproteins and selenium play a role in prostate cancer prevention?", "output": "No, although initial epidemiological studies on humans and on animal and cell- based models indicated that selenoproteins may be protecting against prostate cancer, more research is needed to improve the understanding of selenium metabolism and requirements for optimal health." }, { "input": "What can Nothobranchius furzeri be used as a model system for?", "output": "N. furzeri an interesting model system to investigate the effects of experimental manipulations on longevity and age-related pathologies.\nN. furzeri could represent a model system for studying the genetic control of life-history traits in natural populations.\nN. furzeri could be a very useful model for comparative genomics of aging.\nIt can be employed to test the effects of experimental manipulation on aging and apharmacological research." }, { "input": "What is the function of TALENs?", "output": " These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. Artificial transcription activator-like effector nucleases (TALENs) provide a powerful new approach for targeted zebrafish genome editing and functional genomic applications. Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs." }, { "input": "What is the function of TALENs?", "output": "Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. TALENs provide a powerful new approach for targeted genome editing and functional genomic applications." }, { "input": "Has protein citrullination been implicated in rheumatoid arthritis?", "output": "Yes, protein citrullination been implicated in rheumatoid arthritis." }, { "input": "Show results of randomised controlled trials for certolizumab pegol.", "output": "Improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.\nRandomised controlled trials (RCTs) of CZP have demonstrated rapid improvements in workplace and home productivity." }, { "input": "Which is the mass-tag that reveal the ubiquitination of a lysine residue?", "output": "Lys-\u025b-Gly-Gly (K-\u025b-GG) is the remnant produced by trypsin digestion of proteins having ubiquitinated lysine side chains." }, { "input": "Which gene is involved in CADASIL?", "output": "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene." }, { "input": "What is the role of thyroid hormone receptor alpha1 in insulin secretion?", "output": "Liganded TR(alpha) plays a critical role in beta-cell replication and in expansion of the beta-cell mass. the TRalpha P398H mutation which cannot bind T3, is associated with insulin resistance. Loss of Thra protects mice from high-fat diet-induced hepatic and peripheral insulin resistance." }, { "input": "Do R-loops tend to form at sites of DNA replication?", "output": "R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins. Physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. One mechanism may be that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed. Thus, the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery." }, { "input": "Do R-loops tend to form at sites of DNA replication?", "output": "We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication. ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop. We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. We review evidence suggesting that R-loops are frequent during normal cell growth and that R-loops are critical for the maintenance of genome integrity." }, { "input": "Which two catechol-O-methyl transferase (COMT) inhibitors can be used for treatment of Parkinson disease?", "output": "Tolcapone (central and peripheral) and entacapone (peripheral) are catechol-O-methyl transferase inhibitors that are used for treatment of Parkinson disease." }, { "input": "What are the structures formed when keratin molecules come together?", "output": "Keratins form the intermediate filaments of the cytoskeleton and provide scaffold structures within cells." }, { "input": "Which is the prognostic impact of hypothyroidism in patients with acute myocardial infarction?", "output": "Thyroid dysfunction, particularly low T3 syndrome, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions." }, { "input": "Which are the main features of CREST and other ALS-linked proteins?", "output": "CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity." }, { "input": "Which are the main features of CREST and other ALS-linked proteins?", "output": "Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles. Like several other ALS-associated proteins, CREST is recruited to induced stress granules. Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity." }, { "input": "Which are the main features of CREST and other ALS-linked proteins?", "output": "Like several other ALS-associated proteins, CREST is recruited to induced stress granules. " }, { "input": "Mutations of which genes have been associated with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?", "output": "Mutations in five genes \u2013 ryanodine receptor 2 (RYR2), calsequestrin 2(CASQ2), triadic (TRDN), calmodulin 1 (CALM1) and potassium channel, inwardly rectifying subfamily J, member 2 (KCNJ2) \u2013 have been found to be associated with CPVT" }, { "input": "What is the relationship between nucleosomes and exons?", "output": "Nucleosomes are preferentially located within exons compared to nearby intronic sequences. Preferential positioning within the exons is indepedent of gene expression levels, stronger in exons with weak splice sites and conserved through metazoan evolution." }, { "input": "List programs suitable for pharmacophore modelling", "output": "A pharmacophore is an abstract description of molecular features which are necessary for molecular recognition of a ligand by a biological macromolecule. The IUPAC defines a pharmacophore to be \"an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response\". A pharmacophore model explains how structurally diverse ligands can bind to a common receptor site. Furthermore pharmacophore models can be used to identify through denovo design or virtual screening novel ligands that will bind to the same receptor. Nowadays there are many programs suitable for pharmacophore modelling such as LigandScout, Discovery Studio, Catalyst, PharmaGist, Genetic Algorithm Similarity and Molecular Operating Environment." }, { "input": "Is selenium deficiency involved in autoimmune thyroid disease?", "output": "Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interactionIn areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells" }, { "input": "Is selenium deficiency involved in autoimmune thyroid disease?", "output": "The essential trace element selenium was recently recognized as being incorporated as selenocysteine in all three deiodinases of the thyroid gland. This has decisively confirmed the clear-cut link between selenium and thyroid function. Additionally, it has been established that the thyroid contains more selenium than any other tissue, and that selenium deficiency aggravates the manifestation of autoimmune thyroid disease." }, { "input": "Is selenium deficiency involved in autoimmune thyroid disease?", "output": "The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease " }, { "input": "List disorders that are caused by mutations in the mitochondrial MTND6 gene.", "output": "Mitochondrial MTND6 gene mutations are the cause of Leigh syndrome and Leber's hereditary optic neuropathy and/or dystonia." }, { "input": "Which are the most common methods for ctDNA (circulating tumour DNA) detection?", "output": "Recently, nanoplasmonics has emerged as a platform for one-step dual detection with high sensitivity and specificity. The practice of \"liquid biopsy\" as a diagnostic, prognostic and theranostic tool in non-small cell lung cancer (NSCLC) patients is an appealing approach, at least in theory, since it is noninvasive and easily repeated. Cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]\u00b72ClO(4)) as the electrochemical probe was developed. The sensor is very sensitive and selective for calf thymus DNA (ctDNA) detection in aqueous medium." }, { "input": "Which are the most common methods for ctDNA (circulating tumour DNA) detection?", "output": "A new DNA sensor using a nickel(II) phenanthroline complex ([Ni(phen)(2)PHPIP]\u00b72ClO(4)) as the electrochemical probe was developed. The calculated dynamics parameters of the electrode process indicate that there are obvious interactions between the probe and the ctDNA in aqueous solution. Under constant potential conditions, the redox current peak of the probe (Ni-complex) decreases obviously as the probe interacts/binds with ctDNAs. These results demonstrate that the sensor can simultaneously detect the hot-spot mutation and epigenetic changes on the ctDNA." }, { "input": "Which gene is associated with Muenke syndrome?", "output": "Muenke syndrome has been related to a mutation on the Fibroblast Growth Factor Receptor (FGFR3) gene." }, { "input": "Is it safe to use Abatacept during pregnancy?", "output": "It is not safe to use the drug abatacept during pregnancy, since there is very limited experience/knowledge yet. Additionally, it is recommended to withdraw the drug before pregnancy." }, { "input": "Is it safe to use Abatacept during pregnancy?", "output": "Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept." }, { "input": "What is DeepCAGE?", "output": "The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. DeepCAGE can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network." }, { "input": "Is STAT3 involved in EIF2AK2-dependent suppression of autophagy?", "output": "STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy" }, { "input": "Is STAT3 involved in EIF2AK2-dependent suppression of autophagy?", "output": "Pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. On the other hand, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy. Therefore, STAT3 may act as a competitive inhibitor of EIF2AK2 to suppress autophagy." }, { "input": "RTS S AS01 vaccine was developed to prevent which disease?", "output": "RTS,S/AS01 vaccine was developed for prevention of malaria." }, { "input": "What are the Topological Domains (TADs)?", "output": "Topolological domains or TADs are megabase-sized local chromatin interaction domains which are a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. The boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome." }, { "input": "What is the vibrational theory of olfaction?", "output": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. The theory proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations. It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling. Thus, the authors, that have proposed this theory, suggest that olfaction, like colour vision and hearing, is a spectral sense." }, { "input": "Are CTCF and BORIS involved in genome regulation and cancer?", "output": "Yes. CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation." }, { "input": "What is the application of the ASSET algorithm in C.elegans?", "output": "ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) is a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos. It gathers quantitative information with subcellular precision in the early Caenorhabditis elegans embryo, which is an attractive model to investigate evolutionarily conserved cellular mechanisms. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos." }, { "input": "What is the application of the ASSET algorithm in C.elegans?", "output": "The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms. In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos." }, { "input": "Are Sidekick proteins members of the immunoglobulin superfamily?", "output": "Yes, sidekick are cell adhesion molecules of the immunoglobulin superfamily." }, { "input": "What are the pyknons?", "output": "Using an unsupervised pattern-discovery method, the human intergenic and intronic regions were processed and all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance were catalogued. Among the millions of discovered patterns, a subset of 127,998 patterns was found, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Pyknons might represent a biologically important link between coding and non-coding DNA." }, { "input": "Which deiodinases are best known to be present in brain?", "output": "All the 3 deiodinases (Type 1, Type 2 and Type 3 deiodinase) are present in the \"brain\" but Type 1 deiodinase is only found in neurohypophysis that cannot be actually considered true \"brain tissue\"." }, { "input": "What are the computational methods for the prediction of beta-barrel transmembrane proteins?", "output": "Computational tools have been developed for beta-barrel transmembrane protein discrimination, topology prediction and prediction of their structural features.\nInitial methods developed for the prediction of the transmembrane beta strands were based on hydrophobicity analysis, using sliding windows along the sequence, in order to capture the alternating patterns of hydrophobic-hydrophilic residues of the transmembrane strands, or using generalized secondary structure prediction methods. Other approaches included the construction of special empirical rules using amino-acid propensities and prior knowledge of the structural nature of the proteins, and the development of Neural Network-based predictors to predict the location of alpha-carbon atoms with respect to the membrane. During the last few years, other more refined methods, appeared, including: Neural Networks, Hidden Markov Models, Support Vector Machines, k-Nearest Neighbors, Radial Basis Functions, Bayesian Networks, Genetic Algorithms, Mahalanobis Discriminant Functions, Cellular Automata, N-to-1 Extreme Learning Machines. Hidden Markov Model-based methods are among the most successful in topology prediction, being able to capture the unique architecture of beta-barrel transmembrane proteins. Consensus methods, as well as pipelines of several related tools (e.g. subcellular localization prediciton, alpha-helical transmembrane protein prediction, signal-peptide/lipoprotein prediction) have also used for discriminating beta-barrel transmembrane proteins. Recently, a number of methods for predicting more detailed structural features (e.g. surface accessibility, residue contacts, even detailed atomic 3D models) tailored to beta-barrel transmembrane proteins have been developed, based on knowledge-based potential functions, graph theoretic models, physical models and multi-tape S-attribute grammars. Methods/tools falling in the aforementioned classes are (listed in alphabetical order): BBF (beta-barrel finder), BETAWARE, BOCTOPUS, BOMP, BTMX (Beta barrel TransMembrane eXposure), HHomp, HMM-B2TMR, OMBBpred, PROFtmb, PRED-TMBB, TMB-Hunt, TBBPred, TMBETAPRED-RBF, TMBHMM, TransFold, TMBpro, TMBKNN, Wimley" }, { "input": "Describe what is the usage of the Theatre software tool for genomic analysis.", "output": "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. In addition to web-based output, Theatre can produce publication quality colour hardcopies showing predicted features in aligned genomic sequences." }, { "input": "Describe what is the usage of the Theatre software tool for genomic analysis.", "output": "Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. Theatre can be accessed at http://www.hgmp.mrc.ac.uk/Registered/Webapp/theatre/." }, { "input": "How are CRM (cis-regulatory modules) defined?", "output": "Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules." }, { "input": "How are CRM (cis-regulatory modules) defined?", "output": "In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs)." }, { "input": "How are CRM (cis-regulatory modules) defined?", "output": "Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). " }, { "input": "How are CRM (cis-regulatory modules) defined?", "output": "CisMiner can be queried for the results presented in this work and can also perform a customized cis-regulatory module prediction on a query set of transcription factor binding sites provided by the user. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules. Our web server is available at http://creme.dcode.org." }, { "input": "Which is the main regulatory molecule of SERCA2A function in the cardiac muscle?", "output": "SERCA2a activity is regulated by phosphorylation of another SR protein, Phospholamban (PLN). Phospholamban (PLB) inhibits the activity of SERCA2a, the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, by decreasing the apparent affinity of the enzyme for Ca(2+)." }, { "input": "Which gene is responsible for the development of the Mowat-Wilson syndrome?", "output": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene." }, { "input": "Which gene is responsible for the development of the Mowat-Wilson syndrome?", "output": "Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndromezfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies." }, { "input": "Which gene is responsible for the development of the Mowat-Wilson syndrome?", "output": "Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B, also known as ZEB2 or SIP-1)." }, { "input": "Which gene is responsible for the development of the Mowat-Wilson syndrome?", "output": "zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies. Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development" }, { "input": "How is active neurotoxin of Clostridium botulinum detected?", "output": "Active neurotoxin of Clostridium botulinum can be detected by:\nmouse lethality assay\nby mass spectrometry\nbioassay\ndifferentiated cell models\npeptide cleavage assay\nFDC (functional dual coating) microtitre plate immuno-biochemical assay\nendopeptidase activity monitored via UV-Visible spectroscopy" }, { "input": "Which factor interacts with Treslin/TICRR throughout the cell cycle of human cells?", "output": "MDM two binding protein (MTBP) is a factor that interacts with Treslin/TICRR throughout the cell cycle. MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, it is required for DNA replication irrespective of a cell's p53 status. MTBP is proposed to act with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells." }, { "input": "What is oprozomib?", "output": "Oprozomib is a second-generation, highly-selective, orally administered proteasome inhibitor with promising activity against multiple myeloma.\nOprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Consequently, oprozomib seems to be able to effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM.\nOprozomib effectively decreases multiple myeloma cell viability.\nOprozomib potently inhibit cell survival and induce apoptosis in HNSCC cell lines via upregulation of pro-apoptotic Bik. Upregulation of Mcl-1 by these agents served to dampen their efficacies. Oprozomib also induced autophagy, mediated, in part, by activation of the UPR pathway involving upregulation of ATF4 transcription factor. Autophagy induction served a prosurvival role. Oral administration of ONX 0912 inhibited the growth of HNSCC xenograft tumors in a dose-dependent manner.\nOprozomib inhibited NF-\u03baB expression." }, { "input": "Is there a relationship between junctin and ryanodine receptors?", "output": "Yes, junctin binds to ryanodine receptors within the junctional sarcoplasmic reticulum of calcium release units, and normally acts as an activator of RyR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)]." }, { "input": "Which medication should be administered when managing patients with suspected acute opioid overdose?", "output": "Naloxone is opioid anagonist that should be administered for all patients with suspected acute opioid overdose. Intravenous naltrexone hydrochloride is usually administered, however, other formulations, including enteral methylnaltrexone, nebulized naloxone and subcutaneous naloxone, are under investigation and can be used under certain circumstances." }, { "input": "In which nuclear compartments is heterochromatin located?", "output": "This compartment localizes into three main regions: the peripheral heterochromatin, perinucleolar heterochromatin, and pericentromeric heterochromatin. Silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modification" }, { "input": "Have mutations in the ZEB2 gene been found in any human syndrome?", "output": "Yes, the Mowat-Wilson syndrome" }, { "input": "Which enzymes are involved in global genome nucleotide excision repair (GG-NER) in bacteria?", "output": "Nucleotide excision repair (NER) is universally used to recognize and remove many types of DNA damage. In eubacteria, the NER system typically consists of UvrA, UvrB, UvrC, the UvrD helicase, DNA polymerase I, and ligase. Damage recognition during bacterial NER depends upon UvrA, which binds to the damage and loads UvrB onto the DNA. Subsequently, UvrA, UvrB and UvrC form the excinuclease protein UvrABC endonuclease, a multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. In some cases, Cho may be the effective nuclease for NER, rather than UvrC. UvrC nuclease and the short oligonucleotide that contains the DNA lesion are removed from the post-incision complex by UvrD, a superfamily 1A helicase. In gram-positive organisms, PcrA helicase can also displace UvrC and the excised oligonucleotide from a post-incision NER complex." }, { "input": "Is JTV519 (K201) a potential drug for the prevention of arrhythmias?", "output": "Yes, JTV519 has antiarrhythmic properties." }, { "input": "What is the mechanism of microRNA deregulation in carcinogenesis?", "output": "MicroRNAs (miRNAs) are endogenous non-protein coding single-stranded RNAs (19\u201325 nucleotides in length) generated from cleavage of larger non-coding RNAs by the ribonuclease III enzyme Dicer. They become part of the RNA-induced silencing complex and negatively regulate gene expression by binding to homologous 3'-UTR region of target protein-coding mRNAs as an imperfect match, causing translational repression or degradation. Approximately one-third of the protein-coding genes are susceptible to miRNA regulation. Accumulating evidence indicates that deregulated miRNA expression is associated with the onset and progression of a number of human cancers. Therefore, cancer-associated miRNAs (CA-miRNAs) could regulate target genes by acting either as \"oncogenes\" or \"tumor suppressor miRNA (TS-miRNAs)\". In line with this, numerous cancers (e.g. breast, lung, oesophageal, prostate, pancreatic, gastric and colon cancer) have been classified based on their unique miRNA expression profile." }, { "input": "Which type of GTPases is required for amino acid-dependent activation of mTORC1?", "output": "Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome" }, { "input": "Which type of GTPases is required for amino acid-dependent activation of mTORC1?", "output": "Amino acids act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation." }, { "input": "In which genomic regions are Alu enriched?", "output": "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. Alu elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins.\nThis bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions." }, { "input": "In which genomic regions are Alu enriched?", "output": "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome." }, { "input": "What is the synonym of the lubag disease?", "output": "Lubag disease is also known as X-linked dystonia-parkinsonism (XDP). This disease is characterized by dystonia and parkinsonism, and afflicts Filipino men, and rarely, women originating principally from the Panay Island." }, { "input": "Dracorhodin perchlorate was tested for treatment of which cancers?", "output": "Dracorhodin perchlorate induce apoptosis in prostate cancer, gastric tumor, melanoma and premyelocytic leukemia." }, { "input": "What is the role of venous angioplasty in multiple sclerosis?", "output": "Chronic cerebrospinal venous insufficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS. There have been reports to suggest that venous angioplasty in MS patients is a feasible and safe procedure and is associated with improved disease symptom severity, quality of life, and corrects blood pressure deviation, improves CSF dynamics. Open venous reconstruction of the internal jugular vein has also been tried with good results.\nHowever, some authors have failed to document beneficial value of venous angioplasty in MS patients and systematic review has suggested that there is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS." }, { "input": "Are the Fanconi anemia genes a part of the same signalling pathway?", "output": "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA " }, { "input": "Are the Fanconi anemia genes a part of the same signalling pathway?", "output": "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNAMutations in at least 14 different genes have been shown to cause FA" }, { "input": "Are the Fanconi anemia genes a part of the same signalling pathway?", "output": "Mutations in at least 14 different genes have been shown to cause FA. The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA. " }, { "input": "Are the Fanconi anemia genes a part of the same signalling pathway?", "output": "The Fanconi anemia genes code for proteins that act in complexes to coordinate the repair of damaged DNA." }, { "input": "Are the Fanconi anemia genes a part of the same signalling pathway?", "output": "The FA genes code for proteins that act in complexes to coordinate the repair of damaged DNA. Mutations in at least 14 different genes have been shown to cause FA. " }, { "input": "Are there clinical trials using stem cells for the treatment of cardiac disease?", "output": "Yes, there exists clinical trials for cardiac stem cell based treatment." }, { "input": "Are there clinical trials using stem cells for the treatment of cardiac disease?", "output": "Yes, there are several clinical trials on the use of stem cells for the treatment of cardiac (heart) disease." }, { "input": "Is DNA methylation an epigenetic modification of chromatin related to gene expression?", "output": "Epigenetic changes such as DNA methylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely." }, { "input": "Is Growth factor independence 1b (GFI1B) important for hematopoiesis?", "output": "Yes. Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes." }, { "input": "Has Revlimid been approved by the US Food and Drug Administration?", "output": "Yes, Revlimid has been approved by the US Food and Drug Administration for treatment of multiple myeloma." }, { "input": "Which is the execution time (complexity) of the Smith-Waterman algorithm for the alignment of two sequences", "output": "The complexity of the Smith-Waterman dynamic programming algorithm is quadratic, that is, it runs in time proportional to the product of lengths of the sequences being aligned." }, { "input": "List mutations that are implicated in the Gray Platelet Syndrome.", "output": "GFI1B and NBEAL2 mutations are implicated in the Gray Platelet Syndrome." }, { "input": "Has single guide RNA been used on human cells?", "output": "Yes, sgRNA has been used in human cell lines." }, { "input": "Is Fibroblast Growth Factor 23 a phosphaturic hormone?", "output": "Yes, fbroblast growth factor 23 (FGF23) is a phosphaturic hormone." }, { "input": "Which type of cell death is known as anoikis?", "output": "Anoikis (Greek for Homelessness) is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonizing of distant organs. Anoikis is important in the normal physiologic development of the human body, as well as in disease states. Adhesion to structural glycoproteins of the extracellular matrix is necessary for survival of the differentiated adherent cells. Cancer cells harbor anoikis resistance allowing spread to occur." }, { "input": "Which type of cell death is known as anoikis?", "output": "Ano?kis is defined as programmed cell death induced by the loss of cell/matrix interactions. Adhesion to structural glycoproteins of the extracellular matrix is necessary for survival of the differentiated adherent cells in the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts, and cardiac myocytes.Developed organs display strict spatial organization of differentiated cells which is required for proper organ function. One important device that prevents tissue disorganization is the death of cells that lose anchorage to their native matrix, a signal that indicates potential loss of proper tissue context. Termed anoikis (Greek for Homelessness), this form of cell death is a specialized form of apoptosis." }, { "input": "The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger?", "output": "The effects of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger (NCX), on Na(+)-dependent Ca(2+) uptake and catecholamine (CA) release were examined in bovine adrenal chromaffin cells that were loaded with Na(+) by treatment with ouabain and veratridine. SEA0400 inhibited Na(+)-dependent (45)Ca(2+) uptake and CA release, with the IC(50) values of 40 and 100 nM, respectively. " }, { "input": "The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger?", "output": "SEA0400 is a selective inhibitor of the Na(+)/Ca(2+) exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na(+)/Ca(2+) exchanger. SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline), is a selective NCX inhibitor in vivo." }, { "input": "What is Piebaldism?", "output": "Piebaldism is a rare autosomal dominant disorder of melanocyte development characterized by a congenital white forelock and multiple symmetrical stable hypopigmented or depigmented macules." }, { "input": "Which SLC family is FLVCR1 a member of?", "output": "Feline leukemia virus subgroup C receptor (FLVCR1) is a member of the SLC49 family." }, { "input": "Is amoxicillin used for treatment of malnutrition in children?", "output": "Yes, amoxicillin is used for treatment of malnutrition in children." }, { "input": "Where are the orexigenic peptides synthesized?", "output": "The orexigenic peptides are sythesized in the hypothalamus." }, { "input": "What is the mechanism of action of APOBEC3G cytidine deaminase to inhibit HIV-1 replication?", "output": "During reverse transcription, APOBEC3G deaminates dC to dU in nascent minus-strand viral DNA, resulting in G-to-A hypermutation in the plus strand DNA to inhibit replication of HIV-1, due to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. In an additional line of antiviral defense, APOBEC3G induces deamination of the apical loop cytidine of the trans-activation response (TAR) element, a short stem-loop RNA structure required for binding of elongation factors during HIV-1 transcription elongation, resulting in accumulation of short viral transcripts and production of lower amounts of full-length HIV-1 transcripts in Vif-deficient HIV-1-infected cells." }, { "input": "Which inherited disorder is known to be caused by mutations in the NEMO gene?", "output": "Incontinentia pigmenti (IP) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait" }, { "input": "Which inherited disorder is known to be caused by mutations in the NEMO gene?", "output": "Incontinentia pigmenti (IP) or Bloch-Sulzberger syndrome (BSS) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait." }, { "input": "What is ISMARA?", "output": "ISMARA (Integrated System for Motif Activity Response Analysis) is a web-based tool that models gene expression or chromatin modifications in terms of genome-wide predictions of regulatory sites. Given only gene expression or chromatin state data across a set of samples as input, ISMARA identifies the key TFs and miRNAs driving expression/chromatin changes and makes detailed predictions regarding their regulatory roles. These include predicted activities of the regulators across the samples, their genome-wide targets, enriched gene categories among the targets, and direct interactions between the regulators." }, { "input": "Is it possible to purify pseudopodia to be used for proteomic analysis?", "output": "Pseudopodia can be purified, using different strategies, in order to be used in proteomic studies." }, { "input": "Where does TDP43 localize in ALS neurons?", "output": "In control motor neurons, TDP43 was almost exclusively nuclear, whereas in ALS spinal motor neurons, TDP43 was predominantly localized to the cytosol and not the nucleus. " }, { "input": "Where does TDP43 localize in ALS neurons?", "output": "In control motor neurons, TDP43 was almost exclusively nuclear, whereas in ALS spinal motor neurons, TDP43 was predominantly localized to the cytosol and not the nucleus." }, { "input": "List interaction partners for the protein GATA1.", "output": "GATA-1 interact with factor Gfi-1b, the repressive MeCP1 complex, the chromatin remodeling ACF/WCRF complex, FOG-1, TAL-1, Ldb-1 and LMO2-C." }, { "input": "List interaction partners for the protein GATA1.", "output": "GATA1 interacts with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. Ldb1 is a known partners of GATA1. LMO2-C can bind endogenous GATA1. Novel transcription factor binding partners for PIAS3 include GATA1. Combinatorial interactions occurre between RUNX1 and its coregulator GATA1. Ski interacts with GATA1. GATA-1 interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1." }, { "input": "Is farnesoid X receptor (FXR) a nuclear receptor?", "output": "Yes, farnesoid X receptor (FXR) is a nuclear receptor." }, { "input": "What histone variants play a role in the DNA damage reponse?", "output": "Mostly H2A.X, but H2A.Z and H1R have also been associated to DNA damage" }, { "input": "List tele monitoring applications of miniaturised sensors", "output": "Home-polysomnography (HPSG)\nBody weight\nBlood pressure control\nHeart failure control\nVital signs - disaster relief, dangerous outdoor sports and adventure monitoring, and antiterrorism activities.\nTelemetric fetal home monitoring system for recording the trans-abdominal fetal heart signal and the uterine contractions\nVital signs - electrocardiograms (ECGs), temperature (T), and oxygen saturation (SaO2) , breath rate\nStep-counting for tele-rehabilitation\nDetection of falls in elderly" }, { "input": "How are ultraconserved elements called when they form clusters?", "output": "Ultraconserved non-coding elements (UCNEs) are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes. Their molecular functions and the reasons for their high degree of conservation remain enigmatic." }, { "input": "What is the basis of the methodology of \"functional class scoring\" (FCS) for the analysis of gene expression data?", "output": "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step." }, { "input": "What is the basis of the methodology of \"functional class scoring\" (FCS) for the analysis of gene expression data?", "output": "Functional class scoring (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. It consists of a semi-supervised method exploring both the expression pattern and the functional annotation of the genes." }, { "input": "What is the basis of the methodology of \"functional class scoring\" (FCS) for the analysis of gene expression data?", "output": "The second method, \"functional class scoring\" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. " }, { "input": "What is the Timothy syndrome?", "output": "Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years." }, { "input": "Which disease has been associated to a disruptive ALX1 protein?", "output": "Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia." }, { "input": "How many selenoproteins are encoded in the human genome?", "output": "25. 15kDa, DI1, DI2, DI3, GPx1, GPx2, GPx3, GPx4, GPx6, SelH, SelI, SelK, SelM, SelN, SelO, SelP, SelR, SelS, SPS2, SelT, TR1, TR2, TR3, SelV and SelW." }, { "input": "In which process Src, Cortactin and MT1-MMP are playing an essential role?", "output": "Src was shown to be required for invadopodia formation and function, whereas Cortactin was found to regulate cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. Finally, membrane type 1 matrix metalloproteinase (MT1-MMP) was demostrated as the key invadopodial enzyme responsible for gelatin matrix degradation in cancer cells." }, { "input": "In which yeast chromosome does the rDNA cluster reside?", "output": "Chromosome XII context is important for rDNA function in yeast" }, { "input": "In which yeast chromosome does the rDNA cluster reside?", "output": "The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit." }, { "input": "In which yeast chromosome does the rDNA cluster reside?", "output": "Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast. The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit. However, in cells arrested in late mitosis (M) by a cdc15 mutation, the unique DNA appeared decondensed while the repetitive rDNA region appeared condensed, suggesting that the condensation state of separate regions of the genome may be regulated differently. Finally our FISH method provides a new tool to analyze centromeres, telomeres, and gene expression in budding yeast." }, { "input": "Which is the underlying mechanism for exon skipping used to treat Duchenne muscular dystrophy?", "output": "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein. Many Duchenne Muscular Dystrophy patients need exon skipping of multiple exons in order to restore the reading frame, depending on how many base pairs the mutated exon(s) and adjacent exons have." }, { "input": "Which is the underlying mechanism for exon skipping used to treat Duchenne muscular dystrophy?", "output": "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein " }, { "input": "Which is the underlying mechanism for exon skipping used to treat Duchenne muscular dystrophy?", "output": "Antisense-mediated exon skipping therapy is a promising therapeutic approach that uses short DNA-like molecules called antisense oligonucleotides (AOs) to skip over/splice out the mutated part of the gene to produce a shortened but functional dystrophin protein" }, { "input": "Which is the underlying mechanism for exon skipping used to treat Duchenne muscular dystrophy?", "output": "Antisense oligonucleotides (AONs) that bind to complementary sequences of the dystrophin pre-mRNA to induce skipping of the targeted exon by modulating pre-mRNA splicing are promising therapeutic agents for DMD. In addition, multiple exon skipping could be used to select deletions that optimize the functionality of the truncated dystrophin protein. Theoretically, multiple exon skipping could be used to treat approximately 90%, 80%, and 98% of DMD patients with deletion, duplication, and nonsense mutations, respectively. One major challenge has been its limited applicability." }, { "input": "What is the advantage of using long nano columns in proteomics?", "output": "The longer the columns, the longer gradients are applied and finally more proteins (increased peak capacity) are identified in a complex proteomic experiment" }, { "input": "During which stage of the cell cycle is cohesin deposited on the yeast genome?", "output": "In the budding yeast, cohesin is loaded onto the chromosome during the late G1 phase, establishes sister chromatid cohesion concomitant with DNA replication, and dissociates by the telophase." }, { "input": "During which stage of the cell cycle is cohesin deposited on the yeast genome?", "output": "In the budding yeast, cohesin is loaded onto the chromosome during the late G1 phase, establishes sister chromatid cohesion concomitant with DNA replication, and dissociates by the telophase. " }, { "input": "During which stage of the cell cycle is cohesin deposited on the yeast genome?", "output": "Cohesin association with G1 chromosomes requires continued activity of the cohesin loader Mis4/Ssl3, suggesting that repeated loading cycles maintain cohesin binding. In mammalian cells, cohesin binding to chromatin is dynamic in G1, but becomes stabilized during S-phase. Instead, we find that cohesin stability increases at the time of S-phase in a reaction that can be uncoupled from DNA replication. Budding yeast Scc1p/Mcd1p, an essential subunit, is cleaved and dissociates from chromosomes in anaphase, leading to sister chromatid separation." }, { "input": "Which is the neurodevelopmental disorder associated to mutations in the X- linked gene mecp2?", "output": "The neurodevelopmental disorder named Rett syndrome, originally termed as cerebroatrophic hyperammonemia. Although most exclusively affects females, has also been found in male patients." }, { "input": "What is the treatment of Riedel disease (thyroiditis)?", "output": "Riedel thyroiditis is a rare disorder related to a systemic extracervical fibrotic process of unknown origin. The tratment of choice is the surgical treatment: Corticosteroids may be also useful" }, { "input": "What is the link between Dax1 and Esrrb?", "output": "Dax1 associates with Esrrb and regulates its function in embryonic stem cells" }, { "input": "What is the link between Dax1 and Esrrb?", "output": "Dax1 associates with Esrrb and regulates its function in embryonic stem cells." }, { "input": "What is dovitinib?", "output": "Dovitinib (TKI258) is a tyrosine kinase receptor inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR)." }, { "input": "Are DNA helicases involved in progeroid syndromes?", "output": "Yes, mutations in genes coding for DNA helicases were found to induce progeroid syndromes, such as Werner syndrome (WS) or Bloom syndrome (BS)." }, { "input": "List the diseases for which there are point-of-care breath tests", "output": "Point of care breath tests are available for lung cancer, pulmonary embolism, respiratory distress syndrome, methanol intoxication, kidney diseases, liver diseases, Helicobacter pylori infection, asthma, sepsis, heart failure, diabetes and tuberculosis." }, { "input": "Is there association of matrix metalloproteinases with behaviour of pituitary adenomas?", "output": "Yes, there is evidence to suggest that matrix metalloproteinases are associated with more aggressive of pituitary adenomas." }, { "input": "What is the evolutionary process described by the \"Muller's ratchet\" model?", "output": "The vast majority of mutations are deleterious and are eliminated by purifying selection. Yet in finite populations, purifying selection cannot completely prevent the accumulation of deleterious mutations. Muller's ratchet is a paradigmatic model for the accumulation of deleterious mutations in a population of finite size, due to genetic drift. Muller's ratchet suggests that population bottlenecks, which may constrain the genetic diversity of a population, could lead to extinction of all individuals with the least number of deleterious mutations, due to a stochastic fluctuation. When the most-fit class of genotypes is lost, it is lost irreversibly." }, { "input": "Which heat shock protein is found to be upregulated during Hsp90 inhibition?", "output": "HSP90 inhibition was found to be associated with induction of HSP70 expression." }, { "input": "Which gene is responsible for the development of Sotos syndrome?", "output": "Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS." }, { "input": "Which gene is responsible for the development of Sotos syndrome?", "output": "Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability. This disorder is caused by mutations or deletions in NSD1 gene" }, { "input": "What is the name for anorexia in gymnasts?", "output": "Anorexia athletica" }, { "input": "Is Vitamin D deficiency in pregnant women associated with gestational diabetes?", "output": "Yes, there are multiple studies reporting an association between low VitD in pregnancy and impaired glucose tolerance, but it is not entirely clear if this translates directly to the increased risk of Gestational diabetes or via maternal obesity and/or genetic polymorphisms." }, { "input": "What are the indications for alteplase?", "output": "Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke.\nFood and Drug Administration approval of alteplase for central venous catheter (CVC) occlusions. \nAlteplase is now firmly established as a treatment of choice in the management of acute myocardial infarction. The efficacy of intravenous alteplase in the treatment of pulmonary thromboembolism has also been established and appears to be similar to that of streptokinase and urokinase in this indication and in arterial thrombotic occlusion. However, its use in this latter indication and in other vascular disorders has not been as extensively documented. \nPreliminary data suggest efficacy of alteplase of deep vein thrombosis and arterial thrombotic occlusion." }, { "input": "List scaffold proteins of the ERK signaling pathway.", "output": "Originally identified in yeast, scaffold proteins are now recognized to contribute to the specificity of MEK/ERK pathways in mammalian cells. These scaffolds include kinase suppressor of Ras (KSR), beta-arrestin, MEK partner-1 (MP-1), Sef and IQ motif-containing GTPase-activating protein 1(IQGAP1). Human disc-large homolog (hDlg) acts as a MEK2-specific scaffold protein for the ERK signaling pathway. Two scaffold proteins, caveolin-1 and IQGAP1, are required for phosphorylation of the actin associated pool of extracellular signal regulated kinase 1 and 2 (ERK1/2). Several 14-3-3 isotypes bind to protein kinase C (PKC)-zeta and facilitate coupling of PKC-zeta to Raf-1 an event that boosts the mitogen-activated protein kinase (ERK) pathway." }, { "input": "List scaffold proteins of the ERK signaling pathway.", "output": "kinase suppressor of Ras 1\nMEK Partner 1\nBeta-arrestin\nIQ motif containing GTPase-activating protein 1\nkinase suppressor of Ras 2\nmitogen-activated protein kinase organizer 1" }, { "input": "Which are the families of mammalian DNA-(cytosine-5)-methyltransferases?", "output": "DNA (cytosine-5)-methyltransferases catalyze the specific transfer of a methyl group to the C5 position of cytosine residues in DNA. Three families of DNA (cytosine-5)-methyltransferases have been identified in mammals: DNMT1, DNMT2 and DNMT3 (including DNMT3a, DNMT3b and DNMT3L isoforms). All of them share homologous catalytic domains. DNMT1 is the \ufffd\ufffd\ufffdmaintenance\u201d methyltransferase family. DNMT1 is specific for hemi-methylated DNA and ensures the faithful transmission of DNA methylation patterns in every replication cycle. DNMT3 is required for de novo methylation of DNA. DNMT3 targets unmethylated DNA and is responsible for the establishment of new methylation patterns. Dnmt2, in contrast to all other mammalian DNA (cytosine-5)-methyltransferases, does not possess a large N-terminal regulatory domain. The DNA methylation activity of DNMT2 is still controversial." }, { "input": "Which classes of endogenous retroelements are known to date?", "output": "Endogenous retroelements fall into two distinct classes: retrotransposons containing LTRs (Long Terminal Repeats), and retrostransposons lacking LTRs." }, { "input": "What is the association between proBNP serum concentrations and stroke outcomes?", "output": "ProBNP serum concentrations are elevated in stroke patients relative to healthy controls. Greater proBNP serum concentrations are associated with greater stroke severity and with increased risk for unfvorable functional outcomes." }, { "input": "What is the effect that EZH2 has on chromatin?", "output": "Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms" }, { "input": "What is the effect that EZH2 has on chromatin?", "output": "Ez that catalyzes di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. The mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles. PRC2-Ezh2 catalyzes H3K27me2/3 and its knockdown affects global H3K27me2/3 levels. EZH2 thus maintains chromatin in a repressive state." }, { "input": "Does Chromatin Immunoprecipitation (ChIP) show a bias for highly expressed loci?", "output": "Several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control) subtraction and normalization within and across arrays. We detected a chromatin-state bias: open chromatin regions yielded higher coverage, which led to false positives if not corrected. The localization of unrelated proteins, including the entire silencing complex, to the most highly transcribed genes was highly suggestive of a technical issue with the immunoprecipitations." }, { "input": "Is clathrin involved in E-cadherin endocytosis?", "output": "E-cadherin is a central component of the adherens junction in epithelial cells and continuously undergoes endocytosis via clathrin-coated vesicles and/or caveolae depending on the cell type." }, { "input": "What are the generic versions of Viagra", "output": "Sildenafil Citrate and Elonza in Thailand are the generic versions of Viagra" }, { "input": "List GATA-1 interacting partners as discovered with the help of the biotinylation tagging approach.", "output": "Our work describes, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes" }, { "input": "List GATA-1 interacting partners as discovered with the help of the biotinylation tagging approach.", "output": "Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes " }, { "input": "List GATA-1 interacting partners as discovered with the help of the biotinylation tagging approach.", "output": "The biotinylation tagging approach revealed, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes." }, { "input": "Which diseases are associated with Alu element insertion?", "output": "Diseases associated with Alu element insertion are the following: myotonic dystrophy type 2, Friedreich ataxia, spinocerebellar ataxia type 10, autosomal dominant optic atrophy, Menkes disease, hyper-IgM with immunodeficiency syndrome (HIGM), and anterior pituitary aplasia." }, { "input": "Approximately how many recombination hotspots have been found in the yeast genome?", "output": "In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs." }, { "input": "How could iPSCs be used for the treatment of diabetes?", "output": "One of the promising approaches to cure diabetes is to use induced PCSs (iPSCs) and to differentiate them into insulin-secreting \u03b2 cells. The induction of iPSC differentiation into insulin-secreting cells can be achieved in several ways, such as with the use of microRNAs, or adenoviral transfection with selected genes." }, { "input": "What is the name of the stem loop present in the 3' end of genes encoding for selenoproteins?", "output": "SECIS (selenocysteine insertion sequence)" }, { "input": "Is Propofol used for short-term sedation?", "output": "Yes. Propofol is the most frequently used sedating agent for patients with expected duration of ICU admission less than 24 hours. There are numerous studies of its efficacy and comparisons with other sedatives." }, { "input": "Which proteins are the different members of the NF-kappaB family of transcription factors?", "output": "Nuclear factor kappa B (NF\u03baB) is a dimeric transcription factor comprised of five family members RelA (p65), RelB, c-Rel, NF-kB1/p50 and NF-kB2/p52." }, { "input": "What are the symptoms of Rotor syndrome?", "output": "Rotor syndrome is characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics." }, { "input": "Does splicing occur co-transcriptionally?", "output": "The consensus view, based on four organisms, is that the majority of splicing events take place co-transcriptionally in most cells and tissues. RNA processing events that take place on the transcribed pre-mRNA include capping, splicing, editing, 3' processing, and polyadenylation. Most of these processes occur co-transcriptionally while the RNA polymerase II (Pol II) enzyme is engaged in transcriptional elongation." }, { "input": "List the existing methods for genetic manipulation of cells.", "output": "Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence, or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or \"knocked out\", using a nuclease. Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations. Based on results there are developed many methods for genetic manipulation of cells such as Microinjection, electroporation, liposomes and via viral vectors." }, { "input": "List the existing methods for genetic manipulation of cells.", "output": "The existing methods for genetic manipulation of cells include Agrobacterium-mediated or direct delivery methods, as well as methods using plant artificial chromosomes, site-directed plasmid mutagenesis, combined use of Red/ET recombination and unique restriction site elimination, Bacterial artificial chromosomes (BACs), direct in vitro transposition of viral genomes with a BAC cassette, and subsequent recovery in Escherichia coli, as well as transformation-competent artificial chromosome (TAC)-based acceptor vector, by exploiting the CreloxP recombination system and homing endonucleases." }, { "input": "Are there clinical trials on stem cells in multiple sclerosis", "output": "Yes. Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for multiple sclerosis. Several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair." }, { "input": "Which SWI/SNF protein complex subunit has been demonstrated to interact with the FANCA gene product?", "output": "The Fanconi anemia protein FANCA has been shown to interact with the brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity." }, { "input": "Which SWI/SNF protein complex subunit has been demonstrated to interact with the FANCA gene product?", "output": "FANCA was demonstrated to associate with the endogenous SWI/SNF complexFANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair" }, { "input": "Are piRNAs involved in gene silencing?", "output": "Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire. Transcriptional silencing implies a piRNA-mediated formation of repressive chromatin which diminishes the transcriptional capacity of the target locus." }, { "input": "List representatives of the major fungal hypoxanthine-adenine-guanine transporter families.", "output": "AzgA and Fcy21p are prototypes of the two major fungal hypoxanthine-adenine-guanine transporter families." }, { "input": "Which proteins have been identified as RET ligands?", "output": "RET is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin, artemin, and persephin." }, { "input": "Which proteins have been identified as RET ligands?", "output": "The RET proto-oncogene encodes a receptor tyrosine kinase, which is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN)." }, { "input": "Which substances are dangerous to g6PD deficient individuals?", "output": "Antimalarial drugs (primaquine, pamaquine, chloriquine), fava beans, sulfonamides, some antibiotics( nalidixic acid, nitrofurantoin, isoniazid, dapsone, and furazolidone) and henna" }, { "input": "Which mutations of SCN5A gene are implicated in Brugada syndrome?", "output": "The following mutations of SCN5A gene have been linked to Brugada syndrome:I137M, p.W1095X; c.3284G>A, R27H, E901K, G1743R, V728I, N1443S, E1152X, c.664C>T; p.Arg222X, Ala2>Thr, Ala735, Ala735>Thr, Val1340>Ile, IVS18-1G>A, E1784K (14x), F861WfsX90 (11x), D356N (8x), G1408R (7x), G400A, H558R, W822X, Q55X, V95I, A1649V, delF1617, c.4810+3_4810+6dupGGGT, K1527R, A1569P, R367H, A735V, R1192Q, D1795." }, { "input": "What is Sotos syndrome?", "output": "Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability" }, { "input": "What is Sotos syndrome?", "output": "Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability." }, { "input": "What is the CRAPome database?", "output": "The CRAPome is a contaminant repository for affinity purification-mass spectrometry data." }, { "input": "List all articles on network meta-analysis for smoking cessation", "output": "Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis.\nPharmacological interventions for smoking cessation: an overview and network meta-analysis\nEffectiveness and cost-effectiveness of computer and other electronic aids for smoking cessation: a systematic review and network meta-analysis.\nSmoking cessation interventions in COPD: a network meta-analysis of randomised trials." }, { "input": "Can RG7112 inhibit MDM2?", "output": "Yes, RG7112 is a small molecule MDM2 antagonist." }, { "input": "Which clotting factor is inhibited by betrixaban?", "output": "Betrixaban is an orally administered direct clotting factor Xa inhibitor." }, { "input": "Which are the most frequent syndromes associated with inherited bone marrow failure?", "output": "The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS) " }, { "input": "Which are the most frequent syndromes associated with inherited bone marrow failure?", "output": "The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS)." }, { "input": "How is yellow fever virus transmitted?", "output": "Yellow fever virus is transmitted by mosquitoes and is restricted to Africa, Central and South America and the Caribbean. \nYellow fever virus is a flavivirus, and there is only one antigenic type. It was taken to the Americas by the early slave traders, and nowadays reported in Africa, America, Asia and Europe. Yellow fever virus is transmitted by two different cycles: \n-from human to human by the mosquito Aedes aegypti; which is well-adapted to breeding around human habitations; the infection can be maintained in this way as \u2018urban\u2019 yellow fever.\n-from infected monkeys to humans by mosquitoes such as Haemagogus. This is \u2018jungle\u2019 yellow fever and is seen in Africa and South America.\n\nYellow fever is not transmitted directly from human to human by day-to-day contact, but transmission from ill patients to healthcare workers has been reported, notably after needlestick injury." }, { "input": "Are there any specific antidotes for dabigatran?", "output": "No specific antidote currently exists for dabigatran" }, { "input": "What is the outcome of TAF10 interacting with the GATA1 transcription factor?", "output": "TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis." }, { "input": "How does TNF affect thyroid hormone receptors?", "output": "TNF-alpha inhibits the T3-induced expression of thyroid hormone receptor-beta" }, { "input": "Which ones are the ESKAPE organisms?", "output": "The 6 ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species." }, { "input": "What is the effect of dovitinib on the cell cycle?", "output": "Dovitinib triggers a G2 /M arrest. It promotes a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induce a G2 arrest similar to the G2 DNA damage checkpoint." }, { "input": "What is the involvement of PDGFRB in metastatic medulloblastoma?", "output": "Platelet-derived growth factor (PDGF) receptor B (PDGFRB) expression was shown to correlate with metastatic medulloblastoma, while PDGFRB tyrosine kinase activity was demonstrated to be critical for migration and invasion of medulloblastoma cells possibly by transactivating EGFR." }, { "input": "What is known as Calcium Induced Calcium Release (CICR) and its role in cardiomyocyte contractility?", "output": "the cicr mechanism has been understood mainly based on binding of cytosolic ca(2+) with ryanodine receptors (ryrs) and inducing ca(2+) release from the sarcoplasmic reticulum (sr). l-type ca(2+) channels activate ryrs to produce cicr in smooth muscle cells in the form of ca(2+) sparks and propagated ca(2+) waves. in heart cells, a tight coupling between the gating of single l-type ca(2+) channels and ryanodine receptors (ryrs) underlies calcium release. the importance of ca-induced ca release in excitation-contraction coupling in the heart. waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias. in mammals, ca(2+) influx as l-type ca(2+) current (ica) triggers the release of ca(2+) from sarcoplasmic reticulum (sr) and ca(2+)-induced ca(2+) release (cicr) is critical for excitation-contraction coupling. " }, { "input": "What is known as Calcium Induced Calcium Release (CICR) and its role in cardiomyocyte contractility?", "output": "Cardiomyocyte contraction depends on rapid changes in intracellular Ca(2+). Ca(2+) influx as L-type Ca(2+) current (ICa) triggers the release of Ca(2+) from sarcoplasmic reticulum (SR) and Ca(2+)-induced Ca(2+) release (CICR) is critical for excitation-contraction coupling. Calcium-induced calcium-release in cardiac myocytes takes place in spatially restricted regions known as dyads, where discrete patches of junctional sarcoplasmic reticulum tightly associate with the t-tubule membrane. Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca(2+) channels. Waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias." }, { "input": "What is the action of molindone?", "output": "Molindone is a short-acting antipsychotic.\nMolindone, along with other antipsychotic drugs which elicit little or no Parkinsonism, bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.\nMolindone is D2-selective in vitro and has a dual D1-D2 receptor profile in vivo.\nMolindone can selectively block the presynaptic DA receptors.\nMolindone causes a statistically significant up-regulation of both the long and short isoforms of the D2 receptor mRNAs in the prefrontal and temporal cortex, but has no effect on D4 mRNA levels in either cortical or striatal tissue.\nMolindone elevates Fos-like immunoreactivity (FLI) in the dorsolateral striatum.\nMolindone exhibits selectivity for cortical serotonin-stimulated cyclase versus dopamine-stimulated cyclase.\nMolindone in low intravenous doses (0.4-0.8 mg/kg) was found to reverse d-amphetamine and apomorphine induced depression of DA neurons and to block apomorphine induced depression of these cells. Molindone was also found to increase dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfacotry tubercles. In all of these respects molindone behaves identically to most classical neuroleptics. However, unlike most antipsychotic drugs previously tested, molindone failed to increase the baseline firing rate of DA cells and blocked haloperidol induced increases in DA neuron activity. In this regard molindone most closely resembles thioridazine and clozapine." }, { "input": "What is the function of the enzymes known as dual specificity phoshpatases (DUSPs)?", "output": "DUSPs (dual-specificity phosphatases) are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. DUSPs have been implicated as major modulators of critical signalling pathways that are dysregulated in various diseases. DUSPs can be divided into six subgroups on the basis of sequence similarity that include slingshots, PRLs (phosphatases of regenerating liver), Cdc14 phosphatases (Cdc is cell division cycle), PTENs (phosphatase and tensin homologues deleted on chromosome 10), myotubularins, MKPs (mitogen-activated protein kinase phosphatases) and atypical DUSPs." }, { "input": "What is the function of the enzymes known as dual specificity phoshpatases (DUSPs)?", "output": "Dual-specificity protein phosphatases participate in signal transduction pathways inactivating mitogen-activated protein kinases (MAP kinases). \nDual-specificity phosphatases (DUSPs) dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues on target MAPKs. \nThese signaling pathways are of critical importance in the regulation of numerous biological processes, including cell proliferation, differentiation and development." }, { "input": "How is bladder wall thickness measured?", "output": "Ultrasound" }, { "input": "LY450139 is investigational name of which drug?", "output": "LY450139 is investigational name of Semagacestat. It is a \u03b3-secretase inhibitor developed for treatment for Alzheimer's disease. Chemical name of LY450139 is hydroxylvaleryl monobenzocaprolactam." }, { "input": "Are there any Decision support systems for chronic pain management ?", "output": "Yes, there is a variety of decision support systems for chronic pain management." }, { "input": "Are there any Decision support systems for chronic pain management ?", "output": "Clinical decision support systems are promising tools for improving behavioral medicine care for chronic pain.The use of a computer-based decision support system facilitates primary care physicians' management of chronic pain." }, { "input": "Which gene has been found to be mutant in Lesch-Nyhan Disease patients?", "output": "Lesch-Nyhan Disease (LND) is the result of mutations in the X-linked gene encoding the purine metabolic enzyme, hypoxanthine guanine phosphoribosyl transferase (HPRT)." }, { "input": "Which is the methyl donor of histone methyltransferases?", "output": "The major methyl donor of histone methyltransferases (HMTs) is S-adenosyl-L\u2013methionine (SAM, AdoMet)." }, { "input": "How are human accelerated regions (HAR) defined?", "output": "Human accelerated regions (HAR) are defined as previously slowly evolving regions of the genome that have evolved most quickly along the human lineage. These represent genomic regions that are conserved among vertebrates but have accumulated substitutions on the human lineage at an accelerated rate." }, { "input": "Carbapenemase-producing gram-negative bacteria is a major health concern because their resistance to antibiotics.\nList the most frequent carbapenemases found in Enterobacteriaceae.", "output": "The most frequent carbapenemases in Enterobacteriaceae are OXA-48, KPC, VIM, NDM, IMP, SME, NMC, GES, IMI and MBL." }, { "input": "How are GRBs (Genomic Regulatory Blocks) defined?", "output": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene." }, { "input": "How are GRBs (Genomic Regulatory Blocks) defined?", "output": "Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, often immobilizing other, unrelated genes into long-lasting syntenic arrangements. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. Although gene order in hox and other gene clusters has long been known to be conserved because of shared regulatory sequences or overlapping transcriptional units, the chromosomal areas found through insertional hotspots contain only one or a few developmental regulatory genes as well as phylogenetically unrelated genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development." }, { "input": "How are GRBs (Genomic Regulatory Blocks) defined?", "output": "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. " }, { "input": "What is the gene frequently mutated in Multiple endocrine neoplasia 2 (MEN2) and Hisrchsprung disease?", "output": "The Ret gene may have gain of mutation functions in MEN2 cancer as well as loss of function mutations in Hirschprung disease." }, { "input": "Which are the clinical characteristics of isolated Non-compaction cardiomyopathy?", "output": "The clinical characteristics of isolated Non-compaction cardiomyopathy are excessively thickened endocardial layer with deep intertrabecular recesses (with ratio of non-compacted to compacted myocardium >2), heart failure, syncope, ventricular arrhythmias, stroke, pulmonary hypertension, complete left branch conductive block, sick sinus syndrome and paroxysmal supraventricular tachycardia" }, { "input": "What is STARR-seq?", "output": "STARR-seq is a method to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans." }, { "input": "In which genomic positions is the histone variant macroH2A enriched?", "output": "macroH2A1 is enriched on the inactive X chromosome in female mammalian cells, where it functions to maintain gene silencing. The transcribed regions of most active genes are depleted of macroH2A, often in sharply localized domains that show depletion of 4-fold or more relative to bulk mouse liver chromatin. This repressor activity of marcroH2A is further supported by the substantial and relatively uniform macroH2A1 enrichment along the inactive X chromosome, which averages 4-fold. In addition to localizing to the MCB, macroH2A accumulates at a perinuclear structure centered at the centrosome" }, { "input": "Does amiodarone affect thyroid hormone receptors in the myocardium?", "output": "Yes" }, { "input": "From which sequence does the Alu repeat originate from?", "output": "The presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element, The origin of Alu subfamilies in human populations may be related to evolution of chromosome Y." }, { "input": "Abnormality in which vertebral region is important in the Bertolotti's syndrome?", "output": "Lumbosacral vertebral region is implicated in the Bertolotti's syndrome. Lumbosacral transitional vertebra is an anatomical variation of the fifth lumbar vertebra in which an enlarged transverse process can form a joint or fusion with the sacrum or ilium. Patients often complain of intractable sciatica that arises from impingement of the nerve root extraforaminally by compression caused by the enlarged transverse process." }, { "input": "What does iBAQ stand for in proteomic analysis?", "output": "iBAQ stands for intensity-based absolute quantification." }, { "input": "Which is the main target of the anti-arrhythmic activity of flecainide?", "output": "Flecainide is a class 1c antiarrhythmic that acts by blocking sodium channels and is used mainly in the treatment of supraventricular arrhythmias." }, { "input": "Does thyroid hormone affect cardiac remodeling?", "output": "TH affects cardiac remodeling" }, { "input": "What is the effect of ROS on cyclin B1?", "output": "Reactive oxygen species (ROS) production is able to cause growth arrest at the G2-M checkpoint of the cell cycle, partly by deregulation of Cyclin B1 expression." }, { "input": "Are there any HCV replication inhibitors available?", "output": "Chronic hepatitis C virus (HCV) infection is a worldwide health problem causing serious complications, such as liver cirrhosis and hepatoma. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) have been reported to suppress gene expression significantly. HCV seems a suitable candidate for targets of siRNAs, as HCV is a positive single-strand RNA virus and replicates in the cytoplasm. Based on results, nowadays there are few HCV replication inhibitors such as GS-563253, PSI-6130, NA-808, BMS-790052, GS-9132 and BMS-788329." }, { "input": "Provide examples of how molecular transporters contribute to multi-drug resistance in bacteria.", "output": "MDR efflux pumps began causing clinical problems relatively recently, in parallel with the extensive use of antibiotics in medicine and as supplements in animal feeds. However, our analyses indicate that these MDR efflux pumps did not arise through recent mutations in genes encoding transporters that changed their substrate specificities.\n\nInstead, such MDR pumps are encoded within the genomes of virtually all microorganisms, so these genes are present and thus need only to be activated to become problematic. Moreover, lateral transfer of genes among bacteria has occurred frequently, particularly for plasmid-encoded systems, suggesting that such genes can be acquired fairly readily even if they are not initially present. Finally, although mutations that enable transporters to act on different types of substrate are rare, experiments and phylogenetic analyses indicate that simple point mutations can readily narrow or broaden a particular transporter's specificity toward a single class of compounds (e.g., sugars, amino acids, or drugs)." }, { "input": "What is the minimal genome build?", "output": "The identification of the essential genes of bacteria and the minimal genome for the free-living cellular life could provide insights into the origin, evolution, and essence of life forms. The field of Synthetic Biology seeks to apply engineering principles to biology in order to produce novel biological systems. One approach to accomplish this goal is the genome-driven cell engineering approach, which searches for functioning minimal genomes in naturally occurring microorganisms, which can then be used as a template for future systems. Currently a prototypical minimal genome has not been discovered." }, { "input": "Is cocaine use associated with increased risk for intracerebral hemorrhage?", "output": "Cocaine use is associated with increased incidence of intracranial hemorrhages most likely due to pressure increases." }, { "input": "Is miR-21 related to carcinogenesis?", "output": "Yes. It has been demonstrated in several experimental studies that miR-21 has oncogenic potential, and is significantly dysregulated in numerous types of cancer. Therefore, miR-21 is closely related to carcinogenesis." }, { "input": "Which is the most prevalent form of arrhythmia worldwide?", "output": "Atrial fibrillation (AF) is the most common arrhythmia worldwide, and it has a significant effect on morbidity and mortality. It is a significant risk factor for stroke and peripheral embolization, and it has an effect on cardiac function. Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting up to 1-1.5% of the population." }, { "input": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "output": "thyroid hormone receptor alpha1 mutations are implicated in thyroid hormone resistance syndrome" }, { "input": "Which agents are included in the FLAMSA chemotherapy regimen?", "output": "Fludarabine, cytarabine and amsacrine are included in the FLAMSA chemotherapy regimen." }, { "input": "Which are the subunits of the IkB protein kinase (IKK)?", "output": "Proinflammatory NF-kappaB activation requires the IkappaB (inhibitor of NF-kappaB) kinase (IKK) complex that contains two catalytic subunits named IKKalpha and IKKbeta and a regulatory subunit named NF-kappaB essential modulator (NEMO).Additional components may exist, transiently or permanently, but their characterization is still unsure." }, { "input": "Which are the subunits of the IkB protein kinase (IKK)?", "output": "The IKK kinase complex is the core element of the NF-kappaB cascade. It is essentially made of two kinases (IKKalpha and IKKbeta) and a regulatory subunit, NEMO (NF-kB Essential Modulator)/IKKgamma. Additional components may exist, transiently or permanently, but their characterization is still unsure." }, { "input": "Which are the subunits of the IkB protein kinase (IKK)?", "output": " The IKK protein complex is comprised of IKK\u03b1, IKK\u03b2 and NEMO subunits, with IKK\u03b2 thought to play the dominant role in modulating NF-\u03baB activity. The IkappaB-Kinase (IKK) complex is a multisubunit protein complex crucial for signal-induced phosphorylation of the IkappaB proteins and thus controls the activity of the transcription factor NF-kappaB. Besides the two kinases IKKalpha and IKKbeta, the IKK complex contains NEMO/IKKgamma, an additional subunit with regulatory and adaptor functions. " }, { "input": "Is PLK2 involved in alpha-synuclein phosphorylation in Parkinson disease?", "output": "PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assayThese results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system." }, { "input": "Is PLK2 involved in alpha-synuclein phosphorylation in Parkinson disease?", "output": "Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances \u03b1-synuclein autophagic degradation in a kinase activity-dependent manner. These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system." }, { "input": "Is PLK2 involved in alpha-synuclein phosphorylation in Parkinson disease?", "output": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system " }, { "input": "Which glands are subject to attack by lymphocytes in Sjogren's syndrome?", "output": "Sj\u00f6gren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands." }, { "input": "Describe Malgaigne fracture.", "output": "Bilateral pubic rami fractures are characteristic to Malgaigne fractures. Patients with Malgaigne fractures are particularly prone to additional injuries." }, { "input": "Name five popular computer programs used to identify genes in genomic sequences", "output": "Any five from the following not exhaustive list: AUGUSTUS, MGENE, CRAIG, Agene, EUGENE, Fgenesh++C, Fgenesh++, Fgenesh, GeneID, GeneMark.hmm, GENOMIX, GESECA, GLEAN, GlimmerHMM, Gramene,JIGSAW, MAKER, ,MGENE, N-SCAN, SGP2, SNAP, ExonHunter, Evigan, Genescan, HMMGene, MZEF, Genie, Twinscan, SLAM, GRAIL." }, { "input": "Which are the major transcription factors regulating glycolysis in mammals?", "output": "The main positive transcriptional regulator of Glycolysis in mammals is HIF1-alpha (Hypoxia Inducible Factor 1a). HIF1-alpha is upregulated by the oncogenes c-Myc and Src, which therefore also positively regulate glycolysis. Several reports have linked HIF-1\u03b1 induction with STAT3 activation. SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha. NF-\u03baB also stimulates glycolysis through the inhibition of PDK4 expression. Loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced. HNF4alpha is critical for regulating glucose transport and glycolysis and in doing so is crucial for maintaining glucose homeostasis." }, { "input": "Mutations in which gene determine response to both erlotinib and gefitinib?", "output": "Patients who carry somatic activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene, respond well to erlotinib and gefitinib." }, { "input": "Which protein complexes contain mitofilin?", "output": "mitochondrial inter-membrane space bridging (MIB) complex \nmitochondrial inner membrane organizing system (MINOS)\nMitOS for mitochondrial organizing structure" }, { "input": "Define marine metaproteomics", "output": "Marine metaproteomics is the study of the activities of whole marine microbial communities. The proteomic analyses are applied directly without the need for prior microbial culturing. The samples can be sediments,seawater, etc." }, { "input": "Mutation of which gene and which chromosome cause Neurofibromatosis type I?", "output": "Neurofibromatosis Type I is an autosomal dominant condition associated with NF-1 gene mutation that is located in the long arm of chromosome 17 (17q11.2). In the majority (95%) of Neurofibromatosis Type I individuals, the mutation is found in the NF1 gene, while the remaining 5% of the patients have different types of genetic abnormalities.\n" }, { "input": "Which genes does thyroid hormone receptor alpha1 regulate in the heart?", "output": "\u03b2-myosin heavy chain, alpha-myosin heavy chain, SR(Ca)ATPase, phospholamban, nucleotide-gated potassium channel 2, KCNE1, HCN2, HCN4, KCND2, KCND3, KCNA4" }, { "input": "What is the content of the METLIN database?", "output": "METLIN is a metabolite database containing tandem mass spectrometry data for each metabolite." }, { "input": "Which is the RNA sequence of the canonical polyadenylation signal?", "output": "A polyadenylation signal (AAUAAA) nearby the 3' end of pre-mRNA is required for poly(A) synthesis." }, { "input": "Which computational frameworks are available for predicting enhancers?", "output": "DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. The PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells." }, { "input": "Which proteins in the cerebro-spinal fluid can be used for early diagnosis of Alzheimer's disease?", "output": "CSF is a clear fluid that bathes and cushions the brain and spinal cord. Adults have about 1 pint of CSF, which physicians can sample through a minimally invasive procedure called a lumbar puncture, or spinal tap. Research suggests that Alzheimer's disease in its earliest stages may cause changes in CSF levels of tau and beta-amyloid, two proteins that form abnormal brain deposits strongly linked to the disease." }, { "input": "Is there evidence for somatic mosaicism in Tuberous Sclerosis?", "output": "Yes, somatic mosaicism in Tuberous Sclerosis has been documented with the use of mutation identification, and subsequent linkage analysis in the affected families. In a large family with both parents unaffected, 3 affected children and 5 unaffected siblings, a 4 bp insertion in TSC2 gene was shown to be inherited from the mother." }, { "input": "What is GRO-seq?", "output": "Global run-on sequencing (Gro-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome." }, { "input": "What is the role of the RUNX1-MYEF2 complex?", "output": "A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells." }, { "input": "Does smoking increase risk for glioblastoma?", "output": "No. Smoking does not increase risk for glioblastoma." }, { "input": "Which genes are implicated in short QT syndrome?", "output": "The genes that are implicated in short QT syndrome are KCNJ2, KCNH2, CACNA2D1 and KCNQ1." }, { "input": "What is SCENAR therapy used for?", "output": "all patients experienced substantial relief of pain from the first treatment. an electronic biofeedback device (scenar) may be successfully utilized in the management of post-herpetic neuralgia. scenar) as effective in the treatment of neurogenic dysfunction of the bladder in children with nocturnal enuresis. post-herpetic neuralgia using a bioelectronical device (scenar). addition of scenar therapy to the complex conventional pharmacotherapy fastened ulcer healing, increased the effectiveness of helicobacter pylori eradication, and improved the condition of the gastroduodenal mucosa. scenar therapy to patients with localized suppurative peritonitis in the postoperative period. a new technique of low-frequency modulated electric current therapy, scenar therapy, was used in treatment of 103 patients with duodenal ulcer (du). " }, { "input": "What is SCENAR therapy used for?", "output": "localized suppurative peritonitis in the postoperative period\nmanagement of post-herpetic neuralgia\ntreatment of 103 patients with duodenal ulcer\ntreatment of neurogenic dysfunction of the bladder in children with nocturnal enuresis" }, { "input": "List symptoms of Gradenigo's syndrome.", "output": "Gradenigo's syndrome is a rare but life threatening complication of acute otitis media, which includes a classic triad of otitis media, deep facial pain and ipsilateral abducens nerve paralysis." }, { "input": "Is Wnt16b secreted in response to chemotherapy?", "output": "Yes, WNT16B is secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation." }, { "input": "Do DNA double-strand breaks play a causal role in carcinogenesis?", "output": "Yes. It has been demonstrated that induction of DNA double-strand breaks (DSBs) and defects in overall DSBs repair capacity can lead to an accumulation of mutations, resulting in genomic instability of cells. Given that genomic instability is the hallmark of cancer, DSBs play a causal role in carcinogenesis." }, { "input": "Do conserved noncoding elements co-occur with matrix-attachment regions?", "output": "Yes. It is estimated that 11% of the conserved noncoding DNA consists of predicted MARs. Conversely, more than half of the predicted MARs co-occur with one or more independently identified conserved sequence blocks. An excess of conserved predicted MARs is seen in intergenic regions preceding 5' ends of genes, suggesting that these MARs are primarily involved in transcriptional control." }, { "input": "What is the relationship between thyroid hormone and inflammatory markers in heart failure patients?", "output": "There is an inverse correlation between inflammatory markers (IL-6 and TNF alfa and PCR) and FT3 levels in patients with heart failure" }, { "input": "Which variables are included in the SPAN-100 score?", "output": "SPAN-100 score includes patient's age and NIH Stroke Scale score. SPAN-100 is used for prognostication of stroke patients." }, { "input": "Are Drosophila ultraconserved elements candidate ncRNAs?", "output": "Yes. Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs." }, { "input": "Which genes does thyroid hormone receptor alpha1 regulate in the liver?", "output": "phosphoenolpyruvate-carboxykinase\"//\n\"pyruvate kinase\"//\n\"D1\", \"deiodinase 1\"//" }, { "input": "What is the color of the protein Ranasmurfin?", "output": "Ranasmurfin is a blue protein." }, { "input": "What is the role of Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) in development?", "output": "Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism. HPL-2 regulates the expression of germline genes, extracellular matrix components and genes involved in lipid metabolism. In addition, HPL-2 regulates the dauer developmental decision, a striking example of phenotypic plasticity in which environmental conditions determine developmental fate. Furthermore, it is required for the formation of a functional germline and for the development of the vulva by acting in an Rb-related pathway." }, { "input": "Does surgery for ovarian endometriomas improve fertility?", "output": "Yes, endometrioma surgery seems to improve the success rates of fertility treatment." }, { "input": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "output": "Yes, most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes." }, { "input": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "output": "Yes. Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007)." }, { "input": "What are the pregnancy outcomes in rheumatoid arthritis?", "output": "There is increased obstetrical and neonatal morbidity. Women with RA had an increased risk of LBW, SGA babies, preeclampsia and CS compared with unaffected women.\nWomen with RA appear to have a higher age-adjusted risk of adverse outcomes of pregnancy and longer hospital stays than do pregnant women in the general population, and careful antenatal monitoring should be performed.Patients with rheumatic disease can have successful pregnancy outcomes, particularly when a collaborative approach between the rheumatologist and obstetrician is applied.\nIn general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes." }, { "input": "What is DNAshape?", "output": "DNAshape is a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/." }, { "input": "How are thyroid hormones involved in the development of diabetic cardiomyopathy?", "output": "The diabetic state is associated with lowered T3 and T4 levels. Thyroid hormone treatment in diabetic cardiomyopathy may partially reverse cardiac dysfunction" }, { "input": "By which methods can we evaluate the reliability of a phylogenetic tree?", "output": "The methods for assessing the robustness/reliability of the topology of the inferred phylogenetic trees are: the widely used bootstrap method and the jackknife method." }, { "input": "By which methods can we evaluate the reliability of a phylogenetic tree?", "output": "In contrast to other similar software, the program FreeTree (available at http://www.natur.cuni.cz/~flegr/programs/freetree or http://ijs.sgmjournals.org/content/vol51/issue3/) can also assess the robustness of the tree topology by bootstrap, jackknife or operational taxonomic unit-jackknife analysis. (PMID: 11411692)" }, { "input": "Which histone modification is primarily linked to elongating transcription?", "output": "Similarly, H3K36 trimethylation, a mark associated with transcription elongation, was specifically increased at the HD locus in the striatum and not in the cerebellum. Recent studies reviewed here demonstrate that histone deacetylation on the body of a transcribed gene is regulated via Set2-mediated methylation of histone H3-K36." }, { "input": "Could RG7112 be used as cancer therapy?", "output": "Yes, RG7112 has shown promising results in early phases of trials in cancer patients." }, { "input": "Which interleukin is blocked by Siltuximab?", "output": "Siltuximab is a monoclonal antibody that binds to interleukin-6 with high affinity and specificity." }, { "input": "ROSIER scale is used for which disorder?", "output": "ROSIER (Recognition of Stroke in the Emergency Room) scale was developed as a stroke recognition tool on suspected patients in the prehospital setting." }, { "input": "How histone deacetylation causes transcriptional gene silencing?", "output": "Histone deacetylation, catalyzed by the histone deacetylase (HDAC) enzymes, is an epigenetic modification. Histone deacetylation leads to the formation of a condensed and transcriptionally repressive chromatin structure which inhibits gene transcription. " }, { "input": "Which is the subcellular localization of the protein angiogenin?", "output": "Under growth conditions, ANG is located in nucleolus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth. In adverse conditions, ANG is relocated to cytoplasm to promote damage repairs and cell survival." }, { "input": "List FDA approved treatments for androgenetic allopecia", "output": "Recently, in addition to the two currently approved U.S. Food and Drug Administration (FDA) medications (minoxidil and finasteride), a novel device was FDA-approved for the treatment of hair loss, the laser hair comb." }, { "input": "Which bone protein is used in archaelogy for dating and species identification?", "output": "Collagen is the main protein extracted from bones and analyzed by mass spectrometry. It is traditionally used for radiocarbon dating but sophisticated new technologies are using collagen for species identification as well." }, { "input": "Does thyroid hormone affect cardiac remodeling ?", "output": "Cardiac function and mechanics are significantly affected by low thyroid function. l-T4 therapy improves but does not completely recover cardiac function in patients with mild hypothyroidism.\nLong-term T4 treatment after myocardial infarction has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area." }, { "input": "What is the effect of SAHA treatment in Huntington's disease?", "output": "Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, protects dopaminergic neurons from neurotoxin-induced damage. SAHA is predominantly an inhibitor of class I HDACs. However, it can also bind to class IIa HDACs and has been shown to degrade class IIa HDACs at the protein level in vitro. The neuroprotective effects of SAHA were mediated in part by promoting release of neurotrophic factors from astroglia through inhibition of histone deacetylation. SAHA can lead to the degradation of class IIa HDACs 4 and 5 via RANBP2 mediated proteasome degradation in vitro." }, { "input": "What is known about the role of mHealth in the prevention of disease?", "output": "Most reported uses of mHealth are for treatment, we identified report on approaches to child obesity prevention." }, { "input": "Which receptors are targeted by suvorexant?", "output": "Suvorexant is a potent, selective, and orally bioavailable antagonist of orexin 1 receptor and orexin 2 receptor currently under clinical investigation as a novel therapy for insomnia." }, { "input": "Is armodafinil used for treatment of insomnia?", "output": "No, armodafinil is not used for treatment of insomnia. Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD." }, { "input": "A common problem in proteomics is the contamination of samples with exogenous proteins (often from other species). These proteins can be found in specific databases. List some contaminants.", "output": "Some common contaminants in proteomics are proteases (used for the digestion of the proteins), keratins (usually from the skin), proteins originated from the serum of the culture media and antibodies if used in the experiment." }, { "input": "Which gene has been implicated in Majeed Syndrome?", "output": "Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)." }, { "input": "Which gene has been implicated in Majeed Syndrome?", "output": "Genetic alteration of LPIN2 in humans is known to cause Majeed syndrome." }, { "input": "What is Trypan blue used for?", "output": "Trypan blue is used in the \"trypan blue exclusion assay\" for assessing cell viability/cell death." }, { "input": "Selexipag is used for which disease?", "output": "Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor agonist in clinical development for the treatment of pulmonary arterial hypertension." }, { "input": "How does ranolazine affect kinase signaling activation in the heart?", "output": "Ranolazine inhibits Ca(2+)/calmodulin kinase II (CaMKII) activity" }, { "input": "List features of the DEND syndrome.", "output": "Clinical features of the DEND syndrome include developmental delay, epilepsy and neonatal diabetes." }, { "input": "What is the RESID database?", "output": "The RESID Database of Protein Modifications is a comprehensive collection of annotations and structures for protein modifications and cross-links including pre-, co-, and post-translational modifications" }, { "input": "Pridopidine has been tested for treatment of which disorder?", "output": "Pridopidine is a dopaminergic stabilizer that has shown promising results for treatment of Huntington disease patients." }, { "input": "Are there currently applications of deep learning in genomics?", "output": "Yes. Deep learning has been used so far in genomics for predicting splicing patterns in individual tissues and differences in splicing patterns across tissues. The deep architecture surpasses the performance of the previous Bayesian method for predicting alternative splicing (AS) patterns." }, { "input": "Are CpG islands located close to housekeeping genes?", "output": "Our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated. These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes. In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands. It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes. CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes. CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes. " }, { "input": "Are CpG islands located close to housekeeping genes?", "output": "Yes, CpG islands are preferentially located at the start of transcription of housekeeping genes and are associated with tissue-specific genes." }, { "input": "Are CpG islands located close to housekeeping genes?", "output": "These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes. Our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated. In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands. It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes. CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes. CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes. " }, { "input": "Is COL5A2 gene associated to ischemic heart disease?", "output": "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease " }, { "input": "Is COL5A2 gene associated to ischemic heart disease?", "output": "In a gene co-expression network from microarray data originating from a mouse model of myocardial infraction, Col5a2 shows predictive potential, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease." }, { "input": "Which is the target of bortezomib used in cancer therapy?", "output": "Bortezomib is a potent and specific reversible ubiquitin/proteasome pathway inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies." }, { "input": "Have microRNAs been implicated in pharmacogenomics? ", "output": "Yes. MicroRNAs have been implicated in pharmacogenomics." }, { "input": "Which genes are known to be involved in Diamond-Blackfan anemia?", "output": "Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26, as well as in GATA1, in about 60-65 % of patients." }, { "input": "Is nicotinamide effective for skin cancer prevention?", "output": "Yes, oral nicotinamide is safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients." }, { "input": "Which is the chromosomal location of the gene MAOA?", "output": "The MAOA gene is locatad on chromosome X (Xp21-p11)." }, { "input": "Do Parkinson's disease patients experience stridor?", "output": "Yes. Stridor has been described in Parkinon's disease patients. Stridor has been linked to deep brain stimulation and L-Dopa medication use. \nHowever, stridor was shown to be more common in multiple system atrophy patients." }, { "input": "Which depression rating scales were shown to have acceptable psychometric properties for screening of poststroke depression?", "output": "The Center of Epidemiological Studies-Depression Scale, Hamilton Depression Rating Scale, and the Patient Health Questionnaire, The Beck Depression Inventory, Hospital Anxiety and Depression Scale-depression subscale, Montgomery-Asberg Depression Rating Scale, Poststroke Depression Rating Scale and Clinical Global Impression scale appeared to have acceptable psychometric properties for identifying depression in patients after stroke. Therefore, these scales can be used for screening of post-stroke depression. Signs of Depression Scale and Visual Analogue Mood Scale showed inferior psychometric properties and therefore should not be used for screening for post-stroke depression." }, { "input": "What is the mechanism of action of trichostatin A (TSA) as an antitumoral agent?", "output": "Trichostatin A (TSA) exerts antitumoral activity as a histone deacetylase inhibitor" }, { "input": "Is there an association between serum interleukin-6 concentrations and outcomes of stroke patients?", "output": "Yes. Greater serum interleukin-6 concentrations are associated with worse outcomes in ischemic and hemmorhagic stroke patients" }, { "input": "Could bioprinting be used in regenerative medicine against bone disease?", "output": "The developments in bioprinting (3D cell printing) techniques will be used in regenerative medicine and may allow the fabrication of customized implants for patients suffering in bone diseases in the future, once several technological limitations are addressed." }, { "input": "Idarucizumab is an antidote of which drug?", "output": "Idarucizumab is an antidote of Dabigatran. It is used for Dabigatran Reversal." }, { "input": "What are the main clinical characteristics of Pendred syndrome?", "output": "Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification." }, { "input": "What is the Pfam database?", "output": "The Pfam database provides a collection of curated protein families." }, { "input": "What is a popular mesaure of gene expression in RNA-seq experiments?", "output": "A commonly used measure for gene expression in RNA-seq experiments is Reads Per Kilobase per Million mapped reads (RPKM). In ocasions, and to account for partially mapped read, read Fragments per Kilobase per Million mapped reads (FPKM) is alternatively used." }, { "input": "Is macroautophagy a selective degradation process?", "output": "Yes. Macroautophagy (commonly referred to simply as autophagy) is a catabolic process conserved throughout the eukaryotes, and is distinct from other forms of autophagy by the formation of the autophagosome: this is a vesicle-like formation surrounded by a double membrane that sequesters the cytoplasmic material to be degraded. It was initially considered that macroautophagy was a bulk process; however, recent findings illustrate that specific cargos (ranging from misfolded or excess proteins, to organelles or even bacterial cells) can be selectively targeted to the pre-autophagosome membrane (i.e. the phagophore) and finally to the vacuoles/lysosomes for their degradation." }, { "input": "Inhibition of which enzyme is mechanism of action of alisertib?", "output": "Alisertib (MLN8237) is selective Aurora kinase inhibitor that acts by interfering with spindle organization and chromosome alignment during mitosis. It has been tested in patients with gastric cancer, breast cancer, relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas, epithelial ovarian, fallopian tube, and primary peritoneal carcinoma." }, { "input": "List the three most prevalent pathogenic species of Borrelia in Europe.", "output": "The most prevalent pathogenic species of Borrelia in Europe are: B. afzelii, B. garinii and B. burgdorferi ss." }, { "input": "Which thyroid hormone transporter is implicated in thyroid hormone resistance syndrome?", "output": "thyroid hormone transporter MCT8 is implicated in thyroid hormone resistance syndrome" }, { "input": "Which thyroid hormone transporter is implicated in thyroid hormone resistance syndrome?", "output": "Hemizygous MCT8 mutations cuases TH resistance syndrome in males characterized by severe psychomotor retardation, known as the Allan-Herndon-Dudley syndrome (AHDS)." }, { "input": "Which are the subunits of the transcription factor NF-kappaB in the canonical pathway activation?", "output": "The NF-\u03baB canonical pathway is mediated by the p65/relA and p50 subunits." }, { "input": "Is there any link between conserved noncoding elements and alternative splicing in vertebrates?", "output": "Yes. Some of the most highly conserved sequences occur in genes encoding RNA binding proteins, particularly the RNA splicing-associated SR genes." }, { "input": "Which protein is affected by dusp8 activation?", "output": "dusp8 (M3/6) is a dual-specificity phosphatase selective for JNK." }, { "input": "Which receptors are targeted by a drug Macitentan?", "output": "Endothelin receptor A and endothelin receptor B are targeted by a drug Macitentan. Macitentan is a potent, orally active, non-peptide dual antagonist of endothelin receptors A and B that is approved for the treatment of pulmonary arterial hypertension." }, { "input": "What is known as the cause of subacute thyroiditis?", "output": "Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus" }, { "input": "Which drugs are utilized to treat eosinophilic esophagitis?", "output": "Therapeutic options of eosinophilic esophagitis include use of proton-pump inhibitors, immunosuppressive drugs, elimination diets, and esophageal dilatation.\nOral viscous budesonide (OVB) is an effective treatment of pan-esophageal disease in children with EoE. OVB improves symptoms and endoscopic and histologic features." }, { "input": "What is the incidence of cystic fibrosis in the caucasian population?", "output": "Estimates of the newborn frequency of cystic fibrosis in different Caucasian groups range from 4 times more to 40 times less common than the generally accepted figure of 1:2000." }, { "input": "What is the incidence of cystic fibrosis in the caucasian population?", "output": "Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000-1/2,500 live births, but the actual estimate varies with the geographic location." }, { "input": "What is the effect of thapsigargin treatment?", "output": "Thapsigargin is an endoplasmic stress inducer. \tIt is a sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA) inhibitor." }, { "input": "What is the Her2 status in Li-Fraumeni syndrome?", "output": "In the background of a germline TP53 mutation of the Li-Fraumeni syndrome, the Her2 status was found to be positive in 63-83% of the cases." }, { "input": "Where is X-ray free electron laser used?", "output": "X-ray free electron laser (XFEL) technologies provide coherent and extremely intense photon pulses of short duration. XFELs are particularly useful in structural biology and imaging, in structural studies of single biological macromolecules (e.g. high resolution protein structure determination) and assemblies (e.g. viruses) or nanocrystals, which are not amenable to investigation with traditional crystallographic methods. Moreover, XFELs have the potential to be used for studying enzyme kinetics." }, { "input": "Which protein kinases have been found to phosphorylate Phospholamban and affect its biological activity?", "output": "Phosphorylation of phospholamban at Ser16 is mainly mediated by PKA and at Thr17 by Ca(2+) /calmodulin-dependent protein kinase (CaMKII). Phospholamban is also a reporter for PKG activity and akt kinase interacts with and phosphorylates PLN at Thr(17)." }, { "input": "Why can't humans synthesize Neu5Gc (N-Glycolylneuraminic acid)?", "output": "N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid synthesized by animals, but not by humans or birds. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. Losing this sugar changed how humans interact with some of our deadliest pathogens: malaria, influenza, and streptococcus among others." }, { "input": "Which enzyme is inhibited by Orteronel?", "output": "Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. Orteronel is used for treatment for castration-resistant prostate cancer." }, { "input": "What is the disorder in which mutations in U4atac snRNA are detected?", "output": "Mutations in U4atac snRNA are thought to be the cause of Microcephalic Osteodysplastic Primordial Dwarfism type I (MOPDI), a recessive form of developmental disorder." }, { "input": "What is the disorder in which mutations in U4atac snRNA are detected?", "output": "Biallelic mutations of the human RNU4ATAC gene, which codes for the minor spliceosomal U4atac snRNA, cause the developmental disorder, MOPD I/TALS " }, { "input": "Which is the binding site motif of Sp1?", "output": "Sp1 binds to a GC-rich sequence element containing the decanucleotide consensus sequence 5\u2032-(G/T)GGGCGG(G/A)(G/A)(C/T)-3\u2032 (GC box element) in double stranded DNA (dsDNA). Gel shift competition studies and DNase I footprinting analyses revealed that Sp1 specifically interacts with the CACCC motif." }, { "input": "List autoimmune disorders associated with GAD65 autoantibodies.", "output": "Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis." }, { "input": "Elaborate on the TREAT-NMD initiative for DMD patients", "output": "TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients in Europe. TREAT-NMD has worked on the generation of brief standards of care for DMD. Guidelines are presented for diagnostics, neurological follow up, gastrointestinal and nutritional issues, respiratory and cardiac care as well as orthopaedics, rehabilitation, psychosocial interventions and oral care." }, { "input": "Is muscle regeneration possible in mdx mice with the use of induced mesenchymal stem cells?", "output": "Purified induced mesenchymal stem cells (iMSCs) display fibroblast-like morphology, form three-dimensional spheroid structures, express characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105, and are capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplantation of iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowers oxidative damage, and restores the expression levels of normal dystrophin, leading to skeletal muscle regeneration." }, { "input": "Is muscle regeneration possible in mdx mice with the use of induced mesenchymal stem cells?", "output": "Purified iMSCs displayed fibroblast-like morphology, formed three-dimensional spheroid structures, and expressed characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105. Moreover, iMSCs were capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored" }, { "input": "List the different subtypes of thyroid cancer.", "output": "The different histologic subtypes of thyroid cancer include papillary, follicular, anaplastic, medullary, and H\u00fcrthle cell carcinomas." }, { "input": "What are the characteristics of Christianson syndrome?", "output": "Christianson syndrome (CS) is caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). Patients present with prominent neurological, medical, and behavioral symptoms. All CS participants were nonverbal and had intellectual disability, epilepsy, and ataxia. Other neurologic symptoms included eye movement abnormalities (79%), postnatal microcephaly (92%), and magnetic resonance imaging evidence of cerebellar atrophy (33%). Regression was noted in 50%, with recurrent presentations involving loss of words and/or the ability to walk. Medical symptoms, particularly gastrointestinal symptoms, are common. Height and body mass index measures were below normal ranges in most participants. Behavioral symptoms included hyperkinetic behavior (100%), and a majority exhibited high pain threshold." }, { "input": "Is the SDHAF2 gene encoding a protein necessary for flavination of SDHA?", "output": "Yes, SDHAF2 or hSDH5, is the gene encoding the enzyme responsible for the flavination of SDHA." }, { "input": "Is the SDHAF2 gene encoding a protein necessary for flavination of SDHA?", "output": "Yes, SDHAF2 is required for flavination of SDHA." }, { "input": "What is the physiological role of LKB1 involved in Peutz-Jeghers syndrome?", "output": "LKB1 plays a physiological role in controlling the Wnt-signaling." }, { "input": "What heterotachy states about molecular evolutionary processes?", "output": "Functional constraints may account for heterogeneity in the evolutionary rates among different sites of amino acid or DNA sequences. Apart from variations of substitution rates among different sites (spatial variation), heterotachy states that there are variations of substitution rates of a given site throughout time. Heterotachy is the within-site evolutionary rate variations across different lineages over time. Heterotachy (temporal rate variation) occurs with varying severity because the intensity of purifying selection and adaptive forces acting at a given position of a homologous amino acid or DNA sequence are not the same in different species. Heterotachy may mislead phylogenetic inferences." }, { "input": "What is known about depression in caregivers of brain tumor patients?", "output": "Depression is common affecting up to 40% of caregivers of brain tumor patients. Depression is associated with poor quality of life of caregivers of brain tumor patients. Greater anxiety, patients\u2019 emotional distress, economic hardship, lower caregivers\u2019 age, lower income, less social support and lower patient functioning were associated with more caregivers\u2019 depressive symptoms. Reports of caregiver depressive symptoms were lower when paired with higher reports of spirituality. It is important to monitor and treat caregiver's depression." }, { "input": "What are the effects of homozygosity of EDNRB mutations in addition to Hirschsprung disease?", "output": "Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB an EDN3 missense mutations have been reported in isolated HSCR patients " }, { "input": "What are the effects of homozygosity of EDNRB mutations in addition to Hirschsprung disease?", "output": "EDNRB homozygous mutations have been found to account for the rare Waardenburg-Hirschsprung syndrome (WS), whereas heterozygous EDNRB missense mutations have been reported in isolated Hirschsprung disease patients." }, { "input": "What is the prognostic role of alterred thyroid profile after cardiosurgery?", "output": "Altered thyroid profile after cardiosurgery is associated with high incidence of atrial fibrillation e delay in recovery (prolonged hospitalisation) in adults and higher score on The Pediatric Risk of Mortality (PRISM; P < 0.042) and a longer duration of ventilation in children.Impportantly in transplanted patients altered thyroid metabolism,low T3 syndrome, is characterized by highest mortality, highest incidence of acute rejection or reoperations and infections" }, { "input": "List Pentalogy of Fallot.", "output": "Pentalogy of Fallot consists of a pulmonic stenosis, a ventricular septal defect, an overriding aorta, a right ventricular hypertrophy and a patent foramen ovale." }, { "input": "Which is the major function of sororin?", "output": "Sororin is a positive regulator of sister chromatid cohesion that interacts with the cohesin complex." }, { "input": "Which gene fusion is the result of the \"philadelphia translocation\" or the \"philadelphia chromosome\" mutation?", "output": "Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. The Philadelphia chromosome and its corresponding fusion gene, BCR-ABL, is one of the best-known genetic abnormalities in hematological malignancies. Major BCR-ABL translocation is much more common in chronic myelogenous leukemia (CML) and minor BCR-ABL in acute lymphoblastic leukemia. " }, { "input": "Which gene fusion is the result of the \"philadelphia translocation\" or the \"philadelphia chromosome\" mutation?", "output": "Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. " }, { "input": "Which gene fusion is the result of the \"philadelphia translocation\" or the \"philadelphia chromosome\" mutation?", "output": "The Philadelphia chromosome is recognized as the cytogenetic result of a rearrangement of the ABL gene on chromosome 9 and the BCL gene on chromosome 22, which leads to the creation of a BCR/ABL fusion gene on chromosome 22." }, { "input": "Is zolpidem an antibiotic?", "output": "No, zolpidem is a short-acting imidazopyridine hypnotic drug" }, { "input": "Can desvenlafaxine be used at a dose of 50mg/day?", "output": "Yes, desvenlafaxine can be at 50mg/day to treat patients with major depressive disorder. Studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. The recommended dose of DVS ranges from 50 to 100 mg." }, { "input": "Which syndrome is associated with OATP1B1 and OATP1B3 deficiency?", "output": "Complete and simultaneous deficiency of the organic anion transporting polypeptides OATP1B1 and OATP1B3 due to mutations in their corresponding genes, has been linked to Rotor syndrome." }, { "input": "Which type of lung cancer is afatinib used for?", "output": "Afatinib is a small molecule covalently binding and inhibiting the EGFR, HER2 and HER4 receptor tyrosine kinases. Trials showed promising efficacy in patients with EGFR-mutant NSCLC or enriched for clinical benefit from EGFR tyrosine kinase inhibitors gefitinib or erlotinib." }, { "input": "Which type of lung cancer is afatinib used for?", "output": "Afatinib is a novel irreversible inhibitor of the ErbB family members EGFR, tyrosine kinase-type cell surface receptors HER2 and HER4. It shows preclinical efficacy in NSCLC with common EGFR-activating mutations and the T790M mutation typically associated with EGFR TKI resistanceBIBW2992 is an irreversible EGFR TKI that also inhibits HER2 and vascular epidermal growth factor receptors" }, { "input": "Can ferric carboxymaltose be used to treat anemia in inflammatory bowel disease patients?", "output": "Ferric carboxymaltose can be used to treat anemia in patients with inflammatory bowel disease, and prevents recurrence of anemia in these patients, compared with placebo. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients." }, { "input": "Which disease is treated with Eliglustat?", "output": "Eliglustat was developed for treatment of Gaucher's disease type 1." }, { "input": "List algorithms suitable for predicting protein complexes", "output": "Protein-Protein interactions (PPI) play a key role in determining the outcome of most cellular processes. The correct identification and characterization of protein interactions and the networks, which they comprise, is critical for understanding the molecular mechanisms within the cell. Large-scale techniques such as pull down assays and tandem affinity purification are used in order to detect protein interactions in an organism. Today, relatively new high-throughput methods like yeast two hybrid, mass spectrometry, microarrays, and phage display are also used to reveal protein interaction networks. Some suitable algorithms for predicting protein complexes are Naive Bayes Classifier, Negatome, Support Vector Machine, PEWCC, iPTMClust, NDComplex, PROCOMOSS, PPI network, metaPIS, EPOF, EAGLE, NFC, MCODE, DPClus, IPCA, CPM, MCL, CMC, SPICi, Core-Attachment, ProRank, ClusterONE, CFinder, Spectral, RNSC, Affinity Propagation, HKC, NWE, CP-DR, Struct2net and PIPE." }, { "input": "What are piggyBAC transposons?", "output": "The piggyBAC transposons are a nonviral gene delivery approach, that have been developed as tools for insertional mutagenesis. It can mobilize 100-kb DNA fragments in mouse embryonic stem (ES) cells, making it the only known transposon with such a large cargo capacity. The integrity of the cargo is maintained during transposition, the copy number can be controlled and the inserted giant transposons express the genomic cargo. Furthermore, these 100-kb transposons can also be excised from the genome without leaving a footprint. The development of piggyBac as a large cargo vector will facilitate a wider range of genetic and genomic applications." }, { "input": "Is there any association of the chromosomal region harboring the gene ITIH3 with schizophrenia?", "output": "Yes, genome-wide significant associations in schizophrenia has been linked to the locus harboring the ITIH3/4 genes." }, { "input": "Is APOBEC3B protein predominantly cytoplasmic or nuclear?", "output": "Contrary to other APOBEC family members, APOBEC3B was found to predominantly concentrate to the cell nucleus." }, { "input": "Is the regulation of Vsr endonuclease independent of the growth phase of bacteria?", "output": "The regulation of Vsr endonuclease levels is growth phase dependent." }, { "input": "Are there interactomes available for POU5F1 and SOX2?", "output": "Yes. Long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) have been assayed using 4C-Seq technique. Their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites." }, { "input": "Which tool is used for promoterome mining using CAGE data?", "output": "Despite their high resolution and functional significance, published CAGE data are still underused in promoter analysis due to the absence of tools that enable its efficient manipulation and integration with other genome data types. CAGEr is an R implementation of novel methods for the analysis of differential TSS usage and promoter dynamics, integrated with CAGE data processing and promoterome mining into a first comprehensive CAGE toolbox on a common analysis platform." }, { "input": "Is Rheumatoid Arthritis related to myopathy?", "output": "Vacuolar myopathy and statin-induced myopathy have been reported in rheumatoid arthritis patients, but this association may be due to the anti-malarial treatment received. An increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls has been reported." }, { "input": "what is the role of GATA-4 in regeneration of the heart after myocardial infarction?", "output": "GATA-4 is implicated in cardiogenic differentiation of cardiac c-kit+AT2+ cells that represent approximately 0.19% of total cardiac cells in infarcted heart. GATA-4 overexpression in mesenchymal stem cells increases both survival and angiogenic potential in ischemic myocardium and may therefore represent a novel and efficient therapeutic approach for postinfarct regenaration. In addition, interventions, such as hypergravity and 5-Aza treatment, induce expression of early muscle and cardiac markers like GATA-4 in BMSCs. A subpopulation of primitive cells from rat heart, expressing c-kit and myogenic transcriptional factors, GATA-4 and MEF 2C, exhibit a high in vitro proliferative potential. Progeny of these implanted cells have been shown to migrate along the infarcted scar, reconstitute regenerated cardiomyocytes with incorporation into host myocardium, and inhibit cardiac remodeling with decreased scar formation. In another study, TGF-beta has been shown to conduct the myogenic differentiation of stem cells by upregulating GATA-4 and NKx-2.5 expression and the intramyocardial implantation of TGF-beta-preprogrammed stem cells effectively assisted the myocardial regeneration. Furthermore, G-CSF treatment in postinfarcted murine hearts appears to be an effective approach for treating heart failure and also leads to induction of GATA-4 resulting in expression of various sarcomeric proteins." }, { "input": "What is the life expectancy of professional athletes in respect to the general population?", "output": "Elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes show higher longevity than the general population, but results about power (anaerobic) athletes are inconsistent." }, { "input": "What is the life expectancy of professional athletes in respect to the general population?", "output": "It remains unclear if high-intensity sports activities further increase life expectancy.\nCompetitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy\nIt appears that elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes survive longer than the general population, as indicated by lower mortality and higher longevity." }, { "input": "Is EZH2 associated with prostate cancer?", "output": "EZH2 is an epigenetic driver of prostate cancer. EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer. EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells. EZH2 knockdown markedly reduces the proteolytic activity of MMP-9, thereby decreasing the invasive activity of prostate cancer cells. Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly." }, { "input": "How does adrenergic signaling affect thyroid hormone receptors?", "output": "alpha1- adrenergic signalling increases TRalpha1 expression in nucleus and decreases TRalpha1 expression in cytosol." }, { "input": "What are the computational tools for the prediction of beta-barrel transmembrane proteins?", "output": "The computational tools for the prediction of beta-barrel transmembrane proteins (TMBs) are based mainly on the following methodologies: Hidden Markov Models (HMMs), hydrophobicity, structural data, k-nearest neighbor algorithm, Neural Networks and Support Vector Machines. The state-of-the-art computational tools for the prediction of TMBs are: BETAWARE, BOCTOPUS, BOMP, BTMX, HMM-B2TMR, OMPdb,PRED-TMBB, PROB, ProfTMB, PV, TMBETA-NET, TMB finding pipeline, TMBETADISC-RBF, TMBETAPRED-RBF, TMBHMM, TMB-Hunt, TMB-Hunt2, TMBKNN, TMBpro, transFold." }, { "input": "Which kinase is regulating stress granule biogenesis?", "output": "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis" }, { "input": "Which kinase is regulating stress granule biogenesis?", "output": "Multiple lines of evidence define the master metabolic regulator 5'-AMP-activated protein kinase alpha (AMPK-alpha) as a novel component of stress granules (SGs) that also controls their biogenesis." }, { "input": "What is the association between cell phone use and glioblastoma?", "output": "The association between cell phone use and incident glioblastoma remains unclear. Some studies have reported that cell phone use was associated with incident glioblastoma, and with reduced survival of patients diagnosed with glioblastoma. However, other studies have repeatedly replicated to find an association between cell phone use and glioblastoma." }, { "input": "Is there any cross-talk between the Wnt and the Akt pathways?", "output": "The Wnt/\u03b2-catenin and PI3K/Akt signaling pathways cross-talk mainly through the activity of GSK-3\u03b2, a common component of both pathways, but also through the activity of other signaling transducers, such as Cby or WISP-1." }, { "input": "Has the protein GFP been used in transgenesis for live protein imaging?", "output": "Yes, the stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology." }, { "input": "Is the Snord116 cluster associated with the Prader-Willi syndrome?", "output": "Yes, SNORD116 has a major role in Prader-Willi syndrome etiology." }, { "input": "Aleglitazar is agonist of which receptor?", "output": "Aleglitazar is a balanced peroxisome proliferator-activated receptor-\u03b1/\u03b3 agonist." }, { "input": "What are the main characteristics of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?", "output": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The phenotype of CPVT is characterized by polymorphic ventricular arrhythmias under stress and it potentially leads to syncope and/or sudden cardiac death (SCD). Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10\u2009000 and is caused by mutations in proteins controlling Ca(2+) homeostasis. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis." }, { "input": "What are the main characteristics of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?", "output": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10\u2009000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis. Catecholaminergic polymorphic ventricular tachycardia is a malignant disease, due to mutations in proteins controlling Ca(2+) homeostasis " }, { "input": "Is poly (ADP- ribosylation) involved in transcriptional control?", "output": "Yes, poly (ADP- ribosylation) plays a role in the maintenance of transcriptional fidelity." }, { "input": "Is nimodipine recommended for prevention of vasospasm in aneurysmal subarachnoid hemorrhage patients?", "output": "Yes, nimodipine is recommended and FDA approved for prevention of vasospasm after aneurysmal subarachnoid hemorrhage. Multiple studies have demonstrated that nimodipine (administered orally or intravenously) is safe and effective for prevention of vasospasm, and reduce frequency of ischemic complications, lowered mortality and improved overall outcomes. Other preventive medication can be also effective for vasomotor prevention in aneurysmal subarachnoid hemorrhage patients." }, { "input": "what is the role of prostaglandins in cardiac regenaration after myocardial infarction?", "output": "Prostaglandins are involved in tissue regeneration after myocardial infarction and inhibitors of prostanoid production, such as aspirin and COX-2 inhibitors, have negative impact in this process. Furthermore, pharmacological interference with prostaglandin synthesis following myocardial infarction is associated with reduced fibrillar collagen formation." }, { "input": "What is the general function of H3K79 methylation?", "output": "ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. " }, { "input": "What is the general function of H3K79 methylation?", "output": "ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. Findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin.\nMethylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes." }, { "input": "What is the general function of H3K79 methylation?", "output": "H3K79 methylation is a histone modification that correlates with histone H4 hyperacetylation prior to histone-to-protamine transition, and is accompanied by chromatin reorganization, playing an important role in the regulation of cell proliferation." }, { "input": "Where can we find the protein lacritin?", "output": "The protein lacritin can be found in lacrimal and salivary glands as well as in tear fluid and in the thyroid." }, { "input": "Where can we find the protein dermcidin?", "output": "Dermcidin is a secretes protein found mainly in sweat but it is also found in serum." }, { "input": "Where can we find the protein dermcidin?", "output": "In previous work we reported the expression of Y-P30 \\/ dermcidin in maternal peripheral blood mononuclear cells and the transport of the protein to the fetal brain. In this study we analyzed hormonal regulation of Y-P30 in human immune cells and expression of Y-P30 in the placenta. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate immune defense of human skin against infection. Several reports also state that peptides processed from the dermcidin precursor protein exhibit a range of other biological functions in neuronal and cancer cells. Using an immunoaffinity approach followed by multipoint validation, we identified the target of seriniquinone as the small protein, dermcidin. Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease. ``Pustulosis palmaris et plantaris'', or palmoplantar pustulosis, is a chronic pustular dermatitis characterized by intraepidermal palmoplantar pustules. Semi-quantitative dot-blot analysis revealed higher concentrations of hCAP-18 \\/ LL-37 in PPP-VF compared to healthy sweat. In conclusion, the expression of various AMPs is altered in acne vulgaris. " }, { "input": "What is the triple screening test performed during pregnancy measuring?", "output": "Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)" }, { "input": "What are the generic versions of Viagra?", "output": "Generic versions of sildenafil are Elonza, Caverta, Zenegra-100, Vega Asia, Suhagra-100, Vega, Revatio." }, { "input": "Which protein interacts with the Ragulator-RAG GTPases to control mTOR activity?", "output": "Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery that controls the activation of mTOR." }, { "input": "Which protein interacts with the Ragulator-RAG GTPases to control mTOR activity?", "output": "SLC38A9 localizes with Rag-Ragulator complex components on lysosomes and associates with Rag GTPases in an amino acid-sensitive and nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1 activity in the presence of amino acids and in response to amino acid replenishment following starvation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR. The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues, such as nutrient status and energy level." }, { "input": "Against which organisms has reverse vaccinology been used?", "output": "Reverse Vaccinology (RV) was first applied to serogroup B Neisseria meningitidis. This work induced further research of other pathogens in the same way: Porphyromonas gingivalis, Streptococcus pneumoniae, Chlamydia pneumoniae, Bacillus anthracis, group B streptococci, Helicobacter pylori and Mycobacterium tuberculosis. Concerning animal-affecting organisms, RV has been applied for vaccine design against Theileria parva, Brachyspira hyodysenteriae, Echinococcus granulosus, Ehrlichia ruminantium, Leishmania spp, Rhipicephalus microplus and Brucella melitensis." }, { "input": "Galassi classification is used for which disorder?", "output": "Galassi classification system is used to classify arachnoid cysts." }, { "input": "Describe Mozart effect.", "output": "The Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448." }, { "input": "What is the purpose of the Tokuhashi scoring system?", "output": "Tokuhashi scoring system was developed to predict life expectancy of patients with spinal metastases. The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease." }, { "input": "Which compounds exist that are thyroid hormone analogs?", "output": "Compoounds such as 3,5-diiodo-L-thyronine, T2, GC-24, CO23, DITPA, 3,5-diiodothyropropionic acid, GC-1, Tetrac, 3,3',5,5'-tetraiodo-thyroacetic acid, KB- 2115, KB - 141, thyronamines, T4-agarose, CGS 23425, D-T3, 3,3',5-triiodo-D-thyronine, 3,5-T2, 3,5-diiodo-L-thyronine, DIT, 3,5-diiodo-L-tyrosine, MIT, 3-monoiodo-L-tyrosine, triac, 3, 3',5-triiodo-thyroacetic acid, 3,5-Diiodo-4-hydroxyphenylpropionic acid, DIHPA, 3,5-Dimethyl-3'-isopropyl-L-thyronine, DIMIT, 3,5-diiodo-3'-isopropylthyroacetic acid and IpTA2 are compounds that are thyroid hormone analogs." }, { "input": "Is lenvatinib effective for thyroid cancer?", "output": "Yes, lenvatinib is effective for thyroid cancer." }, { "input": "What genes are related to breast cancer?", "output": "Breast cancer is a disease in which certain cells in the breast become abnormal and multiply without control or order to form a tumor. The most common form of breast cancer begins in cells lining the ducts that carry milk to the nipple (ductal cancer). Other forms of breast cancer begin in the glands that produce milk (lobular cancer) or in other parts of the breast.\nEarly breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, or scaliness. These changes can occur as part of many different conditions, however. Having one or more of these symptoms does not mean that a person definitely has breast cancer.\nIn some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.\nA small percentage of all breast cancers cluster in families. Hereditary cancers are those associated with inherited gene mutations. Hereditary breast cancers tend to occur earlier in life than noninherited (sporadic) cases and are more likely to involve both breasts.\n\nVariations of the BRCA1, BRCA2, BRCT, and P53 genes increase the risk of developing breast cancer.\nThe and NFR2, HER2 and TOP2A genes are associated with breast cancer." }, { "input": "To the ligand of which receptors does Denosumab (Prolia) bind?", "output": "Denosumab is a monoclonal antibody against the RANKL" }, { "input": "List fluorescent reporter proteins.", "output": "Fluorescent and luminescent reporter genes have become popular tools for the real-time monitoring of gene expression in living cells:\ngreen fluorescent protein\nTimer\nred fluorescent protein\nyellow fluorescent protein\nbeta-phycoerythrin\ncoral fluorescent reporter protein\nenhanced green fluorescent reporter protein\nmCherry" }, { "input": "By which mechanism MutT proteins act against DNA lesions in bacteria?", "output": "MutT proteins belong to a class of Nudix hydrolases. The common substrate structure for the proteins of the functionally diverse Nudix superfamily is nucleotide-diphosphate-X, where X is a large variety of leaving groups. The activities of Nudix hydrolases usually result in the release of an inorganic phosphate ion or of a product bearing a terminal phosphate moiety. MutT proteins hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool. MutT proteins cleave 8-oxo-dGTP (8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate) at the \u03b1-\u03b2 position; they also cleave 8-oxo-dGTP at the \u03b2-\u03b3 phosphate bond at a rate of 3% of that recorded for hydrolysis at the \u03b1-\u03b2 position. 8-oxo-dGTP induces A to C transversions when misincorporated in DNA opposite to template A. By hydrolyzing 8-oxo-dGTP before their incorporation into DNA, MutT proteins play a critical role in allowing bacteria to avoid A-to-C mutations, which are a hallmark of MutT deficiency. Thus, MutT proteins prevent oxidative DNA lesions, as part of the GO system. Oxidized nucleotides can occur when bacteria are exposed to reactive oxygen species. Also, reactive oxygen species are produced as side products of oxygen utilization, leading to the oxidation of nucleic acids and their precursor nucleotides. Distinct from the Escherichia coli MutT, which hydrolyzes 8-oxo-dGTP and 8-oxo-GTP, the mycobacterial proteins hydrolyze not only 8-oxo-dGTP and 8-oxo-GTP but also dCTP and 5-methyl-dCTP. Moreover, the hydrolysis of 8-oxo-dGTP and 8-oxo-GTP in mycobacteria seems to be catalysed in a two-stage mechanism, since MutT converts these oxidized nucleoside triphosphates to their corresponding nucleoside diphosphates, and not to monophosphates." }, { "input": "Was tamoxifen tested for treatment of glioma patients?", "output": "Yes, tamoxifen was tested for glioma treatment. However, clinical efficacy of tamoxifen in glioma patients remains unclear and should be tested in further studies." }, { "input": "Which transcription factors are known as the four (4) \"Yamanaka factors\" that have been used to create induced pluripotent stem cells (iPSCs)?", "output": "Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM). In particular, the mechanisms how the Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) directly drive reprogramming and which additional components are involved are still not yet understood." }, { "input": "Which transcription factors are known as the four (4) \"Yamanaka factors\" that have been used to create induced pluripotent stem cells (iPSCs)?", "output": "Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2 and cMyc, human somatic cells can be converted to a pluripotent state, generating so-called induced pluripotent stem cells (iPSCs)(1-4). Delivery of the transcription factors Oct4, Klf4, Sox2 and c-Myc via integrating viral vectors has been widely employed to generate induced pluripotent stem cell (iPSC) lines from both normal and disease-specific somatic tissues, providing an invaluable resource for medical research and drug development. " }, { "input": "Which transcription factors are known as the four (4) \"Yamanaka factors\" that have been used to create induced pluripotent stem cells (iPSCs)?", "output": "Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2 and cMyc, human somatic cells can be converted to a pluripotent state, generating so-called induced pluripotent stem cells (iPSCs)(1-4).Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM), but the mechanisms underlying this reprogramming remain poorly understood." }, { "input": "What is the role of anhedonia in coronary disease patients?", "output": "Anhedonia is associated with poor prognosis in patients with coronary disease. Namely, in patients with coronary disease, anhedonia was associated with increased mortality, greater risk for major cardiac event, impaired physical health status, more cardiac symptoms, more feelings of disability. These associations were independent from clinical and demographic factors." }, { "input": "What is the clinical value of naltrexone in Parkinson's disease patients?", "output": "Naltrexone does not improve clinical features, including motor function, in Parkinson's disease patients. Naltrexone was shown to be effective for treatment of pathological gambling in Parkinson's disease patients." }, { "input": "What is the efficacy of oxaliplatin monotherapy in the management of colorectal cancer?", "output": "Oxaliplatin is a promising treatment option for patients with metastatic colorectal cancer. It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with fluorouracil/calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over fluorouracil/calcium folinate alone. Promising results have been found in studies of the drug as monotherapy, and oxaliplatin may also prove useful in the neoadjuvant setting in patients with unresectable liver metastases; however, data are limited at present" }, { "input": "Are there any animal models for Niemann-Pick C1 disease?", "output": "Yes, murine models of Niemann-Pick type C disease (NPC) exist. They are either homozygous or heterozygous NPC1-deficient [NPC1 (-/-)]/ [NPC1 (+/-)] mouse models." }, { "input": "Which type of genes are modulated by SATB1?", "output": "Lack of effector T cell (T(eff) cell) function and gain of suppressive activity by T(reg) cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells. Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines. At an Associative t-test threshold of P" }, { "input": "Which type of genes are modulated by SATB1?", "output": "Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation" }, { "input": "Which type of genes are modulated by SATB1?", "output": "Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines." }, { "input": "Does HER2 under-expression lead to favorable response to trastuzumab?", "output": "No, trastuzumab is effective only in cancers where Her2 is over-expessed." }, { "input": "Which are the most abundant human lincRNA?", "output": "MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) locus is misregulated in many human cancers and produces an abundant long nuclear-retained noncoding RNA. MALAT/NEAT2 highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2." }, { "input": "Which is the molecular function of the protein CCDC40?", "output": "The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation and mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms." }, { "input": "Can administration of the thyrotropin releasing hormone reduce fatigue in cancer patients?", "output": "yes, in cancer patients, thyrotropin releasing hormone (TRH) administration was associated with significant improvement in cancer related fatigue levels as measured by the Visual Analog Scale-Energy, fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F. TRH administration was safe and tolerable in the treatment of cancer-related with a positive impact on quality of life, suggesting the need for further studies investigating TRH for treatment of fatigue in cancer patients." }, { "input": "What is the role of chromomethylases in plants?", "output": "Chromomethylases (CMTs), which constitute a plant-specific DNA (cytosine-5)-methyltransferase family, are involved primarily in the maintenance of symmetrical CpNpG (N = A, T, C, or G) methylation and they also play a role in de novo methylation. CMTs are characterized by the presence of a chromatin-associated domain (chromodomain) inserted within the catalytic protein motifs I and IV. CMTs have likely evolved because of the high levels of CpNpG methylation present in plant genomes relative to animal genomes. The targeting of CMT methylation is accomplished by short interfering RNA (siRNA) pathways and histone methylation (H3K9, H3K27). It has been shown that transposons are in vivo targets of CMT-dependent methylation, suggesting that CMTs play a role in the plant genome surveillance. In Arabidopsis, CMTs play a key role in egg cell reprogramming and normal embryogenesis during the first few divisions of the zygote by mediating transposon and euchromatin epigenetic gene silencing. In tomatoes, CMTs are preferentially expressed in the pericarp during fruit development which suggests involvement of CMTs in the locus-specific control of methylation in the pericarp during fruit growth." }, { "input": "Is curcumin a phytochemical?", "output": "Yes, curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa." }, { "input": "What is Cerebral Cavernous Malformation?", "output": "Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences" }, { "input": "What is Cerebral Cavernous Malformation?", "output": "Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences " }, { "input": "What is Cerebral Cavernous Malformation?", "output": "Cerebral cavernous malformations (CMs) are vascular malformations of the central nervous system, causing hemorrhagic strokes, seizures, and neurological deficits." }, { "input": "Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity?", "output": "Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified " }, { "input": "Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity?", "output": "Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been identified, biallelic disruption of any one of which results in this clinically defined syndrome." }, { "input": "Which protein pathway is regulating SGK1-mediated phosphorylation of FOXO3a to control cell proliferation?", "output": "mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FOXO3a at Ser314." }, { "input": "Which drugs have been found effective for the treatment of chordoma?", "output": "Established chordoma cell lines, and patient-derived primary cell cultures, as well as chordoma tumors in vivo were found to be sensitive to treatment with bortezomib, vincristine, doxorubicin, etoposide, cisplatin, fludarabine and SD-1029 Stat3 inhibitor. Moreover, percutaneous intratumoral injection with pingyangmycin lipiodol emulsion was shown to be effective against chordoma. It should be stressed that combination treatment with the use of the above drugs was always able to increase the therapeutic potency." }, { "input": "Which components of the stress granules are known to be related to motor neuron degeneration in Amyotrophic Lateral Sclerosis?", "output": "Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS." }, { "input": "Which components of the stress granules are known to be related to motor neuron degeneration in Amyotrophic Lateral Sclerosis?", "output": "TDP-43 and FUS have been identified as key proteins in the pathogenesis of some cases of ALS. Although their role in motor neuron degeneration is not yet known, TDP-43 and FUS have been shown to accumulate in RNA stress granules (SGs) in cell models and in spinal cord tissue from Amyotrophic Lateral Sclerosis (ALS) patients." }, { "input": "Is there evidence for de novo genesis of enhancers in vertebrates?", "output": "Yes." }, { "input": "Which could be some of the possible causes of hypersomnia?", "output": "Sleep-wake disturbances (SWD) with hypersomnia are common after traumatic brain injury (TBI), with decreased CSF levels of hypocretin-1, a wake-promoting neurotransmitter, in cases of sleep apnea, as well as in up to half the patients with dementia, particularly in vascular dementia, Korsakow syndrome, Parkinson's disease, and depression, where the alteration of sleep architecture may be pronounced, whereas in Alzheimer's disease prominent hypersomnolence or insomnia is typically only found in later stages of the diseases." }, { "input": "What is the function of caspases?", "output": "Caspases are intracellular proteases that propagate programmed cell death, proliferation, and inflammation." }, { "input": "Is TNNI3K a cardiac-specific protein?", "output": "Yes, TNNI3K is highly expressed in heart but is undetectable in other tissues." }, { "input": "How does Rif1 regulate DNA replication?", "output": "Rif1 (Rap1-interacting-factor-1), originally identified as a telomere-binding factor in yeast, is a critical determinant of the replication timing programme in human cells. Rif1 tightly binds to nuclear-insoluble structures at late-M-to-early-G1 and regulates chromatin-loop sizes. Furthermore, Rif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early-S-phase. Overall, Rif1 plays crucial roles in determining the replication timing domain structures in human cells through regulating higher-order chromatin architecture. This function of Rif1 depends on its interaction with PP1 phosphatases and the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK." }, { "input": "Is factor XI deficient in Hemophilia C?", "output": "Factor XI deficiency is associated with a bleeding tendency called Hemophilia C." }, { "input": "What is known about food intolerance and gluten ?", "output": "Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals.\nEmerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS." }, { "input": "What is known about food intolerance and gluten ?", "output": "Coeliac disease is a multifactorial disease characterized by a dysregulated immune response to ingested wheat gluten and related cereal proteins. With an incidence of about 1% of the general population, it is considered the most common food intolerance disorder.Emerging research into a syndrome known as nonceliac gluten sensitivity suggests a heterogeneous condition with some features of celiac disease but often categorized as FGIDs, including IBS." }, { "input": "Are EDNRB mutations involved in the development of Hirschsprung disease?", "output": "Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. Molecular genetic analyses have revealed that interactions between mutations in the genes encoding the RET receptor tyrosine kinase and the endothelin receptor type B (EDNRB) are central to the genesis of HSCR." }, { "input": "Are EDNRB mutations involved in the development of Hirschsprung disease?", "output": "Hirschsprung's disease (HSCR) is one the most common congenital intestinal disease, which leads to aganglionic megacolon in the early childhood. Several susceptibility genes have been identified, including RET protooncogene and its ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3) and its receptor B (EDNRB). More specifically, EDNRB mutations are found in 5% of familial or sporadic HSCR." }, { "input": "What is known about the effectiveness of electronic food diaries ?", "output": "Electronic dietary records were better than food diaries in terms of fat percentage reduction in our trials, indicating that teledietetics increases healthy-eating awareness." }, { "input": "Can the apoptosis regulator BAX trigger the release of cytochrome c?", "output": "Yes, altered Bax conformation trigger its redistribution from the cytosol to mitochondria. Subsequently, cytochrome c is released from mitochondria to cytosol." }, { "input": "Which biological process in known as Endoplasmic Reticulum-Associated Protein Degradation (ERAD)?", "output": "Endoplasmic reticulum-associated protein degradation (ERAD) is the quality control system in the endoplasmic reticulum of eukaryotic cells which ensures that newly synthesized proteins that fail to fold into the correct conformation or unassembled orphan subunits of oligomeric proteins are rapidly eliminated by proteolytic degradation. This entails the export of proteins from the endoplasmic reticulum to the cytosol followed by their destruction by the cytosolic ubiquitin/proteasome pathway. While this mechanism effectively prevents the cellular accumulation of non-functional or unwanted endogenous proteins, it renders the cell vulnerable to certain viruses and toxins that are able to subvert this degradative mechanism for their own advantage." }, { "input": "Which biological process in known as Endoplasmic Reticulum-Associated Protein Degradation (ERAD)?", "output": "In the secretory pathway, quality control for the correct folding of proteins is largely occurring in the endoplasmic reticulum (ER), at the earliest possible stage and in an environment where early folding intermediates mix with terminally misfolded species. An elaborate cellular mechanism aims at dividing the former from the latter and promotes the selective transport of misfolded species back into the cytosol, a step called retrotranslocation. During retrotranslocation proteins will become ubiquitinated on the cytosolic side of the ER membrane by dedicated machineries and will be targeted to the proteasome for degradation. The entire process, from protein recognition to final degradation, has been named ER-associated protein degradation, or simply ERAD. " }, { "input": "List BRAF inhibitors that have been tested in clinical trials for treatment of melanoma patients", "output": "Vemurafenib and dabrafenib are BRAF inhibitors that have been tested in clinical trials for treatment of melanoma patients." }, { "input": "which are the risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy?", "output": "The following risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy have been identified: 1) previous cardiac arrest; 2) sustained ventricular tachycardia; 3) family history of sudden cardiac death; 4) high-risk genetic mutations; 5) unexplained syncope; 6) non-sustained ventricular tachycardia; 7) hypotensive response to exercise; 8) marked left ventricular hypertrophy; 9) J-wave on ECG and 10) myocardial fibrosis using late gadolinium enhancement" }, { "input": "What is known about the economic cost of urinary incontinence?", "output": "The estimated total economic cost in treating overactive bladder was 117 billion Korean Won (KRW, the currency of South Koea) in 2006 and 145 billion KRW in 2007. The estimated total cost in treating stress urinary incontinence was 122 billion KRW in 2006 and 59 billion KRW in 2007.\nThe estimated total economic cost of OAB was 12.02 billion dollars in 2000, with 9.17 and 2.85 billion dollars incurred in the community and institutions, respectively. Community female and male OAB costs totaled 7.37 and 1.79 billion dollars, respectively. The estimated total cost was sensitive to the estimated prevalence of OAB; therefore, we calculated the average cost per community-dwelling person with OAB, which was 267 dollars per year.\nAn estimated 1835628 community-dwelling women over the age of 18 years had urinary incontinence in 1998. The total annual cost of this urinary incontinence is estimated at $710.44 million, or $387 per incontinent woman, comprising $338.47 million in treatment costs and $371.97 million in personal costs. An estimated 60% of women with incontinence in 1998 were aged 40 years or over. Assuming the prevalence of incontinence remains constant and, allowing for inflation, we project that the total annual cost in 20 years' time will be $1267.85 million, 93% ($1.18 billion) of which will constitute costs associated with women aged over 40 years.\nFor individuals 65 years of age and older these costs are substantial, increasing from $8.2 billion (1984 dollars) to $16.4 billion (1993 dollars). The 1995 societal cost of incontinence for individuals aged 65 years and older was $26.3 billion, or $3565 per individual with urinary incontinence." }, { "input": "Which are the coactivators of the Yes-associated protein (yap)?", "output": "The Yap protein forms complex with Tead (TEA domain) transcription factors." }, { "input": "How many genes outside of the MHC locus have been genetically associated to Rheumatoid Arthritis through GWAS?", "output": "Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. To date, over 30 non-MHC RA-associated loci have been identified in humans, and over 100 arthritis-associated loci have been identified in rodent models of RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases." }, { "input": "Are optogenetics tools used in the study and treatment of epilepsy?", "output": "Using optogenetics tools it is possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies." }, { "input": "In which phase of cell cycle does stress-induced transcription-associated mutagenesis (TAM) occur?", "output": "Factors involved in RNA polymerase (RNAP) processivity or transcriptional derepression, such as Mfd (transcription coupling repair factor), contribute to the generation of stress-induced mutations. Under stress, transcription-associated mutagenesis is increased. Stress-induced transcription-associated mutations are acquired by nondividing cells, during stationary phase, and are not observed under conditions of exponential growth." }, { "input": "Which proteins are related to the loss of cell-cell adhesion during EMT (epithelial-mesenchymal transition)?", "output": "Transcriptional and post-transcriptional regulatory mechanisms mediated by several inducers of EMT, in particular the ZEB and Snail factors, downregulate the expression and/or functional organization of core polarity complexes. Functional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion. Recently, we found that aPKC can also phosphorylate Par6 to drive EMT and increase the migratory potential of non-small cell lung cancer cells. We propose that the regulation of EMT by SIRT1 involves modulation of, and cooperation with, the EMT inducing transcription factor ZEB1. Knockdown of Numb by shRNA in MDCK cells led to a lateral to apical translocation of E-cadherin and beta-catenin, active F-actin polymerization, mis-localization of Par3 and aPKC, a decrease in cell-cell adhesion and an increase in cell migration and proliferation. Growth factors such as TGFb and EGF have also been shown to be related to EMT." }, { "input": "Is micro RNA 1 (miR-1) implicated in cardiac arrhythmias?", "output": "Yes. miR-1 overexpression may contribute to the increased susceptibility of the heart to AVB, which provides us novel insights into the molecular mechanisms underlying ischemic cardiac arrhythmias. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients." }, { "input": "Is micro RNA 1 (miR-1) implicated in cardiac arrhythmias?", "output": "Yes, changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure. it has been shown that miR-1 over-expression in normal or infarcted rat hearts exacerbates arrhythmogenesis, while elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target." }, { "input": "Are there Conserved Noncoding Elements (CNEs) in invertebrate genomes?", "output": "Yes." }, { "input": "Are there Conserved Noncoding Elements (CNEs) in invertebrate genomes?", "output": "Yes. Conserved Noncoding Elements (CNEs) have also been found in invertebrate genomes." }, { "input": "Which tumor suppressor is referred to as \"the guardian of the genome\"?", "output": "The major tumour suppressor protein, p53, is one of the most well-studied proteins in cell biology. It plays a crucial role in regulating the transcription of numerous genes responsible for cells cycle arrest, DNA repair, angiogenesis, cell senescence, or apoptosis in response to various stress signals, and is considered one of the most important players in the development of cancer. p53 contributes to the maintenance of genomic stability. Thus, p53 has been described as \"the guardian of the genome\"." }, { "input": "What is known about diseases associated with mutations in the CHCHD10 gene?", "output": "Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. \nMutations in the CHCHD10 gene have been identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment.\nOther findings links CHCHD10 mutations to mitochondrial myopathy." }, { "input": "What is known about diseases associated with mutations in the CHCHD10 gene?", "output": "Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment." }, { "input": "Which drug should be used as an antidote in benzodiazepine overdose?", "output": "Flumazenil should be used in all patients presenting with suspected benzodiazepine overdose. Flumazenil is a potent benzodiazepine receptor antagonist that competitively blocks the central effects of benzodiazepines and reverses behavioral, neurologic, and electrophysiologic effects of benzodiazepine overdose. Clinical efficacy and safety of flumazenil in treatment of benzodiazepine overdose has been confirmed in a number of rigorous clinical trials. In addition, flumazenil is also useful to to reverse benzodiazepine induced sedation and to and to diagnose benzodiazepine overdose." }, { "input": "Does thyroid hormone signaling affect microRNAs expression in the heart?", "output": "YES" }, { "input": "Give examples of next-generation sequencing applications in mutation screening?", "output": "Next generation sequencing data for a particular genomic region can be seen as the summation of all the individual sequences (reads) obtained for that region and no longer as the mean of this sum as it is the case for traditional Sanger sequencing. NGS is introduced to an increasing number of mutation screening applications. An NGS based mutation screening procedure allowing the detection of inherited Alu insertions within any predefined sequence was used for the case of c.1739_1740insAlu in BRCA1 and c.156_157insAlu in BRCA2. Another NGS study screened BRCA1 and BRCA2 resulting in overall sensitivity for SOLiD and PGM of 97.8% (95% CI = 94.7 to 100.0) and 98.9% (95% CI = 96.8 to 100.0) respectively. The specificity for the SOLiD platform was high, at 100.0% (95% CI = 99.3 to 100.0). PGM correctly identified all 3 indels, but 68 false-positive indels were also called. Genes known to cause deafness were sequenced by the Illumina NGS platform. Results demonstrated that targeted exons captured by our approach achieved specificity, multiplexicity, uniformity, and depth of coverage suitable for accurate sequencing applications by the NGS systems. Reliable genotype calls for various homozygous and heterozygous mutations were achieved. In the context of von Willebrand disease 43 mutations, including 36 substitutions, 2 intronic splice site mutations, 2 indels, and 3 deletions were screened on the next-generation sequencing instrument. This demonstrated that at least 350 patients and relatives per run can be simultaneously analyzed in a fast, inexpensive manner. The Alport syndrome is caused by mutations in three key genes namely COL4A3, COL4A4 and COL4A5, each of which consists of approximately 50 exons, thus rendering mutations screening a highly time consuming and expensive endeavor. NGS is now being established for the simultaneous, fast and cost-effective detection of all possible variants in these three genes. NGS has also been used screening EGFR, KRAS and BRAF for mutations associated with cancer diagnosis and/or response to several anticancer therapies. NGS has also been used in mutation screening for hereditary spastic paraplegias, X linked leucoencephalopathy, retinitis pigmentosa, inherited urea cycle disorders, as well as the Marfan (MFS), Loeys-Dietz (LDS) and Meckel syndromes." }, { "input": "List common features of Shapiro syndrome", "output": "Shapiro syndrome is a rare entity, comprising a triad of recurrent hypothermia, hyperhidrosis and congenital agenesis of the corpus callosum. Hypermelatoninemia has also been described in a patient with Shapiro syndrome." }, { "input": "List mouse models for autism spectrum disorder (ASD).", "output": "Numerous mouse models exists for autism spectrum disorder, such as: BTBR T+tf/J (BTBR), maternal immune, activation (MIA) mouse model of gestational poly(IC) exposure, C58/J and ProSAP1/Shank2." }, { "input": "What is BioASQ?", "output": "BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies. " }, { "input": "What is BioASQ?", "output": "The BioASQ challenge is a competition on large-scale biomedical semantic indexing and question answering (QA). BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies. BIOASQ helped obtain a unified view of how techniques from text classification, semantic indexing, document and passage retrieval, question answering, and text summarization can be combined to allow biomedical experts to obtain concise, user-understandable answers to questions reflecting their real information needs." }, { "input": "Which are the main functions of G3BP1 and G3BP2 proteins?", "output": "The main functions of G3BP1 and/or G3BP2 include translation of interferon stimulated mRNAs during dengue virus infection, initiation of assembly of stress granules, regulation of PMP22 mRNA which was found to affect cell proliferation in breast cancer cells, participation in several signaling pathways involved in growth, differentiation and apoptosis in human tumor cells after overexpression, limit viral replication events during Sindbis virus (SINV) infection, and modulation of p53 and MDM2 activity." }, { "input": "What is the definitive treatment for low pressure headache?", "output": "epidural blood patch" }, { "input": "What is the role of the histidine rich calcium binding protein (HRC) in cardiomyopathy?", "output": "The histidine-rich Ca-binding protein (HRC), a 165 kDa sarcoplasmic reticulum (SR) protein, regulates SR Ca cycling during excitation\u2013contraction coupling. HRC mutations or polymorphisms lead to cardiac dysfunction. The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias and sudden death in idiopathic dilated cardiomyopathy (DCM)." }, { "input": "What is the incidence of sudden cardiac death among young athletes?", "output": "the incidence of sudden cardiac death among young athletes ranges from 0.5 to 3 per 100,000 athletes per year ." }, { "input": "What is the effect of amitriptyline in the mdx mouse model of Duchenne muscular dystrophy?", "output": "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy" }, { "input": "What is the effect of amitriptyline in the mdx mouse model of Duchenne muscular dystrophy?", "output": "Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. On the other hand, inflammation in mdx skeletal muscle tissue was also reduced as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-\u03b1 and interleukin-6 in the forelimb flexors." }, { "input": "What is the effect of amitriptyline in the mdx mouse model of Duchenne muscular dystrophy?", "output": "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy " }, { "input": "Which post-translational histone modifications are characteristic of facultative heterochromatin?", "output": "Nuclear VapB methyltransferase diminishes the establishment of facultative heterochromatin by decreasing histone 3 lysine 9 trimethylation (H3K9me3). Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin." }, { "input": "Mutations in which genes have been associated with Aicardi-Goutieres syndrome?", "output": "Aicardi-Gouti\u00e8res syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR)." }, { "input": "List bacteria that may be useful in uranium bioremediation.", "output": "The main bacteria studied in uranium bioremediation are Geobacteraceae. Other bacteria are: \nFirmicutes, \nShewanella oneidensis\nPseudomonas aeruginosa\nAnaeromyxobacter dehalogenans \nstrain Rf4T" }, { "input": "How much should be the duration of the QT interval in patients with short QT syndrome?", "output": "The short-QT syndrome is characterized by QT intervals <300-330 msec" }, { "input": "What is known about potential implication of thyroid hormone receptors in arterial hypertension?", "output": "thyroid hormone receptors are implicated in arterial hypertension" }, { "input": "What is known about potential implication of thyroid hormone receptors in arterial hypertension?", "output": "An associations between the THRA rs939348 polymorphism and systolic BP and the risk of hypertension has been observed\nThe levels of the three thyroid hormone receptors isoforms do not differ significantly between spontaneous hypertensive rats and control rats of the same age, either in the left or in the right ventricle.\nThe published results are still unconclusive." }, { "input": "What is the mechanism of action of abiraterone?", "output": "Abiraterone acts by inhibiting cytochrome P450 17\u03b1-hydroxylase (CYP17A1), a critical step in androgen biosynthesis, thus leading to inhibition of androgen biosynthesis." }, { "input": "The protein neprilysin has an positive effect on Alzheimer disease, how can it be delivered to the brain?", "output": "The protein neprilysin can be deliverered to the brain (crossing the blood brain barrier) through: gene tranfer, transgenesis, gene induction, ex-vivo gene therapy, intracardiac (peripheral) administration of viral neprilysin construct, syringe-focused ultrasound device, convection-enhanced delivery and the use of human adipose tissue-derived mesenchymal stem cells that secrete functional neprilysin-bound exosomes" }, { "input": "Which species of bacteria did the mitochondria originate from?", "output": "Biologists agree that the ancestor of mitochondria was an alpha-proteobacterium. Although the Alphaproteobacteria are thought to be the closest relatives of the mitochondrial progenitor, there is dispute as to what its particular sister group is. Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales. Phylogenetic analyses indicate that R. prowazekii is more closely related to mitochondria than is any other microbe studied so far." }, { "input": "Which disease is linked to mutations within BRAG1?", "output": "Mutations in BRAG1 have been identified in families with X-linked intellectual disability (XLID)." }, { "input": "Which is the main calcium pump of the sarcoplasmic reticulum?", "output": "Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis. SERCA is a membrane protein that belongs to the family of P-type ion translocating ATPases and pumps free cytosolic calcium into intracellular stores." }, { "input": "What is the inheritance pattern of Hunter disease or mucopolysaccharidosis II?", "output": "X- linked recessive" }, { "input": "Do ephrins play a role in brain cancer?", "output": "Eph receptors and ephrin ligands are involved in the development of the central nervous system. Their expression is often reported to be up-regulated in brain tumours and they may be considered molecular markers for the diagnosis of invasive and metastatic tumours. However, there are also reports describing the down-regulation of the Eph/ephrin family in brain cancer." }, { "input": "What is the effect of the absence of Saccharomyces cerevisiae Rrm3p?", "output": "The Saccharomyces cerevisiae RRM3 gene encodes a 5' to 3' DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Delta cells, especially at low temperatures." }, { "input": "What is the effect of the absence of Saccharomyces cerevisiae Rrm3p?", "output": "The Saccharomyces cerevisiae RRM3 gene encodes a 5 to 3 DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Delta cells, especially at low temperatures " }, { "input": "Do all archaea possess multiple origins of DNA replication?", "output": "Origins of DNA replication differ in number and structure across the three domains of life and their properties determine the dynamics of chromosome replication. Though most archaea replicate their chromosomes using multiple origins, there are also certain archaea that possess a single origin of DNA replication (such as Pyrococcus abyssi and some archaea belonging in the hyperthermophilic order of Themococcales)." }, { "input": "What is the ubiquitin proteome?", "output": "The ubiquitin proteome is the entire set ubiquitinated proteins and of their respective ubiquitination sites." }, { "input": "Which major signaling pathways are regulated by RIP1?", "output": "necroptosis\napoptosis \npro-survival/inflammation NF-\u03baB activation" }, { "input": "What is the effect induced by sympathetic nervous system on pupil size?", "output": "Pupil size is determined by the interaction of the parasympathetic and the sympathetic nervous system. The sympathetic nervous system acts either directly on the dilator muscle (peripherally) or centrally by inhibiting the Edinger-Westphal nucleus. Thus, the sympathetic nervous system mediates pupillary dilatation." }, { "input": "Is p100 the precursor protein molecule of the NF-kappaB transcription factor subunit p50?", "output": "No, the precursor molecule for NF-kappaB p50 is p105 and not p100. Nfkb2 encodes two members of the NF-kappa B/Rel family of proteins: p52 and p100. The p100 polypeptide has been proposed to serve as a precursor of p52 (and not of p50), which corresponds to the N-terminal half of p100. NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel." }, { "input": "What is the definition and the biological role of epithelial-mesenchymal transition (EMT)", "output": "Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT. The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma." }, { "input": "What is the definition and the biological role of epithelial-mesenchymal transition (EMT)", "output": "This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma. This term is used to describe the mechanisms facilitating cellular repositioning and redeployment during embryonic development and tissue reconstruction after injury. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT. Recently, EMT has also been applied to potential mechanisms for malignant progression and has appeared as a specific diagnostic category of tumors. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. EMT has also been reported to produce cells with stem cell-like properties. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Epithelial-to-mesenchymal transition (EMT) is a process known to contribute to metastasis in cancer and it is mainly characterized by loss of E-cadherin expression. " }, { "input": "What is the definition and the biological role of epithelial-mesenchymal transition (EMT)", "output": "This term is used to describe the mechanisms facilitating cellular repositioning and redeployment during embryonic development and tissue reconstruction after injury. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma. Several oncogenic pathways such as transforming growth factor (TGF) -\u03b2, Wnt, and Notch signaling pathways, have been shown to induce EMT. Recently, EMT has also been applied to potential mechanisms for malignant progression and has appeared as a specific diagnostic category of tumors. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. EMT has also been reported to produce cells with stem cell-like properties. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Epithelial-to-mesenchymal transition (EMT) is a process known to contribute to metastasis in cancer and it is mainly characterized by loss of E-cadherin expression. " }, { "input": "Is there a difference in the rate between gene fusion and gene fission?", "output": "Yes. Several studies have estimated that gene fusion and fission are relatively rare events and the gene fusion/fission rate is approximately between 2 and 6. A conflicting case has been discovered in an analysis of plant genomes, where in Oryza sativa the opposite trend was observed." }, { "input": "What type of cancers and inherited diseases have been associated to mutations in the Notch pathway?", "output": "So far, mutations in Notch and other components of its signaling pathway have been implicated in an array of human diseases (T-cell leukemia and other cancers, Multiple Sclerosis, CADASIL, Alagille Syndrome, Spondylocostal Dysostosis), but more pathologies are likely to be associated with Notch in the future due to its network complexity." }, { "input": "Can cognitive behavioral therapy improve fatigue in cancer patients?", "output": "Yes, it has been documented that cognitive behavioral therapy reduces fatigue symptom severity in cancer patients. In addition, cognitive behavioral therapy has been also shown to improve mood and overall quality of life, and it can be successfully delivered through a variety of treatment modalities in patients with cancer." }, { "input": "Is protein Fbw7 a SCF type of E3 ubiquitin ligase?", "output": "Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members.The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun." }, { "input": "Is protein Fbw7 a SCF type of E3 ubiquitin ligase?", "output": "The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun." }, { "input": "Is there increased incidence of incontinence in athletes?", "output": "There is a very high prevalence of urinary incontinence in women athletes." }, { "input": "What is the inheritance pattern of Apert syndrome?", "output": "The Apert syndrome is a disorder of autosomal dominant inheritance." }, { "input": "Which is the most widely used model for the study of multiple sclerosis (MS)?", "output": "Experimental autoimmune encephalomyelitis (EAE) is a classical, conventional and widely recognized animal model for studying multiple sclerosis (MS). EAE is the best available model for the inflammatory processes that occur in MS, and for the disease process. A less commonly used model is that of Theiler's murine encephalomyelitis virus (TMEV)." }, { "input": "What is the usual HER-2 status in breast cancer associated with Li-Fraumeni syndrome?", "output": "In up to two thirds of breast cancer patients associated with Li-Fraumeni syndrome, the HER-2 status was found to be positive." }, { "input": "What is the treatment of triiodothyronine toxicosis?", "output": "Treatment of T3 toxicosis is a complex medical problem because not well responsive to the various options. Usual treatment includes antithyroid drugs such as propyltiouracil, radioactive iodine or beta blockers like propanol; surgery may be also necessary in some cases." }, { "input": "Are there enhancer RNAs (eRNAs)?", "output": "Yes. Active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription." }, { "input": "Which are the known human transmembrane nucleoporins?", "output": "Transmembrane nucleoporins (NUPs) are integral membrane components of the eukaryotic nuclear pore, playing an important role in the Nuclear Pore Complex (NPC) assembly. Even though the NPC is a conserved feature of all eukaryotes, different lineages possess some distinct transmembrane NUP subunits. Currently, four human transmembrane NUPs have been characterized, namely: NDC1 (also known as TMEM48 or NET3 or hNDC1), POM121 (also known as Nup121), GP210 (also known as Nuclear pore membrane glycoprotein 210 or Nuclear envelope pore membrane protein POM 210, POM210 or Nup210) and TMEM33 (or DB83)." }, { "input": "Which E3 ubiquitin ligase mediates the ubiquitination and degradation of the interferon receptor type 1 (IFNAR1)?", "output": "Ubiquitination and degradation of the IFNAR1 (interferon alpha receptor 1) subunit of the type I interferon (IFN) receptor is mediated by the SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein) E3 ubiquitin ligase in a phosphorylation-dependent manner." }, { "input": "Which E3 ubiquitin ligase mediates the ubiquitination and degradation of the interferon receptor type 1 (IFNAR1)?", "output": "Ubiquitination, endocytosis, and lysosomal degradation of the IFNAR1 (interferon alpha receptor 1) subunit of the type I interferon (IFN) receptor is mediated by the SCFbeta-Trcp (Skp1-Cullin1-F-box protein beta transducin repeat-containing protein) E3 ubiquitin ligase in a phosphorylation-dependent manner. " }, { "input": "Are conserved noncoding elements associated with the evolution of animal body plans?", "output": "Yes. Cis-regulatory inputs identified by CNEs arose during the \"re-wiring\" of regulatory interactions that occurred during early animal evolution. Consequently, different animal groups, with different core GRNs, contain alternative sets of CNEs. Due to the subsequent stability of animal body plans, these core regulatory sequences have been evolving in parallel under strong purifying selection in different animal groups." }, { "input": "Which genes were found to be methylated in bladder cancer cells?", "output": "In bladder cancer, hepaCAM (hepatocyte cell adhesion molecule), RAR\u03b2(2), APC, TPEF (transmembrane protein containing epidermal growth factor and follistatin domain), RASSF1A, p14(ARF) and p16 genes were found to be methylated. These methylation events were demostrated to associate with downregulation of gene expression." }, { "input": "Are DNA methylation maps applicable to the diagnosis of non-small-cell lung carcinomas?", "output": "Yes." }, { "input": "Are DNA methylation maps applicable to the diagnosis of non-small-cell lung carcinomas?", "output": "yes" }, { "input": "Which domain of TIA-1 is necessary for stress granule assembly?", "output": "TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD). Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cells." }, { "input": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "output": "CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling. " }, { "input": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "output": "The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF-kappaB. " }, { "input": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "output": "The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis, an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor \u03baB (NF-\u03baB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-\u03baB activating proteins." }, { "input": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "output": "Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling.CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Loss of the deubiquitinating activity of CYLD is correlated with tumorigenesis." }, { "input": "What is the characteristic domain of histone methyltransferases?", "output": "SET (suppressor of variegation, enhancer of zest and trithorax) domain" }, { "input": "What is smFISH?", "output": "smFISH (Single-molecule fluorescence in situ hybridization) allows for quantitative imaging of single RNA molecules. Multi-color, single-molecule fluorescence in situ hybridization (smFISH) is particularly useful since it enables analysis of several different transcripts simultaneously. Combining smFISH with immunofluorescent protein detection provides additional information about the association between transcription level, cellular localization, and protein expression in individual cells." }, { "input": "Which are the bioinformatics tools for gene structure prediction?\n", "output": "The in silico prediction of the complete structure of genes is one of the main challenges of bioinformatics. A critical part in the gene structure prediction is to identify the boundaries between exons and introns (i.e. splice sites) in the coding region. Several advanced bioinformatics tools have been developed for the precise delineation of a given gene structure: WPSS, SCGPred, TICO, GLIMMER, MetWAMer, WebScipio, GeneSeqer, SplicePredictor, DGSplicer, Transcript Assembly Program (TAP), GeneBuilder, SeqHelp, HSPL, RNASPL, HEXON, CDSB, HBR, FGENE and FGENEH for human genes." }, { "input": "Which are the bioinformatics tools for gene structure prediction?\n", "output": "SCGPred: a score-based method for gene structure prediction by combining multiple sources of evidence. MetWAMer.gthXML is a special-purpose variant of the software, specifically tailored to refine gene structure predictions generated by the GenomeThreader [30] and GeneSeqer [31] programs for spliced alignment-based gene structure annotation. WebScipio: an online tool for the determination of gene structures using protein sequences. " }, { "input": "Which is the major phytoalexin in alfalfa (Medicago sativa L.)?", "output": "The major phytoalexin in alfalfa (Medicago sativa L.) is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin. Medicarpin is synthesized via the isoflavonoid branch of phenylpropanoid metabolism." }, { "input": "What is the correlation between SPARC expression and growth inhibition in human cancer?", "output": "Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell-cell and cell-matrix interactions. SPARC seems to act as a tumour suppressor, as it has been found that loss of SPARC accelerates the development of certain types of cancer, whereas its expression impairs tumor growth. However it has also been associated with a aggressive phenotypes of some tumours. The role of SPARC may depend on its subcellular localization." }, { "input": "Which syndrome is associated with mutations in the LYST gene?", "output": "Mutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Ch\u00e9diak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism. A small number of reports of rare, attenuated forms of CHS exist, with affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction." }, { "input": "Has the presence of delayed enhancement been documented in athletes performing strenuous exercise?", "output": "There are contrasting literature data on the presence of delayed enhancement, as a sign of myocardial fibrosis, in healthy athletes. More studies are necessary to define the presence, incidence and severity, as well clinical and prognostic meaning, of delayed enhancement magnetic resonance in healthy athletes." }, { "input": "How does dronedarone affect thyroid hormone signaling in the heart?", "output": "Dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor and selectively mimicks hypothyroidism.\nDronedarone decreases TRalpha 1 and beta 1 expression by about 50% in the right atrium (RA) while in the left ventricle, only TRbeta1 is found to be decreased." }, { "input": "Name the factors required for selenoprotein synthesis in eukaryotes", "output": "eFSec, SBP2, SECp43, PSTK, Sec synthase (Sec S, SLA/LP), SPS2 (SelD), tRNASec, SECIS element, (L30), SPS1" }, { "input": "What are the functions of the ESCRT machinery?", "output": "The endosomal sorting complexes required for transport (ESCRT) are needed for three distinct cellular functions in higher eukaryotes: (i) Multivesicular body formation for the degradation of transmembrane proteins in lysosomes, (ii) midbody abscission during cytokinesis and (iii) retroviral budding." }, { "input": "Which genes/proteins have been found to inhibit cyclin dependent kinase 4 (CDK4)?", "output": "The p15(ink4b) and p16(ink4a) CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in various cancers.The Cdk4 inhibitor p18(Ink4c) is a tumor suppressor. Recent studies of Cyclin D1/Cdk4 have proposed that p21(Waf1/Cip1/Sdi1) plays a key role as a potent Cdk4 inhibitor. p27KIP1 is also a cdk4 ihibitor." }, { "input": "What is the role of TRH in hypertension?", "output": "TRH gene overexpression induces hypertension in normal rats and spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. TRH antisense treatment reduces hypertension.\ncentral TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity.\nthe pressor effect of intravenous TRH is mediated primarily by a stimulation of alpha-adrenergic receptors. Activation of cardiac beta-adrenoceptors seems to contribute to the blood pressure increasing effect of intravenous TRH. Ang II system is involved in the TRH cardiovascular effects. \nPolymorphisms in TRH (thyrotropin-releasing hormone) are significantly associated with both blood pressure variation and hypertension.\nTRH may mediate the central leptin-induced hypertension effect\nA parallel increase in the density of brain TRH receptors with elevation of blood pressure has been shown and suggests that brain TRH receptors may play an important role in the pathophysiology of hypertension. TRH Receptor gene participates in the etiopathogenesis of essential hypertension." }, { "input": "Is triadin involved in cardiac function?", "output": "Yes, triadin is involved in the regulation of cardiac excitation-contraction coupling." }, { "input": "Which disorders are associated to mutated Hepcidin (HAMP)?", "output": "Juvenile hemochromatosis (JH) is the most severe form of heriditary hemochromatosis, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP)." }, { "input": "Which protein is the main inhibitor of protein phosphatase 1 (PP1)?", "output": "Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), a major eukaryotic Ser/Thr phosphatase. Nonphosphorylated I-1 is inactive, whereas phosphorylated I-1 is a potent PP1 inhibitor. " }, { "input": "Which protein is the main inhibitor of protein phosphatase 1 (PP1)?", "output": "Protein Phosphatase-1 is restrained by its endogenous inhibitor, protein phosphatase inhibitor-1 (PPI-1). Inhibition of the protein phosphatase 1, by inhibitor-1, significantly increases cardiac contractility and calcium handling. Inhibitor-1 becomes a potent inhibitor of protein phosphatase 1 when phosphorylated by cAMP-dependent protein kinase." }, { "input": "What is the role of NETs in systemic lupus erythematosus?", "output": "Neutrophil extracellular traps (NETs) are released via a novel form of cell death called NETosis. NETs, consisting of a chromatin meshwork decorated with antimicrobial peptides, play an important role in the innate response to microbial infections. Clearance of NETs is impaired in a subset of patients with systemic lupus erythematosus, and NETosis is increased in these patients low-density granulocytes, a phenotype that correlates with disease activity. NETs are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. NETs can directly damage tissues - including the endothelium - with implications for lupus nephritis and accelerated atherosclerosis." }, { "input": "Which protein is required for Argonaute 2 recruitment to stress granules and P-bodies?", "output": "Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies." }, { "input": "Is Mammaprint approved by the United States Food and Drug Administration?", "output": "Yes, Mammaprint has been approved by the US Food and Drug Administration." }, { "input": "What is known as Von Hippel\u2013Lindau disease or syndrome?", "output": "von Hippel-Lindau (VHL) disease is a rare, autosomal dominantly inherited multisystem disorder characterized by development of a variety of benign and malignant tumors, which are usually accompanied with cysts. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The most common causes of death in VHL disease patients are renal cell carcinoma and neurologic complications from cerebellar hemangioblastomas. von Hippel-Lindau (VHL) syndrome is associated with mutations of the VHL tumor suppressor gene (3p25-26). Its estimated incidence ranges from 1 in 36,000 to 1 in 53,000 with a penetrance of up to 95% by age 60. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation. Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes.In addition, many HIFalpha-independent functions of pVHL have recently been identified. These include microtubule-based processes, extracellular matrix assembly and suppression of kidney cyst formation." }, { "input": "What is known as Von Hippel\u2013Lindau disease or syndrome?", "output": "VHL is the result of a germline mutation in the VHL tumor suppressor gene. Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes. These include microtubule-based processes, extracellular matrix assembly and suppression of kidney cyst formation. Clinical symptoms occur first after an age of approximately 30\u00a0years. Main manifestations include central nervous system (CNS) and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors. Type 1 VHL is predominantly associated with large deletion or truncation mutations which result in an encoded protein with very little or no activity. It is further classified into three other subtypes (2A, 2B, 2C) based on the presence of hemangioblastoma and renal cell carcinoma. In addition, many HIFalpha-independent functions of pVHL have recently been identified. It is associated with retinal and CNS hemangioblastoma and renal cell carcinoma but not pheochromocytoma. Incidence of VHLS is roughly 1 in 36,000 live births and has over 90% penetrance by the age of 65. " }, { "input": "Is HER2 active only when it dimerizes?", "output": "Yes, HER2 activation is driven by the formation of various dimer complexes between members of this receptor family." }, { "input": "Which pharmacogenetic test is available for abacavir?", "output": "The pharmacogenetic test recommended prior to abacavir administration is the HLA B*5701 genotyping." }, { "input": "Are microRNA (miR) regulated through DNA methylation of their promoters?", "output": "Dysregulation of miRNA expression involved in cancer and Alzheimer's disease can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter. Epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM)." }, { "input": "Are microRNA (miR) regulated through DNA methylation of their promoters?", "output": "Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoterRecently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM)" }, { "input": "Are nucleosomes positioned at DNA replication origins?", "output": "No, origins of replication occur in nucleosome-free regions in both budding yeast and Drosophila. Open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication." }, { "input": "Which are the most under-represented oligonucleotides in higher eukaryote genomes?", "output": "The oligonucleotides containing the CG and TA dinucleotide are generally under-represented in higher eukaryote genomes" }, { "input": "Which are the most under-represented oligonucleotides in higher eukaryote genomes?", "output": "TpA is the most underepresented dinucleotide followed closely by CpG. For trinucleotides, GCA/TGC tends to be under-represented in phage, human viral, and eukaryotic sequences, and CTA/TAG is strongly under-represented in many prokaryotic, eukaryotic, and viral sequences. For higher lengts alternating Purine/Pyrimidine tracts are underepresented up to 60%." }, { "input": "Which are the most under-represented oligonucleotides in higher eukaryote genomes?", "output": "Oligonucleotides containing CG and TA dinucleoides" }, { "input": "Does nimotuzumab improve survival of glioblastoma patients?", "output": "Yes. Nimotuzumab improves survival of adult and pediatric patients diagnosed with glioblastoma and with other high-grade gliomas." }, { "input": "List co-morbidities that may occur together with \"Stiff man Syndrome\"", "output": "SMS (Stiff man Syndrome) is is a rare disorder of the central nervous system of probable autoimmune origin and as such is associated with other autoimmune diseases, such as Insulin Dependent Diabetes Mellitus . GAD-65 is a dominant auto-antigen that is found both in in stiff-man syndrome and insulin-dependent diabetes mellitus. TRAB -positive Graves' disease has been reported to occur together with SMS. \nIn a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.\n\nHCV may be the etiologic virus of progressive encephalomyelitis with rigidity; a rare disorder similar to stiff-man syndrome although different because it is progressive and fatal.\nIt is possible that the reported case of association of progressive dementia with concomitant development of stiff-man syndrome in an elderly man represents an exaggerated form of such motor disturbances in dementia, and that clinical and electromyographic features of stiff-man syndrome may be present with increased incidence in patients with dementia." }, { "input": "Which mechanisms underlie adaptive mutagenesis (stationary-phase mutagenesis) in Bacillus subtilis?", "output": "Increased transcription levels potentiate adaptive mutagenesis. Central to stationary-phase mutagenesis in B. subtilis is the requirement for Mfd protein (transcription repair coupling factor). The B. subtilis' ability to accumulate chromosomal mutations under conditions of starvation is influenced by cell differentiation and transcriptional derepression, as well as by proteins homologous to transcription and repair factors. Under conditions of nutritional stress, the processing of deaminated bases in B. subtilis may normally occur in an error-prone manner to promote adaptive mutagenesis. A functional RecA protein is not required for adaptive mutagenesis, which seems to be independent of recombination-dependent repair and, in some cases, of the Y DNA polymerases. Oxidative stress-induced DNA damage has been associated with adaptive mutagenesis. The occurrence of such mutations is exacerbated by reactive oxygen species. Starved B. subtilis cells lacking a functional error prevention GO (8-oxo-G) system (composed of YtkD, MutM, and YfhQ) had a dramatic propensity to increase the number of stationary-phase-induced revertants. The MMR (encoded by the mutSL operon) protects B. subtilis from stationary-phase mutations. The MMR modulation of the mutagenic/antimutagenic properties of MutY regulates stationary-phase mutagenesis. Two of the genes that are involved in the regulation of post-exponential phase prokaryotic differentiation, comA and comK, are involved in adaptive mutagenesis. Also, YqjH, a homolog of DinB protein, plays a role in stationary phase mutagenesis." }, { "input": "What personality traits can be evaluated with the Ten Item Personality Inventory.", "output": "The Ten Item Personality Inventory measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism." }, { "input": "Which are the enzymes involved in the control of tubulin acetylation?", "output": "Acetyltransferase MEC-17, and deacetylases SIRT2 (Sirtuin 2), HDAC6 (histone deacetylase 6) and dTip60 are known to control the levels of tubulin acetylation." }, { "input": "Is there a relation between ANP and transcapillary albumin escape?", "output": "A possible role of ANP gene in conferring protection from nephropathy and microvascular damage in type 1 diabetes is present.\nANP infusion in healthy subjects caused a shift of plasma water and electrolytes from the circulation, with albumin escape as a secondary phenomenon" }, { "input": "List all approved indications for Glivec", "output": "CML - blast crisis, in accelerated phase, and in chronic phase after interferon failure or intolerance. Glivec received orphan drug status from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development on January 31, 2001, and accelerated approval from the FDA for the above three indications on May 10, 2001.\n\nGastrointestinal stromal tumor (GIST\nTreatment with adjuvant imatinib following surgical resection of localized Kit-positive GIST\n In locally advanced inoperable patients and metastatic patients, Imatinib is the standard treatment." }, { "input": "List all approved indications for Glivec", "output": "Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous neoplasm." }, { "input": "Which proteins induce inhibition of LINE-1 and Alu retrotransposition?", "output": "It was demonstrated that antiretroviral restriction factors, human APOBEC3 proteins A to H, differentially inhibit LINE-1 and Alu retrotransposition. The same effect was shown to be induced by the Aicardi-Gouti\u00e8res syndrome gene product SAMHD1." }, { "input": "Can chronological age be predicted by measuring telomere length?", "output": "No, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths." }, { "input": "What is a benefit of being g6PD-deficient?", "output": "Increased resistance to malaria, reduces the risk of coronary diseases, beneficial effect in terms of longevity" }, { "input": "Describe the usefulness of Macrostomum lignano in ion channel and stem cell research", "output": "Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. The flatworm Macrostomum lignano is a versatile model organism for addressing these topics. Experimental tools have been developed which demonstrate how manipulation of membrane potential influences regeneration in M. lignano." }, { "input": "Is there an association between c-reactive protein concentrations and outcomes of subarachnoid hemorrhage patients? ", "output": "Yes. Higher concentrations of C-reactive protein are associated with worse outcomes of subarachnoid hemorrhage patients." }, { "input": "Which drug is benserazide usually co-administered with?", "output": "Co-administration of L-Dopa with carbidopa or benserazide is the most effective symptomatic treatment for Parkinson Disease (PD)." }, { "input": "What is the inheritance pattern of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) caused by RYR2 mutations?", "output": "Autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT) was mapped to chromosome 1q42-43 with identification of pathogenic mutations in RYR2." }, { "input": "What is the INSURE procedure in premature babies.", "output": "The INSURE procedure includes intubation, surfactant administration, and extubation (InSurE). It is used to treat respiratory distress syndrome in newborns." }, { "input": "What is the INSURE procedure in premature babies.", "output": "InSurE stands for Intubation-surfactant-extubation and is a method in the treatment of neonatal respiratory distress syndrome (NRDS)" }, { "input": "Which are the available biomedical text mining tools for the detection of protein-protein interactions?", "output": "Protein-protein interactions (PPI) can be extracted from biomedical literature using text mining approaches. These approaches have been classified into two categories, the statistical calculation of the co-occurrence of proteins and the computational linguistic method. Moreover, bioinformatics methods based on sequence, structural, or evolutionary information have been developed to predict protein-protein interactions. The available state-of-the-art biomedical text mining tools are: eFIP (Extracting Functional Impact of Phosphorylation), a system for text mining of protein interaction networks of phosphorylated proteins; GeneView, a suite of state-of-the-art text-mining tools designed for the automated identification of protein\u2013protein interactions; PPI finder, a text mining tool for human protein-protein interactions based on computational linguistic methods. PPI Finder system consists of the Information Retrieval module and Information Extraction module; PreBIND and Textomy are two components of a biomedical literature-mining system optimized to discover protein-protein interactions using a support vector machine; BioMap system is optimized for the identification of protein-protein interactions from large biomedical literature datasets; Protopia searches for and integrates protein-protein interactions and the information about them contained in five different Protein Interaction Web Databases; STRING uses Natural Language Processing to extract a subset of semantically specified known and predicted protein-protein interactions." }, { "input": "Which are the available biomedical text mining tools for the detection of protein-protein interactions?", "output": "Several tools have been developed to detect protein-protein interactions (PPIs) by text mining the biomedical literature. Two main computational approaches used for this task are co-occurrence-based methods and Natural Language Processing methods. Biomedical text mining tools for PPI identification are the following (in alphabetical order): BioCreative Meta Server, BioMap, eFIP, Extracting Functional Impact of Phosphorylation, GeneView, HAPPI, Hidden Vector State model, iHop, LAITOR, OntoGene, OpenDMAP, PIE (Protein interaction information extraction system), PPI finder (Paired-PPI Finder), PPInterFinder, PPIs, PolySearch, PreBind and Textomy, Protopia, STRING, TafTalent." }, { "input": "How thyrocyte destruction is induced in autoimmune thyroiditis?", "output": "Thyrocytes from Hashimoto's thyroiditis (HT) glands, but not from nonautoimmune thyroids, expressed Fas (CD95), therefore autonomous interaction between thyrocyte Fas (CD95) and FasL (CD95L) has been proposed as a major mechanism of thyrocyte depletion in HT. Moreover, experimental evidence has showed that Infiltrating T Lymphocytes (ITLs) do not express significant amounts of FasL, suggesting that ITLs are not directly involved in thyrocyte destruction." }, { "input": "Do A-type lamins bind euchromatin or heterochromatin?", "output": "These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(\u03948-11/\u03948-11) mice" }, { "input": "Do A-type lamins bind euchromatin or heterochromatin?", "output": "Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebs. On the other hand, the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(\u03948-11/\u03948-11) mice" }, { "input": "Which is the most abundant membrane protein on Earth?", "output": "LHCII, the largest plant photosynthetic pigment-protein complex of photosystem II, is a most abundant membrane protein in living organisms and comprises approximately half of the pool of chlorophyll molecules in the biosphere." }, { "input": "Can RNASeq be used for the analysis of nascent transcripts?", "output": "Efficient cellular fractionation improves RNA sequencing analysis of mature and nascent transcripts from human tissues. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation." }, { "input": "Do RNA:DNA hybrids preferentially form in high or low GC regions?", "output": "Transcription through a GC-rich region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand." }, { "input": "Which are the most commonly reported pathological states associated with the formation of DNA G-quadruplexes?", "output": "There is a growing recognition for the profound role of G-quadruplexes in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) were recently shown to be caused by expansion of a (GGGGCC)n/(GGCCCC)n repeat in the C9ORF72 gene. Treatment with a G-quadruplex interactive ligand was shown to achieve antifibrotic action. G-quadruplex forming sequences have also been linked with ADAM10 a primary candidate for anti-amyloidogenic activity in Alzheimer's. A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia." }, { "input": "Are shadow enhancers associated with development?", "output": "Yes. Critical developmental control genes sometimes contain shadow enhancers that can be located in remote positions, including the introns of neighboring genes" }, { "input": "Does prudent diet reduce cardiovascular risk?", "output": "a high adherence to prudent diet is associated with reduced risk of CVD. The adherence to prudent diet was associated to a 28% lower risk of cardiovascular mortality and a 17% lower risk of all-cause mortality in a large cohort of healthy women" }, { "input": "Is Crohn's disease (CD) linked to the consumption of refrigerated food?", "output": "All findings point to refrigeration as a potential risk factor for Crohn's disease. Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home." }, { "input": "Which drugs are included in TAS-102?", "output": "TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5." }, { "input": "What is the most probable defect underlying triple negative breast cancer?", "output": "The most probable defect underlying triple negative breast cancer is BRCA1 dysfunction." }, { "input": "What causes erucism?", "output": "Erucism is defined as urtication by Lepidoptera larvae. It is a skin reaction to envenomation from certain poisonous caterpillar bristles. The hair on the dorsum of the last instar larvae of the moth may cause urticarial reactions (erucism) as well as eye problems and temporary blindness." }, { "input": "How does Hst5 (histatin 5) affect infections by Candida glabrata?", "output": "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva" }, { "input": "How does Hst5 (histatin 5) affect infections by Candida glabrata?", "output": "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. We found that Hst 54-15-Spd was significantly more effective in killing C. albicans and Candida glabrata than Hst 5 alone in both planktonic and biofilm growth and that Hst 54-15-Spd retained high activity in both serum and saliva. Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54-15), based upon our findings that C. albicans spermidine transporters are required for Hst 5 uptake and fungicidal activity." }, { "input": "How does Hst5 (histatin 5) affect infections by Candida glabrata?", "output": "Our results, taken together, demonstrated that histatin-5 possessed the fungicidal activity against Candida species other than C. glabrata. " }, { "input": "How does Hst5 (histatin 5) affect infections by Candida glabrata?", "output": "Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. Histatin 5, a human salivary protein with broad-spectrum antifungal activity, is remarkably ineffective against Candida glabrata. Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. Since Hst 5 requires fungal binding to cell wall components prior to intracellular translocation, reduced Hst 5 binding to C. glabrata may be the reason for its insensitivity. Hst 5 enters C. albicans cell through polyamine transporters Dur3p and Dur31p that are uncharacterized in C. glabrata. The crucial rate limiting step is reduced uptake that can be overcome by expression of C. albicans Dur proteins in C. glabrata." }, { "input": "Which enzyme is deficient in Krabbe disease?", "output": "Galactocerebrosidase is an enzyme that is deficient in Krabbe disease (also known as globoid-cell leukodystrophy). This leads to accumulation of psychosine (galactosylsphingosine) primarily in oligodendrocytes." }, { "input": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "output": "The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp. Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. " }, { "input": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "output": "Grass genes have dramatically fewer and much smaller CNSs than mammalian genes. The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp. Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. " }, { "input": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "output": "Yes. Conserved, UltraConserved and other classes of Constrained Noncoding Sequences have been found in plant genomes." }, { "input": "Which is the localization of the RIFIN family of proteins?", "output": "Plasmodium falciparum rifin proteins are mainly surface-expressed. Data has shown that while A-type RIFINs were found to be associated with the parasite and transported to the surface of infected erythrocytes via Maurer's clefts, B-type RIFINs appeared to be mostly retained inside the parasite." }, { "input": "What are the current treatments for generalised anxiety disorder in teenagers?", "output": "Cognitive-behavioral treatment (CBT) - both in individual and in group treatment\nRandomised, placebo controlled trials have found Sertraline efficacious for GAD in adults, children and adolescents.\nWhile both CBT and SSRIs are beneficial, some evidence suggests that the effects of CBT may be more long lasting." }, { "input": "Can tetracycline affect tooth formation?", "output": "Tetracycline is incorporated in the teeth during their formation and leads to their permanent staining. A definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days." }, { "input": "Is there any genetic determinant of hair pigmentation that could be useful in forensic analyses?", "output": "Yes, there are at least 12 genes associated with human hair color variation such as: TYR, TYRP1, OCA2, SLC45A2, SLC24A5, MC1R, ASIP and KITLG." }, { "input": "What is the suggested clinical management of Fanconi anemia?", "output": "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential.In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity" }, { "input": "What is the suggested clinical management of Fanconi anemia?", "output": "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity. In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. " }, { "input": "What is the suggested clinical management of Fanconi anemia?", "output": "Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential." }, { "input": "What is the suggested clinical management of Fanconi anemia?", "output": "Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity. In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Hematopoietic stem cell transplantation is the only proven cure for the hematopoietic manifestations of FA and aggressive lifelong surveillance for solid tumors is essential. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. " }, { "input": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) cause sudden cardiac death?", "output": "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death." }, { "input": "Does Apolipoprotein E (ApoE) have anti-inflammatory activity?", "output": "Yes. ApoE has anti-inflammatory activity" }, { "input": "Which drugs acting via bradykinin system are effective for treatment of ACE-inhibitor-induced angioedema?", "output": "Icatibant and ecallantide are medication acting via bradykinin system that are used for treatment of ACE-inhibitor-induced angioedema." }, { "input": "Is the ACE inhibitor indicated for lung cancer treatment?", "output": "No, the angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents. On the contrary, it has been suggested that they decrease the risk of some cancers, although available data are conflicting. One study proposes that captopril could be a promising option for the treatment of lung cancer. Furthermore, angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models" }, { "input": "Which forms of cancer is the Tpl2 gene associated with?", "output": "Tpl2/Map3K8, also known as tumor progression locus 2 has been identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. Types of cancer associated with Tpl2 include skin and epithelial cancers, ADI prostate cancer, gastric and colon adenocarcinomas, colitis-associated cancer (CAC), breast cancer, Hodgkin lymphomas, nasopharyngeal carcinomas and several types of T-cell neoplasias." }, { "input": "What are the indications for hydrochlorothiazide?", "output": "Hydrochlorothiazide is a diuretic, often used in combination with others. Hydrochlorothiazide are used to treat hypertension. Hydrochlorothiazide has been shown to decrease diastolic blood pressure." }, { "input": "Are genes symmetrically distributed between leading and lagging DNA strand in bacteria?", "output": "In most bacteria, genes are preferentially encoded on the leading strand than on the lagging strand. This avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand. Head-on collisions are more deleterious than codirectional collisions, and may lead to replication fork arrest and genomic instability. Genes of some functional categories such as ribosome have higher preferences to be on the leading strands, while genes of other functional categories such as transcription factor have higher preferences on the lagging strands. Strand-biased gene distribution correlates with replication-associated purine asymmetry and the presence or absence of polC. Especially essential and highly transcribed genes and genes whose expression is important for fitness are more preferentially situated at the leading strand in bacteria." }, { "input": "What hand deformities do patients with Apert syndrome present with?", "output": "In patients with Apert syndrome, the hands demonstrate many disturbances of soft tissue and bony structures. These include a short thumb with radial clinodactyly, complex syndactyly with a bony fusion involving the index, long and ring fingers, symphalangism and simple syndactyly of the fourth web space. The soft tissue anomalies involve the intrinsic muscles, the extrinsic tendon insertions and the neurovascular bundles." }, { "input": "Is c-myc subject to regulation by the circadian clock?", "output": "Yes, the expression of c-myc is regulated by the circadian clock protein Per2." }, { "input": "What disease is Velcade (bortezomib) mainly used for?", "output": "Velcade (bortezomid), a proteasome inhibitor drug indicated for multiple myeloma (MM) treatment. Velcade is also approved for the treatment of patients with mantle cell lymphoma." }, { "input": "Which genes are thought to be involved in medulloblastoma development?", "output": "Medulloblastomas are the most frequent malignant brain tumors affecting children. Disease development has been suggested to be associated with a significant number of genes, such as PTCH1, SUFU, PTEN, CREBBP, PTEN, MYT1L, NFIA, NFIB, TEAD1, TGIF2, IGF2, PCDH10, BMI1, MYC, OTX2, RASSF1A, HIC1, and CASP8." }, { "input": "What is the prevalence of short QT syndrome?", "output": "The prevalence of short QT syndrome is low and varies between 0.01% and 0.1%" }, { "input": "Which sports have a risk for commotio cordis?", "output": "Participation in sports such as baseball, football, soccer, cricket, hockey and lacrosse has a risk for commotio cordis." }, { "input": "is there an increase in ultrasound comets after intense exercise?", "output": "Strenuous exercise and exercise perfomed in extreme conditions provoke increase in interstitial pulmonary water content as shown by the increased number of ultrasuond comets" }, { "input": "Describe Hot water reflex epilepsy.", "output": "Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. HWE can be symptomatic of focal cortical malformation, and few cases were reported. Intermittent clobazam prophylaxis prior to head water bath might be a preferred mode of treatment of pure HWE." }, { "input": "What are the breath test biomarkers of pulmonary tuberculosis", "output": "Nitric oxide, urea, volatile organic compounds, hydrogen peroxide and end products of lipid peroxidation are the breath test biomarkers of pulmonary tuberculosis." }, { "input": "What types of DNA mutations are induced by 2-hydroxy-dATP (2-OH-dATP)?", "output": "2-hydroxy-dATP mainly elicits G:C --> A:T transitions, and, to a lesser extent, G:C --> T:A transversions The induction of G:C --> T:A transversions by 2-OH-dATP indicates the formation of G*2-OH-dATP pairs. 2-OH-dATP also induces tandem (CC --> TT) mutations. Altogether, 2-OH-dATP induces both transition and transvertion mutations, such as A:T --> G:C, A:T --> C:G and G:C --> T:A mutations." }, { "input": "Which diseases can be treated with Afamelanotide?", "output": "Afamelanotide was ivestigated for treatment of erythropoietic protoporphyria, vitiligo, Hailey-Hailey disease, acne vulgaris, polymorphic light eruption, prevention of actinic keratoses in organ transplant recipients and nonmelanoma skin cancer." }, { "input": "Which is the mechanism used by bacteria to induce tumors in Arabidopsis?", "output": "The bacteria Agrobacterium tumefaciens infects Arabidopsis, as well as other plants, and induces the formation of tumors by integrating the transferred-DNA (T-DNA) region of the Ti-plasmid into the plant nuclear genome." }, { "input": "Can cffDNA be used for non-invasive testing?", "output": "Yes, cell-free fetal DNA (cffDNA) has made non-invasive prenatal testing possible." }, { "input": "List features of the Perry syndrome.", "output": "Perry syndrome is a familial parkinsonism associated with central hypoventilation, mental depression, and weight loss." }, { "input": "Which is the main calcium binding protein of the sarcoplasmic reticulum?", "output": "Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR)." }, { "input": "Which is the main calcium binding protein of the sarcoplasmic reticulum?", "output": "Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR). " }, { "input": "Is the UGT1A1*28 polymorphism associated with irinotecan response in Caucasians?", "output": "Yes, it has been shown that the polymorphism UGT1A1*28 is associated with irinotecan response in Caucasians." }, { "input": "For which diseases members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics?", "output": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)." }, { "input": "For which diseases members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics?", "output": "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)" }, { "input": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "output": "SMN interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6." }, { "input": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "output": "yes" }, { "input": "Do U6-associated proteins Lsm4 and Lsm6 interact with SMN?", "output": "SMN was found to interact with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6." }, { "input": "List anti-amyloid-beta monoclonal antibodies that have been investigated in clinical trials for treatment of Alzheimer disease.", "output": "Ponezumab, solanezumab and bapineuzumab are humanized antiamyloid beta (A\u03b2) monoclonal antibodies that have been designed for treatment of Alzheimer disease." }, { "input": "List anti-amyloid-beta monoclonal antibodies that have been investigated in clinical trials for treatment of Alzheimer disease.", "output": "Bapineuzumab\nSolanezumab\nPonezumab\nGantenerumab" }, { "input": "Does MVIIA and MVIIC bind to the same calcium channel?", "output": "No, the omega-conotoxin MVIIC blocks P/Q-type calcium channels with high affinity and N-type calcium channels with low affinity, while the highly homologous omega-conotoxin MVIIA blocks only N-type calcium channels." }, { "input": "What is the idea behind the fractal globule that has been proposed as a model of chromatin conformation in the nucleus of a cell?", "output": "The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10 Mb (Lieberman-Aiden et al. 2009). The fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus is distinct from the more commonly used globular equilibrium model and emphasizes topological constraints as a primary factor driving formation of chromosomal territories." }, { "input": "What is the idea behind the fractal globule that has been proposed as a model of chromatin conformation in the nucleus of a cell?", "output": "The fractal globule is a compact polymer state that emerges during polymer condensation as a result of topological constraints which prevent one region of the chain from passing across another one. This long-lived intermediate state was introduced in 1988 (Grosberg et al. 1988) and has not been observed in experiments or simulations until recently (Lieberman-Aiden et al. 2009). Recent characterization of human chromatin using a novel chromosome conformational capture technique brought the fractal globule into the spotlight as a structural model of human chromosome on the scale of up to 10\u00a0Mb (Lieberman-Aiden et al. 2009). The fractal globule, a self-similar compact polymer conformation where the chain is spatially segregated on all length scales, has been proposed to result from a sudden polymer collapse. This state has gained renewed interest as one of the prime candidates for the non-entangled states of DNA molecules inside cell nuclei " }, { "input": "Which anticancer drugs target human topoisomerase II?", "output": "Etoposide (VP-16) and Teniposide (VM-26) are effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Doxorubicin, Daunorubicin and Aclarubicin are anthracyclins that act as DNA topoisomerase II inhibitors and may be used in combination. Benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity. F14512 is a polyamine-containing epipodophyllotoxin derivative that acts as an inhibitor of DNA topoisomerase II. Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II. \nAmong topoisomerase II inhibitors, the cytostatic potency was by decreasing order: mitoxantrone; doxorubicin, which was slightly greater than DuP 941, azatoxin; DuP 937; and amsacrine, which was much greater than VP-16" }, { "input": "What is SHAPE-Seq?", "output": "SHAPE-Seq is a high-throughput technique that can simultaneously measure quantitative, single nucleotide-resolution secondary and tertiary structural information for hundreds of RNA molecules of arbitrary sequence. SHAPE-Seq combines selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry with multiplexed paired-end deep sequencing of primer extension products. This generates millions of sequencing reads, which are then analyzed using a fully automated data analysis pipeline, based on a rigorous maximum likelihood model of the SHAPE-Seq experiment. SHAPE-Seq has the ability to accurately infer secondary and tertiary structural information, detect subtle conformational changes due to single nucleotide point mutations, and simultaneously measure the structures of a complex pool of different RNA molecules. SHAPE-Seq thus represents a powerful step toward making the study of RNA secondary and tertiary structures high throughput and accessible to a wide array of scientific pursuits, from fundamental biological investigations to engineering RNA for synthetic biological systems. SHAPE-Seq v2.0 is a 'universal' method that can obtain reactivity information for every nucleotide of an RNA without having to use or introduce a specific reverse transcriptase priming site within the RNA. It is a highly reproducible method, with reactivity data that can be used as constraints in RNA folding algorithms to predict structures on par with those generated using data from other SHAPE methods. SHAPE-Seq v2.0 is expected to be broadly applicable to understanding the RNA sequence-structure relationship at the heart of some of life's most fundamental processes." }, { "input": "Which are the known inhibitors of the TPL2/MAP3K8 protein?", "output": "[1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles were the first Tumor Progression Loci-2 (Tpl2) kinase inhibitors. 4-alkylamino-[1,7]naphthyridine-3-carbonitriles are also known to inhibit Tpl2 function as well as quinoline-3-carbonitrile derivatives, thieno[3,2-d]pyrimidines and 2,4-disubstituted thieno[2,3-c]pyridines, indazoles, 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles and generally molecules belonging to the wide categories of quinoline-3-carbonitriles, indazoles and thieno-pyrimidines." }, { "input": "Which are the known inhibitors of the TPL2/MAP3K8 protein?", "output": "Honokiol\nThieno[3,2-d]pyrimidines and thieno[2,3-c]pyridine\nQuinoline-3-carbonitrile derivatives (8-halo-4-(3-chloro-4-fluoro-phenylamino)-6-[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles; 8-bromo-4-(3-chloro-4-fluorophenylamino)-6-[(1-methyl-1H-imidazol-4-yl)methylamino]quinoline-3-carbonitrile; 4-alkylamino-[1,7]naphthyridine-3-carbonitrile; 1,7-naphthyridine-3-carbonitriles)\nIndazoles\nLuteolin\n1,7-naphtyridine-3-carbonitrile" }, { "input": "What is the mode of inheritance in Fanconi anemia?", "output": "Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked " }, { "input": "What is the mode of inheritance in Fanconi anemia?", "output": "Fanconi anemia (FA) is a rare inherited syndrome. So far, fifteen genetic subtypes have been distinguished. The mode of inheritance for all subtypes is autosomal recessive, except for FANCB, which is X-linked." }, { "input": "Describe the involvement of conserved noncoding sequences in the regulation of Hox genes.", "output": "Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes. The b-paralogs of the duplicated fugu Hox clusters are virtually devoid of unique ancient CNEs. Elephant shark and human Hox clusters have lost fewer ancient CNEs. If these ancient CNEs are indeed enhancers directing tissue-specific expression of Hox genes, divergence of their sequences in vertebrate lineages might have led to altered expression patterns and presumably the functions of their associated Hox genes. When compared, the amphioxus Hox cluster with the human HoxA, HoxB, HoxC, and HoxD clusters were found to have several conserved noncoding regions, both in intergenic and intronic regions. This suggests that the regulation of Hox genes is highly conserved across chordates, consistent with the similar Hox expression patterns in vertebrates and amphioxus." }, { "input": "Give an overview of visualizing genomes with oligopaint FISH probes.", "output": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases. Coupled with fluorescence in situ hybridization (FISH) and a bioinformatic platform, this technology could be extended to any organism whose genome has been sequenced. The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads. The method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of chromosomal regions. It is anticipated that this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes." }, { "input": "What is Targeted Chromatin Capture (T2C)?", "output": "Targeted Chromatin Capture (T2C) is an efficient, easy, and affordable with high (restriction fragment) resolution tool to address both genome compartmentalization and chromatin-interaction networks for specific genomic regions at high resolution for both clinical and non-clinical research." }, { "input": "What is Targeted Chromatin Capture (T2C)?", "output": "Significant efforts have recently been put into the investigation of the spatial organization and the chromatin-interaction networks of genomes. T2C provides an unbiased view of the spatial organization of selected loci at superior resolution (single restriction fragment resolution, from 2 to 6 kbp) at much lower costs than Hi-C due to the lower sequencing effort." }, { "input": "What are the reported adverse effects of topical minoxidil?", "output": "Typical side effects of this topical treatment include irritative dermatitis going along with pruritus, erythema, scaling and dryness, which occur especially at the onset of the therapy. In some cases, allergic contact dermatitis or exacerbation of seborrheic dermatitis has been reported.\nHypertrichosis is a well-recognized adverse effect of therapy with either oral or topical minoxidil.\nWe observed an as yet unreported \"polymyalgia syndrome\" in four otherwise healthy males whose sole medication was topically applied minoxidil. They experienced fatigue, weight loss and severe pain in the shoulders and pelvic girdle, suggesting connective tissue disease. Three patients had a transient rise in liver enzymes, while other laboratory analyses remained normal. Tritanomaly was detected in two patients who underwent systematic color vision testing.\nA case of central serous chorioretinopathy after application of topical minoxidil solution.\nA case of acute myocardial infarction associated with topical use of minoxidil (RiUP) for treatment of baldness.\nCompared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2).\nTwo of our patients developed smoking intolerance during treatment with topical minoxidil for androgenital alopecia." }, { "input": "Is arimoclomol a co-inducer of the heat shock response?", "output": "Yes, arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress." }, { "input": "What memory problems are reported in the \" Gulf war syndrome\"", "output": "memory loss" }, { "input": "Describe Heyde syndrome.", "output": "Classical Heyde syndrome is described as the association of aortic stenosis, bleeding gastrointestinal angiodysplasia and secondary anemia. A deficiency of high molecular weight multimers of von Willebrand factor (type 2A von Willebrand disease) provides the link between this association." }, { "input": "Has silicon been used in treatment of incontinence ?", "output": "Yes" }, { "input": "Which proteins compose the error prevention GO (8-oxo-G) system in Pseudomonas putida?", "output": "In P. putida (Pseudomonas putida) the error prevention GO (8-oxo-G) system is composed of MutY, MutM, and MutT enzymes." }, { "input": "List five applications of machine learning algorithms in medical diagnosis.", "output": "Machine learning technology is well suited for the induction of diagnostic and prognostic rules and solving of small and specialized diagnostic and prognostic problems. The medical diagnostic knowledge can be automatically derived from the description of cases solved in the past. In several medical domains we actually applied machine learning algorithms. Typically, the automatically generated diagnostic rules achieved the same or slightly better diagnostic accuracy than physicians specialists. There many several application of machine learning algorithms in medical diagnosis such as Brain glioma progression, Microarray classification, Mass spectral proteomics, Lymph disease classification and Parkinson's disease." }, { "input": "Does the 3D structure of the genome remain stable during cell differentiation?", "output": "Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation. The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state. The relation between alterations in chromatin structure and changes in gene expression during cell differentiation has served as a paradigm to understand the link between genome organization and function. Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation. Architectural proteins orchestrate higher-order chromatin organization through the establishment of interactions between regulatory elements across multiple spatial scales. The regulation of these proteins, their interaction with DNA, and their co-occurrence in the genome, may be responsible for the plasticity of 3D chromatin architecture that dictates cell and time-specific blueprints of gene expression." }, { "input": "Does the 3D structure of the genome remain stable during cell differentiation?", "output": "Chromatin insulators have emerged as one of the central components of the genome organization tool-kit across species. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development." }, { "input": "What is the main biological function of the CRISPR-CAS9 genome editing system?", "output": "The CRISPR/Cas9 system (clustered regularly interspaced short palindromic repeats/CRISPR-associated) has recently emerged as an efficient and simple tool for site-specific engineering of eukaryotic genomes. The CRISPR/Cas9 system has attracted significant attention for its potential to transform genome engineering. It has been shown that the RNA-guided Cas9 nuclease can be employed to engineer the Drosophila genome, and that these modifications are efficiently transmitted through the germline. The CRISPR/Cas9 system has been reported to efficiently induce targeted gene disruption and homologous recombination in both prokaryotic and eukaryotic cells. The CRISPR/Cas9 system has been used to create knock-out alleles with great efficiency, and it has also been employed in knock-in of DNA cassettes at defined loci via homologous recombination (HR). The ease and efficiency of the CRISPR/Cas9 system with limited off-target effects make it a powerful genome engineering tool for in vivo studies." }, { "input": "Does dronedarone affect T3 and T4 levels?", "output": "NO." }, { "input": "What is 2d 4d ratio in athletes.", "output": "Lower 2D:4D ratio was reported to be lower in handball players, kabaddi players, varsity athletes, football players, soccer players and rugby players. Low 2D:4D ratio correlates with better performance and with enhanced sporting prowess, particularly with regard to activities requiring endurance and dependent upon slow-twitch muscles." }, { "input": "What is the association between moon cycle and rupture risk of intracranial aneurysms?", "output": "The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH." }, { "input": "What is the role of brain natriuretic peptide in traumatic brain injury patients ?", "output": "Brain natriuretic peptide concentrations are elevated in patients with traumatic brain during the acute phase and correlate with poor outcomes. In traumatic brain injury patients higher brain natriuretic peptide concentrations are associated with more extensive SAH, elevated ICP and hyponatremia. Brain natriuretic peptide may play an adaptive role in recovery through augmentation of cerebral blood flow." }, { "input": "Which molecule is targeted by Daratumumab?", "output": "Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma." }, { "input": "Which molecule is targeted by Daratumumab?", "output": "Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity." }, { "input": "Which mutation is associated with PLMS (periodic limb movements in sleep)?", "output": "missense substitution, Met1Val (M1V), was identified in the DCX gene" }, { "input": "Which DNA repair system is involved in HNPCC?", "output": "In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development." }, { "input": "Mention the only available genomics and developmental transcriptomics resource for the urochordate Oikopleura dioica", "output": "OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/) is a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates. OikoBase facilitates retrieval and mining of a variety of useful genomics information and will provide a valuable resource for research in chordate development, genome evolution and plasticity and the molecular ecology of this important marine planktonic organism." }, { "input": "What is the association between NT-proBNP and cognitive function?", "output": "Greater NT-proBNP serum concentration is associated with poorer cognitive function and cognitive decline. In community-dwelling older adults, greater NT-proBNP levels were strongly associated with poor cognitive function independently from age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and previous cardiovascular disease. However, other authors did not find an association between NT-proBNP and severe cognitive impairment (SCI)." }, { "input": "List functional roles of the FtsZ protein.", "output": "Four major roles of FtsZ have been characterized: cell elongation, GTPase, cell division, and bacterial cytoskeleton." }, { "input": "Intetumumab has been tested in clinical trials for treatment of which cancers?", "output": "Intetumumab has been tested in clinical trials for treatment of prostate cancer, melanoma and angiosarcoma." }, { "input": "Is there any evidence of dysregulated long non coding RNAs and Alzheimer's disease?", "output": "It is becoming increasingly evident that long non coding RNAs (lncRNAs) play a role on neurodegenerative diseases such as Alzheimer (AD). BACE1-AS, GDNFOS and 17A are examples of these lncRNAs. In some instances those lncRNAs are embedded or transcribed from the opposite strand of coding genes." }, { "input": "Which hormone receptor function is altered in patients with Donohue syndrome?", "output": "Donohue syndrome (leprechaunism) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. This syndrome is characterized by excessive hyperglycemia with hyperinsulinism, pre- and postnatal growth retardation, distinct dysmorphism and early death. Progressive obstructive cardiomyopathy and renal tubular dysfunction have been described in patients with Donohue syndrome. Milder form of insulin resistance due to insulin receptor gene mutation is coined as Rabson-Mendenhall syndrome." }, { "input": "Does triiodothyronine (T3) has cardiac angiogenic effects?", "output": "T3-induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF-BB, PDGFR-\u03b2 and downstream activation of Akt.\nT(3) administration restored TRbeta mRNA expression level in AAC hearts to the control level.\nTRbeta in the coronary ECs regulates capillary density during cardiac development, and down-regulation of TRbeta results in coronary microvascular rarefaction during pathological hypertrophy." }, { "input": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "output": "The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers.The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM." }, { "input": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "output": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy.The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events." }, { "input": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "output": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy.The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers." }, { "input": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "output": "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias and sudden death in idiopathic DCM." }, { "input": "Are BRAF mutations common in melanoma?", "output": "Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors. BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid." }, { "input": "Are BRAF mutations common in melanoma?", "output": "Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K. BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma." }, { "input": "Is it possible to determine the proteome of a formalin fixed and paraffin embedded (FFPE) tissue?", "output": "Yes, advances in sample preparation has enabled the proteomic analysis of formalin-fixed and paraffin-embedded tissues." }, { "input": "What is known about type D personality trait in cancer patients?", "output": "Reported prevalence rates of type D personality ranges from 19% to 22% in patients with cancer. In patients with cancer, Type D personality is associated with poor quality of life and mental health. Cancer patients with a Type D personality as compared with non-Type D patients perceive that they receive less information, report less satisfaction with the amount of received information, believe that their illness has significantly more serious consequences, will last significantly longer, and experience significantly more symptoms that they attribute to their illness. Also, they are more concerned about their illness, and their disease more often influences them emotionally. Also, Type D cancer patients are at an increased risk for comorbidity burden and increased health care utilization." }, { "input": "List available tools for genomic visualisation in comparative genomics", "output": "Insyght, Genomicus and Sockeye." }, { "input": "Which species may be used for the biotechnological production of itaconic acid?", "output": "In 1955, the production of itaconic acid was firstly described for Ustilago maydis. Some Aspergillus species, like A. itaconicus and A. terreus, show the ability to synthesize this organic acid and A. terreus can secrete significant amounts to the media. Itaconic acid is mainly supplied by biotechnological processes with the fungus Aspergillus terreus. Cloning of the cadA gene into the citric acid producing fungus A. niger showed that it is possible to produce itaconic acid also in a different host organism." }, { "input": "Which types of cancer can be recognized and treated by the use of immunotherapy?", "output": "When normal cells turn into cancer cells, some of the antigens on their surface change. These cells, like many body cells, constantly shed bits of protein from their surface into the circulatory system. Often, tumor antigens are among the shed proteins.\nThese shed antigens prompt action from immune defenders, including cytotoxic T cells, natural killer cells, and macrophages. According to one theory, patrolling cells of the immune system provide continuous bodywide surveillance, catching and eliminating cells that undergo malignant transformation. Tumors develop when this immune surveillance breaks down or is overwhelmed.\nA new approach to cancer therapy uses antibodies that have been specially made to recognize specific cancers such as Melanoma, Leukaemia, Lung Cancer, Colorectal Cancer, Breast Cancer, Head Cancer and Pancreatic Cancer." }, { "input": "What is the typical rash associated with gluten ?", "output": "Dermatitis herpetiformis is a lifelong, gluten-sensitive, blistering skin disease with pathognomonic immunoglobulin (Ig)A deposits in the papillary dermis." }, { "input": "Which proteins constitute the methyl-directed mismatch repair system (MMR) in bacteria?", "output": "The mismatch repair system (MMR) recognizes and corrects mismatched or unpaired bases caused mainly by DNA polymerase, and contributes to the fidelity of DNA replication in living cells. In bacteria, the methyldirected mismatch repair (MMR) is comprised of MutS and MutL proteins, encoded by the mutS/L operon." }, { "input": "Is aganglionic megacolon a feature of Down syndrome?", "output": "Down syndrome (DS) is recognized by characteristic facial features, intellectual disability, and an increased risk for cardiac malformations and duodenal atresia. Recently, Hirschsprung disease (HSCR), or congenital aganglionic megacolon, has been seen more often among patients with DS." }, { "input": "Which is the vector of Louping ill virus?", "output": "Louping ill virus (LIV) belongs to the mammalian tick-borne virus group of the genus Flavivirus which cause central nervous system disease. LIV infects the red grouse Lagopus lagopus scoticus, causing high mortality. LIV is transmitted by the tick Ixodes ricinus." }, { "input": "Which is the vector of Louping ill virus?", "output": "Deer are the key hosts of the vector (Ixodes ricinus) that transmits LIV to red grouse Lagopus lagopus scoticus, causing high mortality. (PMID: 22939093)" }, { "input": "Does HuR protein regulate the splicing process?", "output": "Recent research demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce different isoforms, such as SIRT1 full-length and SIRT1-\u2206Exon8 variants. Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances: HuR increased SIRT1-\u2206Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-\u2206Exon8 mRNA levels. This study provides novel insight into how the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental implications for understanding the critical and multifunctional roles of SIRT1. Further, endothelial-specific Elavl1 knockout mice exhibited reduced revascularization after hind limb ischemia and tumor angiogenesis in oncogene-induced mammary cancer, resulting in attenuated blood flow and tumor growth, respectively." }, { "input": "Does HuR protein regulate the splicing process?", "output": "HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA" }, { "input": "Does HuR protein regulate the splicing process?", "output": "Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition. HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances. Overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern." }, { "input": "Is Titin the largest single protein molecule found in Nature?", "output": "Titin, is definitely the largest protein in the body, with a molecular weight of 3 million Dalton and composed of 27,000 amino acids. Titin is the largest protein known to date and acts as a mechanosensor that regulates muscle protein expression in a sarcomere strain-dependent fashion." }, { "input": "Is Titin the largest single protein molecule found in Nature?", "output": "Yes. Titin, the largest protein in the human body, is well known as a molecular spring in muscle cells and scaffold protein aiding myofibrillar assembly. Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions." }, { "input": "Is Titin the largest single protein molecule found in Nature?", "output": "Titin is the largest protein known to date and acts as a mechanosensor that regulates muscle protein expression in a sarcomere strain-dependent fashion.Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere." }, { "input": "Is Titin the largest single protein molecule found in Nature?", "output": "Titin is the largest protein known, and is essential for organising muscle sarcomeres.The giant sarcomere protein titin/connectin is the largest protein known to date." }, { "input": "what is the role of MEF-2 in cardiomyocyte differentiation?", "output": "The myocyte enhancer factor-2 (MEF2) proteins are MADS-box transcription factors that are essential for differentiation of all muscle lineages but their mechanisms of action remain largely undefined. MEF2C expression initiates cardiomyogenesis, resulting in the up-regulation of Brachyury T, bone morphogenetic protein-4, Nkx2-5, GATA-4, cardiac alpha-actin, and myosin heavy chain expression. Inactivation of the MEF2C gene causes cardiac developmental arrest and severe downregulation of a number of cardiac markers including atrial natriuretic factor (ANF). BMP-2, a regulator of cardiac development during embryogenesis, was shown to increase PI 3-kinase activity in cardiac precursor cells, resulting in increased expression of sarcomeric myosin heavy chain (MHC) and MEF-2A. Furthermore, expression of MEF-2A increased MHC expression in a PI 3-kinase-dependent manner. Other studies showed that Gli2 and MEF2C proteins form a complex, capable of synergizing on cardiomyogenesis-related promoters. Dominant interference of calcineurin/mAKAP binding blunts the increase in MEF2 transcriptional activity seen during myoblast differentiation, as well as the expression of endogenous MEF2-target genes. These findings show that MEF-2 can direct early stages of cell differentiation into a cardiomyogenic pathway." }, { "input": "Which are the main components of mTORC1?", "output": "The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth and is a key target for therapeutic intervention in cancer. Two complexes of mTOR have been identified: complex 1 (mTORC1), consisting of mTOR, Raptor (regulatory associated protein of mTOR) and mLST8 (mammalian lethal with SEC13 protein 8) and complex 2 (mTORC2) consisting of mTOR, Rictor (rapamycin-insensitive companion of mTOR), Sin1 (stress-activated protein kinase-interacting protein 1), and mLST8." }, { "input": "What is the the Menzerath-Altmann law?", "output": "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics. The random breakage and variants keeping genome size and chromosome number independent raise no serious objection to the relevance of correlations consistent with Menzerath-Altmann law across taxonomic groups and the possibility of a connection between human language and genomes through that law. " }, { "input": "What is the the Menzerath-Altmann law?", "output": "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics" }, { "input": "What is the the Menzerath-Altmann law?", "output": "Menzerath-Altmann law is a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics." }, { "input": "What is the the Menzerath-Altmann law?", "output": "Recently, a random breakage model has been proposed to explain the negative correlation between mean chromosome length and chromosome number that is found in many groups of species and is consistent with Menzerath-Altmann law, a statistical law that defines the dependency between the mean size of the whole and the number of parts in quantitative linguistics " }, { "input": "Which receptor(s) recognize lysosomal hydrolases in trans-Golgi network (TGN)?", "output": "The majority of lysosomal hydrolases in trans-Golgi network (TGN) are specifically recognized by mannose 6-phosphate (M6P) receptors (MPRs), which ensure their transport to the endosomal/lysosomal system. Other receptors can also carry lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system. These M6P alternative receptors are the lysosomal integral membrane protein (LIMP-2) and the multi-ligand receptor sortilin. These reseptors enable a mannose-6-phosphate-independent pathway from TGN to lysosomes." }, { "input": "List the diseases that can be treated using Vedolizumab.", "output": "Ulcerative colitis and Crohn's disease are inflammatory bowel diseases that have been successfully treated with Vedolizumab, a gut-selective, anti-inflammatory monoclonal antibody." }, { "input": "Can clonidine be used to reduce agitation in children.", "output": "Yes, clonidine is effective in prevention of post-anesthesia agitation in children." }, { "input": "Which value of nuchal translucency thickness is set as the threshold for high-risk for Down Syndrome?", "output": "NT is physiological for a measurement < 3 mm but the incidence of chromosomal abnormalities (essentially trisomies 21, 18 and 13) increases when NT > or = 3 mm. As women aged, this upper NT threshold value changed according to gestational age. In women aged 35 to 37 years, combined prenatal screening was always positive when NT exceeded 2.8 mm, 3.0 mm, and 3.4 mm at 11, 12, and 13 weeks of gestation, respectively." }, { "input": "Does ventriculoperitoneal shunt improve normal pressure hydrocephalus?", "output": "Yes" }, { "input": "Does Serca2a bind PLN in the heart?", "output": "Yes, Serca2a bind PLN in the heart." }, { "input": "What is the function of the spliceosome complex?", "output": "The excision of introns from nascent eukaryotic transcripts is catalyzed by the spliceosome, a highly complex and dynamic macromolecular machine composed of RNA and protein." }, { "input": "Is there any role for long noncoding RNAs in adipogenesis?", "output": "Yes. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and CCAAT/enhancer-binding protein \u03b1 (CEBP\u03b1). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, numerous lncRNAs are functionally required for proper adipogenesis." }, { "input": "Which genes code for the alpha subunit of the DNA polymerase III in most Firmicutes?", "output": "Bacterial DNA polymerase III is the primary complex of DNA replication. In most Firmicutes, which are low-GC, gram-positive bacteria, the alpha subunit of their DNA polymerase III is encoded by polC and dnaE. DnaE is widely conserved in most bacteria, while PolC is present mainly in Firmicutes clade." }, { "input": "Is there any research that relates the function of Notch Signaling with Alzheimer Disease?", "output": "Notch signaling is an evolutionarily conserved pathway, which is fundamental for neuronal development and specification. In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury" }, { "input": "Describe the known functions for the prothymosin alpha c-terminal peptide?", "output": "Prothymosin alpha (ProT\u03b1) (encoded in human by the PTMA gene) is a ubiquitous, highly acidic nuclear polypeptide. During early apoptosis, proT\u03b1 is cleaved by activated caspase-3, with a primary attach site being D99, close to its carboxyl-terminus. The role of the cleaved decapeptide -- proT\u03b1(100-109) -- is not fully understood. proT\u03b1(100-109), which contains the nuclear localization signal (NLS) for ProT\u03b1, has been demonstrated to have immunostimulatory properties, such as to stimulate lymphocytes and neutrophils and induce dendritic cell maturation." }, { "input": "Was modafinil tested for schizophrenia treatment?", "output": "Yes. Modafinil has been shown to improve attention, memory, executive function and antipsychotic-induced parkinsonism in patients with schizophrenia. However, some authors have failed to demonstrate beneficial action of modafinil for schizophrenia." }, { "input": "What is the role of the Ada O6-alkylguanine alkyltransferase in bacteria?", "output": "The Ada O6-methylguanine-DNA methyltransferase is a multifunctional protein, product of the ada gene. Ada functions in DNA repair by direct dealkylation of alkylated DNA lesions, such as the toxic, mutagenic and carcinogenic O6-alkylguanine (O6-AlkG) and O4-alkylthymine (O4-AlkT) which are restored to guanine and thymine. Ada accepts stoichiometrically the alkyl group from O6-alkylguanine in DNA at the Cys-321 residue and from alkyl phosphotriester at the Cys-69 residue. When methylated at Cys-69, Ada becomes a transcriptional activator of the genes in the ada regulon, including its own. The ada gene controls the inducible resistance to alkylation mutagenesis and killing (the adaptive response). Ada alkyltransferase (ATase) is induced by exposure to low doses of methylating agents. During exponential growth, Ada removes lesions responsible for G:C to A:T transitions and G:C to C:G transversions, while in stationary populations it removes lesions causing G:C to A:T and A:T to G:C transitions, and G:C to C:G, A:T to C:G, and A:T to T:A transversions. Thus, Ada protein acts both as a positive regulator of the ada response and as a DNA repair enzyme." }, { "input": "List the neurotransmitters that are metabolized by MAOA.", "output": "The monoamine oxidase-A (MAOA) gene plays a vital role in the metabolism of neurotransmitters, e.g, serotonin, norepinephrine, and dopamine." }, { "input": "What is the effect of enamel matrix derivative on pulp regeneration?", "output": "EMD increased the osteogenic potential of hDPCs. The expression levels of osteogenesis-related genes, such as ALP, DSPP, BMP, and OPN were also upregulated. In addition, the expression levels of odontogenesis-related transcription factors Osterix and Runx2 were upregulated. Proliferated pulp tissue partly filled the space initially occupied by EMDgel and isolated masses within the proliferated pulp tissue." }, { "input": "Is depression associated with poor prognosis of brain tumor patients?", "output": "Yes. In brain tumor patients depression is associated with shorter survival and worse functional outcomes." }, { "input": "Super-SILAC is a method used in quantitative proteomics. What is the super-SILAC mix?\n(SILAC: Stable Isotopic labelling by aminoacids in cell culture)", "output": "The Super-SILAC mix consists of the combination of multiple SILAC-labeled cell lines." }, { "input": "What is an acceptable sequence coverage(depth) required for human whole-exome sequencing?", "output": "A medium depth may be considered as 8x while the most common values vary between 30x and 60x. Values more than 75x or even up to 125x may be considered for the investigation of rare disease variants." }, { "input": "To what extent does HPV vaccination reduce the risk for cervical cancer?", "output": "The most effective strategy therein was vaccination of 12-year-olds, plus a temporary 12-24-year-old catch-up program covering both sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical precancer, and genital wart incidence was reduced by 84-98% during year 50 following vaccine introduction. Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%" }, { "input": "Have germline variants been associated to colorectal cancer?", "output": "Yes. Whole-genome sequencing (WGS) applied to medical research has revealed how germline variants and mutations may be associated with colorectal cancer. It is likely that this level of knowledge can be translated into predictions of predisposition." }, { "input": "Can Alzheimer's disease related miRNAs be detected in patients' blood?", "output": "Yes. It has been demonstrated that blood miRNAs could be useful as biomarkers in Alzheimer's disease." }, { "input": "Which is the clinical meaning of the presence of delayed enhancement in patients with hypertrophic cardiomyopathy?", "output": "Occurrence of myocardial fibrosis in hypertrophic cardiomyopathy is associated with left atrial and ventricular dysfunction as well as with the severity of heart failure symptoms and arrhythmic risk factors." }, { "input": "What disease is mirtazapine predominantly used for?", "output": "Mirtazapine is predominantly used in the treatment of major depression." }, { "input": "Is it possible to visualize subtahalamic nucleus by using transcranial ultrasound?", "output": "Yes, it has been shown that it is possible to visualize subtahalamic nucleus by using transcranial ultrasound. Transcranial ultrasound is safe and reliable method that can be employed to monitor lead location and intraoperative visualization of deep-brain stimulation (DBS) electrodes." }, { "input": "Is cancer related to global DNA hypo or hypermethylation?", "output": "DNA hypermethylation and hypomethylation are independent processes and appear to play different roles in tumor progression. Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of particular CpG islands. Tumors have reduced levels of genomic DNA methylation and contain hypermethylated CpG islands." }, { "input": "Do thyroid hormone receptors change after brain injury?", "output": "thyroid hormone receptors increase after brain injury" }, { "input": "What is known about efficacy of the high dose intravenous ascorbate in the treatment of cancer patients?", "output": "It was reported that ascorbate, given orally and intravenously at doses of up to 10\u2009g/day, was effective in the treatment of cancer. However, double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. Pharmacologic actions of ascorbate against cancer cells remain to be fully understood. It is thought that high dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide. High dose intravenous ascorbate (IVC) may be able to modulate inflammation, which in turn might improve outcomes for cancer patients. IVC may serve as a safe, adjunctive therapy in clinical cancer care" }, { "input": "Alpha-spectrin and beta-spectrin subunits form parallel or antiparallel heterodimers?", "output": "Alpha and beta spectrin subunits form antiparallel spectrin heterodimers by lateral association." }, { "input": "Is gastro esophageal reflux related to burning mouth syndrome?", "output": "No data indicate causal connection between gastro esophageal/laryngopharyngeal(LPR) reflux disease and the occurrence of intraoral burning sensations" }, { "input": "Which is the protein (antigen) targeted by anti-Vel antibodies in the Vel blood group?", "output": "Disruption of SMIM1 causes the Vel- blood type. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel- cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. (PMID: 23505126)" }, { "input": "Which is the protein (antigen) targeted by anti-Vel antibodies in the Vel blood group?", "output": "SMIM1" }, { "input": "Which are the subtypes of Pfeiffer syndrome?", "output": "Pfeiffer syndrome is divided into three clinical subtypes." }, { "input": "Which are the subtypes of Pfeiffer syndrome?", "output": "Pfeiffer syndrome is divided into three clinical subtypes. Type 1 \"classic\" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull." }, { "input": "Is thrombophilia related to increased risk of miscarriage?", "output": "Thrombophilia has been found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period. In particular there is an increased risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia. When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management." }, { "input": "Intact macromolecular assemblies are analysed by advanced mass spectrometry. How large complexes (in molecular weight) have been studied?", "output": "2.3 megadalton" }, { "input": "What is targeted by Palbociclib?", "output": "Necitumumab is a fully human IgG(1) monoclonal antibody directed at the epidermal growth factor receptor (EGFR). It is used for treatment of nonsmall cell lung cancer." }, { "input": "Which peptide plays a pivotal role in human cystatin C fibrillization?", "output": "Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm developed in our lab. This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization." }, { "input": "Which peptide plays a pivotal role in human cystatin C fibrillization?", "output": "Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm. This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization." }, { "input": "What is ChiRP-seq (Chromatin Isolation by RNA Purification sequencing)?", "output": "ChiRP-seq (Chromatin Isolation by RNA Purification sequencing) is a method where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide." }, { "input": "What is the use of MammaPrint and Oncotype DX?", "output": "The MammaPrint and Oncotype DX assays are used to predict breast cancer recurrence risk and guide adjuvant chemotherapy decisions." }, { "input": "Does nifedipine inhibit L-type calcium channels?", "output": "Yes, nifedipine is a typical blocker of L-type calcium channels." }, { "input": "Is there any data to suggest that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients?", "output": "Yes, there are studies demonstrating that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients. However, some studies have failed to demonstrate symptom improvement following TRH administration." }, { "input": "Is there any data to suggest that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients?", "output": "Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion. " }, { "input": "How can DUF families be deciphered?", "output": "The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization. These genes, as most others, can be grouped into families based on sequence similarity. The PFAM database currently contains over 2,200 such families, referred to as domains of unknown function (DUF). \nCritically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge. \nIn a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families." }, { "input": "Which genes does thyroid hormone receptor beta1 regulate in the heart?", "output": "\u03b2-MHC, HCN4, KCND2/3, SERCA, TRbeta1, alpha-MHC" }, { "input": "Can siRNA affect response to afatinib treatment?", "output": "When afatinib was combined with an EGFR-specific siRNA there was a strong biological effect on growth inhibition and induction of apoptosis." }, { "input": "What is the gold standard treatment for Iatrogenic male incontinence?", "output": "The artificial urethral sphincter has represented, until today, the gold standard but, in the recent years, sling systems have been investigated as minimally invasive alternative options." }, { "input": "Which is the main CHEK2 genetic variant, thought to be involved in familial breast cancer?", "output": "CHEK2 1100delC mutation is recurrently detected in the general population and is thought to confer a moderate risk for breast cancer." }, { "input": "Is there an association between presenteeism and depression?", "output": "Yes. Presenteeism is associated with depression. Remission of depression is associated with improvement of presenteeism." }, { "input": "Which hormone abnormalities are common in Williams syndrome", "output": "Elevated Thyrotropin - TSH\nLow FT4\nGrowth Hormone deficiency\nCalcitonin deficiency\nElevated Prolactin\nElevated Cortisol\nElevated Oxytocin\nElevated Vasopressin" }, { "input": "What is the treatment of choice for gastric lymphoma?", "output": "The treatment of choice for localized primary GI lymphoma is controversial. Complete surgical resection may increase the chance of complete remission, but mortality and relapse rates might be higher than those observed with combination chemotherapy alone.\nIn early stages of disease, H. pylori eradication alone may lead to complete lymphoma remission in up to 75% of cases. Nonresponder or locally advanced lymphoma should be treated with radiation therapy." }, { "input": "Which assays can be used for detecting DNA fragmentation resulting from programmed cell death (apoptosis)?", "output": "The biochemical hallmark of apoptosis is internucleosomal DNA cleavage into oligonucleosome-length fragments. Measurement of apoptosis-associated internucleosomal DNA fragmentation through determination of the percentage of fragmented DNA by electrophoresis or centrifugation of whole cell lysates is by far the most common means of quantifying apoptosis. DNA fragmentation due to apoptosis can also be identified using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragments (TUNEL), in situ end labeling (ISEL) of the genomic DNA in fragmented nuclei, and measurement of cytosolic histone-bound DNA fragments (cell death ELISA assays)." }, { "input": "Does triiodothyronine stimulate red blood cell sodium potassium pump?", "output": "An inverse correlation between this enzymatic action and free triiodothyronine (FT3) levels.\nThe effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity in red blood cells may be different in vivo and in vitro." }, { "input": "Which hormone concentrations are altered in patients with the Allan\u2013Herndon\u2013Dudley syndrome?", "output": "Thyroid hormone concentrations are altered in patients with the Allan-Herndon-Dudley syndrome. In particular, high serum T3 levels and low-normal to low T4 serum levels are common in the Allan-Herndon-Dudley syndrome. It is, an X linked condition, is characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia in combination." }, { "input": "Is selumetinib effective in thyroid cancer?", "output": "Yes, selumetinib was shown to be effective treatment for thyroid cancer. Selumetinib may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. Clinical efficacy of selumetinib was also investigated in other solid tumors." }, { "input": "Where in the cell does the proteins S100A4 and p53 interact ?", "output": "S100A4 interacts with p53 in the cell nucleus." }, { "input": "What are the applications of a Dermaroller ?", "output": "Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.\nMicroneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy." }, { "input": "What are the applications of a Dermaroller ?", "output": "Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy." }, { "input": "What are the applications of a Dermaroller ?", "output": "Microneedling therapy seems to be a simple and effective treatment option for the management of atrophic facial scars. Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery. Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy. " }, { "input": "Are immune cells affected in Amyotrophic Lateral Sclerosis?", "output": "In ALS T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it." }, { "input": "Are immune cells affected in Amyotrophic Lateral Sclerosis?", "output": "The intrathymic injection of donor spleen cells into antilymphocyte serum (ALS)-treated mice induces significant prolongation of donor skin grafts. To elucidate possible mechanisms involved in the induction of unresponsiveness in ALS-treated mice after intrathymic injection of donor spleen cells, we have analysed the reactivity of lymphoid cells from unresponsive mice in various ways. Here, we show that in the mutant superoxide dismutase 1 G93A (mSOD1) mouse model of ALS, the levels of natural killer T (NKT) cells increased dramatically, and T-cell distribution was altered both in lymphoid organs and in the spinal cord relative to wild-type mice. Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma." }, { "input": "Are immune cells affected in Amyotrophic Lateral Sclerosis?", "output": "Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma" }, { "input": "Are OATP1B1 and OATP1B3 associated with bilirubin transport?", "output": "Yes, OATP1B1 and OATP1B3 are involved in the transport of bilirubin." }, { "input": "What is the mechanism of action of eprotirome?", "output": "Eprotirome belongs to thyromimetics and has selective TR\u03b21 activity. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity." }, { "input": "What is the role of music therapy in coma patients.", "output": "Several studies have shown that music can boost cognitive functions in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. Active improvised music therapy may offer an adjuvant form of treatment in the early rehabilitation of severe brain-injured patients." }, { "input": "Which is the causative agent of malaria?", "output": "Four Plasmodium species commonly infect humans (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale). Plasmodium falciparum infects about 5-10% of the world human population per year and it is the causative agent of the most severe and lethal form of malaria. P. falciparum causes fatal cerebral malaria and is responsible for most deaths, particularly in pregnant women and children under the age of five. P. falciparum is transmitted to the human host by Anopheles mosquitoes and is the most tremendous malaria vector in sub-Saharan Africa. Plasmodium vivax is the causative agent of benign malaria in more temperate climates of the world. Plasmodium gallinaceum is the main bird malaria causative agent and Plasmodium yoelli is the principle rodent malaria agent." }, { "input": "What is the major adverse effect of adriamycin(doxorubicin)?", "output": "Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy " }, { "input": "What is the major adverse effect of adriamycin(doxorubicin)?", "output": "Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy. In spite of the routine use of this drug its major adverse effect, the dose-dependent cardiotoxicity, cannot be prevented yet. Cardiotoxicity is a major adverse effect of the anthracycline antibiotics and can be acute or chronic." }, { "input": "What is GDF10?", "output": "The growth/differentiation factor-10 (GDF-10) is a new member of the transforming growth factor-beta (TGF-beta) superfamily. It is highly related to bone morphogenetic protein-3 (BMP-3) and often referred to as BMP3b. The nucleotide sequence of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight of approximately 52,000. The GDF-10 polypeptide contains a potential signal sequence for secretion, a putative RXXR proteolytic processing site, and a carboxy-terminal domain with considerable homology to other known members of the TGF-beta superfamily. GDF10 is found primarily in murine uterus, adipose tissue, and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA was present in both neonatal and adult bone samples, with higher levels being detected in calvaria than in long bone. These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect." }, { "input": "Is thyroid hormone therapy indicated in patients with heart failure?", "output": "There are several experimental and clinical evidences of the potential benefits of Thyroid hormone replacement therapy in heart failure. Initial clinical data showed also a good safety profile and tolerance of TH replacement therapy in patients withheart failure. \nHowever currently there is no indication to treat patients with heart failure withTHreplacementtherapy." }, { "input": "Is there a mouse model for Fanconi anemia?", "output": "A number of mouse models have already been generated with a targeted disruption of several Fanconi anemia genes, such as FANCA, FANCF, FANCM, FANCD1, etc." }, { "input": "Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?", "output": "There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials " }, { "input": "Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?", "output": "Yes. In the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival." }, { "input": "Which is the most common editing modification in eukaryotic mRNA?", "output": "One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation." }, { "input": "Is Rac1 involved in cancer cell invasion?", "output": "A number of signalling pathways have been found to converge to and activate Rac1, which, in turn, activates a number of downstream targets to control actin-cytoskeleton rearrangements at membrane ruffles, as well as formation and activity of lamellipodia, to regulate the migratory processes leading to cell invasion." }, { "input": "Which are the APOBEC3 protein family members able to inhibit Vif-deficient HIV-1 replication?", "output": "APOBEC3G, APOBEC3F, APOBEC3DE, APOBEC3A, and APOBEC3H haplotypes II, V, and VII, provide protection against Vif-deficient HIV-1, through hypermutation of the viral genome, inhibition of reverse transcription, and inhibition of viral DNA integration into the host genome." }, { "input": "Is the gene SLC6A2 associated with orthostatic intolerance?", "output": "Yes, variants of the SLC6A2 (or NET) gene are associated with orthostatic intolerance." }, { "input": "Other than protein coding potential, what features set apart long non-coding RNAs from protein coding genes?", "output": "Compared to protein coding genes, long non-coding RNAs (lncRNAs) display a bias towards two-exon transcripts. They are predominantly localized in the chromatin and nucleous. They are lower expressed and display a more tissue-specific expression pattern. LncRNAs are overall more weakly conserved than protein coding genes." }, { "input": "Is macitentan an ET agonist?", "output": "No, macitentan is anendothelin receptor antagonist." }, { "input": "Can we use platelet biomarkers to study Alzheimer's disease?", "output": "Yes, platelet biomarkers can be used to study Alzheimer's disease." }, { "input": "Which genetic defects are observed in Prader-Willi syndrome?", "output": "The predominant genetic defects in Prader-Willi syndrome are 15q11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy, or rare imprinting mutations, combined with monoallelic expression of the paternal alleles." }, { "input": "What is the most likely age of diagnosis of Crohn's disease (CD)?", "output": "Crohn's disease has a bimodal age distribution of disease onset diagnosis. The peaks (20 and 50 years) may represent different phenotypes or different genetic and/or environmental influences between younger- and older-onset individuals. When the age-related incidence of Crohn's disease was plotted for all countries from which such data were available, the peaks of greatest case frequency occurred at ages 15 to 25 years and paralleled a similar peak representing the number of Peyer's patches as a function of age. For those with biologic use, average age at time of diagnosis of Crohn's disease was 32.3 \u00b1 12.2 years, compared with 43.7 \u00b1 16.3 years for those who had not received biologics (P = 0.005)." }, { "input": "How does thyroid hormone affect insulin resistance in the heart?", "output": "T3 potentiates insulin signaling and improves insulin sensitivity. In addition, T3 lowers blood glucose in a model of type 2 diabetes. TRalpha P398H mutation is associated with insulin resistance. Circulating T(1)AM is produced from thyroid hormones and is found to be increased in diabetic patients." }, { "input": "Which are the state-of-the-art computational tools for the prediction of gene fusion events?", "output": "Gene fusion detection - also known as the 'Rosetta Stone' method - involves the identification of fused composite genes in a set of reference genomes, which indicates potential interactions between its un-fused counterpart genes in query genomes. A few methods/tools and computational pipelines for the detection of gene fusion events have been introduced. The basic steps followed in these approaches consist of (i) all-against-all sequence comparison, (ii) detection of non-overlapping similarities of two genes/proteins (components) to a single gene/protein (composite), and optionally (iii) elimination of putative spurious hits (e.g. due to promiscuous domains) achieves via clustering based on sequence similarity and examining dense regions of the resulting graph or by querying the PFAM database. An advantage of gene fusion analysis is that functional associations can be predicted even in cases of genes of unknown function. Due to the computationally intense nature of these approaches, precompiled data of this type are often organized in specialized databases. Tools and databases developed for this purpose include (in alphabetical order): fdfBLAST, FusionDB, InPrePPI, (Integrated method for Prediction of Protein-Protein Interactions), MosaicFinder, Phydbac2, PLEX, Predictome, Rosetta Stone method, STRING." }, { "input": "Is CHEK2 involved in cell cycle control?", "output": "CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage." }, { "input": "Describe mechanism of action of PLX3397 drug.", "output": "PLX3397 works by inhibiting colony-stimulating-factor-1 receptor (CSF1R)." }, { "input": "What disease is small bowel lymphoma commonly associated with", "output": "Small bowel lymphoma is commonly associated with celiac disease." }, { "input": "Are the proteins Erbin (LAP2) and Merlin cooperating?", "output": "Yes, Erbin and Merlin are cooperating." }, { "input": "Which molecule is targeted by a monoclonal antibody Secukinumab?", "output": "Secukinumab (AIN457) is a fully human anti-interleukin-17A monoclonal antibody that neutralizes interleukin-17A." }, { "input": "Which calcium/calmodulin dependent protein phosphatase is involved in the activation of the family of NFAT transcription factors (Nuclear Factors of Activated T cells)?", "output": "The activity of NFAT proteins is tightly regulated by the Ca(2+)/calmodulin-dependent protein phosphatase 2B/calcineurin (CaN).Dephosphorylation of NFAT by CaN is required for NFAT nuclear localization." }, { "input": "Is abdominal pain a common symptom in autism?", "output": "Yes, although there are no precise data. There is data that Lactase deficiency, not associated with intestinal inflammation or injury, is common in autistic children and may contribute to abdominal discomfort, pain and observed aberrant behavior." }, { "input": "Are cyclophilins ubiquitously expressed?", "output": "Yes, \tcyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily." }, { "input": "Are adenylyl cyclases always transmembrane proteins?", "output": "Adenylyl cyclases exists both as transmembrane and soluble proteins." }, { "input": "What histone trimethylation has been associated to RNA splicing?", "output": "Mostly H3K36me3 but there is some evidence that H3K4me3 may also play a role in splicing" }, { "input": "What was the purpose of the FANTOM4 project?", "output": "The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments." }, { "input": "Does low T3 negatively affect prognosis of patients after cardiac surgery?", "output": "Low cardiac output syndrome after cardiac surgery for congenital heart diseases is associated with decreased T3\nLow T3 concentrations are associated with occurrence of post operative atrial fibrillation\nLow T3 concentrations are inversely correlated with the days of post operative hospitalization" }, { "input": "Which deficiency is the cause of restless leg syndrome", "output": "Iron deficiency (low serum ferritin) is a recognized cause for RLS. Further, in the striatum of subjects with restless legs syndrome, the dopamine transporter is decreased, which leads to impaired dopaminergic neurotransmission. There is also a report of magnesium deficiency underlying RLS." }, { "input": "List the results of mutated casein kinase 1 epsilon. ", "output": "Mutation in casein kinase 1 epsilon results in a short circadian period, abnormal entrainment to light cycles, and potentiated resetting responses to light.\nMutations of CK1epsilon found in breast cancer can suppress Wnt/beta-catenin as well as promote the Wnt/Rac-1/JNK and Wnt/NFAT pathways, thus contributing to breast cancer development via effects on cell adhesion and migration.\nCsnk1e is regulating not only the timing of sleep, but also the REM sleep amount and NREM sleep architecture." }, { "input": "Does neuroglobin has neuroprotective properties in the setting of traumatic brain injury?", "output": "Yes, neuroglobin has neuroprotective properties in the setting of traumatic brain injury." }, { "input": "What gene test is recommended for clopidogrel?", "output": "The genetic test recommended for clopidogrel is CYP2C19 genotyping." }, { "input": "What is the role of eteplirsen in DMD patients?", "output": "AVI-4658(eteplirsen) induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection." }, { "input": "Describe clinical presentation of Parkinsonism with dementia of Guadeloupe syndrome.", "output": "Parkinsonism with dementia of Guadeloupe is a unique combination of levodopa-resistant parkinsonism, tremor, myoclonus, hallucinations, REM sleep behavior disorder and fronto-subcortical dementia. Based on the presence or the absence of supranuclear gaze palsy, two subgroups of patients can be distinguished." }, { "input": "Does the concentration of protein HIF-1\u03b1 increase after the administration of the cytoprotective prodrug\"amifostine\" (ethyol) ?", "output": "The key-protein that when associated with HREs leads to the activation of all of these genes, is identified as\u201cHypoxia Inducible Factor-1\u201d (HIF1). It is a heterodimer composed of two subunits (IIF1a 120kDa and HIF-1b 91-94kDa), both of which belong to the group of \"basic helix-loop-helix\" (bHLH)-Pas proteins. The heterodimer HIF1 and IIF2 increase in the cytoplasm of cells exposed to hypoxia." }, { "input": "Which diseases can Oncotype DX be used for?", "output": "Oncotype can be used for predicting breast cancer and colon cancer recurrence." }, { "input": "Which are the DNA (cytosine-5-)-methyltransferases inhibitors?", "output": "DNA (Cytosine-5-)-methyltransferases are a family of enzymes that methylate DNA at the C5 position of cytosine residues. Given that methylation of tumour suppressor gene promoters leads to carcinogenesis, inhibition of DNA (Cytosine-5-)-methyltransferases is a promising strategy for the treatment of cancer. There are several inhibitors of DNA (Cytosine-5-)-methyltransferases that uses different modes of action: 5-azacytidine (5-aza-CR, Vidaza\u00ae), 5-azadeoxycytidine (5-aza-CdR, decitabine, Dacogen\u00ae), 5-azacytosine (ZCyt), 5-fluorodeoxycytidine (FdC), 5,6-dihydro-5-azacytosine (DZCyt), 4'-thio-2'-deoxycytidine, hydralazine, 2-(1H)-pyrimidinone riboside (zebularine), 2-(1H)-pyrimidinone (zebularine aglycon), procaine, procainamide, psammaplin A, and RSC133, a new synthetic derivative of indoleacrylic acid/indolepropionic acid." }, { "input": "Describe armoured brain syndrome.", "output": "Armoured brain syndrome is defined by calcified chronic subdural haematoma." }, { "input": "Which are the main histone modifications associated with enhancers?", "output": "Histone 3 lysine 4 mono- (H3K4me1) and di-methylation (H3K4me2) are the main post-transcriptional histone modifications related to enhancer activity." }, { "input": "Which are the main histone modifications associated with enhancers?", "output": "Using H3K4me2 as a mark for active enhancers (PMID: 22270183) Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances (PMID: 19021773) The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region (PMID: 19021773) H3K4 methylation to monovalent and bivalent domains (PMID: 20621055)" }, { "input": "Which are the main histone modifications associated with enhancers?", "output": "H3K4 methylation to monovalent and bivalent domains. The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region. Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances. Using H3K4me2 as a mark for active enhancers. " }, { "input": "What is the role of Thyrotropin Releasing Hormone in the treatment of comatose patients?", "output": "Thyrotropin Releasing Hormone and its analogs are used for treatment of comatose patients. In animal models, Thyrotropin Releasing Hormone and its analogs have been shown to improve the disturbance of consciousness caused by head concussion and pentobarbital. This analeptic action is attributable to stimulation of cholinergic neurons in the septo-hippocampal area and to the presence of terminals containing TRH in the lateral septum and TRH receptors concentrated especially in the medial septum and diagonal band of Broca. It has also been suggested that TRH localized in the pineal gland has a part in activating the neuronal mechanisms of arousal. Associated with the arousal effect and especially evident in variously originated shock conditions are the activating effects of TRH on vegetative functions (body temperature, circulation, the gastrointestinal tract). These stimulatory activities on the CNS were the rationale for therapeutic use of TRH in the initial treatment of coma due to brain trauma. Thyrotropin Releasing Hormone has been shown to induce recovery in comatose patients with extrapontine and pontine myelinosis syndromes." }, { "input": "Do Conserved noncoding elements act as enhancers?", "output": "An important percentage of noncoding elements conserved across distant species shows enhancer activity and other forms of regulatory functionality." }, { "input": "Can the iPS cell technology be used in Fanconi anemia therapy?", "output": "iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications in Fanconi anemia." }, { "input": "Which drug is considered as the first line treatment of fibromyalgia?", "output": "Pregabalin is, therefore, a valuable option in the first-line treatment of patients with fibromyalgia." }, { "input": "What are the signatures of aggressive periodontitis?", "output": "Aggressive periodontitis does not differ from chronic periodontitis from a microbial profile point of view but there are distinctive immunological signatures, including a higher expression in IgG against most periodontal pathogens and a more intense regulatory mechanism of metabolic processes." }, { "input": "With which complexes is the protein SUS1 associated?", "output": "Sus1/ENY2 is a component of the SAGA and TREX-2 complexes" }, { "input": "Can Preimplantation Genetic Diagnosis (PGD) be used for gender selection?", "output": "Preimplantation Genetic Diagnosis can be used for gender selection." }, { "input": "What is the principle of ATAC (Assay for Transposase-Accessible Chromatin) technique?", "output": "ATAC-seq (Assay for Transposase-Accessible Chromatin) is an assay for transposase-accessible chromatin using sequencing, based on direct in vitro transposition of sequencing adaptors into native chromatin. ATAC is a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution." }, { "input": "What is the principle of ATAC (Assay for Transposase-Accessible Chromatin) technique?", "output": "To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. In conclusion, we show that FAIRE-seq and ATAC-seq based open chromatin profiling, combined with motif discovery, is a straightforward approach to identify functional genomic regulatory regions, master regulators, and gene regulatory networks controlling complex in vivo processes. We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis." }, { "input": "What is the principle of ATAC (Assay for Transposase-Accessible Chromatin) technique?", "output": "We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis " }, { "input": "Which are the main NMD factors in Saccharomyces cerevisiae?", "output": "Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that accelerates the degradation of mRNAs containing premature translation termination codons. This quality control pathway depends on the NMD-specific factors, Upf1p, Upf2p/Nmd2p, and Upf3p, as well as the two release factors, eRF1 and eRF3 (respectively designated Sup45p and Sup35p in yeast). NMD activation is also enabled by the absence of the poly(A)-binding protein, Pab1p, downstream of a termination event" }, { "input": "Which are the main NMD factors in Saccharomyces cerevisiae?", "output": "In Saccharomyces cerevisiae, rapid degradation of nonsense-containing mRNAs requires the three nonsense-mediated mRNA decay (NMD) factors, Upf1p, Nmd2p, and Upf3p." }, { "input": "Which are the main NMD factors in Saccharomyces cerevisiae?", "output": "In addition to their well-documented roles in the promotion of nonsense-mediated mRNA decay (NMD), yeast Upf proteins (Upf1, Upf2/Nmd2, and Upf3) also manifest translational regulatory functions, at least in vitro, including roles in premature translation termination and subsequent reinitiation" }, { "input": "Which histone marks are deposited by Set7?", "output": "Set7 is H4K20 monomethyltransferase. Upregulation of PR-Set7 expression upon loss of HCF-1 leads to improper mitotic H4-K20 methylation. Set7 (or some variant) has also been reported to perform mono-methylation on lysine-4 of H3." }, { "input": "Has proteomics been used in the study of the dry eye syndrome?", "output": "Yes, tears obtained from patients with the dry eye syndrome have been analyzed using different proteomic technologies." }, { "input": "What is the indication for isradipine?", "output": "Isradipine is safe and effective when administered long-term in the treatment of hypertensive patients" }, { "input": "What is the indication for isradipine?", "output": "The calcium antagonist isradipine is used for hypertensive therapy." }, { "input": "List non-surgical treatment modalities that are included in the Stupp protocol.", "output": "Radiotherapy and chemotherapy are non-surgical treatment modalities that are included in the Stupp protocol. This protocol is widely used for treatment of glioblastoma." }, { "input": "Which genes are associated with Ehlers-Danlos syndrome type I/II?", "output": "It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively" }, { "input": "Which genes are associated with Ehlers-Danlos syndrome type I/II?", "output": "Ehlers-Danlos syndrome (EDS) type I (the classical variety) is a dominantly inherited, genetically heterogeneous connective-tissue disorder. Mutations in the COL5A1 and COL5A2 genes, which encode type V collagen, have been identified in several individuals. Most mutations affect either the triple-helical domain of the protein or the expression of one COL5A1 allele It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively " }, { "input": "Which genes are associated with Ehlers-Danlos syndrome type I/II?", "output": "It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the \u03b11 and the \u03b12-chain of type V collagen, respectively." }, { "input": "Which genes are associated with Ehlers-Danlos syndrome type I/II?", "output": "Ehlers-Danlos syndrome (EDS) type I (the classical variety) is a dominantly inherited, genetically heterogeneous connective-tissue disorder. Mutations in the COL5A1 and COL5A2 genes, which encode type V collagen, have been identified in several individuals. Most mutations affect either the triple-helical domain of the protein or the expression of one COL5A1 allele " }, { "input": "Which factors are considered in the ABCD2 score?", "output": "Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes are included in the ABCD2 score, which is used to identify patients having a transient ischemic attack who are at high risk for imminent stroke." }, { "input": "Is Tuberous Sclerosis a genetic disease?", "output": "Tuberous sclerosis is a genetic disorder with an autosomal dominant pattern of inheritance, variable expressivity, and incomplete penetrance. Two thirds of TSC cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in approximately 20% of individuals diagnosed with the disease. So far it has been mapped to two genetic loci, TSC1 and TSC2.\nTSC1 encodes for the protein hamartin, is located on chromosome 9 q34 and was discovered in 1997. TSC2 encodes for the protein Tuberin, is located on chromosome 16 p13.3 and was discovered in 1993. TSC2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with TSC who also develop PKD in childhood. TSC2 has been associated with a more severe form of TSC. However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of TSC caused by TSC2 range from 55% to 80-90%." }, { "input": "Is Tuberous Sclerosis a genetic disease?", "output": "Yes, Tuberous Sclerosis is a genetic disease, caused by mutations in the TSC1 or TSC2 gene." }, { "input": "Does TRIM37 gene mutation causes Mulibrey nanism?", "output": "Yes, Mulibrey nanism is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity." }, { "input": "Have thyronamines effects on fat tissue?", "output": "thyronamines cause reduction of fat mass" }, { "input": "What is the genetic basis of progeria", "output": "Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome in around 90% of patients" }, { "input": "What type of DNA repair pathways is initiated by AlkA glycosylase?", "output": "The AlkA protein (3-methyladenine DNA glycosylase II protein) is a monofunctional DNA glycosylase that recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair (BER) pathway." }, { "input": "Is there any protein that undergoes both mono-ubiquitination and poly-ubiquitination?", "output": "Yes, there are some rare cases where a protein can be both mono-ubiquitinated and poly-ubiquitinated." }, { "input": "Which are the musculoskeletal manifestations of Marfan syndrome?", "output": "Musculoskeletal manifestations of Marfan syndrome include scoliosis, dural ectasia, pectus excavatum and carinatum, arachnodactyly, otto pelvis (protrusio acetabuli), dolichostenomelia and ligamentous laxity." }, { "input": "What is the \"Proteomic ruler\"?", "output": "The MS signal of histones can be used as a \"proteomic ruler\" because it is proportional to the amount of DNA in the sample, which in turn depends on the number of cells. As a result, our proteomic ruler approach adds an absolute scale to the MS readout and allows estimation of the copy numbers of individual proteins per cell." }, { "input": "What is the mechanism by which HIV-1-encoded Vif protein allows virus replication?", "output": "The HIV-1 Vif protein counteracts the antiviral activity of the APOBEC3 family by targeting the proteins for degradation through the ubiquitin-proteasome pathway. More specifically, Vif, serving as a substrate receptor, facilitates ubiquitination of APOBEC3 proteins by forming a Cullin5-based E3 ubiquitin ligase complex, which targets APOBEC3 proteins for rapid proteasomal degradation." }, { "input": "Which proteins are the different isoforms of the p38 MAP kinase?", "output": "The p38 Mitogen-Activated Protein (MAP) kinase, a serine/threonine kinase, is one of the best characterized kinases in the inflammatory process. There are four isoforms of the enzyme (p38alpha, p38beta, p38gamma and p38delta), which differ in tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates. Among the four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), the \u03b1-form is the most fully studied." }, { "input": "Which proteins are the different isoforms of the p38 MAP kinase?", "output": "The mammalian p38 mitogen-activated protein kinases (MAPKs) family is composed of four members (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), which are very similar in amino acid sequence but differ in their expression patterns." }, { "input": "Which proteins are the different isoforms of the p38 MAP kinase?", "output": "The mitogen-activated protein kinase (MAPK) p38 is a Ser/Thr kinase, originally isolated from lipopolysaccharide-stimulated monocytes. There are four isoforms of the enzyme (p38alpha, p38beta, p38gamma and p38delta), which differ in tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates. The p38 Mitogen-Activated Protein (MAP) kinase, a serine/threonine kinase, is one of the best characterized kinases in the inflammatory process. Among the four identified p38 isoforms (p38\u03b1, p38\u03b2, p38\u03b3, and p38\u03b4), the \u03b1-form is the most fully studied and plays a central role in the biosynthesis of the proinflammatory cytokines i.e. IL-1\u03b2 and TNF-\u03b1 at the translational and transcriptional levels. " }, { "input": "Are pseudogenes enriched with housekeeping protein families?", "output": "Yes, housekeeping families tend to be enriched with a large number of pseudogenes." }, { "input": "What is the mechanism of cementogenesis in pulp regeneration?", "output": "The dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone. Dental follicle cells attach to Hertwig's epithelial root sheath (HERS), and pulp cells in the cementum promoting cementogenesis. The temporospatial regulation of Wnt/\u00df-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts." }, { "input": "What is the mechanism of cementogenesis in pulp regeneration?", "output": "Our results indicate that persistent stabilization of \u00df-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. It is known that the dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone. Wnt/\u00df-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. New vital tissues can be regenerated in permanent canine teeth after pulpectomy and enlargement of the apical foramen. Constitutive stabilization of \u00df-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. These results suggest that temporospatial regulation of Wnt/\u00df-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/\u00df-catenin signaling may be important for the formation of dentin and cementum during tooth development. HERS cells played a role in the induction and maturation of cementum-like tissues formed by DF cells. Essential roles of Wnt/\u00df-catenin signaling in tooth morphogenesis have been well known. " }, { "input": "What are the reported adverse effects of gabapentin used in children?", "output": "Limited literature data, suggest that gabapentin may cause rash that is severe enough to necessitate discontinuation in a small percentage of children.\nIn a large survey of all age groups: The commonest adverse effects seen were somnolence, fainting, ataxia, nystagmus, tremor and headache, fatigue. However, their incidence was low and intensity mild. In a pediatric group only somnolence and dizziness were reported in 2 out of 33 patients.\nBehavioural adverse effects are more common in children with intellectual disability and attention deficit, worse in <10yo : hyperactivity, defiance, irritability, agitation, aggression, explosive outbursts, oppositional behavior, often warranting discontinuation of the medication." }, { "input": "What is the effect of ranolazine in diastolic heart failure?", "output": "Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current. Ranolazine is an innovative anti-ischemic and antianginal agent that reduces the Na-dependent Ca-overload, which improves diastolic tone and oxygen handling during myocardial ischemia. Furthermore, ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity." }, { "input": "Elaborate on the potential efficacy of gemcitabine for the treatment of recurrent, platinum-resistant epithelial ovarian cancer.", "output": "Gemcitabine is a novel agent that has shown consistent activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile. Because of its clinical and preclinical synergism with platinum analogs, gemcitabine has been combined with carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients. Gemcitabine and prolonged oral etoposide have shown reproducible single-agent activity in patients with platinum/paclitaxel-resistant ovarian cancer. The combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer. Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer. Gemcitabine plus endostar significantly improved the prognosis in patients with platinum-resistant recurrent ovarian cancer, especially in those with malignant effusion. Though the endostar cohort also improved median OS by 2.1 months, there was no statistically significant difference compared with gemcitabine alone cohort in this case." }, { "input": "How does Foxa transcription factor exhibits its pioneering function?", "output": "The conceptional framework of the mechanism of action of the FoxA proteins is that these 'pioneer factors' that can engage chromatin before other transcription factors. The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably. FoxA induces local DNA demethylation, nucleosome destabilization and binds to mitotic chromosomes. When associated with mitotic chromatin, FoxA may \"bookmark\" active genes and ensure their reactivation in postmitotic cells (epigenetic memory). About one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. The \"pioneer\" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and distinguish the factors with respect to their regulatory and mechanistic functions." }, { "input": "How does Foxa transcription factor exhibits its pioneering function?", "output": "FoxA proteins are pioneer transcription factors, among the first to bind chromatin domains in development and enable gene activity. There exists a hierarchy by which transcription factors can engage their target sites in chromatin, in that a subset of factors can bind transcriptionally silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is reflected, at least in part, in the developmental function of the factors. These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors." }, { "input": "Which are the 3 basic transcription factors that have been used for the direct reprogramming of fibroblasts into cardiomyocytes or cardiomyocyte like-cells?", "output": "Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We found that functional cardiomyocytes can be directly induced from fibroblasts by a combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5, in vitro and in vivo." }, { "input": "Which are the 3 basic transcription factors that have been used for the direct reprogramming of fibroblasts into cardiomyocytes or cardiomyocyte like-cells?", "output": "Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse cardiac fibroblasts in vitro and vivo by transduction of three transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT. " }, { "input": "Which are the 3 basic transcription factors that have been used for the direct reprogramming of fibroblasts into cardiomyocytes or cardiomyocyte like-cells?", "output": "Cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously." }, { "input": "What is the name of Bruton's tyrosine kinase inhibitor that can be used for treatment of chronic lymphocytic leukemia?", "output": "Ibrutinib is the covalent inhibitor of Bruton's tyrosine kinase that can be used for treatment of chronic lymphocytic leukemia (CLL). Ibrutinib has shown highly encouraging results in phase I/II trials in patients with treatment-naive, relapsed and refractory CLL even in the presence of high risk disease or poor prognostic markers. Ibrutinib demonstrated that Bruton's tyrosine kinase inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior. Ibrutinib has excellent activity in other B cell malignancies, including in particular mantle cell lymphoma and Waldenstrom macroglobulinemia." }, { "input": "Is physical performance influenced by thyroid hormone metabolism?", "output": "Yes." }, { "input": "Do plant genomes contain CpG islands?", "output": "In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at the 5 -terminus, share similarities with human genes having CpG islands " }, { "input": "Do plant genomes contain CpG islands?", "output": "Yes. In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster." }, { "input": "Describe the isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads, as applied for the case of the essential hematopoietic transcription factor GATA-1.", "output": "Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of the biotin/(strept)avidin system also offers the potential for the single-step capture of lower abundance protein complexes, such as transcription factor complexes. The identification of short peptide tags that are efficiently biotinylated by the bacterial BirA biotin ligase led to an approach for the single-step purification of transcription factor complexes by specific in vivo biotinylation tagging. A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry. This led to the characterization of several distinct GATA-1 complexes with other transcription factors and chromatin remodeling cofactors, which are involved in activation and repression of gene targets. Thus, BirA-mediated tagging is an efficient approach for the direct capture and characterization of transcription factor complexes." }, { "input": "Are high-flow nasal cannulae effective for treatment of preterm infants?", "output": "Yes. The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure for noninvasive respiratory support of preterm infants after extubation. However, the use of high-flow nasal cannulae in preterm infants was shown to be associated with a higher rate of reintubation, increased exposure to oxygen and longer duration of respiratory support. High-flow nasal cannulae are also effective for treatment of apnea of prematurity." }, { "input": "What are the molecular characteristics of the FAA (FANCA) cDNA?", "output": "The 5.5-kb cDNA of the FAA (FANCA) gene has an open reading frame of 4,368 nucleotides, whereas the FAA protein is predicted to have a molecular weight of approximately 163 kDa." }, { "input": "What are the skeletal muscle satellite cells?", "output": "Skeletal muscle satellite cells (SCs) are Pax7(+) myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury" }, { "input": "What are the skeletal muscle satellite cells?", "output": "Skeletal muscle satellite cells (SCs) are Pax7(+) myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury." }, { "input": "What is the role of neurogranin in Alzheimer's disease patients?", "output": "Dendritic protein neurogranin is markedly increased in cerebrospinal fluid in Alzheimer's disease patients. Neurogranin might reflect the neurodegenerative processes within the brain, indicating a role for neurogranin as a potential novel clinical biomarker for synaptic degeneration in AD.\nNeurogranin is important for synaptic plasticity and memory." }, { "input": "Does triiodothyronine play a regulatory role in insulin secretion from pancreas?", "output": "YES" }, { "input": "How many disulfide bridges has the protein hepcidin got?", "output": "Hepcidin contains eight cysteine residues that form four disulfide bridges." }, { "input": "What is the association between GERD and gluten ?", "output": "GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.\nFood intolerance is a common complaint amongst patients with functional gastrointestinal (GI) disorders (FGIDs), including those with irritable bowel syndrome (IBS), functional dyspepsia, as well as gastroesophageal reflux disease. There is a great interest in the role of a major dietary protein, gluten, in the production of symptoms...several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence" }, { "input": "Which are the major intramolecular phosphorylation sites of human Chk2 involved in cell cycle control?", "output": "The major phosphorylation sites of human Chk2 involved in cell cycle control are T68, S19, and S33/35." }, { "input": "Is the Histidine-Rich Calcium Binding protein (HRC) related to arrhythmias and cardiac disease?", "output": "Histidine-rich calcium binding protein (HRC) is a high capacity, low affinity Ca(2+) binding protein with a potential role in heart failure and arrhythmogenesis due to its activity as regulator of SR Ca(2+) uptake and Ca(2+) release.In addition, HRC null mice displayed a significantly exaggerated response to the induction of cardiac hypertrophy by isoproterenol compared to their wild-type littermates. A human genetic variant (Ser96Ala) in HRC has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy." }, { "input": "Which are the methods for in silico prediction of the origin of replication (ori) among bacteria?", "output": "Several in silico methods have been applied for prediction of the origin of replication (ori). DNA base composition asymmetry, such as GC skew, is the basis of numerous in silico methods used to detect the ori in prokaryotes. The Z curve analysis is also used for ori identification. Comparative genomics, by BLAST analyses of the intergenic sequences compared to related species have been applied in ori prediction. The finding of the dnaA gene and its binding sites, DnaA boxes, as well as the finding of the binding sites of other proteins, such as CtrA and IHF, are fundamental characteristics used for in silico prediction of the ori. Also, the localization of boundary genes, such as cell division cycle (cdc6) gene, and consensus origin recognition box (ORB) sequences have been employed for ori detection. The study of the gene order around the origin sequence and the distribution of the genes encoded in the leading versus the lagging strand are also used for in silico detection of the ori." }, { "input": "What is the use of emulsion PCR in Next Generation Sequencing?", "output": "Prior to Next Generation Sequencing reactions, DNA libraries are constructed, amplified with emulsion PCR, and enriched with the use of enrichment beads. The library samples are then loaded to a sequencing chip and analyzed on an NGS platform." }, { "input": "Can adult humans be induced to produce fetal hemoglobin?", "output": "Fetal hemoglobin, or foetal haemoglobin, is the main oxygen transport protein in the human fetus during the last seven months of development in the uterus and in the newborn until roughly 6 months old. Functionally, fetal hemoglobin differs most from adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the developing fetus better access to oxygen from the mother's bloodstream.\nUnusually high levels of fetal haemoglobin production can ameliorate sickle cell disease and \u03b2 thalassaemia. Although efforts directed at the pharmacological stimulation of fetal haemoglobin as an approach to managing these conditions have met with limited success, there is wide variation in individual responses. \nBased on results, adults humans could be induced to produce fetal hemoglobin." }, { "input": "What is the role of thyroid hormone in Stem cell differentiation?", "output": "Thyroid hormone treatment of Human-induced pluripotent stem cell-derived cardiomyocytes attenuates the fetal gene expression and induces differentiation. Liganded T3 receptor (TR) regulates cell autonomous formation of adult intestinal progenitor cells and that T3 action in the connective tissue is important for the establishment of the stem cell niche. In the intestinal epithelium, TR\u03b11 and TR\u03b22 are expressed at the level of stem/progenitor cell populations where they induce cell proliferation and differentiation, respectively. Thyroid hormone is implicated in neural stem cell function and differentiation and acts as a neurogenic switch in the adult neural stem cell niche. Furthermore, thyroid hormone enhances maturation of oligodendrocyte precursor cells. Thyroid hormones also induce hemopoietic pluripotent stem cell differentiation toward erythropoiesis and c-erbA/TR appears to act as a binary switch affecting erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation. Finally, thyroid hormone modulates late differentiation stages of mesenchymal stem cells chondrogenesis via BMP signaling." }, { "input": "Which receptors can be evaluated with the [18F]altanserin?", "output": "5-HT2A (5-hydroxytryptamine type 2a) receptor can be evaluated with the [18F]altanserin." }, { "input": "Which diseases have been associated with the PTPN22 620W allele?", "output": "The functional polymorphism 620W in the intracellular tyrosine phosphatase PTPN22 gene has been shown to confer susceptibility to the development of type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, Hashimoto thyroiditis, and Wegener's granulomatosis (granulomatosis with polyangiitis)." }, { "input": "Which extra thyroid tissues have thyrotropin (TSH) receptors?", "output": "TSH receptors are expressed also in extrathyroid tissues. TSH receptors seem to be functional. Extrathyroid tissues include fibrobasts of the orbit and adipose tissue\nThe principal tissues with TSH receptors are:\nadippose tissue\n orbital fibrotic tissue" }, { "input": "Which histone modifications distinguish between promoters and enhancers?", "output": "H3K27ac is a marker of active enhancers. An enhancer chromatin state signature associated with active developmental enhancers may be defined by high levels of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and strong depletion of H3K27me3." }, { "input": "Where is the metaxin complex localized?", "output": "The metaxin complex is localized to the outer mitochondrial membrane." }, { "input": "What are the major classes of retrotransposons active in the human genome?", "output": "LINE-1 (L1), Alu, SVA" }, { "input": "Which are the clinical characteristics of Diamond-Blackfan anemia?", "output": "Diamond-Blackfan anemia (DBA) is a rare congenital erythroid hypoplastic anemia that usually presents early in infancy and is characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer." }, { "input": "How can the expression of SerH3 immobilization antigen be regulated?", "output": "The expression of Tetrahymena surface proteins serotype H3 (SerH3) is under temperature regulation. SerH3 is expressed when cells are incubated between the temperatures of 20 and 35 degrees C." }, { "input": "Which factors play a role in promoter proximal pausing of RNA polymerase II?", "output": "NELF (negative elongator factor) and DSIF (DRB Sensitivity Inducing Factor)" }, { "input": "Which are the main clinical features of Fanconi anemia?", "output": "Fanconi anaemia (FA) is an autosomal recessive disease characterised by congenital abnormalities, defective haemopoiesis, and increased risk of malignancies." }, { "input": "Which are the main clinical features of Fanconi anemia?", "output": "Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors" }, { "input": "Which is the receptor for the immunosuppressive drug cyclosporin A (CsA)?", "output": "Cyclophilin is the intracellular receptor protein for cyclosporin A (CsA)." }, { "input": "Which drugs may interfere thyroxine absorption?", "output": "bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine\nsevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours" }, { "input": "Is Turcot syndrome associated with glioblastoma?", "output": "Yes, Turcot syndrome is associated with glioblastoma. Turcot syndrome is an autosomal recessive disorder clinically characterized by the occurrence of primary glial tumors of the central nervous system, including glioblastoma, and adenomatous colonic polyps during the first or second decades of life, with a spectrum of clinical features such as \"caf\u00e9-au-lait\" spots, axillary freckling, and hyperpigmented spots." }, { "input": "Which is the gene most commonly mutated in Tay-Sachs disease?", "output": "HEXA gene, encoding the alpha-subunit of the lysosomal enzyme, beta-N-acetylhexosaminidase A" }, { "input": "In which types of DNA repair is the UvrAB complex involved?", "output": "UvrB and the lesion-recognition factor UvrA form the UvrAB complex, which plays a key role in bacterial nucleotide excision repair (NER). In transcription-coupled repair (TCR), the transcription repair coupling factor Mfd recruits uvrA, and the assembled UvrAB complex initiates repair. UvrAB complex also suppresses illegitimate recombination." }, { "input": "What is the localization of the protein encoded by the gene DNAJC11?", "output": "mitochondrial inner membrane" }, { "input": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "output": "Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias. " }, { "input": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "output": "Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias." }, { "input": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "output": "Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias.The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies." }, { "input": "What is the lay name of the treatment for CCSVI (chronic cerebro-spinal venous insufficiency) in multiple sclerosis.", "output": "The so-called \"LIberation therapy\" is in fact Endovascular Treatment and consists of PTA (Percutaneous Transluminal Angioplasty), which is dilatation of the internal jugular and/or azygous veins by a catheter venography. Stent placement is optional but has been strongly advised against as being dangerous." }, { "input": "Which hormone abnormalities are characteristic to Pendred syndrome?", "output": "Thyroid hormone abnormalities are characteristic to Pendred syndrome. Hypothyroidism is the most common thyroid hormone abnormality in Pendred syndrome. Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter and a partial defect in iodide organification." }, { "input": "What is the mode of inheritance of long QT Jervell and Lange-Nielsen syndrome?", "output": "Jervell and Lange-Nielsen long QT syndrome (JLNS) is characterized by autosomal recessive mode of inheritance" }, { "input": "List programs suitable for protein docking", "output": "Macromolecular docking is the computational modelling of the quaternary structure of complexes formed by two or more interacting biological macromolecules. Protein\u2013protein complexes are the most commonly attempted targets of such modelling, followed by protein\u2013nucleic acid complexes.\nThe ultimate goal of docking is the prediction of the three-dimensional structure of the macromolecular complex of interest as it would occur in a living organism. Docking itself only produces plausible candidate structures. These candidates must be ranked using methods such as scoring functions to identify structures that are most likely to occur in nature.\nNowadays there a lot of programs suitable for proteins docking such as CSBB-ConeExclusion, HADDOCK, ZDOCK, GalaxyDock, PHASE, DockRank, HotLig, SOL, AutodockVina, DockoMatic, DockoMatic, DockTrina, CAVITY, LiGenDock and DOCK." }, { "input": "Which genes have been found mutated in Gray platelet syndrome patients?", "output": "The genetic defects responsible for gray platelet syndrome are mutations in the genes NBEAL2, GATA1 and GFI1B." }, { "input": "Which genes have been found mutated in Gray platelet syndrome patients?", "output": "The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.\nA nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.\nX-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation." }, { "input": "Does dasatinib promote or inhibit T-cell proliferation?", "output": "Dasatinib inhibits T-cell proliferation" }, { "input": "Does SCRIB deregulation promote cancer?", "output": "Yes, deregulation of scribble promotes cancer." }, { "input": "Is cardiac magnetic resonance imaging indicated in the pre-participation screening of athletes?", "output": "Currently cardiac magnetic resonance imaging is not indicated in the pre-participation screening of athletes. However the potential of this imaging technique to provide new information on cardiac function morphology and myocardial composition, in particular with regard to myocardial fibrosis, gets it potentially suitable to be applied in the pre-participation screening of athletes" }, { "input": "Is imatinib an antidepressant drug?", "output": "No. Imatinib is a tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably Chronic myelogenous leukemia (CML) and Gastrointestinal stromal tumor (GIST)." }, { "input": "What is the function of the MTH1 enzyme in cancer cells?", "output": "The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against mutagenesis, carcinogenesis, and cell death induced by oxidized purine nucleotides." }, { "input": "Are ultraconserved elements depleted among copy number variants (CNVs)?", "output": "Yes. Interestingly, human ultraconserved elements (UCEs) have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs). These elements may be interpreted as hallmarks for dose-sensitive genes, particularly for those genes whose gain or loss may be directly implied in neurodevelopmental disorders. Therefore, their presence in genomic imbalances of unknown effect might be suggestive of a clinically relevant condition" }, { "input": "Is the microRNA 132 (miR-132) involved in brain pathologies?", "output": "Yes. MicroRNA 132 (miR-132), is involved in brain pathologies." }, { "input": "What is an approximate number of CTCF binding sites in the human genome?", "output": "The number of CTCF binding sites in the human genome lies between 31,000 and 50,000." }, { "input": "Does cucumber lower blood sugar in diabetics?", "output": "Yes. Based on several scientific reports, ethanolic extract of cucumber and some other Cucurbitaceae plants are associated with a significant reduction of elevated blood glucose level, suggesting that cucumber could have antidiabetic activity." }, { "input": "Which mutations in the cardiac isoform of the ryanodine receptor (RyR2) have been found to be related to CPVT?", "output": "Recently, a novel CPVT RyR2 mutation, G230C, was found to increase the cytosolic, but not the luminal, Ca2+ sensitivity of single RyR2 channels in lipid bilayers. The novel RYR2-S4153R mutation has been implicated as a cause of CPVT and atrial fibrillation. A novel RyR2-V2475F mutation is associated with CPVT in humans. 3 CPVT mouse models are: RyR2-R2474S+/-, RyR2-N2386I+/-, and RyR2-L433P+/-. The E189D RyR2 mutation is causative for CPVT. A knock-in mouse model carrier of the R4496C mutation is the mouse equivalent to the R4497C mutations identified in CPVT families. Scanning of 12 Finnish CPVT probands identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals. Three CPVT-linked human RyR2 (hRyR2) mutations are: S2246L, N4104K, and R4497C." }, { "input": "Which population has a high frequency of the HLA-B*1502 allele?", "output": "HLA-B*1502 has a high frequency in Han Chinese and other Asian populations, except Japanese. (There is a strong association between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced Stevens-Johnson syndrome (SJS))." }, { "input": "What are the observations regarding telomere integrity and function in Fanconi anemia?", "output": "In Fanconi anemia patients, a higher rate of breakage at TTAGGG sequences in vivo is causing telomere erosion in differentiated cells. Moreover, it has been demonstrated that \u03b1IISp is important for telomere maintenance after DNA damage due to interstrand cross-links (ICL), localizing to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of \u03b1IISp by siRNA or in Fanconi anemia, complementation group A (FANCA) cells, where \u03b1IISp levels are 35-40% of normal, ICL damage results in failure of XPF to localize to telomeres, with markedly increased telomere dysfunction-induced foci, and catastrophic loss of telomeres." }, { "input": "What are the observations regarding telomere integrity and function in Fanconi anemia?", "output": "A higher frequency of extra-chromosomic TTAGGG signals and of chromosome ends with undetectable TTAGGG repeats was observed in FA cells by fluorescence in situ hybridization (FISH), suggesting intensive breakage at telomeric sequences. This was proven by measuring the frequency of excess of telomeric signals per cell, which was 2.8-fold higher in FAWe now demonstrate that \u03b1IISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recruitment of the ICL repair protein, XPF, to damage-induced foci at telomeres. In telomerase-positive normal cells depleted of \u03b1IISp by siRNA or in Fanconi anemia, complementation group A (FA-A) cells, where \u03b1IISp levels are 35-40% of normal, ICL damage results in failure of XPF to localize to telomeres, markedly increased telomere dysfunction-induced foci, followed by catastrophic loss of telomeres" }, { "input": "Are Notch mutations related to T-cell Acute Lymphoblastic Leukemia (T-ALL)?", "output": "Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). " }, { "input": "Are Notch mutations related to T-cell Acute Lymphoblastic Leukemia (T-ALL)?", "output": "Yes, Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL).T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases." }, { "input": "What is the role of the Tsix gene during X chromosome inactivation?", "output": "One of the two X chromosomes in female mammalian cells is subject to inactivation (XCI) initiated by the Xist gene. Xist works as a functional RNA molecule that recruits repressive chromatin factors towards one of the female Xs for inactivation. The Tsix gene, antisense of Xist, through transcription negatively regulates Xist and protects one X-chromosome in cis from inactivation by Xist. Although, the precise molecular mechanism is still unclear it has been shown that Tsix transcription regulates the chromatin structure by altering histone tail modifications and DNA methylation at the Xist promoter. In addition, Xist and Tsix RNAs form duplexes in vivo and are processed to small RNAs, which have a potential regulatory function." }, { "input": "Is the protein FAK (Focal Adhesion Kinase) phosphorylated?", "output": "yes, the protein FAK (Focal Adhesion Kinase) is phosphorylated." }, { "input": "Which is the substrate of the haspin kinase during mitosis?", "output": "Haspin phosphorylates histone H3 at Thr3 (H3T3ph) during mitosis" }, { "input": "Which are the most widely reported side-effects in the treatment of Crohn's disease?", "output": "Leukopenia, paresthesia, psoriasis, alopecia and hemolysis are the most commonly reported side effects depending on the treatment. Severe adverse effects include myelosuppression, liver toxicity and hyperplasia, pancreatitis and pericarditis. The most severe but rare side-effects reported are progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma." }, { "input": "Are most driver gene mutations synonymous or non-synonymous?", "output": "A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency. " }, { "input": "Are most driver gene mutations synonymous or non-synonymous?", "output": "A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency." }, { "input": "What is the advantage of neutral loss detection in phosphoproteomics?", "output": "The localization of phosphorylation sites in peptide sequences is a challenging problem in large-scale phosphoproteomics analysis. The intense neutral loss peaks and the coexistence of multiple serine/threonine and/or tyrosine residues are limiting factors for objectively scoring site patterns across thousands of peptides.\nCID of phosphopeptides typically results in spectra dominated by a neutral loss of the phosphate group allowing detection and sequencing of phosphopeptides." }, { "input": "Does ghrelin play a role in ischemic stroke?", "output": "Yes. It has been shown that serum ghrelin levels are reduced after ischemic stroke and ghrelin is associated with stroke type. Ghrelin can be a useful marker for the prediction of stoke after cardiopulmonary bypass. Ghrelin may be neuroprotective after injury in animal models of cerebral ischemia by inhibiting apoptotic processes, inflammation, nNOS activity and modulating gastrointestinal motility." }, { "input": "What is the mechanism of drug-induced gingival overgrowth?", "output": "Drug-induced gingival overgrowth (GO) is a frequent and adverse side-effect associated principally with the administration of the immunosuppressive drug cyclosporin A (CsA) and also certain anti-epileptic and anti-hypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and the accumulation of excessive amounts of connective tissue. Keratinocyte growth factor (KGF), which is a potent epithelial cell mitogen that has been implicated in other hyperplastic conditions could be involved in the molecular pathology of GO. Also, since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease. In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth. Furthermore, the enhanced proliferation of gingival fibroblasts observed in this disease could be caused at least partly by the effects of the drugs on the cell cycle and cyclin expression in these cells. The increase in cell growth that occurs in drug-induced gingival overgrowth may be mediated by over-expression of cyclin B1." }, { "input": "Is LPS a microbial product?", "output": "Yes, the lipopolysaccharide (LPS) is a component of the bacterial cell wall." }, { "input": "Which cyclin- dependent kinase inhibitor is regulated by Bmi-1?", "output": "p16INK4 (also known as CDKN2A)" }, { "input": "Which microRNAs are involved in exercise adaptation?", "output": "miR-1, miR-133, miR-208a, miR-206, miR-494, miR-146a, miR-222, miR-21, miR-221, miR-20a, miR-133a, miR-133b, miR-23, miR-107 and miR-181 are involved in exercise adaptation" }, { "input": "Has field-programmable gate array (FPGA) technology been used to solve sequence alignment problems?", "output": "Yes. Field-Programmable Gate Arrays (FPGAs) are reconfigurable computing platforms that have found several applications in diverse domains, including digital signal processing, medical imaging and bioinformatics. Specific applications of FPGAs for biological sequence alignment have been reported for dynamic programming-based pairwise (local or global) sequence alignment, progressive multiple sequence alignment, profile alignment, Burrows-Wheeler transform (BWT) based alignment, heuristic pairwise alignment." }, { "input": "List inhibtors targeting the mitochondrial permeability transition pore.", "output": "Cyclosporine A\nAtractyloside\nN-metyl-4-isoleucine-cyclosporine\nSanglifehrin A \nTRO-19622" }, { "input": "List inhibtors targeting the mitochondrial permeability transition pore.", "output": "The opening of the mitochondrial permeability transition pore appears to be inhibited by KB-R 7943, diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol, cyclosporin A (CsA) and BRL37344." }, { "input": "What is ceritinib?", "output": "Ceritinib is a second generation tyrosine kinase inhibitor, that serves as an effective and approved oral therapy for patients with ALK-rearranged non-small cell lung cancer." }, { "input": "Which protein is found to be mutated in Friedreich's ataxia?", "output": "It is generally accepted that Friedreich's ataxia (FRDA) is caused by a deficiency in frataxin expression, a mitochondrial protein involved in iron homeostasis, which mainly affects the brain, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas" }, { "input": "Which protein is found to be mutated in Friedreich's ataxia?", "output": "It is generally accepted that Friedreich's ataxia (FRDA) is caused by a deficiency in frataxin expression, a mitochondrial protein involved in iron homeostasis, which mainly affects the brain, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas." }, { "input": "Which is the process that Conserved noncoding elements mostly regulate?", "output": "Conserved noncoding elements play a fundamental role in regulating animal development" }, { "input": "What is the main mechanism by which human papillomavirus proteins E6 and E7 contribute to cell transformation?", "output": "Although they may have other targets, human papillomavirus proteins E6 and E7 interact with and block the function of p53 and pRb, respectively, therefore deregulating cell cycle and leading to cellular transformation." }, { "input": "List bacterial species identified in the iceman tissues.", "output": "Spirochete Treponema denticola\nClostridium perfringens\nClostridium ghonii\nClostridium sordellii\nEubacterium tenue\nBacteroides sp\nVibrio\nSphingomonas\nAfipia\nCurtobacterium\nMicrobacterium\nAgromyces" }, { "input": "Which properties of the mRNA does N6-methyladenosine (m6A) affect?", "output": "N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate. m6A predominantly and directly reduces mRNA stability." }, { "input": "What is the implication of histone lysine methylation in medulloblastoma?", "output": "Aberrant patterns of H3K4, H3K9, and H3K27 histone lysine methylation were shown to result in histone code alterations, which induce changes in gene expression, and affect the proliferation rate of cells in medulloblastoma." }, { "input": "What is the Orco protein in mosquitos?", "output": "Odorant co-receptor." }, { "input": "List some ways to reverse Tau hyperphosphorylation in Tauopathies?", "output": "Different ways have been used to try to reverse Tau hyperphosphorylation through administration of inhibitors such as: 7-nitroindazole, memantine, glycogen synthase kinase-3 inhibitors. \nOther approaches are transplantation of Human umbilical cord blood-derived mesenchymal stem cells and administration of M1 muscarinic agonists." }, { "input": "What is the role of 5hmC (5 hydroxy-methyl-Cytocine) in differentiation?", "output": "The balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development. By mapping DNA methylation and hydroxymethylation at base resolution, we find that deletion of Tet2 causes extensive loss of 5hmC at enhancers, accompanied by enhancer hypermethylation, reduction of enhancer activity, and delayed gene induction in the early steps of differentiation." }, { "input": "What is the role of 5hmC (5 hydroxy-methyl-Cytocine) in differentiation?", "output": "Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers " }, { "input": "Which is the histone residue methylated by MLL1?", "output": "Histone H3 at lysine 4 (H3K4)" }, { "input": "What is CRISPRi?", "output": "Clustered regularly interspaced palindromic repeats interference (CRISPRi). This discovery tool is is used for genetic screening based on loss-of-function phenotypes." }, { "input": "What is CRISPRi?", "output": "The Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) system is used for targeted silencing of transcription in different types of cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). The Cas9-sgRNA complex binds to DNA elements complementary to the sgRNA and causes a steric block that halts transcript elongation by RNA polymerase, resulting in the repression of the target gene. CRISPRi provides a simplified approach for rapid gene repression within 1-2 weeks. The method can also be adapted for high-throughput interrogation of genome-wide gene functions and genetic interactions, thus providing a complementary approach to RNA interference, which can be used in a wider variety of organisms." }, { "input": "Which type of cells is affected in Amyotrophic Lateral Sclerosis?", "output": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which motor neurons are affected." }, { "input": "Is Achondroplasia associated with hearing loss?", "output": "Yes, there is hearing deficit in achondroplasia" }, { "input": "Is the JNK pathway activated during liver regeneration?", "output": "Yes, the Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy." }, { "input": "Is STAT3 transcription factor regulated by mTORC1?", "output": "mTORC1 was found to regulate STAT3 activity in, at least, three ways: 1) after induction by IL6, 2) by direct phosphorylation during hypoxia, to promote HIF-1\u03b1 mRNA transcription, and 3) after activation by excess amino acids, which then positively regulate Notch1 expression through STAT3 activation." }, { "input": "How is mTORC1 involved in the regulation of heat stress?", "output": "mTORC1 attenuates stress response by inhibiting cap-independent Hsp70 translation." }, { "input": "List components of the CRSP/Med complex.", "output": "Mediator of RNA polymerase II transcription subunit 7\nMediator of RNA polymerase II transcription subunit 14\nMediator of RNA polymerase II transcription subunit 17\nMediator of RNA polymerase II transcription subunit 23\nMediator of RNA polymerase II transcription subunit 24\nMediator of RNA polymerase II transcription subunit 26\nMediator of RNA polymerase II transcription subunit 27" }, { "input": "Patients of which disease could be treated by utilizing knowledge obtained from experiments suppressing TDP-43 toxicity in yeast?", "output": "Amyotrophic lateral sclerosis (ALS)." }, { "input": "Patients of which disease could be treated by utilizing knowledge obtained from experiments suppressing TDP-43 toxicity in yeast?", "output": "The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS " }, { "input": "Is calcium overload involved in the development of diabetic cardiomyopathy?", "output": "Yes." }, { "input": "What is the mechanism of viroid replication?", "output": "The replication of many viral and subviral pathogens as well as the amplification of certain cellular genes proceeds via a rolling circle mechanism. Viroid replication occurs via a rolling circle mechanism using either a symmetric or asymmetric pathway in three steps, RNA transcription, processing and ligation. Replication of these minimal genomes, composed exclusively by a circular RNA of 246-401 nt, occurs in the nucleus (family Pospiviroidae) or in the chloroplast (family Avsunviroidae) by an RNA-based rolling-circle mechanism with three steps: (1) synthesis of longer-than-unit strands catalyzed by host DNA-dependent RNA polymerases recruited and redirected to transcribe RNA templates, (2) cleavage to unit-length, which in family Avsunviroidae is mediated by hammerhead ribozymes, and (3) circularization through an RNA ligase or autocatalytically." }, { "input": "Which mitochondrial genes are regulated by thyroid hormone?", "output": "subunit 6 of ATP synthase, ATPase-6, mitochondrial II and III subunits of cytochrome-c oxidase, NADH dehydrogenase subunit 3" }, { "input": "Mutation of which gene is associated with McLeod syndrome?", "output": "Mutation of XK gene is associated with McLeod syndrome. The XK gene is an X-chromosomal gene. The McLeod phenotype is derived from various forms of XK gene defects that result in the absence of XK protein, and is defined hematologically by the absence of Kx antigen, weakening of Kell system antigens, and red cell acanthocytosis." }, { "input": "Is RIP1 (RIP-1) part of the necrosome?", "output": "Yes, RIP1 is part of the necrosome." }, { "input": "Which is the molecular target of the immunosuppressant drug Rapamycin?", "output": "The molecular target of Rapamycin is mTOR" }, { "input": "Is the protein KCNQ2 associated with idiopathic epilepsy?", "output": "Yes, sequence variations of the KCNQ2 gene may contribute to the etiology of idiopathic epilepsy" }, { "input": "PBT2 has been tested for which disorder?", "output": "PBT2 has been tested for treatment of Alzheimer's disease." }, { "input": "What is the basic secondary structure of the variable domains of a typical antibody?", "output": "The variable domains of heavy and light chains of antibodies consist of two \u03b2-sheets. The first one is composed of four strands, A, B, E and D, and the second one is composed of six strands, named A', G, F, C, C' and C''. The antigen binding site is formed by the inter-strand links BC, C\u2032C\u2033 and FG from each domain." }, { "input": "How does long-range epigenetic silencing (LRES) occur?", "output": "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types." }, { "input": "How does long-range epigenetic silencing (LRES) occur?", "output": "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types. LRES can span megabases of DNA and involves broad heterochromatin formation accompanied by hypermethylation of clusters of contiguous CpG islands within the region. It is not clear if LRES is initiated by one critical gene target that spreads and conscripts innocent bystanders, analogous to large genetic deletions or if coordinate silencing of multiple genes is important in carcinogenesis. Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity." }, { "input": "What is the mode of inheritance of Acromicric dysplasia?", "output": "Acromicric dysplasia has an autosomal dominant mode of inheritance" }, { "input": "Can RNAPolII function as an RNA-dependent RNA-polymerase?", "output": "RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated in the replication of the RNA genomes of hepatitis delta virus (HDV) and plant viroids. The RdRP activity of Pol II provides a missing link in molecular evolution, because it suggests that Pol II evolved from an ancient replicase that duplicated RNA genomes." }, { "input": "Can RNAPolII function as an RNA-dependent RNA-polymerase?", "output": "There is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Here we show the intrinsic RdRP activity of Pol II with only pure polymerase, an RNA template-product scaffold and nucleoside triphosphates (NTPs). RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity. We conclude that influenza A virus replication requires RNAP-II activity not just to provide capped mRNA substrates but also to facilitate nuclear export of selected viral mRNAs." }, { "input": "Can RNAPolII function as an RNA-dependent RNA-polymerase?", "output": "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA" }, { "input": "Which are the best treatment options to treat Helicobacter pylori?", "output": "The best treatment options for eradication of Helicobacter pylori involve triple or quadruple drugs therapy with different types of antibiotics.\nBismuth may be also an additional option. Proton pump inhibitors are also included in treatment.\nThe more effective drug list includes: amoxicillin, claritromycin, metronidazole rifabutin.\nAlso chitosan microspheres with Eudragit L100 have been tested." }, { "input": "List sclerostin interaction partners.", "output": "alkaline phosphatase\ncarbonic anhydrase\ngremlin-1\nfetuin A\nmidkine\nannexin A1 \nannexin A2\ncollagen \u03b11\ncasein kinase II \nsecreted frizzled related protein 4\nPhex\nasporin\nfollistatin\nerbB-3\nLRP5 \nnoggin" }, { "input": "Under which conditions does AMPK phosphorylate TSC2?", "output": "The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes, and it is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia." }, { "input": "Under which conditions does AMPK phosphorylate TSC2?", "output": "The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes that is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia." }, { "input": "What imaging modalities have been listed as method of choice to diagnose CSF leak?", "output": "CT cisternography in the investigation of cerebrospinal fluid rhinorrhoea. CTC is an accurate, well-tolerated procedure and should be regarded as the method of choice for investigation of this condition.\n...unenhanced (three-dimensional constructive interference in steady state (3D-CISS)...In conclusion, 3D-CISS is a non-invasive and reliable technique, and should be the first-choice method to localise CSF leak." }, { "input": "Which are currently available software tools for detecting rare codon clusters in coding sequences?", "output": "Rare codon clusters (RCCs) correspond to regions along mRNA sequences where among the possible choices of synonymous codons those with lower usage are observed. Due to the fact that relative codon frequencies have been shown to correlate with their cognate tRNA frequencies, RCCs indicate possible translational attenuation sites. A few tools specific for this task have been described in the literature, namely: LaTcOm, %MinMax, PAUSE, Sherlocc, Sliding Window (RiboTempo)" }, { "input": "How many tissue kallikrein genes are present in the human genome?", "output": "Tissue kallikreins (KLKs) are a group of closely related serine proteinases that are represented by multigene families in the human genome. The human tissue kallikrein gene family consists of 15 genes, denoted KLK1\u2013KLK15, tandemly arranged on chromosomal locus 19q13.4." }, { "input": "Does the Oncotype DX test work with paraffin embedded tissues?", "output": "Yes, the Oncotype DX test works with paraffin embedded tissue." }, { "input": "Where does CTCF colocalize with cohesin?", "output": "Cohesin subunits associate with viral and cellular CTCF sites involved in complex gene regulation and chromatin organization. Cohesin cobinds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help to mediate tissue-specific transcriptional responses via long-range chromosomal interactions.\nNumerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. Cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci." }, { "input": "Name triad of Wernicke encephalopathy.", "output": "Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency." }, { "input": "Is the PTPN22 gene a biomarker for Rheumatoid Arthritis?", "output": "Most association studies have indeed confirmed an association between mutations at the PTPN22 gene and rheumatoid arthritis" }, { "input": "Is the PTPN22 gene a biomarker for Rheumatoid Arthritis?", "output": "The PTPN22 gene has been repeatedly associated with RA-susceptibility in populations of European ancestry." }, { "input": "Is marijuana use associated with increased risk for stroke?", "output": "Yes, the use of marijuana is associated with increased risk for ischemic stroke, especially in young adults. The mechanisms underlying such association remain largely unclear, but increased vascular reactivity and increased cerebrovascular resistance were implicated." }, { "input": "How many and which are the different isoforms for the ryanodine receptor?", "output": "Generally, three ryanodine receptor isoforms (RyR1-RyR3) are known. RyR1, expressed in skeletal muscle; RyR2, expressed in cardiac muscle; and RyR3, expressed in various cells. RyR3 is preferentially expressed in the brain especially in the hippocampus and striatum." }, { "input": "Which compound is a specific inhibitor for Nox1 and Nox4?", "output": "GKT136901 is a specific inhibitor of Nox1 and Nox4." }, { "input": "Which molecule is targeted by the drug Gevokizumab?", "output": "Gevokizumab is an allosteric anti-IL-1\u03b2 monoclonal antibody." }, { "input": "Which protein phosphatases have been found to dephosphorylate phospholamban?", "output": "The protein phosphatases which dephosphorylate native, sarcoplasmic reticulum (SR)-associated phospholamban were studied in cardiac muscle extracts and in a Triton fraction prepared by detergent extraction of myofibrils, the latter fraction containing 70-80% of the SR-associated proteins present in the tissue. At physiological concentrations of free Mg2+ (1 mM), protein phosphatase 1 (PP1) accounted for approximately 70% of the total phospholamban phosphatase activity in these fractions towards either Ser-16 (the residue labelled by cAMP-dependent protein kinase, PK-A) or Thr-17 (the residue phosphorylated by an SR-associated Ca2+/calmodulin-dependent protein kinase). Protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) accounted for the remainder of the activity. " }, { "input": "Which protein phosphatases have been found to dephosphorylate phospholamban?", "output": "The protein phosphatases which dephosphorylate native, sarcoplasmic reticulum (SR)-associated phospholamban were studied in cardiac muscle extracts and in a Triton fraction prepared by detergent extraction of myofibrils, the latter fraction containing 70-80% of the SR-associated proteins present in the tissue. At physiological concentrations of free Mg2+ (1 mM), protein phosphatase 1 (PP1) accounted for approximately 70% of the total phospholamban phosphatase activity in these fractions towards either Ser-16 (the residue labelled by cAMP-dependent protein kinase, PK-A) or Thr-17 (the residue phosphorylated by an SR-associated Ca2+/calmodulin-dependent protein kinase). Protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) accounted for the remainder of the activity." }, { "input": "What is the most prominent sequence consensus for the polyadenylation site?", "output": "Functional polyadenylation [poly(A)] sites consist of two sequence elements, the AAUAAA and G/U box signals, that closely flank the site of mRNA 3'-end formation. The canonical polyadenylation signal sequence AATAAA" }, { "input": "Does fibronectin constitute a serum biomarker for Duchenne muscular dystrophy?", "output": "Compared to age-matched controls, fibronectin levels in DMD patients were found to be significantly increased, whereas in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were close to the control levels. Additionally, progressive elevation in fibronectin levels was observed in longitudinal samples from DMD patients followed up for a period of 6 months up to 4 years. Therefore, fibronectin is a serum biomarker for Duchenne muscular dystrophy." }, { "input": "Does fibronectin constitute a serum biomarker for Duchenne muscular dystrophy?", "output": "Fibronectin is a serum biomarker for Duchenne muscular dystrophy" }, { "input": "What colonoscopy findings have been reported in autism", "output": "Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls." }, { "input": "What is a disordered protein?", "output": "Intrinsically disordered proteins lack stable tertiary and/or secondary structures under physiological conditions in vitro. Intrinsically disordered proteins undergo significant conformational transitions to well folded forms only on binding to partner." }, { "input": "What is the Drosophila melanogaster Groucho protein?", "output": "Groucho proteins are abundant and broadly expressed nuclear factors that lack intrinsic DNA-binding activity but can interact with a variety of DNA-binding proteins. The recruitment of Groucho to specific gene regulatory sequences results in transcriptional repression.\nGroucho (Gro) is a Drosophila melanogaster transcriptional corepressor." }, { "input": "Which enzyme is inhibited by Imetelstat?", "output": "Imetelstat works by inhibiting telomerase." }, { "input": "What is the catalytic mechanism of DNA (cytosine-5) methyltransferases? ", "output": "The catalytic mechanism of the DNA (Cytosine-5-)-methyltransferase involves nucleophilic attack of the C6 of the substrate cytosine by the single conserved cysteine of the enzyme, followed by C5 nucleophilic replacement of the methyl group of the cofactor S-adenosyl-L-methionine (AdoMet) to produce 5-methyl-6-Cys-81-S-5,6-dihydrocytosine. It has been also demonstrated that Phe and Glu, which are found in the catalytic motifs I and II of the enzyme are important for AdoMet binding and catalysis." }, { "input": "Are mutations in the STXBP1 gene associated with epilepsy?", "output": "Yes,mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies." }, { "input": "What is the mechanism of action of geldanamycin?", "output": "Geldanamycin is an ansamycin antibiotic which holds the ability to bind heat-shock protein 90. This interaction can lead to the disruption of heat-shock protein 90-containing multimolecular complexes. Additionally, it can induce inhibition or even degradation of partner proteins dissociated from the 90 kDa chaperone and, eventually, cause apoptosis in a variety of cell types." }, { "input": "Which is the most widely used anti-TNF drug?", "output": "Etanercept is the most widely used anti-TNF drug." }, { "input": "What is the association between number of pregnancies and rheumatoid arthritis", "output": "Greater parity significantly reduced the odds of RA. A larger number of pregnancies and late menopause show a protective effect, delaying the onset of the disease." }, { "input": "Is mitofusin 2 a receptor for parkin?", "output": "Yes, Mfn2 functions as a mitochondrial receptor for Parkin." }, { "input": "What are the main benefits of pharmacophore models?", "output": "As researchers continue to search for new targets of therapeutic interest, transmembrane and G-protein coupled receptors are of ever-increasing importance. However, crystal structures for these targets may be impossible to resolve, posing great challenges in rational drug design. Structure-based virtual screening is not an option when the active site geometry is unknown, but assaying an entire library for hits is an inefficient and expensive proposition.\nPharmacophore modeling solves this problem by determining the spatial arrangement of chemical features that confer drug activity toward a target receptor. Having established the chemical space occupied by active ligands, pharmacophore modeling software allows researchers to create 3-D structure-activity relationships, screen databases, and generate hits without the benefit of a receptor structure." }, { "input": "How Flaviviridae family of viruses infects vertebrates?", "output": "A wide range of about 500 different viruses is transmitted by arthropods such as ticks, mosquitoes and sandflies. These arboviruses multiply in the arthropod vector, and for each virus there is a natural cycle involving vertebrates (various birds or mammals) and arthropods. The virus enters the arthropod when the latter takes a blood meal from the infected vertebrate, and passes through the gut wall to reach the salivary gland where replication takes place. Once this has occurred, 1\u20132 weeks after ingesting the virus, the arthropod becomes infectious, and can transmit the virus to another vertebrate during a blood meal. Certain arboviruses that infect ticks are also transmitted directly from adult tick to egg (transovarial transmission), so that future generations of ticks are infected without the need for a vertebrate host." }, { "input": "What was the aim of the HAMLET clinical trial?", "output": "The aim of the HAMLET (Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema Trial) clinical trial was to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction." }, { "input": "What was the aim of the HAMLET clinical trial?", "output": "The Hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial (HAMLET) is a newly-conceived randomised multi-centre clinical trial that compares the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction. " }, { "input": "Can we use prodrug amifostine to protect healthy cell during chemotherapy?", "output": "Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can be delivered without causing severe damage to surrounding normal tissues are often insufficient to eradicate a tumor. Recently, a number of agents have been developed to protect normal tissue from the harmful effects of antitumor therapies. The aminothiol amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) has been the subject of extensive research as a prospective protector. While this drug has been approved for use to reduce toxicities associated with cisplatin, several studies also have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. Consequently, higher radiation doses could be used with less than or equal risk to surrounding normal tissues." }, { "input": "Which is the main difference between Alu and B1 repeats?", "output": "B1 is a murine homolog of the human SINE Alu. B1 (Alu-equivalent) is a murine short interspersed element whose amplification probably involved an RNA intermediate. The modern B1 elements are similar to the left Alu monomer, but with a 9 bp deletion and a 29 bp duplication." }, { "input": "Which is the main difference between Alu and B1 repeats?", "output": "The mouse B1 sequence is congruent to 130 nucleotides long and shows homology with the monomeric units of the dimeric 300-nucleotide primate sequence. " }, { "input": "Is there a relationship between thyroid hormone altered metabolism and coronary artery disease?", "output": "The major part of the studies and metaanalysis data show that hypothyroidism, both primary and secondary forms, is associated with higher incidence and severity of coronary artery disease." }, { "input": "What is the frequency of mutations induced spontaneously through Ethylnitrosourea (ENU) mutagenesis?", "output": "Theoretical considerations and empirical analysis suggest that the per-base mutation frequency for a fractionated-dose treatment protocol is on the order of 1 sequence change per 10(5) bp." }, { "input": "What is the molecular pathogenesis of Spinal Muscular Atrophy?", "output": "Spinal muscular atrophy is an autosomal recessive neurodegenerative disease characterised by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalised weakness. It is caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion, or mutation, resulting in downregulated biogenesis of uridine-rich small nuclear RNAs (U snRNAs), which are major components of the splicing machinery." }, { "input": "Which drugs affect insulin resistance in obesity?", "output": "Enistein treatment could help reduce insulin resistance\nACE inhibitor drugs may improve insulin resistance" }, { "input": "Elaborate on the link between conserved noncoding elements (CNEs) and fractality.", "output": "Well-developed fractality is revealed for the chromosomal distribution of different classes of CNEs in the human genome by employing the scaling of block entropy and box-counting. This is characteristic of elements that are either extremely conserved between species or are of ancient origin, i.e. conserved between distant organisms across evolution. There are also power-law-like distributions, i.e. linearity in double logarithmic scale, in the inter-CNE distances, a feature which is connected with fractality and self-similarity." }, { "input": "Which is the primary protein component of Lewy bodies?", "output": "The primary protein component of Lewy bodies are fibrils composed of alpha-synuclein." }, { "input": "Are microtubules marked by glutamylation?", "output": "Yes, glutamylation is the most prevalent tubulin posttranslational modification and marks stable microtubules." }, { "input": "What is known about the Kub5-Hera/RPRD1B interactome?", "output": "Ku70-binding protein 5 (Kub5)-Hera (K-H)/RPRD1B maintains genetic integrity by concomitantly minimizing persistent R-loops and promoting repair of DNA double strand breaks (DSBs). Thus, the Kub5-Hera/RPRD1B interactome plays a novel role in preserving genetic stability by regulating DNA mismatch repair." }, { "input": "Willis-Ekbom disease is also known as?", "output": "Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterized by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement." }, { "input": "List two most common symptoms of Aagenaes syndrome.", "output": "Aagenaes syndrome, also called lymphoedema cholestasis syndrome 1, is characterized by neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age and severe chronic lymphoedema, mainly affecting the lower extremities." }, { "input": "Which are the side effects during tacrine administration in patients with Alzheimer's Disease?", "output": "The side effects during tacrine administration in patients with Alzheimer's Disease are:\r\n1) Hepatotoxicity\r\n2) Gastrointestinal (diarrhea, anorexia, dyspepsia, abdominal pain, nausea, vomiting)\r\n3) Mitochondrial impairement" }, { "input": "Is synapsin a phosphoprotein?", "output": "Yes, synapsin is an evolutionarily conserved presynaptic phosphoprotein." }, { "input": "Is Thalidomide currently a marketed drug?", "output": "Several mechanisms for the teratogenic action of thalidomide are currently under review, but this mode of action of the drug still remains unclear and we review evidence-based hypotheses for the teratogenicity of thalidomide. Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered. THE USE OF A DRUG WITH A TEMPORARY MARKETING AUTHORISATION: Thalidomide is currently available in France for nominative or cohort use with a temporary marketing authorisation (TMA). Examples of the basis for such regulation are drawn from historical situations (thalidomide, benoxaprofen) as well as currently marketed drugs (arylpropionic acids, disopyramide, indacrinone). In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects. The US Food and Drug Administration (FDA) has approved Thalomid (thalidomide) capsules for the acute treatment of the cutaneous manifestations of moderate to severe ENL. The revival of thalidomide began shortly after the drug was withdrawn from the market because of its teratogenic properties." }, { "input": "Is Thalidomide currently a marketed drug?", "output": "Thalidomide is currently used to treat multiple Myeloma, possibly POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes ) syndrome and IBS" }, { "input": "Which enzymes synthesize catecholamines in adrenal glands?", "output": "The enzymes that synthesize catecholamines in adrenal glands are:\n1) Tyrosine Hydroxylase (TH)\n2) Aromatic L-amino acid decarboxylase (AAAD)\n3) Dopamine \u03b2-hydroxylase (DBH)\n4) Phenylethanolamine N-methyltransferase (PNMT)" }, { "input": "How many cysteines have alpha-defensins?", "output": "Alpha defensins contain six cysteines, which form three well defined disulfide bridges under oxidizing conditions." }, { "input": "Could BRCA gene test used for breast and ovarian cancer risk?", "output": "Yes, BRCA gene test could be used for breast and ovarian cancer risk, as female BRCA1 and BRCA2 mutations are significantly associated with risk of developing breast and ovarian cancers." }, { "input": "What is Desomorphine?", "output": "Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil" }, { "input": "What is Desomorphine?", "output": "Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin" }, { "input": "What is Desomorphine?", "output": "Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil" }, { "input": "What is Desomorphine?", "output": "\"Krokodil\" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin." }, { "input": "What is Desomorphine?", "output": "Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil Desomorphine is an opioid misused as \"crocodile\", a cheaper alternative to heroin" }, { "input": "What is Desomorphine?", "output": "Desomorphine is an opioid drug which is often synthsised using a combination of readily available ingredients and is often available on the \"street\" as a cheaper alternative to heroin." }, { "input": "Which two drugs are included in the Harvoni pill?", "output": "Harvoni contains 400 mg sofosbuvir and 90 mg ledipasvir. It used for treatment of hepatitis C virus infection." }, { "input": "What is the result of Mff overexpression in mitochondria?", "output": "The Drp1 receptor Mff is a major regulator of mitochondrial fission, and its overexpression results in increased fission." }, { "input": "Has Glucose-6-phosphate dehydrogenase (G6PD) deficiency an X-linked inheritance?", "output": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance." }, { "input": "What is FFI, fatal familial insomnia", "output": "Familial fatal insomnia (FFI) is a prion disease caused by a mutation (D178N-129M haplotype) in the Prion Protein gene (PRNP). FFI is manifested by sleep disturbances with insomnia, autonomic disorders and spontaneous and evoked myoclonus, among other symptoms. FFI is considered to be a rare disease." }, { "input": "Which mutated genes are associated with the Tourette's syndrome?", "output": "A mutation in histidine decarboxylase (Hdc) gene as well as mutations in the SLITRK1 (Slit and Trk-like 1) gene have been implicated as rare genetic causes of Tourette's syndrome." }, { "input": "Which enzyme is inhibited by niraparib?", "output": "Niraparib is a Poly(ADP-ribose) Polymerase (PARP) Inhibitor. It is used for ovarian cancer treatment." }, { "input": "Which peak calling algorithm employs mixture model clustering under the hood?", "output": "JAMM (Joint Analysis of NGS replicates via Mixture Model clustering) is a peak finder that can integrate information from biological replicates, determine enrichment site widths accurately and resolve neighboring narrow peaks. JAMM is a universal peak finder that is applicable to different types of datasets." }, { "input": "Data from which major epigenome projects are contained in the DeepBlue epigenomic data server?", "output": "The DeepBlue Epigenomic Data Server contains data from four major epigenome projects, namely ENCODE, ROADMAP, BLUEPRINT and DEEP." }, { "input": "Which diseases that can be treated using the focused ultrasound thalamotomy.", "output": "Focused ultrasound thalamotomy is used for treatment of Parkinson disease, essential tremor, obsessive-compulsive disorder and chronic neuropathic pain." }, { "input": "Is the toxin produced by Clostridium botulinum always deadly?", "output": "There are numerous examples where children and animals survived infection with clostridium botulinum." }, { "input": "Is ocrelizumab effective for treatment of multiple sclerosis?", "output": "Yes, ocrelizumab is effective for primary progressive form of multiple sclerosis." }, { "input": "Elaborate on the role of CARMEN in cardiac specification.", "output": "CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA, is a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). CARMEN expression is activated during pathological remodeling in the mouse and human hearts, and is necessary for maintaining cardiac identity in differentiated cardiomyocytes." }, { "input": "Is there a role of regorafenib for sarcoma treatment?", "output": "Yes, there is evidence to suggest that regorafenib can be effective for sarcoma treatment. Clinical trials are under-way." }, { "input": "Which drug was tested in the TEMSO Trial for multiple sclerosis?", "output": "Teriflunomide was evaluated in the Teriflunomide Multiple Sclerosis Oral (TEMSO) trial." }, { "input": "What is the mechanism of action of peginesatide?", "output": "Peginesatide (Omontys) is synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent that is designed to specifically stimulate the erythropoietin receptor. It was recalled because of serious side-effects including cases of death." }, { "input": "Describe mechanism of action of Eteplirsen?", "output": "Eteplirsen (Exondys 51) is an antisense oligonucleotide designed to induce exon 51 skipping. Eteplirsen is approved for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping." }, { "input": "Which genes of the marmoset genome exhibit rapid sequence evolution?", "output": "Both protein-coding and microRNA genes related to reproduction exhibit evidence of rapid sequence evolution in the marmoset genome." }, { "input": "What is the importance of Janus Kinases in dermatology?", "output": "Janus Kinase (JAK) is active in many skin diseases and recent evidence show that inhibitors of JAK kinase could be used to treat vitiligo, psoriasis, lupus, alopecia areata and other inflammatory skin diseases." }, { "input": "What is the importance of Janus Kinases in dermatology?", "output": "Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis" }, { "input": "What is the incidence of beta-thalassemia in Greek population?", "output": "The incidence of beta-thalassemia trait is 8% in Greek population." }, { "input": "Is exon skipping correlated with exon circularization?", "output": "Yes. Circularization of exons is widespread and correlates with exon skipping, a feature that adds considerably to the regulatory complexity of the human transcriptome." }, { "input": "What is the target of daratumumab?", "output": "Daratumumab is a fully human anti-CD38 IgG1-\u03ba monoclonal antibody. It is approved for treatment of multiple myeloma." }, { "input": "Which gene-defect causes the Vel-blood type?", "output": "A cohort of 70 Vel- individuals was found to be uniformly homozygous for a 17 nucleotide deletion in the coding sequence of SMIM" }, { "input": "Is NADPH oxidase 5 expressed in rodents?", "output": "No, NADPH oxidase 5 is not expressed in rodents, because the gene is absent." }, { "input": "List selective estrogen receptor degraders.", "output": "Selective estrogen receptor degraders (SERD) are fulvestrant, RAD1901 and ARN-810. Fulvestrant is the only SERD approved for the treatment of breast cancer." }, { "input": "What is the role of ZNF335 in microcephaly?", "output": "Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that ZNF335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation." }, { "input": "What is the role of ZNF335 in microcephaly?", "output": "Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. RNA-interference and postmortem human studies show that ZNF335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size." }, { "input": "What is the role of ZNF335 in microcephaly?", "output": "Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that ZNF335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation." }, { "input": "What molecule is targeted by Avelumab?", "output": "Avelumab is a monoclonal antibody that binds programmed death-ligand 1 (PD-L1)." }, { "input": "What are the exonic splice enhancers?", "output": "In mammals there is a bias in amino acid usage near splice sites that is explained, in large part, by the high density of exonic splicing enhancers (ESEs) in these regions. Exonic splicing enhancers (ESEs) activate pre-mRNA splicing by promoting the use of the flanking splice sites. Some of these variants may have an effect on pre-mRNA splicing, either by altering degenerate positions of splice site sequences or by affecting intronic or exonic splicing regulatory sequences such as exonic splicing enhancers (ESEs). For inherited disease, the main mechanism responsible for the splicing defect is splice site loss, whereas for cancer the predominant mechanism of splicing disruption is predicted to be exon skipping via loss of exonic splicing enhancers or gain of exonic splicing silencer elements. FELINES was shown to be useful for characterizing branchsites, polypyrimidine tracts and 5' and 3' splice sites in the intron databases and exonic splicing enhancers (ESEs) in S.pombe exons. Unexpectedly, a fully experimental dataset identifies motifs that commonly behave opposite to the consensus, for example, being enriched in exon cores where splice-associated mutations are rare.Prior analyses that used the RESCUE-ESE set of hexamers captured the properties of consensus exonic splice enhancers." }, { "input": "What are the exonic splice enhancers?", "output": "Exonic splice enhancers are one of the principle non-splice site motifs. Four high-throughput studies have provided a compendium of motifs that function as exonic splice enhancers, but only one, RESCUE-ESE, has been generally employed to examine the properties of enhancers. In humans, much of the information specifying splice sites is not at the splice site." }, { "input": "What are the exonic splice enhancers?", "output": "In humans, much of the information specifying splice sites is not at the splice site. Exonic splice enhancers are one of the principle non-splice site motifs. Four high-throughput studies have provided a compendium of motifs that function as exonic splice enhancers, but only one, RESCUE-ESE, has been generally employed to examine the properties of enhancers." }, { "input": "What are the birth defects associated with Zika-virus infection?", "output": "Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype-the congenital Zika syndrome-has emerged. Zika virus infection during pregnancy is a cause of microcephaly and other severe birth defects." }, { "input": "What is Neisseria adhesin A?", "output": "Neisseria adhesin A (NadA) is one of the antigens of Bexsero, the recently licensed multicomponent vaccine against serogroup B Neisseria meningitidis (MenB). NadA belongs to the class of oligomeric coiled-coil adhesins and is able to mediate adhesion and invasion of human epithelial cells. As a vaccine antigen, NadA has been shown to induce high levels of bactericidal antibodies. More than 89 distinct NadA allele sequences and 43 distinct peptides have been described." }, { "input": "Which R package is used for the detection of chromosomal abnormalities from microarray data?", "output": "CAFE is an R package for the detection of gross chromosomal abnormalities from gene expression microarray data." }, { "input": "List all the available databases of super enhancers", "output": "dbSUPER and SEA are the available databases of super enhancers." }, { "input": "List all the available databases of super enhancers", "output": "dbSUPER and SEA are the most well-known and widely used Super-Enhancer Databases." }, { "input": "Which are the consequences of the hyperphosphorylated tau in Alzheimers' Disease?", "output": "The consequences of the hyperphosphorylated tau in Alzheimers' Disease is:\n1) The formation of neurofibrillary tangles (NFTs)\n2) Impaired glutamate metabolism\n3) Decreased tau affinity for microtubules binding\n4) Dendritic and axonal instability\n5) Synaptic degeneration\n6) Neuronal loss." }, { "input": "Which is the \"bonding hormone\"?", "output": "Oxytocin is known as the 'bonding hormone' due its role in promoting mother-child and pair bonding." }, { "input": "What causes Scurvy?", "output": " Scurvy, or \"Barlow's disease\", is a widely described disease involving cutaneous and mucosal lesions resulting from vitamin C deficiency." }, { "input": "What causes Scurvy?", "output": "Scurvy, or \"Barlow's disease\", is a widely described disease resulting from vitamin C deficiency" }, { "input": "Describe clinical presentation of Ambras syndrome.", "output": "Ambras syndrome is a distinct form of congenital hypertrichosis characterized by excessive hair growth over the body and face associated with facial and occasional dental anomalies. In patients with this syndrome, the whole body is covered with fine long hair, except for areas where normally no hair grows. There is accompanying facial dysmorphism and teeth abnormalities, including retarded first and second dentition and absence of teeth." }, { "input": "Which diseases are involved in the severe cutaneous reactions (SCAR) spectrum?", "output": "The diseases that are involved in the severe cutaneous reactions (SCAR) spectrum are:\n1) Stevens-Johnson syndrome (SJS)\n2) Toxic epidermal necrolysis (TEN)\n3) Acute generalized exanthematous pustulosis (AGEP)." }, { "input": "Which tool employs self organizing maps for analyzing synonymous codon usage?", "output": "INteractive Codon usage Analysis (INCA) provides an array of features useful in analysis of synonymous codon usage in whole genomes. In addition to computing codon frequencies and several usage indices, such as 'codon bias', effective Nc and CAI, the primary strength of INCA has numerous options for the interactive graphical display of calculated values, thus allowing visual detection of various trends in codon usage. Finally, INCA includes a specific unsupervised neural network algorithm, the self-organizing map, used for gene clustering according to the preferred utilization of codons." }, { "input": "Which tool employs self organizing maps for analyzing synonymous codon usage?", "output": "INteractive Codon usage Analysis (INCA) provides an array of features useful in analysis of synonymous codon usage in whole genomes. In addition to computing codon frequencies and several usage indices, such as 'codon bias', effective Nc and CAI, the primary strength of INCA has numerous options for the interactive graphical display of calculated values, thus allowing visual detection of various trends in codon usage." }, { "input": "What is MINDY-1?", "output": "MINDY-1 (motif interacting with Ub-containing novel DUB family) is a member of an evolutionarily conserved and structurally distinct new family of deubiquitinating enzymes. Found in all eukaryotes, MINDY-family DUBs are highly selective at cleaving K48-linked polyUb, a signal that targets proteins for degradation. MINDY-1 prefers cleaving long polyUb chains and works by trimming chains from the distal end." }, { "input": "What is MINDY-1?", "output": "MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes" }, { "input": "What is the benserazide's mechanism of function when co-administered with L-DOPA in patients with Parkinson's Disease?", "output": "Benserazide is a peripheral decarboxylase inhibitor. Benserazide in combination with L-DOPA constitutes a slow-release formulation of L-DOPA in patients with Parkinson's disease (PD), it reduces peaks and rapid fluctuations of L-DOPA plasma levels (possibly responsible for peak-dose dyskinesias and end-of-dose deterioration) and considered as the best available therapy." }, { "input": "What is regioneR?", "output": "Statistically assessing the relation between a set of genomic regions and other genomic features is a common challenging task in genomic and epigenomic analyses. regioneR is an R package that implements a permutation test framework specifically designed to work with genomic regions. In addition to the predefined randomization and evaluation strategies, regioneR is fully customizable allowing the use of custom strategies to adapt it to specific questions. Finally, it also implements a novel function to evaluate the local specificity of the detected association. regioneR is an R package released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor (http://www.bioconductor.org/packages/regioneR)." }, { "input": "What is regioneR?", "output": "RegioneR is an R/Bioconductor package for the association analysis of genomic regions based on permutation tests. It implements a permutation test framework specifically designed to work with genomic regions. In addition to the predefined randomization and evaluation strategies, regioneR is fully customizable allowing the use of custom strategies to adapt it to specific questions. Finally, it also implements a novel function to evaluate the local specificity of the detected association." }, { "input": "What is regioneR?", "output": "Statistically assessing the relation between a set of genomic regions and other genomic features is a common challenging task in genomic and epigenomic analyses. Randomization based approaches implicitly take into account the complexity of the genome without the need of assuming an underlying statistical model. regioneR is an R package that implements a permutation test framework specifically designed to work with genomic regions. In addition to the predefined randomization and evaluation strategies, regioneR is fully customizable allowing the use of custom strategies to adapt it to specific questions. Finally, it also implements a novel function to evaluate the local specificity of the detected association. The source code and documents are freely available through Bioconductor (http://www.bioconductor.org/packages/regioneR)." }, { "input": "For what indications is thalidomide currently marketed?", "output": "Drug repositioning, exemplified by sildenafil and thalidomide, is a promising way to explore alternative indications for existing drugs. THE USE OF A DRUG WITH A TEMPORARY MARKETING AUTHORISATION: Thalidomide is currently available in France for nominative or cohort use with a temporary marketing authorisation (TMA). Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported.We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil.A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) Currently it includes a group of new drugs (immunosuppressives tacrolimus mycophenolate, thalidomide, biologic therapy, probiotics, neuroinflammation blockers), new treatment techniques (cytaphereses, sequential immunosuppression, immunosuppression with high doses), and finally new indications (chemoprophylaxis). A review of the therapeutic indications for thalidomide in dermatology as well as the mechanisms of action and side-effects of this drug are presented." }, { "input": "For what indications is thalidomide currently marketed?", "output": "Thalidomide can be used to treat multiple myeloma, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome and possibly Irritable Bowel Syndrome." }, { "input": "What are reactive metabolites?", "output": "Reactive metabolites are generated when a small molecule, commonly a drug or hydrocarbon, is broken down in the body. Reactive metabolites can cause cancer and other diseases as well as hepatoxicty. " }, { "input": "What is the \"wearing-off\" phenomenon in levodopa-treated patients with Parkinson's Disease?", "output": "Chronic administration of traditional levodopa/dopa decarboxylase inhibitor formulations to Paskinson's Disease patients is associated with the development of complications, such as wearing-off phenomenon. Wearing-off phenomenon is characterized by the predictable emergence of motor symptoms (e.g. rigidity and freezing) and nonmotor PD symptoms (e.g. anxiety and shortness of breath), before the next scheduled dose of medication." }, { "input": "What are prions?", "output": "Prion diseases are protein conformation disorders and neither caused by viroid or virus but is a transmissible particle labeled a prion by Pruisner. Normal prion protein becomes infectious by a different folding, but the triggers are not known. " }, { "input": "What are prions?", "output": "A prion is an infectious agent composed entirely of protein and is responsible for a number of neurodegenerative diseases. Prions are self-propagating infectious protein isoforms. " }, { "input": "Does Vitamin D induce autophagy?", "output": "Yes, vitamin D induces autophagy." }, { "input": "What is sQTLseekeR?", "output": "sQTLseekeR is an R package for the identification of genetic variants associated with alternative splicing. It is based on a statistical framework that uses a distance-based approach to compute the variability of splicing ratios across observations, and a non-parametric analogue to multivariate analysis of variance." }, { "input": "What is Creutzfeldt-Jakob Disease (CJD)?", "output": "Creutzfeldt-Jakob disease (CJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of CJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc)." }, { "input": "What is Creutzfeldt-Jakob Disease (CJD)?", "output": "Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)" }, { "input": "What is Creutzfeldt-Jakob Disease (CJD)?", "output": "Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system" }, { "input": "Describe what is athelia syndrome?", "output": "Athelia is a very rare entity that is defined by the absence of the nipple-areola complex." }, { "input": "Is RASA2 involved in melanoma?", "output": "Yes. Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in \u226530% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer." }, { "input": "What is BioCreative?", "output": "A community wide effort to evaluate biomedical information extraction and text mining." }, { "input": "What is Contrave prescribed for?", "output": "Contrave(?) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity" }, { "input": "What is Contrave prescribed for?", "output": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity" }, { "input": "What is Contrave prescribed for?", "output": "Contrave(\u00ae) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity." }, { "input": "Which is the chromosome area that the human gene coding for the dopamine transporter (DAT1) is located to?", "output": "The gene encoding DAT1 consists of 15 exons spanning 60 kb and is located on chromosome 5p15.3." }, { "input": "What type of mutation is causing the industrial melanism phenotype in peppered moths?", "output": "The mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex." }, { "input": "What gene is mutated in Huntington's disease?", "output": "Huntington disease (HD; OMIM 143100), a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene. Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD)." }, { "input": "What gene is mutated in Huntington's disease?", "output": "Huntington disease is a progressive neurodegenerative disorder and is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene." }, { "input": "Which software package is available for the analysis of conserved genomic loci?", "output": "PHYLUCE is a software package for the analysis of conserved genomic loci. It identifies targeted, enriched loci from the off-target background data; aligns enriched contigs representing conserved loci to one another; and prepare and manipulate these alignments for subsequent phylogenomic inference. PHYLUCE is an efficient and easy-to-install software package that accomplishes these tasks across hundreds of taxa and thousands of enriched loci" }, { "input": "Which software package is available for the analysis of conserved genomic loci?", "output": "PHYLUCE is a software package for the analysis of conserved genomic loci" }, { "input": "Mutation of which gene is implicated in the Christianson syndrome?", "output": "Christianson syndrome is caused by mutations in SLC9A6 and is characterized by severe intellectual disability, absent speech, microcephaly, ataxia, seizures, and behavioral abnormalities." }, { "input": "What is Eteplirsen (Exondys 51)?", "output": "Eteplirsen (Exondys 51) is an antisense oligonucleotide designed to induce exon 51 skipping that is developed by Sarepta Therapeutics. Intravenous eteplirsen has received accelerated approval from the US FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping.\nBy the method of exon skipping in dystrophin pre-mRNA the reading frame is restored and the internally deleted but functional dystrophin is produced." }, { "input": "What are the SINEUPs?", "output": "SINEUPs represent a new class of natural and synthetic antisense long non-coding RNAs that activate translation. These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation. Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs. Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest." }, { "input": "What is trichotillomania?", "output": "Trichotillomania is a hair pulling disorder." }, { "input": "What is the mechanism of action of raxibacumab?", "output": "Raxibacumab is a recombinant human IgG1 monoclonal antibody that binds the protective antigen of Bacillus anthracis, thus blocking toxin effects.\nIt is approved to treat inhalational anthrax." }, { "input": "What is the effect of CPEB3 binding to the CPE domain?", "output": "The cytoplasmic polyadenylation element (CPE) is the binding platform for CPE-binding protein (CPEB), which promotes polyadenylation-induced translation." }, { "input": "Is SUMOylation a post-translational modification in eukaryotes?", "output": "Yes, SUMOylation that is the conjugation of target proteins with SUMO (small ubiquitin-related modifier), is a type of post-translational modification in eukaryotes." }, { "input": "What is the Shelterin complex?", "output": "Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state." }, { "input": "What disease is the drug aducanumab targeting?", "output": "Aducanumab is an anti-A\u03b2 antibody being developed for the treatment of Alzheimer's disease (AD)." }, { "input": "Which human syndromes have been detected with Fluorescence in situ hybridization (FISH)?", "output": "To explore the clonal evolution of monosomy 7 in patients with aplastic anemia (AA).Monosomy 7 (-7) in 81 AA patients with normal karyotype at diagnosis and 46 AA treated with immunosuppressive therapy (IST) and more than 6 months of recombinant human granulocyte colony-stimulating factor (rhuG-CSF) were detected by interphase- fluorescence in situ hybridization (FISH) retrospectively.There were 5.4% - 7.6% of -7 cells in 11 (13.6%) of 81 patients at diagnosis, the survival and response rate to IST in -7 positive patients did not differ s Former molecular cytogenetic studies showed that such aberrations as an equivalent of intrinsic radiosensitivity can be detected by fluorescence in-situ hybridization (FISH) techniques using whole chromosome painting (wcp) probes. Five-color FISH was performed using human DNA segments specific for peri-CEN or subTEL, which were labeled with five different fluorescent dyes [7-diethylaminocoumarin (DEAC): blue, fluorescein isothiocyanate (FITC): green, rhodamine 6G (R6G): yellow, TexRed: red, and cyanine5 (Cy5): purple]. Using this technique, followed by cell-by-cell multicolor fluorescence in situ hybridization (FISH) analysis of purified FNRBCs, we were able to detect some of the most common human aneuploidies (including Down syndrome, Klinefelter syndrome, and trisomy 13) in 33 pregnant women referred for amniocentesis." }, { "input": "Which human syndromes have been detected with Fluorescence in situ hybridization (FISH)?", "output": "The human syndromes which can be detected with FISH are:\n1) Myelodysplastic Syndrome (MDS)\n2) Genetic syndromes caused by somatic chromosomal mosaicism\n3) Prader Willi syndrome (PWS)\n4) Angelman syndrome (AS)\n5) Williams syndrome\n6) Smith Magenis syndrome \n7) Velocardiofacial syndrome\n8) Jacobsen syndrome\n9) Shwachman-Diamond syndrome\n10) Saethre-Chotzen syndrome \n11) DiGeorge syndrome (DGS) \n12) Velo-cardio-facial syndrome (VCFS)\n13) Miller-Dieker syndrome\n14) Deletion 22q11.2 syndrome (D22S)" }, { "input": "List symptoms of EAST syndrome.", "output": "Epilepsy, ataxia, sensorineural deafness, and tubulopathy comprise EAST syndrome that is associated with recessive mutations in the KCNJ10 gene." }, { "input": "When did the polio vaccine becomes available?", "output": "Inactivated poliovirus vaccine (IPV), developed in the USA by Jonas Salk in the early 1950s, was field tested in 1954," }, { "input": "When did the polio vaccine becomes available?", "output": "The Salk polio Vaccine was field tested in 1954." }, { "input": "Is Annexin V an apoptotic marker?", "output": "Yes, annexin V is an early apoptotic marker." }, { "input": "Is Annexin V an apoptotic marker?", "output": "Yes, Annexin V is an apoptotic marker." }, { "input": "Which are the lipid lowering drugs administered in patients with Coronary Artery Disease (CAD)?", "output": "The lipid lowering drugs administered in patients with Coronary Artery Disease (CAD) are:\n1) Statins\n2) Fibrates\n3) Resins\n4) Niacin\n5) Cholesterol absorption-inhibiting drugs." }, { "input": "What are PD-1 inhibitors?", "output": "The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) are used to treat cancer. " }, { "input": "Is the protein lefty an inhibitor of nodal?", "output": "Yes, lefty is an inhibitor of nodal." }, { "input": "List drugs withdrawn from the market for cardiovascular adverse events.", "output": "Over the years, a number of different drugs have been withdrawn for Cardiotoxicity. Drugs like Clobutinol, that induce cardiac arrhythmias by a blockade of the potassium channel coded by the hERG channel, sibutramine for weight loss and Cox2 inhibitors, Rofecoxib and Valdecoxib have been withdrawn from the market." }, { "input": "Is Migalastat used for treatment of Fabry Disease?", "output": "Yes, Migalastat is approved for treatment of Fabry disease. Migalastat is an oral pharmacological chaperone developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of \u03b1-Gal to facilitate normal lysosomal trafficking." }, { "input": "Where are Paneth cells located?", "output": "Paneth cells are located in the intestinal crypt base columnar cells (CBCCs)." }, { "input": "Which are the types of viral meningitis?", "output": "Aseptic meningitis is the most common type of meningitis and is characterized by meningeal inflammation that is not linked to identifiable bacterial pathogens in cerebrospinal fluid (CSF). It can be originated from infection from:\n1) Varicella-zoster virus (VZV)\n2) Herpes simplex types I and II (HSV-1, HSV-2)\n3) Epstein-Barr virus (EBV) \n4) Cytomegalovirus (CMV) \n5) Enteroviruses (EV) \n6) Parechoviruses (HPeV) \n7) Human rhinoviruses (HRVs) \n8) Echovirus types 6, 9, 11\n9) West Nile Virus (WNV)" }, { "input": "What are the different classes of orally administered drugs used to treat diabetes", "output": "There are a number of classes of medications tha are used to treat Type 2 diabetes. These include biguanides like metformin, which decreased hepatic glucose release; sulfonyureas like Glimepride, metglitinides like repaglin and d-phenylalanine derivatives, all of which stimulate pancreatic insulin release; Glitizones or thiazolidinediones which make the body more sensitive to insulin; DPP-4 inhibitors which lower the amount of glucose made in the body; alpha-glucosidase inhibitors which slow the absorbtion of carbohydrate in the blood; and bile acid sequestrants that lower blood glucose" }, { "input": "Which pipelines are used for analyzing data from ChIP-nexus experiments?", "output": "PeakXus and Q-nexus enable comprehensive transcription factor binding site discovery from ChIP-nexus experiments." }, { "input": "What do statins do?", "output": "Statins lower high cholesterol" }, { "input": "What do statins do?", "output": "Statins, which specifically inhibit HMG Co-A reductase, the rate-limiting step of cholesterol biosynthesis, are widely prescribed to reduce serum cholesterol and cardiac risk," }, { "input": "Which cells secretes alpha defensin 5?", "output": "Human enteric \u03b1-defensins (HD5 and HD6), major antimicrobial peptides produced by Paneth cells in the intestine, play important roles in intestinal innate immunity." }, { "input": "Do statins cause diabetes?", "output": "The relationship between T2DM and statins is further complicated since these drugs can cause new onset diabetes (NOD) although there is an overall benefit in terms of preventing vascular events." }, { "input": "Do statins cause diabetes?", "output": "Statin use has been associated with increased risk of developing type 2 diabetes (T2DM), and with impaired glycemic control in T2DM patients" }, { "input": "What is the effect of nocodazole cell treatment?", "output": "Nocodazole trigger mitotic arrest." }, { "input": "What is Path2PPI?", "output": "Path2PPI is an R package to identify protein-protein interaction (PPI) networks for fully sequenced organisms for which nearly none PPI are known. Path2PPI predicts PPI networks based on sets of proteins from well-established model organisms, providing an intuitive visualization and usability. It can be used to combine and transfer information of a certain pathway or biological process from several reference organisms to one target organism." }, { "input": "SPAG5 was implicated in which cancers?", "output": "SPAG5 was implicated in prostate cancer, lung cancer and cervical cancer." }, { "input": "What are some of the effects of Zika Virus in infected individuals?", "output": "While most of the symptoms of zika virus are relatively mild, zika virus in pregnant mothers can cause microcephaly and other congenital defects in the fetus." }, { "input": "What is the function of Oseltamivir when administered during flu?", "output": "Oseltamivir (has known by its brand name 'Tamiflu') is a prodrug, requiring ester hydrolysis for conversion to the active form, Oseltamivir carboxylate. Oseltamivir is the first orally active neuraminidase inhibitor and it is an antiviral drug for the treatment of Swine Flu." }, { "input": "What is the composition of the gamma-secretase complex?", "output": "Gamma-secretase is a multisubunit enzyme complex which is consists of four proteins: presenilin 1 (PS1) or presenilin 2 (PS2), nicastrin, Aph-1 and Pen-2." }, { "input": "List kinases that phosphorylates the protein Bora.", "output": "During cell division Bora becomes multiply phosphorylated by a variety of cell cycle kinases, including Aurora A and Plk1, and GSK3\u03b2 and Cdk1 albeit at distinctive sites." }, { "input": "Are deletions of chromosomal regulatory boundaries associated with congenital disease?", "output": "Yes. Enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation." }, { "input": "What is the role of the UBC9 enzyme in the protein sumoylation pathway?", "output": "The small ubiquitin-like modifier (SUMO) pathway in eukaryotes is an essential post-translational modification required for a variety of cellular processes, development and organelle biogenesis. SUMO-conjugating enzyme (Ubc9) is the sole conjunction enzyme in the SUMO pathway." }, { "input": "Can the Micro-C XL method achieve mononucleosome resolution?", "output": "Yes. Micro-C XL is an improved method for analysis of chromosome folding at mononucleosome resolution." }, { "input": "Can Diabetes be caused by a defect in a potassium chanel?", "output": "Mutations in the KATP channel can lead to neonatal diabetes." }, { "input": "Can Diabetes be caused by a defect in a potassium chanel?", "output": "Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively." }, { "input": "Which fimA genotypes are associated with disease?", "output": "FimA has been characterized as an important virulence factor for P. gingivalis, and many studies, both animal experiments and clinical investigations, have characterized fimA genotypes II, Ib, and IV to be associated with disease (periodontitis and cardiovascular disease)" }, { "input": "Is rucaparib used for ovarian cancer treatment?", "output": "Yes, rucaparib is a PARP inhibitor that is used for ovarian cancer treatment." }, { "input": "What is the role of cohesins at the IFNG locus?", "output": "Cohesins form cell-type-specific long-range chromosomal cis-interactions at the developmentally regulated IFNG locus. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development and disease." }, { "input": "Describe Wellens' Syndrome.", "output": "Wellens Syndrome (WS) is a condition characterized by typical changes in ECG, which are biphasic T-wave inversions (less common) or symmetric and deeply inverted T waves (including 75%) in lead V2-V3 chest derivations." }, { "input": "Which human disease is associated with mutated UBQLN2", "output": "Ggene mutations in UBQLN2 cause dominant inheritance of amyotrophic lateral sclerosis (ALS)." }, { "input": "Which ApoE isoform is associated with hyperlipoproteinemia?", "output": "Type III hyperlipoproteinemia (HLP) is characterized by the accumulation of remnant lipoproteins in the plasma and it is associated with ApoE2 isoform. ApoE2 binds poorly to low density lipoprotein receptors, resulting in defective remnant lipoprotein clearance." }, { "input": "Could hypophosphatemic rickets cause craniosynostosis?", "output": "Yes, hypophosphatemic rickets could cause craniosynostosis." }, { "input": "Is vortioxetine effective for treatment of depression?", "output": "Yes. Vortioxetine is the most recently approved medication for the treatment of major depressive disorder." }, { "input": "Is vortioxetine effective for treatment of depression?", "output": "Yes, vortioxetine (Lu AA21004) is effective for treatment of major depressive disorder (MDD). Vortioxetine is approved for MDD in the USA. Vortioxetine has been also shown to be effective for treatment of generalized anxiety disorder." }, { "input": "Which server is used for simulation of macromolecular diffusional association?", "output": "Macromolecular interactions play a crucial role in biological systems. Simulation of diffusional association (SDA) is a software for carrying out Brownian dynamics simulations that can be used to study the interactions between two or more biological macromolecules. webSDA allows users to run Brownian dynamics simulations with SDA to study bimolecular association and encounter complex formation, to compute association rate constants, and to investigate macromolecular crowding using atomically detailed macromolecular structures. webSDA facilitates and automates the use of the SDA software, and offers user-friendly visualization of results." }, { "input": "Which server is used for simulation of macromolecular diffusional association?", "output": "Simulation of diffusional association (SDA) is a software for carrying out Brownian dynamics simulations that can be used to study the interactions between two or more biological macromolecules. webSDA allows users to run Brownian dynamics simulations with SDA to study bimolecular association and encounter complex formation, to compute association rate constants, and to investigate macromolecular crowding using atomically detailed macromolecular structures." }, { "input": "Which server is used for simulation of macromolecular diffusional association?", "output": "webSDA allows users to run Brownian dynamics simulations with SDA to study bimolecular association and encounter complex formation, to compute association rate constants, and to investigate macromolecular crowding using atomically detailed macromolecular structures. webSDA currently has three modules: 'SDA docking' to generate structures of the diffusional encounter complexes of two macromolecules, 'SDA association' to calculate bimolecular diffusional association rate constants, and 'SDA multiple molecules' to simulate the diffusive motion of hundreds of macromolecules." }, { "input": "Can beans induce apoptosis?", "output": "White kidney bean lectin has been shown to exert anti-proliferative and apoptotic effects on cancer cells" }, { "input": "What is the function of transthyretin in cerebrospinal fluid?", "output": "Transthyretin (TTR) is a protein synthesized in the choroid plexus, which forms the blood-cerebrospinal fluid barrier. TTR is the physiological carrier of thyroxine (T4) and retinol from the blood into the cerebrospinal fluid and their distribution in the brain. The transport of T4 is important for normal development of the brain." }, { "input": "Can you define iatrogenic disease?", "output": "An iatrogenic disease is one that arises from treatment of another illness, such as an arrythmia that results from surgery or and hospital aquired infection in an immunocompromised patient." }, { "input": "Where do the Schwann cells and melanocytes originate from?", "output": "Schwann cells and melanocytes originate from the multipotent population of neural crest cells." }, { "input": "Please list 3 diseases associated with the PIEZO2 gene.", "output": "Recently, Gordon syndrome has been associated to heterozygous mutations in the piezo-type mechanosensitive ion channel component 2 gene (PIEZO2). Different mutations of this gene also cause distal arthrogryposis type 5 and Marden-Walker syndrome." }, { "input": "Is treatment resistant depression related to vitamin B9?", "output": "Treatment with SAMe, as well as with various formulations of folates and analogues, appears to be efficacious and well tolerated in reducing depressive symptoms in treatment resistant depression." }, { "input": "Where is the protein slitrk1 localized?", "output": "Slitrk1 is enriched in postsynaptic fractions and is localized to excitatory synapses. " }, { "input": "Describe clinical manifestation of the Harlequin syndrome.", "output": "Harlequin syndrome is characterized by the sudden onset of unilateral facial flushing and sweating, often preceded by exercise, excessive heat, or, rarely, regional anesthesia. It is a rare autonomic disorder due to a hemifacial cutaneous sympathetic denervation." }, { "input": "What is the role of the constitutive photomorphogenesis 9 signalosome (CSN)?", "output": "The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a protein complex involved in the ubiquitin proteasome system and plays a role in regulating the degradation of polyubiquitinated proteins. The mammalian CSN is also involved in embryonic development, in cancer and the DNA damage response, whereas in plants CSN plays a role in innate immunity." }, { "input": "Is adalimumab effective for hidradenitis suppurativa?", "output": "Yes, Adalimumab, a recombinant, fully humanized, anti-tumor necrosis factor alpha (anti-TNF-\u03b1) monoclonal antibody, is the only officially approved treatment for the management of moderate-to-severe hidradenitis suppurativa." }, { "input": "What is Legg-Calv\u00e9-Perthes Disease", "output": "Legg-Calve-Perthes disease is idiopathic avascular necrosis of the hip, usually occurring in pediatric populations." }, { "input": "What is Legg-Calv\u00e9-Perthes Disease", "output": "Legg-Calv\u00e9-Perthes' (Perthes') disease is a developmental disease of the hip joint that may result in numerous short and long term problems. Legg-Calve-Perthes disease (LCPD) is the insidious onset of idiopathic avascular necrosis of the hip in the pediatric population." }, { "input": "What is promoted by ERAP1-ERAP2 dimerization?", "output": "ERAP1-ERAP2 dimerization increases peptide-trimming efficiency." }, { "input": "What is promoted by ERAP1-ERAP2 dimerization?", "output": "ERAP1-ERAP2 dimerization increases peptide-trimming efficiency. ERAP1-ERAP2 heterodimers produce several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize. Physical interaction with ERAP2 changes basic enzymatic parameters of ERAP1 and improves its substrate-binding affinity. Thus, by bringing the two enzymes in proximity and by producing allosteric effects on ERAP1, dimerization of ERAP1/2 creates complexes with superior peptide-trimming efficacy. Such complexes are likely to enhance Ag presentation by cells displaying coordinated expression of the two enzymes." }, { "input": "What is promoted by ERAP1-ERAP2 dimerization?", "output": "The endoplasmic reticulum aminopeptidases (ERAP)1 and ERAP2 play a critical role in the production of final epitopes presented by MHC class I molecules." }, { "input": "What is plantar fasciitis", "output": "Plantar fascia (PF) disorders like plantar fasciitis commonly cause heel pain and disability and are thought to be degenerative rather than inflammatory in nature" }, { "input": "Which is the enzymatic activity of OTULIN?", "output": "OTULIN is a deubiquitinase, that specifically cleaves Met1-linked polyUb." }, { "input": "List diseases that could be targeted by disaggregases?", "output": "UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act." }, { "input": "Can NEECHAM Confusion Scale be used for evaluation of postoperative delirium?", "output": "Yes, NEECHAM Confusion Scale can be used for evaluation of postoperative delirium." }, { "input": "What is adhesive capsulitis", "output": "Adhesive capsulitis also known as \"frozen shoulder\" is characterized by painful, gradual loss of active and passive shoulder motion resulting from fibrosis and contracture of the joint capsule." }, { "input": "Describe the applicability of Semantic MediaWiki in the case of FANTOM5", "output": "To make the heterogeneous data set accessible and useful for investigators, a web-based database called Semantic catalog of Samples, Transcription initiation And Regulators (SSTAR) has been developed. SSTAR utilizes the open source wiki software MediaWiki along with the Semantic MediaWiki (SMW) extension, which provides flexibility to model, store, and display a series of data sets produced during the course of the FANTOM5 project. The use of SMW demonstrates the utility of the framework for dissemination of large-scale analysis results. SSTAR is a case study in handling biological data generated from a large-scale research project in terms of maintenance and growth alongside research activities" }, { "input": "Is there an association between Muenke Syndrome and FGFR3 gene mutation?", "output": "Yes, Muenke syndrome is caused by point mutation (C749G) in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. It affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis." }, { "input": "Which R package is used for visualization of linear and circular karyotypes?", "output": "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix. The output graphics, saved in two different formats (EPS and SVG), can be easily imported to and modified in presentation and image-editing computer programs. The tool is freely distributed under GNU General Public License (GPL) and can be installed from Bioconductor or from the chromDraw home page." }, { "input": "Which R package is used for visualization of linear and circular karyotypes?", "output": "The chromDraw graphical tool was developed as a user-friendly graphical tool for visualizing both linear and circular karyotypes based on the same input data matrix. The tool is freely distributed under GNU General Public License (GPL) and can be installed from Bioconductor or from the chromDraw home page." }, { "input": "Has small pox been eradicated from the world?", "output": "smallpox is now eradicated." }, { "input": "Has small pox been eradicated from the world?", "output": "Yes, small pox has been eradicated." }, { "input": "Has small pox been eradicated from the world?", "output": "smallpox is now eradicated" }, { "input": "Has small pox been eradicated from the world?", "output": "small pox has been eradicated." }, { "input": "Where is Akkermansia muciniphila found?", "output": "Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals." }, { "input": "Where is Akkermansia muciniphila found?", "output": "RYGB led to altered relative abundances of 31 species (P\u2009<\u20090.05, q\u2009<\u20090.15) within the first 3\u00a0months, including those of Escherichia coli, Klebsiella pneumoniae, Veillonella spp., Streptococcus spp., Alistipes spp., and Akkermansia muciniphila. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia m However, faeces from the UC cohort had lower proportions of Akkermansia muciniphila and increased diversity within Clostridium cluster XIVa compared to controls.Gut fermentation of NSP and starch is diminished in patients with UC. Specific members of the microbiota such as Akkermansia muciniphila might be decreased in diabetes and when administered to murines exerted antidiabetic effects. In parallel, the antibiotic susceptibility of Akkermansia muciniphila Muc(T) strain was studied and this strain was observed by electron microscopy." }, { "input": "Is there alternative polyadenylation during zebrafish development?", "output": "Yes. There is extensive alternative polyadenylation during zebrafish development." }, { "input": "Which NADPH oxidase family member requires interaction with NOXO1 for function?", "output": "NADPH oxidase 1 (NOX1) requires interaction with NOXO1 for function." }, { "input": "Are alterations in ultraconserved elements implicated in breast cancer?", "output": "Yes. SNPs in ultraconserved elements (UCEs) might be associated with cancer risk." }, { "input": "What is the mechanism of action of Osimertinib?", "output": "Osimertinib is a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation." }, { "input": "What is Bartter syndrome?", "output": "All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism" }, { "input": "What is Bartter syndrome?", "output": "All forms of hereditary Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism." }, { "input": "Is there any tool that facilitates the functional analysis of cis-regulatory regions in zebrafish?", "output": "Yes. The zebrafish enhancer detection (ZED) vector is a tool that facilitates transgenesis and the functional analysis of cis-regulatory regions in zebrafish." }, { "input": "List RNA modifications databases", "output": "RMBase and MODOMICS" }, { "input": "Please list the 3 findings in HELLP syndrome.", "output": "hemolysis, elevated liver enzymes and low platelets constitute the hellp syndrome." }, { "input": "Please list the 3 findings in HELLP syndrome.", "output": "HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is an obstetric complication and is characterized by microangiopathic hemolytic anemia, elevated liver enzymes by intravascular breakdown of fibrin in hepatic sinusoids and reduction of platelet circulation by its increased consumption" }, { "input": "Which mutated gene is associated with Waardenburg and Tietz syndromes?", "output": "Mutations in microphthalmia-associated transcription factor (MITF) gene cause Waardenburg and Tietz syndromes." }, { "input": "List the three most abundant bacterial phyla present in mouse feces.", "output": "Firmicutes\nProteobacteria \nBacteroidetes" }, { "input": "What gene is mutated in Sickle Cell Anemia?", "output": "Sickle cell anemia (SCA) is an autosomal recessive disease caused by by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis." }, { "input": "What gene is mutated in Sickle Cell Anemia?", "output": " sca patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene." }, { "input": "What is the function of the Indian hedgehog protein in chondrocytes?", "output": "Indian hedgehog is a protein that regulates endochondral differentiation and ossification in both a parathyroid hormone-related protein (PTHrP)-dependent and -independent manner by activating transcriptional mediator Gli2 and is an essential factor for proper skeletal development." }, { "input": "What is the function of R-spondin 1 and noggin in non-damaged gallbladders?", "output": "R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders." }, { "input": "List the classical triad of symptoms of the Melkersson\u2013Rosenthal syndrome.", "output": "The Melkersson-Rosenthal syndrome consists of the classical triad of symptoms:\n1) orofacial oedema \n2) fissured tongue (lingua plicata) and\n3) facial paralysis." }, { "input": "Which disease is treated with taliglucerase alfa?", "output": "Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease." }, { "input": "What is formin associated with in the snail?", "output": "Formin is associated with Left-Right asymmetry in the pond snail and the frog." }, { "input": "What is formin associated with in the snail?", "output": "Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog" }, { "input": "What is the major difference between eucaryotes and procaryotes?", "output": "Eucaryotes have a nucleolus, Procaryotes do not. Eucrayotes have a nuclear membrane, organelles and differ in transcription and translation. Procaryotes have polycistronic RNA and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes. " }, { "input": "What is the major difference between eucaryotes and procaryotes?", "output": "The nucleolus is the most prominent compartment in the nucleus and known as the site for ribosome biogenesis in eucaryotes. In contrast, there is no such equivalent structure for ribosome synthesis in procaryotes Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes." }, { "input": "What is the major difference between eucaryotes and procaryotes?", "output": "The nucleolus is the most prominent compartment in the nucleus and known as the site for ribosome biogenesis in eucaryotes. In contrast, there is no such equivalent structure for ribosome synthesis in procaryotes Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes. extra guanylate at the 5' end of mature E. coli tRNAHis is encoded in the gene and is found in tRNA as the result of an unusual cleavage by RNase P There are considerable differences of run distributions in DNA sequences of procaryotes, invertebrates and vertebrates. However, some interesting exceptions from this rule exist for the run distribution of adenine in procaryotes and for the arrangement of purine-pyrimidine runs in eucaryotes" }, { "input": "What is the HSP70-HSP110 disaggregase machinery?", "output": "Clearance of misfolded and aggregated proteins is central to cell survival. UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act." }, { "input": "Has whole exome sequencing been performed in Alzheimer patients?", "output": "Yes, numerous whole exome sequencing studies of ALzheimer patients have been conducted." }, { "input": "Which is the genome browser database for DNA shape annotations?", "output": "GBshape provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution." }, { "input": "Is Stat4 a transcription factor?", "output": "Yes, Stat4 is a transcription factor.\nStat4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus." }, { "input": "Have the promoter regions of the genes implicated in Rett Syndrome been characterized with CAGE?", "output": "Yes. Promoter regions of the genes implicated in Rett Syndrome have been characterized using CAGE." }, { "input": "Has \"RNA interference\" been awarded Nobel prize?", "output": "Since the first unequivocal description of RNA interference (RNAi) in 1998, it has remained one of the hottest topics under investigation, culminating in the award of a Nobel Prize to its discoverers in 2006." }, { "input": "Is there any role for Pds5b in cohesion establishment?", "output": "Yes. Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin." }, { "input": "Which factors are considered in the FUNC score for intracerebral hemorrhage?", "output": "FUNC score includes Age, Glasgow Coma Scale, ICH location, volume and pre-ICH cognitive impairment." }, { "input": "Where is the respirasome located?", "output": "Respirasomes are macromolecular assemblies of the respiratory chain complexes I, III and IV in the inner mitochondrial membrane. The 4.0 \u00c5 cryo-EM structure of one of the most intricate enzyme systems, the respirasome, in the mitochondrial inner membrane is now available." }, { "input": "Describe the usefulness of MiRduplexSVM.", "output": "MiRduplexSVM is a high-performing miRNA-duplex prediction and evaluation methodology. It's a method that combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model. It is the first model that provides precise information about all four ends of the miRNA duplex." }, { "input": "What genes are drug targets for Fibrodysplasia Ossificans Progressiva (FOP)?", "output": " Recently, FOP has been associated with a specific mutation of ACVR1, the gene coding for a bone morphogenetic protein type I receptor. " }, { "input": "What genes are drug targets for Fibrodysplasia Ossificans Progressiva (FOP)?", "output": "here, it is noted that if b cells are found to be the lymphocytes responsible for excess bmp-4 production in fop, use of rituximab, a monoclonal anti-cd20 antibody which effectively targets b cells, could be a less permanent and less risky treatment alternative for fop." }, { "input": "What genes are drug targets for Fibrodysplasia Ossificans Progressiva (FOP)?", "output": "Inhibitors of ALK2(ACVR1) are used for the treatment of FOP. Current therapies for FOP are Dorsomorphin analogues which function as BMP inhibitor. if B cells control excess BMP-4 production in FOP, use of Rituximab, a monoclonal which targets B cells, could be a treatment alternative for FOP." }, { "input": "What kind of analyses are performed with the software tool \"unipept\"", "output": "The Unipept web application (http://unipept.ugent.be) supports biodiversity analysis of large and complex metaproteome samples using tryptic peptide information obtained from shotgun MS/MS experiments. The application designed for metaproteomics analysis with a focus on interactive datavisualization." }, { "input": "What is the role of gamma-secreatase complex in Alzheimer's Disease?", "output": "The gamma-secretase complex has a decisive role in the development of Alzheimer's disease, as it cleaves a precursor protein to create the amyloid beta peptide whose aggregates form the senile plaques encountered in the brains of patients. Gamma-secretase is a member of the intramembrane-cleaving proteases which process their transmembrane substrates within the bilayer." }, { "input": "Which syndromes are associated with heterochromia iridum?", "output": "The syndromes that are associated with heterochromia iridum are:\n1) Ascher's syndrome\n2) Waardenburg Syndrome type II (WS2)\n3) Horner's syndrome." }, { "input": "What is the target of tanezumab?", "output": "Tanezumab is a humanized monoclonal antibody against nerve growth factor." }, { "input": "Could plasmepsins be used as targets for developing anti-malaria drugs?", "output": "Yes, plasmepsins, which are essential Plasmodium proteases, could be highly promising anti-malarial drug targets." }, { "input": "What is MRSA?", "output": "community-associated methicillin resistant staphylococcus aureus (ca-mrsa) has become a severe health concern because of its treatment difficulties." }, { "input": "What is MRSA?", "output": "Methicillin resistant Staphylococcus aureus (MRSA) has become a severe health concern because of its treatment difficulties." }, { "input": "What is MRSA?", "output": "(MRSA, methicillin-resistant S. aureus)" }, { "input": "List peptide fragmentations methods in mass spectrometry", "output": "CID, HCD, ECD, ETD and PSD are different peptide fragmentation technologies used in mass spectrometry." }, { "input": "Is avanafil indicated for treatment of erectile dysfunction?", "output": "Yes, avanafil is indicated for treatment of erectile dysfunction." }, { "input": "What is \"Epitranscriptome analysis\"?", "output": "Modified nucleotides in messenger RNA (mRNA) have been discovered over 40 years ago, but until recently little was known about which transcripts contain them and what their function is. High-throughput sequencing approaches revealed a dynamic landscape of the 'Epitranscriptome' for many mRNA modifications in various organisms from yeast to humans.\t\t\nThe detection methods of RNA modifications has enabled investigation of a new layer of gene regulation - the epitranscriptome." }, { "input": "Which infection can be prevented with Dapivirine?", "output": "Vaginal ring containing Dapivirine is used for HIV prevention in women." }, { "input": "What is Bexsero?", "output": "Bexsero is a 4-component vaccine against capsular Meningococcus serogroup B (4CMenB), which has recently been licensed in Europe, Canada and Australia." }, { "input": "What is Bexsero?", "output": "Bexsero is amulticomponent vaccine against serogroup B Neisseria meningitidis (MenB)." }, { "input": "Is there a role for gamma knife in treatment of Obsessive-Compulsive Disorder?", "output": "Yes. Gamma knife radiosurgery is being increasingly to treat refractory obsessive- compulsive disorder (OCD). It is reserved for severe, treatment-refractory disease that has not responded to multiple treatments." }, { "input": "What is the mechanism of action of the biguanide class of diabetes drugs?", "output": "this biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels." }, { "input": "What is the mechanism of action of the biguanide class of diabetes drugs?", "output": "Bioguaides like Metformin, decrease amount of glucose released from liver and increases insulin sensitivity. " }, { "input": "Where is the proteasome located?", "output": "The proteasome can be found in perinuclear and nuclear location, as well as in cytosolic compartments, such as mitochondria and endoplasmic reticulum. Proteasome-mediated degradation of cell cycle regulatory proteins, production and loading of antigenic peptides onto HLA molecules, and transient homing of diverse virion proteins required for entry and/or egress have been also shown to be coordinated at the centrosome." }, { "input": "What is clinical presentation of the Gardner-Diamond syndrome?", "output": "Psychogenic purpura, also known as Gardner-Diamond syndrome, is a rare, distinctive, localized cutaneous reaction pattern mostly affecting psychologically disturbed adult women. Repeated crops of tender, ill-defined ecchymotic lesions on the extremities and external bleeding from other sites characterize the condition." }, { "input": "Where can you find the annulus of Zinn?", "output": "Annulus of Zinn is in the orbit." }, { "input": "What is the indication for SLCO1B1 genotyping?", "output": "HMG Co-A reductase inhibitors, commonly known as statins, also display wide interindividual variability in plasma concentration, response and toxicity due in part to polymorphisms in transporter genes, including SLCO1B1 and ABCG2. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin." }, { "input": "List available circular RNA prediction tools.", "output": "circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice." }, { "input": "Which disease is treated with Nusinersen?", "output": "Nusinersen us used for treatment of Spinal Muscular Atrophy." }, { "input": "Which disease the London mutation involved in?", "output": "London mutation that is the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile) is involved in Alzheimer's Disease." }, { "input": "Define lncRNA.", "output": "Long noncoding RNAs (lncRNAs) represent a newly discovered class of regulatory molecules that impact a variety of biological processes in cells and organ systems. In humans, it is estimated that there may be more than twice as many lncRNA genes than protein-coding genes. However, only a handful of lncRNAs have been analyzed in detail.\nLong non-coding RNAs (lncRNAs) are emerging as key molecules in cancers, yet their potential molecular mechanisms are not well understood.\nlong noncoding RNAs (lncRNAs), the largest family of noncoding transcripts, have emerged as common regulators of many cellular stressors; including heat shock, metabolic deprivation and DNA damage." }, { "input": "How many microorganisms are present in human normal gut?", "output": "Human gut microbiota is home to 10 to 100 trillions microorganisms." }, { "input": "What is the role of 3,4-diaminobenzoic acid derivatives in the immune system?", "output": "3,4-diaminobenzoic acid derivatives are inhibitors of the oxytocinase subfamily of M1 aminopeptidases with immune-regulating properties. Cell-based analysis indicated that the lead compounds can be effective in downregulating macrophage activation induced by lipopolysaccharide and interferon-\u03b3 as well as cross-presentation by bone marrow-derived dendritic cells." }, { "input": "Can NADPH oxidase be inhibited by apocynin and diphenylene iodonium?", "output": "Yes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can be inhibited by apocynin or diphenylene iodonium (DPI)." }, { "input": "Viliuisk encephalomyelitis is diagnosed in which geographical area?", "output": "Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic." }, { "input": "What are Septins?", "output": "Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. In yeast, septins assemble into a highly ordered array of filaments at the mother bud neck in Saccharomyces cerevisiae cells. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear." }, { "input": "What are Septins?", "output": "Septins are an evolutionarily conserved family of GTP-binding proteins. discover that septins, a component of the cytoskeleton, recognize membrane curvature at the micron scale, a common morphological hallmark of eukaryotic cellular processes. eptins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. " }, { "input": "What is the drug target for Simtuzumab?", "output": " These results suggest that LOXL2 could be an appealing target for treatment of scar formation after glaucoma surgery, and point to the potential therapeutic benefits of simtuzumab, a humanized monoclonal antibody derived from GS-607601." }, { "input": "What is the drug target for Simtuzumab?", "output": " these results suggest that loxl2 could be an appealing target for treatment of scar formation after glaucoma surgery, and point to the potential therapeutic benefits of simtuzumab, a humanized monoclonal antibody derived from gs-607601." }, { "input": "What is the drug target for Simtuzumab?", "output": "Simtuzumab is a humanized monoclonal antibody drug that targets LOXL2" }, { "input": "What is Dravet syndrome?", "output": "Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality. It is likely that Dravet syndrome is underdiagnosed in adults with treatment-resistant epilepsy." }, { "input": "What is Dravet syndrome?", "output": "dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality." }, { "input": "What is Dravet syndrome?", "output": "Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality. The typical presentation is characterized by hemiclonic or generalized clonic seizures triggered by fever during the first year of life, followed by myoclonic, absence, focal and generalized tonic-clonic seizures." }, { "input": "What is Dravet syndrome?", "output": "Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality." }, { "input": "What is Dravet syndrome?", "output": "Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and is associated with high morbidity and mortality. The typical presentation is characterized by hemiclonic or generalized clonic seizures triggered by fever during the first year of life, followed by myoclonic, absence, focal and generalized tonic-clonic seizures." }, { "input": "What makes telomerase a good drug target?", "output": "Human telomerase is absent in most normal tissues, but is abnormally activated in all major cancer cells. Telomerase enables tumor cells to maintain telomere length, allowing indefinite replicative capacity." }, { "input": "What makes telomerase a good drug target?", "output": "Telomerase, a ribonucleoprotein enzyme is considered as a universal therapeutic target of cancer because of its preferential expression in cancer cells and its presence in 90 % of tumors. Human telomerase is absent in most normal tissues, but is abnormally activated in all major cancer cells." }, { "input": "What makes telomerase a good drug target?", "output": " telomerase, a ribonucleoprotein enzyme is considered as a universal therapeutic target of cancer because of its preferential expression in cancer cells and its presence in 90 % of tumors." }, { "input": "What makes telomerase a good drug target?", "output": "Human telomerase is absent in most normal tissues, but is abnormally activated in all major cancer cells. Telomerase enables tumor cells to maintain telomere length, allowing indefinite replicative capacity. telomerase is believed to be necessary for cancer cells to grow without limit" }, { "input": "What makes telomerase a good drug target?", "output": " Telomerase, a ribonucleoprotein enzyme is considered as a universal therapeutic target of cancer because of its preferential expression in cancer cells and its presence in 90 % of tumors. " }, { "input": "What is DENdb?", "output": "DENdb is a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information." }, { "input": "List scales that are used for scoring of patients with spinal metastasis?", "output": "Tokuhashi, Tomita, Bauer, and Oswestry scores are used for survival prediction of patients with spinal metastases." }, { "input": "Does NADPH oxidase 5 require any subunit for function?", "output": "No, NADPH oxidase 5 (NOX5) does not require any subunits for function." }, { "input": "What are the side effects during statins administration in patients with atherosclerosis?", "output": "The side effects during statins administration in patients with atherosclerosis are:\n1) Myopathy\n2) Transaminase elevations\n3) Diabetes mellitus \n4) Renal and neurologic adverse effects." }, { "input": "Entresto is composed of which two drugs?", "output": "Entresto is composed of sacubitril and valsartan. It is newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure." }, { "input": "What is the doRiNA database?", "output": "doRina is a database of RNA interactions in post-transcriptional regulation." }, { "input": "Is NSD-1015 an inhibitor of Aromatic L-Amino Acid Decarboxylase?", "output": "Yes, NSD-1015 is an ihnibitor of Aromatic L-Amino Decarboxylase." }, { "input": "Is pseudouridine a RNA modification?", "output": "Yes, pseudouridine (\u03a8) is the most abundant of>150 nucleoside modifications in RNA." }, { "input": "What does the human ABCC gene product do?", "output": "The important drug resistance-conferring members belong to three subfamilies of the human ABC family; these are ABCB1 (MDR1/P-glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of subfamily ABCG), which are expressed in various organs. The ATP-binding cassette (ABC) transporters constitute a large family of membrane proteins, which transport a variety of compounds through the membrane against a concentration gradient at the cost of ATP hydrolysis" }, { "input": "What is the connection between furin and hepcidin?", "output": "The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation. The hepatic prohormone convertase furin mediates the posttranslational processing of hepcidin." }, { "input": "Which cells express CIDEC protein in humans?", "output": "The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage. CIDEC is highly expressed in adipocytes, but undetectable in normal liver. However, its hepatic expression rises during fasting or under genetic or diet-induced hepatosteatosis in patients." }, { "input": "Which is the relation between coffee consumption and stroke risk?", "output": "The coffee paradox in stroke: Increased consumption linked with fewer strokes." }, { "input": "What is the purpose of the Orpington Prognostic Scale?", "output": "The Orpington Prognostic Scale (OPS) is used to predict futue functional status of stroke patients, to asses stroke severity, outcome and response to subacute rehabilitation. In patients with stroke, OPS and NIHSS had significant contribution to the estimation of the functional status and OPS was more effective than NIHSS. However, other reported that the OPS has limited predictive accuracy for discharge destination and is a poor predictor of follow-up services." }, { "input": "Do IEG create a ripple effect of transcription?", "output": "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes." }, { "input": "Do IEG create a ripple effect of transcription?", "output": "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Profiling the primary transcripts in the nucleus with whole-genome tiling arrays delineated simultaneous activation of transcription centred on IEGs." }, { "input": "Do IEG create a ripple effect of transcription?", "output": "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Even in surrounding intergenic regions, transcriptional activation took place at the same time." }, { "input": "Do IEG create a ripple effect of transcription?", "output": "rapid induction of immediate-early genes (iegs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes." }, { "input": "Do IEG create a ripple effect of transcription?", "output": "Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes." }, { "input": "Which R package is used for the analysis of genome-wide DNA methylation profiles?", "output": "MethylKit is a comprehensive R package for the analysis of genome-wide DNA methylation profiles. MethylKit includes functions for clustering, sample quality visualization, differential methylation analysis and annotation features, thus automating and simplifying many of the steps for discerning statistically significant bases or regions of DNA methylation." }, { "input": "Do T-Cells regulate neuropathic pain?", "output": "Macrophage-T cell interactions can mediate neuropathic pain through the glucocorticoid-induced TNF" }, { "input": "What is the incidence of new cases of X-linked adrenoleukodystrophy (ALD) in Australian and New Zealand in the late 1990's?", "output": "cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. " }, { "input": "What is the incidence of new cases of X-linked adrenoleukodystrophy (ALD) in Australian and New Zealand in the late 1990's?", "output": "cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000." }, { "input": "What is the incidence of new cases of X-linked adrenoleukodystrophy (ALD) in Australian and New Zealand in the late 1990's?", "output": "When looking cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996, it was estimated that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000." }, { "input": "Can telomere length shortening be reversed by telomerase?", "output": "Yes, telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia." }, { "input": "Is ABCE1 involved in ribosomal recycling?", "output": "Yes, recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea" }, { "input": "What are clinical features of the de Morsier syndrome?", "output": "Classic triad of the De Morsier syndrome (septooptic dysplasia) includes optic nerve hypoplasia, the absence of septum pellucidum, and pituitary hypoplasia." }, { "input": "Does oculocutaneous albinism show an autosomal recessive inheritance?", "output": "Yes, oculocutaneous albinism shows an autosomal recessive inheritance." }, { "input": "Which is the largest metabolic gene cluster in yeast?", "output": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source." }, { "input": "Which is the largest metabolic gene cluster in yeast?", "output": "the dal cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable saccharomyces cerevisiae to use allantoin as a nitrogen source." }, { "input": "Which is the largest metabolic gene cluster in yeast?", "output": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source. The DAL cluster is located in a domain of modified chromatin involving both H2A.Z histone exchange and Hst1-Sum1-mediated histone deacetylation, and it may be a coadapted gene complex formed by epistatic selection." }, { "input": "Which is the largest metabolic gene cluster in yeast?", "output": "The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source. Six of the eight genes involved in allantoin degradation, which were previously scattered around the genome, became relocated to a single subtelomeric site in an ancestor of S. cerevisiae and Saccharomyces castellii." }, { "input": "What is the applicability of the MCAST algorithm?", "output": "The MCAST algorithm uses a hidden Markov model with a P-value-based scoring scheme to identify candidate CRMs." }, { "input": "Which ApoE isoform is associated with atherosclerosis and Alzheimer's disease?", "output": "The ApoE4 isoform is associated with increased frequency of atherosclerosis and Alzheimer's disease (AD)." }, { "input": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "output": "ULEs are located in intergenic or intronic regions and are depleted from segmental duplications. In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes." }, { "input": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "output": "we begin by showing that depletion for uces characterizes the most recent large-scale human cnv datasets and then find that even newly formed de novo cnvs, which have passed through meiosis at most once, are significantly depleted for uces." }, { "input": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "output": "Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell. These elements are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development." }, { "input": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "output": "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset." }, { "input": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "output": "Here we address the process by which CNVs become depleted of UCEs. We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs." }, { "input": "Are Ultra-conserved elements (UCEs) enriched in segmental duplications?", "output": "Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants." }, { "input": "What organism causes woolsorter's disease", "output": "Woolsorter's disease is caused by the same organism as Anthrax, bacillus Anthrax. " }, { "input": "Which annotated database of A-to-I RNA editing is available?", "output": "RADAR is a rigorously annotated database of A-to-I RNA editing. RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice (Mus musculus) and flies (Drosophila melanogaster), together with extensive manually curated annotations for each editing site. RADAR also includes an expandable listing of tissue-specific editing levels for each editing site, which will facilitate the assignment of biological functions to specific editing sites." }, { "input": "Which annotated database of A-to-I RNA editing is available?", "output": "The identification of A-to-I RNA editing sites has been dramatically accelerated in the past few years by high-throughput RNA sequencing studies. RADAR includes a comprehensive collection of A-to-I RNA editing sites identified in humans (Homo sapiens), mice (Mus musculus) and flies (Drosophila melanogaster), together with extensive manually curated annotations for each editing site." }, { "input": "Do normal cells express the protein TERT?", "output": "\u039d\u03bf, telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity." }, { "input": "Which protein complexes recognize centromeric (CEN) DNA in yeast?", "output": "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated. In budding yeast, as well as in other eukaryotes, the Cse4 histone variant (known in vertebrates as CENP-A) is believed to substitute for histone H3 at the centromeric nucleosome." }, { "input": "Which protein complexes recognize centromeric (CEN) DNA in yeast?", "output": "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated Histone H3 localizes to the centromeric DNA in budding yeast In budding yeast, as well as in other eukaryotes, the Cse4 histone variant (known in vertebrates as CENP-A) is believed to substitute for histone H3 at the centromeric nucleosome" }, { "input": "Which protein complexes recognize centromeric (CEN) DNA in yeast?", "output": "The Schizosaccharomyces pombe centromere-linked genes, LYS1 and CYH1 on chromosome I and TPS13 and RAN1 on chromosome II, have been isolated" }, { "input": "Is there any involvement of the long non-coding RNA Gomafu in schizophrenia?", "output": "Yes. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing." }, { "input": "Is butterfly rash a symptom of Systemic lupus erythematosus?", "output": "Yes, butterfly rash is symptom of Systemic lupus erythematosus." }, { "input": "What is the function of yeast Clr4 on chromatin?", "output": "Clr4 is known to regulate silencing and switching at the mating-type loci and to affect chromatin structure at centromeres. The Clr4 methyltransferase determines the subnuclear localization of the mating-type region in fission yeast. Heterochromatin assembly in fission yeast depends on the Clr4 histone methyltransferase, which targets H3K9." }, { "input": "What is the role of LIMT lncRNA?", "output": "LINC01089 (LncRNA Inhibiting Metastasis; LIMT) is a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo." }, { "input": "What is the role of LIMT lncRNA?", "output": "LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer." }, { "input": "Is infertility characteristic of individuals with Fanconi anemia?", "output": "Yes, infertility is characteristic of individuals with Fanconi anemia." }, { "input": "What are Kupffer cells and what is their role?", "output": "Kupffer cells (KCs)are hepatic macrophages which can secrete matrix metalloproteinases (MMPs), and can contribute to decreased hepatic insulin sensitivity. KCs may play a role in the development of drug induced liver injury (DILI)" }, { "input": "What are Kupffer cells and what is their role?", "output": "Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Hepatic macrophages consist of Kupffer cells, which are originated from the fetal yolk-sack, and infiltrated bone marrow-derived monocytes/macrophages. " }, { "input": "What is known about saponins in crops and human consumption?", "output": "Saponins are considered antinutrients for humans and have a bitter taste. They should be removed from the crops before consumption." }, { "input": "Is golimumab effective for ulcerative colitis?", "output": "Yes. Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis." }, { "input": "What is the role of histone variant H2A.W?", "output": "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis. The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants. " }, { "input": "What is the role of histone variant H2A.W?", "output": "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants Covalent histone modifications (e.g." }, { "input": "What is the role of histone variant H2A.W?", "output": "The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. Histone chaperones escort histones, and play key functions during nucleosome assembly/disassembly and in nucleosome structure configuration. Here we focus on plant histone H2A/H2B chaperones, particularly members of the NUCLEOSOME ASSEMBLY PROTEIN-1 (NAP1) and FACILITATES CHROMATIN TRANSCRIPTION (FACT) families, discussing their molecular features, properties, regulation and function. We further discuss roles of NAP1 and FACT in chromatin-based processes, such as transcription, DNA replication and repair. Future major challenges remain in order to define in more detail the overlapping and specific roles of various members of the NAP1 family as well as differences and similarities between NAP1 and FACT family members, and to identify and characterize their partners as well as new families of chaperones to understand histone variant incorporation and chromatin target specificity." }, { "input": "What is the role of histone variant H2A.W?", "output": " In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization." }, { "input": "What is the role of histone variant H2A.W?", "output": "The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis" }, { "input": "What is the role of histone variant H2A.W?", "output": "Histone variants play crucial roles in gene expression, genome integrity, and chromosome segregation. The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. Histone chaperones escort histones, and play key functions during nucleosome assembly/disassembly and in nucleosome structure configuration. Covalent histone modifications (e.g. ubiquitination, phosphorylation, methylation, acetylation) and H2A variants (H2A.Z, H2A.X and H2A.W) are also discussed in view of their crucial importance in modulating nucleosome organization and function." }, { "input": "What is the role of histone variant H2A.W?", "output": "The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization." }, { "input": "Which are the main brain dysfunctions caused by hyperbilirubinemia?", "output": "Bilirubin-induced neurologic dysfunction (BIND) and classical kernicterus are the main dysfunctions of hyperbilirubinemia, whenever bilirubin levels exceed the capacity of the brain defensive mechanisms in preventing its entrance and cytotoxicity. Bilirubin accumulation may lead to deficits in auditory, cognitive, and motor processing, due to neuronal cell death, reduced myelination and glial activation." }, { "input": "Does mTOR regulate the translation of MAPKAPK2?", "output": "Yes. mTOR regulates the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous senescence-associated secretory phenotype (SASP) components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts." }, { "input": "What chromosome is affected in Turner's syndrome?", "output": "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome. " }, { "input": "What chromosome is affected in Turner's syndrome?", "output": "turner's syndrome (ts) is a chromosomal defect with partial or total absence of the x chromosome." }, { "input": "What chromosome is affected in Turner's syndrome?", "output": "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome" }, { "input": "What chromosome is affected in Turner's syndrome?", "output": "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome." }, { "input": "What is the aim of the TRAP assay?", "output": "Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP)." }, { "input": "Describe clinical applications of the PIM2 scoring system.", "output": "The Pediatric Index of Mortality 2 (PIM2) is one of the most commonly used scoring systems to predict mortality in patients admitted to pediatric intensive care units. The PIM2 score adequately discriminates survivors from non-survivor" }, { "input": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "output": "MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells. In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to na\u00efve pluripotency." }, { "input": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "output": "1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development." }, { "input": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "output": "Histone variant macroH2A confers resistance to nuclear reprogramming Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency." }, { "input": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "output": "Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. The histone variant macroH2A acts as a component of an epigenetic multilayer that heritably maintains the silent X chromosome and has been shown to restrict tumor development." }, { "input": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "output": "Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming. In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming" }, { "input": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "output": "MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency." }, { "input": "Which disease is associated with mutations in SLC40A1 gene?", "output": "Mutations in the SLC40A1 gene, which encodes the cellular iron exporter ferroportin, are associated with the autosomal dominant hemochromatosis type 4 or Ferroportin disease. The patients characteristically have hyperferritinemia and iron overload." }, { "input": "Could divalent metal transporter 1 deficiency lead to anemia?", "output": "Yes, divalent metal transporter 1 (DMT1) deficiency could result in anemia, as DMT1 is a major iron transporter required for iron absorption and erythropoiesis. DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells." }, { "input": "Does the hERG gene code for a protein which is part of a sodium channel?", "output": "The hERG AKA Human ether-a-go-go-related gene coded for a protein subunit of a potassium channel that conducts delayed rectifier K(+) current" }, { "input": "Is lenvatinib effective for renal cell carcinoma?", "output": "Yes, combination of lenvatinib and everolimus is approved to treat advanced or metastatic renal cell carcinoma." }, { "input": "Which proteins form part of the NRD complex in S. cerevisiae?", "output": "The purification of an ATR complex allowed identification of chromodomain-helicase-DNA-binding protein 4 (CHD4) as an ATR-associated protein by tandem mass spectrometric sequencing. CHD4 (also called Mi-2beta) is a component of a histone-deacetylase-2 (HDAC2)-containing complex, the nucleosome remodeling and deacetylating (NRD) complex. Endogenous ATR, CHD4, and HDAC2 are shown to coimmunoprecipitate, and ATR and HDAC2 coelute through two biochemical purification steps. Other members of the NRD complex, HDAC1, MTA1, and MTA2, are also detectable in ATR immunoprecipitates. Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termination through the action of its C-terminal domain (CTD)-interacting domain (CID)." }, { "input": "Which R / bioconductor package is used for performing SNP enrichment analysis?", "output": "traseR is an easy-to-use R Bioconductor package that performs enrichment analyses of trait-associated SNPs in arbitrary genomic intervals with flexible options, including testing method, type of background and inclusion of SNPs in LD." }, { "input": "Does HuR bind to the untranslated regions (UTRs) of mRNAs?", "output": "Yes, the RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation." }, { "input": "Describe Exploding head syndrome.", "output": "Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up." }, { "input": "Is H4K20 methylation associated with DNA replication?", "output": "We employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and genome stability in Drosophila cells. Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes. The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing. \u00a9 2016 by The American Society for Biochemistry and Molecular Biology, Inc. lysine) form of TFIIB adversely affects looping at every gene tested, including BLM10, SAC3, GAL10, SEN1, and HEM3. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP." }, { "input": "Which protein mediates gene loop formation in the yeast S. cerevisiae?", "output": "Gene-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of genes, such as TFIIB. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP" }, { "input": "Which protein mediates gene loop formation in the yeast S. cerevisiae?", "output": "Gene looping, defined as the interaction of the promoter and the terminator regions of a gene during transcription, requires transcription factor IIB (TFIIB)." }, { "input": "Which protein mediates gene loop formation in the yeast S. cerevisiae?", "output": "A transcription-independent role for TFIIB in gene looping." }, { "input": "Which two drugs were compared in the ARISTOTLE Trial?", "output": "Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial compared apixaban and warfarin." }, { "input": "What is REVIGO?", "output": "REVIGO summarizes and visualizes long lists of gene ontology terms." }, { "input": "What is REVIGO?", "output": "REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures. Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views. REVIGO is freely available at http://revigo.irb.hr/." }, { "input": "What is REVIGO?", "output": "Outcomes of high-throughput biological experiments are typically interpreted by statistical testing for enriched gene functional categories defined by the Gene Ontology (GO). The resulting lists of GO terms may be large and highly redundant, and thus difficult to interpret.REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures. Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views. REVIGO is freely available at http://revigo.irb.hr/." }, { "input": "What is the mechanism of action of onartuzumab?", "output": "Onartuzumab is monoclonal antibody targeting MET. It works by inhibiting MET. Onartuzumab was tested for treatment of non-small cell lung carcinoma, adenocarcinoma of the stomach and gastroesophageal Junction, and recurrent glioblastoma." }, { "input": "Is there a relationship between B cells and Multiple Sclerosis?", "output": "MS patients with high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status" }, { "input": "Which virus type causes Molluscum contagiosum?", "output": "Molluscum contagiosum virus (MCV) is a human poxvirus that causes tumor-like skin lesions." }, { "input": "Which disease(s) are caused by HEX A deficiency?", "output": "Mutations in the HEX A gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), are the cause of Tay-Sachs disease as well as of juvenile, chronic, and adult GM2 gangliosidoses." }, { "input": "What is Beh\u00e7et's disease", "output": "Behet's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology." }, { "input": "What is Beh\u00e7et's disease", "output": "Beh\u00e7et's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology." }, { "input": "What is Beh\u00e7et's disease", "output": "Beh\u00e7et's disease (BD) is a complex chronic relapsing inflammatory disorder of unknown etiology. " }, { "input": "What is Beh\u00e7et's disease", "output": "beh\u00e7et's disease (bd) is a complex chronic relapsing inflammatory disorder of unknown etiology." }, { "input": "Does Yersinia pestis causes a respiratory infection?", "output": "Inhalation of Yersinia pestis results in primary pneumonic plague." }, { "input": "List 3 indications for Bupropion", "output": "Bupropion is used to treat Obesity, for smoking cessation and for depression" }, { "input": "What is the function of BAX", "output": "BAX is a central death regulator that controls apoptosis in normal and cancer cells" }, { "input": "What is the function of BAX", "output": "pro-apoptotic protein Bax" }, { "input": "What is the link between Ctf4 and Chl1 in cohesion establishment?", "output": "Ctf4 links DNA replication with sister chromatid cohesion establishment by recruiting the Chl1 helicase to the replisome. The Eco1 acetyltransferase, helped by factors including Ctf4 and Chl1, concomitantly acetylates the chromosomal cohesin complex to stabilize its cohesive links." }, { "input": "What is the link between Ctf4 and Chl1 in cohesion establishment?", "output": "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3. Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment." }, { "input": "How is primary intestinal lymphangiectasia (PIL) caused?", "output": "Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia." }, { "input": "What are congenital disorders of glycosylation?", "output": "Congenital disorders of glycosylation (CDG) are a growing group of inherited metabolic disorders where enzymatic defects in the formation or processing of glycolipids and/or glycoproteins lead to variety of different diseases.\nMore than 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today.\t\nThe patients have hundreds of misglycosylated products, which afflict a myriad of processes, including cell signaling, cell-cell interaction, and cell migration." }, { "input": "Which are the additions of the JASPAR 2016 open-access database of transcription factor binding profiles?", "output": "Compared to the JASPAR CORE collection, JASPAR 2016 has been expanded with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and 59 profiles (58 in vertebrates and 1 in fungi) have been updated. The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. The structural annotation of the TF DNA binding domains (DBDs) has been updated following a published hierarchical structural classification. In addition, 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites were introduced . The new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, users are provided with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. JASPAR2016 R/Bioconductor data package is also provided with the data of this release." }, { "input": "What is the function of the protein tafazzin?", "output": "Tafazzin is a phospholipid transacylase that transfers acyl chains with unsaturated fatty acids from phospholipids to monolysocardiolipin to generate cardiolipin with unsaturated fatty acids on mitochondrial membrane." }, { "input": "What are assassin bugs?", "output": "The family Reduviidae (Hemiptera: Heteroptera), or assassin bugs, is among the most diverse families of the true bugs, with more than 6,000 species." }, { "input": "Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?", "output": "These clusters are unlikely to have arisen by horizontal gene transfer, and the mechanisms behind their formation are poorly understood. Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation." }, { "input": "Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?", "output": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. " }, { "input": "Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?", "output": "Genes for marneral synthesis are organized in an operon-like gene cluster in thale cress (A. thaliana)." }, { "input": "Is Dupilumab used for treatment of atopic dermatitis?", "output": "Yes, patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity." }, { "input": "Where is base J found in the genome of Leishmania tarentolae?", "output": "Base J (\u03b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei." }, { "input": "Where is base J found in the genome of Leishmania tarentolae?", "output": "Base J (-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei. J is enriched at sites involved in RNA polymerase (RNAP) II initiation and termination. " }, { "input": "Where is base J found in the genome of Leishmania tarentolae?", "output": "Base J (\u00ce\u00b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. Base J is found predominantly in repetitive DNA and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in Trypanosoma brucei." }, { "input": "Where is base J found in the genome of Leishmania tarentolae?", "output": "Base J (\u03b2-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops." }, { "input": "Where is base J found in the genome of Leishmania tarentolae?", "output": "j (\u03b2-d-glucosyl-hydroxymethyluracil) replaces 1% of t in the leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. . j is found predominantly in repetitive dna and correlates with epigenetic silencing of telomeric variant surface glycoprotein genes in trypanosoma brucei. . " }, { "input": "Where is base J found in the genome of Leishmania tarentolae?", "output": "base j (\u03b2-d-glucosyl-hydroxymethyluracil) replaces 1% of t in the leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops." }, { "input": "Which tool is available for predicting regulatory interactions from ChIP-seq data?", "output": "CisMapper predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues. CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression. CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF." }, { "input": "Where are the unipolar brush cells localized?", "output": "Unipolar brush cells (UBCs) are glutamatergic interneurons localized in granule cell regions of the cochlear nucleus and the vestibulocerebellum of cerebellum." }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs" }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "found conservation of heterozygous k27m mutations in h3f3a (n\u2009=\u20094) or hist1h3b (n\u2009=\u20093) across all primary , contiguous , and metastatic tumor sites in all dipgs . h3k27m ubiquitously-associated mutations involve alterations in tp53 cell-cycle (tp53/ppm1d) or specific growth factor pathways (acvr1/pik3r1) . reconstruction indicates histone 3 (h3) k27m--including h3.2k27m--mutations potentially arise first and are invariably associated with specific , high-fidelity obligate partners throughout the tumour and its spread , from diagnosis to end-stage disease , suggesting mutual need for tumorigenesis. . aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. . " }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n\u00e2\u0080\u0089=\u00e2\u0080\u00894) or HIST1H3B (n\u00e2\u0080\u0089=\u00e2\u0080\u00893) across all primary, contiguous, and metastatic tumor sites in all DIPGs. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1)." }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n=4) or HIST1H3B (n=3) across all primary, contiguous, and metastatic tumor sites in all DIPGs. ACVR1 (n=2), PIK3CA (n=2), FGFR1 (n=2), and MET (n=1) were also intra-tumorally conserved. TP53 aberrations (n=3 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). " }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "Recurrent mutations within the histone H3 genes H3F3A and HIST1H3B that convert K27 to methionine (H3K27M) and disrupt the global H3K27 methylation landscape and PRC2-dependent silencing, have recently been identified in pediatric high-grade gliomas including Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma multiforme (GBM; Type IV glioma). The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships. TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved.Spatial conservation of prognostically-relevant and therapeutically-targetable somatic mutations in DIPG and mHGG contrasts the significant heterogeneity of driver mutations seen in adult HGG and supports uniform implementation of diagnostic biopsy in DIPG and mHGG to classify molecular risk groups and guide therapeutic strategy. Recently, a subset of these same mutations of ACVR1 have been identified in diffuse intrinsic pontine glioma (DIPG) tumors. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77\u00a0% of our DIPG cohort. Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Two distinct subgroups of DIPG were identified." }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs ACVR1 (n\u2009=\u20092), PIK3CA (n\u2009=\u20092), FGFR1 (n\u2009=\u20092), and MET (n\u2009=\u20091) were also intra-tumorally conserved TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved." }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. Conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) was observed across all primary, contiguous, and metastatic tumor sites in all DIPGs. ACVR1 (n\u2009=\u20092), PIK3CA (n\u2009=\u20092), FGFR1 (n\u2009=\u20092), and MET (n\u2009=\u20091) were also intra-tumorally conserved. TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved." }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs TP53 aberrations (n\u2009=\u20093 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1)." }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n=4) or HIST1H3B (n=3) across all primary, contiguous, and metastatic tumor sites in all DIPGs. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). TP53 aberrations (n=3 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. ACVR1 (n=2), PIK3CA (n=2), FGFR1 (n=2), and MET (n=1) were also intra-tumorally conserved. " }, { "input": "Which driver mutations have been identified for Diffuse Intrinsic Pontine Glioma (DIPG)?", "output": "We found conservation of heterozygous K27M mutations in H3F3A (n\u2009=\u20094) or HIST1H3B (n\u2009=\u20093) across all primary, contiguous, and metastatic tumor sites in all DIPGs These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). " }, { "input": "Does Jarid2 play a role in early embryo development?", "output": "Yes. Jarid2 coordinates Nanog expression and PCP/Wnt signaling required for efficient ESC differentiation and early embryo development." }, { "input": "Is PUVA therapy indicated for eczema treatment?", "output": "Yes, PUVA (psoralen plus UVA) therapy is effective for eczema treatment and has relatively few side effects." }, { "input": "What is DECKO?", "output": "DECKO (Double Excision CRISPR Knockout) is a dual CRISPR tool, which is cloned using a single starting oligonucleotide, thereby affording simplicity and scalability to CRISPR knockout studies of non-coding genomic elements, including long non-coding RNAs." }, { "input": "List genes associated with hypolipidemia.", "output": "PCSK9\nAPOB \nANGPTL3\nANGPTL4\nMTP" }, { "input": "What is the enzymatic activity of PARL?", "output": "the mitochondrial protease presenilin-associated rhomboid-like (PARL). Rhomboids are a recently discovered family of widely distributed intramembrane serine proteases." }, { "input": "Do brown fat cells produce heat?", "output": "Yes, brown fat cells produce heat." }, { "input": "What is a mimotope vaccine?", "output": "A mimotope vaccine contains peptide mimics of specific antigen epitopes, which alter the antigen presentation and/or T cell activation to increase the expansion of tumor-specific T cells and are able to induce polyclonal antibodies response." }, { "input": "Describe clinical manifestation of the Mal de debarquement syndrome.", "output": "Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years." }, { "input": "Is Melioidosis caused by the bacterium\u00a0Burkholderia pseudomallei?", "output": "Burkholderia pseudomallei is the causative agent of melioidosis" }, { "input": "What is the mechanism of action of verubecestat?", "output": "Verubecestat (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of A\u03b240, A\u03b242, and sAPP\u03b2 (a direct product of BACE1 enzymatic activity)." }, { "input": "How are triple negative gliomas characterized?", "output": "of these markers - 1p/19q deletions , mgmt methylation status , and mutations in the idh1 gene - are so potent that a new brain tumor subtype , the \"triple negative\" glioma (1p/19q intact , mgmt unmethylated , idh1 non-mutated) has entered common parlance . " }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis." }, { "input": "How are triple negative gliomas characterized?", "output": "Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. " }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. (Funded by the National Institutes of Health and others. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance." }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance. " }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative (IDH-/p53-/1p19q-), this last subgroup having the worst prognosis." }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance. " }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations" }, { "input": "How are triple negative gliomas characterized?", "output": "According to IDH, TP53, and 1p19q status, four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-, IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst prognosis. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the \"triple negative\" glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance" }, { "input": "What is ectopia lentis?", "output": "Ectopia Lentis is dislocation of the optic lens in the eye." }, { "input": "Can glyburide reduce cerebral edema?", "output": "Yes. Glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing and attenuating cerebral edema." }, { "input": "What is the function of gasdermin D?", "output": "The gasdermin-N domains of the gasdermin proteins can bind membrane lipids, phosphoinositides and cardiolipin to produce membrane-disrupting cytotoxicity." }, { "input": "What is TOPAZ1?", "output": "TOPAZ1 is a novel germ cell-specific expressed gene conserved during evolution across vertebrates. Its PAZ-domain protein is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line." }, { "input": "What is TOPAZ1?", "output": "TOPAZ1 (Testis and Ovary-specific PAZ domain gene 1) is a germ cell specific factor that is essential for male meiotic progression. Topaz1 is supposed to have a role during gametogenesis and may be involved in the piRNA pathway and contribute to silencing of transposable elements and maintenance of genome integrity. It is highly conserved in vertebrates." }, { "input": "Which are the symptoms of glucose-6-phosphate dehydrogenase (G6PD) deficiency?", "output": "Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common symptoms of this condition are:\n1) acute hemolysis, \n2) chronic hemolysis, \n3) neonatal hyperbilirubinemia." }, { "input": "Has the gorilla genome been determined?", "output": "Yes, the gorilla genome has been sequenced." }, { "input": "Is vemurafenib used for thyroid cancer?", "output": "Yes. Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation." }, { "input": "Are mutations in the C9orf72 gene associated with macular degeneration?", "output": "Amyotrophic lateral sclerosis (ALS) is characterized by motor neurone loss resulting in muscle weakness, spasticity and ultimately death. 5-10% are caused by inherited mutations, most commonly C9ORF72, SOD1, TARDBP and FUS." }, { "input": "What is the Genome 10K Project?", "output": "The Genome 10K Project was established in 2009 by a consortium of biologists and genome scientists determined to facilitate the sequencing and analysis of the complete genomes of 10,000 vertebrate species." }, { "input": "Which gene controls the expression of GATA-1 isoforms?", "output": "In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript." }, { "input": "Which gene controls the expression of GATA-1 isoforms?", "output": "A transcriptional network has been reported, in which PU.1 positively regulates GATA-1 expression in mast cell development." }, { "input": "Which gene controls the expression of GATA-1 isoforms?", "output": "In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation." }, { "input": "Which gene controls the expression of GATA-1 isoforms?", "output": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development." }, { "input": "Which gene controls the expression of GATA-1 isoforms?", "output": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. " }, { "input": "Which gene controls the expression of GATA-1 isoforms?", "output": "Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s." }, { "input": "What is MIRA-seq?", "output": "MIRA-seq is a reliable, genome-scale DNA methylation analysis platform for scoring DNA methylation differences at CpG-rich genomic regions. The method is not limited by primer or probe design and is cost effective." }, { "input": "How does Ssu72 mediate gene looping?", "output": "Investigation of chromosome folding in mutants confirms roles for RSC, \"gene looping\" factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and the N-terminal tail of H4 in folding of the yeast genome. The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP. We propose a model for RNAP II transcription in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation. The first 300 amino acids of Pta1 are sufficient for interactions with Ssu72, which is needed for pre-mRNA cleavage. " }, { "input": "How does Ssu72 mediate gene looping?", "output": "In RNAP II transcription, promoter and terminator regions are juxtaposed and the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation. These interactions are transcription-dependent, require the Ssu72 and Pta1 components of the CPF 3'-end processing complex, and require the phosphatase activity of Ssu72." }, { "input": "How does Ssu72 mediate gene looping?", "output": "tfiib crosslinks to both the promoter and terminator regions of the pma1 and blm10 genes, and its association with the terminator, but not the promoter, is adversely affected by e62k and by depletion of the ssu72 component of the cpf 3' end processing complex, and is independent of tbp." }, { "input": "How does Ssu72 mediate gene looping?", "output": "Investigation of chromosome folding in mutants confirms roles for RSC, \"gene looping\" factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and the N-terminal tail of H4 in folding of the yeast genome. TFIIB crosslinks to both the promoter and terminator regions of the PMA1 and BLM10 genes, and its association with the terminator, but not the promoter, is adversely affected by E62K and by depletion of the Ssu72 component of the CPF 3' end processing complex, and is independent of TBP. We propose a model for RNAP II transcription in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation. The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing These interactions are transcription-dependent, require the Ssu72 and Pta1 components of the CPF 3'-end processing complex, and require the phosphatase activity of Ssu72. Furthermore, different regions of Pta1 interact with the CPF subunits Ssu72, Pti1, and Ysh1, supporting the idea that Pta1 acts as a scaffold to organize CPF." }, { "input": "How does Ssu72 mediate gene looping?", "output": "The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing" }, { "input": "Is the number of described human nuclear mutations less than 50000?", "output": "No, The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database)." }, { "input": "What is the role of peptide aptamers?", "output": "Peptide aptamers are artificial short peptides which are able to specifically bind to defined functional domains, track, and inhibit a given target molecule with high affinity, even molecules with poor immunogenicity or high toxicity. They represent a remarkable alternative to antibodies in many different applications." }, { "input": "Which are the clinical symptoms of left ventricular noncompaction?", "output": "The clinical symptoms of left ventricular noncompaction are:\n1) heart failure, \n2) systemic thromboembolic events, \n3) ventricular arrhythmias and\n4) sudden cardiac death." }, { "input": "What is the Glasgow Coma score?", "output": "Glasgow coma sore is used to determine injury severity on admission to a hospital emergency department or by the duration of unconsciousness." }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a specific reversal agent for Factor Xa inhibitors." }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. " }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin." }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. " }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "andexanet alfa is a factor xa (fxa) decoy that binds to direct and indirect inhibitors in phase iii trials in healthy volunteers , andexanet alfa reduced anti-fxa activity by more than 90% , reduced the concentration of unbound direct fxa inhibitor , and inhibited thrombin generation . andexanet is an antidote targeted to reverse the oral direct factor xa inhibitors as well as the indirect inhibitor enoxaparin. . " }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. In Phase III trials in healthy volunteers, andexanet alfa reduced anti-FXa activity by more than 90%, reduced the concentration of unbound direct FXa inhibitor, and inhibited thrombin generation. Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. " }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. Antidotes that experimentally reverse the anti-coagulant effect of dabigatran (Idarucizumab; BI 655075; Boehringer Ingelheim); of rivaroxaban, apixaban, or edoxaban (Andexanet alfa, r-Antidote, PRT064445; Portola Pharmaceuticals) or of all DOACs (Aripazine, PER-977, ciraparantag; Perosphere Inc.) are discussed. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively." }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly." }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin." }, { "input": "Andexanet Alfa is an antidote of which clotting factor inhibitors?", "output": "Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Andexanet alfa is a factor Xa (FXa) decoy that binds to direct and indirect FXa inhibitors." }, { "input": "Which is the main cause of the Patau syndrome?", "output": "Patau syndrome is caused by trisomy 13." }, { "input": "Which is the main abnormality that arises with Sox9 locus duplication?", "output": "The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. A complex network of genes determines sex in mammals. Differentiation of testicular tissue in 46,XX individuals is seen either in XX males, the majority of them with SRY gene, or in individuals, usually SRY(-), with ovotesticular disorder of sex development (OT-DSD). SOX9 is one of the genes that play critical roles in male sexual differentiation." }, { "input": "Which is the main abnormality that arises with Sox9 locus duplication?", "output": "Thus, SOX9 duplication is the most likely cause for the sex reversal in this case because it plays an important role in male sex determination and differentiation. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY." }, { "input": "Which is the main abnormality that arises with Sox9 locus duplication?", "output": "Autosomal XX sex reversal caused by duplication of SOX9. Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal. We report here evidence supporting that SOX9 duplication can cause XX sex reversal. Fluorescent in situ hybridization (FISH) with a BAC clone containing the SOX9 gene demonstrated that the SOX9 gene is duplicated on the rearranged chromosome 17. SOX9 duplication linked to intersex in deer. " }, { "input": "Which is the main abnormality that arises with Sox9 locus duplication?", "output": "SOX9 duplication can cause XX sex reversal. SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans." }, { "input": "Which is the main abnormality that arises with Sox9 locus duplication?", "output": "Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans." }, { "input": "Which is the main abnormality that arises with Sox9 locus duplication?", "output": "Autosomal XX sex reversal caused by duplication of SOX9" }, { "input": "Is Musclin a secretory peptide?", "output": "Yes, musclin has been described as a muscle-derived secretory peptide." }, { "input": "What tissue is commonly affected in Marfan's syndrome", "output": "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents " }, { "input": "What tissue is commonly affected in Marfan's syndrome", "output": "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents" }, { "input": "What tissue is commonly affected in Marfan's syndrome", "output": "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents. " }, { "input": "What tissue is commonly affected in Marfan's syndrome", "output": "Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents." }, { "input": "What tissue is commonly affected in Marfan's syndrome", "output": "marfan syndrome (ms) is a connective tissue disorder that affects thousands of adolescents ." }, { "input": "To which disease does the loss of CD28 expression by liver-infiltrating T cells contribute?", "output": "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis." }, { "input": "To which disease does the loss of CD28 expression by liver-infiltrating T cells contribute?", "output": "Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis. " }, { "input": "To which disease does the loss of CD28 expression by liver-infiltrating T cells contribute?", "output": "loss of cd28 expression by liver-infiltrating t cells contributes to pathogenesis of primary sclerosing cholangitis." }, { "input": "Are cutaneous porphyrias inherited with a recessive pattern?", "output": "No, cutaneous porphyrias are inherited in a dominant (not recessive) pattern." }, { "input": "Which disease is treated with ZMapp?", "output": "ZMapp is a combination of antibodies for treatment of Ebola virus disease." }, { "input": "Which disease is treated with ZMapp?", "output": "Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7, and c13C6) by using recombinant adeno-associated viruses (rAAVs) is useful for preventive immunization against Ebola virus infection." }, { "input": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "output": "Yes, several methylenetetrahydrofolate reductase (MTHFR) gene mutations can cause homocystinuria and hyperhomocysteinemia." }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": " Phosphorylated H2AX (\u03b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR)" }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": " phosphorylated h2ax (\u03b3h2ax) is rapidly concentrated in chromatin domains around dna double-strand breaks (dsbs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress." }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": "Defective or inefficient DNA double-strand break (DSB) repair results in failure to preserve genomic integrity leading to apoptotic cell death, a hallmark of systemic lupus erythematosus (SLE). Phosphorylated H2AX (\u00ce\u00b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress." }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": "The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). Phosphorylated H2AX (\u03b3H2AX) is rapidly concentrated in chromatin domains around DNA double-strand breaks (DSBs) after the action of ionizing radiation or chemical agents and at stalled replication forks during replication stress. DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin" }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": "Histone H2AX phosphorylation as a measure of DNA double-strand breaks and a marker of environmental stress and disease activity in lupus. DSBs were quantified in peripheral blood mononuclear cell subsets from patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry. Most hydrogen peroxide-induced histone H2AX phosphorylation is mediated by ATR and is not dependent on DNA double-strand breaks. The nuclear foci of phosphorylated histone H2AX (H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). These results suggest that a major fraction of H2AX induced by oxidative stress is not associated with DSBs. " }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": "Defective or inefficient DNA double-strand break (DSB) repair results in failure to preserve genomic integrity leading to apoptotic cell death, a hallmark of systemic lupus erythematosus (SLE). The nuclear foci of phosphorylated histone H2AX (\u03b3H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). A sequence variant of histone H2A called H2AX is one of the key components of chromatin involved in DNA damage response induced by different genotoxic stresses. DNA double-strand breaks (DSBs) can induce chromosomal aberrations and carcinogenesis and their correct repair is crucial for genetic stability." }, { "input": "What happens to H2AX upon DNA bouble strand breaks?", "output": "DSBs were quantified in peripheral blood mononuclear cell subsets from patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin" }, { "input": "Can valproic acid prolong survival of glioblastoma patients?", "output": "Yes, there is evidence to suggest that valproic acid (VPA) is associated with prolonged survival of glioblastoma patients. Several studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons." }, { "input": "What is the effect of the direct interaction of Ikaros and Foxp1 in B-lymphocytes?", "output": "Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia." }, { "input": "What is the effect of the direct interaction of Ikaros and Foxp1 in B-lymphocytes?", "output": "The effect of the direct interaction of Ikaros and Foxp1 in B-lymphocytesis is modulation of expression of the G protein-coupled receptor G2A." }, { "input": "Which syndrome is caused by deletion of Pds5b in mice?", "output": "mice lacking sister chromatid cohesion protein pds5b exhibit developmental abnormalities reminiscent of cornelia de lange syndrome." }, { "input": "Which syndrome is caused by deletion of Pds5b in mice?", "output": "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome. " }, { "input": "Which syndrome is caused by deletion of Pds5b in mice?", "output": "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome." }, { "input": "Which syndrome is caused by deletion of Pds5b in mice?", "output": "Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome" }, { "input": "Which syndrome is caused by deletion of Pds5b in mice?", "output": "Mice lacking sister chromatid cohesion protein Pds5b exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome." }, { "input": "What is the inheritance of Barth syndrome?", "output": "Barth syndrome (BTHS) has an X-linked recessive pattern of inheritance." }, { "input": "Is Cryptococcus neoformans a frequent cause of isolated skin infections in immunocompromised individuals", "output": "Primary cutaneous cryptococcosis (PCC) without systemic infection is rare." }, { "input": "What is the mechanism of action of Pictilisib?", "output": "Pictilisib acts by inhibiting PI3K. It is used for breast cancer treatment." }, { "input": "What are sirtuins?", "output": "Seven sirtuins have been identified in humans, and their functions currently surpass their originally identified role as histone deacetylase and chromatin silencers to encompass nutrient sensing and metabolic function. All seven sirtuins require NAD(+) in order to carry out their enzymatic activity, and thus become activated in conditions of nutrient depletion, starvation, and cellular stress." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "The testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon" }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Does the linear Sry transcript function as a ceRNA for miR-138?. Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1 (HIF-1), and overexpression of SOX4 and HIF-1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. " }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": ", the sex determining region y ( sry) and the cerebellar degeneration-related protein 1 ( cdr1as) rna transcripts have been described to function as a new class of post-transcriptional regulatory rnas that behave as circular endogenous rna sponges for the micro rnas (mirnas) mir-138 and mir-7 , respectively . " }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Does the linear Sry transcript function as a ceRNA for miR-138?. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1 (HIF-1), and overexpression of SOX4 and HIF-1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138. Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. " }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "recently, the sex determining region y ( sry) and the cerebellar degeneration-related protein 1 ( cdr1as) rna transcripts have been described to function as a new class of post-transcriptional regulatory rnas that behave as circular endogenous rna sponges for the micro rnas (mirnas) mir-138 and mir-7, respectively." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. Metastasis is the major factor affecting patient survival in ovarian cancer. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1\u00ce\u00b1 (HIF-1\u00ce\u00b1), and overexpression of SOX4 and HIF-1\u00ce\u00b1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Does the linear Sry transcript function as a ceRNA for miR-138? Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. Epidermal growth factor receptor acted as the downstream molecule of SOX4 by way of direct transcriptional control, whereas Slug was the downstream molecule of HIF-1\u00ce\u00b1 by way of proteasome-mediated degradation." }, { "input": "Which miRNA is targeted by SRY/Sox9?", "output": "Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), and overexpression of SOX4 and HIF-1\u03b1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. " }, { "input": "Which technique led to the elucidation of the role of HOXD10 in regulating lymphatic endothelial responses to VEGF-C?", "output": "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C." }, { "input": "Which technique led to the elucidation of the role of HOXD10 in regulating lymphatic endothelial responses to VEGF-C?", "output": "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C" }, { "input": "Which technique led to the elucidation of the role of HOXD10 in regulating lymphatic endothelial responses to VEGF-C?", "output": "DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C. " }, { "input": "Is Obeticholic Acid used for treatment of Primary Biliary Cholangitis?", "output": "Yes, obeticholic acid is a farnesoid-X receptor agonist that is approved for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid." }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter. Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy." }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy. Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter. " }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction and can potential treat atrial fibrillation" }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy. Vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter." }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "vanoxerine's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter." }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "Vanoxerine 's effects were strongly frequency-dependent and we repositioned it for treatment of atrial fibrillation and flutter." }, { "input": "What alternate indication has Vanoxerine been repositioned for?", "output": "vanoxerine's were strongly frequency-dependent and repositioned it for treatment of atrial fibrillation and flutter. . has been in clinical trials for parkinsonism , depression and cocaine addiction but lacked efficacy. . " }, { "input": "What is the applicability of the No Promoter Left Behind method?", "output": "No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing promoter architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements." }, { "input": "What is the applicability of the No Promoter Left Behind method?", "output": "Promoters have diverse regulatory architectures and thus activate genes differently. No Promoter Left Behind (NPLB) is an efficient, organism-independent method for characterizing such diverse architectures directly from experimentally identified genome-wide TSSs, without relying on known promoter elements." }, { "input": "Which mutated genes are associated with isolated ectopia lentis?", "output": "Isolated ectopia lentis (EL) is caused by mutation in genes:\n1) ADAMTSL4 and \n2) Fibrillin-1 (FBN1)." }, { "input": "Does the word ovine refers to goats?", "output": "Ovine refers to sheep." }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). " }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "in exon 2 interfere with the synthesis of the full-length isoform of gata-1 and lead to the production of a shortened isoform , gata-1s these mutations have been found in patients with diamond-blackfan anemia (dba) , a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. . of the corresponding transcription factors are of particular interest , as they are housekeeping genes or show a direct link to hematopoiesis , tumorigenesis or leukemia (e.g gata-1/2 , pu.1 , mzf-1). . " }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). " }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g." }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. The Ribosomal protein S19 gene locus (RPS19) has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA) and Transient Erythroblastopenia in Childhood (TEC)." }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins." }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "mutations in exon 2 interfere with the synthesis of the full-length isoform of gata-1 and lead to the production of a shortened isoform, gata-1s." }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "yes" }, { "input": "Does GATA-1 regulate ribosomal protein genes?", "output": "Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins." }, { "input": "Which gene mutations cause the Marfan syndrome?", "output": "Marfan syndrome (MFS) is an autosomal dominant disorder caused by mutations in the fibrillin 1 gene (FBN1)." }, { "input": "What is the indication of ARCALYST?", "output": "In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older." }, { "input": "What is ChIPpeakAnno?", "output": "ChIPpeakAnno is a Bioconductor package within the statistical programming environment R that facilitates batch annotation of enriched peaks identified from ChIP-seq, ChIP-chip, cap analysis of gene expression (CAGE) or any experiments resulting in a large number of enriched genomic regions." }, { "input": "Signaling of which pathways is inhibited by Dupilumab?", "output": "Dupilumab, a fully human anti-interleukin-4 receptor \u03b1 monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling. It is used for treatment of atopic or allergic diseases." }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype." }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia. Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). " }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype." }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the top2b/top2a ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (hr, 0.24; p=0.002) and overall survival (hr, 0.29; p=0.005)." }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "yes" }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype." }, { "input": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "output": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia" }, { "input": "List the three main structures of the cytoskeleton.", "output": "Fibrillar polymers-actin filaments, microtubules, and intermediate filaments-are major constituents of the cytoskeleton." }, { "input": "What is the genus for the common European honey bee?", "output": "The genus and species of the European honey bee is Apis mellifera." }, { "input": "Where is the TAZ (G4.5) is located in humans?", "output": "TAZ gene (G4.5) is located on Xq28 in humans." }, { "input": "What do nerve-associated peripheral glial progenitors give rise to?", "output": "Nerve-associated peripheral glial progenitors give rise to parasympathetic neurons. The parasympathetic system in mice--including trunk ganglia and the cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia--arise from glial cells in nerves, not neural crest cells. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites." }, { "input": "What do nerve-associated peripheral glial progenitors give rise to?", "output": "Parasympathetic neurons originate from nerve-associated peripheral glial progenitors. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites." }, { "input": "What do nerve-associated peripheral glial progenitors give rise to?", "output": "Parasympathetic neurons originate from nerve-associated peripheral glial progenitors." }, { "input": "How many topological associated domains are contained in the human Hox cluster?", "output": "transcriptional activation is associated with a dynamic bi-modal 3d organization, whereby the genes switch autonomously from an inactive to an active compartment." }, { "input": "How many topological associated domains are contained in the human Hox cluster?", "output": "Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. " }, { "input": "How many topological associated domains are contained in the human Hox cluster?", "output": ", hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. . activation is associated with a dynamic bi-modal 3d organization , whereby the genes switch autonomously from an inactive to an active compartment. . " }, { "input": "How many topological associated domains are contained in the human Hox cluster?", "output": "Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment." }, { "input": "Is Lennox-Gastaut Syndrome usually diagnosed in older adults?", "output": " children with Lennox-Gastaut syndrome Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 Hz) spike wave discharges on electroencephalography" }, { "input": "Is Lennox-Gastaut Syndrome usually diagnosed in older adults?", "output": "Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 Hz) spike wave discharges on electroencephalography." }, { "input": "Is Lennox-Gastaut Syndrome usually diagnosed in older adults?", "output": "lennox-gastaut syndrome (lgs) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 hz) spike wave discharges on electroencephalography." }, { "input": "Which treatment methods were compared in the EXCEL Trial?", "output": "EXCEL trial compared Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization." }, { "input": "Describe ATR-16 syndrome.", "output": "ATR-16 syndrome is due to alterations on chromosome 16p13.3, and is usually accompanied by alpha-thalassemia, mild-moderate mental retardation, dysmorphic facial features, skeletal and genitourinary malformations." }, { "input": "What is the results of inactivated ANGPLT3?", "output": "Complete ANGPTL3 deficiency caused by loss-of-function mutations of ANGPTL3 is associated with a recessive hypolipidemia" }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. " }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "The introduction of anti-TNF therapy has dramatically improved the outlook for patients suffering from a number of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients." }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. A substantial proportion of Rheumatoid Arthritis patients (approximately 30-40%) fail to respond to anti-TNF therapies." }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients." }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. " }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "strategies blocking tumor necrosis factor (anti-tnf) have proven very successful in patients with rheumatoid arthritis (ra) , showing beneficial effects in approximately 50-60% of the patients. . this , a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies . " }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. The introduction of anti-TNF therapy has dramatically improved the outlook for patients suffering from a number of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease." }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "treatment strategies blocking tumor necrosis factor (anti-tnf) have proven very successful in patients with rheumatoid arthritis (ra), showing beneficial effects in approximately 50-60% of the patients." }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. " }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients." }, { "input": "What percentage of rheumatoid arthritis patients are responsive to anti-TNF therapy?", "output": "Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies." }, { "input": "Which disease is treated with semaglutide?", "output": "Semaglutide is glucagon-like peptide-1 receptor agonist that is being used for the treatment of type 2 diabetes mellitus." }, { "input": "What condition is usually represented by the acronym SUDEP?", "output": "Sudden Unexpected Death in Epilepsy (SUDEP). sudden unexpected death in epilepsy (SUDEP),. " }, { "input": "What condition is usually represented by the acronym SUDEP?", "output": "The acronym SUDEP refers to Sudden Unexpected Death in Epilepsy" }, { "input": "What condition is usually represented by the acronym SUDEP?", "output": " sudden unexpected death in epilepsy (SUDEP), Sudden Unexpected Death in Epilepsy (SUDEP)" }, { "input": "What condition is usually represented by the acronym SUDEP?", "output": "Sudden Unexpected Death in Epilepsy (SUDEP)" }, { "input": "Which proteins does the yeast Cleavage and Polyadenylation Complex contain?", "output": "The proteins Nrd1, Rap1, Trf4, Rrp6, Ssu72, Cstf64, Pcf11 and PAP are the major components of the 3' cleavage and polyadenylation complex." }, { "input": "Which disease can be categorized using the Koos grading system?", "output": "Koos grading system is used for vestibular schwannoma." }, { "input": "What is the inheritance of the glucose-6-phosphate dehydrogenase (G6PD) deficiency?", "output": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has a recessive X-linked inheritance." }, { "input": "Which deep learning-based algorithms are used for enhancer prediction?", "output": "EP-DNN and DEEP." }, { "input": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "output": "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains" }, { "input": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "output": "beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains." }, { "input": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "output": "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of -globin chains. " }, { "input": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "output": "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains." }, { "input": "Is diphosphatidylglycerol (cardiolipin) a phospholipid of the mitochondrial membranes?", "output": "Yes, diphosphatidylglycerol (cardiolipin) is a phospholipid of the mitochondrial membranes." }, { "input": "Have studies shown that there is no link between DNA methylation patterns and Post Traumatic Stress Disorder?", "output": "Studies do show a correlation of PTSD-related accelerated aging in DNA methylation patterns." }, { "input": "Is POLD3 essential for mouse development?", "output": "Yes. The Pold3 gene encodes a subunit of the Pol\u03b4 DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. In mouse, POLD3 is essential for development and is also required for viability in adult animals." }, { "input": "Is POLD3 essential for mouse development?", "output": "yes" }, { "input": "What is the mechanism of action of Romosozumab?", "output": "Romosozumab is humanized monoclonal antibody to sclerostin. It inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density as measured by dual-energy X-ray absorptiometry. It is developed for osteoporosis treatment." }, { "input": "Symptoms of which disorder are evaluated with the Davidson Trauma Scale?", "output": "Davidson Trauma Scale is used for evaluation of post-traumatic stress disorder." }, { "input": "What is the function of the Mis18 protein?", "output": "Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. Further, we demonstrate Mis18\u00ce\u00b1's crucial role for epigenetic regulation of centromeric chromatin by reinforcing centromeric localization of DNMT3A/3B. Mis18\u00ce\u00b1 interacts with DNMT3A/3B, and this interaction is critical for maintaining DNA methylation and hence regulating epigenetic states of centromeric chromatin. Together, our findings uncover the functional mechanism of Mis18\u00ce\u00b1 and its pivotal role in mammalian cell cycle. The Mis18 complex is a critical player in determining when and where centromeres are built." }, { "input": "What is the function of the Mis18 protein?", "output": "Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres Here we report identification of five fission yeast centromere proteins, Mis14-18. Mis14 is recruited to kinetochores independently of CENP-A, and, conversely, CENP-A does not require Mis14 to associate with centromeres. In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway. Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. Mis16 and Mis18 are the most upstream factors in kinetochore assembly as they can associate with kinetochores in all kinetochore mutants except for mis18 and mis16, respectively." }, { "input": "What is the function of the Mis18 protein?", "output": "The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome." }, { "input": "What is the function of the Mis18 protein?", "output": "Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly. The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. This is a critical step that is essential for proper centromere function and maintaining the integrity of the genome." }, { "input": "What is the function of the Mis18 protein?", "output": "The Mis18 complex is a critical player in determining when and where centromeres are built. The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. Centromeres contain specialized chromatin that includes the centromere-specific histone H3 variant, spCENP-A/Cnp1." }, { "input": "What is the function of the Mis18 protein?", "output": "Together, our findings uncover the functional mechanism of Mis18\u03b1 and its pivotal role in mammalian cell cycle. The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome." }, { "input": "What is the function of the Mis18 protein?", "output": "the mis18 complex has been identified as a critical factor for the centromeric localization of a histone h3 variant, centromeric protein a (cenp-a), which is responsible for the specification of centromere identity in the chromosome." }, { "input": "Are hepadnaviral minichromosomes free of nucleosomes?", "output": "Nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned." }, { "input": "Are hepadnaviral minichromosomes free of nucleosomes?", "output": "In vitro assembled minichromosomes were able to replicate efficiently in vitro, when the DNA was preincubated with T-antigen, a cytosolic S100 extract and three deoxynucleoside triphosphates prior to chromatin assembly, indicating that the origin has to be free of nucleosomes for replication initiation. The transcriptionally inactive locus is covered by an array of positioned nucleosomes extending over 1,400 bp. In minichromosomes with a (mu)LCR or DNase I-hypersensitive site 2 (HS2) which actively transcribe the epsilon-globin gene, the nucleosome at the promoter is altered or disrupted while positioning of nucleosomes in the rest of the locus is retained. Viral minichromosomes were found to exist in at least two defined structures covered with 11 or 12 nucleosomes, leaving open gaps accessible for interactions with other host factors. Minichromosomes from both preparations contain the full complement of nucleosomes, but salt treatment removes histone H1 and a fraction of nonhistone chromatin proteins. This double-stranded DNA serves as a template for replication as well as transcription and is assembled into host nucleosomes, yielding circular viral minichromosomes. In contrast, the replicated untreated minichromosomes were found to be densely packed with nucleosomes, indicating that an assembly of new nucleosomes occurred during in vitro replication." }, { "input": "Are hepadnaviral minichromosomes free of nucleosomes?", "output": "Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples. In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings." }, { "input": "Are hepadnaviral minichromosomes free of nucleosomes?", "output": "nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned. In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings." }, { "input": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "output": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5" }, { "input": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "output": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. " }, { "input": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "output": "syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5 . " }, { "input": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "output": "cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5." }, { "input": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "output": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5." }, { "input": "What are the roles of Smyd3 in zebrafish?", "output": "Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish. Transcripts of smyd3 are expressed in zebrafish embryos at all developmental stages and knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes are associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog." }, { "input": "Which enzyme is inhibited by ribociclib?", "output": "Ribociclib is inhibitor of cyclin D-cyclin-dependent kinase 4/6 (CDK 4/6). It is used for breast cancer treatment." }, { "input": "Which histone mutations have been associated with pediatric gliomas?", "output": "About 80% of Diffuse intrinsic pontine glioma (DIPG) cases and 70% of midline glioblastomas contain a mutation at one allele of the H3F3A gene (encoding histone H3 variant H3.3), replacing the lysine 27 with methionine (K27M). Moreover, approximately 30% of pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome. Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1)" }, { "input": "Which histone mutations have been associated with pediatric gliomas?", "output": "Moreover, approximately 30% of pediatric high grade gliomas (pedHGG) including GBM and DIPG harbor a lysine 27 mutation (K27M) in histone 3.3 (H3.3) which is correlated with poor outcome and was shown to influence EZH2 function Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1) Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases." }, { "input": "Which histone mutations have been associated with pediatric gliomas?", "output": "Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1). Two new studies show that the known histone H3 alteration p.Lys27Met in pediatric glioma leads to globally diminished trimethylation at histone H3 lysine 27. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis." }, { "input": "Which histone mutations have been associated with pediatric gliomas?", "output": ", approximately 30% of pediatric high grade gliomas (pedhgg) including gbm and dipg harbor a lysine 27 mutation (k27m) in histone 3.3 (h3.3) which is correlated with poor outcome and was shown to influence ezh2 function . the h3f3a mutant allele found in high-grade pediatric glioma by real-time pcr . studies on high-grade pediatric gbm have identified two recurrent mutations (k27m and g34r/v) in genes encoding histone h3 (h3f3a for h3.3 and hist1h3b for h3.1) . has been reported recently that about 80% of dipg cases and 70% of midline glioblastomas contain a mutation at one allele of the h3f3a gene (encoding histone h3 variant h3.3) , replacing the lysine 27 with methionine (k27m). . , discuss vaccine treatment for children diagnosed with malignant glioma , through targeting epha2 , il-13r\u03b12 and/or histone h3 k27m , while in adults , treatments with rintega , prophage series g-100 and dendritic cells are explored. . studies have identified a lys 27-to-methionine (k27m) mutation at one allele of h3f3a , one of the two genes encoding histone h3 variant h3.3 , in 60% of high-grade pediatric glioma cases. . new studies show that the known histone h3 alteration p.lys27met in pediatric glioma leads to globally diminished trimethylation at histone h3 lysine 27 . were able to discern the h3f3a k27m mutation in a newly obtained pediatric brainstem glioblastoma sample whose h3.3 status was not known previously , and in three other dipg samples as well as paraffin embedded samples these results demonstrate that have developed a new reliable procedure for detecting the h3f3a k27m mutation in pediatric glioblastoma patient samples. . " }, { "input": "Is it feasible to obtain DNA read lengths that exceed 30 Kb?", "output": "The emergence and development of so called third generation sequencing platforms such as PacBio has permitted exceptionally long reads (over 20\u2009kb) to be generated but not yet read length >30 Kb." }, { "input": "Is osteocrin expressed exclusively in the bone?", "output": "No, Osteocrin (Ostn) has been detected in the bones and the brain." }, { "input": "What is Achondroplasia?", "output": "Achondrogenesis type II also known as Achondroplasia is an autosomal-dominant disease leading to severe micromelic dwarfism" }, { "input": "What is Achondroplasia?", "output": "Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism. " }, { "input": "What is Achondroplasia?", "output": "Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism." }, { "input": "What is Achondroplasia?", "output": "achondrogenesis type ii is an autosomal-dominant disease leading to severe micromelic dwarfism." }, { "input": "What is Achondroplasia?", "output": "achondrogenesis type ii is an autosomal-dominant disease to severe micromelic dwarfism. . " }, { "input": "What is the indication for Mirabegron?", "output": "Mirabegron, the first \u5c3e3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms." }, { "input": "What is the indication for Mirabegron?", "output": "mirabegron, the first \u03b23-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (oab) syndrome symptoms." }, { "input": "What is the indication for Mirabegron?", "output": "Mirabegron, the first \u03b23-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms." }, { "input": "What is the indication for Mirabegron?", "output": "Mirabegron, the first \ufffd3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms." }, { "input": "What is the indication for Mirabegron?", "output": "Mirabegron, the first 3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. " }, { "input": "What is the cause of Tardive dyskinesia?", "output": "Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications." }, { "input": "Are alterations in ultraconserved elements associated with colorectal adenocarcinoma?", "output": "yes" }, { "input": "Are alterations in ultraconserved elements associated with colorectal adenocarcinoma?", "output": "Yes. SNPs within ultraconserved elements (UCEs) may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5-fluorouracil-based chemotherapy." }, { "input": "What is PANTHER-PSEP?", "output": "PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. " }, { "input": "What is PANTHER-PSEP?", "output": "PANTHER-PSEP is a software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors." }, { "input": "What is PANTHER-PSEP?", "output": "PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease." }, { "input": "What is MPE-seq?", "output": "MPE-seq (methidiumpropyl-EDTA sequencing) is a new method for the genome-wide characterization of chromatin that involves the digestion of nuclei with MPE-Fe(II) followed by massively parallel sequencing. Like micrococcal nuclease (MNase), MPE-Fe(II) preferentially cleaves the linker DNA between nucleosomes. However, there are differences in the cleavage of nuclear chromatin by MPE-Fe(II) relative to MNase. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias. In particular, the combined use of MPE-seq and MNase-seq enables the identification of noncanonical chromatin structures that are likely to be important for the regulation of gene expression." }, { "input": "Describe the mechanism of action of Bezlotoxumab?", "output": "Bezlotoxumab (Zinplava\u2122) is a human monoclonal antibody against Clostridium difficile toxin B (TcdB). It is used for prevention of recurrent C. difficile infections." }, { "input": "Is apremilast effective for psoriasis?", "output": "Yes, apremilast is effective for treatment of psoriasis." }, { "input": "Is skin color affected by variations of the SLC24A5 gene?", "output": "Yes. The alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) are associated with light skin pigmentation in Eurasian population." }, { "input": "How are Arboviruses transmitted?", "output": "Arboviruses are transmitted by arthropods." }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "Our results reveal that Nasuia-ALF has the smallest bacterial genome yet sequenced (112 kb), and that the Sulcia-ALF genome (190 kb) is smaller than that of Sulcia in other insect lineages. Both regions exhibit a significant reduction in length and gene number in B. aphidicola BCc, as it could be expected since it possess the smallest bacterial genome. We sequenced genomes of the obligate symbionts, Sulcia muelleri and Nasuia deltocephalinicola, of the phloem-feeding pest insect, Macrosteles quadrilineatus (Auchenorrhyncha: Cicadellidae). " }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "our results reveal that nasuia-alf has the smallest bacterial genome yet sequenced (112 kb), and that the sulcia-alf genome (190 kb) is smaller than that of sulcia in other insect lineages." }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "Nasuia deltocephalinicola, of the phloem-feeding pest insect, Macrosteles quadrilineatus has the smallest bacterial genome yet sequenced (112 kb)." }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "Our results reveal that Nasuia-ALF has the smallest bacterial genome yet sequenced (112 kb), and that the Sulcia-ALF genome (190 kb) is smaller than that of Sulcia in other insect lineages. We sequenced genomes of the obligate symbionts, Sulcia muelleri and Nasuia deltocephalinicola, of the phloem-feeding pest insect, Macrosteles quadrilineatus (Auchenorrhyncha: Cicadellidae)." }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "Our results reveal that Nasuia-ALF has the smallest bacterial genome yet sequenced (112 kb), and that the Sulcia-ALF genome (190 kb) is smaller than that of Sulcia in other insect lineages. Both regions exhibit a significant reduction in length and gene number in B. aphidicola BCc, as it could be expected since it possess the smallest bacterial genome." }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "sequenced genomes of the obligate symbionts , sulcia muelleri and nasuia deltocephalinicola , of the phloem-feeding pest insect , macrosteles quadrilineatus (auchenorrhyncha: cicadellidae). . regions exhibit a significant reduction in length and gene number in b aphidicola bcc , as it could be expected since it possess the smallest bacterial genome. . results reveal that nasuia-alf has the smallest bacterial genome yet sequenced (112 kb) , and that the sulcia-alf genome (190 kb) is smaller than that of sulcia in other insect lineages. . " }, { "input": "Which bacterium has the smallest genome in base pairs yet found?", "output": "Our results reveal that Nasuia-ALF has the smallest bacterial genome yet sequenced (112 kb), and that the Sulcia-ALF genome (190 kb) is smaller than that of Sulcia in other insect lineages." }, { "input": "Which are the triad symptoms of pheochromocytoma?", "output": "The classic triad of symptoms are episodic headache, excessive sweating (diaphoresis) and palpitation." }, { "input": "List the types of the Cardiorenal syndrome (CRS) according to the five-part classification system.", "output": "Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. \nCRS type 1: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. \nCRS type 2: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. \nCRS type 3: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. \nCRS type 4: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. \nCRS type 5: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney." }, { "input": "What is a miR?", "output": "The discovery of microRNAs (miRNAs) has opened an entire new avenue for drug development. These short (15-22 nucleotides) noncoding RNAs, which function in RNA silencing and posttranscriptional regulation of gene expression, have been shown to critically affect numerous pathways in both development and disease progression." }, { "input": "Do circRNAs remain untranslated?", "output": "The resulting circRNA can be translated to generate functional proteins." }, { "input": "Do circRNAs remain untranslated?", "output": "We demonstrate that the circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression" }, { "input": "Do circRNAs remain untranslated?", "output": "yes" }, { "input": "What is the biological function of the SRY circular RNA (circRNA)?", "output": "We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse. While this result does not prove a direct interaction between the two genes, it defines the critical period during which Sry must act to initiate Sertoli cell differentiation. We also attempted to make clear whether the equine SRY gene transcript is expressed in the adult testis, and whether the type of transcript is expressed as linear or circular RNA. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the \"microRNA sponge\" function of circRNA is discovered" }, { "input": "What is the biological function of the SRY circular RNA (circRNA)?", "output": "Sox5, Sox6, and Sox13 constitute the group D of sex-determining region (Sry)-related transcription factors. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. These observations support the hypothesis that the Q-rich domain may contribute to the biological function(s) of mouse Sry through a protein-protein interactive role(s)." }, { "input": "What is the biological function of the SRY circular RNA (circRNA)?", "output": "Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the \"microRNA sponge\" function of circRNA is discovered" }, { "input": "What is the biological function of the SRY circular RNA (circRNA)?", "output": "We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively We also attempted to make clear whether the equine SRY gene transcript is expressed in the adult testis, and whether the type of transcript is expressed as linear or circular RNA. However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the \"microRNA sponge\" function of circRNA is discovered We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse. While this result does not prove a direct interaction between the two genes, it defines the critical period during which Sry must act to initiate Sertoli cell differentiation." }, { "input": "What is the biological function of the SRY circular RNA (circRNA)?", "output": "The testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon." }, { "input": "What is Uhl's anomaly?", "output": "uhl's anomaly is an extremely rare cardiac defect characterized by absence of the myocardium of the right ventricle." }, { "input": "What is Uhl's anomaly?", "output": "Uhl's anomaly is an evolutive disease leading to terminal right ventricular failure. Uhl's anomaly is an extremely rare cardiac defect characterized by absence of the myocardium of the right ventricle." }, { "input": "What is Uhl's anomaly?", "output": "Uhl's anomaly is an extremely rare cardiac defect characterized by absence of the myocardium of the right ventricle. Uhl's anomaly is an evolutive disease leading to terminal right ventricular failure. " }, { "input": "What is Uhl's anomaly?", "output": "Uhl's anomaly is an extremely rare cardiac defect characterized by absence of the myocardium of the right ventricle. Uhl's anomaly is an evolutive disease leading to terminal right ventricular failure" }, { "input": "What is Uhl's anomaly?", "output": "Uhl's anomaly is an extremely rare cardiac defect characterized by absence of the myocardium of the right ventricle." }, { "input": "Is autophagy the process where bacteria ingest viral particles?", "output": "Autophagy, a cellular degradation process" }, { "input": "Can aspirin be used in cancer prevention?", "output": "Long-term aspirin use was associated with a modest but significantly reduced risk for overall cancer, especially gastrointestinal tract tumors. Regular aspirin use may prevent a substantial proportion of colorectal cancers and complement the benefits of screening." }, { "input": "Which are the components of the pre-replication complex (pre-RC) in eukaryotes?", "output": "The components of the pre-replication complex (pre-RC) in eukaryotes are:\n1) Cdc6/Cdc18, \n2) MCM, \n3) ORC1-6,\n4) Cdt1 and\n5) Sap1/Gi." }, { "input": "What is the inheritance of hypophosphatemic rickets?", "output": "Hypophosphatemic rickets are transmitted with:\n1) autosomal recessive\n2) autosomal dominant\n3) X-linked recessive and\n4) X-linked dominant inheritance." }, { "input": "Which mushroom is poisonous, Amanita phalloides or Agaricus Bisporus", "output": "The well-known cultivated species Agaricus bisporus is safe to eat while Amanita Phalloides is poisonous." }, { "input": "Which is the most common gene signature in Rheumatoid Arthritis patients?", "output": "A five gene type I IFN signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type I IFN pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the WB with clinical measurements.R Baseline disease activity measurements correlated with a type I IFN gene signature in the WB of subjects with SLE, PM and SSc, as did various serum autoantibody levels in subjects with SLE and DM." }, { "input": "Which is the most common gene signature in Rheumatoid Arthritis patients?", "output": "Baseline disease activity measurements correlated with a type I IFN gene signature in the WB of subjects. The type I IFN signature negatively predicts the clinical response to rituximab treatment in patients with RA." }, { "input": "Which is the most common gene signature in Rheumatoid Arthritis patients?", "output": "a five gene type i ifn signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type i ifn pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the wb with clinical measurements." }, { "input": "Which is the most common gene signature in Rheumatoid Arthritis patients?", "output": "A five gene type I IFN signature was assessed in these subjects to identify subpopulations showing both activation and concordance of the type I IFN pathway in the peripheral blood and disease-affected tissues of each disease and to correlate activation of this pathway in the WB with clinical measurements.R" }, { "input": "Which NGS alignment software implement the Burrows-Wheeler Transform?", "output": "The most widely used software belong to the family of the Burrows-Wheeler Aligner (BWA) and its variants for local alignment BWASW, map reduce BWASW-PMR and multi-threaded implementation BWA-MT. Other approaches include Bowtie, SOAP2, BWBBLE, SOAP2 and FANSe2." }, { "input": "Is intraoperative radiotherapy used for treatment of glioblastoma?", "output": "Yes, intraoperative radiotherapy (IORT) is being used for treatment of glioblastoma. IORT combined with extensive tumor removal has an acceptable toxicity in previously irradiated patients and can be effective for selected recurrent malignant brain tumors." }, { "input": "Which server is used for generating modes of pseudo components of DNA, RNA and protein sequences?", "output": "Pse-in-One is a web server for generating various modes of pseudo components of DNA, RNA, and protein sequences. It can, through its 28 different modes, generate nearly all the possible feature vectors for DNA, RNA and protein sequences. Particularly, it can also generate those feature vectors with the properties defined by users themselves. These feature vectors can be easily combined with machine-learning algorithms to develop computational predictors and analysis methods for various tasks in bioinformatics and system biology." }, { "input": "What is the link between TB (Turbeculosis) infection and TNFa inhibition?", "output": "The occurrence of tuberculosis (TB) in patients treated with immunosuppressive drugs (ISD) is an old problem that has been highlighted by cases occurring in patients using anti-TNFalpha drugs." }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. Diamond Blackfan anemia (DBA) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Diamond-Blackfan anemia (DBA) is a rare congenital disease affecting erythroid precursor differentiation. Diamond-Blackfan anemia (DBA) is a congenital disease characterized by defective erythroid progenitor maturation and physical malformations." }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients." }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "In 25% of patients with Diamond-Blackfan anaemia 19q13 gene mutation was detected, and recent findings suggest another gene located on 8p23.3-p22 chromosome. Diamond Blackfan anemia (DBA) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. We also report the prevalence of RPS 19 mutations in the Italian DBA population, as shown by an analysis of 56 patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. " }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "blackfan anemia (dba) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. . genes encoding ribosomal proteins have been associated to dba: after rps19 , mutations in genes rps24 and rps17 were recently identified in a fraction of the patients. . 25% of patients with diamond-blackfan anaemia 19q13 gene mutation was detected , and recent findings suggest another gene located on 8p23.3-p22 chromosome. . transgenic mouse model demonstrates a dominant negative effect of a point mutation in the rps19 gene associated with diamond-blackfan anemia . also report the prevalence of rps 19 mutations in the italian dba population , as shown by an analysis of 56 patients. . in the gene encoding ribosomal protein (rp) s19 have recently been found in 25% of patients with either the dominant or the sporadic form. . " }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "Diamond Blackfan anemia (DBA) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes." }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "three genes encoding ribosomal proteins have been associated to dba: after rps19, mutations in genes rps24 and rps17 were recently identified in a fraction of the patients." }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "Small ribosomal subunit genes RPS19, RPS24, and RPS17 are mutated in approximately one-third of patients. Currently two genes are associated with the DBA phenotype--the ribosomal protein (RP) S19 mutated in 25% of DBA patients and RPS24 mutated in approximately 1.4% of DBA patients. As a proof of concept, we designed a multiplex ligation-dependent probe amplification assay targeted to screen the six genes that are most frequently mutated in Diamond-Blackfan anemia patients: RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A. We sequenced GATA-1 in 23 patients that were negative for mutations in the most frequently mutated DBA genes. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. More than a decade has passed since the initial identification of ribosomal protein gene mutations in patients with Diamond-Blackfan anemia (DBA), a hematologic disorder that became the founding member of a class of diseases known as ribosomopathies. In this study, nine Korean DBA patients were screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10, RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method." }, { "input": "Which class of genes are mutated in Diamond Blackfan Anemia patients?", "output": "Diamond Blackfan anemia (DBA) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder." }, { "input": "List the human acrocentric chromosomes that are involved in Robertsonian translocation.", "output": "Robertsonian translocations (ROBs) are the most common chromosomal rearrangements in humans. ROBs are whole-arm rearrangements between the acrocentric chromosomes 13, 14, 15, 21, and 22." }, { "input": "Is tirilazad effective for treatment of aneurysmal subarachnoid haemorrhage?", "output": "No. Based on meta-analysis, there is no evidence that tirilazad, in addition to nimodipine, reduces mortality or improves poor outcome in patients with aneurysmal subarachnoid haemorrhage." }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "Coilin is widely known as the protein marker of the Cajal body, a subnuclear domain important to the biogenesis of small nuclear ribonucleoproteins and telomerase, complexes that are crucial to pre-messenger RNA splicing and telomere maintenance, respectively The Cajal body has now regained the interest of biologists, due to the isolation of a protein marker, coilin." }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "Coilin is widely known as the protein marker of the Cajal body, a subnuclear domain important to the biogenesis of small nuclear ribonucleoproteins and telomerase, complexes that are crucial to pre-messenger RNA splicing and telomere maintenance, respectively Extensive studies have characterized the interaction between coilin and the various other protein components of CBs and related subnuclear domains; however, only a few have examined interactions between coilin and nucleic acid." }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "Coilin is widely known as the protein marker of the Cajal body, a subnuclear domain important to the biogenesis of small nuclear ribonucleoproteins and telomerase, complexes that are crucial to pre-messenger RNA splicing and telomere maintenance, respectively. The Cajal (coiled) body is a discrete nuclear organelle that was first described in mammalian neurons in 1903." }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "coilin" }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "Coilin is widely known as the protein marker of the Cajal body, a subnuclear domain important to the biogenesis of small nuclear ribonucleoproteins and telomerase, complexes that are crucial to pre-messenger RNA splicing and telomere maintenance, respectively" }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "Coilin, more than a molecular marker of the cajal (coiled) body The Cajal body has now regained the interest of biologists, due to the isolation of a protein marker, coilin." }, { "input": "Which protein is the main marker of Cajal bodies?", "output": "Coilin is widely known as the protein marker of the Cajal body, a subnuclear domain important to the biogenesis of small nuclear ribonucleoproteins and telomerase, complexes that are crucial to pre-messenger RNA splicing and telomere maintenance, respectively." }, { "input": "Which mutated gene causes the Ch\u00e9diak\u2013Higashi Syndrome?", "output": "Mutation in the lysosomal trafficking regulator (LYST) gene causes the Ch\u00e9diak-Higashi syndrome (CHS)." }, { "input": "The pathogen Fusarium graminearum affects what type of plant species?", "output": "Fusarium graminearum is a broad host pathogen threatening cereal crops in temperate regions around the world." }, { "input": "The pathogen Fusarium graminearum affects what type of plant species?", "output": "Fusarium graminearum is a broad host pathogen threatening cereal crops in temperate regions around the world. " }, { "input": "List viral vectors used in gene therapy.", "output": "adeno-associated viruses\nlentiviruses\nherpes simplex viral vector" }, { "input": "Is dexamethasone recommended for treatment of intracerebral hemorrhage?", "output": "No. Dexamethasone and other glucocorticoids should be avoided for treatment of intracerebral hemorrhage because they do not improve patient outcome and are associated with increased risk of side effects." }, { "input": "What happens upon disruption of a TAD boundary?", "output": "rewiring occurred only if the variant disrupted a ctcf-associated boundary domain . of a tad boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. . of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions . " }, { "input": "What happens upon disruption of a TAD boundary?", "output": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. " }, { "input": "What happens upon disruption of a TAD boundary?", "output": "This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus." }, { "input": "What happens upon disruption of a TAD boundary?", "output": "both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding dna, and a cluster of limb enhancers normally associated with epha4 is misplaced relative to tad boundaries and drives ectopic limb expression of another gene in the locus." }, { "input": "What happens upon disruption of a TAD boundary?", "output": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. " }, { "input": "What happens upon disruption of a TAD boundary?", "output": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. " }, { "input": "What happens upon disruption of a TAD boundary?", "output": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation." }, { "input": "What happens upon disruption of a TAD boundary?", "output": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. In this way, disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain." }, { "input": "What happens upon disruption of a TAD boundary?", "output": "Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. " }, { "input": "List the classical symptoms of the Moschcowitz syndrome (Thrombotic thrombocytopenic purpura).", "output": "The typical manifestations of Moschocowitz syndrome (Thrombotic-thrombocytopenic purpura) are:\n1) thrombocytopenia, \n2) haemolysis, \n3) fever, \n4) coma and \n5) renal failure." }, { "input": "Is airplane stroke syndrome a common disease.", "output": "No. Only 37 cases of stroke during or soon after long-haul flights have been published. A single center study reported that 42 out of 5727 stroke admissions (0.73%) were flight-related strokes." }, { "input": "Which R / bioconductor package is used for enrichment analysis of genomic regions?", "output": "locus overlap analysis (lola) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data." }, { "input": "Which R / bioconductor package is used for enrichment analysis of genomic regions?", "output": "Genomic datasets are often interpreted in the context of large-scale reference databases. Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data." }, { "input": "Which R / bioconductor package is used for enrichment analysis of genomic regions?", "output": "Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data." }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. TIRs were deduced to form dsRNAs as a putative target of ADAR. Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. " }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "The ADAR (adenosine deaminase, RNA-specific) RNA editing enzyme controls neuronal excitability in Drosophila melanogaster." }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. TIRs were deduced to form dsRNAs as a putative target of ADAR. we show that expression of the editing enzyme, ADAR (adenosine deaminase acting on RNA), is dramatically decreased at elevated temperatures, partially, but not fully, explaining some target responses to temperature. " }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "Adenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. RNA editing by deamination of specific adenosine bases to inosines during pre-mRNA processing generates edited isoforms of proteins. RNA editing is proposed as a modulator of transcriptomes, but its biological impact has not been fully elucidated. Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts." }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "adar" }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. Adenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans." }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. TIRs were deduced to form dsRNAs as a putative target of ADAR. " }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts. TIRs were deduced to form dsRNAs as a putative target of ADAR. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. " }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "GABA inhibitory signalling is impaired in human epileptic and autistic conditions, and vertebrate ADARs may have a relevant evolutionarily conserved control over neuronal excitability. RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets." }, { "input": "Which is the major RNA editing enzyme in Drosophila melanogaster?", "output": "Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)] catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts." }, { "input": "What is the CEGA catalog?", "output": "CEGA is a catalog of conserved elements from genomic alignments. Harnessing the power of multiple species comparisons to detect genomic elements under purifying selection, CEGA provides a comprehensive set of CNCs identified at different radiations along the vertebrate lineage. Evolutionary constraint is identified using threshold-free phylogenetic modeling of unbiased and sensitive global alignments of genomic synteny blocks identified using protein orthology. The dynamic CEGA web interface displays alignments, genomic locations, as well as biologically relevant data to help prioritize and select CNCs of interest for further functional investigations." }, { "input": "Which protein is associated with hyperemesis gravidarum during pregrancy?", "output": "Human chorionic gonadotropin (hCG) is associated with hyperemesis gravidarum during pregrancy." }, { "input": "Is hydroxyurea usually used to treated infectious disease?", "output": "Hydroxyurea represents the only available disease-modifying therapy for Sickle Cell Anemia (SCA)." }, { "input": "What is magnetoreception?", "output": "Magnetoreception is an enigmatic, poorly understood sensory ability, described mainly on the basis of behavioural studies in animals of diverse taxa. The ability to perceive geomagnetic fields (GMFs) represents a fascinating biological phenomenon. Studies on transgenic flies have provided evidence that photosensitive Cryptochromes (Cry) are involved in the response to magnetic fields (MFs). The photoreceptor protein cryptochrome is thought to host, upon light absorption, a radical pair that is sensitive to very weak magnetic fields, endowing migratory birds with a magnetic compass sense." }, { "input": "Can acupuncture cause spinal epidural hematoma?", "output": "Yes, acupuncture can cause spinal epidural hematoma." }, { "input": "Is edema a symptom of nephrotic syndrome?", "output": "Yes, edema is the commonest presenting symptom and sign in nephrotic syndrome." }, { "input": "Angelman syndrome is associated with deletion of a part of Chromosome 15 but if the deletion occurs in the paternally inherited chromosome 15, what is the disease?", "output": "Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13." }, { "input": "Angelman syndrome is associated with deletion of a part of Chromosome 15 but if the deletion occurs in the paternally inherited chromosome 15, what is the disease?", "output": " prader-willi syndrome (pws) results from a deletion of the paternal genes in the region of chromosome 15q11-q13." }, { "input": "Angelman syndrome is associated with deletion of a part of Chromosome 15 but if the deletion occurs in the paternally inherited chromosome 15, what is the disease?", "output": "Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13. " }, { "input": "Angelman syndrome is associated with deletion of a part of Chromosome 15 but if the deletion occurs in the paternally inherited chromosome 15, what is the disease?", "output": " Prader-Willi syndrome (PWS) results from a deletion of the paternal genes in the region of chromosome 15q11-q13." }, { "input": "What is the phenotype of people carrying mutations in the gene PRDM12?", "output": "New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families." }, { "input": "Is there an association between Histone H3.3 mutations and glioma?", "output": "Yes, histone H3.3 mutation in the codon for lysine 27 has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas." }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. " }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase. Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. They both bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins." }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Here we describe the remaining two genes, fhl1 and fkh2, that code for proteins containing fork-head-associated domains (FHA) besides their FKHs. This may reflect a general feature of gene regulation in eukaryotes. " }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae." }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. " }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing." }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan." }, { "input": "Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?", "output": "Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing." }, { "input": "What is the role of the Ctf4-interacting-peptide or CIP-box?", "output": "Crystallographic analysis classifies CIP-boxes into two related groups that target different sites on Ctf4. Mutations in the CIP-box motifs of the Dna2 nuclease or the rDNA-associated protein Tof2 do not perturb DNA synthesis genome-wide, but instead lead to a dramatic shortening of chromosome 12 that contains the large array of rDNA repeats. Data reveal unexpected complexity of Ctf4 function, as a hub that connects multiple accessory factors to the replisome. Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation." }, { "input": "What type of genome, (RNA or DNA, double stranded single stranded) is found in the the virus that causes blue tongue disease?", "output": "The Bluetongue virus (BTV) genome contains ten double-stranded RNA segments." }, { "input": "What type of genome, (RNA or DNA, double stranded single stranded) is found in the the virus that causes blue tongue disease?", "output": "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments. " }, { "input": "What type of genome, (RNA or DNA, double stranded single stranded) is found in the the virus that causes blue tongue disease?", "output": "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments." }, { "input": "What type of genome, (RNA or DNA, double stranded single stranded) is found in the the virus that causes blue tongue disease?", "output": "Bluetongue virus (BTV) genome contains ten double-stranded RNA segments" }, { "input": "What type of genome, (RNA or DNA, double stranded single stranded) is found in the the virus that causes blue tongue disease?", "output": "bluetongue virus (btv) genome contains ten double-stranded rna segments." }, { "input": "What is a \"chemobrain\"?", "output": "The term \"chemobrain\" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment." }, { "input": "Borden classification is used for which disease?", "output": "Borden classification systems is used for the prediction of clinical behavior of cranial dural arteriovenous fistulas." }, { "input": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "output": "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation. " }, { "input": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "output": "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions." }, { "input": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "output": " we propose that enhancer sharing is commonplace among eukaryotes, and that ep distance is an important layer of information in gene regulation." }, { "input": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "output": "Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation." }, { "input": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "output": "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes" }, { "input": "Which effects create neighborhoods of transcriptional regulation in eukaryotes?", "output": "Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation." }, { "input": "Is Pfh1 a component of the replisome?", "output": "No. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity. DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase." }, { "input": "What is the function of mTOR?", "output": "The mTOR protein regulates assembly of the translation initiation machinery and are master regulators of cellular survival, growth and metabolism." }, { "input": "What is the indication for valbenazine?", "output": "Valbenazine granted breakthrough drug status for treating tardive dyskinesia." }, { "input": "List features of the Kaufman Oculocerebrofacial Syndrome.", "output": "Clinical features of the Kaufman Oculocerebrofacial Syndrome include hypotonia, developmental delay, intellectual disability, low cholesterol levels, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet." }, { "input": "What is the role of DNA Repair Cofactors ATMIN and NBS1?", "output": "The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability. The role of a second ATM cofactor, ATMIN (also known as ASCIZ) in T cells is much less clear, and whether ATMIN and NBS1 function in synergy in T cells is unknown." }, { "input": "What is the role of DNA Repair Cofactors ATMIN and NBS1?", "output": "The DNA Repair Cofactors ATMIN and NBS1 are required to suppress T Cell activation. Loss of NBS1 led to a developmental block at the double-positive stage of T cell development, as well as reduced TCR\u03b1 recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant loss of ATMIN. In contrast, loss of both ATMIN and NBS1 enhanced DNA damage that drove spontaneous peripheral T cell hyperactivation, proliferation as well as excessive production of proinflammatory cytokines and chemokines, leading to a highly inflammatory environment. Intriguingly, the disease causing T cells were largely proficient for both ATMIN and NBS1. In vivo this resulted in severe intestinal inflammation, colitis and premature death." }, { "input": "The MMR vaccine protects against what 3 viruses?", "output": "The MMR vaccine provides immunity to measles, mumps and rubella." }, { "input": "The MMR vaccine protects against what 3 viruses?", "output": " measles, mumps and rubella (mmr) vaccine ." }, { "input": "List cardinal features of the Triple A syndrome.", "output": "Triple A syndrome, also known as Allgrove syndrome, is a rare disease, and presents mainly in children. Its cardinal symptoms are achalasia, alacrima, and adrenal insufficiency." }, { "input": "Describe the applicability of Basset in the context of deep learning", "output": "Basset is an open source package which applies CNNs to learn the functional activity of DNA sequences from genomics data. Basset was trained on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrated greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome." }, { "input": "Does the Abelson-related gene (ARG) gene encode for a serine kinase?", "output": "No, the ARG gene encodes for a nonreceptor tyrosine kinase." }, { "input": "What organism causes tularemia?", "output": "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. F. tularensis is the causative agent of zoonotic tularemia. " }, { "input": "What organism causes tularemia?", "output": "francisella tularensis, the agent of tularemia, is a gram-negative coccobacillus primarily pathogen for animals and occasionally for humans." }, { "input": "What organism causes tularemia?", "output": "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. " }, { "input": "What organism causes tularemia?", "output": "Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans." }, { "input": "Is Prochlorococcus the most abundant photosynthetic organism?", "output": "Yes, the marine cyanobacterium Prochlorococcus is the smallest and most abundant photosynthetic organism on Earth." }, { "input": "List 3 features of IRVAN syndrome.", "output": "Idiopathic retinal vasculitis, aneurysms, and neuroretinitis is coined as IRVAN syndrome." }, { "input": "Which are the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) inhibitors that are FDA approved?", "output": "The PCSK9 inhibitors that are FDA approved are:\n1) Alirocumab and \n2) Evolocumab." }, { "input": "Is dupilumab an antibody targeting the IL-1 receptor?", "output": "No, Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor \u03b1 subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways." }, { "input": "List active ingredients of the Stribild polypill.", "output": "Active ingredients of Stribild are elvitegravir, cobicistat, emtricitabine and tenofovir. It is used for treatment of HIV infection." }, { "input": "List clinical features of the IMAGe syndrome.", "output": "Clinical features of IMAGe syndrome include intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities. It is s caused by gain-of-function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5." }, { "input": "Which gene mutations are predictive of response to anti-TNF therapy in Rheumatoid Arthritis patients?", "output": "\u039cutations in TLR5 and TLR1 genes contribute to differential response to anti-TNF treatment in RA. Variation at FCGR2A and functionally related genes such as DHX32 and RGS12 is also associated with the response to anti-TNF therapy in rheumatoid arthritis." }, { "input": "Which method is used for prediction of novel microRNA genes in cancer-associated genomic regions?", "output": "SSCprofiler is a computational tool utilizing a probabilistic method based on Profile Hidden Markov Models to predict novel miRNA precursors. Via the simultaneous integration of biological features such as sequence, structure and conservation, SSCprofiler achieves a performance accuracy of 88.95% sensitivity and 84.16% specificity on a large set of human miRNA genes. The trained classifier is used to identify novel miRNA gene candidates located within cancer-associated genomic regions and rank the resulting predictions using expression information from a full genome tiling array. SSCprofiler is freely available as a web service at http://www.imbb.forth.gr/SSCprofiler.html." }, { "input": "Does the histone chaperone ASF1 interact with histones H1/H2?", "output": "No, the histone chaperone ASF1 interacts with histones H3/H4." }, { "input": "Is Hepatic mesenchymal hamartoma usually a malignant tumor?", "output": "Mesenchymal hamartoma of the liver (MHL) is an uncommon benign hepatic tumor typically affecting children under 2 years of age." }, { "input": "Is Hepatic mesenchymal hamartoma usually a malignant tumor?", "output": "Mesenchymal hamartoma of the liver (MHL) is a benign and rare hepatic lesion, " }, { "input": "Is Hepatic mesenchymal hamartoma usually a malignant tumor?", "output": "mesenchymal hamartoma of the liver (mhl) is an uncommon benign hepatic tumor typically affecting children under 2 years of age." }, { "input": "List clinical features of EEM syndrome.", "output": "EEM syndrome is characterized by ectodermal dysplasia, ectrodactyly and macular dystrophy." }, { "input": "How many times is CLAST faster than BLAST?", "output": "was capable of identifying sequence similarities ~80.8 times faster than blast and 9.6 times faster than blat . " }, { "input": "How many times is CLAST faster than BLAST?", "output": "CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT. " }, { "input": "How many times is CLAST faster than BLAST?", "output": "CLAST was capable of identifying sequence similarities ~80.8 times faster than BLAST and 9.6 times faster than BLAT" }, { "input": "How many times is CLAST faster than BLAST?", "output": "clast was capable of identifying sequence similarities ~80.8 times faster than blast and 9.6 times faster than blat." }, { "input": "How many times is CLAST faster than BLAST?", "output": "CLAST is capable of identifying sequence similarities ~80.8 times faster than BLAST" }, { "input": "Which are the most common methods for circular RNA detection from RNASeq?", "output": "The main algorithms are circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice." }, { "input": "Which are the most common methods for circular RNA detection from RNASeq?", "output": "Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. " }, { "input": "Which are the most common methods for circular RNA detection from RNASeq?", "output": "Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance." }, { "input": "Which are the most common methods for circular RNA detection from RNASeq?", "output": "CircRNAs are novel members of the non-coding RNA family. Several pipelines have been developed to specifically identify these non-linear reads and consequently predict the landscape of circRNAs based on deep sequencing datasets. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance." }, { "input": "Which are the most common methods for circular RNA detection from RNASeq?", "output": ", use common rnaseq datasets to scrutinize and compare the output from five different algorithms; circrna_finder , find_circ , circexplorer , ciri , and mapsplice and evaluate the levels of bona fide and false positive circrnas based on rnase r resistance. . " }, { "input": "Which are the most common methods for circular RNA detection from RNASeq?", "output": "here, we use common rnaseq datasets to scrutinize and compare the output from five different algorithms; circrna.finder, find.circ, circexplorer, ciri, and mapsplice and evaluate the levels of bona fide and false positive circrnas based on rnase r resistance." }, { "input": "From which cell type is leptin secreted?", "output": "leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode." }, { "input": "From which cell type is leptin secreted?", "output": " Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland." }, { "input": "From which cell type is leptin secreted?", "output": " Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland. Lipolysis (stimulated by beta-adrenergic agents) and leptin secretion by adipocytes are down-regulated by neurons in coculture, effects apparently mediated by neuropeptide Y (NPY)" }, { "input": "From which cell type is leptin secreted?", "output": "Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland. Lipolysis (stimulated by beta-adrenergic agents) and leptin secretion by adipocytes are down-regulated by neurons in coculture, effects apparently mediated by neuropeptide Y (NPY). Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands. " }, { "input": "From which cell type is leptin secreted?", "output": "Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands." }, { "input": "From which cell type is leptin secreted?", "output": "Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode." }, { "input": "From which cell type is leptin secreted?", "output": "Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands. Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode." }, { "input": "From which cell type is leptin secreted?", "output": "Leptin is a 16 kDa protein that exerts important effects on the regulation of food intake and energy expenditure by interacting with the leptin receptor in the brain and in many other tissues. Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland." }, { "input": "From which cell type is leptin secreted?", "output": "Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co-localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands. Although leptin is produced mainly by white adipose tissue, several laboratories have shown low levels of leptin production by a growing number of tissues including the anterior pituitary gland." }, { "input": "Which tool is used for the identification of recurrent variants in noncoding regions?", "output": "LARVA is an integrative framework for large-scale analysis of recurrent variants in noncoding annotations. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a \u03b2-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers." }, { "input": "What body parts are also known as phalanges?", "output": "The anatomical structure of each finger is comprised of four phalanges (distal, middle, proximal, and metacarpal phalange). Toes are also known as phalages" }, { "input": "Are selenium supplements recommended for prostate cancer prevention?", "output": "No. The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations." }, { "input": "Which disease is treated with lucinactant?", "output": "Lucinactant us used for the prevention of respiratory distress syndrome in premature infants." }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. " }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. " }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery." }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3 These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene." }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). " }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3" }, { "input": "Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?", "output": "Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome and Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complexes. The termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity." }, { "input": "Is there any involvement of L1 retrotransposition in the Rett syndrome?", "output": "Yes. Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia." }, { "input": "Is Downs syndrome associated with decreased risk of leukemia?", "output": "No, multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population." }, { "input": "Which enzyme is inhibited by ixazomib?", "output": "Ixazomib is proteasome inhibitor. It is used for treatment of multiple myeloma." }, { "input": "Does PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds with HDL-receptor (HDL-R)?", "output": "No, Proprotein Convertase Subtilisin Kexin 9 (PCSK9) binds with LDL-receptor (LDL-R) causing its degradation in the lysosome with the result of LDL-C accumulating in the blood." }, { "input": "Hy's law measures failure for what organ?", "output": "Hy's law correlates enzyme elevations with liver injury ad subsequent failure." }, { "input": "Is apremilast effective for psoriatic arthritis?", "output": "Yes, apremilast, an oral phosphodiesterase 4 inhibitor, is effective for psoriatic arthritis." }, { "input": "Is there any role of TBR1 in autism?", "output": "Yes. Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including T-Brain-1 (TBR1), a master regulator of cortical development. T-brain-1 (TBR1) is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1 (-\u2215-) mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala, and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1." }, { "input": "What is the role of the MCM2-7 complex?", "output": "The MCM2-7 complex is a ring-shaped heterohexamer helicase, that unwinds the DNA double helix ahead of the other replication machinery. During pre-replication complex (pre-RC) formation, origin recognition complex (ORC), Cdc6, and Cdt1 cooperatively load a double-hexameric MCM2-7 complex onto DNA. Loading of MCM2-7 is a prerequisite for licensing of eukaryotic DNA replication. During S phase MCM2-7 functions as part of the replicative helicase but within the pre-RC MCM2-7 is inactive." }, { "input": "In which fields of DNA sequencing are Bloom filters applied?", "output": "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters Lighter is a fast, memory-efficient tool for correcting sequencing errors." }, { "input": "In which fields of DNA sequencing are Bloom filters applied?", "output": "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters. Further, we note that Bloom filters would be suitable to implicitly store spaced seeds and be tolerant to sequencing errors. Lighter avoids counting k-mers. Fast lossless compression via cascading Bloom filters. " }, { "input": "In which fields of DNA sequencing are Bloom filters applied?", "output": "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters. Instead, it uses a pair of Bloom filters, one holding a sample of the input k-mers and the other holding k-mers likely to be correct. Fast lossless compression via cascading Bloom filters. Lighter is a fast, memory-efficient tool for correcting sequencing errors. " }, { "input": "In which fields of DNA sequencing are Bloom filters applied?", "output": "A novel algorithm, fast and accurate classification of sequences (FACSs), is introduced that can accurately and rapidly classify sequences as belonging or not belonging to a reference sequence. Classification of DNA sequences using Bloom filters. Instead, it uses a pair of Bloom filters, one holding a sample of the input k-mers and the other holding k-mers likely to be correct. Lighter is a fast, memory-efficient tool for correcting sequencing errors. Lighter avoids counting k-mers. " }, { "input": "In which fields of DNA sequencing are Bloom filters applied?", "output": "Bloom Filters (BFs) reduce the memory footprint required to store millions of k-mers while allowing for fast set containment queries, at the cost of a low false positive rate (FPR). Cascading Bloom filters have been used to improve the memory usage and speed of DNA sequence compression." }, { "input": "In which fields of DNA sequencing are Bloom filters applied?", "output": "Further, we note that Bloom filters would be suitable to implicitly store spaced seeds and be tolerant to sequencing errors. It uses a pair of cache oblivious Bloom filters, one holding a uniform sample of [Formula: see text]-spaced sequenced [Formula: see text]-mers and the other holding [Formula: see text]-mers classified as likely correct, using a simple statistical test." }, { "input": "Which 2 medications are included in the Qsymia pill?", "output": "Qsymia pill includes phentermine and topiramate. It is used for treatment of obesity." }, { "input": "Is sonidegib effective for basal cell carcinoma?", "output": "Yes. Sonidegib, an oral smoothened antagonist, is indicated for the treatment of adults with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy." }, { "input": "Which R package could be used for the identification of pediatric brain tumors?", "output": "MethPed" }, { "input": "Which R package could be used for the identification of pediatric brain tumors?", "output": "The MethPed R package efficiently classifies pediatric brain tumors using the developed MethPed classifier. MethPed is available via Bioconductor: http://bioconductor.org/packages/MethPed/" }, { "input": "Which R package could be used for the identification of pediatric brain tumors?", "output": "The MethPed classifier, which is a multiclass random forest algorithm, based on DNA methylation profiles from many subgroups of pediatric brain tumors" }, { "input": "Describe the usefulness of CAMUR in The Cancer Genome Atlas (TCGA)", "output": "CAMUR is a new method that extracts multiple and equivalent classification models. CAMUR iteratively computes a rule-based classification model, calculates the power set of the genes present in the rules, iteratively eliminates those combinations from the data set, and performs again the classification procedure until a stopping criterion is verified. CAMUR includes an ad-hoc knowledge repository (database) and a querying tool. Three different types of RNA-seq data sets (Breast, Head and Neck, and Stomach Cancer) were analyzed from The Cancer Genome Atlas (TCGA) and CAMUR and its models were validated also on non-TCGA data. Experimental results show the efficacy of CAMUR by obtaining several reliable equivalent classification models, from which the most frequent genes, their relationships, and the relation with a particular cancer are deduced." }, { "input": "Which markers are screened with the triple test for the detection of syndromes in fetus?", "output": "The markers that are screened with the triple test for the detection of syndromes in fetus are:\n1) alpha-fetoprotein (AFP), \n2) beta-chorionic gonadotrophin (beta-CG) and \n3) unconjugated oestriol (uE3)." }, { "input": "What is the role of TAD protein domain?", "output": "TAD domain is a transcription activation domain found in transcription factors." }, { "input": "What is the function of lncRNA?", "output": "Long noncoding RNAs (lncRNAs) are involved in a variety of biological processes, including the epigenetic control of gene expression, post-transcriptional regulation of mRNA, and cellular proliferation and differentiation" }, { "input": "What is the function of the exosome?", "output": "Exosomes are 40-100-nm vesicles released by most cell types after fusion of multivesicular endosomes with the plasma membrane. Exosomes contain proteins and RNA species and can mediate communication and immune responses." }, { "input": "Which factors drive replisome disassembly during DNA replication termination and mitosis?", "output": "CUL-2LRR-1 and UBXN-3." }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex." }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II." }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process." }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage." }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex. The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II" }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage. The RNA polymerase II elongation complex." }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "yes" }, { "input": "Does RNA polymerase II have RNA cleavage activity?", "output": "The RNA polymerase II elongation complex.SII is an RNA polymerase II-binding protein that stimulates transcription elongation and also activates nascent transcript cleavage by RNA polymerase II in elongation complexes in vitroFactor-dependent transcription elongation involves nascent RNA cleavage.The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase IIThe eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex.Here we show that in the presence of SII and nucleotides, transcript cleavage is detected during SII-dependent elongation but not during SII-independent transcription.Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA.In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage.msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process.Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage." }, { "input": "Is there a sequence bias in MNase digestion patterns?", "output": "The cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments." }, { "input": "Is there a sequence bias in MNase digestion patterns?", "output": "yes" }, { "input": "Is there a sequence bias in MNase digestion patterns?", "output": "Micrococcal nuclease does not substantially bias nucleosome mapping. Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques." }, { "input": "Is NEMO a zinc finger protein?", "output": "NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain." }, { "input": "Does TFIIS affect nucleosome positioning?", "output": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT" }, { "input": "Does TFIIS affect nucleosome positioning?", "output": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. Efficient and rapid nucleosome traversal by RNA polymerase II depends on a combination of transcript elongation factors." }, { "input": "Does TFIIS affect nucleosome positioning?", "output": "We now show that although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner. Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. " }, { "input": "Does TFIIS affect nucleosome positioning?", "output": "yes" }, { "input": "Does TFIIS affect nucleosome positioning?", "output": "After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. Histone chaperones and transcription factors TFIIS, TFIIF and FACT facilitate transcription through chromatin using different molecular mechanisms. Although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner." }, { "input": "Does TFIIS affect nucleosome positioning?", "output": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. " }, { "input": "Which two cotransporters are inhibited by sotagliflozin?", "output": "Sotagliflozin works by inhibiting sodium-glucose cotransporter 1 (SGLT1) and sodium-glucose cotransporter 2 (SGLT2). It is used for treatment of diabetes." }, { "input": "What is the administration route of IVIG in Alzheimer's disease patients?", "output": "IVIG is administered intravenously." }, { "input": "What is metaSPAdes?", "output": "MetaSPAdes is a new versatile metagenomic assembler." }, { "input": "What is metaSPAdes?", "output": "While metagenomics has emerged as a technology of choice for analyzing bacterial populations, the assembly of metagenomic data remains challenging, thus stifling biological discoveries. Moreover, recent studies revealed that complex bacterial populations may be composed from dozens of related strains, thus further amplifying the challenge of metagenomic assembly. MetaSPAdes is a new versatile metagenomic assembler which addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes." }, { "input": "What is measured through the NOMe-Seq methodology?", "output": "We have developed a method (NOMe-seq) that uses a GpC methyltransferase (M.CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome positioning genome-wide using less than 1 million cells while retaining endogenous DNA methylation information from the same DNA strand. DNaseI-seq and NOMe-seq." }, { "input": "What is measured through the NOMe-Seq methodology?", "output": "NOMe-seq is a method that uses a GpC methyltransferase (M.CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome positioning genome-wide using less than 1 million cells while retaining endogenous DNA methylation information from the same DNA strand." }, { "input": "What is the function of the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state." }, { "input": "What is the function of the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence to anti-tuberculosis drugs. The DosR regulon enables the pathogen to persist during lengthy hypoxia. Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions." }, { "input": "Which are the effects of ALDH2 deficiency?", "output": "In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. Diabetic patients with ALDH2 mutations are predisposed to worse diastolic dysfunction.\nThese data demonstrate that ALDH2 deficiency enhances EtOH-induced disruption of intestinal epithelial tight junctions, barrier dysfunction, and liver damage." }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA." }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "PET (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA." }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. This element, which we have named pet , exerts its effect in cis in a position and orientation-dependent manner, suggesting that pregenome transcription complexes fail to reach the downstream promoters. We speculate that pet , exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. " }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript.In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters.In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template.We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA." }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template." }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript." }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "This element, which we have named pet (positive effector of transcription), exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. " }, { "input": "What is the role of the positive effector of transcription (pet) in the hepatitis B virus?", "output": "This element, which we have named pet , exerts its effect in cis in a position and orientation-dependent manner, suggesting that it may function as part of the nascent pregenome transcript. In vitro transcription experiments support the model that pet is required for transcription elongation on the DHBV template. We speculate that pet is required to suppress transcription termination during the first passage of pregenome transcription complexes through a viral termination region on the circular viral DNA. In the presence of this region, deletion of pet activates transcription from downstream promoters, suggesting that pregenome transcription complexes fail to reach the downstream promoters. " }, { "input": "What is the role of Kmt5a in liver?", "output": "H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. In non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK) activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage." }, { "input": "What is the role of Kmt5a in liver?", "output": "Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions. H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability." }, { "input": "Is tretinoin effective for photoaging?", "output": "Yes, Tretinoin is commonly used topically in the treatment of photoaging." }, { "input": "What is the difference between ganglion mother cells (GMC) and intermediate neural precursor cells (INP) in Drosophila?", "output": "GMC divides only once to give rise to two post-mitotic cells (neurons or glia), whereas the INP can also self-renew, albeit for fewer rounds than a NSC, and generate GMCs" }, { "input": "What is the FIRE (Functional Inference of Regulators of Expression) tool?", "output": "FIRE (Functional Inference of Regulators of Expression) is a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes." }, { "input": "What is the FIRE (Functional Inference of Regulators of Expression) tool?", "output": "Methods to predict whether or not individual SNVs are likely to regulate gene expression would aid interpretation of variants of unknown significance identified in whole-genome sequencing studies. FIRE (Functional Inference of Regulators of Expression) is a tool to score both noncoding and coding SNVs based on their potential to regulate the expression levels of nearby genes. FIRE consists of 23 random forests trained to recognize SNVs in cis -expression quantitative trait loci (cis -eQTLs) using a set of 92 genomic annotations as predictive features." }, { "input": "Does TUC.338 inhibit colorectal cancer?", "output": "No. TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis. TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion." }, { "input": "Describe mechanism of action of Napabucasin.", "output": "Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 (STAT3) pathway." }, { "input": "Has ruxolitinib received FDA approval?", "output": "Yes, ruxolitinib is FDA approved. In 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis." }, { "input": "Do origins of replication close to yeast centromeres fire early or late?", "output": "Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome." }, { "input": "Do origins of replication close to yeast centromeres fire early or late?", "output": "In yeast each centromere is associated with a replication origin that is the first to fire on its respective chromosome." }, { "input": "Do origins of replication close to yeast centromeres fire early or late?", "output": "Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. " }, { "input": "Is scuba diving safe during pregnancy?", "output": "No, scuba diving should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity." }, { "input": "Does deflazacort have more side effects than prednisone?", "output": "Deflazacort produces fewer side effects than Prednisone in DMD patients." }, { "input": "Does echinacea increase anaphylaxis risk?", "output": "Yes, there is evidence that echinacea use is associated with anaphylaxis." }, { "input": "Are neurexins localized at pre-synapses?", "output": "Yes, neurexins are localized at pre-synapses." }, { "input": "Is there any role of 5hmC in T-cell development and differentiation?", "output": "Yes. 5hmC is enriched in the gene body of highly expressed genes at all different stages of T-cell development in the thymus and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, 5hmC is enriched in active thymus-specific enhancers and genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect." }, { "input": "Which are the properties of mammalian GA-sequences?", "output": " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined<0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum." }, { "input": "Which are the properties of mammalian GA-sequences?", "output": "GA-sequences are DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300. All pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins. Although this could have made them less subject to natural selection, they contained many [corrected] times fewer point mutations than one should expect from the genome at large." }, { "input": "Which are the properties of mammalian GA-sequences?", "output": " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300 [b]." }, { "input": "Which are the properties of mammalian GA-sequences?", "output": "GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome." }, { "input": "Which are the properties of mammalian GA-sequences?", "output": "The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins. The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's . Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly-segment. With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences , all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. " }, { "input": "Which are the properties of mammalian GA-sequences?", "output": "The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. With the exception of a small number of poly-A-, poly-G-, poly-GA-, and poly-GAAA-sequences (combined<0.5%), all pure GA-sequences of the mammals tested were unique individuals, contained several repeated short GA-containing motifs, and shared a common hexa-nucleotide spectrum. At most 2% of the human GA-sequences were transcribed into mRNAs; all others were not coding for proteins The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment" }, { "input": "Which are the properties of mammalian GA-sequences?", "output": " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way" }, { "input": "Which are the properties of mammalian GA-sequences?", "output": " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome." }, { "input": "Which are the properties of mammalian GA-sequences?", "output": " In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way The article describes DNA sequences of mammalian genomes that are longer than 50 bases, but consist exclusively of G's and A's ('pure GA-sequences'). Although their frequency of incidence should be 10(-16) or smaller, the chromosomes of human, chimpanzee, dog, cat, rat, and mouse contained many tens of thousands of them ubiquitously located along the chromosomes with a species-dependent density, reaching sizes of up to 1300 [b]. Alternating polypurine d(GA)n, sequences exhibit a considerable polymorphism Hence, guanine and thymine share significant properties regarding complementarity to adenine, while the TA and GA sequences can stack in at least two mutually compatible ways within the DNA duplexes analyzed here" }, { "input": "What is the main focus of the CVE R/Bioconductor package?", "output": "The CVE package allows interactive variant prioritisation to expedite the analysis of cancer sequencing studies." }, { "input": "What is the main focus of the CVE R/Bioconductor package?", "output": "CVE is an R package for interactive variant prioritisation in precision oncology. Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability." }, { "input": "What is the main focus of the CVE R/Bioconductor package?", "output": "interactive variant prioritisation" }, { "input": "Are there ultraconserved genomic regions in the budding yeast?", "output": "Yes. In addition to some fundamental biological functions, ultraconserved genomic regions play an important role in the adaptation of S. cerevisiae to the acidic environment." }, { "input": "Is davunetide being considered for the treatment of progressive supranuclear palsy?", "output": "Yes, Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients." }, { "input": "What is the origin of XUT transcripts in yeast?", "output": "XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast" }, { "input": "What is the origin of XUT transcripts in yeast?", "output": "XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast." }, { "input": "What is the origin of XUT transcripts in yeast?", "output": "Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses, and double-stranded (ds)RNA mapping revealed that 3'-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated, locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anticomplementary transcripts protects cryptic intergenic lncRNAs from NMD." }, { "input": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "The Mycobacterium dormancy survival regulator (DosR) regulon is composed of 48 co-regulated genes." }, { "input": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. DosR/DevR of M. tuberculosis is a two component dormancy survival response regulator which induces the expression of 48 genes. " }, { "input": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence." }, { "input": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "The dormancy survival regulator regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence. The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M. tuberculosis to hypoxia and controls a regulon of approximately 50 genes that are induced under this condition. " }, { "input": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions." }, { "input": "How many genes constitute the DosR regulon, controlled by the dormancy survival regulator (DosR) in Mycobacterium tuberculosis?", "output": "The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence. During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions." }, { "input": "Is autophagy modulated in a circadian fashion?", "output": "Yes, metabolic pathways, bile acid synthesis, and autophagic and immune/inflammatory processes are driven by the biological clock." }, { "input": "Is Drk essential for anesthesia-resistant memory (ARM) in Drosophila?", "output": "Yes. Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons in Drosophila." }, { "input": "What is oclacitinib?", "output": "Oclacitinib (APOQUEL(\u00ae)) is a Janus kinase inhibitor with activity against cytokines involved in allergy. It is a potent inhibitor of JAK1. It effectively controls clinical signs associated with allergic skin disease in dogs." }, { "input": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "output": "Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes." }, { "input": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "output": "Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them. Drosophila inter-TADs harbor active chromatin and constitutively transcribed genes. We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome. " }, { "input": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "output": "Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them." }, { "input": "List the two most important hematological features of the Evans syndrome", "output": "Evans syndrome is a rare autoimmune disorder, which is characterized by immune thrombocytopenia and autoimmune hemolytic anemia." }, { "input": "Is there increased recombination rate in human regulatory domains?", "output": "No. There is evidence of significantly reduced recombination rate compared to matched control regions at human regulatory domains." }, { "input": "Is enzastaurin effective treatment of glioblastoma?", "output": "No. Enzastaurin does not improve prognosis of glioblastoma patients." }, { "input": "Which yeast nucleosomes are preferentially marked by H2A.Z?", "output": "Yeast nucleosomes containing histone variant H2A.Z (Htz1p in yeast) are primarily composed of H4 K12ac and H3 K4me3." }, { "input": "Which yeast nucleosomes are preferentially marked by H2A.Z?", "output": "H2A.Z represses gene expression by establishing low gene accessibility at +1 nucleosome and maintaining high gene accessibility at -1 nucleosome. \u0397igh measures of gene responsiveness correlate with the H2A.Z-associated closed +1 nucleosome structure." }, { "input": "Which yeast nucleosomes are preferentially marked by H2A.Z?", "output": "The H2A and H2A.Z nucleosomes have different sequence preferences. The shifted peaks coincide with DNA regions interacting with the histone loops. Deposition of the histone variant H2A.Z at gene bodies regulates transcription by modifying chromatin accessibility in plants. We showed that H2A.Z preferentially associated with H3K4me3 at promoters, while it was found with H3K27me3 at enhancers, and that H2A.Z deposition negatively correlated with gene expression. In addition, we demonstrated that H2A.Z represses gene expression by establishing low gene accessibility at\u00a0+1 nucleosome\u00a0and maintaining high gene accessibility at -1 nucleosome. We further showed that the high measures of gene responsiveness correlate with the H2A.Z-associated closed\u00a0+1 nucleosome structure." }, { "input": "Is dasatinib effective for treatment of glioblastoma?", "output": "No, dasatinib is ineffective for treatment of glioblastoma and is associated with significant toxicity." }, { "input": "Which algorithm is available for computing minimal absent words using external memory?", "output": "emMAW" }, { "input": "Which algorithm is available for computing minimal absent words using external memory?", "output": "emMAW is the first external-memory algorithm for computing minimal absent words. A free open-source implementation of this algorithm is available. This implementation requires less than 3\u2009h on a standard workstation to process the full human genome when as little as 1\u2009GB of RAM is made available." }, { "input": "Has IVIG been tested in clinical trials for the treatment of Alzheimer's disease?", "output": "Yes, IVIG has been tested in clinical trials for the treatment of Alzheimer's disease." }, { "input": "Which type of urinary incontinence is diagnosed with the Q tip test?", "output": "Stress urinary incontinence is diagnosed with the Q tip test. The test evaluates urethral mobility." }, { "input": "Does a tonsillectomy affect the patient's voice?", "output": "Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy. Group B had a better awareness of tooth damage . There were no differences in secondary outcomes across treatment groups. The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. " }, { "input": "Does a tonsillectomy affect the patient's voice?", "output": "yes" }, { "input": "Does a tonsillectomy affect the patient's voice?", "output": " Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy. There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change." }, { "input": "Does a tonsillectomy affect the patient's voice?", "output": "Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances." }, { "input": "List the four most important interferonopathies", "output": "Aicardi-Gouti\u00e8res syndrome\nchilblain lupus\nubiquitin specific peptidase 18 (USP18)-deficiency\nSingleton-Merten syndrome" }, { "input": "List the four most important interferonopathies", "output": "Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed \"interferonopathies\" including Aicardi-Goutieres syndrome, ubiquitin specific peptidase 18 (USP18)-deficiency, haploinsufficiency in A20, otulipenia, familial chiblain lupus." }, { "input": "List the partners of budding yeast Cdc48 that are important for disassembly of ubiquitylated CMG helicase at the end of chromosome replication", "output": "The ubiquitin-binding Ufd1-Npl4 complex recruits Cdc48 to ubiquitylated CMG helicase at the end of chromosome replication." }, { "input": "How are topologically associating domains (TAD) associated with replication timing?", "output": "Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program. Topologically associating domains are stable units of replication-timing regulation." }, { "input": "How are topologically associating domains (TAD) associated with replication timing?", "output": "Topologically associating domains are stable units of replication-timing regulation. Both TADs and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program. Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs)." }, { "input": "How are topologically associating domains (TAD) associated with replication timing?", "output": "Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program." }, { "input": "How are cryptic unstable transcripts (CUTs) defined?", "output": "This resource includes deletions of small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and other annotated ncRNAs as well as the more recently identified stable unannotated transcripts (SUTs) and cryptic unstable transcripts (CUTs) whose functions are largely unknown There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs)" }, { "input": "How are cryptic unstable transcripts (CUTs) defined?", "output": "There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. The transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes. Most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. Regulatory mechanisms involving expression of a CUT are diverse and include attenuation, transcriptional interference, and alternative transcription start site choice" }, { "input": "How are cryptic unstable transcripts (CUTs) defined?", "output": "Here, by examining the overlap of stable (SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable transcripts) transcripts with protein-coding genes, we show that the predicted Nrd1 and Nab3-binding site sequences occur at differing frequencies. It is well established that eukaryotic genomes are pervasively transcribed producing cryptic unstable transcripts (CUTs). These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs) There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts." }, { "input": "How are cryptic unstable transcripts (CUTs) defined?", "output": "Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae." }, { "input": "How are cryptic unstable transcripts (CUTs) defined?", "output": "This resource includes deletions of small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and other annotated ncRNAs as well as the more recently identified stable unannotated transcripts (SUTs) and cryptic unstable transcripts (CUTs) whose functions are largely unknown There is extensive transcription throughout the eukaryotic genome resulting in both antisense transcripts from coding regions and cryptic unstable transcripts (CUTs) from intergenic regions These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. In this paper, we show that Nrd1 and Nab3 are required for transcription termination of CUTs These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. It is likely that many of these are cryptic unstable transcripts (CUTs), which are rapidly degraded and whose function(s) within the cell are still unclear, while others may be novel functional transcripts." }, { "input": "How many Groucho-related genes (GRG) are contained in the mouse genome?", "output": "The groucho-related genes of the mouse comprise at least four family members. The Grg gene encodes a 197 amino acid protein homologous to the amino-terminal domain of the product of the groucho gene of the Drosophila Enhancer of split complex. The murine grg products are believed to interact with transcription factors and repress transcription, thereby regulating cell proliferation and differentiation. " }, { "input": "How many Groucho-related genes (GRG) are contained in the mouse genome?", "output": "We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes. The groucho-related genes (Grg) of the mouse comprise at least four family members." }, { "input": "How many Groucho-related genes (GRG) are contained in the mouse genome?", "output": "The groucho-related genes (Grg) of the mouse comprise at least four family members." }, { "input": "How many Groucho-related genes (GRG) are contained in the mouse genome?", "output": "It spans approximately 7 kb on chromosome 10 and consists of seven exons. The groucho-related genes (Grg) of the mouse comprise at least four family members." }, { "input": "What is mechanism of action of galunisertib?", "output": "Galunisertib is a transforming growth factor-\u03b2 receptor type I kinase inhibitor (TGF-\u03b2RI). It was tested for treatment of solid cancers, including glioblastoma and neuroblastoma, and liver fibrosis." }, { "input": "What is a coligo?", "output": "Coligos are circularized oligodeoxynucleotides" }, { "input": "What is the relationship of fyn kinase and tau?", "output": "The Fyn kinase interacts with tau. The activated Fyn kinase hyperphosphorylates the tau protein." }, { "input": "Which are the main manifestations of Ohdo syndrome?", "output": "Severe ID, absent or deficient language, skeletal manifestations including bilateral patella dislocations." }, { "input": "Which algorithm is used by the UCSC Genome Browser?", "output": "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files." }, { "input": "Which algorithm is used by the UCSC Genome Browser?", "output": "The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Binary Alignment/Map , where the differences between the data set and the reference assembly may be displayed graphically. The Saved Session feature allows users to store and share customized views, enhancing the utility of the system for organizing multiple trains of thought. The University of California Santa Cruz is a popular Web-based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation \"tracks\". The UCSC Genome Browser organizes data and annotations around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. " }, { "input": "Which algorithm is used by the UCSC Genome Browser?", "output": "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels." }, { "input": "Which algorithm is used by the UCSC Genome Browser?", "output": "The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser." }, { "input": "Which aminoacid position in the human CREB protein is phosphorylated?", "output": "pCREB is phosphorylated at its Serine 133." }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "the related transcription factors Ecm22 and Upc2 play a crucial role in Saccharomyces cerevisiae filamentation." }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. " }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "zinc cluster proteins Upc2 and Ecm22 promote filamentation" }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.Here, we examine the role of the related transcription factors ecm22 and upc2 in saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways.Here, we examine the role of the related transcription factors ecm22 and upc2 in saccharomyces cerevisiae filamentation." }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. " }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways. Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation." }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways." }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation.The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis-dependent and -independent pathways." }, { "input": "Which gene is the paralog of yeast UPC2?", "output": "Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation." }, { "input": "Where is the enzyme PM20D1 localized?", "output": "PM20D1 is enriched in UCP1+ adipocytes" }, { "input": "Which test is used to diagnose colour synesthesia?", "output": "A standardized test battery for the study of synesthesia. We used synesthetic versions of the Stroop test with colored letters and numbers presented either in the right or the left visual field of thirty-four synesthetes. Assessment of the hemispheric lateralization of grapheme-color synesthesia with Stroop-type tests. " }, { "input": "Which test is used to diagnose colour synesthesia?", "output": "Stroop-type testsWe" }, { "input": "Which test is used to diagnose colour synesthesia?", "output": "We used synesthetic versions of the Stroop test with colored letters and numbers presented either in the right or the left visual field of thirty-four synesthetes" }, { "input": "How does increased GDF15 affect body weight?", "output": "In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake." }, { "input": "Which are the best methods for the prediction of circular RNA (circRNA)?", "output": "A circRNA prediction software for plants . Circular RNA profile in gliomas revealed by identification tool UROBORUS. Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. MiARma-Seq: a comprehensive tool for miRNA, mRNA and circRNA analysis. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. " }, { "input": "Which are the best methods for the prediction of circular RNA (circRNA)?", "output": "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. A circRNA prediction software for plants (termed PcircRNA_finder) was developed that is more sensitive in detecting circRNAs than other frequently used programs (such as find_circ and CIRCexplorer)" }, { "input": "Which are the best methods for the prediction of circular RNA (circRNA)?", "output": "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. Circular RNA profile in gliomas revealed by identification tool UROBORUS. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance." }, { "input": "Which are the best methods for the prediction of circular RNA (circRNA)?", "output": "PcircRNAfinder : a software for circRNA prediction in plants. A circRNA expression from RNA sequencing here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNAfinder, findcirc, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. Numerous algorithms that are used to detect genome-wide circRNA prediction software for plants was developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect circRNAs in total RNA-seq data. MiARma-Seq : a comprehensive tool for miRNA, mRNA and circRNA analysis. Circular RNA profile in gliomas revealed by identification tool UROBORUS. " }, { "input": "Which are the best methods for the prediction of circular RNA (circRNA)?", "output": "The best methods for the prediction of circular RNA are: circRNA_finder, find_circ, CIRCexplorer, CIRI, MapSplice, UROBORUS, Circ TEST DCC and miARma-Seq. " }, { "input": "Which are the best methods for the prediction of circular RNA (circRNA)?", "output": "Numerous algorithms that are used to detect genome-wide circRNA expression from RNA sequencing (RNA-seq) data have been developed in the past few years, but there is little overlap in their predictions and no clear gold-standard method to assess the accuracy of these algorithms. We developed the software tandem, DCC and CircTest DCC uses output from the STAR read mapper to systematically detect back-splice junctions in next-generation sequencing data. Circular RNA profile in gliomas revealed by identification tool UROBORUS." }, { "input": "What is inhibited by a drug rilotumumab?", "output": "Rilotumumab is a fully human monoclonal antibody that selectively targets the hepatocyte growth factor (HGF). It is used for treatment of cancer." }, { "input": "Which RNA polymerase II subunit carries RNA cleavage activity?", "output": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex." }, { "input": "Which RNA polymerase II subunit carries RNA cleavage activity?", "output": "The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex. The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II." }, { "input": "Which RNA polymerase II subunit carries RNA cleavage activity?", "output": "In contrast, Pol II is fully protected through association with the cleavage stimulatory factor TFIIS, which enables rapid recovery from any depth by RNA cleavage." }, { "input": "Which RNA polymerase II subunit carries RNA cleavage activity?", "output": "In contrast, Pol II is fully protected through association with the cleavage stimulatory factor TFIIS, which enables rapid recovery from any depth by RNA cleavage. This mechanism is also used by transcription factor IIS, a factor that can bind Pol II and induce strong RNA cleavage. " }, { "input": "Which is the transcriptome of RNA polymerase III?", "output": "RNA polymerase III (Pol III) transcribes a limited set of short genes in eukaryotes producing abundant small RNAs, mostly tRNA. The originally defined yeast Pol III transcriptome appears to be expanding owing to the application of new methods. Newly identified Pol III transcripts include small nucleolar RNAs, microRNAs, short interspersed nuclear element-encoded or tRNA-derived RNAs and novel classes of ncRNA that can display significant sequence complementarity to protein-coding genes and might thus regulate their expression." }, { "input": "How many PML isoforms exist in the human genome?", "output": "PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene." }, { "input": "How many PML isoforms exist in the human genome?", "output": "The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene." }, { "input": "Do cephalopods use RNA editing less frequently than other species?", "output": "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. " }, { "input": "Do cephalopods use RNA editing less frequently than other species?", "output": "No. Extensive messenger RNA editing generates transcript and protein diversity in cephalopod genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions" }, { "input": "Do cephalopods use RNA editing less frequently than other species?", "output": "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions" }, { "input": "Is there an RNAi drug being developed to treat amyloidosis?", "output": "Yes, patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis." }, { "input": "Which receptor does GDF15 bind?", "output": "GDF15 binds specifically to GDNF family receptor \u03b1-like (GFRAL)" }, { "input": "Is there an association between carcinoid syndrome and mitral valve disease?", "output": "Yes, mitral valve damage was reported in patients with carcinoid syndrome." }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not the PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. " }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. " }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "Using a system in which only a single EYFP-linked PML isoform is expressed, PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not" }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not" }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do notThe PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1." }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "The PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1. Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not. " }, { "input": "How many of the human PML isoforms are cytosolic?", "output": "Using a system in which only a single EYFP-linked PML isoform is expressed, we demonstrate that PMLI, PMLII and PMLVI accumulate in the cytoplasm following arsenic treatment, whereas PMLIII, PMLIV and PMLV do not the PML isoforms that are most sensitive to virus infection correspond closely to those which have recently been identified as being covalently conjugated to PIC1." }, { "input": "Which tendons are affected in the Dequervain's tenosynovitis?", "output": "DeQuervain's tenosynovitis is a common cause of radial-sided wrist pain. Symptoms result from a narrow first dorsal compartment and associated tendinosis of the enclosed extensor pollicis brevis and/or abductor pollicis longus." }, { "input": "Are there RNAi approaches considered for the treatment of kidney injury?", "output": "Yes, RNAi approaches are being considered for the treatment of kidney injury." }, { "input": "What does davunetide do to microtubules?", "output": "Davunetide or NAP is a microtubule-stabilizer." }, { "input": "Is propranolol used for treatment of infantile hemangioma?", "output": "Yes, propranolol is becoming the treatment of choice for complicated infantile hemangioma." }, { "input": "Can the CEP290 gene mutations be targeted by AAV-mediated gene therapy?", "output": "The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy." }, { "input": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "output": "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans" }, { "input": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "output": "UCP2 and its major targets ERG11, ERG2, NCP1 as well as Osh1p-Osh7p" }, { "input": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "output": "Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans. The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport. Northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets . Taken together, our results indicate that Upc2p is a key regulator of ergosterol metabolism. " }, { "input": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "output": "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p included 12 genes involved in ergosterol biosynthesis to better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo. Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. They also suggest that Upc2p may contribute to azole resistance by regulating the expression of drug efflux pump-encoding genes in addition to ergosterol metabolism. Overrepresented functional groups of genes whose promoters were bound by Upc2p is a key regulator of ergosterol metabolism. We have taken advantage of this property to study the regulation of the Delta8-Delta7-sterol isomerase-encoding ERG2 gene in an ergosterol auxotrophic mutant devoid of squalene-synthase activity. Ergosterol starvation leads to an 8-16-fold increase in ERG2 gene expression. " }, { "input": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "output": "Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans. The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport. Northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets . Taken together, our results indicate that Upc2p is a key regulator of ergosterol metabolism. To better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo. Overrepresented functional groups of genes whose promoters were bound by Upc2p included 12 genes involved in ergosterol biosynthesis . They also suggest that Upc2p may contribute to azole resistance by regulating the expression of drug efflux pump-encoding genes in addition to ergosterol biosynthesis genes. We have taken advantage of this property to study the regulation of the Delta8-Delta7-sterol isomerase-encoding ERG2 gene in an ergosterol auxotrophic mutant devoid of squalene-synthase activity. " }, { "input": "Which proteins are controlling sterol metabolism in S. cerevisiae?", "output": "The yeast genome encodes seven oxysterol binding protein homologs, Osh1p-Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets ( ERG11, MDR1, CDR1, YOR1, SUT1, SMF12, and CBP1 ).Taken together, our results indicate that upc2p is a key regulator of ergosterol metabolism.Overrepresented functional groups of genes whose promoters were bound by upc2p included 12 genes involved in ergosterol biosynthesis ( ncp1, erg11, erg2, and others ) to better understand upc2p function in c. albicans, we used genomewide location profiling to identify the transcriptional targets of upc2p in vivo.Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in candida albicans sterol metabolism and erg2 gene regulation in the yeast saccharomyces cerevisiae.We have taken advantage of this property to study the regulation of the delta8-delta7-sterol isomerase-encoding erg2 gene expression.Ergosterol starvation leads to an 8-16-fold increase in ERG2 gene expression." }, { "input": "Which enzymes are responsible for base J creation in Trypanosoma brucei?", "output": "The base is synthesized in a two-step pathway. Initially, a thymidine residue in DNA is hydroxylated by a thymidine hydroxylase (TH). This intermediate (HOMedU) is then glucosylated to form base J. Two proteins involved in J synthesis, JBP1 (J binding protein 1) and JBP2, contain a putative TH domain related to the family of Fe(2+)/2-oxoglutarate-dependent hydroxylases. JBP2 is a chromatin re-modeling protein that induces de novo J-synthesis, allowing JBP1, a J-DNA binding protein, to stimulate additional J-synthesis. A recent computational screen identified a possible candidate for the base J-associated glucosyltransferase (JGT) in trypanosomatid genomes." }, { "input": "Which enzymes are responsible for base J creation in Trypanosoma brucei?", "output": "JBP2 and JBP1" }, { "input": "Which enzymes are responsible for base J creation in Trypanosoma brucei?", "output": "The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base J. We conclude that JBP2 and JBP1 are the TH enzymes involved in J biosynthesis. -d-glucopyranosyloxymethyluracil . The base is synthesized in a two-step pathway. Synthesis of the modified thymine base, beta-d-glucosyl-hydroxymethyluracil or J, within telomeric DNA of Trypanosoma brucei correlates with the bloodstream form specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation. Two thymidine hydroxylases differentially regulate the formation of glucosylated DNA at regions flanking polymerase II polycistronic transcription units throughout the genome of Trypanosoma brucei. A recent computational screen identified a possible candidate for the base J-associated glucosyltransferase in trypanosomatid genomes. This intermediate is then glucosylated to form base J. Here we discuss the regulation of hmU and base J formation in the trypanosome genome by JGT and base J-binding protein. Chromosome-internal J deposition is primarily mediated by JBP1, whereas JBP2-stimulated J deposition at the telomeric regions. Two proteins involved in J synthesis, JBP1 /2-oxoglutarate-dependent hydroxylases. JBP2 and JBP1 are capable of stimulating de novo J-synthesis. " }, { "input": "Which enzymes are responsible for base J creation in Trypanosoma brucei?", "output": "We have previously characterized two thymidine-hydroxylases (TH), JBP1 and JBP2, which regulate J-biosynthesis.JBP2 is a chromatin re-modeling protein that induces de novo J-synthesis, allowing JBP1, a J-DNA binding protein, to stimulate additional J-synthesis.Chromosome-internal J deposition is primarily mediated by JBP1, whereas JBP2-stimulated J deposition at the telomeric regions.Here we show that mutation of key residues in the TH domain of JBP2 ablate its ability to induce de novo J synthesis.JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes.Here we discuss the regulation of hmU and base J formation in the trypanosome genome by JGT and base J-binding protein.The deletion of both alleles of JGT from the genome of Trypanosoma brucei generates a cell line that completely lacks base JWe have recently proposed a model in which chromatin remodeling by a SWI2/SNF2-like protein (JBP2) regulates the developmental and de novo site-specific localization of J synthesis within bloodstream form trypanosome DNA." }, { "input": "Which method for subsampling of NGS reads requires only gene counts?", "output": "SamExploreR : exploring reproducibility and robustness of RNA-seq results based on SAM files.We introduce the subseq r package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth required to inform a broad range of functional and evolutionary studies.Our methods are broadly applicable for polymorphism discovery in moderate to large genomes even at highly diverged loci, and we established by subsampling the illumina sbs coverage depth related questions for the experimental design.SubSeq : determining appropriate sequencing depth through efficient read subsampling." }, { "input": "Which method for subsampling of NGS reads requires only gene counts?", "output": "Our methods are broadly applicable for polymorphism discovery in moderate to large genomes even at highly diverged loci, and we established by subsampling the Illumina SBS coverage depth required to inform a broad range of functional and evolutionary studies. We introduce the subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth" }, { "input": "Which method for subsampling of NGS reads requires only gene counts?", "output": "The subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth" }, { "input": "Which method for subsampling of NGS reads requires only gene counts?", "output": "We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models . We introduce the subSeq R package, which uses a novel efficient approach to perform this subsampling and to calculate informative metrics at each depth. Interestingly, after subsampling to the same coverage for GSNAP and TopHat, we find that both mappers have similar performance, implying that the advantage of TopHat is mainly an artifact of the lower coverage. " }, { "input": "Which topoisomerase is essential in yeast?", "output": "Eukaryotic DNA topoisomerase II is an abundant nuclear enzyme that is essential for cell proliferation. Yeast DNA topoisomerase II is encoded by a single-copy, essential gene." }, { "input": "Which topoisomerase is essential in yeast?", "output": "Yeast DNA topoisomerase II is encoded by a single-copy, essential gene. Disruption of one copy of the gene in a diploid yeast creates a recessive lethal mutation, indicating that the single DNA topoisomerase II gene of yeast has an essential function." }, { "input": "Which topoisomerase is essential in yeast?", "output": "Yeast DNA topoisomerase II is encoded by a single-copy, essential gene." }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "MED12 cause X-linked Ohdo syndromeIn" }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "Mutations in MED12 cause X-linked Ohdo syndrome" }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "Mutations in MED12 cause X-linked Ohdo syndrome The occurrence of three different hemizygous missense mutations in three unrelated families affected by Ohdo syndrome MKB type shows that mutations in MED12 are the underlying cause of this X-linked form of Ohdo syndrome." }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "Mutations in MED12 cause X-linked Ohdo syndrome In the two families, MED12 missense mutations (c.3443G>A [p.Arg1148His] or c.3493T>C [p.Ser1165Pro]) segregating with the phenotype were identified." }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, have been described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them. Mutations in MED12 cause X-linked Ohdo syndrome" }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "The occurrence of three different hemizygous missense mutations in three unrelated families affected by Ohdo syndrome MKB type shows that mutations in MED12 are the underlying cause of this X-linked form of Ohdo syndrome." }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "Mutations in MED12 cause X-linked Ohdo syndrome FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, have been described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them." }, { "input": "What is the genetic basis of Ohdo syndrome?", "output": "MED12" }, { "input": "Which drugs were tested in the KEYNOTE-006 study?", "output": "KEYNOTE-006 study compared pembrolizumab versus ipilimumab for advanced melanoma." }, { "input": "What is the purpose of the FRAX scale?", "output": "The FRAX score (The WHO Fracture Risk Assessment Tool), is a free web-based clinical scale assessing the 10-year probability of major osteoporotic fracture risk and need for lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or preventive treatment." }, { "input": "Are mutations in the nf1 gene associated with memory?", "output": "Yes, distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation." }, { "input": "Has Cas9 gene editing the potential to correct inhereted hearing loss?", "output": "CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo.\r\nThe genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation." }, { "input": "How may CTCF mediate splicing?", "output": "Two different mechanisms convey DNA methylation information into the regulation of alternative splicing. The first involves modulation of the elongation rate of RNA polymerase II (Pol II) by CCCTC-binding factor (CTCF) and methyl-CpG binding protein 2 (MeCP2); the second involves the formation of a protein bridge by heterochromatin protein 1 (HP1) that recruits splicing factors onto transcribed alternative exons." }, { "input": "How may CTCF mediate splicing?", "output": "CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Intragenic 5-methylcytosine and CTCF mediate opposing effects on pre-mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5-methylcytosine evicts CTCF, leading to exon exclusion." }, { "input": "How may CTCF mediate splicing?", "output": "CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.Here we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wideCTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events.CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing.In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII.Furthermore, we found mutations in the splicing factor SFPQ and in the nonclassic regulators of mRNA processing CTCF and RAD21.However, there was no correlation between the KTS+/KTS- splicing variants of WT1 and the methylation status of the CpGs of the CTCF binding site." }, { "input": "Is ACI-35 a passive vaccine?", "output": "No, ACI-35 is an active vaccine." }, { "input": "Which main ribotype of Clostridium difficile is responsible of the recent outbreak?", "output": "The outbreak of the hypervirulent strain belonging to ribotype 027 has increased the incidence and severity of CDI in some countries." }, { "input": "What is the function of the TFIIS transcriptional factor (Dst1) in yeast?", "output": "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II." }, { "input": "What is the function of the TFIIS transcriptional factor (Dst1) in yeast?", "output": "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II. Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. It is proposed that TFIIS and the Spt8-containing form of SAGA co-operate to rescue RNA polymerase II from unproductive elongation complexes, and that the Cdk8 module temporarily blocks transcription during transcript cleavage." }, { "input": "What is the function of the TFIIS transcriptional factor (Dst1) in yeast?", "output": "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II. Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. It is proposed that TFIIS and the Spt8-containing form of SAGA co-operate to rescue RNA polymerase II from unproductive elongation complexes, and that the Cdk8 module temporarily blocks transcription during transcript cleavage. TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA. TFIIS and Rpb9 are essential when the cells are challenged with microtubule-destabilizing drugs;" }, { "input": "What is the function of the TFIIS transcriptional factor (Dst1) in yeast?", "output": "Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation. TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA. Recent studies revealed that TFIIS has also a role in Pol II transcription initiation. TFIIS is required under stress conditions and that TFIIS is important for the transition between initiation and elongation in vivo." }, { "input": "What is the function of the TFIIS transcriptional factor (Dst1) in yeast?", "output": "TFIIS, an elongation factor encoded by DST1 in Saccharomyces cerevisiae, stimulates transcript cleavage in arrested RNA polymerase II. Co-immunoprecipitation experiments showed that TFIIS can bind the Cdk8 module and SAGA in cell-free extracts Members of the SAGA and Mediator complexes are partners of the transcription elongation factor TFIIS. TFIIS and Pol III occupancies correlated well genome-wide on this novel class of targets. These data provide strong in vivo and in vitro evidence in favor of a role of TFIIS as a general Pol III transcription factor. Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation." }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "DNA methylation can determine nucleosome positioning. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression. In order to systematically evaluate potential diversities among CGIs and ultimately to illuminate the link between diversity of CGIs and their epigenetic variation, we analyzed the nucleotide-resolution DNA methylation maps of multiple cellular origins. Using this global approach, we observe the dependency of nucleosome occupancy upon the DNA methylation status. Exonic DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. Transcription, histone modifications, and DNA methylation alter this \"ground state\" by having distinct effects on both nucleosome positioning and occupancy. " }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free.Exonic dna methylation can determine nucleosome positioning.In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy.Using this global approach, we observe the dependency of nucleosome occupancy upon the dna methylation seems to function together with exonic nucleosomes and h3k36me3 for the proper splicing of transcripts with different expression levels.In order to systematically evaluate potential diversities among cgis and ultimately to illuminate the link between diversity of cgis and their epigenetic variation, we analyzed the nucleotide-resolution dna methylation status.Transcription, histone modifications, and dna methylation determines nucleosome occupancy in the 5'-cpg islands of tumor suppressor genes.Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression.Using this global approach, we analyzed the nucleotide-resolution dna methylation maps ( methylomes ) of multiple cellular origins.Dna methylation alter this \"ground state\" by having distinct effects on both nucleosome positioning." }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy.Nucleosome-free regions were observed only in promoters containing a CpG islandHere I show that CpG islands were associated not only with methylation-free promoters but also with nucleosome-free promoters.In contrast to the methylation-and nucleosome-free states of CpG-island promoters, exons were densely methylated at CpGs and packaged into nucleosomes.I also found that nucleosomes, DNA methylation, and H3K36me3 marked the exons of transcripts with low, medium, and high gene expression levels, respectively.DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes.DNA methylation can determine nucleosome positioning.DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter.The mostly unmethylated CpG islands have reduced nucleosome occupancy and are enriched in cell type-independent binding sites for CTCF.Three positions at the splice sites show high CpG abundance and accompany elevated nucleosome occupancy in a leveled GC architecture." }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "Here I show that CpG islands were associated not only with methylation-free promoters but also with nucleosome-free promoters. Nucleosome-free regions were observed only in promoters containing a CpG island In contrast to the methylation-and nucleosome-free states of CpG-island promoters, exons were densely methylated at CpGs and packaged into nucleosomes. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy." }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "Using this global approach, we observe the dependency of nucleosome occupancy upon the DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation maps of multiple cellular origins. Transcription, histone modifications, and DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. Exonic DNA methylation can determine nucleosome positioning. In order to systematically evaluate potential diversities among CGIs and ultimately to illuminate the link between diversity of CGIs and their epigenetic variation, we analyzed the nucleotide-resolution DNA methylation and nucleosome occupancy. Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key determinant of gene expression levels. Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free. In contrast, exons demonstrate a high degree of methylation status. DNA methylation at CTCF regions that is not present at promoters. " }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "Recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter. Using a novel bioinformatics pipeline a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters can be shown. The induction of DNA hypomethylation events by genetic (DNMT1/DNMT3B deficient cells) or drug (a DNA demethylating agent) approaches is associated with the eviction of nucleosomes from previously hypermethylated CpG islands of tumor suppressor genes." }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "DNA methylation can determine nucleosome positioning. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. " }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosome occupancy and DNA methylation at CTCF regions that is not present at promoters. " }, { "input": "Is DNA methylation correlated with nucleosome occupancy?", "output": "yes" }, { "input": "Which R/Bioconductor package has been developed for the analysis of psychiatric disease genes?", "output": "PsyGeNET is a knowledge resource on psychiatric diseases and their genes, developed by text mining and curated by domain experts. Psygenet2r is an R package that contains a variety of functions for leveraging PsyGeNET database and facilitating its analysis and interpretation. The package offers different types of queries to the database along with variety of analysis and visualization tools, including the study of the anatomical structures in which the genes are expressed and gaining insight of gene's molecular function. Psygenet2r is especially suited for network medicine analysis of psychiatric disorders." }, { "input": "Which R/Bioconductor package has been developed for the analysis of psychiatric disease genes?", "output": "psygenet2r" }, { "input": "Which Janus kinase does decernotinib target?", "output": "Decernotinib (VX-509) is a potent and selective inhibitor of janus kinase 3 (JAK3)." }, { "input": "What is the genetic basis of the Delayed Sleep-Phase Syndrome (DSPS)?", "output": "Circadian gene mutations are also associated with circadian rhythm disorders such as familial advanced sleep phase syndrome, delayed sleep phase syndrome, and non-24-hour sleep-wake syndrome. Possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome. The study investigated the human leucocyte antigen (HLA), types A, B and DR, of 42 patients with delayed sleep phase syndrome (DSPS) and compared the frequencies of the antigens with those in 117 healthy controls. The comparison revealed that the gene frequencies and positivities of HLA-A, -B and -DR, except for DR1, had no significant differences between the patients and controls. The frequency of HLA-DR1 was increased in the DSPS patients as compared with that in the healthy controls (P = 0.0069 in positivity). In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. " }, { "input": "What is the genetic basis of the Delayed Sleep-Phase Syndrome (DSPS)?", "output": "Circadian gene mutations are also associated with circadian rhythm disorders such as familial advanced sleep phase syndrome, delayed sleep phase syndrome, and non-24-hour sleep-wake syndrome. A possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome has been reported. In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. The data suggest that AA-NAT could be a susceptibility gene for DSPS." }, { "input": "What is the genetic basis of the Delayed Sleep-Phase Syndrome (DSPS)?", "output": "We studied the association between the AA-NAT gene and delayed sleep phase syndrome . Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it?. Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome . One of the haplotypes was significantly associated with DSPS in our study population. In human leukocyte antigen typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. Polymorphisms in the CLOCK, BMAL1, Per3 and TIMELESS genes have been associated with susceptibility to mood disorder, and single nucleotide polymorphisms and haplotypes in several circadian genes have been observed among those displaying certain circadian phenotypes, including worse mood in the evening, insomnia in mania and early, middle or late insomnia in depression. The Per3 polymorphism correlated significantly with extreme diurnal preference, the longer allele associating with morningness and the shorter allele with eveningness. The frequency of the 129 threonine allele is significantly higher in the patients than in the controls . " }, { "input": "What are jakinibs?", "output": "Jakinibs are Janus kinase (JAK) inhibitors. They are considered a new class of kinase inhibitors in cancer and autoimmune disease. Jakinibs can differ substantially in their selectivity against JAKs." }, { "input": "What is the function of the gene MDA5?", "output": "Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases." }, { "input": "Which is the conserved motif of DEAD box proteins?", "output": "The conserved motif is: Asp(D)-Glu-(E)-Ala(A)-Asp(D)" }, { "input": "Which individuals show preferential colonization of the Prevotellaceae bacteria in their guts?", "output": "Although the distinction of enterotypes as either discrete clusters or a continuum will require additional investigation, numerous studies have demonstrated the co-exclusion of the closely related Prevotellaceae and Bacteroides genera in the gut microbiota of healthy human subjects where Prevotella appears to be a discriminatory taxon for residence in more agrarian societies." }, { "input": "Describe GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types)", "output": "GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types) is a bioinformatic toolkit for aetiologically connecting diseases and cell type-specific regulatory maps. GARLIC can be used to retrieve potential disease-causative genetic variants overlapping regulatory sequences of interest. Overall, GARLIC can satisfy several important needs within the field of medical genetics, thus potentially assisting in the ultimate goal of uncovering the elusive and complex genetic basis of common human disorders." }, { "input": "Describe GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types)", "output": "GARLIC is a bioinformatic toolkit for aetiologically connecting diseases and cell type-specific regulatory maps." }, { "input": "How does Dst1 knock-out affect transcription in yeast?", "output": "While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability. We showed that: dst1 and rpb9 mutants have a synthetic growth defective phenotype when combined with fyv4, gim5, htz1, yal011w, ybr231c, soh1, vps71, and vps72 mutants that is exacerbated during germination or at high salt concentrations. In vivo, some dst1 mutants were partly defective in tRNA synthesis and showed a reduced Pol III occupancy at the restrictive temperature." }, { "input": "How does Dst1 knock-out affect transcription in yeast?", "output": "While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability." }, { "input": "Which drug can be reversed with idarucizumab?", "output": "Idarucizumab is an antibody fragment that specifically reverses dabigatran mediated anticoagulation." }, { "input": "What is the function of the TMEM132 genes?", "output": "The extra-cellular portions of TMEM132 proteins contain five conserved domains including three tandem immunoglobulin domains, and a cohesin domain homologue, the first such domain found in animals. These findings strongly predict a cellular adhesion function for TMEM132 family, connecting the extracellular medium with the intracellular actin cytoskeleton." }, { "input": "Does DDX54 play a role in DNA damage response?", "output": "Yes. DDX54, a candidate genotoxic stress responsive RNA helicase, regulates transcriptome dynamics during DNA damage response." }, { "input": "List main clinical features of the POEMS syndrome.", "output": "POEMS is an acronym for the main clinical features of the syndrome, namely, Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin abnormalities. Other features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, and Castleman disease. It is a multisystemc disorder with a good long-term prognosis." }, { "input": "Which retinal dystrophy related gene is targeted by the AAV2-hRPE65v2 drug?", "output": "AAV2-hRPE65v2, also called voretigene neparvovec, targets the RPE65 gene, whose mutations lead to retinal dystrophy." }, { "input": "What is the function of yeast TERRA RNAs?", "output": "The ends of linear eukaryotic chromosomes are transcribed into different species of non-coding transcripts (the telomeric transcriptome), including TERRA (telomeric repeat-containing RNA) molecules. TERRA are part of the DNA damage response triggered by dysfunctional telomeres. In addition to its role as a template-encoding telomeric DNA synthesis, telomerase RNA has been shown to function as a flexible scaffold for protein subunits of the RNP holoenzyme." }, { "input": "What is the function of yeast TERRA RNAs?", "output": "We further show that TERRA (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short telomeres and correlates with telomere rearrangements" }, { "input": "What is the function of yeast TERRA RNAs?", "output": "We further show that TERRA (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short telomeres and correlates with telomere rearrangements Like human and budding yeast, fission yeast harbours a population of telomeric RNA molecules containing G-rich telomeric repeats transcribed from the subtelomere to the telomere. The ends of linear eukaryotic chromosomes are transcribed into different species of non-coding transcripts (the telomeric transcriptome), including TERRA (telomeric repeat-containing RNA) molecules TERRA is part of the DNA damage response triggered by dysfunctional telomeres Telomeric repeat-containing RNA (TERRA) has been implicated in the control of heterochromatin and telomerase. yeast TERRA is regulated by telomere-binding proteins in a chromosome-end-specific manner that is dependent on subtelomeric repetitive DNA elements" }, { "input": "What are the 4 cardinal signs of inflammation according to Celsus?", "output": "redness or rubor , heat or calor, swelling or tumor, and pain or dolor" }, { "input": "What are the 4 cardinal signs of inflammation according to Celsus?", "output": "Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. " }, { "input": "Do bacteria from the genus Morexella cause respiratory infections?", "output": "Bacteria from the genus Morexella can cause respiratory infections" }, { "input": "Which two genes are implicated in Juvenile polyposis syndrome?", "output": "Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder predisposing to gastrointestinal hamartomatous polyps and cancer with a pathogenic SMAD4 or BMPR1A germline mutation being identified in about 40-50% of patients." }, { "input": "Do chromatin features predict genes associated with eQTLs?", "output": "Yes, genomic proximity plus five TF and chromatin features are able to predict>90% of target genes within 1 megabase of eQTLs" }, { "input": "List the 6 genes associated with the autosomal recessive form of Osteogenesis imperfecta", "output": "There are at least 6 genes associated with osteogenesis imperfecta, Sp7/Osx, FK506-binding protein, Hsp47/SERPINH1, WNT1, CRTAP, P3H1, and PPIB, LEPRE1,PLOD2, TMEM38B" }, { "input": "What is masitinib an inhibitor of?", "output": "Masitinib is an inhibitor of mast cell-glia axis and a Fyn kinase blocker. It is an oral tyrosine kinase inhibitor with activity against c-Kit and platelet-derived growth factor receptors (PDGFR)." }, { "input": "What is the name of the RNAi investigational drug being developed against hereditary amyloidosis?", "output": "Patisiran." }, { "input": "What is the name of the RNAi investigational drug being developed against hereditary amyloidosis?", "output": "The investigational RNAi drug in development for the treatment of hereditary amyloidosis is patisiran." }, { "input": "What is the function of the H19 (ICR) locus in the human genome?", "output": "We found that localized DNA demethylation at the H19 imprinting control region (ICR) induced by 5-AzaCdR, reduced IGF2, increased H19 expression, increased CTCF and cohesin recruitment and changed histone modifications." }, { "input": "What is the function of the H19 (ICR) locus in the human genome?", "output": "The H19 locus acts in vivo as a tumor suppressor. The H19 locus belongs to a cluster of imprinted genes that is linked to the human Beckwith-Wiedemann syndrome. The expression of H19 and its closely associated IGF2 gene is frequently deregulated in some human tumors, such as Wilms' tumors." }, { "input": "What is the mode of action of teriparatide?", "output": "Teripartide is is an effective anabolic (i.e., bone growing) agent used in the treatment of some forms of osteoporosis." }, { "input": "What is the Strelka workflow?", "output": "Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity. Strelka is a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. Strelka has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests." }, { "input": "Describe the Manta algorithm for detection of structural variants", "output": "Manta is a method to discover structural variants and indels from next generation sequencing data. Manta is optimized for rapid germline and somatic analysis, calling structural variants, medium-sized indels and large insertions on standard compute hardware in less than a tenth of the time that comparable methods require to identify only subsets of these variant types: for example NA12878 at 50\u00d7 genomic coverage is analyzed in less than 20\u2009min. Manta can discover and score variants based on supporting paired and split-read evidence, with scoring models optimized for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs. Call quality is similar to or better than comparable methods, as determined by pedigree consistency of germline calls and comparison of somatic calls to COSMIC database variants. Manta consistently assembles a higher fraction of its calls to base-pair resolution, allowing for improved downstream annotation and analysis of clinical significance." }, { "input": "Is Kummell\u2019s disease an avascular necrosis of the vertebral body?", "output": "Yes, Kummell\u2019s disease is an avascular necrosis of the vertebral body." }, { "input": "What causes \"Puffy hand syndrome\"?", "output": "Puffy hand syndrome is a complication of intravenous drug abuse." }, { "input": "Describe mechanism of action of Ozanimod.", "output": "Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in clinical development for the treatment of chronic immune-mediated, inflammatory diseases, such as multiple sclerosis and inflammatory bowel disease. Yet its exact mechanism of action is unknown." }, { "input": "Describe swirl sign in intracerebral hemorrhage.", "output": "Swirl sign is described as areas of low attenuation, radiolucency or irregular density. It was previously described in epidural hematomas. In intracerebral hemorrhage swirl sign is associated with greater hematoma volume, unfavorable outcomes and greater mortality risk." }, { "input": "What is Morgellons disease?", "output": "It is a skin condition in which individuals have skin lesions that contain some kind of fibers. Patients often complain of bugs crawling under their skin. The disease is of unknown origin and may be psychosomatic, however recent evidence indicates it could be transmitted by a tick." }, { "input": "What is Cellbase?", "output": "CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources." }, { "input": "What is Cellbase?", "output": "Cellbase is a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources. CellBase documentation can be found at http://docs.bioinfo.cipf.es/projects/cellbase." }, { "input": "What is Cellbase?", "output": "CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources. CellBase provides a solution to the growing necessity of integration by easing the access to biological data." }, { "input": "What is Cellbase?", "output": "CellBase is a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources." }, { "input": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "output": "Palatal musculature is known to be responsible for the active opening of the eustachian tube. " }, { "input": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "output": "The palatine musculature is involved in the opening of the eustachian tube." }, { "input": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "output": "Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube" }, { "input": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "output": " Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube" }, { "input": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "output": "Palatal musculature is known to be responsible for the active opening of the eustachian tube. " }, { "input": "What is the asosciation between the eustachian tube and the palatine muscle of the uvula?", "output": "Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube. " }, { "input": "Are Conserved Nonexonic Elements (CNEEs) important in phylogenomics research?", "output": "Yes. Conserved Nonexonic Elements (CNEEs) appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis." }, { "input": "What is the definition of General Regulatory Factors (GRFs)?", "output": "GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains." }, { "input": "What is the definition of General Regulatory Factors (GRFs)?", "output": "In Saccharomyces cerevisiae, a group of more than 200 co-regulated genes (Ribi genes) is involved in ribosome biogenesis. This regulon has been shown to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1, Tbf1 and Rap1) referred to as general regulatory factors (GRFs) because of their widespread binding and action at many promoters and other specialized genomic regions." }, { "input": "What is the definition of General Regulatory Factors (GRFs)?", "output": "General regulatory factors (GRFs) as genome partitioners GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains. Abf1 and Rap1 are general regulatory factors (GRFs) that contribute to transcriptional activation of a large number of genes, as well as to replication, silencing and telomere structure in yeast. " }, { "input": "What is the definition of General Regulatory Factors (GRFs)?", "output": "We speculate that an important function of general regulatory factors such as Reb1p is to establish and maintain proper transcription start sites at promoters, and that when binding of such factors is compromised, resulting effects on mRNA translation may be an underappreciated aspect of gene regulation studies. We found that nucleosomes and specific DNA-binding proteins, including the general regulatory factors Reb1p, Rap1p, and Abf1p, and Pol III transcription factors enhance the efficiency of NNS termination by physically blocking Pol II progression. In the model organism Saccharomyces cerevisiae, these regions are adjacent to binding sites for general regulatory transcription factors, and the Reb1 protein is commonly bound to promoter DNA near such regions. Here, we use high resolution tiling arrays to examine the contributions of two general regulatory factors, Abf1 and Rap1, to nucleosome occupancy in Saccharomyces cerevisiae. Multiple roles of the general regulatory factor Abf1 in yeast ribosome biogenesis. GRFs, which bind to sites scattered throughout the genome within promoters, would not only play a key role in regulating gene expression but also partition the genome in functionally independent domains. " }, { "input": "Which virus can be diagnosed with the monospot test?", "output": "Epstein-Barr virus (EBV) can be detected with the monospot test. EBV is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious mononucleosis in adolescents." }, { "input": "Why is the Fyn kinase considered a promising therapeutic target for Alzheimer's Disease?", "output": "Fyn is an attractive target for AD therapeutics, not only based on its activation by A\u03b2 via cellular prion protein but also due to its known interaction with tau, uniquely linking the two key pathologies in AD." }, { "input": "What is the link between TADs and GRBs?", "output": "Topologically associating domains (TADs) are ancient features that coincide with Metazoan clusters of extreme noncoding conservation (aka GRBs)." }, { "input": "What is the link between TADs and GRBs?", "output": "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation" }, { "input": "What is Target Explorer?", "output": "Target Explorer is an automated tool for the identification of new target genes for a specified set of transcription factors. It was specifically designed for the well-annotated Drosophila melanogaster genome, but most options can be used for sequences from other genomes as well. Target Explorer is available at http://trantor.bioc.columbia.edu/Target_Explorer/" }, { "input": "Can the yeast protein Abf1 act as insulator?", "output": "Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a potent insulating capacity" }, { "input": "Can the yeast protein Abf1 act as insulator?", "output": "yes" }, { "input": "Can the yeast protein Abf1 act as insulator?", "output": "Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a potent insulating capacity." }, { "input": "What does the human IVIG treatment for Alzheimer's disease contain?", "output": "Human intravenous immunoglobulin (IVIG) is a mixture of polyclonal IgG antibodies isolated and pooled from thousands of healthy human donors." }, { "input": "Is there any linear-time and linear-space algorithm for the computation of avoided words in biological sequences?", "output": "Yes. There is a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x." }, { "input": "What is the mechanism of the auxin-inducible degron system?", "output": "Fusion of inducible degradation signals, so-called degrons, to cellular proteins is an elegant method of controlling protein levels in vivo. The auxin-inducible degron (AID) system allows the rapid and reversible proteolysis of proteins of interest, and enables the generation of conditional mutants of budding yeast. Strategies that use ubiquitin-mediated protein degradation to eliminate the product of a gene of interest, such as heat-inducible degron (td) and auxin-inducible degron (AID), are powerful methods for constructing conditional mutants. Auxin-inducible degron (AID) technology allows rapid depletion of proteins in animal cells and fungi, but its application to human cells has been limited by the difficulties of tagging endogenous proteins. The auxin-inducible degron harbors great potential for dynamic protein depletion in yeast. Here, we thoroughly and quantitatively characterize the auxin-inducible degron in single yeast cells." }, { "input": "What is the mechanism of the auxin-inducible degron system?", "output": "Plants have evolved a unique system in which the plant hormone auxin directly induces rapid degradation of the AUX/IAA family of transcription repressors by a specific form of the SCF E3 ubiquitin ligase. Other eukaryotes lack the auxin response but share the SCF degradation pathway, allowing the transplantation of the auxin-inducible degron (AID) system into nonplant cells and the use of a small molecule to conditionally control protein stability." }, { "input": "Which bacteria causes erythrasma?", "output": "Corynebacterium minutissimum is the bacteria that leads to cutaneous eruptions of erythrasma and is the most common cause of interdigital foot infections." }, { "input": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "output": "SMARCAL1, also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia, an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. " }, { "input": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "output": "Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage." }, { "input": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "output": "Smarcal1 , also known as harp, is an atp-dependent annealing helicase that stabilizes replication forks during dna damage. Mutations in this gene are the cause of schimke immune-osseous dysplasia , an autosomal recessive disorder characterized by t-cell immunodeficiency and growth dysfunctions. " }, { "input": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "output": "Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. " }, { "input": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "output": "Mutations in this gene are the cause of Schimke immune-osseous dysplasia , an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. SMARCAL1 , also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. " }, { "input": "Mutations in which gene cause Schimke immune-osseous dysplasia?", "output": "SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions." }, { "input": "What is the most common histological diagnosis of \"butterfly glioma\"?", "output": "Butterfly glioma is glioblastoma multiforme invading corpus callosum ." }, { "input": "Which chromosomes are implicated in the Emanuel syndrome?", "output": "Emanuel syndrome is associated with supernumerary chromosome t(11;22)(q23;q11), which consists of the extra genetic material from chromosomes 11 and 22." }, { "input": "Is a CpG island methylator phenotype involved in ependymomas?", "output": "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype" }, { "input": "Is a CpG island methylator phenotype involved in ependymomas?", "output": "yes" }, { "input": "Is a CpG island methylator phenotype involved in ependymomas?", "output": "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death." }, { "input": "Is a CpG island methylator phenotype involved in ependymomas?", "output": "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas. " }, { "input": "Is a CpG island methylator phenotype involved in ependymomas?", "output": "Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype." }, { "input": "Are loop domains preserved upon cohesin loss?", "output": "No. Degradation of cohesin leads to elimination of loop domains. Neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes." }, { "input": "Which workflow in Bioconductor has been developed for accessing human RNA-seq samples?", "output": "The recount2 resource is composed of over 70,000 uniformly processed human RNA-seq samples spanning TCGA and SRA, including GTEx." }, { "input": "What does VBP15 do to skeletal muscle?", "output": "VBP15 protects and promotes efficient repair of skeletal muscle cells. Potent inhibition of NF-\u03baB is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. In DMD model mice it improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens." }, { "input": "What is filgotinib?", "output": "Filgotinib is an oral selective Janus kinase inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be safe and efficacious." }, { "input": "What is Q-nexus?", "output": "Q-nexus is a comprehensive and efficient analysis pipeline designed for ChIP-nexus." }, { "input": "What is the mechanism of action of Tisagenlecleucel?", "output": "Tisagenlecleucel CD19-directed chimeric antigen receptor T cells (CART19) product that cause reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. Its is is approved for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia." }, { "input": "What is LHON, also known as Lebers syndrome?", "output": "Leber's hereditary optic neuropathy (LHON) is a common inherited mitochondrial disorder that is characterized by the degeneration of the optic nerves, leading to vision loss." }, { "input": "What is the ReliableGenome?", "output": "The increasing adoption of clinical whole-genome resequencing (WGS) demands for highly accurate and reproducible variant calling (VC) methods. The observed discordance between state-of-the-art VC pipelines, however, indicates that the current practice still suffers from non-negligible numbers of false positive and negative SNV and INDEL calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity. ReliableGenome is a method for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines. It combines call sets derived by multiple pipelines from arbitrary numbers of datasets and interpolates expected concordance for genomic regions without data." }, { "input": "List polyubiquitin binding proteins involved in NF-kappaB signaling.", "output": "NEMO\nA20\nABIN-1\nABIN-2\noptineurin\np62" }, { "input": "What are the prednisone side effects in DMD patients?", "output": "Side effects of prednisone in DMD patients include reduced growth rate and increase in body weight." }, { "input": "Which is the specificity of deubiquitinase USP25?", "output": "Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. It specially catalyzes the hydrolysis of the K48-linked and K63-linked polyubiquitin chains." }, { "input": "Is Loss of function one of the cardinal signs of inflammation?", "output": "Functio Laesa also known as loss of function is considered to be the 5th cardinal sign of inflammation." }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "yes" }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity." }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity." }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains . Parp1- and ctcf-regulated contacts between circadian loci to the lamina, followed by the acquisition of repressive h3k9me2 marks and transcriptional attenuation here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains . PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. " }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. " }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains . PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. " }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. Here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains. " }, { "input": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "output": "Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity." }, { "input": "What induces Arabidopsis ROF1 expression?", "output": "The abundance of ROF1 increased several-fold under stress conditions such as wounding, heat stress or exposure to elevated NaCl levels." }, { "input": "What is the preferred orientation of CTCF binding sites for chromatin looping?", "output": "chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs \"facing\" one another." }, { "input": "What is the preferred orientation of CTCF binding sites for chromatin looping?", "output": "As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner. Recent studies identified a correlation between the orientation of CTCF-binding sites and chromatin loops. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. " }, { "input": "What is the preferred orientation of CTCF binding sites for chromatin looping?", "output": "As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function." }, { "input": "Does erythromycin increase risk of hypertrophic pyloric stenosis?", "output": "Yes, post-natal erythromycin exposure is associated with increased risk of hypertrophic pyloric stenosis. The association is stronger when exposure occurs in the first 2 weeks of life." }, { "input": "How many amino acids does davunetide consist of?", "output": "Davunetide or NAP is an eight amino acid peptide." }, { "input": "Can a circRNA be translated into protein?", "output": "Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circRNA in eukaryotes.\nCircular RNAs (circRNAs) represent a large class of noncoding RNAs (ncRNAs) that have recently emerged as regulators of gene expression\t\nHowever, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported" }, { "input": "Can a circRNA be translated into protein?", "output": "\u039cost circRNAs were not associated with translating ribosomes, therefore, circRNAs were deemed to be noncoding. However, the latest research findings revealed that some circRNAs could generate proteins in vivo, which expands the landscape of transcriptome and proteome" }, { "input": "What is the phenomenon of gene kissing?", "output": "Clustering of genes with similar expression patterns constitutes a phenomenon sometimes called \"gene kissing.\"" }, { "input": "What is the phenomenon of gene kissing?", "output": "This positioning can also result in the clustering of genes with similar expression patterns, a phenomenon sometimes called \"gene kissing.\" " }, { "input": "What is the phenomenon of gene kissing?", "output": "This positioning can also result in the clustering of genes with similar expression patterns, a phenomenon sometimes called \"gene kissing.\" We speculate that our findings might provide insight into other types of gene kissing, some of which also require cis-acting DNA sequences and trans-acting proteins." }, { "input": "What protein is the most common cause of hereditary renal amyloidosis?", "output": "The most common cause of hereditary renal amyloidosis is over expression of a mutant form of the Fibrinogen A Alpha protein" }, { "input": "What are the side effects of deflazacort in DMD patients?", "output": "The side effects observed in DMD patients following deflazacort treatment include growth failure and weight gain, facial fullness, blood pressure, bone health, cataracts, gastrointestinal symptoms, behavior, hypertrichosis, and need for medication interventions." }, { "input": "With which cancers has the loss of SMARCB1 been associated?", "output": "Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1 Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs)" }, { "input": "With which cancers has the loss of SMARCB1 been associated?", "output": "We therefore sought to identify novel mutations to better understand chordoma biology and to potentially identify therapeutic targets Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1" }, { "input": "With which cancers has the loss of SMARCB1 been associated?", "output": "The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC) Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs)" }, { "input": "With which cancers has the loss of SMARCB1 been associated?", "output": "Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas (CCs)." }, { "input": "With which cancers has the loss of SMARCB1 been associated?", "output": "Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1. Loss of SMARCB1/INI1 expression is considered to be a hallmark for childhood chordomas . The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas . " }, { "input": "Where do centromeres locate according to the Rabl orientation of eukaryotic nuclei?", "output": "The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres." }, { "input": "Where do centromeres locate according to the Rabl orientation of eukaryotic nuclei?", "output": "The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres. telomeric Yq12 sequence also localized together with perinucleolar centromeres in a completely non-Rabl orientation. During interphase in the budding yeast, Saccharomyces cerevisiae, centromeres are clustered near one pole of the nucleus as a rosette with the spindle pole body at its hub. We show that most of this preferential association is not due to vegetative (also known as somatic) pairing but is caused by the polar orientation of interphase chromosomes (Rabl orientation) This was taken as good evidence for the maintenance of the chromosome arrangement - the Rabl orientation - and of the peripheral location of the centromere and its association with the nuclear membrane. Homologous chromosomes were spatially separated in nuclei." }, { "input": "Where do centromeres locate according to the Rabl orientation of eukaryotic nuclei?", "output": "the nuclear membrane" }, { "input": "Where do centromeres locate according to the Rabl orientation of eukaryotic nuclei?", "output": "This was taken as good evidence for the maintenance of the chromosome arrangement - the Rabl orientation - and of the peripheral location of the centromere and its association with the nuclear membrane." }, { "input": "What is the function of STAR elements in yeast telomeres?", "output": "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR. The telomere-proximal portion of either X or Y' dampened silencing when located between the telomere and the reporter gene. These elements were named STARs, for subtelomeric anti-silencing regions. STARs can also counteract silencer-driven repression at the mating-type HML locus. When two STARs bracket a reporter gene, its expression is no longer influenced by surrounding silencing elements, although these are still active on a second reporter gene." }, { "input": "What is the function of STAR elements in yeast telomeres?", "output": "These elements were named STARs, for subtelomeric anti-silencing regions. Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR. In addition, an intervening STAR uncouples the silencing of neighboring genes. The telomere-proximal portion of either X or Y' dampened silencing when located between the telomere and the reporter gene. STARs thus display the hallmarks of insulators." }, { "input": "What is the function of STAR elements in yeast telomeres?", "output": "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs)." }, { "input": "What is the function of STAR elements in yeast telomeres?", "output": "Subtelomeres also contain Sub-Telomeric Anti-silencing Regions (STARs). We also show that the deletion of Histone-Acetyltransferase genes reduce the silencing activity of an ACS proto-silencer, but also reduce the anti-silencing activity of a STAR." }, { "input": "What is the function of STAR elements in yeast telomeres?", "output": "STARs are subtelomeric anti-silencing regions that can counteract silencer-driven repression at the mating-type HML locus. When two STARs bracket a reporter gene, its expression is no longer influenced by surrounding silencing elements, although these are still active on a second reporter gene. In addition, an intervening STAR uncouples the silencing of neighboring genes. STARs thus display the hallmarks of insulators." }, { "input": "Name the phase 3 clinical trials for tofacitinib in colitis.", "output": "There are three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis: OCTAVE Induction 1, OCTAVE Induction 2, OCTAVE Sustain." }, { "input": "Name the phase 3 clinical trials for tofacitinib in colitis.", "output": "OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 ." }, { "input": "What is the mode of action of the drug Prolia?", "output": "Prolia, also known as denosumab is an anti-RANKL agent for the treatment of osteoporosis. It works by preventing the development of osteoclasts which are cells that break down bone." }, { "input": "How does parathyroid hormone affect circulating levels of periostin?", "output": "Parathyroid hormone can upregulate periostin levels." }, { "input": "What is MINDY (motif interacting with Ub-containing novel DUB family)?", "output": "MINDY-1 is a member of an evolutionarily conserved and structurally distinct new family of deubiquitinating enzymes." }, { "input": "Has the proteome of mice hippocampus been analysed?", "output": "Yes, numerous proteomic studies of mice hippcampi has been performed." }, { "input": "Was saracatinib being considered as a treatment for Alzheimer's disease in November 2017?", "output": "Yes, saracatinib is being studied as a treatment against Alzheimer's Disease. A clinical Phase Ib study has been completed, and a clinical Phase IIa study is ongoing." }, { "input": "Are mouse chromosomes acrocentric?", "output": "yes" }, { "input": "Are mouse chromosomes acrocentric?", "output": "Mouse chromosomes are acrocentric and of similar size." }, { "input": "Is overproduction of transthyretin is associated with amyloidosis associated neuropathy?", "output": "Yes, an overproduction of transthyretin is associated with amyloidosis associated neuropathy." }, { "input": "Is overproduction of transthyretin is associated with amyloidosis associated neuropathy?", "output": "Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a disease caused by the deposit of abnormal transthyretin on tissues, mainly nerves" }, { "input": "What is cebocephaly", "output": "Cebocephaly is a developmental anomaly of the head characterized by a small head, with a defective small, flattened nose with a single nostril or absent nose and closely set eyes." }, { "input": "How can network assortativity be applied in the three-dimensional analysis of the genome?", "output": "Chromatin assortativity is a way to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts." }, { "input": "Which phase III clinical trials for rheumatoid arthritis involve baricitinib? (November 2017)", "output": "The phase 3 clinical trials of baricitinib in rheumatoid arthritis patients are: RA-BEACON, RA-BUILD, RA-BEAM." }, { "input": "Which disease risk can be estimated with the Stop-Bang questionnaire?", "output": "Stop-Bang questionnaire is used to predict risk of obstructive sleep apnea (OSA)." }, { "input": "List indications for palivizumab for treatment of RSV-induced bronchiolitis. ", "output": "According to guidelines palivizumab is available for treatment of RSV-induced bronchiolitis in high-risk infants: born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease. Palivizumab reduces the burden of bronchiolitis but does not prevent infection." }, { "input": "List factors that promote lymphangiogenesis.", "output": "VEGF-C\nVEGF-D\nVEGF-R3" }, { "input": "Which siRNA based drug is in clinical trials for the treatment of pancreatic cancer?", "output": "siG12D-LODERTM has been tested in a phase 1/2a clinical trial of patients with pancreatic cancer." }, { "input": "Which siRNA based drug is in clinical trials for the treatment of pancreatic cancer?", "output": "siG12D-LODER\u2122" }, { "input": "How is CTCF activated post-translationally?", "output": "The chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation." }, { "input": "How is CTCF activated post-translationally?", "output": "Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation. the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation Chromatin immunoprecipitation-on-chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. " }, { "input": "How is CTCF activated post-translationally?", "output": "Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation." }, { "input": "What is the HPG pore?", "output": "The use of nanopore technologies is expected to spread in the future because they are portable and can sequence long fragments of DNA molecules without prior amplification. The first nanopore sequencer available, the MinION\u2122 from Oxford Nanopore Technologies, is a USB-connected, portable device that allows real-time DNA analysis. In addition, other new instruments are expected to be released soon, which promise to outperform the current short-read technologies in terms of throughput. Despite the flood of data expected from this technology, the data analysis solutions currently available are only designed to manage small projects and are not scalable. HPG pore is a toolkit for exploring and analysing nanopore sequencing data. HPG Pore can run on both individual computers and in the Hadoop distributed computing framework, which allows easy scale-up to manage the large amounts of data expected to result from extensive use of nanopore technologies in the future." }, { "input": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "output": "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT)," }, { "input": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "output": "Aspartate transaminase or aspartate aminotransferase, also known as AspAT/ASAT/AAT/AST is also known as serum glutamic oxaloacetic transaminase SGOT" }, { "input": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "output": "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), aspartate aminotransferase (AST-SGOT), alanine amino-transferase (ALT-SGPT)" }, { "input": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "output": "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), Alanine amino transferase (SGPT), " }, { "input": "Is patisiran currently (November 2017) in clinical phase II trials?", "output": "No, patisiran is in phase 3 clinical studies." }, { "input": "Is patisiran currently (November 2017) in clinical phase II trials?", "output": "No, patisiran is in clinical phase 3 trials" }, { "input": "Which R/Bioconductor package has been developed for cancer subtype identification?", "output": "Identifying molecular cancer subtypes from multi-omics data is an important step in the personalized medicine. CancerSubtypes is an R/Bioconductor package for molecular cancer subtype identification, validation and visualization. CancerSubtypes integrates four main computational methods which are highly cited for cancer subtype identification and provides a standardized framework for data pre-processing, feature selection, and result follow-up analyses, including results computing, biology validation and visualization. The input and output of each step in the framework are packaged in the same data format, making it convenience to compare different methods." }, { "input": "Is Solanezumab effective for Alzheimer's Disease?", "output": "No. Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability in patients with Alzheimer's Disease." }, { "input": "Are organisms in the genus Morexella associated with sepsis?", "output": "Moraxella species may cause neonatal sepsis" }, { "input": "Are there mammalian promoters with distal enhancer functions?", "output": "Yes. Several studies have suggested that some promoters might have enhancer functions. By exploiting a high-throughput enhancer reporter assay, scientists have unraveled a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci." }, { "input": "What gene is mutated in Familial Mediterranean Fever?", "output": "The MEFV gene which encodes the pyrin protein is mutated in Familial Mediterranean Fever(FMF)." }, { "input": "Which R/bioconductor package has been developed to aid in epigenomic analysis?", "output": "DeepBlueR is a package that allows for large-scale epigenomic analysis in R." }, { "input": "Which R/bioconductor package has been developed to aid in epigenomic analysis?", "output": "DeepBlueR" }, { "input": "Is autosomal dominant inheritanced form of Osteogenesis imperfecta caused by mutations in the genes associated with collagen production?", "output": "Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones. The autosomal dominant form of the disease is cause by a mutation in the COL1A1 or COL1A2 genes which produce type I collagen." }, { "input": "Is autosomal dominant inheritanced form of Osteogenesis imperfecta caused by mutations in the genes associated with collagen production?", "output": "steogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations inCOL1A1orCOL1A2and show autosomal dominant inheritance," }, { "input": "Is Apremilast effective for Behcet\u2019s syndrome?", "output": "Yes. Apremilast was proven to be effective for treatment of Behcet\u2019s syndrome." }, { "input": "Are splicing speckles associated with transcription?", "output": "Speckles contain little detectable transcriptional activity." }, { "input": "Are splicing speckles associated with transcription?", "output": "yes" }, { "input": "What is miravirsen?", "output": "Miravirsen is the first miRNA-targeting drug for the treatment of hepatitis C." }, { "input": "What is miravirsen?", "output": "Miravirsen is an AntimiR-122 for hepatitis C virus infection. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication." }, { "input": "Centor criteria are used for which disease?", "output": "Centor criteria were developed to diagnose streptococcal pharyngitis." }, { "input": "Does Enzastaurin improve survival of glioblastoma patients?", "output": "No. Treatment with enzastaurin does not improve survival of glioblastoma patients." }, { "input": "Is Tofacitinib effective for Ulcerative Colitis?", "output": "Yes. Tofacitinib, an oral small-molecule Janus kinase inhibitor, is effective in the treatment of moderate-severe ulcerative colitis. It is also effective treatment of rheumatoid arthritis and autoimmune encephalomyelitis." }, { "input": "Which are the main transcriptional activators of circadian oscillations?", "output": "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop." }, { "input": "Which are the main transcriptional activators of circadian oscillations?", "output": "BMAL1 and CLOCK." }, { "input": "Which are the main transcriptional activators of circadian oscillations?", "output": "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation." }, { "input": "Which are the main transcriptional activators of circadian oscillations?", "output": "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG)." }, { "input": "Which are the main transcriptional activators of circadian oscillations?", "output": "Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Formation of CLOCK/BMAL1 complex following ectopic coexpression of both proteins is followed by their codependent phosphorylation, which is tightly coupled to CLOCK nuclear translocation and degradation" }, { "input": "Is CREB a key memory protein?", "output": "The creb protein is associated with memory" }, { "input": "Is CREB a key memory protein?", "output": "Yes, human cyclic AMP response element binding protein (CREB) transcription factor plays a crucial role in memory." }, { "input": "Which clinical trials for psoriasis involved tofacitinib? (November 2017)", "output": "Four phase 3 clinical trials have been performed to assess tofacitinib in psoriasis patients: OPT Retreatment, OPT Pivotal 1, OPT Pivotal 2, OPT Compare" }, { "input": "Which two interleukins are inhibited by Ustekinumab?", "output": "Ustekinumab, a monoclonal antibody that binds to the shared p40 subunit of interleukin-12 and interleukin-23, is approved in the USA and Europe for moderate to severe plaque psoriasis." }, { "input": "What is a potential side effect for Tymlos?", "output": "Possible bone cancer (osteosarcoma). During animal drug testing, TYMLOS caused some rats to develop a bone cancer called osteosarcoma." }, { "input": "Which disorder has been approved for treatment with Alk inhibitors?", "output": "Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer." }, { "input": "Which disorder has been approved for treatment with Alk inhibitors?", "output": "Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011" }, { "input": "List proteins that are targeted by \"immune checkpoints inhibitors\".", "output": "The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab." }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors" }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression" }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Auxin enhances the binding of Aux/IAA proteins to the receptor TIR1, which is an F-box protein that is part of the E3 ubiquitin ligase complex SCF(TIR1)." }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "Auxin is sensed by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, which leads to IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Evidence also exists for SCF(TIR1)-mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12" }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. Auxin dose-response assays revealed that IAA9 downregulated lines were hypersensitive to auxin, although the only early auxin-responsive gene that was found to be upregulated in the antisense lines was IAA3. We report here that the downregulation of IAA9, a tomato (Solanum lycopersicum) gene from a distinct subfamily of Aux/IAA genes, results in a pleiotropic phenotype, consistent with its ubiquitous expression pattern. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family. Aux/IAA proteins are short-lived nuclear proteins that repress expression of primary/early auxin response genes in protoplast transfection assays. Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. Binding of Aux/IAA proteins leads to degradation via the 26S proteasome, but evidence for SCF(TIR1)-mediated poly-ubiquitination of Aux/IAA proteins is lacking. " }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. The tomato Aux/IAA transcription factor IAA9 is involved in fruit development and leaf morphogenesis. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family. Nce for SCF-mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12. Aux/IAA proteins are short-lived nuclear proteins that repress expression of primary/early auxin response genes in protoplast transfection assays. We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. " }, { "input": "Which genes belong to the AUX/IAA family of transcription repressors in plants?", "output": "Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors. The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants [1, 2]. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but partially overlapping patterns of expression. The tomato Aux/IAA transcription factor IAA9 is involved in fruit development and leaf morphogenesis. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Here, we systematically dissect auxin sensing by SCFTIR1-IAA6 and SCFTIR1-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Auxin dose-response assays revealed that IAA9 downregulated lines were hypersensitive to auxin, although the only early auxin-responsive gene that was found to be upregulated in the antisense lines was IAA3. While no mutation in any member of subfamily IV has been reported to date, the phenotypes associated with the downregulation of IAA9 reveal distinct and novel roles for members of the Aux/IAA gene family. " }, { "input": "What is GenomeVIP?", "output": "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure.GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface." }, { "input": "What is GenomeVIP?", "output": "The Genome Variant Investigation Platform (GenomeVIP) is an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface." }, { "input": "What is GenomeVIP?", "output": "Genome Variant Investigation Platform (GenomeVIP) is an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure." }, { "input": "What is GenomeVIP?", "output": "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface." }, { "input": "What is GenomeVIP?", "output": "Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. " }, { "input": "List the ten types of conjoined twins.", "output": "Thoraco-omphalopagus: Two bodies fused from the upper chest to the lower chest. These twins usually share a heart, and may also share the liver or part of the digestive system.\nThoracopagus:Two bodies fused from the upper thorax to lower belly. The heart is always involved in these cases.\nOmphalopagus: Two bodies fused at the lower abdomen. Unlike thoracopagus, the heart is never involved in these cases.\nPyopagus: joined at the buttocks with sacrum and coccyx anomalies\nRachipagus: Joined at the spine with vertebral and neural tube defects\nIschiopagus: joined at the hip from umbilicus to conjoined pelvis\nParasitic twins: Twins that are asymmetrically conjoined, resulting in one twin that is small, less formed, and dependent on the larger twin for survival.\nCraniopagus: Fused skulls, but separate bodies\nCephalopagus: head but not face or foramen magnum, brains are usually separate\nDicephalus dipus dibrachius: 2 heads and one body" }, { "input": "Which algorithm has been developed in order to improve multiple circular sequence alignment using refined sequences?", "output": "MARS improves multiple circular sequence alignment using refined sequences. MARS was implemented in the C++ programming language as a program to compute the rotations (cyclic shifts) required to best align a set of input sequences. Experimental results, using real and synthetic data, show that MARS improves the alignments, with respect to standard genetic measures and the inferred maximum-likelihood-based phylogenies, and outperforms state-of-the-art methods both in terms of accuracy and efficiency." }, { "input": "Which stapled peptide has been designed to target Ctf4?", "output": "The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase\u2005\u03b1 from the replisome in yeast extracts." }, { "input": "Mutation of which gene causes arterial tortuosity syndrome?", "output": "Arterial tortuosity syndrome is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10)." }, { "input": "Fusarium oxysporum f. sp lycopersici. is a plant pathogen in plants producing what common food?", "output": "Fusarium oxysporum f. sp lycopersici.produces causes vascular wilt disease in tomatoes." }, { "input": "Fusarium oxysporum f. sp lycopersici. is a plant pathogen in plants producing what common food?", "output": "Fusarium wilt caused by Fusarium oxysporum f. sp lycopersici (Fol) is one of the main diseases affecting tomatoes. " }, { "input": "Is cilengitide effective for treatment of glioblastoma?", "output": "No, cilengitide does not improve survival of glioblastoma (GBM) patients. Cilengitide is a cyclic pentapeptide that demonstrated efficacy for GBM treatment by targeting the integrins av\u03b23 and av\u03b25 over-expressed on GBM cells. However, randomized phase III CENTRIC and phase II CORE trials explored failed to meet their primary endpoints. However, in CORE, higher \u03b1v\u03b23 levels in tumor cells were associated with improved progression-free survival by central review and with improved overall survival in patients treated with cilengitide. Analysis of randomized clinical trials of antiangiogenic drugs (including cilengitide) showed no improvement in overall survival and a trend for an inferior outcome, in terms of overall survival, in patients receiving antiangiogenic drug alone compared to cytotoxic drug alone." }, { "input": "What is BBCAnalyzer?", "output": "BBCAnalyzer (Bases By CIGAR Analyzer) provides a novel visual approach to facilitate this step of time-consuming, manual inspection of common mutation sites. BBCAnalyzer is able to visualize base counts at predefined positions or regions in any sequence alignment data that are available as BAM files. Thereby, the tool provides a straightforward solution for evaluating any list of expected mutations like hotspot mutations, or even whole regions of interest. In addition to an ordinary textual report, BBCAnalyzer reports highly customizable plots. Information on the counted number of bases, the reference bases, known mutations or polymorphisms, called mutations and base qualities is summarized in a single plot. By uniting this information in a graphical way, the user may easily decide on a variant being present or not - completely independent of any internal filters or frequency thresholds." }, { "input": "Can multiple myeloma patients develop hyperviscosity syndrome?", "output": "Yes, multiple myeloma patients can develop hyperviscosity syndrome. Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems." }, { "input": "What is the purpose of the FaceBase consortium?", "output": "The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients." }, { "input": "What is the purpose of the FaceBase consortium?", "output": "The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients. " }, { "input": "What is TCGA2BED?", "output": "Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. TCGA2BED is a software tool to search and retrieve TCGA (The Cancer Genome Atlas) data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase)." }, { "input": "Does the human lncRNA LINC-PINT promote tumorigenesis?", "output": "No. LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells." }, { "input": "Is LDB1-mediated enhancer looping dependent on cohesin?", "output": "No. LDB1-mediated enhancer looping can be established independent of mediator and cohesin." }, { "input": "Describe nursemaid's elbow injury.", "output": "Nursemaid's elbow is a radial head subluxation caused by axial traction on the extended arm while the forearm is pronated, allowing for slippage of the radial head. Nursemaid's elbow usually occurs in young children when longitudinal traction is placed on the arm." }, { "input": "What is trismus?", "output": "Trimus is defined as restricted mouth opening due to disorder of the temporomandibular joint." }, { "input": "What is mechanism of action of Benralizumab?", "output": "Benralizumab is a humanised, anti-interleukin 5 receptor \u03b1 monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma." }, { "input": "Is there any link between ERCC1-XPF and cohesin?", "output": "Yes. ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes." }, { "input": "Describe the Match BAM to VCF (MBV) method.", "output": "MBV (Match BAM to VCF) is a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias." }, { "input": "Does Evolocumab improve cognitive function?", "output": "No, Evolocumab does not improve cognitive functioning." }, { "input": "Can radius fracture cause carpal tunnel syndrome?", "output": "Yes, carpal tunnel syndrome is a common complication associated with distal radius fractures." }, { "input": "Can Logic Alignment Free (LAF) be used for bacterial genomes classification?", "output": "Yes. Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms can be used in order to assign biological samples to their taxa." }, { "input": "Is Marfan syndrome associated with chordal rupture?", "output": "Yes, chordal rupture was described in patients with Marfan syndrome." }, { "input": "What is the mechanism of action of Fremanezumab?", "output": "Fremanezumab is a monoclonal antibody directed against calcitonin-gene-related peptide (CGRP). It was shown to be effective for migraine preventive therapy. Other three monoclonal antibodies targeting the CGRP pathway are eptinezumab, erenumab and galcanezumab." }, { "input": "Is trastuzumab associated cardiotoxicity reversible?", "output": "Cardiotoxicity is a potential adverse effect of trastuzumab, manifesting as either an asymptomatic decline in left-ventricular ejection fraction or infrequently as largely reversible symptomatic heart failure (HF). Reduction of cardiac function by trastuzumab is mostly reversible, however, some patients, especially those with cardiac risk factors, may rarely experience chronic heart failure or prolonged left ventricular ejection fraction reduction." }, { "input": "What is the role of nimotuzumab in treatment of pontine glioma?", "output": "Nimotuzumab (an anti-EGFR monoclonal antibody) is being used for treatment of pontine gliomas. Nimotuzumab is a very well-tolerated drug with acceptable toxicity, and it may have promising value in the combination treatment. Clinical trials evaluating efficacy of nimotuzumab are ongoing." }, { "input": "Describe annotatr", "output": "Analysis of next-generation sequencing data often results in a list of genomic regions. These may include differentially methylated CpGs/regions, transcription factor binding sites, interacting chromatin regions, or GWAS-associated SNPs, among others. A common analysis step is to annotate such genomic regions to genomic annotations (promoters, exons, enhancers, etc.). The annotatr Bioconductor package flexibly and quickly summarizes and plots annotations of genomic regions. The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions." }, { "input": "What is Blount's disease?", "output": "Blount's disease (tibia vara) is a progressive form of genu varum due to asymmetrical inhibition of the postero medial portion of the proximal tibial epiphysis. It causes causes genu varum and internal tibial torsion. It is the most common cause of pathologic genu varum in children and adolescents" }, { "input": "Describe mechanism of action of Nusinersen.", "output": "Nusinersen is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene. This modulates the splicing of the SMN2 mRNA transcript to include exon 7, thereby increasing the production of full-length SMN protein. It is approved for treatment of spinal muscular atrophy." }, { "input": "Describe King\u2013Kopetzky syndrome.", "output": "The principal symptom of subjects suffering from King-Kopetzky syndrome (Obscure Auditory Dysfunction) is perceived difficulty in recognizing and understanding speech in noisy backgrounds. For some patients, minor disturbances in auditory function, e.g. a deteriorated signal-to-noise ratio for speech, can be demonstrated; for others, all measurements of hearing are normal." }, { "input": "What is the 959 Nematode Genomes initiative?", "output": "The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/) has been launched. Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, it is anticipated that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla." }, { "input": "What is the 959 Nematode Genomes initiative?", "output": "The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla." }, { "input": "Which are the constitutive parts of a Genomic Regulatory Block (GRB)?", "output": "GRBs are spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes." }, { "input": "Glecaprevir and Pibrentasvir are used for tratment of which disease?", "output": "The combination of direct-acting antivirals glecaprevir and pibrentasvir is effective for treatment of Hepatitis C virus infection." }, { "input": "What is the drug target(s) for Belsomra?", "output": "Belsomra is a dual orexin receptor antagonist for both the Ox1 and Ox2 receptors" }, { "input": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "output": "Yes, canagliflozin use can cause euglycemic diabetic ketoacidosis. In May 2015, the FDA issued a warning of ketoacidosis with use of sodium-glucose cotransporter-2 (SGLT-2) drug class." }, { "input": "What is CellMaps?", "output": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them." }, { "input": "What is CellMaps?", "output": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. CellMaps can easily be integrated in any web page by using an available JavaScript API. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. " }, { "input": "What is CellMaps?", "output": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. CellMaps can easily be integrated in any web page by using an available JavaScript API. " }, { "input": "What is CellMaps?", "output": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. CellMaps can easily be integrated in any web page by using an available JavaScript API." }, { "input": "What is CellMaps?", "output": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. " }, { "input": "What is CellMaps?", "output": "CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. CellMaps can easily be integrated in any web page by using an available JavaScript API. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services." }, { "input": "Is there an association between Klinefelter syndrome and breast cancer?", "output": "Yes, Klinefelter syndrome is associated with increased risk of male breast cancer. Other risk factors of male breast cancer are positive family history, and mutations in BRCA1 and specially BRCA2." }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "signeR: an empirical Bayesian approach to mutational signature discovery. Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques. The extraction of mutational signatures from high-throughput data still remains a daunting task.RESULTS: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model." }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "SomaticSignatures: inferring mutational signatures from single-nucleotide variants.Mutational signatures are patterns in the occurrence of somatic single-nucleotide variants that can reflect underlying mutational processes.The SomaticSignatures package provides flexible, interoperable and easy-to-use tools that identify such signatures in cancer sequencing data.It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows.AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project.Its documentation provides additional details on the methods and demonstrates applications to biological datasets.These mutagenic processes often produce characteristic mutational patterns called mutational signatures.The decomposition of a cancer genome's mutation catalog into mutations consistent with such signatures can provide valuable information about cancer etiology.Hence, one needs to be able to not only decompose a patient's mutational profile into signatures but also establish the accuracy of such decomposition.Results: We proposed two complementary ways of measuring confidence and stability of decomposition results and applied them to analyze mutational signatures in breast cancer genomes." }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "signeR is an R package for a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model." }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "signeR: an empirical Bayesian approach to mutational signature discovery. Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques." }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "signeR: an empirical Bayesian approach to mutational signature discovery. The extraction of mutational signatures from high-throughput data still remains a daunting task.RESULTS: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model. Results on real data agree well with current knowledge.AVAILABILITY AND IMPLEMENTATION: signeR is implemented in R and C\u2009++, and is available as a R package at http://bioconductor.org/packages/signeR" }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "signeR: an empirical Bayesian approach to mutational signature discovery." }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "It facilitates large-scale, cross-dataset estimation of mutational signatures, implements existing methods for pattern decomposition, supports extension through user-defined approaches and integrates with existing Bioconductor workflows.AVAILABILITY AND IMPLEMENTATION: The R package SomaticSignatures is available as part of the Bioconductor project. " }, { "input": "Which R packages have been developed for the discovery of mutational signatures in cancer?", "output": "Cancers arise as the result of somatically acquired changes in the DNA of cancer cells. However, in addition to the mutations that confer a growth advantage, cancer genomes accumulate a large number of somatic mutations resulting from normal DNA damage and repair processes as well as carcinogenic exposures or cancer related aberrations of DNA maintenance machinery. These mutagenic processes often produce characteristic mutational patterns called mutational signatures. The decomposition of a cancer genome's mutation catalog into mutations consistent with such signatures can provide valuable information about cancer etiology. SigneR, SignatureEstimation, pmsignature and SomaticSignatures are R packages that have been developed for the discovery of mutational signatures in cancer." }, { "input": "According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.", "output": "Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity." }, { "input": "According to guidelines, insulin resistance is one risk factor in the diagnosis of metabolic syndrome, name 3 more risk factors.", "output": "Metabolic syndrome (MetS) is generally defined as a cluster of metabolically related cardiovascular risk factors which are often associated with the condition of insulin resistance, elevated blood pressure, and abdominal obesity. " }, { "input": "Silent Allosteric Modulation of mGluR5 is a form of treatment for what disease?", "output": "silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window. " }, { "input": "Silent Allosteric Modulation of mGluR5 is a form of treatment for what disease?", "output": "silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window." }, { "input": "Silent Allosteric Modulation of mGluR5 is a form of treatment for what disease?", "output": "Silent allosteric modulation of mGluR5 has promise as a disease-modifying Alzheimer's Disease therapy." }, { "input": "What are check point inhibitors?", "output": "Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. These mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, they enhance the anti-tumor response of the immune system by targeting immune regulatory pathways." }, { "input": "Are the human bombesin receptors, GRPR and NMBR, frequently overexpressed G-protein-coupled-receptors by lung-cancers?", "output": "The human bombesin receptors, GRPR and NMBR, are two of the most frequently overexpressed G-protein-coupled-receptors by lung-cancers" }, { "input": "Are the human bombesin receptors, GRPR and NMBR, frequently overexpressed G-protein-coupled-receptors by lung-cancers?", "output": "All 3 bombesin receptor subtypes (GRPR, NMBR, and BRS-3) were present on pulmonary and intestinal carcinoids by immunohistochemistry. " }, { "input": "Which data simulator is available for CLIP-SEQ experiments?", "output": "CLIP-Seq protocols such as PAR-CLIP, HITS-CLIP or iCLIP allow a genome-wide analysis of protein-RNA interactions. For the processing of the resulting short read data, various tools are utilized. Some of these tools were specifically developed for CLIP-Seq data, whereas others were designed for the analysis of RNA-Seq data. To this date, however, it has not been assessed which of the available tools are most appropriate for the analysis of CLIP-Seq data. This is because an experimental gold standard dataset on which methods can be accessed and compared, is still not available. To address this lack of a gold-standard dataset, Cseq-Simulator was developed as a simulator for PAR-CLIP, HITS-CLIP and iCLIP-data. This simulator can be applied to generate realistic datasets that can serve as surrogates for experimental gold standard dataset." }, { "input": "Falciform ligament sign is characteristic to which disease?", "output": "The falciform ligament sign (gas outlining the falciform ligament) is characteristic to pneumoperitoneum due to intestinal perforation." }, { "input": "Is vorinostat effective for glioblastoma?", "output": "No. Although vorinostat is well tolerated it does not improve survival of glioblastoma patients." }, { "input": "Is there any role of Dlx1 and Dlx2 transcription factors in cortical interneurons?", "output": "Yes. DLX2 directly drives Gad1, Gad2, and Vgat expression, and mutants have reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and have reduced mIPSC frequency. Furthermore, Dlx1/2 CKO have hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input." }, { "input": "Describe SNP2TFBS", "output": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/." }, { "input": "Describe SNP2TFBS", "output": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs." }, { "input": "What is SMiLE-seq?", "output": "Selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq) is a semiautomated protein-DNA interaction characterization technology. SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion." }, { "input": "What is SMiLE-seq?", "output": "SMiLE-Seq is a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing for de novo transcription factor motif discovery." }, { "input": "What is SMiLE-seq?", "output": "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays." }, { "input": "What is SMiLE-seq?", "output": "Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays. De novo motif discovery on all JUN-FOS heterodimers and several nuclear receptor-TF complexes provided novel insights into partner-specific heterodimer DNA-binding preferences." }, { "input": "What is libgapmis?", "output": "libgapmis is a library for extending pairwise short-read alignments. Apart from the standard CPU version, it includes ultrafast SSE- and GPU-based implementations. libgapmis is based on an algorithm computing a modified version of the traditional dynamic-programming matrix for sequence alignment. The open-source code of libgapmis is available at http://www.exelixis-lab.org/gapmis." }, { "input": "Has ATF4 transcription factor been linked to cancer and neoplastic transformation?", "output": "Yes, ATF4 transcription factor has been linked to cancer and neoplastic transformation." }, { "input": "Are patients with Sjogren syndrome at increased risk for lymphoma?", "output": "Yes, the heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome is well established. Five per cent of patients with primary Sjogren's syndrome develop malignant non-Hodgkin's lymphoma, usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. The incidence of lymphoma is higher in patients with Sj\u00f6gren's syndrome than in the general population." }, { "input": "Describe JACUSA", "output": "JACUSA detects single nucleotide variants by comparing data from next-generation sequencing experiments (RNA-DNA or RNA-RNA). In practice, JACUSA shows higher recall and comparable precision in detecting A\u2192I sites from RNA-DNA comparisons, while showing higher precision and recall in RNA-RNA comparisons." }, { "input": "What is the mechanism of action of Tezepelumab?", "output": "Tezepelumab is human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP)." }, { "input": "What is the association between kidney donation risk of gestational complications?", "output": "Kidney donation seems to elevate the risks of gestational complications. Postdonation pregnancies were associated with a higher risk of gestational diabetes, gestational hypertension, proteinuria and preeclampsia. However, others reported that donor nephrectomy is not detrimental to the prenatal course or outcome of future pregnancies." }, { "input": "Does prolactinoma increase osteoporosis risk?", "output": "Yes, prolactinomas increase risk of osteoporosis. Prolactinomas also cause hypogonadism, infertility, and tumor mass effects." }, { "input": "In November 2017, in what phase was the clinical trial for the drug SYL040012?", "output": "SYL040012 is in phase 2 clinical trials" }, { "input": "Describe the RNA Centric Annotation System (RCAS)", "output": "The RNA Centric Annotation System (RCAS) is an R package which is designed to ease the process of creating gene-centric annotations and analysis for the genomic regions of interest obtained from various RNA-based omics technologies. The design of RCAS is modular, which enables flexible usage and convenient integration with other bioinformatics workflows. RCAS is an R/Bioconductor package but there are also graphical user interfaces including a Galaxy wrapper and a stand-alone web service. The application of RCAS on published datasets shows that RCAS is not only able to reproduce published findings but also helps generate novel knowledge and hypotheses. The meta-gene profiles, gene-centric annotation, motif analysis and gene-set analysis provided by RCAS provide contextual knowledge which is necessary for understanding the functional aspects of different biological events that involve RNAs. In addition, the array of different interfaces and deployment options adds the convenience of use for different levels of users. RCAS is available at http://bioconductor.org/packages/release/bioc/html/RCAS.html and http://rcas.mdc-berlin.de." }, { "input": "What is Chronic Wasting Disease (CWD) in deer?", "output": "Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting members of the cervid species, and is one of the few TSEs with an expanding geographic range." }, { "input": "What does A1C measure?", "output": "Glycated proteins, such as glycated hemoglobin (HbA1c) or glycated albumin (GA) in the blood, are essential indicators of glycemic control for diabetes mellitus. " }, { "input": "What does A1C measure?", "output": "The A1C measures the amount of glycated hemoglobin in the blood and is a marker for control of blood glucose. Poor glucose control is indicative of diabetes mellitus." }, { "input": "Down's syndrome occurs when an individual has an extra copy or part of a copy of chromosome 21, yes or no?", "output": "Yes, Downs syndrome is caused by a duplication or all or part of chromosome 21." }, { "input": "Down's syndrome occurs when an individual has an extra copy or part of a copy of chromosome 21, yes or no?", "output": "Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). " }, { "input": "Down's syndrome occurs when an individual has an extra copy or part of a copy of chromosome 21, yes or no?", "output": "Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy." }, { "input": "What is craniosynostosis?", "output": "Craniosynostosis is a result of premature fusion of cranial sutures, leading to alterations of the pattern of cranial growth, resulting in abnormal shape of the head and dysmorphic facial features." }, { "input": "Which method has been developed for assignment of enhancers to target genes?", "output": "While genomic assays can identify putative enhancers en masse, assigning target genes is a complex challenge. McEnhancer is a machine learning approach, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features. Predicted expression patterns were 73-98% accurate, predicted assignments showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident, and known functional motifs were recovered." }, { "input": "Describe Click-PEGylation", "output": "One approach that can facilitate a targeted assessment of candidate proteins, as well as proteins that are low in abundance or proteomically challenging, is by electrophoretic mobility shift assays. Redox-modified cysteine residues are selectively tagged with a large group, such as a polyethylene glycol (PEG) polymer, and then the proteins are separated by electrophoresis followed by immunoblotting, which allows the inference of redox changes based on band shifts. However, the applicability of this method has been impaired by the difficulty of cleanly modifying protein thiols by large PEG reagents. To establish a more robust method for redox-selective PEGylation a Click chemistry approach has been developed where free thiol groups are first labelled with a reagent modified to contain an alkyne moiety, which is subsequently Click-reacted with a PEG molecule containing a complementary azide function. This strategy can be adapted to study reversibly reduced or oxidised cysteines. Separation of the thiol labelling step from the PEG conjugation greatly facilitates the fidelity and flexibility of this approach." }, { "input": "A SLEDAI score is associated with Systemic Lupus Erythematosus. What is a SLEDAI score?", "output": "Disease activity of Systemic Lupus Erythematosis was evaluated according to the SLE Disease Activity Index (SLEDAI) score which score disease activity based on a number of parameters." }, { "input": "A SLEDAI score is associated with Systemic Lupus Erythematosus. What is a SLEDAI score?", "output": "A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient." }, { "input": "A SLEDAI score is associated with Systemic Lupus Erythematosus. What is a SLEDAI score?", "output": "Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score." }, { "input": "What disease is the ALK tyrosine kinase associated with?", "output": "The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas" }, { "input": "CURB65 score is used for stratification of which disease?", "output": "CURB65 (confusion, urea, respiration, blood pressure; age>65\u2009years) is used for assessment of pneumonia severity." }, { "input": "Which resource has been developed in order to study the transcriptional regulation of GABAergic cell fate?", "output": "Subpallial Enhancer Transgenic Lines is a data and tool resource to study transcriptional regulation of GABAergic cell fate." }, { "input": "Is creatinine assessment included in the MELD score?", "output": "Yes, creatinine is included in the Model For End-Stage Liver Disease (MELD) score. Other components of the MELD score are international normalized ratio and serum billirubin. The MELD score is used for evaluation of liver cirrhosis." }, { "input": "List the two most important synaptic markers.", "output": "postsynaptic density 95\nsynaptophysin" }, { "input": "List the two most important synaptic markers.", "output": "Synaptic markers include acetylcholine, gamma-aminobutyric acid (GABA), glutamine, glycine and synaptophysin." }, { "input": "What is a SERM?", "output": "A SERM is a Selective Estrogen Receptor Modulator." }, { "input": "What is a SERM?", "output": "selective estrogen receptor modulator (SERM)," }, { "input": "What is a SERM?", "output": "elective estrogen receptor modulator (SERM)," }, { "input": "What is a SERM?", "output": "elective estrogen receptor modulator (SERM),. " }, { "input": "Is celiac disease caused by gliadin-induced transglutaminase-2 (TG2)-dependent events ?", "output": "Celiac disease is caused by gliadin-induced transglutaminase-2 (TG2)-dependent events following ingestion of dietary gluten." }, { "input": "Which resource contains accurate enhancer predictions in the developing limb?", "output": "Limb-Enhancer Genie (LEG) is a collection of highly accurate, genome-wide predictions of enhancers in the developing limb, available through a user-friendly online interface. Limb enhancers are predicted using a combination of >50 published limb-specific datasets and clusters of evolutionarily conserved transcription factor binding sites, taking advantage of the patterns observed at previously in vivo validated elements." }, { "input": "What is the first line treatment for sarcoidosis?", "output": "Sarcoidosis is a systemic granulomatous disease that affects numerous organs, commonly manifesting at the lungs and skin. Corticosteroids remain the first line of treatment." }, { "input": "Which personality disorder is treated using dialectical behavior therapy?", "output": "Dialectical behavior therapy is an evidence-based psychosocial treatment with efficacy in reducing self-harm behaviors in borderline personality disorder." }, { "input": "What cellular process are okazaki fragments associated with?", "output": "Okazaki fragments are involved in DNA replication" }, { "input": "Does wheat belongs to the genus Avena, yes or no?", "output": "oat seedlings (Avena sativa)" }, { "input": "Does wheat belongs to the genus Avena, yes or no?", "output": "Wheat belongs to the species Triticum not to the genus Avena." }, { "input": "Does wheat belongs to the genus Avena, yes or no?", "output": "oat seedlings (Avena sativa). " }, { "input": "Clue cells are characteristics to which causative bacteria of vaginitis?", "output": "Clue cells are characteristic to Gardnerella vaginalis vaginitis (bacterial vaginosis). Depopulation of lactobacilli from the normal vaginal flora and overgrowth of Gardnerella vaginalis and other anaerobic species are the presumed etiology. The diagnosis is confirmed when at least three of the following four findings are present (Amsel's criteria): 1) thin, homogenous discharge, 2) pH greater than 4.5, 3) positive amine test, and 4) presence of clue cell." }, { "input": "What is included in the fourth generation HIV test?", "output": "Fourth generation assays detect simultaneously antibodies for HIV and the p24 antigen. It identifies HIV infection earlier than previous generation tests." }, { "input": "Which disease is diagnosed using the Finkelstein's test?", "output": "Finkelstein's test is the classic diagnostic test for de Quervain's disease." }, { "input": "For which type of cancer can uc.189 be used as a potential prognostic biomarker?", "output": "ESCC" }, { "input": "For which type of cancer can uc.189 be used as a potential prognostic biomarker?", "output": "High expression of uc.189 might reflect poor prognosis of Esophageal squamous cell carcinomas (ESCC) and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target." }, { "input": "For which type of cancer can uc.189 be used as a potential prognostic biomarker?", "output": "Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target." }, { "input": "Does Uc.160 promote cancer?", "output": "No. Uc.160+ is a T-UCR reported to be downregulated in human cancer. In addition, Uc.160+ could possibly have a tumor suppressive role in gastric cancer." }, { "input": "What causes Black Lung?", "output": "Black lung, also known as pneumoconiosis, is caused by chronic exposure to coal dust." }, { "input": "List four principles of medical ethics.", "output": "The four principles of medical ethics proposed by Beauchamp and Childress are autonomy, non-maleficence, beneficence and justice. They have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care." }, { "input": "Which package in Bioconductor has been developed with the aim to analyze differential DNA loops from sequencing data?", "output": "Diffloop is an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops." }, { "input": "Which package in Bioconductor has been developed with the aim to analyze differential DNA loops from sequencing data?", "output": "diffloop" }, { "input": "Which disease can be diagnosed with the \"probe to bone\" test?", "output": "Probe-to-bone test is used for the diagnosis of diabetic foot osteomyelitis. The test has good sensitivity and specificity. Other diagnostic tests of diabetic foot osteomyelitis are plain films and magnetic resonance imaging." }, { "input": "Can doxycycline cause photosensitivity?", "output": "Yes, one of the most important dermatologic side effects of doxycycline is photosensitivity. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis." }, { "input": "What body process does the Dentate Gyrus Mossy Cell control?", "output": "Dentate gyrus mossy cells control spontaneous convulsive seizures and cognition" }, { "input": "Which ligament is most commonly injured in dashboard injury?", "output": "Posterior cruciate ligament injuries have a reported incidence of between 3 and 37%, depending on the clinical setting. The most common mechanism of injury in motor vehicle accidents is a dashboard injury or direct force to the proximal anterior tibia." }, { "input": "What is the normal body temperature in dogs?", "output": "According to the American Kennel Club (AKC), a temperature of 101 to 102.5 degrees Fahrenheit (38.3 to 39.2 degrees Celsius) is typical for dogs" }, { "input": "List symptoms of Heerfordt syndrome.", "output": "Heerfordt syndrome (also known as Heerfordt-Waldenstr\u00f6m or uveoparotid fever) is a rare presentation of sarcoidosis characterized by the presence of parotid gland enlargement, facial palsy, anterior uveitis, and fever." }, { "input": "In quadruped mammals, what bones make up the stifle?", "output": "In quadruped mammals, the stifle is composed of 3 bones, the femur, the tibia and the patella." }, { "input": "Are paralog genes co-regulated?", "output": "Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression." }, { "input": "Are paralog genes co-regulated?", "output": "Co-regulation of paralog genes in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization." }, { "input": "Are paralog genes co-regulated?", "output": "Co-regulation of paralog genes in the three-dimensional chromatin architecture. Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear." }, { "input": "Are paralog genes co-regulated?", "output": "Co-regulation of paralog genes in the three-dimensional chromatin architecture. Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters." }, { "input": "Are paralog genes co-regulated?", "output": "Yes. Paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization." }, { "input": "Are paralog genes co-regulated?", "output": "yes" }, { "input": "Are paralog genes co-regulated?", "output": "Co-regulation of paralog genes in the three-dimensional chromatin architecture. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters." }, { "input": "List 2 approved drug treatments for Inflammatory Bowel Disease (IBD).", "output": "Patients with IBD, inflammtory Bowel Disease can be treated with steroids, or 2 approved biosimilar drugs infliximab (IFX) or adalimumab (ADA)" }, { "input": "Which tool exists for microsatellite (SSR) loci detection and primer design?", "output": "Microsatellites are genomic sequences comprised of tandem repeats of short nucleotide motifs widely used as molecular markers in population genetics. FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay." }, { "input": "Which tool exists for microsatellite (SSR) loci detection and primer design?", "output": "FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay. " }, { "input": "Name curated data resources for ChIP-seq data", "output": "The MGA repository, Cistrome Data Browser and CR Cistrome are curated data resources for ChIP-seq data." }, { "input": "Treatment of which disease was studied in the Gore REDUCE Clinical Study?", "output": "The Gore REDUCE Clinical Study studied superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke." }, { "input": "Which comparisons demonstrate the applicability of StereoGene in regulatory genomics?", "output": "StereoGene rapidly estimates genome-wide correlation among pairs of genomic features. These features may represent high-throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. Numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE demonstrate the wide applicability of StereoGene in regulatory genomics." }, { "input": "What is the aim of the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions." }, { "input": "What is the aim of the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. " }, { "input": "What is the aim of the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions.The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions.Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells." }, { "input": "What is the aim of the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells." }, { "input": "What is the aim of the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. " }, { "input": "List symptoms of the Zieve's syndrome.", "output": "Zieve's syndrome, characterized by jaundice, hyperlipidaemia and haemolytic anaemia. It usually develops in young, chronically alcoholic subjects with enlarged fatty liver. It may rarely occur with intracranial haemorrhage." }, { "input": "What is the link between psoriatic arthritis and depression", "output": "Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis. " }, { "input": "What is the link between psoriatic arthritis and depression", "output": "Psoriasis is a common chronic inflammatory disease which is associated with extensive comorbidities, including psoriatic arthritis. " }, { "input": "Is polyadenylation a process that stabilizes a protein by adding a string of Adenosine residues to the end of the molecule?", "output": "No, polyadenylation is a process that stabilizes mRNA by adding up to 200 adenosine residues to the 3' end of the trabscript" }, { "input": "Which cancers compose Carney's triad?", "output": "Carney's triad is a rare pathogenic entity which consists of 3 rare soft tissue tumors: gastric leiomyosarcoma, pulmonary chondroma and extraadrenal paraganglioma. It is usually diagnosed in young women. The presence of three tumors at the same time is not required for its diagnosis (incomplete Carney's Triad)." }, { "input": "What is the preDIVA clinical trial?", "output": "The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years." }, { "input": "What effect does azeliragon have on RAGE?", "output": "Azeliragon is an inhibitor of receptor for advanced glycation end products (RAGE)." }, { "input": "What is the drug forxiga used for?", "output": "Dapagliflozin (Forxiga\u00ae) is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes." }, { "input": "What is the most common feature of the Doege\u2013Potter syndrome?", "output": "Doege-Potter syndrome is a paraneoplastic syndrome characterized by hypoglycemia secondary to a solitary fibrous tumor of the pleura." }, { "input": "Milwaukee protocol was tested for treatment of which disease?", "output": "The Milwaukee protocol was tested for treatment of rabies. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. The Milwaukee Protocol has proved to be ineffective for rabies and should no longer be used." }, { "input": "Are stress granules membraneous?", "output": "Stress granules (SG) are membrane-less compartments involved in regulating mRNAs during stress." }, { "input": "When is 16S rRNA Gene Sequencing used?", "output": "Taxonomic characterization is performed by genotypic approaches such as 16S rRNA gene sequencing." }, { "input": "What does intepirdine target?", "output": "Intepiridine is a 5-HT6 antagonist." }, { "input": "Is the consumption of chocolate associated with an increase in cardiovascular disease?", "output": "The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke." }, { "input": "Is the consumption of chocolate associated with an increase in cardiovascular disease?", "output": "Chocolate consumption can reduce cardio-cerebrovascular risk." }, { "input": "What is the association of circular RNA to breast cancer?", "output": "circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs. circRNA frequency may be a marker for cell proliferation in breast cancer." }, { "input": "List 3 symptoms of Wernicke encephalopathy.", "output": "Wernicke's encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion." }, { "input": "List 3 symptoms of Wernicke encephalopathy.", "output": "Wernicke's encephalopathy (WE) is a neurological syndrome caused by thiamine deficiency, and clinically characterized by ophthalmoplegia, ataxia and acute confusion. " }, { "input": "Describe RIblast", "output": "LncRNAs play important roles in various biological processes. Although more than 58\u2009000 human lncRNA genes have been discovered, most known lncRNAs are still poorly characterized. One approach to understanding the functions of lncRNAs is the detection of the interacting RNA target of each lncRNA. Because experimental detections of comprehensive lncRNA-RNA interactions are difficult, computational prediction of lncRNA-RNA interactions is an indispensable technique. However, the high computational costs of existing RNA-RNA interaction prediction tools prevent their application to large-scale lncRNA datasets. 'RIblast' is an ultrafast RNA-RNA interaction prediction method based on the seed-and-extension approach. RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model. Computational experiments indicate that RIblast achieves a level of prediction accuracy similar to those of existing programs, but at speeds over 64 times faster than existing programs." }, { "input": "What is Alzheimers disease resilience?", "output": "Some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia." }, { "input": "Which R package has been developed for analyzing Non-invasive prenatal testing (NIPT) data?", "output": "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex. RAPIDR has been extensively tested with a large sample set as part of the RAPID project in the UK. The package contains quality control steps to make it robust for use in the clinical setting." }, { "input": "Which R package has been developed for analyzing Non-invasive prenatal testing (NIPT) data?", "output": "RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex." }, { "input": "Is the gene CDKN2A nevogenic?", "output": "Yes, CDKN2A is nevogenic" }, { "input": "Are there ways of joint Bayesian inference of risk variants?", "output": "Yes. RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) is a Bayesian model for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations." }, { "input": "Describe Achenbach\u2019s syndrome.", "output": "Achenbach\u2019s syndrome is Paroxysmal finger haematoma. It is benign condition resulting in the sudden appearance of bruising on one or more fingers, either spontaneously or after minimal trauma, and resolving without treatment.It can be differentiated from other pathologies by clinical spectrum, patient demographics and in doubtful circumstances (acute limb ischemia) by Doppler sonography." }, { "input": "Has intepirdine been evaluated in clinical trials? (November 2017)", "output": "Yes, intepirdine was in Phase III clinical trials in November 2017." }, { "input": "Is subacute sclerosing panencephalitis caused by the Measles vaccine?", "output": "Subacute sclerosing panencephalitis is caused by the Measles and can be prevented by the measles vaccine." }, { "input": "Is subacute sclerosing panencephalitis caused by the Measles vaccine?", "output": "Subacute sclerosing panencephalitis (SSPE) is a potentially fatal complication of measles. " }, { "input": "What is host induced gene silencing?", "output": "Host-induced gene silencing (HIGS) is a transgenic technology used to silence fungal genes in planta during attempted infection and thereby reduces disease levels. HIGS relies on the host plant's ability to produce mobile small interfering RNA molecules, generated from long double-stranded RNA, which are complementary to targeted fungal genes. These molecules are transferred from the plant to invading fungi via an uncharacterised mechanism, to cause gene silencing." }, { "input": "What is maternal spindle transfer?", "output": "Maternal spindle transfer (MST) is a cutting edge germline-altering, IVF-based embryonic technique used to prevent the maternal transmission of serious mitochondrial diseases." }, { "input": "Does armodafinil improve fatigue of glioma patients?", "output": "No. Eight week course of armodafinil did not improve fatigue or quality of life in glioma patients undergoing radiotherapy. However, this conclusion is based on one identified clinical trial." }, { "input": "What is the role of tankyrases in response to Double Strand Breaks (DSBs)?", "output": "Tankyrases promote homologous recombination and check point activation in response to DSBs." }, { "input": "Which molecules are inhibited by anticancer drug Dovitinib?", "output": "Dovitinib (TKI-258/CHIR-258) is a pan receptor tyrosine kinase (RTK) inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It is being widely tested for treatment of various cancers." }, { "input": "How do circRNAs relate to tumorigenesis?", "output": "Circular RNA may promote or repress tumorigenesis." }, { "input": "Which method is available for whole genome identification of pathogenic regulatory variants in mendelian disease?", "output": "Genomiser" }, { "input": "Is pregabalin effective for sciatica?", "output": "No. Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group." }, { "input": "Can gas vesicles be detected by ultrasound?", "output": "Gas vesicles have been identified as nanoscale reporters for ultrasound." }, { "input": "In what phase of clinical trials is crenezumab? (November 2017)", "output": "Crenezumab is undergoing phase III clinical trials." }, { "input": "Which sequence-based algorithm for branch point prediction has been proposed?", "output": "BPP is a sequence-based algorithm for branch point prediction." }, { "input": "What organism causes scarlet fever also known as scarletina?", "output": "Scarlet fever is a disease which can occur as a result of a group A streptococcus (group A strep), group C Streptococcus and Streptococcus hemolyticus infection." }, { "input": "What is the BioArchive system?", "output": "A small-scale automated cryopreservation and storage system (Mini-BioArchive system) used in the banking of umbilical cord blood (UCB) units." }, { "input": "Which algorithm has been proposed for efficient storage of WGS variant calls?", "output": "Whole-genome sequencing (WGS) data are being generated at an unprecedented rate. Analysis of WGS data requires a flexible data format to store the different types of DNA variation. Variant call format (VCF) is a general text-based format developed to store variant genotypes and their annotations. However, VCF files are large and data retrieval is relatively slow. 'SeqArray' is a new WGS variant data format implemented in the R/Bioconductor package for storing variant calls in an array-oriented manner which provides the same capabilities as VCF, but with multiple high compression options and data access using high-performance parallel computing." }, { "input": "Is Citrobacter rodentium pathogenic?", "output": "Yes, the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases." }, { "input": "List two human monoclonal antibodies against Clostridium difficile toxins.", "output": "Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. They were shown to decrease Clostridium difficile recurrence. Bezlotoxumab was approved by the Food and Drug Administration and the European Medicines Agency for Clostridium difficile recurrence." }, { "input": "List ribosomal biogenesis proteins.", "output": "FGF13\np53\nTGF\u03b2/Activin\nPTEN\nNucleostemin\nHEATR1" }, { "input": "Which protein is regulated by Tudor interacting repair regulator (TIRR)?", "output": "Tudor interacting repair regulator (TIRR) regulates P53-binding protein 1 (53BP1) by masking its histone methyl-lysine binding function." }, { "input": "Which algorithm is used for detection of long repeat expansions?", "output": "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. For that purpose, ExpansionHunter has been developed as a software tool that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length." }, { "input": "Which brain tumors does neuroligin-3 promote?", "output": "Neuroligin-3 promotes the growth of high-grade gliomas." }, { "input": "Which web resource for LIR motif-containing proteins in eukaryotes has been developed?", "output": "In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, the iLIR database ( https://ilir.warwick.ac.uk ) has been developed as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis." }, { "input": "What is liquid liquid phase transition?", "output": "The influence of membrane-free microcompartments resulting from crowding-induced liquid/liquid phase separation (LLPS) on the dynamic spatial organization of FtsZ, the main component of the bacterial division machinery, has been studied using several LLPS systems." }, { "input": "Can CD55 deficiency cause thrombosis?", "output": "Yes, loss of CD55 is associated with thrombosis in patients with Paroxysmal nocturnal hemoglobinuria. CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55" }, { "input": "What is the approximate size of gas vesicles?", "output": "The diameter of gas vesicles is approximately 100nm." }, { "input": "Are sleep apnea and snoring associated with cardiac arrhythmias?", "output": "Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke." }, { "input": "Are osteoclasts specialized in bone degradation?", "output": "Bone degradation is caused by osteoclasts, the normal bone-resorbing cells." }, { "input": "List BET proteins.", "output": "BRD2\nBRD3\nBRD4\nBdf1" }, { "input": "Does temsirolimus improve survival of glioblastoma patients?", "output": "No. Temsirolimus does not prolong survival of gliobalstoma patients." }, { "input": "What is the proteoform?", "output": "Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes" }, { "input": "Are there sex differences in the transcriptome of the mouse hippocampus?", "output": "There are sex differences in the transcriptome of the developing mouse hippocampus." }, { "input": "How does neuronal activity affect neuroligin-3?", "output": "Neuronal activity-induces secretion of neuroligin-3." }, { "input": "What is the role of the blood-brain barrier?", "output": "The blood\u2013brain barrier (BBB) is a highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS). The blood\u2013brain barrier is formed by brain endothelial cells and it allows the passage of water, some gases, and lipid-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function." }, { "input": "Sclerostin regulates what process?", "output": "Sclerostin plays a critical role in bone homeostasis and its deficiency or pharmacological neutralization increases bone formation" }, { "input": "What is PARP inhibitor (PARPi) resistance?", "output": "PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs." }, { "input": "What is the association of the protein RAB10 and Alzheimers disease?", "output": "The genes SEC22B, RAB10 and FLT1 may be potential biomarkers of AD." }, { "input": "Does MC1R palmitoylation reduce pigmentation?", "output": "No, MC1R palmitoylation leads to increased pigmentation." }, { "input": "A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no?", "output": "Conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick, Ambyomma ameriacanum." }, { "input": "A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no?", "output": ".Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick." }, { "input": "What are pQTLs?", "output": "The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways." }, { "input": "What is Dysphoric Milk Ejection Reflex?", "output": "Dysphoric milk ejection reflex (D-MER) is characterized by an abrupt dysphoria, or undesirable feeling that occurs with the MER and continues for no more than a few minutes. After milk ejection, the dysphoria vanishes. Symptoms may decrease by 3 months or they may continue throughout the breastfeeding period." }, { "input": "Is Rucaparib effective for ovarian cancer?", "output": "Yes. Rucaparib is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has been approved for the treatment of patients with advanced ovarian cancer who have been treated with two or more chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test." }, { "input": "What is the \"protein inference problem\"?", "output": "A major challenge in shotgun proteomics has been the assignment of identified peptides to the proteins from which they originate, referred to as the protein inference problem." }, { "input": "What is the link between lithium use during pregnancy and Ebstein anomaly?", "output": "It is generally believed that lithium use is associated with increased risk of Ebstein anomaly. However, more recent studies challenge this association." }, { "input": "Does verubecestat activate BACE?", "output": "No, verubecestat is a potent BACE inhibitor." }, { "input": "What does the Ribosome-bound Quality Control complex do?", "output": "Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation." }, { "input": "What is emicizumab?", "output": "ACE910 (emicizumab) is a humanized bispecific antibody recognizing factor IXa and X mimicking factor VIII function." }, { "input": "What illness is transmitted by the Lone Star Tick, Amblyomma americanum?", "output": "Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness [STARI] or Masters disease" }, { "input": "What illness is transmitted by the Lone Star Tick, Amblyomma americanum?", "output": "Today,A americanumremains an important vector for tick-borne illness. In addition to others, species ofRickettsia,Ehrlichia, andBorreliaare all transmitted by the lone star tick. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness." }, { "input": "Which is the function of ubiquilins?", "output": "Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein degradation pathways. Ubiquilin (UBQLN) proteins are adaptors thought to link ubiquitinated proteins to the proteasome." }, { "input": "Which algorithm has been developed for prediction of protein subcellular localization using deep learning?", "output": "DeepLoc is an algorithm which has been developed for prediction of protein subcellular localization using deep learning." }, { "input": "List the continent of origin for the brown marmorated stinkbug(Halyomorpha halys)", "output": "The brown marmorated stinkbug (Halyomorpha halys) is native to Asia" }, { "input": "Please list 6 symptoms of Scarlet fever.", "output": "Symptoms of scarlet fever include fever, rash, strawberry tongue and sore throat. In some cases other symptoms, angular stomatitis, tonsular exudate, and swollen lymph nodes are seen." }, { "input": "Gallbladder carriage is a well recognised means of spread of which bacteria?", "output": "Gallbladder carriage is associated with spread of Salmonella Typhi." }, { "input": "What is included in the Mentzer index?", "output": "Mentzer index (MCV/RBC) is mean corpuscular volume (MCV) and red blood cell count (RBC) ratio. It is used for differentiation of thalassemia and iron deficiency anemia." }, { "input": "Which disease is treated with Fexinidazole?", "output": "Oral fexinidazole is effective for late-stage human african trypanosomiasis." }, { "input": "Is Tocilizumab effective for Giant-Cell Arteritis?", "output": "Yes, Tocilizumab effective for Giant-Cell Arteritis. Its efficacy was proven in clinical trials. Tocilizumab may exert its therapeutic effects in Giant-Cell Arteritis by increasing the proliferation and activation of Tregs, and by reverting the pathogenic Treg phenotype seen during active disease." }, { "input": "Is there a link between nuclear position and DNA repair pathway choice?", "output": "Yes. Nuclear position dictates DNA repair pathway choice, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus." }, { "input": "Can non ubiquitinated Tomm20 promote mitophagy?", "output": "The translocase of outer mitochondrial membrane 20 (Tomm20), is a mitochondrial translocase that, when ubiquitinated, promotes mitophagy. " }, { "input": "Does SARM1 deletion cause neurodegeneration?", "output": "Mouse strain with Sarm1 deletion (Sarm1-/-) is highly resistant to axon neurodegeneration." }, { "input": "Is DNA polymerase \u03b8 involved in DNA repair?", "output": "Yes, \tDNA polymerase \u03b8 protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks." }, { "input": "List drugs that are included in the Vosevi polypill.", "output": "Vosevi pill includes sofosbuvir, velpatasvir and voxilaprevir. It is approved by the US Food and Drug Administration (FDA) for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor; and genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor." }, { "input": "What part of what body organ controls the circadian clock?", "output": "the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes " }, { "input": "What part of what body organ controls the circadian clock?", "output": "The mammalian circadian system is composed of a hierarchical multi-oscillator structure, with the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus in the brain" }, { "input": "Which algorithms are used for compression of SAM files?", "output": "The most popular format for genomic data is the SAM (Sequence Alignment/Map) format, which contains information such as alignment, quality values, etc. These files are large (on the order of terabytes), which necessitates compression. GeneComp, NGC, SAMZIP and QVZ are algorithms which perform compression of data stored in SAM files." }, { "input": "What does MetaHIT stand for?", "output": "Metagenomics of the Human Intestinal Tract (MetaHIT) project are focusing mainly on the human microbiome" }, { "input": "List 4 drugs used to treat opioid addiction or overdose", "output": "Suboxone (buprenorphine/naloxone) and methadone are used to assist in opioid withdrawal and Naloxone is used to treat overdoses" }, { "input": "Can nanoparticles be used for afterglow imaging?", "output": "Nanoparticles are used for afterglow imaging." }, { "input": "Describe mechanism of action of Romosozumab.", "output": "Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. In the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain. It is used for osteoporosis treatment." }, { "input": "Which proteins are regulated by Nrf2?", "output": "Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes." }, { "input": "What drug cures hepatitis C?", "output": "Sofosbuvir-based therapy cures hepatitis C virus infection" }, { "input": "Is there any role of interleukin-11 in cardiovascular fibrosis?", "output": "Yes. Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli." }, { "input": "List major risk factors for Alzheimer's disease. ", "output": "Apolipoprotein E4\ntype 2 diabetes\nClusterin\nHypertension\nadvancing age\nobesity" }, { "input": "What can be predicted with the Wells criteria?", "output": "Wells criteria are used to determine clinical probability of pulmonary embolism." }, { "input": "What is the purpose of the Tabix tool?", "output": "Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions. Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access. Tabix is implemented as a free command-line tool as well as a library in C, Java, Perl and Python. It is particularly useful for manually examining local genomic features on the command line and enables genome viewers to support huge data files and remote custom tracks over networks." }, { "input": "What is the purpose of the Tabix tool?", "output": "Tabix is the first generic tool that indexes position sorted files in tab-delimited formats such as gff , bed , psl , sam and sql export , and quickly retrieves features overlapping specified regions . Tabix is implemented as a free command-line tool as well as a library in c , java , perl and python ." }, { "input": "What is MULTOVL?", "output": "MULTOVL is an application suite that detects and statistically analyses multiple overlaps of genomic regions in a fast and efficient manner. The package supports the detection of multiple region intersections, unions and 'solitary' genomic regions. The significance of actually observed overlaps is estimated by comparing them with empirical null distributions generated by random shuffling of the input regions." }, { "input": "How is Hsd17b1 associated with endometriosis?", "output": "Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis. Inhibition of the estradiol-synthesizing enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has been proposed as a promising new therapeutic option to treat estrogen-dependent diseases like endometriosis" }, { "input": "What is the drug Tecfidera used against?", "output": "Tecifidera is approved for the treatment of relapsing-remitting multiple sclerosis." }, { "input": "Is there a disease or condition called Exploding Head Syndrome?", "output": "Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions." }, { "input": "What is INCB3619?", "output": "INCB3619, is avselective, potent, orally bioavailable small-molecule inhibitor of a subset of ADAM proteases that prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. Administration of INCB3619 to tumor-bearing mice reduced ErbB ligand shedding in vivo and inhibited ErbB pathway signaling (e.g., phosphorylation of Akt), tumor cell proliferation, and survival." }, { "input": "What is crenezumab?", "output": "Crenezumab is a humanized antibody targeting Amyloid-\u03b2 (A\u03b2) which is currently tested in multiple clinical trials for the prevention of Alzheimer's disease. It strongly reacts with amyloid plaques and detects N-terminally modified A\u03b2 peptides A\u03b24-42 and pyroglutamate A\u03b23-42." }, { "input": "Describe Vanishing lung syndrome.", "output": "Vanishing lung syndrome, also known as idiopathic giant bullous emphysema, is a rare disease characterized by giant emphysematous bullae. It is a rare radiological syndrome in which the lungs appear to be disappearing on X-ray. It typically occurs in young, thin male smokers with large bullae in one or more upper lobes occupying at least one-third of the hemithorax. This syndrome is associated with significant morbidity and mortality." }, { "input": "What do the trispecific HIV antibodies target?", "output": "Trispecific HIV antibodies (Abs) allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site." }, { "input": "What is calciphylaxis", "output": "Calcific uraemic arteriolopathy also known as calciphylaxis is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis." }, { "input": "What is calciphylaxis", "output": "Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis." }, { "input": "What is the alternative lengthening of telomeres?", "output": "Alternative lengthening of telomeres (ALT) is a telomerase independent telomere maintenance mechanism that occurs in \u223c15% of cancers. It is proposed to occur preferentially at telomeric lagging strands leading to heterogeneous telomere lengths observed in most ALT cancers." }, { "input": "Which organ express and secretes the hormone FGF21?", "output": "Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue." }, { "input": "What is the biological role of Neddylation?", "output": "NEDDylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation. It however has its own enzyme machinery. It is coupled to ubiquitination and is important for maintaining cellular homeostasis." }, { "input": "What is the biological role of Neddylation?", "output": "Neddylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation.Proteins in the neddylation pathway have also been linked to regulating ddr.Blocking neddylation could be a novel strategy for mitigating immune-mediated disease processes." }, { "input": "What is the biological role of Neddylation?", "output": "Neddylation is a process that is similar to ubiquitination. Proteins in the neddylation pathway have also been linked to regulating DDR. Neddylation plays an important role in the regulation of murine and human dendritic cell function. NEDDylation is a post-translational protein modification that is tightly linked to ubiquitination and thereby protein degradation. Utilizing multiple but complementary approaches, we determined the role of an important but less understood type of PTM, namely, neddylation, in regulating DC functions. It is coupled to ubiquitination and is important for maintaining cellular homeostasis. " }, { "input": "What is break induced replication?", "output": "Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases." }, { "input": "What is a fibrocyte?", "output": "Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. Fibrocytes are circulating mesenchymal precursors (CD45+, col 1+) recruited to fibrotic areas." }, { "input": "Which cellular functions are affected by lncRNA H19 in the heart?", "output": "H19 could inhibit autophagy in cardiomyocytes by epigenetically silencing of DIRAS3. Elevated H19 promotes apoptosis through PA2G4. Downregulation of H19 promotes proliferation and inhibits apoptosis. H19 induces mineralization of valve interstitial cells. H19 contributes to cardiac fibroblast proliferation and fibrosis, which act in part through repression of DUSP5/ERK1/2." }, { "input": "Dinutuximab is used for treatment of which disease?", "output": "Dinutuximab, a monoclonal antibody against disialoganglioside, is used for treatment of high-risk neuroblastoma." }, { "input": "What is the ChIP-exo method used for?", "output": "Precise Identification of DNA-Binding Proteins Genomic Location by Exonuclease Coupled Chromatin Immunoprecipitation (ChIP-exo)." }, { "input": "What is the ChIP-exo method used for?", "output": "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. " }, { "input": "What is the ChIP-exo method used for?", "output": "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background. Precise Identification of DNA-Binding Proteins Genomic Location by Exonuclease Coupled Chromatin Immunoprecipitation (ChIP-exo)." }, { "input": "What is the ChIP-exo method used for?", "output": "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy." }, { "input": "What is the ChIP-exo method used for?", "output": "ChIP-exo is a molecular biology method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy." }, { "input": "What is the ChIP-exo method used for?", "output": "ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background." }, { "input": "What is the ChIP-exo method used for?", "output": "ChIP-exo allows identification of a nearly complete set of the binding locations of DNA-binding proteins at near-single-nucleotide resolution with almost no background. The key distinction of the ChIP-exo methodology is the incorporation of lambda exonuclease digestion in the library preparation workflow to effectively footprint the left and right 5' DNA borders of the protein-DNA crosslink site. " }, { "input": "Where do mitochondrial DNA deletion breakpoints tend to occur?", "output": "Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures." }, { "input": "Where do mitochondrial DNA deletion breakpoints tend to occur?", "output": "Non-B DNA conformations are a key element of the mtDNA deletion process and most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. Current findings suggest that mitochondrial G-quadruplexes are also likely to be a source of instability for the mitochondrial genome by perturbing the normal progression of the mitochondrial replication machinery, including DNA unwinding by Twinkle helicase." }, { "input": "Where do mitochondrial DNA deletion breakpoints tend to occur?", "output": "n this work, we performed a computational analysis of the human mitochondrial genome using the \"Pattern Finder\" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints." }, { "input": "Where do mitochondrial DNA deletion breakpoints tend to occur?", "output": "Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys. Most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. N this work, we performed a computational analysis of the human mitochondrial genome using the \"Pattern Finder\" G-quadruplex to known mitochondrial DNA deletion breakpoints. " }, { "input": "Name 4 circular RNA molecules associated with carcinogenesis.", "output": "circ-ABCB10 knockdown suppressed the proliferation and increased apoptosis of breast cancer cells.\nHsa_circ_0058246 was elevated in tumor specimens of patients with poor clinical outcomes.\nCirc-FBXW7 expression positively associated with glioblastoma patient overall survival.\nciRS-7 promotes the development of cancer by acting as sponge of miR-7." }, { "input": "Which is the enzymatic activity of nardilysin?", "output": "Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins." }, { "input": "The Mantoux test detects what latent infection/disease?", "output": "screened for TB infection with a Mantoux tuberculin skin testtuberculin skin test (TST) performed according to the Mantoux method." }, { "input": "The Mantoux test detects what latent infection/disease?", "output": "screened for TB infection with a Mantoux tuberculin skin test " }, { "input": "The Mantoux test detects what latent infection/disease?", "output": "The Mantoux tuberculin skin test tests for latent tuberculosis" }, { "input": "The Mantoux test detects what latent infection/disease?", "output": "screened for TB infection with a Mantoux tuberculin skin test. " }, { "input": "What is measured with the Proseek panels?", "output": "Differnet Proseek multiplex protein biomarker panels exists: CVD, inflammatory, neurology and oncology biomarker." }, { "input": "Is Enlimomab effective for stroke treatment?", "output": "No. Anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in and may significantly worsen stroke outcome." }, { "input": "Are AAV vectors considered for the treatment of retinal dystrophies?", "output": "Yes, AAV vectors are considered for the treatment of retinal dystrophies." }, { "input": "Does International Citicoline Trial on acUte Stroke trial supports efficacy of citicoline for stroke treatment?", "output": "No. The International Citicoline Trial on acUte Stroke (ICTUS) found that citocoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke." }, { "input": "Is human lysyl oxidase-like 2 a glycoprotein?", "output": "Yes, human lysyl oxidase-like 2 is a glycoprotein." }, { "input": "Can GDF15 be a biomarker for metformin treatment?", "output": "Yes, GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin." }, { "input": "Has rituximab been considered as a treatment for chronic fatigues syndrome? (November 2017)", "output": "The use of rituximab may be of benefit for CFS/ME, but the evidence of its effectiveness is still limited." }, { "input": "Does oncogene-induced DNA replication stress inhibit genomic instability?", "output": "No, oncogene-induced DNA replication stress is thought to drive genomic instability." }, { "input": "Is the petrous bone used in ancient DNA sampling?", "output": "Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are currently recognized as the best substrates for such research." }, { "input": "Is recursive splicing more common in short introns?", "output": "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing." }, { "input": "Is recursive splicing more common in short introns?", "output": "Together, these results indicate that recursive splicing is commonly used in Drosophila, occurs in humans, and provides insight into the mechanisms by which some large introns are removed. " }, { "input": "Is recursive splicing more common in short introns?", "output": "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together Cutting a Long Intron Short: Recursive Splicing and Its Implications." }, { "input": "Is recursive splicing more common in short introns?", "output": "Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing. It is more common in large/long introns." }, { "input": "Is recursive splicing more common in short introns?", "output": "Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns > 20 kb , but they are found only at the expected frequency on the antisense strands , and they are underrepresented within introns < 10 kb.Using a computational analysis of the genomic sequences , we show that vertebrates lack the proper enrichment of rp-sites in their large introns , and , therefore , require some other method to aid splicing." }, { "input": "Is recursive splicing more common in short introns?", "output": "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together" }, { "input": "Is Lysyl oxidase crosslinking collagen?", "output": "Yes, lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions." }, { "input": "Is sternotomy closure done using either a sternal ZipFix\u2122 implant or conventional steel wire following cardiac surgery?", "output": "Yes, closure of the sternum following cardiac surgery can be done using a wire closure or sternal ZipFix\u2122 a cable-tie-based system which is fast, easy to use, reliable and safe." }, { "input": "Is transcription of eRNA bidirectional?", "output": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e." }, { "input": "Is transcription of eRNA bidirectional?", "output": "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers A richer picture has taken shape, integrating transcription of coding genes, enhancer RNAs (eRNAs), and various other noncoding transcriptional events." }, { "input": "Is transcription of eRNA bidirectional?", "output": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)." }, { "input": "Is transcription of eRNA bidirectional?", "output": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). A richer picture has taken shape, integrating transcription of coding genes, enhancer RNAs (eRNAs), and various other noncoding transcriptional events." }, { "input": "Is transcription of eRNA bidirectional?", "output": "XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers" }, { "input": "Is transcription of eRNA bidirectional?", "output": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). " }, { "input": "Is the protein pelota a ribosomal rescue factor?", "output": "Yes, in eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation." }, { "input": "Is CXCL7 a chemokine?", "output": "Yes, CXCL7 is a chemokine highly expressed in platelets. " }, { "input": "The TRPM2 gene is associated with development of spontaneous thromboembolism?", "output": "TheTransientReceptorPotentialMelastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel andAdenosine 5'-DiphosPhataseRibose (ADPR) hydrolase function. TRPM2 is involved in Ca2+signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis and may regulate the bacteriocidal activity of Macrophages" }, { "input": "Is a mutation of the ZIKV's membrane protein prM responsible for the microcephaly in new-born infants?", "output": "Yes, a single mutation in the prM protein of Zika virus contributes to fetal microcephaly." }, { "input": "What is the aim of the PhenCode database?", "output": "PhenCode (Phenotypes for ENCODE; http://www.bx.psu.edu/phencode) is a collaborative, exploratory project to help understand phenotypes of human mutations in the context of sequence and functional data from genome projects." }, { "input": "What is the basis of the Sp3 procedure used in proteomics?", "output": "SP3, a novel technology for proteomic sample preparation using magnetic beads. SP3 provides a rapid and unbiased means of proteomic sample preparation in a single tube that facilitates ultrasensitive analysis by outperforming existing protocols in terms of efficiency, scalability, speed, throughput, and flexibility." }, { "input": "What is \"enhancer hijacking\"?", "output": "Enhancer hijacking is the molecular process through which a structural variant removes or moves a TAD boundary to expose TSSs to regulatory enhancers from which they would normally be insulated." }, { "input": "What disease is tinea ?", "output": "Tinea is a superficial fungal infections of the skin." }, { "input": "How are deletion breakpoints defined?", "output": "Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster. We identified 18 deletion breakpoints at the DNA nucleotide sequence level. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats." }, { "input": "How are deletion breakpoints defined?", "output": "We identified 18 deletion breakpoints at the DNA nucleotide sequence level. Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster. In this study, we investigated the deletion breakpoints of the parkin mutations in 22 families with AR-JP and examined the possible association between these deletion events and meiotic recombinations. he hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats." }, { "input": "How are deletion breakpoints defined?", "output": "Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. A promising new workflow relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation." }, { "input": "How are deletion breakpoints defined?", "output": "Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. " }, { "input": "How are deletion breakpoints defined?", "output": "We identified 18 deletion breakpoints at the DNA nucleotide sequence level. Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster." }, { "input": "How is the nuclear localization of lncRNA mediated?", "output": "The lncRNA localization to the nucleus can be mediated by the pentamer sequence AGCCC." }, { "input": "What is ATAC-seq?", "output": "The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was recently established as a method to profile open chromatin, which overcomes the sample size limitations of the alternative methods DNase/MNase-seq." }, { "input": "What is ATAC-seq?", "output": "ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. " }, { "input": "What is ATAC-seq?", "output": "An assay for transposase-accessible chromatin using sequencing (ATAC-seq) is based on in vitro transposition of sequencing adaptors into native chromatin. It is described as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution." }, { "input": "What is the TALE-iD method used for?", "output": "TALE-iD is a methylation-based method for the study of native chromatin structure." }, { "input": "What is the TALE-iD method used for?", "output": "Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, \"TALE-iD\", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions." }, { "input": "What is the TALE-iD method used for?", "output": "Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, \"TALE-iD\", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topologically associating domain restrictions. " }, { "input": "What is Paget's Disease?", "output": "Paget's disease of bone (PDB) is a\u00a0noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. " }, { "input": "What is Paget's Disease?", "output": "Paget's disease of bone interferes with your body's normal recycling process, in which new bone tissue gradually replaces old bone tissue. Over time, the disease can cause affected bones to become fragile and misshapen. Mammary Paget's disease and extramammary Paget's disease are neoplastic conditions, in which there is intraepithelial (usually intraepidermal) infiltration by neoplastic cells showing glandular differentiation." }, { "input": "What is Paget's Disease?", "output": "Paget's disease of bone (PDB) is a\u00a0noninflammatory, metabolic, skeletal disorder characterized by localized excessive osteoclastic bone resorption that is followed by compensatory increased osteoblastic activity leading to unstructured, fibroblastic, and biomechanically unstable bone. As a\u00a0result, there is deformity and enlargement of the bone with a\u00a0defective and disorganized pattern." }, { "input": "What is the function of penicillinase, also known as beta lactamase?", "output": "Beta-lactamases are a family of serine enzymes that hydrolyse beta-lactam antibiotics following an acylation-deacylation mechanism." }, { "input": "The common house cat, Felis silvestris catus and the domestic dog, Canis familiaris both belong to what taxonomic order?", "output": "Domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora. " }, { "input": "The common house cat, Felis silvestris catus and the domestic dog, Canis familiaris both belong to what taxonomic order?", "output": "The common house cat and domestic dog both belong to the order Carnivora in the class Mammalia" }, { "input": "The common house cat, Felis silvestris catus and the domestic dog, Canis familiaris both belong to what taxonomic order?", "output": "domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora. " }, { "input": "The common house cat, Felis silvestris catus and the domestic dog, Canis familiaris both belong to what taxonomic order?", "output": "domestic dogs and cats can be interpreted in terms of their descent from members of the order Carnivora." }, { "input": "What is caused by the ectopic expression of CTCF?", "output": "ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;" }, { "input": "What is caused by the ectopic expression of CTCF?", "output": "Enforced ectopic expression of CTCF inhibits cell growth in culture. ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;" }, { "input": "What is caused by the ectopic expression of CTCF?", "output": "Ectopic expression of CTCF results in severe cell growth inhibition at multiple points within the cell cycle." }, { "input": "What is caused by the ectopic expression of CTCF?", "output": "ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage;. " }, { "input": "What is caused by the ectopic expression of CTCF?", "output": "Enforced ectopic expression of CTCF inhibits cell growth in culture." }, { "input": "What is the dardarin protein?", "output": "Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson\u00b4s disease," }, { "input": "In which syndrome is the RPS19 gene most frequently mutated?", "output": "Ribosomal protein S19 (RPS19), currently the only gene associated with DBA, is mutated in 25% of DBA patients, but its role in erythropoiesis is unknown. " }, { "input": "In which syndrome is the RPS19 gene most frequently mutated?", "output": "Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands. Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families." }, { "input": "In which syndrome is the RPS19 gene most frequently mutated?", "output": "Among these patients, RPS19 was the most frequently mutated gene. It has been proven that defects of ribosomal proteins can lead to this disease and that RPS19 is the most frequently mutated gene in DBA patients. Mutations in the ribosomal protein S19 gene (RPS19) have been found in 25% of patients with Diamond-Blackfan anemia, a rare syndrome of congenital bone marrow failure characterized by erythroblastopenia and various malformations. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated similar alterations of large ribosomal subunit rRNA in both RPL35A-mutated and some RPL35A wild-type patients, suggesting additional large ribosomal subunit gene defects are likely present in some cases of DBA. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. Recent reports show that the ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA." }, { "input": "In which syndrome is the RPS19 gene most frequently mutated?", "output": "The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups." }, { "input": "In which syndrome is the RPS19 gene most frequently mutated?", "output": "Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families. Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands." }, { "input": "What type of sequences do enhancers evolve from?", "output": "Studies have identified enhancers that were pivotal for morphological divergence and highlighted how novel genetic networks shaping form emerged from pre-existing ones.Most of the recently evolved enhancers arise from ancestral dna exaptation , rather than lineage-specific expansions of repeat elements." }, { "input": "What type of sequences do enhancers evolve from?", "output": "Recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements." }, { "input": "What type of sequences do enhancers evolve from?", "output": "Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. The sequences of some gene regulatory elements diverge considerably, even between closely related species. " }, { "input": "What type of sequences do enhancers evolve from?", "output": "The trend is one of high divergence of cis-regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements." }, { "input": "What nerve is involved in carpal tunnel syndrome?", "output": "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the median nerve at the level of the wrist." }, { "input": "What nerve is involved in carpal tunnel syndrome?", "output": "Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel." }, { "input": "What nerve is involved in carpal tunnel syndrome?", "output": "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the median nerve at the level of the wrist. " }, { "input": "What is the function of LOX proteins in the ECM?", "output": "Lysyl oxidases (LOX) are copper-dependent enzymes that oxidize primary amine substrates to reactive aldehydes. The best-studied role of LOX enzymes is the remodeling of the extracellular matrix (ECM) in animals by cross-linking collagens and elastin" }, { "input": "Please list 3 diseases treated with Valtrex(valacyclovir)", "output": "Valtrex (valacyclovir) is an antiviral medication used to treat infections with: herpes zoster (shingles), herpes simplex genitalis (genital herpes),\nand herpes labialis (cold sores)." }, { "input": "Which olfactory gene senses androsterone?", "output": "A previously reported association between the olfactory receptor or7d4 and the androstenone was not detected until we specifically typed this gene p = 1.1 \u00d7 10 -4.Any mammals can decipher these scent codes to discern the gender , age , endocrine status , social status , and genotype of conspecifics using dedicated sensory receptors in their olfactory system." }, { "input": "Which olfactory gene senses androsterone?", "output": "These findings suggest that 1) the perceived intensity of some but not all odorants is a heritable trait, 2) use of a current genome-wide marker panel did not detect a known olfactory genotype-phenotype association, and 3) person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes. A previously reported association between the olfactory receptor OR7D4 and the androstenone was not detected until we specifically typed this gene (P = 1.1 \u00d7 10(-4)). any mammals can decipher these scent codes to discern the gender, age, endocrine status, social status, and genotype of conspecifics using dedicated sensory receptors in their olfactory system. " }, { "input": "Which olfactory gene senses androsterone?", "output": "Person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes." }, { "input": "Which olfactory gene senses androsterone?", "output": "These findings suggest that 1) the perceived intensity of some but not all odorants is a heritable trait, 2) use of a current genome-wide marker panel did not detect a known olfactory genotype-phenotype association, and 3) person-to-person differences in androstenone perception are influenced by OR7D4 genotype and perhaps by variants of other genes. " }, { "input": "Where in the body would the navicular bone be found?", "output": "The navicular bone is located in the foot" }, { "input": "Name an lncRNA associated with dilated cardiomyopathy.", "output": "The lncRNA H19 is significantly upregulated in the myocardial tissue in dilated cardiomyopathy." }, { "input": "Which gene is responsible for red hair?", "output": "Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans." }, { "input": "Which gene is responsible for red hair?", "output": "Red hair is the null phenotype of MC1R. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. " }, { "input": "Which gene is responsible for red hair?", "output": "Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair." }, { "input": "Which gene is responsible for red hair?", "output": "Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR." }, { "input": "Which bacteria was EcoRI, restriction endonuclease isolated from?", "output": "Among hundreds of restriction endonucleases, the Eco R1 enzyme is the most useful and widely investigated enzyme and was isolated from E. coli RY 13" }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis. The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. " }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade." }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis." }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "It is an increasing cause of infection in immunosuppressed patients with aids in the united kingdom are known to have developed cryptococcosis. It is an increasing cause of infection in immunosuppressed patients, most notably those with hiv infection. It is an increasing cause of infection with cryptococcus neoformans has increased four-fold in the last decade. " }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection." }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis." }, { "input": "Which is the main reason for the increase in the incidence of cryptococcal disease?", "output": "The incidence of infection with Cryptococcus neoformans has increased four-fold in the last decade. It is an increasing cause of infection in immunosuppressed patients, most notably those with HIV infection. Currently, 4.0% patients with AIDS in the United Kingdom are known to have developed cryptococcosis. " }, { "input": "Which genes are responsible for the high-altitude adaptation of Tibetans?", "output": "Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. A gene (HMOX2) involved in heme catabolism, harbors potentially adaptive variants in Tibetans." }, { "input": "Which genes are responsible for the high-altitude adaptation of Tibetans?", "output": "Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions. Two functional loci in the promoter of EPAS1 gene involved in high-altitude adaptation of Tibetans." }, { "input": "Which genes are responsible for the high-altitude adaptation of Tibetans?", "output": "EGLN1 (or HIFPH2, MIM 606425) and EPAS1 (or HIF2A, MIM 603349), both related to hypoxia-inducible factor, were found most differentiated in the two regions, respectively. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions." }, { "input": "Which genes are responsible for the high-altitude adaptation of Tibetans?", "output": "Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. " }, { "input": "Which is the main protein in brown adipose tissue (BAT) active in thermogenesis?", "output": "Uncoupling protein 1 (UCP1) is the hallmark protein responsible for cold- and diet-induced thermogenesis in brown adipose tissue (BAT)." }, { "input": "Which method is Proseek based on?", "output": "proximity extension immunoassay" }, { "input": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "output": "Association studies suggest that the low activity variant of the monoamine oxidase A (MAOA)-uVNTR polymorphism confers risk for emotional disturbances associated with antisocial traits, particularly in males. These include antisocial and borderline personality disorders and antisocial aggression." }, { "input": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "output": "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits. The interaction of the low activity variant of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been shown to predict aggression in clinical and non-clinical populations Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in Borderline Personality Disorder." }, { "input": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "output": "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits. " }, { "input": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "output": "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits. Monoamine oxidase a gene is associated with borderline personality disorder. Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder." }, { "input": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "output": "Monoamine oxidase A (MAOA) gene has an important role in the regulation of neurotransmitter levels and a large number of human behaviors. For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans. The purpose of the present study was to examine whether a cumulative genetic score (CGS) containing the monoamine oxidase A (MAOA) and the human serotonin transporter gene linked polymorphism (5-HTTLPR) was associated with IPV perpetration after accounting for the effects of alcohol problems, drug problems, age, and length of relationship. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences." }, { "input": "With which personality traits has the human monoamine oxidase A (MAOA) gene been associated?", "output": "Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits." }, { "input": "What is the function of HDAC proteins?", "output": "Histone deacetylases influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms. Histone deacetylases prevent the relaxation of chromatin, and positively or negatively regulate transcription. " }, { "input": "What is the function of HDAC proteins?", "output": "Histone deacetylases (HDACs) prevent the relaxation of chromatin, and positively or negatively regulate transcription and thus cellular processes" }, { "input": "What is the H4S47C cleavage mapping method used for?", "output": "To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions. To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome." }, { "input": "What is the H4S47C cleavage mapping method used for?", "output": "H4S47C-anchored cleavage mapping reveals the precise position of histone H4 in every nucleosome in the genome." }, { "input": "What is the H4S47C cleavage mapping method used for?", "output": " To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome." }, { "input": "What is the H4S47C cleavage mapping method used for?", "output": "To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing. " }, { "input": "What is the H4S47C cleavage mapping method used for?", "output": "To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions." }, { "input": "What is the H4S47C cleavage mapping method used for?", "output": "To map fission yeast centromeres, we applied H4S47C-anchored cleavage mapping and native and cross-linked chromatin immunoprecipitation with paired-end sequencing." }, { "input": "Which human gene encode for DNA polymerase \u03b8?", "output": "DNA polymerase theta (pol \u03b8) is an evolutionarily conserved protein encoded by the POLQ gene in mammalian genomes" }, { "input": "In what percentage of skeletal muscle fibers is dystrophin expression restored after PPMO- mediated exon skipping?", "output": "PPMO-mediated exon skipping restored the dystrophin expression in nearly 100% skeletal muscle fibers in all age groups." }, { "input": "Which miRNA is associated with the circular RNA ciRS-7?", "output": "circular RNA-7 (ciRS-7) acts as a sponge of miR-7 and thus inhibits its activity." }, { "input": "Which are the two main bacterial phyla in human gut?", "output": "Out of thousands of bacterial species-level phylotypes inhabiting the human gut, the majority belong to two dominant phyla, the Bacteroidetes and Firmicutes" }, { "input": "What are 7 symptoms of yellow fever?", "output": "Yellow fever is considered to be a hemorrhagic fever and illness is characterized by fever, headache, myalgia, gastrointestinal symptoms, hepatic and renal dysfunction, multi-organ failure, shock and coagulopathy." }, { "input": "Which test is used for the definition of colour-blindness?", "output": "Color-blindness problems are detected by the Ishihara Test." }, { "input": "Which test is used for the definition of colour-blindness?", "output": "12 patients had color blindness based on the Ishihara test" }, { "input": "Which test is used for the definition of colour-blindness?", "output": "12 patients had color blindness based on the Ishihara test. " }, { "input": "Of what origin is the MCF-7 cell line?", "output": "MCF7 is an ER+ breast cancer cell line." }, { "input": "Is lumican a secreted protein?", "output": "Yes, Lumican is a secreted proteoglycan that regulates collagen fibril assembly." }, { "input": "Cytochrome p450 CYP3A is induced by rifampicin and compounds used to treat what virus?", "output": "Etravirine is an effective and well-tolerated recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV type-1-infected patients with previous antiretroviral treatment experience. Etravirine is a weak inducer of cytochrome P450 (CYP)3A" }, { "input": "Cytochrome p450 CYP3A is induced by rifampicin and compounds used to treat what virus?", "output": "Four CYP3A inducers were used: rifampicin, rifabutin, carbamazepine, and efavirenz Etravirine is an effective and well-tolerated recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV type-1-infected patients with previous antiretroviral treatment experience." }, { "input": "Which human chromosome is the product of fusion?", "output": "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2. We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. " }, { "input": "Which human chromosome is the product of fusion?", "output": "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2." }, { "input": "Which human chromosome is the product of fusion?", "output": "Origin of human chromosome 2: an ancestral telomere-telomere fusion." }, { "input": "Which human chromosome is the product of fusion?", "output": "Human chromosome 2 originated from the fusion of two ancestral primate chromosomes." }, { "input": "Which human chromosome is the product of fusion?", "output": "Origin of human chromosome 2: an ancestral telomere-telomere fusion. It is known that human chromosome 2 originated from the fusion of two ancestral primate chromosomes. " }, { "input": "Which human chromosome is the product of fusion?", "output": "The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2. " }, { "input": "Where is the EpCam protein mainly located?", "output": "Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein" }, { "input": "What is the drug target for Eliquis (Apixaban)?", "output": "The new oral anticoagulants (NOAC) Apixaban (Eliquis) is a direct anti-Xa inhibitors" }, { "input": "What in vivo tau tracers are being used?", "output": "in-vivo tau PET imaging ligands include [(18)F]THK523, [(18)F]THK5117, [(18)F]THK5105 and [(18)F]THK5351, [(18)F]AV1451(T807) [(11)C]PBB3, (18)F-THK5117, [(18)F]T808, 18F-RO6958948." }, { "input": "What is the Formalin test used for?", "output": "And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. " }, { "input": "What is the Formalin test used for?", "output": "And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test." }, { "input": "What is the Formalin test used for?", "output": "Persistent pain, In vivo antinociceptive activity, is produced by peripheral tissue injury and inflammation and is modeled by formalin test." }, { "input": "What drug treatment can cause a spinal epidural hematoma?", "output": "Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit. Spontaneous SEH is related to minor trauma, bleeding disorders, and anticoagulant medications." }, { "input": "What drug treatment can cause a spinal epidural hematoma?", "output": "Spinal epidural hematomas are rare entity in neurosurgery practice. Most of them are spontaneous due to anticoagulant therapy and called spontaneous spinal epidural hematomas (SSEHs)." }, { "input": "What drug treatment can cause a spinal epidural hematoma?", "output": "Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit.pinal subdural hematoma associated with antiplatelet therapy" }, { "input": "List diseases caused by protein glutamine expanded repeats", "output": "Huntington's Disease,\ndentatorubral-pallidoluysian atrophy" }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment." }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence." }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level" }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells." }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence." }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level" }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. " }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. " }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level." }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level" }, { "input": "What is the nucleotide composition of the Lamin Associated Domains (LADs)?", "output": "Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Cell-type specific LADs also tend to adhere to this \"A/T rule\" in embryonic stem cells, but not in differentiated cells. " }, { "input": "What is the clathrin triskelia structure?", "output": "The clathrin triskelion, which is a three-legged pinwheel-shaped heteropolymer, is a major component in the protein coats of certain post-Golgi and endocytic vesicles." }, { "input": "What is myelin?", "output": "Myelin is a specialized structure of the nervous system that covers the neuron and both enhances electrical conductance and insulates neurons from external risk factors." }, { "input": "Is Brucella abortus the organism that causes brucillosis known to cause spontaneous abortions in humans?", "output": "Human brucellosis symptoms and clinical signs most commonly reported are fever, fatigue, malaise, chills, sweats headaches, myalgia, arthralgia, and weight loss. Some cases have been presented with only joint pain, lower backache, and involuntary limb movement, burning feet, or ischemic heart attacks." }, { "input": "What percentage of Homo sapiens DNA is of Neanderthal origin?", "output": "We find that the power to reject ancient admixture might be particularly low if the population size of Homo sapiens was comparable to the Neanderthal population size. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe." }, { "input": "What percentage of Homo sapiens DNA is of Neanderthal origin?", "output": "Approximately 2-4% of genetic material in human populations outside Africa is derived from Neanderthals who interbred with anatomically modern humans. 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe." }, { "input": "What percentage of Homo sapiens DNA is of Neanderthal origin?", "output": "Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans." }, { "input": "What percentage of Homo sapiens DNA is of Neanderthal origin?", "output": "3.6 % of the neanderthal genome is shared with roughly 65.4 % of the average european gene pool , which clinally diminishes with distance from europe.This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought." }, { "input": "What is Dupuytren's contracture?", "output": "Dupuytren's contracture is a progressive hand condition that affects how much you can move or straighten your fingers. It is a benign fibroproliferative disease leads to hyperplasia of the collagen fibers of the fascia of the palm, which can result in severe impairment of the functionality of the hand." }, { "input": "What phenotype is associated with the V60L mutation in the human MC1R gene?", "output": "The characterization of the melanocortin 1 receptor (MC1R) expressed on human melanocytes and the findings that certain mutations in the POMC gene or the MC1R gene result in red hair phenotype underscore the significance of melanocortins and MC1R in regulating human pigmentation. We describe a minisequencing protocol for screening DNA samples for the presence of 12 mutations in the human melanocortin 1 receptor gene (MC1R), eight of which are associated with the red hair phenotype. The human MC1R gene is highly polymorphic and certain allelic variants of the gene are associated with red hair phenotype, melanoma and non-melanoma skin cancer. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. These loss-of-function mutations have been associated with red hair phenotype and increased risk for skin cancer. Alleles associated with the red hair color (RHC) phenotype and with the risk of melanoma were examined." }, { "input": "What phenotype is associated with the V60L mutation in the human MC1R gene?", "output": "Red hair is usually inherited as a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA and 537insC alleles at this locus. The V60L variant, which is common in the population may act as a partially penetrant recessive allele. V60L is a mutation also associated to red hair and fair skin and even blonde hair." }, { "input": "What phenotype is associated with the V60L mutation in the human MC1R gene?", "output": "The V60L variant, which is common in the population may act as a partially penetrant recessive allele. Both of these Thr(111)/Ala(111) heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant) different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair) Genetic association and cellular function of MC1R variant alleles in human pigmentation." }, { "input": "List proteins with HEAT repeats", "output": "mTOR,\nTOG5, \nDNA-PKcs,\nHEATR1,\nRif1,\nB56\u03b3,\nPR65/A,\nSF3b155,\nPds5B" }, { "input": "What is the aim of perfoming a \"cycloheximide chase assay\"?", "output": "Comparison of protein stability in eukaryotic cells has been achieved by cycloheximide, which is an inhibitor of protein biosynthesis due to its prevention in translational elongation. It is broadly used in cell biology in terms of determining the half-life of a given protein and has gained much popularity in cancer research." }, { "input": "What is an exosome?", "output": "Exosomes are a subset of extracellular vesicles (EVs) that have important roles in intercellular communication. They contain and carry bioactive molecules within their membranes which are delivered to target cells." }, { "input": "Are human enhancers or promoters evolving faster?", "output": "Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. " }, { "input": "Are human enhancers or promoters evolving faster?", "output": "We report that rapid evolution of enhancers is a universal feature of mammalian genomes." }, { "input": "Are human enhancers or promoters evolving faster?", "output": "Rapid evolution of enhancers is a universal feature of mammalian genomes." }, { "input": "What are the 3 antidotes for anticoagulant (anti-blood clotting) drugs, including factor Xa inhibitors, as of November 2017.", "output": " two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015." }, { "input": "What are the 3 antidotes for anticoagulant (anti-blood clotting) drugs, including factor Xa inhibitors, as of November 2017.", "output": " two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015. Idarucizumab and andexanet alfa have been reported to produce anticoagulation reversal effects within minutes of administration. " }, { "input": "What are the 3 antidotes for anticoagulant (anti-blood clotting) drugs, including factor Xa inhibitors, as of November 2017.", "output": "Two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase." }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "In one family studied, inheritance of EBS is linked to the gene encoding keratin 14" }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency." }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "In one family studied, inheritance of EBS is linked to the gene encoding keratin 14 Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14." }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14." }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "Keratin 5 and keratin 14 are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of epidermolysis bullosa simplex. Homozygous deletion mutations in the plectin gene in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. The KRT5 and KRT14 genes encode the proteins keratin 5 and 14, respectively, which are the primary structural components of the 10-nm intermediate filaments of the mitotic epidermal basal cells. Epidermolysis bullosa simplex is mainly caused by mutations in the KRT5 and KRT14 genes. Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene. This is the first report of EBS-generalized intermediate in a newborn with de novo KRT5 gene mutation and KRT14 gene polymorphism, and no familial history of epidermolysis. Study of a family with epidermolysis bullosa simplex resulting from a novel mutation of KRT14 gene. We have systematically scanned genomic sequences of one of these keratins, keratin 14, for mutations in patients from 49 apparently independent kindreds using single-strand conformation polymorphism analysis. " }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene." }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "Recent advances in molecular biology have enabled the association of epidermolysis bullosa simplex (EBS) with point mutations of keratin 14 and/or keratin 5 genes to be established. " }, { "input": "Which genes are associated with Epidermolysis Bullosa Simplex?", "output": "Keratin 14 gene mutations in patients with epidermolysis bullosa simplex. Mutant keratins 5 or 14 are implicated in the etiology of epidermolysis bullosa simplex (EBS). Keratin 14 gene point mutation in the K\u00f6bner and Dowling-Meara types of epidermolysis bullosa simplex as detected by the PASA method." }, { "input": "What biologic process in the body is associated with Mast cells?", "output": "Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. " }, { "input": "What biologic process in the body is associated with Mast cells?", "output": "Mast cells are significantly involved in IgE-mediated allergic reactions but may be involved in defense against parasites as well as other immune mediated diseases including heart disease" }, { "input": "What biologic process in the body is associated with Mast cells?", "output": "Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa" }, { "input": "What are the 3 types of ultraviolet (UV) solar radiation?", "output": "Solar ultraviolet (UV) radiation, an ubiquitous environmental carcinogen, is classified depending on the wavelength, into three regions; short-wave UVC (200-280 nm), mid-wave UVB (280-320 nm), and long-wave UVA (320- 400 nm)" }, { "input": "What are the 3 types of ultraviolet (UV) solar radiation?", "output": "short-wave UVC (200-280 nm), medium-wave UVB (280-320 nm), and long-wave UVA (320-400 nm)." }, { "input": "What are the 3 types of ultraviolet (UV) solar radiation?", "output": "short-wave UVC (200-280 nm), medium-wave UVB (280-320 nm), and long-wave UVA (320-400 nm). " }, { "input": "Please list 10 conditions which play a role in causing atrial fibrillation.", "output": "Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Multiple conditions like hypertension, heart failure, diabetes, sleep apnoea, hyperthyroidism and obesity play a role for the initiation and perpetuation of AF. Other possible causes are alcohol and drug use and atrial ischemia. Risk of AF increases with age." }, { "input": "Is p53 a transcription factor?", "output": "Yes, p53 is a sequence-specific transcription factor." }, { "input": "Is Cystatin D a biomarker?", "output": "Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury" }, { "input": "What causes leishmaniasis?", "output": "Leishmania spp. is a group of very successful protozoan parasites that cause a range of diseases from self-healing cutaneous leishmaniasis to visceral leishmaniasis." }, { "input": "Please list 7 classes of drugs that interact with Warfarin.", "output": "The number of drugs reported to interact with warfarin continues to expand. There are reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, protease inhibitors, amiodarone, fluorouracil, psychotropics, and oral corticosteroids." }, { "input": "Please list 7 classes of drugs that interact with Warfarin.", "output": "Seven drugs/drug classes (ibuprofen, morphine, warfarin, bupropion, paroxetine, rosiglitazone, ACE inhibitors) with known ADEs were selected to evaluate the system. This study was aimed to determine the prevalence of drug-related problems (DRPs), identify the most common drugs, and drug classes involved in DRPs as well as associated factors with the occurrence of DRPs.A prospective cross-sectional study was conducted on 225 patients admitted to medical wards of Tikur Anbessa Specialized Hospital, Addis Ababa from March to June 2014. Analysis of the data showed that albumin possesses a single strong binding site for warfarin with an association constant of 154,000 at 3 degrees C and secondary classes of several sites with a much lower affinity. Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). Drugs such as gentamycin, warfarin, nifedipine, and cimetidine have the highest probability of causing DRP. Drugs with the highest drug risk ratio were gentamycin, warfarin, nifedipine, and cimetidine. The drugs most frequently causing a DRP were angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, diuretics, warfarin, spironolactone, and \u03b2-blockers." }, { "input": "What part of the body is affected by mesotheliomia?", "output": "Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall." }, { "input": "What part of the body is affected by mesotheliomia?", "output": "Malignant pleural mesothelioma (MPM) is a hard to treat malignancy arising from the mesothelial surface of the pleura. " }, { "input": "What part of the body is affected by mesotheliomia?", "output": "Malignant pleural mesothelioma (MPM) is a hard to treat malignancy arising from the mesothelial surface of the pleura." }, { "input": "What is BORSA?", "output": "Borderline oxacillin-resistant Staphylococcus aureus is also known as (BORSA)" }, { "input": "What is BORSA?", "output": "Borderline oxacillin-resistant Staphylococcus aureus (BORSA)" }, { "input": "What is BORSA?", "output": "Borderline oxacillin-resistant Staphylococcus aureus (BORSA). " }, { "input": "Which gene is responsible for proper speech development?", "output": "Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech." }, { "input": "Which gene is responsible for proper speech development?", "output": "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation." }, { "input": "Which gene is responsible for proper speech development?", "output": "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development." }, { "input": "Which gene is responsible for proper speech development?", "output": "Transcription factor forkhead box protein p2 plays an essential role in the development of language and speech.The key regulator for language and speech development , foxp2 , is a novel substrate for sumoylation." }, { "input": "Which gene is responsible for proper speech development?", "output": "The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation. Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech." }, { "input": "What is PNPPP?", "output": "personally normalized plasma protein profiles (PNPPP)" }, { "input": "What is Mendelian randomization?", "output": "Instrumental variable analysis is an approach for obtaining causal inferences on the effect of an exposure (risk factor) on an outcome from observational data. It has gained in popularity over the past decade with the use of genetic variants as instrumental variables, known as Mendelian randomization." }, { "input": "What does the pembrolizumab companion diagnostic test assess?", "output": "Administration of pembrolizumab requires a companion diagnostic test, to assess PD-L1 status of patients." }, { "input": "What is the combined effect of Nfat and miR-25?", "output": "Increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium." }, { "input": "In what states are GDF15 expression increased?", "output": "Growth differentiation factor 15 (GDF-15) is expressed and secreted in response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation." }, { "input": "Which genomic positions are preferentially selected for transposon insertion?", "output": "Preferential integration occurs in non-coding DNA and heterochromatin. A preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was also observed." }, { "input": "Which Lisp framework has been developed for image processing?", "output": "FunImageJ is a Lisp framework for scientific image processing built upon the ImageJ software ecosystem. The framework provides a natural functional-style for programming, while accounting for the performance requirements necessary in big data processing commonly encountered in biological image analysis." }, { "input": "Which gene controls the consistency of cerumen (ear wax)?", "output": "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent Our findings also reveal that ABCC11 genotype alone does not predict the type and relative levels of volatiles found in human cerumen, and suggest that other biochemical pathways must be involved" }, { "input": "Which gene controls the consistency of cerumen (ear wax)?", "output": "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent" }, { "input": "Which gene controls the consistency of cerumen (ear wax)?", "output": "A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent ABCC11 encodes an ATP-driven efflux pump protein that plays an important function in ceruminous apocrine glands of the auditory canal and the secretion of axillary odor precursors." }, { "input": "Which gene controls the consistency of cerumen (ear wax)?", "output": "Recent studies link a single nucleotide polymorphism (SNP) in the adenosine triphosphate (ATP) binding cassette, sub-family C, member 11 gene (ABCC11) to the production of different types of axillary odorants and cerumen. ABCC11 encodes an ATP-driven efflux pump protein that plays an important function in ceruminous apocrine glands of the auditory canal and the secretion of axillary odor precursors." }, { "input": "What is the origin of human breast milk bacteria?", "output": "It is believed that certain bacteria from the maternal gastrointestinal tract could translocate through a mechanism involving mononuclear immune cells, migrate to the mammary glands via an endogenous cellular route (the bacterial entero-mammary pathway), and subsequently colonize the gastrointestinal tract of the breast-fed neonate" }, { "input": "Which species is the carrier of the SFTS ( severe fever with thrombocytopenia syndrome) virus?", "output": "The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in Haemaphysalis longicornis at all developmental stages. Tick-derived sequences shared over 95.6% identity with human- and animal-derived isolates. This study provides evidence that implicates ticks as not only vectors but also, reservoirs of SFTSV." }, { "input": "Which species is the carrier of the SFTS ( severe fever with thrombocytopenia syndrome) virus?", "output": "Seroprevalence in animal species were: goats (66.8%), cattle (28.2%), dogs (7.4%), pigs (4.7%), chickens (1.2%), geese (1.7%), rodents (4.4%) and hedgehogs (2.7%). The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in H. longicornis at all developmental stages. Tick-derived sequences shared over 95.6% identity with human- and animal-derived isolates." }, { "input": "Which species is the carrier of the SFTS ( severe fever with thrombocytopenia syndrome) virus?", "output": "The possibility that SFTSV transmission may occur by both the transstadial and transovarial routes was suggested by the fact that viral RNA was detected in H. longicornis at all developmental stages. Severe fever with thrombocytopenia syndrome (SFTS) is a new emerging zoonosis." }, { "input": "List four features of the WHIM syndrome.", "output": "The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4." }, { "input": "Which algorithm has been developed for the automatic extraction of co-expressed gene clusters from gene expression data?", "output": "Clust is a method for automatic extraction of optimal co-expressed gene clusters from gene expression data. Clust is available at https://github.com/BaselAbujamous/clust." }, { "input": "Which bacteria are enriched in the gut microbiome of infants following exposure to fury pets?", "output": "Pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus in infants." }, { "input": "List the main PPI databases.", "output": "PPIM,\nHPRD,\nSTRING,\nDAPID,\nMIPS,\nINTERACT,\nBioGRID" }, { "input": "Is Baloxavir effective for influenza?", "output": "Yes. Baloxavir is approved for influenza A or B virus infections." }, { "input": "Which member of the human mycobiota is associated to atherosclerosis?", "output": "Mucor racemosus is negatively associated with carotid atherosclerosis" }, { "input": "List intramembrane rhomboid peptidases", "output": "PARL\nPcp1\nhiGlpG\necGlpG\nYqgP" }, { "input": "Where is the protein Bouncer located?", "output": "Bouncer is membrane bound." }, { "input": "How many genes in S. cerevisiae are the result of an ancient whole genome duplication?", "output": "The two genomes subsequently converged onto similar current sizes (5,600 protein-coding genes each) and independently retained sets of duplicated genes that are strikingly similar. Almost half of their surviving single-copy genes are not orthologs but paralogs formed by WGD, as would be expected if most gene pairs were resolved independently." }, { "input": "Which intoxication is associated with Burton's line?", "output": "Burton's line is characteristic for lead poisoning." }, { "input": "Which tool has been developed for coverage calculation for genomes?", "output": "Mosdepth is a command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM or CRAM files at either each nucleotide position in a genome or for sets of genomic regions. Genomic regions may be specified as either a BED file to evaluate coverage across capture regions, or as a fixed-size window as required for copy-number calling. Mosdepth uses a simple algorithm that is computationally efficient and enables it to quickly produce coverage summaries." }, { "input": "Which tool has been developed for coverage calculation for genomes?", "output": "Mosdepth is a new command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM or CRAM files at either each nucleotide position in a genome or for sets of genomic regions." }, { "input": "Which type of sarcoma has been associated with members of the oral microbiome?", "output": "Alterations in the oral microbiota in the immunosuppressed population may be associated with diseases such as Kaposi's sarcoma." }, { "input": "Which complex is bound by estrogen-related receptor \u03b2 (Esrrb)?", "output": "Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells." }, { "input": "Which complex is bound by estrogen-related receptor \u03b2 (Esrrb)?", "output": "Knockdown of Mp1 redirected FGF4 signaling from differentiation toward pluripotency and up-regulated the pluripotency-related genes Esrrb, Rex1, Tcl1, and Sox2. Dax1 associates with Esrrb and regulates its function in embryonic stem cells. Here, we identified an orphan nuclear receptor, Esrrb (estrogen-related receptor beta), as a Dax1-interacting protein." }, { "input": "Which approach was used to diagnose a patient with Cutis Verticis Gyrata-Intellectual Disability (CVG-ID) syndrome?", "output": "Magnetic Resonance Imaging (MRI)" }, { "input": "Cemiplimab is used for treatment of which cancer?", "output": "Cemiplimab is a PD-1 inhibitor that is approved for treatment of metastatic or locally advanced cutaneous squamous cell carcinoma." }, { "input": "Which cancer has the kynureninase pathway been associated to?", "output": "The kynurenine pathway has been associated with human glioma pathophysiology." }, { "input": "Which organs are mostly affected in Systemic Lupus Erythematosus (SLE)?", "output": "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. The heart is one of the most frequently affected organs in SLE. Skin is one of the most commonly affected organs in SLE. Other affected organs in SLE-AAC included hematologic system (11, 84.6%), followed by mucocutaneous (seven, 53.8%), musculoskeletal (seven, 53.8%) and neuropsychiatric (two, 15.4%) systems." }, { "input": "Which organs are mostly affected in Systemic Lupus Erythematosus (SLE)?", "output": "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. The heart is one of the most frequently affected organs in SLE. Skin is one of the most commonly affected organs in SLE" }, { "input": "Which organs are mostly affected in Systemic Lupus Erythematosus (SLE)?", "output": "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. The heart is one of the most frequently affected organs in SLE. Any part of the heart can be affected, including the pericardium, myocardium, coronary arteries, valves, and the conduction system" }, { "input": "Which organs are mostly affected in Systemic Lupus Erythematosus (SLE)?", "output": "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs." }, { "input": "What is a GPI anchor?", "output": "Glycosylphosphatidylinositol (GPI) anchoring of proteins is a conserved posttranslational modification in the endoplasmic reticulum (ER). \tGlycosylphosphatidylinositols (GPIs) are lipid anchors allowing the exposure of proteins at the outer layer of the plasma membrane." }, { "input": "In which way does DNA hydroxymethylation affect patients with Systemic Lupus Erythematosus?", "output": "DNA hydroxymethylation contributes to the aberrant regulation of genes transcription in the pathogenesis of SLE. A combined analysis of differential DNA hydroxymethylation profile and gene expression profile in SLE CD4(+) T cells, shows 131 genes with increased 5-hmC in promoter regions and up-regulated expression in SLE CD4(+) T cells compared with healthy controls, including selected immune-related genes, i.e. SOCS1, NR2F6 and IL15RA." }, { "input": "In which way does DNA hydroxymethylation affect patients with Systemic Lupus Erythematosus?", "output": "Altered DNA methylation and hydroxymethylation as well as histone modifications mediate changes in chromatin accessibility and gene expression in immune cells from SLE patients. 5-Hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine suspected to be an important epigenetic modification in embryonic development, cell differentiation and cancer." }, { "input": "What is the function of PAPOLA/PAP?", "output": "Poly(A)polymerase-alpha (PAPOLA) has been the most extensively investigated mammalian polyadenylating enzyme, mainly in regard to its multifaceted post-translational regulation. PolyA polymerase (PAP) adds a polyA tail onto the 3'-end of RNAs without a nucleic acid template, using adenosine-5'-triphosphate (ATP) as a substrate." }, { "input": "List 3 diseases for which saRNAs have been evaluated as a potential treatment.", "output": "saRNAs have been tested for the treatment of breast, bladder, liver cancer and more." }, { "input": "What is the mechanism of action of Brigatinib?", "output": "Brigatinib targets anaplastic lymphoma kinase. It is used for treatment of lung cancer (NSCLC)." }, { "input": "Which database associates human noncoding SNPs with their three-dimensional interacting genes?", "output": "3DSNP is a database for linking human noncoding SNPs to their three-dimensional interacting genes. It a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes." }, { "input": "In which phase of clinical trials was sutezolid in 2018?", "output": "By 2018 sutezolid had been evaluated in phase II clinical trials." }, { "input": "What is gingipain?", "output": "Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors, and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly)." }, { "input": "For which disease is sutezolid developed?", "output": "Sutezolid is being developed as a treatment against tuberculosis." }, { "input": "What does gepotidacin do to bacteria?", "output": "Gepotidacin inhibits bacterial DNA replication." }, { "input": "What is the role of fucokinase?", "output": "FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases." }, { "input": "Are there microbes in human breast milk?", "output": "Yes, human milk is a rich source of diverse bacteria." }, { "input": "Is cariprazine effective for treatment of bipolar disorder?", "output": "Yes, cariprazine is effective for bipolar disorder." }, { "input": "Is Bobble head doll syndrome associated with hydrocephalus?", "output": "Yes, Bobble head doll syndrome is associated with obstructive hydrocephalus." }, { "input": "Can breastfeeding confer protection from type I diabetes?", "output": "In the neonate and infant lactation confers protection from future type 1 diabetes." }, { "input": "Can pets affect infant microbiomed?", "output": "Yes, exposure to household furry pets influences the gut microbiota of infants." }, { "input": "Is there any association between the human gut microbiome and depression?", "output": "Scientific findings are suggestive of the possibility that dysregulation of the enteric microbiota (i.e., dysbiosis) and associated bacterial translocation across the intestinal epithelium may be involved in the pathophysiology of stress-related psychiatric disorders, particularly depression." }, { "input": "Are whole-genome duplications more divergent than small-scale duplications in yeast?", "output": "Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts." }, { "input": "Do yeast LTR give rise to circular DNA?", "output": "A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements. Circular retrotransposition products are generated by a LINE retrotransposon. Yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs). Circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence." }, { "input": "Is cohesin linked to myeloid differentiation?", "output": "Yes. There has been a link found between cohesin and myeloid differentiation which may help explain the prevalence of cohesin mutations in human acute myeloid leukemia." }, { "input": "Is pembrolizumab effective against Ewing's sarcoma?", "output": "None of the 13 patients with Ewing's sarcoma receiving pembrolizumab had an objective response." }, { "input": "Can gene therapy restore auditory function?", "output": "Yes, gene therapy can restore auditory function." }, { "input": "Is the PINES framework being used for the prediction of coding variants?", "output": "No. PINES (Phenotype-Informed Noncoding Element Scoring) predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest." }, { "input": "Is erythropoietin effective for treatment of amyotrophic lateral sclerosis?", "output": "No, erythropoietin is not effective for treatment of amyotrophic lateral sclerosis." }, { "input": "Is celecoxib effective for treatment of amyotrophic lateral sclerosis?", "output": "No. In clinical trial celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in ALS were not recommended." }, { "input": "What is hemolacria?", "output": "Hemolacria is a rare phenomenon of bloody tears caused by various ocular and systemic conditions, as well as psychological, pharmacologic, and idiopathic etiologies." }, { "input": "Are ultraconserved enhancers important for normal development?", "output": "Yes, ultraconserved enhancers are required for normal development." }, { "input": "Is chlorotoxin a peptide?", "output": "Yes" }, { "input": "Does vesatolimod inhibit TLR7?", "output": "No, vesatolimod is an agonist of toll-like receptor 7." }, { "input": "Is selenocysteine an aminoacid?", "output": "Yes" }, { "input": "Is Tecovirimat effective for smallpox?", "output": "Yes, tecovirimat FDA approved for treatment of smallpox." }, { "input": "Can simvastatin alleviate depressive symptoms?", "output": "Yes, simvastatin decreases depressive symptoms." }, { "input": "Is P. gingivalis bacteria found in brain?", "output": "Yes" }, { "input": "Is ibudilast effective for multiple sclerosis?", "output": "Yes, Ibudilast was shown to be effective for progressive multiple sclerosis. In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression." }, { "input": "Does gepotidacin activate bacterial topoisomerase?", "output": "No, gepotidacin is a bacterial topoisomerase inhibitor." }, { "input": "What is the 3D genome browser?", "output": "The 3D Genome Browser, http://3dgenome.org, allows users to conveniently explore both their own and over 300 publicly available chromatin interaction data of different types. The browser provides multiple methods linking distal cis-regulatory elements with their potential target genes. Users can seamlessly integrate thousands of other omics data to gain a comprehensive view of both regulatory landscape and 3D genome structure." }, { "input": "Are gut proteobacteria associated with inflammatory disease?", "output": "The onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear." }, { "input": "What brain procedure can be done using the NeuroBlate system?", "output": "NeuroBlate System is used for Laser interstitial thermal therapy." }, { "input": "Describe genomiser", "output": "Genomiser is an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases. Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to discover variants associated to specific Mendelian disorders. Genomiser is able to identify causal regulatory variants as the top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease." }, { "input": "Which ultraconserved element is associated with Embryonic Stem Cells (ESC) self-renewal?", "output": "Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. A lncRNA containing the uc.170+, named T-UCstem1, was identified with in vitro and in vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics." }, { "input": "What is TPMCalculator?", "output": "The quantification of RNA sequencing (RNA-seq) abundance using a normalization method that calculates transcripts per million (TPM) is a key step to compare multiple samples from different experiments. TPMCalculator is a one-step software to process RNA-seq alignments in BAM format and reports TPM values, raw read counts and feature lengths for genes, transcripts, exons and introns. The program describes the genomic features through a model generated from the gene transfer format (GTF) file used during alignments reporting of the TPM values and the raw read counts for each feature." }, { "input": "Describe clinical presentation of Escobar syndrome.", "output": "The Escobar variant of multiple pterygium syndrome (MPS) is a rare, autosomal recessive disorder which is characterized by pterygia, arthrogryposis (joint contractures), facial dysmorphism along with other anomalies." }, { "input": "What is small-activating RNA?", "output": "small activating RNAs are double stranded RNAs (dsRNAs) that target gene promoters and trigger gene activation." }, { "input": "What is the mechanism of action of Ivosidenib?", "output": "Ivosidenib is an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models. It is effective for IDH1-mutant relapsed/refractory acute myeloid leukemia." }, { "input": "Which is the basis of the ATAC-Seq protocol?", "output": "This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position. The method is a fast and sensitive alternative to DNase-seq for assaying chromatin accessibility genome-wide, or to MNase-seq for assaying nucleosome positions in accessible regions of the genome." }, { "input": "Which is the basis of the ATAC-Seq protocol?", "output": "ATAC-Seq probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position." }, { "input": "Which is the basis of the ATAC-Seq protocol?", "output": "This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription-factor binding and nucleosome position." }, { "input": "What is vcfanno?", "output": "Vcfanno flexibly extracts and summarizes attributes from multiple annotation files and integrates the annotations within the INFO column of the original VCF file. Substantial performance gains are reported by annotating ~85,000 variants per second with 50 attributes from 17 commonly used genome annotation resources. Vcfanno is available at https://github.com/brentp/vcfanno under the MIT license." }, { "input": "What is the association of Disease-Associated STRs (daSTRs) with domain boundaries?", "output": "Nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains. For instance, Fragile X syndrome patients exhibit severe boundary disruption in a manner that correlates with local loss of CTCF occupancy and the degree of FMR1 silencing." }, { "input": "What is the link between ultraconserved elements and three-dimensional mammalian genome organization?", "output": "Ultraconserved elements (UCEs) occupy specific arenas of three-dimensional mammalian genome organization. UCEs are enriched within contact domains and, further, that the subset of UCEs within domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither overrepresented nor underrepresented, but those present in loop anchors are enriched for splice sites. As the relationships between UCEs and human Hi-C features are conserved in mouse, UCEs contribute to interspecies conservation of genome organization and, thus, genome stability." }, { "input": "What are the \"Ohnologs\"?", "output": "Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation." }, { "input": "What are the \"Ohnologs\"?", "output": "Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs -paralogous gene pairs generated by whole genome duplication- are enriched for dosage sensitive genes, that is, genes that have a phenotype due to copy number changes" }, { "input": "What are the \"Ohnologs\"?", "output": "Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation." }, { "input": "What is TissueEnrich?", "output": "TissueEnrich is a tool that calculates tissue-specific gene enrichment in an input gene set. TissueEnrich can assign tissue identities to single cell clusters and differentiated embryonic stem cells." }, { "input": "Describe OligoSTORM", "output": "OligoSTORM and OligoDNA-PAINT meld the Oligopaint technology for fluorescent in situ hybridization (FISH) with, respectively, Stochastic Optical Reconstruction Microscopy (STORM) and DNA-based Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) to enable in situ single-molecule super-resolution imaging of nucleic acids. Both strategies enable \u226420 nm resolution and are appropriate for imaging nanoscale features of the genomes of a wide range of species, including human, mouse, and fruit fly (Drosophila)." }, { "input": "Which metabolic pathways have been associated with Systemic Lupus Erythematosus?", "output": "Genetic polymorphisms of the xenobiotic metabolic pathway involved in estrogen metabolism might contribute towards pathophysiology of systemic lupus erythematosus (SLE). According to the analysis on metabolic pathway, SLE could cause significant changes in unsaturated fatty acid and amino acid metabolism pathway. Results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism" }, { "input": "What are the 3 main bacteria found in human milk?", "output": "Human milk is rich in diverse bacteria, particularly Staphylococcus, Streptococcus and Pseudomonas genera." }, { "input": "Which algorithm has been developed for trio-based benchmarking of variant calls?", "output": "Geck is a tool for trio-based comparative benchmarking tool of variant calls. It is a statistical mixture model for comparing two variant calling pipelines from genotype data they produce after running on individual members of a trio." }, { "input": "Which molecule is targeted by Caplacizumab?", "output": "Caplacizumab is anti-von Willebrand factor (VWF) antibody that blocks the interaction between VWF and platelets. It is used for treatment of acquired thrombotic thrombocytopenic purpura (aTTP)." }, { "input": "In which tissues is the lincRNA Xist expressed?", "output": "Relative expression of X-linked genes was examined in liver, kidney and brain tissue by real-time PCR in adult XX(Y)* and XY* males and XX females. X-chromosome inactive specific transcript (Xist) was expressed only in female adipose tissue. X-chromosome inactive specific transcript (Xist) was expressed only in female adipose tissue. It was also expressed in duodenum and testis." }, { "input": "Which is the main component of the Lewy body?", "output": "Lewy bodies comprise of aggregated intracellular vesicles and proteins and \u03b1-synuclein is reported to be a major protein component." }, { "input": "What forms part of the senescence associated secretory phenotype, or SASP?", "output": "The diverse arrays of proteins secreted by senescent cells have been described to influence aging and to have both pro-tumorigenic and anti-tumorigenic influences on the surrounding microenvironment. Further characterization of these proteins, known as the senescence-associated secretory phenotype (SASP), and their regulators is required to understand and further manipulate such activities. The senescence-associated secretory phenotype (SASP) is characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A." }, { "input": "What forms part of the senescence associated secretory phenotype, or SASP?", "output": "Numerous activities of senescent cells depend on the aptitude of these cells to secrete myriads of bioactive molecules, a behavior termed the senescence-associated secretory phenotype (SASP) The SASP supports cell-autonomous functions like the senescence-associated growth arrest, and mediates paracrine interactions between senescent cells and their surrounding microenvironment. Cultures enriched with not-diploid cells acquired a senescence-associated secretory phenotype (SASP) characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and other pro-inflammatory factors including a novel SASP component CLEC11A." }, { "input": "How many pseudogenes are contained in the C. elegans genome?", "output": "Evidence suggests that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data. Thus out of 18000 transcripts, around 3500 are expected to be pseudogenes." }, { "input": "How many pseudogenes are contained in the C. elegans genome?", "output": "Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes The remaining explanation is that most of the annotated genes in the recently duplicated category are pseudogenes, a proportion corresponding to 20% of all of the annotated C. elegans genes At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data" }, { "input": "How many pseudogenes are contained in the C. elegans genome?", "output": "Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes" }, { "input": "What is a Aquaporin channel?", "output": "Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics." }, { "input": "What is cluster of differentiation?", "output": "Cluster of Differentiation (CD) are cellular antigens used to identify cell populations, such as T-lymphocyte populations and macrophages." }, { "input": "List two medication included in the Juluca pill.", "output": "Juluca\u00ae pill includes dolutegravir and rilpivirine. It is the first two-drug single-tablet regimen (STR) to be approved for the treatment of HIV-1 infection in adults." }, { "input": "Which tool has been developed for tagging biomedical concepts via interactive learning?", "output": "ezTag is a web-based annotation tool that supports annotating a wide variety of biological concepts with or without pre-existing training data. It allows curators to perform annotation and provide training data with humans in the loop. ezTag supports both abstracts in PubMed and full-text articles in PubMed Central. It also provides lexicon-based concept tagging as well as the state-of-the-art pre-trained taggers such as TaggerOne, GNormPlus and tmVar. ezTag is freely available at http://eztag.bioqrator.org." }, { "input": "Which cells produce Interleukin 17A?", "output": "Interleukin (IL)-17A is secreted from T helper type 17 (TH17) cells." }, { "input": "Is durvalumab used for lung cancer treatment?", "output": "Yes, Durvalumab is an anti-PDL-1 antibody that is used for treatment of non-small-cell lung cancer." }, { "input": "Is LRP1 interacting with Urokinase receptor?", "output": "Yes" }, { "input": "Is obesity related to cognitive decline?", "output": "Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions. Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance." }, { "input": "Describe the mechanism of action of ibalizumab.", "output": "Ibalizumab is a humanized monoclonal antibody that acts as post-attachment inhibitor by binding CD4 2nd domain of T lymphocyte and preventing HIV connection to CCR5 or CXCR4. It has been recently approved by Food and Drug Administration as a new intravenous antiretroviral agent for heavily treated HIV adults with multi -drug resistant infection." }, { "input": "Describe information obtained by immunophenotyping.", "output": "Mass cytomety enables comprehensive single-cell immunophenotyping and functional assessments, capturing the complexity of the immune system, and the molecularly heterogeneous consequences of primary immunodeficiency defects.\nCirculating B, T, and dendritic cells were defined using flow cytometric analysis as recommended by the Human Immunology Project Consortium.\nClinical applications of flow cytometry currently utilized in the laboratory include cell surface antigen determinations or immunophenotyping of hematologic cells, DNA analysis of hematopoietic malignancies and solid tumors, and measurement of CD4 (T helper/inducer cell) absolute counts and T helper/T suppressor (CD4/CD8) ratios in the evaluation of immune deficiency." }, { "input": "What is the mechanism of action of Emicizumab?", "output": "Emicizumab (Hemlibra\u00ae) is a bispecific humanized monoclonal antibody that restores the function of missing activated FVIII by bridging activated FIX and FX to facilitate effective haemostasis in patients with haemophilia A." }, { "input": "What is the genetic cause of Roberts syndrome?", "output": "Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2." }, { "input": "What is DiseaseEnhancer?", "output": "DiseaseEnhancer is a manually curated resource of human disease-associated enhancer catalog. As of July 2017, DiseaseEnhancer includes 847 disease-associated enhancers in 143 human diseases. Database features include basic enhancer information (i.e. genomic location and target genes); disease types; associated variants on the enhancer and their mediated phenotypes (i.e. gain/loss of enhancer and the alterations of transcription factor bindings)." }, { "input": "Is Tisagenlecleucel effective for B-Cell Lymphoma?", "output": "Yes, CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma." }, { "input": "What is the function of GFRAL?", "output": "GFRAL (orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor \u03b1 family) is a high-affinity receptor for GDF15.\nGFRAL expression is limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism." }, { "input": "What is the role of ZCCHC17?", "output": "ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease. Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. Its loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets." }, { "input": "Is ADP-ribosylation a PTM?", "output": "Yes,\nPoly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses." }, { "input": "Does epidural anesthesia for pain management during labor affect the Apgar score of the the infant?", "output": "Epidural analgesia for labor pain management did not appear to have an immediate effect on neonatal status as determined by Apgar scores or in admissions to neonatal intensive care." }, { "input": "What is latex bead phagocytosis?", "output": "Macrophage scavenger function was assessed by an in vitro latex bead phagocytosis assay.\nWe developed a scanning cytometry-based high-throughput assay of macrophage phagocytosis that quantitates bound and internalized unopsonized latex beads." }, { "input": "Is phospholipid hydroperoxide glutathione peroxidase a selenoprotein?", "output": "Yes,\nthe phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) is the major selenoprotein." }, { "input": "Describe CGmapTools", "output": "CGmapTools improves the precision of heterozygous SNV calls and supports allele-specific methylation detection and visualization in bisulfite-sequencing data." }, { "input": "Describe CGmapTools", "output": "DNA methylation is important for gene silencing and imprinting in both plants and animals. Recent advances in bisulfite sequencing allow detection of single nucleotide variations (SNVs) achieving high sensitivity, but accurately identifying heterozygous SNVs from partially C-to-T converted sequences remains challenging. CGmapTools is a software package that integrates 40 applications with the aim to analyze DNA methylomes. This package uses CGmap as the format interface, and designs binary formats to reduce the file size and support fast data retrieval, and can be applied for context-wise, gene-wise, bin-wise, region-wise and sample-wise analyses and visualizations." }, { "input": "Is inositol effective for trichotillomania?", "output": "No, inositol is not effective for trichotillomania" }, { "input": "How is the Regulatory Trait Concordance (RTC) calculated?", "output": "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. After stringently testing for a shared causal variant using both the Joint Likelihood Mapping and Regulatory Trait Concordance frameworks, we found that gene-level quantification significantly underestimated the number of causal cis-eQTLs. We have adapted the regulatory trait concordance (RTC) score to measure the probability of eQTLs being active in multiple tissues and to calculate the probability that a GWAS-associated variant and an eQTL tag the same functional effect." }, { "input": "How is the Regulatory Trait Concordance (RTC) calculated?", "output": "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs." }, { "input": "How is the Regulatory Trait Concordance (RTC) calculated?", "output": "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. After stringently testing for a shared causal variant using both the Joint Likelihood Mapping and Regulatory Trait Concordance frameworks, we found that gene-level quantification significantly underestimated the number of causal cis-eQTLs." }, { "input": "How is the Regulatory Trait Concordance (RTC) calculated?", "output": "Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. We have adapted the regulatory trait concordance (RTC) score to measure the probability of eQTLs being active in multiple tissues and to calculate the probability that a GWAS-associated variant and an eQTL tag the same functional effect." }, { "input": "What is filipin staining used for?", "output": "Intracellular and total cholesterol (TC) were measured using filipin staining." }, { "input": "Is TIAM1 favoring tumor progression in colorectal cancer (CRC)?", "output": "No. In colorectal cancer (CRC) TIAM1 suppresses tumor progression by regulating YAP/TAZ activity." }, { "input": "Which database has been developed that contains experimentally-confirmed carbonylated proteins?", "output": "Protein carbonylation, a chemically diverse oxidative post-translational modification, is widely considered as the biomarker for oxidative stress and protein damage. CarbonylDB has been developed as a manually curated data-resource of experimentally-confirmed carbonylated proteins/sites. The CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species." }, { "input": "What is the function of the Nup153 protein?", "output": "Nup153 is a large (153 kD) O-linked glyco-protein which is a component of the basket structure located on the nucleoplasmic face of nuclear pore complexes. Nup153 is a nucleoporin mediating nuclear import. In addition to being important to pore architecture, Nup153 is a key participant in both import and export. During the transition into mitosis, Nup153 directs proteins involved in membrane remodeling to the nuclear envelope." }, { "input": "Is pacritinib effective for treatment of myelofibrosis?", "output": "Yes. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in myelofibrosis with minimal myelosuppression." }, { "input": "How can PEGylation improve recombinant drugs?", "output": "PEGylation primarily improves pharmacokinetics and helps to prevent adverse drug reactions, by increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes." }, { "input": "Can exposure to heavy metals like lead(Pb) or cadmium(Cd) cause changes in DNA methylation patterns in Isoetes sinensis?", "output": "Changes in DNA methylation of the endangered plant, Isoetes sinensis, have be shown to be affected by both Pb and Cd" }, { "input": "Describe GeneCodeq", "output": "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. Its model leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods. GeneCodeq can be combined with existing lossy compression schemes to further reduce entropy and allows the user to specify a reference panel of expected sequence variations to improve the model accuracy." }, { "input": "Has Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) been reported to be a plasminogen receptor in pathogenic bacteria?", "output": "Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been reported to be a plasminogen receptor in many pathogenic bacteria." }, { "input": "Which de novo truncating mutations in WASF1 cause intellectual disability?", "output": "De novo truncating mutations in WAS protein family member 1 (WASF1) were identified in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling." }, { "input": "Can CPX-351 be used for the treatment of tuberculosis?", "output": "No, CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML)." }, { "input": "Which proteins form the nuclear pore basket in human cells?", "output": "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription. The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins" }, { "input": "Which proteins form the nuclear pore basket in human cells?", "output": "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Here we show that the NPC basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription." }, { "input": "Which proteins form the nuclear pore basket in human cells?", "output": "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. The nuclear pore complex basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer. The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins." }, { "input": "Which proteins form the nuclear pore basket in human cells?", "output": "Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. Here we show that the NPC basket proteins Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion into the lipid bilayer The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins" }, { "input": "Does lucatumumab bind to CD140?", "output": "No, lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC)." }, { "input": "What is the mechanism of action of arimoclomol?", "output": "Arimoclomol is a heat shock protein co-inducer that promotes nascent protein folding. It enhances the ability of differentiated neurons to survive heat shock." }, { "input": "What are the effects of STEF depletion?", "output": "The mechanisms regulating the actin cap are currently poorly understood. STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap." }, { "input": "Please list symptoms of measles.", "output": "The leading symptoms of the disease are high fever that presents after an incubation period of 9-10 days and the red rash that begins several days after the fever starts. Beyond specific generalized symptoms, measles may have ocular symptoms. The most commonly occuring satellite symptoms are conjunctivitis, coryza and cough." }, { "input": "Does simvastatin improve outcomes of aneurysmal subarachnoid hemorrhage?", "output": "No. Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal subarachnoid hemorrhage. Patients with aneurysmal subarachnoid hemorrhage should not be treated routinely with simvastatin during the acute stage." }, { "input": "Which databases can exchange data using Matchmaker Exchange's API?", "output": "Matchmaker Exchange (MME) was created to establish a federated network connecting databases of genomic and phenotypic data using a common application programming interface (API). To date, seven databases can exchange data using the API: GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching." }, { "input": "Is pazopanib an effective treatment of glioblastoma?", "output": "No. Pazopanib does not improve survival of glioblastoma patients." }, { "input": "What is the purpose of the Ottawa Ankle Rule?", "output": "Ottawa Ankle Rules is a clinical decision tool used to minimize unnecessary radiographs in ankle and foot injuries. It shows the areas of tenderness to be evaluated in ankle trauma patients to determine the need for imaging." }, { "input": "What is CIBERSORT used for?", "output": "CIBERSORT is a versatile computational method for characterizing cell composition of complex tissues from their gene expression profiles." }, { "input": "What is CIBERSORT used for?", "output": "We recently described CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs)." }, { "input": "Are de novo mutations in regulatory elements responsible for neurodevelopmental disorders?", "output": "Yes. De novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. It is estimated that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism." }, { "input": "Which molecule is targeted by Olaratumab?", "output": "Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-\u03b1 (PDGFR\u03b1). It is used for treatment of soft tissue sarcoma." }, { "input": "What is PANDAS disease?", "output": "PANDAS stands for (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and has been suggested to be a result of a disordered immune response following an infection causing neuropsychiatric symptoms." }, { "input": "Are phagosomal proteins ubiquitinated?", "output": "Yes,\nPhagosomal proteins are ubiquitylated, and ubiquitylation was found to be required for formation of acidic multivesicular structures." }, { "input": "A herd immunity of what percentage of the population is required to prevent sporadic outbreaks?", "output": "A herd immunity of 95% of the population is required to prevent sporadic outbreaks." }, { "input": "Does tremelimumab improve survival of mesothelioma patients?", "output": "No. Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma." }, { "input": "Can enasidenib be used for the treatment of acute myeloid leukemia?", "output": "Yes, enasidenib has been approved for the treatment of adults with relapsed and refracctory acture myelogenous leukemia with an IDH2 mutation." }, { "input": "What membrane proteins constitute TAM family of receptor tyrosine kinases (RTKs)?", "output": "Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs)." }, { "input": "What membrane proteins constitute TAM family of receptor tyrosine kinases (RTKs)?", "output": "TAM-family RTKs AXL and Mer (MerTK)." }, { "input": "What are the effects of the deletion of all three Pcdh clusters (tricluster deletion) in mice?", "output": "Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly. The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdh\u03b1, Pcdh\u03b2, and Pcdh\u03b3). Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance." }, { "input": "What are the effects of the deletion of all three Pcdh clusters (tricluster deletion) in mice?", "output": "The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdh\u03b1, Pcdh\u03b2, and Pcdh\u03b3). Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance." }, { "input": "What is CPX351?", "output": "CPX-351, a novel liposomal formulation which encapsulates cytarabine and daunorubicin in 5:1 molar ratio, has shown promising efficacy, leading to recent US FDA approval for front-line therapy for patients with therapy-related AML and AML with myelodysplasia-related changes based on a large multicenter Phase III clinical trial." }, { "input": "Is collagen the most abundant human protein?", "output": "Yes, collagen is the most abundant protein family in mammals." }, { "input": "What micro-RNAs are useful in the diagnosis and prognosis of Heart Failure?", "output": "In particular, miR-214, miR-423-5p, appear to be promising for the diagnosis, prognosis and management of HF patients." }, { "input": "What is ivosidenib?", "output": "AG-120 (ivosidenib) ia an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity." }, { "input": "List proteins interacting with Star-PAP", "output": "Phosphorylation regulates the Star-PAP-PIPKI\u03b1 interaction and directs specificity toward mRNA targets.\nStar-PAP directly associated with cleavage and polyadenylation specificity factor (CPSF) 160 and 73 subunits and also the targeted pre-mRNA.\nwe show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability." }, { "input": "Describe symptoms of the Visual snow syndrome.", "output": "Visual snow (VS) is a constant visual disturbance described as flickering dots occupying the entire visual field. Recently, it was characterized as the defining feature of a VS syndrome (VSS), which includes palinopsia, photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus." }, { "input": "What is the role of the Leucosporidium ice-binding protein", "output": "Arctic yeast Leucosporidium sp. produces a glycosylated ice-binding protein (LeIBP) with a molecular mass of \u223c25 kDa, which can lower the freezing point below the melting point once it binds to ice. ce-binding proteins (IBPs) inhibit ice growth through direct interaction with ice crystals to permit the survival of polar organisms in extremely cold environments." }, { "input": "Is the enzyme ERAP2 associated with the disease birdshot chorioretinopathy?", "output": "Yes,\nBSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands." }, { "input": "As of September 2018, what machine learning algorithm is used to for cardiac arrhythmia detection from a short single-lead ECG recorded by a wearable device?", "output": "Support Vector machines( SVM) can be used for cardiac arrhythmia detection in from an ECG recorded by a wearable device." }, { "input": "As of September 2018, what machine learning algorithm is used to for cardiac arrhythmia detection from a short single-lead ECG recorded by a wearable device?", "output": "SVM approach for cardiac arrhythmias detection in short single-lead ECG recorded by a wearable device" }, { "input": "Does Panitumumab prolong survival of biliary tract cancer patients?", "output": "No. Panitumumab in combination with chemotherapy does not improve survival of biliary cancer patients." }, { "input": "Which microRNA is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions?", "output": "MIR137 is the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions." }, { "input": "What is the aim of the METABRIC project?", "output": "The METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort aims at the integration of genomic and transcriptomic profiles of 2000 breast tumours." }, { "input": "Name 3 diseases for which lucatumumab is being tested?", "output": "Lucatumumab is being tested as treatment for malignancies such as chronic lymphatic leukemia (CLL), Multiple Myeloma (MM), and non-Hodgkin's lymphoma (NHL)." }, { "input": "Which transcription factor binding site is contained in Alu repeats?", "output": "A novel abundant NF-\u03baB-binding site resides in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution." }, { "input": "Which transcription factor binding site is contained in Alu repeats?", "output": "Remarkably, we identified a novel abundant NF-\u03baB-binding site residing in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution." }, { "input": "Which transcription factor binding site is contained in Alu repeats?", "output": "Remarkably, we identified a novel abundant NF-\u03baB-binding site residing in specialized Alu-repetitive elements having the potential for long range transcription regulation, thus suggesting that in addition to its known role, NF-\u03baB has a primate-specific function and a role in human evolution. A de novo motif enrichment analysis uncovers secondary TFBSs (AP1, SP1) at characteristic distances from NF-\u03baB/RelA TFBSs." }, { "input": "What is ferroptosis?", "output": "Ferroptosis is a newly defined iron-dependent, non-apoptotic mode of cell death with necrotic morphology. Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment" }, { "input": "What disease is treated with Laparoscopic Heller Myotomy (LHM)?", "output": "To compare the outcome of per oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia" }, { "input": "What disease is treated with Laparoscopic Heller Myotomy (LHM)?", "output": "Laparoscopic Heller myotomy (LHM) is the preferred surgical method for treating achalasia." }, { "input": "Name 4 side effects of enasidenib", "output": "Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels etc." }, { "input": "Is lucatumumab a polyclonal antibody?", "output": "No, lucatumumab is a a monoclonal antibody against CD40." }, { "input": "What is evaluated with the SAD PERSONS scale?", "output": "SAD PERSONS scale was developed to evaluate suicide risk." }, { "input": "Briefly describe a deep learning system that is more accurate than human experts at detecting melanoma.", "output": "in August of 2018 a study was published where a Convolutional Neural Network's (CNN) diagnostic performance was compared with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN, the CNN had both higher sensitivity and specificity." }, { "input": "Which human disease is experimental autoimmune encephalomyelitis (EAE) model for?", "output": "Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS (Multiple Sclerosis)." }, { "input": "What is the cause if the rare disease cystinosis?", "output": "Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene." }, { "input": "Is lithium effective for treatment of amyotrophic lateral sclerosis?", "output": "No, lithium is not effective for treatment of amyotrophic lateral sclerosis." }, { "input": "Should dacomitinib be used for treatment of glioblastoma patients?", "output": "No, dacomitinib has a limited single-agent activity in recurrent glioblastoma with EGFR amplification." }, { "input": "Which molecular does daratumumab target?", "output": "Daratumumab is an anti-CD38 antibody." }, { "input": "What is etarfolatide used for?", "output": "Etarfolatide in the form of 99mTc-etarfolatide is used as a companion imaging agent" }, { "input": "What is the function of Plasminogen activator inhibitor 1?", "output": "Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis." }, { "input": "What is the mechanism of action of durvalumab?", "output": "Durvalumab is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. It is Immune checkpoint inhibitor used of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1." }, { "input": "Which tool has been developed for GPU-accelerated alignment of bisulfite-treated DNA sequences?", "output": "The alignment of bisulfite-treated DNA sequences (BS-seq reads) to a large genome involves a significant computational burden beyond that required to align non-bisulfite-treated reads. In the analysis of BS-seq data, this can present an important performance bottleneck that can be mitigated by appropriate algorithmic and software-engineering improvements. One strategy is to modify the read-alignment algorithms by integrating the logic related to BS-seq alignment, with the goal of making the software implementation amenable to optimizations that lead to higher speed and greater sensitivity than might otherwise be attainable. This strategy was evaluated using Arioc, a short-read aligner that uses GPU (general-purpose graphics processing unit) hardware to accelerate computationally-expensive programming logic." }, { "input": "Which disease is gemtuzumab ozogamicin used for?", "output": "Gemtuzumab ozogamicin is used for the treatment of acute myeloid leukemia" }, { "input": "What is GeneWeaver used for?", "output": "GeneWeaver: a web-based system for integrative functional genomics." }, { "input": "What is GeneWeaver used for?", "output": "GeneWeaver is a freely available resource for storing, curating and analyzing sets of genes from heterogeneous data sources. GeneWeaver enables researchers to store, share, analyze, and compare results of their own genome-wide functional genomics experiments in an environment containing rich companion data obtained from major curated repositories, including the Mouse Genome Database and other model organism databases, along with derived data from highly specialized resources, publications, and user submissions." }, { "input": "What is GeneWeaver used for?", "output": "GeneWeaver: a web-based system for integrative functional genomics. The freely available GeneWeaver (http://www.GeneWeaver.org) powered by the Ontological Discovery Environment is a curated repository of genomic experimental results with an accompanying tool set for dynamic integration of these data sets, enabling users to interactively address questions about sets of biological functions and their relations to sets of genes. The GeneWeaver.org system provides a platform for cross-species integration and interrogation of heterogeneous curated and experimentally derived functional genomics data." }, { "input": "Are there ultraconserved regions in the budding yeast (Saccharomyces cerevisiae)?", "output": "Yes. In addition to some fundamental biological functions, ultraconserved regions play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment." }, { "input": "Which disease can be classified with the Awaji Criteria?", "output": "Awaji Criteria are used for amyotrophic lateral sclerosis." }, { "input": "Endolymphatic hydrops is associated with Meniere\u2019s disease. Please provide a summary of endoymphatic hydrops including the symptoms and affected body part.", "output": "Endolymphatic hydrops is a disorder of the inner ear. It consists of an excessive build-up of the endolymph fluid, which fills the hearing and balance structures of the inner ear. The symptoms of endolymphatic hydrops include the feeling of pressure or fullness in the ears, hearing loss, tinnitus (ringing in the ears) and balance problems." }, { "input": "Where does gemtuzumab ozogamicin bind?", "output": "Gemtuzumab ozogamicin binds to CD33" }, { "input": "Where, in what US state, was there a measles outbreak in an Amish community", "output": "The measles outbreak started an Amish community in Ohio" }, { "input": "Is there any role for HUWE1 in MYC signalling?", "output": "Yes. HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation." }, { "input": "List MHC-I-associated inflammatory disorders.", "output": "ankylosing spondylitis\nbirdshot chorioretinopathy\nBeh\u00e7et's disease \npsoriasis" }, { "input": "What is the predicted function for TMEM132 family?", "output": "The TMEM132 family proteins are strongly predicted to have a cellular adhesion function, connecting the extracellular medium with the intracellular actin cytoskeleton." }, { "input": "What type of topoisomerase inhibitor is gepotidacin?", "output": "Gepotidacin is a type IIA topoisomerase inhibitor." }, { "input": "What is the mechanism of action of Alpelisib?", "output": "Alpelisib is selective inhibitor of Phosphatidylinositol 3-Kinase \u03b1 (PI3K\u03b1). It is used for treatment of cancer." }, { "input": "What is the normal function p53?", "output": "Wild-type p53 can suppress tumour development by multiple pathways." }, { "input": "What is eravacycline?", "output": "Finafloxacin is a fluoroquinolone antimicrobial agent that exhibits optimum efficacy in slightly acidic environments. It is being developed to treat serious bacterial infections associated with an acidic environment, including urinary tract infections, complicated urinary tract infections, pyelonephritis and Helicobacter pylori infections, while it has already received approval for the treatment of acute otitis externa." }, { "input": "What is PEGylation?", "output": "Attachment of a chain of poly(ethylene glycol) (PEG) to a therapeutic protein, a process widely known as PEGylation, can lead to several beneficial effects. It has the potential to significantly delay aggregation of the protein by steric shielding, a frequently encountered issue in the development of protein drugs. Moreover, it can modify the pharmacokinetic profile of the PEGylated protein by delaying renal excretion, leading to a longer half-life (t1/2) of the drug. By steric hindrance, it can also inhibit interactions between the protein drug and proteases as well as the host immune system, thereby inhibiting inactivation of the PEGylated protein and also attenuating its immunogenicity." }, { "input": "What is the 3D tomography imaging technique for diagnosis of eye disease?", "output": "Currently, eye care professionals use optical coherence tomography (OCT) scans to help diagnose eye conditions." }, { "input": "Which was the first mutant IDH2 inhibitor to be approved for patients with acute myeloid leukemia?", "output": "Enasidenib was the first mutant IDH2 inhibitor to be approved for the treatment of refractory and relapsed acute myeloid leukemia." }, { "input": "What part of the body is affected by Meniere's disease?", "output": "The inner ear is the body part that is associated with Meniere's disease." }, { "input": "Which two drugs are included in the MAVYRET pill?", "output": "MAVYRET pill includes glecaprevir and pibrentasvir. It is used for treatment of hepatitis C infection." }, { "input": "Describe the 4D-CHAINS algorithm", "output": "4D-CHAINS/autoNOE-Rosetta is a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta." }, { "input": "What is an organoid?", "output": "Organoids are a three-dimensional in vitro culture platform constructed from self-organizing stem cells. They can almost accurately recapitulate tumor heterogeneity and microenvironment \"in a dish,\" which surpass established cell lines and are not as expensive and time-consuming as PDTXs. As an intermediate model, tumor organoids are also used to study the fundamental issues of tumorigenesis and metastasis. They are specifically applied for drug testing and stored as \"living biobanks.\"" }, { "input": "Do raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes?", "output": "yes, raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes." }, { "input": "Are Mesenchymal stem cells (MSC) multipotent cells?", "output": "Yes, Mesenchymal stem cells (MSC) are multipotent cells." }, { "input": "Which two drugs are included in the Entresto pill?", "output": "Entresto includes Sacubitril and Valsartan." }, { "input": "Is there a deep-learning algorithm for protein solubility prediction?", "output": "Yes. DeepSol is a novel deep learning-based protein solubility predictor. It is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence." }, { "input": "Have machine learning methods been used to predict the severity of major depressive disorder(MDD)?", "output": "Machine-learning (ML) models developed from self-reports can be used to predict persistence and severity of major depressive disorder(MDD)" }, { "input": "What is known about the gut bacteria and depression.", "output": "Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways.\n\nMajor depressive disorder (MDD) is a highly prevalent and debilitating mental illness, which is associated with disorder of gut microbiota." }, { "input": "Can midostaurin inhibit angiogenesis?", "output": "Yes, midostaurin can inhibit angiogenesis through the inhibition of ithe vascular endothelial growth factor receptor." }, { "input": "For which indications has midostaurin received FDA and EMA approval?", "output": "Midostaurin was approved by the Food and Drug Administration (FDA) and the European Medical Agency (EMA) for acute myeloid leukemia with activating FLT3 mutations in combination with intensive induction and consolidation therapy as well as aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia (MCL)." }, { "input": "Does Groucho related gene 5 (GRG5) have a role only in late development?", "output": "Groucho related gene 5 (GRG5) has been described as a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. By both loss and gain of function approaches ablation of GRG5 has been shown to deregulate the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential." }, { "input": "Which drugs are included in the Orkambi pill?", "output": "Orkambi pill includes lumacaftor combined with ivacaftor. It is approved for treatment of cystic fibrosis with F508del-CFTR mutation." }, { "input": "List available R packages for processing NanoString data", "output": "NanoStringNorm and NanoStringNormCNV." }, { "input": "Which disease is PGT121 used for?", "output": "The broadly neutrilizing antibody PGT121 is being tested against HIV-1." }, { "input": "What is the mechanism of action of anlotinib?", "output": "Anlotinib is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGF\u03b2), and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3). It is used for treatment of cancer." }, { "input": "Describe Canvas SPW", "output": "Whole genome sequencing is becoming a diagnostics of choice for the identification of rare inherited and de novo copy number variants in families with various pediatric and late-onset genetic diseases. Joint variant calling in pedigrees is hampered by the complexity of consensus breakpoint alignment across samples within an arbitrary pedigree structure. Canvas SPW is a tool developed for the identification of inherited and de novo copy number variants from pedigree sequencing data. Canvas SPW supports a number of family structures and provides a wide range of scoring and filtering options to automate and streamline identification of de novo variants. The tool is available for download from https://github.com/Illumina/canvas." }, { "input": "List phagosomal markers.", "output": "Rab7\nLAMP1\nCathepsin D\nRab9\nV-ATPase \nCD63" }, { "input": "List bacterial families for which delafloxacin has been shown to be effective.", "output": "Delafloxacin has been shown to be effective against multiple gram-positive and gram-negative bacteria, including Strepotococcus pneumoniae, Haemophilus influenzae, Moraxella atarrhalis, Staphylococcus aureus, Klebsiella pneumoniae and more." }, { "input": "What is the cause of Sandhoff disease?", "output": "Sandhoff disease (SD) is a genetic disorder caused by a mutation of the \u03b2-subunit gene \u03b2-hexosaminidase B (HexB) in humans, which results in the massive accumulation of the ganglioside GM2 and related glycosphingolipids in the nervous system." }, { "input": "Are there tools for reviewing variant calls?", "output": "Yes. Tools such as the Variant InsPector and Expert Rating tool (VIPER) have been developed that speed up the manual inspection of variant calls by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls." }, { "input": "Name one CCR4 targeted drug.", "output": "Mogamulizumab is an anti-CCR4 monoclonal antibody." }, { "input": "What is the mechanism of action of cemiplimab?", "output": "Cemiplimab is human programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and blocks its interaction with programmed death ligands 1 (PD-L1) and 2 (PD-L2). It is approved to treat patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for surgery or radiation." }, { "input": "Which algorithm has been developed for finding conserved non-coding elements (CNEs) in genomes?", "output": "CNEFinder is a tool for identifying CNEs between two given DNA sequences with user-defined criteria." }, { "input": "What causes Bathing suit Ichthyosis(BSI)?", "output": "Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive congenital ichthyosis (ARCI) due to transglutaminase-1 gene (TGM1) mutations leading to a temperature sensitive phenotype." }, { "input": "What type of data does the UK biobank resource contain?", "output": "The UK Biobank contains deep phenotyping and genomic data. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits." }, { "input": "Has ivosidenib been FDA approved for use against acute myeloid leukemia?", "output": "The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia." }, { "input": "Which two surgical methods were compared in the RAZOR trial?", "output": "The RAZOR trial compared open radical cystectomy vs. robot-assisted radical cystectomy in patients with bladder cancer." }, { "input": "Are Copy Number Variants (CNVs) depleted in regions of low mappability?", "output": "No. Low-mappability regions are approximately 5 times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes." }, { "input": "List potential reasons regarding why potentially important genes are ignored", "output": "Differences in attention can be explained, to a large extent, exclusively from a small set of identifiable chemical, physical, and biological properties of genes. Together with knowledge about homologous genes from model organisms, these features accurately predict the number of publications on individual human genes, the year of their first report, the levels of funding awarded by the National Institutes of Health (NIH), and the development of drugs against disease-associated genes." }, { "input": "Which random forest method has been developed for detecting Copy Numbers Variants (CNVs)?", "output": "CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing." }, { "input": "What is the indication for Truvada?", "output": "Truvada is used for HIV pre-exposure prophylaxis (PrEP) in high risk individuals" }, { "input": "What is the indication for Truvada?", "output": "pre-exposure prophylaxis (PrEP) and the recent approval by the FDA of the supplemental indication for Truvada as PrEP" }, { "input": "Is Adar3 involved in learning and memory?", "output": "Yes. Adar3 is involved in learning and memory in mice. Mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice." }, { "input": "List STING agonists.", "output": "CDN 3'3'-cGAMP\ndimethylxanthenone-4-acetic acid \n\u03b1-Mangostin" }, { "input": "List drugs that were tested in the CheckMate 214 trial.", "output": "CheckMate 214 clinical trial compared Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma." }, { "input": "Mutations in which gene have been found in patients with the CLAPO syndrome?", "output": "CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. In a cohort of 13 patients with CLAPO, five activating mutations have been identified in the PIK3CA gene in affected tissues from 6 of the 9 patients studied." }, { "input": "What is CamurWeb?", "output": "CamurWeb is a classification software and a large knowledge base for gene expression data of cancer. It is a web-based software that is able to extract multiple and equivalent classification models in form of logic formulas (\"if then\" rules) and to create a knowledge base of these rules that can be queried and analyzed. The method is based on an iterative classification procedure and an adaptive feature elimination technique that enables the computation of many rule-based models related to the cancer under study. CamurWeb includes a user friendly interface for running the software, querying the results, and managing the performed experiments." }, { "input": "Describe SLIC-CAGE", "output": "SLIC-CAGE is a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. SLIC-CAGE can generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods." }, { "input": "There is no drug available to prevent HIV infection, Pre-exposure prophylaxis (PrEP), yes or no?", "output": "Pre-exposure prophylaxis (PrEP) with the drug combination Truvada can substantially decrease HIV transmission in individuals at risk." }, { "input": "There is no drug available to prevent HIV infection, Pre-exposure prophylaxis (PrEP), yes or no?", "output": "The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations." }, { "input": "Burosumab is used for treatment of which disease?", "output": "Burosumab is a fully human IgG1 monoclonal antibody directed at fibroblast growth factor 23 (FGF23), is indicated for the treatment of X-linked hypophosphatemia (XLH), a condition associated with excessive FGF23 production." }, { "input": "What is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Loss-of-function nuclear factor \u03baB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans." }, { "input": "What is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of common variable immunodeficiency (CVID), which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells." }, { "input": "List two indications of Letermovir?", "output": "Letermovir is approved for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant (HSCT)." }, { "input": "What is achalasia?", "output": "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood." }, { "input": "What is achalasia?", "output": "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood. Idiopathic achalasia is a rare esophageal motor disorder. The pathophysiology of achalasia is largely unknown, and involves the destruction of ganglion cell in the esophageal myenteric plexus." }, { "input": "What is achalasia?", "output": "achalasia is a primary esophageal motility disorder" }, { "input": "What is achalasia?", "output": "Achalasia is a primary esophageal motility disorder characterized by aperistalsis of the esophagus and failed relaxation of the lower esophageal sphincter that presents rarely in childhood. Idiopathic achalasia is a rare esophageal motor disorder." }, { "input": "What is achalasia?", "output": "Achalasia is a rare idiopathic disease, associated with significant morbidity and negative impact on life quality. The disorder is characterized by impairments in the esophageal motility and loss of the lower esophageal sphincter (LES) relaxation." }, { "input": "Does allele phasing improve the phylogenetic utility of ultraconserved elements?", "output": "Yes. Allele phasing greatly improves the phylogenetic utility of ultraconserved elements. Analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences." }, { "input": "What is Burning Mouth Syndrome(BMS)?", "output": "Burning Mouth Syndrome (BMS), a chronic intraoral burning sensation or dysesthesia without clinically evident causes, is one of the most common medically unexplained oral symptoms/syndromes. It predominately affects middle-aged women in the postmenopausal period. The condition is distinguished by burning symptoms of the oral mucosa and the absence of any clinical signs." }, { "input": "What is Burning Mouth Syndrome(BMS)?", "output": "Burning mouth syndrome (BMS) is a chronic oral pain syndrome that primarily affects peri- and postmenopausal women. It is characterized by oral mucosal burning and may be associated with dysgeusia, paresthesia, dysesthesia, and xerostomia." }, { "input": "When is serum AFP used as marker?", "output": "Serum \u03b1-Fetoprotein (AFP) is a widely used diagnostic biomarker, but it has limited sensitivity and is not elevated in all Hepato cellular carcinoma (HCC) cases so, we incorporate a second blood-based biomarker, des'\u03b3 carboxy-prothrombin (DCP), that has shown potential as a screening marker for HCC." }, { "input": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "output": "infectious proteins) were discovered by their outr\u00e9 genetic properties and have become important models for an array of human prion and amyloid diseases." }, { "input": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "output": "Yeast prions have become important models for the study of the basic mechanisms underlying human amyloid diseases and normal yeast cells can eliminate the large majority of prion variants arising." }, { "input": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "output": "Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions" }, { "input": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "output": "These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics." }, { "input": "RV3-BB vaccine is used for prevention of which viral infection?", "output": "The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth." }, { "input": "Is dupilumab effective for treatment of asthma?", "output": "Yes, dupilumab is effective for treatment of asthma. It works by simultaneous targeting of both IL-4 and IL-13 by blocking IL-4 receptor \u03b1." }, { "input": "What is the role of the Mcm2-Ctf4-Pol\u03b1 axis?", "output": "The Mcm2-Ctf4-Pol\u03b1 Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands." }, { "input": "What is the role of the Mcm2-Ctf4-Pol\u03b1 axis?", "output": "The Mcm2-Ctf4-Pol\u03b1 Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands. Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4)2 tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood." }, { "input": "What is the role of the Mcm2-Ctf4-Pol\u03b1 axis?", "output": "The Mcm2-Ctf4-Pol\u03b1 axis facilitates parental histone H3-H4 transfer to lagging strands." }, { "input": "What is anophthalmia?", "output": "Microphthalmia, anophthalmia are the malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball." }, { "input": "What is anophthalmia?", "output": "Anophthalmia is the medical term for the absence of one or both eyes." }, { "input": "What are the roles of LEM-3?", "output": "LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis. The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans. LEM-3 is able to process erroneous recombination intermediates that persist into the second meiotic division." }, { "input": "What is the contribution of ultraconserved elements in Australasian smurf-weevils?", "output": "Ultraconserved elements (UCEs) resolve the phylogeny of Australasian smurf-weevils." }, { "input": "How does botulism toxin act on the muscle?", "output": ". The seven immunologically distinct serotypes of BoNTs (A-G), each produced by various strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis." }, { "input": "How does botulism toxin act on the muscle?", "output": "Botulinum toxin (BTX) is widely used to treat muscle spasticity by acting on motor neurons producing a flaccid paralysis. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction." }, { "input": "What is the most common pediatric glioma?", "output": "Pilocytic astrocytoma is the most common pediatric glioma." }, { "input": "What is the function of the protein encoded by the gene STING?", "output": "Stimulator of interferon genes (STING) is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response." }, { "input": "List uniparental disomy (UPD) detection algorithms", "output": "UPDtool and AsCNAR are tools for detecting uniparental disomy (UPD). UPDtool is a computational tool for detection and classification of uniparental disomy (UPD) in trio SNP-microarray experiments. AsCNAR (allele-specific copy-number analysis using anonymous references) detects the copy-number neutral LOH, or uniparental disomy (UPD), in a large number of acute leukemia samples." }, { "input": "Describe the mechanism of action of apalutamide.", "output": "Apalutamide is a second-generation antiandrogen that inhibits the binding of androgen to androgen receptor (AR), nuclear translocation of the androgen-AR complex, and binding of AR transcription complex to DNA-binding sites and transcription elements. It does not show antagonist-to-agonist switch like bicalutamide. It is emerging as additional new option to treat castration-resistant prostate cancer." }, { "input": "Which molecule is inhibited by larotrectinib?", "output": "Larotrectinib is oral, potent, and selective inhibitor of tropomyosin receptor kinases (TRK). It demonstrated unprecedented efficacy on unresectable or metastatic solid tumors with neurotrophic tropomyosin receptor kinase (NTRK)-fusion proteins in adult and pediatric patients." }, { "input": "What is Bayesian haplotyping used for?", "output": "Bayesian haplotype inference is used for phylogenetic analysis, specifcially multiple linked single-nucleotide polymorphisms and analysis of chromosome copy number and deletions." }, { "input": "List major features of TEMPI Syndrome.", "output": "TEMPI syndrome includes telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting. It is a newly described clinical entity that is generally considered a plasma cell dyscrasia with multiple system involvement." }, { "input": "Describe Herpetic Whitlow.", "output": "Herpetic whitlow is an acute viral infection of the hand caused by either herpes simplex virus (HSV) 1 or 2. Its characteristic findings are significant pain and erythema with overlying nonpurulent vesicles. It can be confirmed by polymerase chain reaction testing." }, { "input": "Sweat Chloride Testing is used for which disease?", "output": "Sweat Chloride Testing is used to diagnose cystic fibrosis. CFTR dysfunction can be demonstrated using sweat chloride testing." }, { "input": "What is nyctinasty in plants?", "output": "Nyctinasty is the circadian rhythmic nastic movement of leguminous plants in response to the onset of darkness; a unique and intriguing phenomenon that has attracted attention for centuries." }, { "input": "What is nyctinasty in plants?", "output": "Leguminous plants open their leaves during the daytime and close them at night as if sleeping, a type of movement that follows circadian rhythms, and is known as nyctinastic movement" }, { "input": "Does Eucommia ulmoides leaf extract ameliorates steatosis/fatty liver induced by high-fat diet?", "output": "Yes, Eucommia ulmoides leaf extract can ameliorate steatosis induced by high-fat diet." }, { "input": "List the releases of tmVar", "output": "TmVar is a text mining approach for extracting sequence variants in biomedical literature. TmVar 2.0 integrates genomic variant information from literature with dbSNP and ClinVar for precision medicine." }, { "input": "Which deep learning algorithm has been developed for variant calling?", "output": "A deep convolutional neural network can call genetic variation in aligned next-generation sequencing read data by learning statistical relationships between images of read pileups around putative variant and true genotype calls. The approach, called DeepVariant, outperforms existing state-of-the-art tools. The learned model generalizes across genome builds and mammalian species, allowing nonhuman sequencing projects to benefit from the wealth of human ground-truth data." }, { "input": "What 2 biological processes are regulated by STAMP2 in adipocytes?", "output": "Inflammation, insulin resistance and metabolic response are regulated by STAMP2 in adipocytes." }, { "input": "What 2 biological processes are regulated by STAMP2 in adipocytes?", "output": "six-transmembrane protein stamp2 as a critical modulator of this integrated response system of inflammation and metabolism" }, { "input": "What is the mechanism of action of Pitolisant?", "output": "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor thus increasing histaminergic tone in the wake promoting system of the brain. It is used for the treatment of narcolepsy." }, { "input": "Which methods have been developed for extracting sequence variants from the literature?", "output": "TmVar and nala" }, { "input": "Which molecules are targeted by defactinib?", "output": "PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2." }, { "input": "What is Chrysophanol?", "output": "Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells" }, { "input": "What is Chrysophanol?", "output": "Chrysophanol is a unique anthraquinone having broad-spectrum therapeutic potential along with ecological importance. A plethora of literature is available on the pharmacological properties of chrysophanol, which include anticancer, anti-inflammatory, and antimicrobial activities." }, { "input": "What is the percentage of individuals at risk of dominant medically actionable disease?", "output": "1 in 38 individuals at risk of a dominant medically actionable disease." }, { "input": "What is the percentage of individuals at risk of dominant medically actionable disease?", "output": "1 in 38 healthy individuals (2.7%) has a (likely) pathogenic variant in one of 59 medically actionable dominant disease genes for which the American College of Medical Genetics and Genomics (ACMG) recommends disclosure." }, { "input": "Please list the 4 genes involved in Sanfilippo syndrome, also known as mucopolysaccharidosis III (MPS-III).", "output": "Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of the four enzymes involved in the catabolism of glycosaminoglycan heparan sulfate. The genes are SGSH, NAGLU, HGSNAT or GNS." }, { "input": "What is CardioClassifier?", "output": "CardioClassifier (http://www.cardioclassifier.org) is a semiautomated decision support tool for clinical genome interpretation. CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data." }, { "input": "List clinical disorders or diseases where uc.189 is involved?", "output": "Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in Cervical squamous cell carcinomas (CSCC) and Endometrial adenocarcinomas (EAC). Thus, several findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors. In addition, high expression of uc.189 might reflect poor prognosis of Esophageal squamous cell carcinoma (ESCC) and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target." }, { "input": "Is verubecestat effective for Alzheimer\u2019s Disease?", "output": "No. Verubecestat is not effective for treatment of Alzheimer\u2019s Disease." }, { "input": "What is the role of metalloproteinase-17 (ADAM17) in NK cells?", "output": "The metalloproteinase-17 (ADAM17) is involved in CD16A cleavage and acts as a regulatory checkpoint in NK cells" }, { "input": "What is the triad of Melkersson-Rosenthal syndrome?", "output": "Melkersson-Rosenthal syndrome is an uncommon granulomatous disease characterized by the triad of relapsing facial paralysis, orofacial edema and fissured tongue." }, { "input": "Is galcanezumab effective for treatment of migraine?", "output": "Yes. Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide that is used for migraine prevention." }, { "input": "Can mitochondria be inherited by both parents in humans?", "output": "Yes. A comprehensive exploration of mtDNA segregation in certain families shows biparental mtDNA transmission with an autosomal dominant-like inheritance mode. Although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring." }, { "input": "Can Diazepam be beneficial in the treatment of traumatic brain injury?", "output": "Diazepam treatment improved cognitive recovery and mortality in brain injured rats." }, { "input": "Name the algorithms for counting multi-mapping reads", "output": "RNA-Seq is currently used routinely, and it provides accurate information on gene transcription. However, the method cannot accurately estimate duplicated genes expression. Several strategies have been previously used (drop duplicated genes, distribute uniformly the reads, or estimate expression), but all of them provide biased results. Mmquant is a tool for computing gene expression, including duplicated genes. If a read maps at different positions, the tool detects that the corresponding genes are duplicated; it merges the genes and creates a merged gene. The counts of ambiguous reads is then based on the input genes and the merged genes. Other methods have been developed that use weighted allocation of read counts but these methods treat the different types of multi-reads equivalently. For instance a hierarchical approach was developed for allocation of read counts that first resolves ambiguities among genes, then among isoforms, and lastly between alleles. The model has been implemented in EMASE software (Expectation-Maximization for Allele Specific Expression) to estimate total gene expression, isoform usage and ASE based on this hierarchical allocation." }, { "input": "In clinical trials, the H3 R antagonist CEP-26401 has a positive effect on cognition, yes or no?", "output": "The H3 R antagonist CEP-26401 had an effect on cognition." }, { "input": "In clinical trials, the H3 R antagonist CEP-26401 has a positive effect on cognition, yes or no?", "output": "CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement" }, { "input": "Fecal transplantation is used to treat infection with what bacteria?", "output": "Fecal microbiota transplantation is used to treat Clostridium difficile infection" }, { "input": "Is pimavanserin effective for Parkinson's disease psychosis?", "output": "Yes. Pimavanserin is effective for treating Parkinson's disease psychosis. It is a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist." }, { "input": "When did delafloxacin receive its first approval in the USA for acute bacterial skin and skin structure infections?", "output": "Delafoxacin received approval in the USA for the treatment of acute bacterial skin and skin structure infections in 2017." }, { "input": "Erenumab, used to treat migraine headaches, binds to what protein?", "output": "Erenumab binds to the CGRP receptor to treat migraine headaches" }, { "input": "What are the CADD scores?", "output": "Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders. CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly." }, { "input": "What is a prolactinoma and where in the body would they be found?", "output": "Prolactinomas are the most common functional tumors of the pituitary gland." }, { "input": "Which integrin genes are activated by the immune system in inflammatory bowel disease?", "output": "ITGA4, ITGB8, ITGAL and ICAM1. In all four cases, the expression-increasing allele also increases disease risk." }, { "input": "Which is the database of somatic mutations in normal cells?", "output": "DSMNC is a database of somatic mutations in normal cells (http://dsmnc.big.ac.cn/) and provides a comprehensive catalogue of somatic SNVs in single cells from various normal tissues. In the current version, the database collected \u223c0.8 million SNVs accumulated in \u223c600 single normal cells (579 human cells and 39 mouse cells). The database interface supports the user-friendly capability of browsing and searching the SNVs and their annotation information." }, { "input": "Which drugs are included in the Lonsurf pill?", "output": "Lunsurf pill includes trifluridine and tipiracil. It is a novel form of chemotherapy for metastatic colorectal cancer." }, { "input": "What is the association of epigallocatechin with the cardiovascular system?", "output": "The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. EGCG was found to exhibit a wide range of therapeutic properties." }, { "input": "What is the association of epigallocatechin with the cardiovascular system?", "output": "Epigallocatechin gallate (EGCG), a bioactive ingredient of green tea, plays a protective role in the cardiovascular system." }, { "input": "What is the mechanism of action of tucatinib?", "output": "Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer." }, { "input": "Which enzyme is inhibited by a drug Lorlatinib?", "output": "Lorlatinib is anaplastic lymphoma kinase inhibitor." }, { "input": "What periodontal disease associated bacteria is also associated with Alzheimer's disease?", "output": "Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD)." }, { "input": "What periodontal disease associated bacteria is also associated with Alzheimer's disease?", "output": "Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD." }, { "input": "Is deletion at 6q24.2-26 associated with longer survival of patients with high-grade serous ovarian carcinoma (HGSOCs)?", "output": "Yes. Loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors. The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019)." }, { "input": "How does the Cholera toxin enter a cell?", "output": "Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells." }, { "input": "Describe the mechanism of action of Lurbinectedin.", "output": "Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells. It inhibits active transcription of protein-coding genes, causing DNA-break accumulation, apoptosis and modulation of the tumor microenvironment." }, { "input": "Can mogamulizumab be used for the treatment of cutaneous T-cell lymphoma?", "output": "Yes, mogamulizumab can be used for the treatment of cutaneous T-cell lymphoma." }, { "input": "Which enzymes are inhibited by Duvelisib?", "output": "Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-\u03b4 (PI3K-\u03b4) and PI3K-\u03b3 in late-stage clinical development for hematologic malignancy treatment." }, { "input": "List search engines used in proteomics.", "output": "Mascot\nX!Tandem\nMS-GF\nMS Amanda \nMyriMatch\nComet\nTide\nAndromeda\nOMSSA" }, { "input": "Is avelumab effective for bladder cancer?", "output": "Yes, avelumab is effective treatment of bladder cancer." }, { "input": "Is cabozantinib effective for Hepatocellular Carcinoma?", "output": "Yes, cabozantinib is approved as second line agent for treatment of Hepatocellular Carcinoma." }, { "input": "Is cabozantinib effective for Hepatocellular Carcinoma?", "output": "Yes, cabozantinib effective for hepatocellular carcinoma. Cabozantinib is useful second-line therapy after the failure of sorafenib." }, { "input": "De novo mutations in which novel genes are involved in systemic lupus erythematosus?", "output": "DNMT3A, PRKCD, and C1QTNF4." }, { "input": "Is there a link between BCL11B haploinsufficiency and syndromic neurodevelopmental delay?", "output": "No. Mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay." }, { "input": "What is the mechanism of action of motolimod?", "output": "Motolimod is the toll-like receptor 8 (TLR8) agonist that stimulates innate and adaptive immunity." }, { "input": "Is Lasmiditan effective for migraine?", "output": "Yes, Lasmiditan is effective for treatment of migraine. This has been demonstrated in clinical trials." }, { "input": "List drugs included in the TRIUMEQ pill.", "output": "Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine." }, { "input": "Are there graph kernel libraries available implemented in JAVA?", "output": "No. Measuring the similarity of graphs is a fundamental step in the analysis of graph-structured data, which is omnipresent in computational biology. Graph kernels have been proposed as a powerful and efficient approach to this problem of graph comparison. Graphkernels are the first R and Python graph kernel libraries including baseline kernels such as label histogram based kernels, classic graph kernels such as random walk based kernels, and the state-of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is implemented in C\u2009++ for efficiency. Using the kernel matrices computed by the package, one can perform tasks such as classification, regression and clustering on graph-structured samples." }, { "input": "What organism causes hepatic capillariasis?", "output": "Hepatic capillariasis is a rare and neglected parasitic disease caused by infection with Capillaria hepatica in human liver." }, { "input": "What organism causes hepatic capillariasis?", "output": "hepatic capillariasis, caused by the parasite Capillaria hepatica," }, { "input": "Cerliponase alfa is apprived for treatment of which disease?", "output": "Cerliponase alfa is a recombinant human tripeptidyl peptidase-1 (TPP1) approved for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1." }, { "input": "Is baricitinib effective for rheumatoid arthritis?", "output": "Yes, baricitinib is effective treatment of rheumatoid arthritis." }, { "input": "What is the function of PARP1?", "output": "parp1 is the most abundant and best-characterized member of the family of parp enzymes. the poly(adp-ribose) polymerases (parps) catalyze poly(adp-ribosyl)ation, a post-translational modification of proteins." }, { "input": "What is the function of PARP1?", "output": "parp1 plays key roles in dna repair, as well as a wide variety of cellular processes, including transcriptional regulation" }, { "input": "What is the function of PARP1?", "output": "PARP1 is an abundant nuclear protein with many pleiotropic functions involved in epigenetic and transcriptional controls. PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on." }, { "input": "What is the function of PARP1?", "output": "PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on" }, { "input": "Is Semagacestat effective for treatment of Alzheimer's disease?", "output": "No. In clinical trial semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections." }, { "input": "Which molecule is inhibited by ivosidenib?", "output": "Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1. It used an effective treatment of leukemia." }, { "input": "What is COG112?", "output": "COG112 is a a modified apoE-mimetic peptide, that results from the fusion of COG133 to a protein transduction domain. COG112 has significantly enhanced anti-inflammatory bioactivities in vitro." }, { "input": "List the four advances integrated into the SHERLOCKv2 platform.", "output": "SHERLOCKv2 presents with four distinct advances: (i) four-channel single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme; and (iv) lateral-flow readout." }, { "input": "Does Rhamnose have any effect on aging?", "output": "Yes, Rhamnose does have an effect on aging." }, { "input": "Is there any approved treatment for NAFLD?", "output": "No,\nNonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy." }, { "input": "Can pazopanib be used for treatment von Hippel-Lindau disease?", "output": "Yes, pazopanib is used for treatment von Hippel-Lindau disease." }, { "input": "Which ploidy-agnostic method has been developed for estimating telomere length from whole genome sequencing data?", "output": "Telomerecat is a ploidy-agnostic method for estimating telomere length from whole genome sequencing data. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors." }, { "input": "What happens to retrotransposons during ageing?", "output": "Retrotransposons are activated as organisms age" }, { "input": "What is the function of Taraxasterol in rheumatoid arthritis?", "output": "Taraxasterol suppresses inflammation in rheumatoid arthritis." }, { "input": "What is the function of Taraxasterol in rheumatoid arthritis?", "output": "Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses" }, { "input": "Is Netrin-1 a secreted protein?", "output": "Yes,\nnetrin-1 is a secreted protein." }, { "input": "Which enzyme is deficient in Wolman disease?", "output": "Deficiency of lysosomal acid lipase (LAL) causes Wolman disease." }, { "input": "Is the yeast (Saccharomyces cerevisiae) genome organized into topologically associated domains (TADs)?", "output": "Yes. By analyzing Hi-C data for budding yeast, 200-kb scale topologically associated domains (TADs) have been identified, whose boundaries are enriched for transcriptional activity." }, { "input": "What is MOV10?", "output": "MOV10 is an RNA helicase" }, { "input": "As of Feb 2019, are major brain gangliosides a target for the treatment of Alzheimer's disease?", "output": "As of Feb 2019, major brain gangliosides are proposed as a target for the treatment of Alzheimer's disease." }, { "input": "Which cancer is associated with increased levels of Serum alpha fetoprotein (AFP) ?", "output": "Serum alpha fetoprotein (AFP) is a marker of germ cell neoplasms,\r\nSerum \u03b1-Fetoprotein (AFP) is a widely used diagnostic biomarker, but it has limited sensitivity and is not elevated in all HCC cases." }, { "input": "Is Miller-Dieker syndrome associated with abnormalities of chromosome 1?", "output": "No. Miller-Dieker syndrome is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE and leads to malformations during cortical development." }, { "input": "List clinical symptoms of the MECOM-associated syndrome", "output": "Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss. No single clinical manifestation was detected in all patients affected by MECOM mutations. Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1." }, { "input": "Does the interaction of MOV10 and RNASEH2 promote L1 retrotransposition?", "output": "MOV10 interacts with RNASEH2, and their interplay is crucial for restricting L1 retrotransposition." }, { "input": "What is the role of CD28 with respect to bacterial superantigen toxins?", "output": "CD28 is a direct receptor of bacterial superantigen toxins." }, { "input": "What is the role of CD28 with respect to bacterial superantigen toxins?", "output": "cd28 is a homodimer expressed on t cells that functions as the principal costimulatory ligand in the immune response" }, { "input": "What is the exoproteome?", "output": "Exoproteomics aims at describing and quantifying the proteins found outside of the cells." }, { "input": "List features of the Triple A syndrome.", "output": "Triple A (Allgrove) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency, achalasia, and alacrimia. It is frequently associated with neurological manifestations like polyneuropathy." }, { "input": "What is the mechanism of the drug CRT0066101?", "output": "Recently developed small molecule PKD inhibitors, CID755673 and CRT0066101, provide potentially important pharmacological approaches to further investigate the effect of PKD in pancreatitis therapy" }, { "input": "What is the mechanism of the drug CRT0066101?", "output": "CRT0066101 inhibits protein kinase D" }, { "input": "Which protein is the Mitochondrial carrier homolog 2 (MTCH2) receptor for?", "output": "Mitochondrial Carrier Homolog 2 (MTCH2) acts as a receptor for the BH3 interacting-domain death agonist (BID) in the mitochondrial outer membrane." }, { "input": "What is PhenomeCentral?", "output": "The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. The PhenomeCentral portal (https://phenomecentral.org) enables the secure sharing of case records by clinicians and rare disease scientists. PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered." }, { "input": "What organism causes Rhombencephalitis?", "output": "Rhombencephalitis caused by Listeria monocytogenes" }, { "input": "What organism causes Rhombencephalitis?", "output": "Rhombencephalitis is caused by Listeria monocytogenes" }, { "input": "Has the protein SIRT2 been associated to cervical cancer?", "output": "Yes.\nA progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal\u2009<\u2009preneoplasia\u2009<\u2009cancer." }, { "input": "Which receptor is targeted by Erenumab?", "output": "Erenumab is a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention." }, { "input": "Are recessive coding variants responsible for the majority of undiagnosed nonconsanguineous individuals?", "output": "No. It is suggested that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration." }, { "input": "How can super-enhancers be used in disease diagnosis?", "output": "Super-enhancers are clusters of transcriptional enhancers that drive cell-type-specific gene expression and are crucial to cell identity. Many disease-associated sequence variations are enriched in super-enhancer regions of disease-relevant cell types. Thus, super-enhancers can be used as potential biomarkers for disease diagnosis and therapeutics. Current studies have identified super-enhancers in more than 100 cell types and demonstrated their functional importance." }, { "input": "List sirtuin inhibitors.", "output": "Sirtinol\nnicotinamide (NAM)\nLC-0296\nBZD9L1" }, { "input": "Is the NLM medical text indexer (MTI) still useful and relevant?", "output": "Yes. The NLM Medical Text Indexer (MTI) is still relevant and useful, and needs to be improved and expanded. The BioASQ Challenge results have shown that more machine learning needs to be incorporated into MTI while still retaining the indexing rules that have earned MTI the indexers' trust over the years. MTI also needs to be expanded through the use of full text, when and where it is available, to provide coverage of indexing terms that are typically only found in the full text." }, { "input": "Has strimvelis been approved by the European Medicines Agency?", "output": "Yes, the gene therapy Strimvelis has been approved by the European Medicines Agency." }, { "input": "What antibiotic is currently used as the standard of care for Clostridium Difficile infection as of 2018", "output": "Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. Fidaxomicin is a new antibiotic used to treat Clostridium difficile infection (CDI)." }, { "input": "What antibiotic is currently used as the standard of care for Clostridium Difficile infection as of 2018", "output": "Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection.Fidaxomicin is a new antibiotic used to treat Clostridium difficile infection (CDI)" }, { "input": "What antibiotic is currently used as the standard of care for Clostridium Difficile infection as of 2018", "output": "fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. fidaxomicin is a new antibiotic used to treat clostridium difficile infection (cdi)." }, { "input": "What antibiotic is currently used as the standard of care for Clostridium Difficile infection as of 2018", "output": "Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent fidaxomicin" }, { "input": "Which proteins are markers of HPV oncogenic activity?", "output": "p16INK4a (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions." }, { "input": "Which features are evaluated with the CRAFFT screening test?", "output": "The CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) was developed as a brief screening instrument for adolescents to measure Alcohol and other substance use disorders." }, { "input": "Describe the bartender algorithm", "output": "Barcode sequencing (bar-seq) is a high-throughput, and cost effective method to assay large numbers of cell lineages or genotypes in complex cell pools. Because of its advantages, applications for bar-seq are quickly growing-from using neutral random barcodes to study the evolution of microbes or cancer, to using pseudo-barcodes, such as shRNAs or sgRNAs to simultaneously screen large numbers of cell perturbations. Bartender is an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data. It comprises a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods. Bartender is available at no charge for non-commercial use at https://github.com/LaoZZZZZ/bartender-1.1" }, { "input": "Which was the first gene therapy to receive marketing authorization in the European Union?", "output": "The first gene therapy to receive marketing authorization in the European Union was Glybera (alipogene tiparvovec)." }, { "input": "Is treatment with Bacillus Calmette Guerin used for bladder cancer?", "output": "Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer." }, { "input": "List lymphocytes that are analyzed by a flow cytometer.", "output": "Quantitation of lymphocyte subsets (B cells, T cells, CD4 and CD8 T cells and NK cells) classically relies on quantitation of lymphocytes and immunophenotyping by flow cytometry." }, { "input": "List two drugs that are included in the Akynzeo pill?", "output": "Akynzeo is an oral fixed combination of netupitant and palonosetron that is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV)." }, { "input": "Describe CapSim", "output": "CapSim is a software package for simulation of targeted capture sequencing. Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms. The simulated data can be used for evaluating the performance of the analysis pipeline, as well as the efficiency of the probe design. Parameters of the various stages in the sequencing process can also be evaluated in order to optimize the experiments.Availability and implementation: CapSim is publicly available under BSD license at https://github.com/Devika1/capsim." }, { "input": "Which company produces Glybera?", "output": "Glybera is a product of Chiesi Pharma." }, { "input": "What is the mode of action of Tetrocarcin-A?", "output": "The anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells." }, { "input": "List some substances important for proper nervous system function that gut microbes produce.", "output": "serotonin\ngamma-aminobutyric acid\nshort-chain fatty acids\nneurotransmitters" }, { "input": "Safinamide is approved for treatment of which disease?", "output": "Safinamide is a monoamine-oxidase B (MAO-B) inhibitor licensed as add-on therapy for people with idiopathic Parkinson's disease who are experiencing motor fluctuations with levodopa." }, { "input": "What is the tradename of apixaban?", "output": "The tradename of apixaban is Eliquis." }, { "input": "Under which environment does SELANSI run?", "output": "SELANSI (SEmi-LAgrangian SImulation of GRNs) is a software toolbox for the simulation of stochastic multidimensional gene regulatory networks. SELANSI exploits intrinsic structural properties of gene regulatory networks to accurately approximate the corresponding Chemical Master Equation with a partial integral differential equation that is solved by a semi-lagrangian method with high efficiency. SELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi." }, { "input": "Under which environment does SELANSI run?", "output": "matlab environment" }, { "input": "Is eculizumab used for treatment of myasthenia gravis?", "output": "Yes, eculizumab is used for treatment of myasthenia gravis." }, { "input": "What is the name of the Cas13 based diagnostic test for the Zika and dengue viruses?", "output": "The Cas13-based platform that can detect Zika and dengue viruses is called SHERLOCK (specific high-sensitivity enzymatic reporter unlocking)." }, { "input": "What are CRISPR-Cas12a proteins?", "output": "CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing on the basis of its ability to generate targeted, double-stranded DNA breaks. RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules" }, { "input": "What type of drug is apixaban?", "output": "Apixaban is an anticoagulant." }, { "input": "Can cardiospheres be produced from skin fibroblasts?", "output": "Yes, induced cardiospheres (iCS) can be produced by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors." }, { "input": "What the chromsomal location of the gene that is deleted in Potocki-Shaffer syndrome?", "output": "In Potocki-Shaffer syndrome (PSS), the full phenotypic spectrum is manifested when deletions are at least 2.1\u2009Mb in size at 11p11.2" }, { "input": "What the chromsomal location of the gene that is deleted in Potocki-Shaffer syndrome?", "output": "Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome caused by heterozygous deletion of 11p11.2p12." }, { "input": "List 3 enterotoxins produced by Clostridium difficile.", "output": "Toxin A (TcdA), toxin B (TcdB), and binary toxin (CDT) produced by Clostridium difficile (CD)" }, { "input": "Which tissue secretes vaspin?", "output": "Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions." }, { "input": "List adipokines.", "output": "adiponectin\nleptin\nresistin" }, { "input": "List features of the DOOR syndrome.", "output": "DOOR syndrome is a rare multisystem genetic disorder, consisting of deafness (sensorineural), onychodystrophy, osteodystrophy, and mental retardation." }, { "input": "Which web-based pedigree editors are available?", "output": "Pedigreejs and Madeline 2.0 Pedigree Drawing Engine (PDE)" }, { "input": "What is the mechanism of action of Solriamfetol?", "output": "Solriamfetol is a selective norepinephrine-dopamine reuptake inhibitor. It is used to treat excessive sleepiness in obstructive sleep apnea and narcolepsy patients." }, { "input": "What is the difference between the nuclease Cas13a and C2c2", "output": "Cas13a was previously called C2c2." }, { "input": "Phlorotannin is extracted from what plant?", "output": "Phlorotannin is extracted from Brown Seaweed or brown Algae" }, { "input": "Phlorotannin is extracted from what plant?", "output": "phlorotannins present in brown seaweeds Phlorotannins, phenolic compounds produced exclusively by seaweeds" }, { "input": "Where are pannexins localized?", "output": "Pannexins (Panxs) are a multifaceted family of ion and metabolite channels that play key roles in a number of physiological and pathophysiological settings. These single membrane large-pore channels exhibit a variety of tissue, cell type, and subcellular distributions." }, { "input": "What is the mechanism of action of cariprazine?", "output": "Cariprazine is a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors. Cariprazine shows also has affinity for 5-HT2B, and 5-HT1A receptors. It also shows moderate affinity toward \u03c31, 5-HT2A, and histamine H1 receptors. It is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder" }, { "input": "Which tool is used to visualise the junction sites of chloroplast genomes?", "output": "IRscope is an online program to visualize the junction sites of chloroplast genomes. It allows the users to depict the genetic architecture of up to ten chloroplast genomes in the vicinity of the sites connecting the inverted repeats to the short and long single copy regions. The software and its dependent libraries are fully coded in R and the reflected plot is scaled up to realistic size of nucleotide base pairs in the vicinity of the junction sites. The input of the program is an annotation GenBank (.gb) file, the accession or GI number of the sequence or a DOGMA output file." }, { "input": "Which curated databases exist for spider-venom toxins?", "output": "ArachnoServer and its updated version ArachnoServer 2.0 are manually curated databases providing information on the sequence, structure and biological activity of protein toxins from spider venoms." }, { "input": "What is the difference between CRISPR-Cas12a and CRISPR-Cpf1?", "output": "CRISPR-Cas12a and CRISPR-Cpf1 refer to the same thing." }, { "input": "Please list 2 antitoxin antibodies approved by the FDA for reducing the recurrence of Clostridium difficile infection", "output": "The antitoxin antibodies actoxumab and bezlotoxumab bind to and neutralize TcdA and TcdB, respectively. Bezlotoxumab was recently approved by the FDA for reducing the recurrence of CDI." }, { "input": "List the functions of the protein lactotransferrin.", "output": "Lactotransferrin has numerous biological roles, including the regulation of iron absorption and modulation of immune responses, and has anti-microbial, anti-viral, antioxidant, anti-cancer, and anti-inflammatory activities." }, { "input": "Does Axitinib prolong survival of Pancreatic Cancer patients?", "output": "No. The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer." }, { "input": "Which Python tool has been developed for network-based stratification of tumor mutations?", "output": "PyNBS is a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes." }, { "input": "Through which protein interaction does MLP regulate F-actin dynamics?", "output": "The interaction of MLP with CFL2 has direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F-actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2 molecular ratio of 2:1. Deregulation of this interaction by intracellular pH variations, CFL2 phosphorylation, MLP or CFL2 gene mutations, or expression changes, as observed in a range of cardiac and skeletal myopathies, could impair F-actin depolymerization, leading to sarcomere dysfunction and disease." }, { "input": "Is there any association between suicide and autism in adolescents, yes or no?", "output": "Adults with autism spectrum disorder (ASD) are at increased risk of suicide compared to the general population." }, { "input": "Is lactotransferrin a tumour suppressor?", "output": "Lactotransferrin (LTF) has been confirmed to act as a tumor suppressor in multiple cancers." }, { "input": "What is CVT-301?", "output": "CVT-301 is inhaled levodopa (LD) formulation for development as a self-administered treatment for relief of OFF periods in Parkinson's disease. CVT-301 provided rapid improvement of motor function, and daily OFF time was significantly reduced at the higher dose." }, { "input": "Are there tools for visualizing and processing long-read sequencing data?", "output": "Yes. Tools such as NanoPack for instance have been developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences." }, { "input": "Name siRNA drugs that have entered phase 2-3 clinical trials (by 2019).", "output": "siRNAs that have entered phase 2-3 clinical trials by 2019 include PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3)." }, { "input": "Where is fatty acid binding protein 2 expressed?", "output": "fatty acid binding protein 2 is expressed by intestinal epithelial cells" }, { "input": "Which gene mutation is associated with Woodhouse Sakati syndrome?", "output": "DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements." }, { "input": "Mention computational tools that have been developed for alternative polyadenylation (APA) sites analysis", "output": "TAPAS, PlantAPA and IntMAP" }, { "input": "What is patisiran?", "output": "Patisiran (ONPATTRO\u2122) is a double-stranded small interfering RNA encapsulated in a lipid nanoparticle for delivery to hepatocytes. By specifically binding to a genetically conserved sequence in the 3' untranslated region of mutant and wild-type transthyretin (TTR) messenger RNA, patisiran causes its degradation (via RNA interference) and subsequently a reduction in serum TTR protein levels and tissue TTR protein deposits. It has been approved in the USA for the treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis (hATTR) in adults and subsequently approved in the EU for the treatment of hATTR in adults with stage 1 or 2 polyneuropathy." }, { "input": "Losigamone can be used for treatment of which disease?", "output": "Losigamone is sometimes used as an add-on therapy for epilepsy." }, { "input": "Which curated data resources for ChIP-seq data are available?", "output": "The MGA repository, Cistrome Data Browser, CR Cistrome and GeneProf data." }, { "input": "How many pseudokinases are there in the human kinome?", "output": "There are approximately 50 pseudokinases in the human kinome." }, { "input": "What is the mechanism of action of Inclisiran?", "output": "Inclisiran, a novel, synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes. Inclisiran targets intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, long-term, significant reduction in LDL-C." }, { "input": "Which tool has been developed for visualization of non-covalent contacts?", "output": "Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. Typical visualizations (such as ball and stick) primarily depict covalent bonds. In contrast, non-covalent contacts between atoms, which govern normal physiology, pathogenesis, and drug action, are seldom visualized. The Protein Contacts Atlas has been developed as an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. This resource enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information." }, { "input": "What is opdivo?", "output": "Opdivo or nivolumab is a treatment for patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor." }, { "input": "Has Hesperidin any role as a Neuroprotective Agent?", "output": "Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease" }, { "input": "Has Hesperidin any role as a Neuroprotective Agent?", "output": "hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury" }, { "input": "Has Hesperidin any role as a Neuroprotective Agent?", "output": "Hesperidin has been shown to have a role as a Neuroprotective Agent" }, { "input": "Has Hesperidin any role as a Neuroprotective Agent?", "output": "Hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury Neuroprotective Effects of Hesperidin on Cerebral Vasospasm" }, { "input": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "output": "Yes, apoE mimetics are being considered as a treatment against Alzheimer's disease, and they have been shown to protect AD mouse models against these AD-like features." }, { "input": "Which diseases are treated with netarsudil?", "output": "In 2 large, randomized, double-masked trials, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma." }, { "input": "Can you computationally predict Molecular Recognition Features (MoRFs) regions in Intrinsically Disordered Proteins (IDPs)?", "output": "Yes. There are various tools available in the literature that enable computational identification of Molecular Recognition Features (MoRFs) regions in intrinsically disordered protein sequences." }, { "input": "Which malignancies is Keytruda approved for before 2017?", "output": "Before 2017 Keytruda was approved for the treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma." }, { "input": "Which was the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body?", "output": "The first approved tumor treatment using a common biomarker rather than specified tumor locations in the body was Keytruda, which is a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers." }, { "input": "What does Prevnar 13 consist of?", "output": "Prevnar 13 consists of 13 serotype-specific polysaccharides of Streptococcus pneumoniae (pneumococcus), each covalently conjugated to a non-toxic immunogenic carrier protein." }, { "input": "What is the route of administration of apixaban?", "output": "Apixaban is administered orally." }, { "input": "What is the cause of a STAG3 truncating variant?", "output": "Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family" }, { "input": "What is the cause of a STAG3 truncating variant?", "output": "Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family." }, { "input": "Which tools have been developed for computing split-networks?", "output": "Split-networks are a generalization of phylogenetic trees that have proven to be a powerful tool in phylogenetics. Tools for computing such networks include SPECTRE, FlatNJ and QNet." }, { "input": "List 3 apoE mimetics.", "output": "COG133, COG112 and Ac-hE18A-NH(2) are apoE mimetics." }, { "input": "What are there sex differences in SAMHD1 activity?", "output": "The host restriction factor SAMHD1 exists in a hyperphosphorylated, less active state in male-derived macrophages. SAMHD1 is an essential modulator of infectivity in a sex-dependent manner in macrophages, constituting a novel component of sex differences in innate immune control of HIV-1." }, { "input": "Which enhancers are characterized as latent?", "output": "Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation." }, { "input": "Which enhancers are characterized as latent?", "output": "Latent enhancers are defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation." }, { "input": "Which enhancers are characterized as latent?", "output": "Here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by TFs" }, { "input": "Which enhancers are characterized as latent?", "output": "here, we describe latent enhancers, defined as regions of the genome that in terminally differentiated cells are unbound by tfs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation." }, { "input": "Which enhancers are characterized as latent?", "output": "Here , we describe latent enhancers , defined as regions of the genome that in terminally differentiated cells are unbound by TFs and lack the histone marks characteristic of enhancers but acquire these features in response to stimulation ." }, { "input": "What is the difference between COG133 and COG112?", "output": "COG112 results from the fusion of COG133 to a protein transduction domain." }, { "input": "Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 21, yes or no?", "output": "Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 22." }, { "input": "Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 21, yes or no?", "output": "The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome." }, { "input": "Is the protein Asporin related to disease?", "output": "Yes,\nAccumulating evidence demonstrates the involvement of asporin in OA pathogenesis. Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer." }, { "input": "Can TAD disruption lead to disease?", "output": "TAD boundaries are insulators of genomic neighborhoods. \u03a4he disruption of these structures by genomic rearrangements can result in gene misexpression and disease." }, { "input": "Can TAD disruption lead to disease?", "output": "We discuss how the disruption of these structures by genomic rearrangements can result in gene misexpression and disease." }, { "input": "Is L-4F an apoE mimetic peptide?", "output": "No, L-4F is an apoA-I mimetic peptide." }, { "input": "Which cells secrete lactotransferrin?", "output": "We conclude that lactotransferrin represents a late stage differentiation marker of neutrophils, macrophages and distinct subtypes of dendritic cells." }, { "input": "Which plant does oleuropein originate from?", "output": "Oleuropein originates from olive trees, and is specifically found in olive leaf extracts." }, { "input": "Reslizumab is a humanized monoclonal antibody to treat what specific type of asthma?", "output": "Reslizumab in the treatment of severe eosinophilic asthma:\u00a0an update." }, { "input": "Reslizumab is a humanized monoclonal antibody to treat what specific type of asthma?", "output": "Reslizumab is a humanized monoclonal antibody to treat eosinophilic asthma" }, { "input": "What is the function of the protein Magt1?", "output": "The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium ([Mg2+]i) levels." }, { "input": "Can oleuropein aglycone interfere with amyloid aggregation?", "output": "Yes, oleuropein aglycone interferes in vitro and in vivo with amyloid aggregates." }, { "input": "What is the function of the transcriptional co-activator p300?", "output": "The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin." }, { "input": "What is another name for the plant Sideritis scardica?", "output": "Sideritis scardica is also known as ironwort or mountain tea." }, { "input": "How are gas vesicle proteins used in imaging?", "output": "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting." }, { "input": "How are gas vesicle proteins used in imaging?", "output": "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting" }, { "input": "How are gas vesicle proteins used in imaging?", "output": "Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents." }, { "input": "From where is gamabufotalin (GBT) isolated?", "output": "gamabufotalin (GBT) was isolated from toad venom." }, { "input": "What are super-enhancers", "output": "Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases." }, { "input": "Is Apelin usually decreased in diabetes?", "output": "Different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes." }, { "input": "What is a mitosome?", "output": "Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. \tThe mitosomes have abandoned typical mitochondrial traits such as the mitochondrial genome and aerobic respiration and their single role known to date is the formation of iron-sulfur clusters" }, { "input": "What is the price of KYMRIAH treatment in 2019?", "output": "Kymriah, produced by Novartis has a price tag of US$475,000." }, { "input": "Human dihydroorotate dehydrogenase is a drug target and is involved in what biosynthetic pathway", "output": "Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis" }, { "input": "Human dihydroorotate dehydrogenase is a drug target and is involved in what biosynthetic pathway", "output": "The flavoenzyme dihydroorotate dehydrogenase (DHODH) catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which exerts vital functions in the cells, especially within DNA and RNA biosynthesis" }, { "input": "Human dihydroorotate dehydrogenase is a drug target and is involved in what biosynthetic pathway", "output": "Dihydroorotate dehydrogenase (DHODH) catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which exerts vital functions in the cells, especially within DNA and RNA biosynthesis." }, { "input": "List targets of classical analgesics.", "output": "Patient phenotypes in pharmacological pain treatment varies between individuals, which could be partly assigned to their genotypes regarding the targets of classical analgesics (OPRM1, PTGS2)" }, { "input": "Is actin present in the nucleus?", "output": "Yes,\nThe revitalization of research into nuclear actin occurred after it was found that cellular stresses induce the nuclear localization and alter the structure of actin." }, { "input": "What is the indication for KYMRIAH?", "output": "Kymriah\u2122 has been approved for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia." }, { "input": "What is the effect of NFIA on astrocyte differentiation?", "output": "NFIA promotes astrocyte differentiation from neural precursor cells." }, { "input": "What is the mode of action for Tocilizumab?", "output": "Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs" }, { "input": "Where is the protein protamine 2 expressed?", "output": "Human sperm express two types of protamine: protamine 1 (P1) and the family of protamine 2 (P2) proteins." }, { "input": "Can miR-122 target RUNX2?", "output": "Yes, miR-122 directly targets RUNX2." }, { "input": "Tocilizumab is an anti-TNF antibody, yes or no?", "output": "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations." }, { "input": "Tocilizumab is an anti-TNF antibody, yes or no?", "output": "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor licensed in 2009" }, { "input": "Tocilizumab is an anti-TNF antibody, yes or no?", "output": "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor" }, { "input": "Tocilizumab is an anti-TNF antibody, yes or no?", "output": "was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody" }, { "input": "Tocilizumab is an anti-TNF antibody, yes or no?", "output": "Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6 receptor licensed in 2009 and recommendations consider TCZ as one of the treatements indicated after methotrexate and/or TNF inhibitors failure in adult RA." }, { "input": "Is it possible to analyze exosomes with FACS?", "output": "Yes,\na novel strategy for generating metabolically-labeled fluorescent exosomes that can be counted by flow cytometry assay (FACS) and characterized." }, { "input": "Which company developed opdivo?", "output": "Opdivo or nivolumab was developed by Bristol-Myers Squibb." }, { "input": "What are DMARDs?", "output": "To determine the utility of ultrasonography in guiding modification of disease-modifying anti-rheumatic drug (DMARD) and steroid therapy for inflammatory arthritis (IA)" }, { "input": "What are DMARDs?", "output": "DMARDs are Disease Modifying anti-rheumatic drugs (DMARD)." }, { "input": "What are DMARDs?", "output": "Treatment with disease-modifying antirheumatic drugs (DMARDs)" }, { "input": "What are DMARDs?", "output": "Treatment with disease-modifying antirheumatic drugs (DMARDs) was 61% (claims data)" }, { "input": "What are DMARDs?", "output": "Treatment with disease-modifying antirheumatic drugs (DMARDs) was 61% (claims data) and" }, { "input": "What is the aim of the MitoCeption protocol?", "output": "The MitoCeption protocol directly and quantitatively transfer mitochondria, isolated from cell type A, to recipient cell type B." }, { "input": "Can prevnar 13 be used in children?", "output": "Yes, PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications." }, { "input": "Was stelara developed by Amgen?", "output": "Stelara was developed by Janssen Pharmaceuticals, Inc., Horsham, PA, USA." }, { "input": "List off label uses for Rituximab.", "output": "Off label uses for rituximab are for poly- and dermatomyositis, multiple sclerosis, immune thrombocytopenia, systemic lupus erythematosus (SLE), lupus nephritis (LN), and other immune diseases." }, { "input": "Can mitochondria pass through membrane nanotubes?", "output": "Yes,\nMembrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs)." }, { "input": "What is Quorum Sensing in bacteria?", "output": "In many pathogenic microorganisms, communication systems, collectively termed quorum sensing (QS)," }, { "input": "What is Quorum Sensing in bacteria?", "output": "In many pathogenic microorganisms, communication systems, collectively termed quorum sensing (QS), have been observed" }, { "input": "What is Quorum Sensing in bacteria?", "output": "In most bacteria, a global level of regulation, termed quorum sensing (QS), exists involving intercellular communication via the production and response to cell density-dependent signal molecules." }, { "input": "What is the cause of Krabbe disease?", "output": "Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase." }, { "input": "Name a CFL2 mutation which is associated with nemaline myopathy?", "output": "A mutation in CFL2 was identified in a family with nemaline myopathy, namely a homozygous missense mutation in exon 2 (c.19G>A, p.Val7Met)." }, { "input": "What cellular process is the gene product of NANOG involved in?", "output": "NANOG is a transcription factor and a biomarker of cancer and pluripotent stem cells." }, { "input": "Name the uses of Sideritis scardica in traditional medicine.", "output": "Sideritis scardica is used in traditional medicine as a loosening agent in bronchitis and bronchial asthma; against the common cold and lung emphysema; in the treatment of inflammation, gastrointestinal disorders and coughs; and as an active constituent of dietary supplements for the prevention of anemia. Sideritis scardica has been attributed a broad range of properties such as antimicrobial, anti-inflammatory, cytotoxic, antioxidant, gastroprotective, antiglioma, and triple monoamine reuptake inhibition." }, { "input": "What are the phenotypic features of the autosomal dominant, development disease, Noonans syndrome", "output": "Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate" }, { "input": "What are the phenotypic features of the autosomal dominant, development disease, Noonans syndrome", "output": "Noonan syndrome is an autosomal dominant disease and is characterized by developmental problems. Symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate" }, { "input": "Are protamines ubiquitously expressed?", "output": "No,\nProtamines are nuclear proteins which are specifically expressed in haploid male germ cells." }, { "input": "Are Crocus sativus compounds being considered against Alzheimer's disease?", "output": "Yes, it has been observed that Crocus sativus extracts and compounds have a positive effect against Alzheimer's disease." }, { "input": "Rickettsia felis was described as a human pathogen almost two decades ago, what is it's main arthropod vector?", "output": "Cat fleas (Ctenocephalides felis) carry Rickettsia felis" }, { "input": "Rickettsia felis was described as a human pathogen almost two decades ago, what is it's main arthropod vector?", "output": "Cat fleas (Ctenocephalides felis) carrying Rickettsia felis and Bartonella species in Hong Kong." }, { "input": "Rickettsia felis was described as a human pathogen almost two decades ago, what is it's main arthropod vector?", "output": "Cat fleas (Ctenocephalides felis) carrying Rickettsia felis and Bartonella species in Hong Kong" }, { "input": "Are there any anti-amyloid antibody approved as drug for Alzheimer's disease treatment?", "output": "No new drugs have been approved during the past 15 years; and the available medications are not cost-effective." }, { "input": "Do Crocus sativus extracts loosen the blood-brain barrier?", "output": "No, in vitro and in vivo experiments show that the Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB)." }, { "input": "Are artificial blood cells available?", "output": "No,\nThe critical point for the break through for artificial blood products did not come yet but could be ahead-" }, { "input": "Have apolipoprotein mimetics been used in clinical trials?", "output": "Yes, apolipoprotein mimetics have entered clinical trials." }, { "input": "What are 2 organisms that can cause Human toxocariasis?", "output": "Human toxocariasis , a worldwide parasitic disease , is caused by the larval stage of intestinal nematodes of dogs and cats , namely Toxocara canis and Toxocara cati" }, { "input": "What are 2 organisms that can cause Human toxocariasis?", "output": "Human toxocariasis, a worldwide parasitic disease, is caused by the larval stage of intestinal nematodes of dogs and cats, namely Toxocara canis and Toxocara cati" }, { "input": "What are 2 organisms that can cause Human toxocariasis?", "output": "human toxocariasis, a worldwide parasitic disease, is caused by the larval stage of intestinal nematodes of dogs and cats, namely toxocara canis and toxocara cati" }, { "input": "What is the dbSUPER database?", "output": "dbSUPER is the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease. dbSUPER provides a responsive and user-friendly web interface to facilitate efficient and comprehensive search and browsing. The data can be easily sent to Galaxy instances, GREAT and Cistrome web-servers for downstream analysis, and can also be visualized in the UCSC genome browser where custom tracks can be added automatically. The data can be downloaded and exported in variety of formats. Furthermore, dbSUPER lists genes associated with super-enhancers and also links to external databases such as GeneCards, UniProt and Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined regions." }, { "input": "List places in the body where somatostatin is produced.", "output": "Somatostatin is a cyclic peptide well known for its strong regulatory effects throughout the body. Also known by the name of growth hormone inhibiting hormone, it is produced in many locations, which include the olfactory bulb, hair follicles, pancreas, retina, and central nervous system (CNS)." }, { "input": "Is the Philadelphia chromosome a fusion between parts of chromosomes 1 and 9?", "output": "No,\nChronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22." }, { "input": "What is YESCARTA?", "output": "Yescarta is an autologous chimeric antigen receptor (CAR) T cell therapy approved by the FDA. Yescarta\u2122 is approved for the treatment of adult patients with R/R large B cell lymphoma. It is a CD19-specific CAR T cell therapy lysing CD19-positive targets." }, { "input": "What are the 3 types of immunoglobulin heavy chain containing antibodies found in human breast milk?", "output": "IgA, IgG, AND IgM can be found in human milk." }, { "input": "What is a exposome?", "output": "The exposome is a novel conceptual framework that allows for concurrent examination of multiple intrinsic and extrinsic factors, including environmental exposures, as well as changes in exposures over time, to elucidate the complex environmental factors that affect health outcomes." }, { "input": "What does the strimvelis treatment consist of?", "output": "Strimvelis consists of autologous CD34+ cells transduced to express adenosine deaminase [ADA]." }, { "input": "Can therapeutic levels of Vedolizumab be found in the breast milk of nursing mothers following treatment for Inflammatory bowel disease?", "output": "vedolizumab can be detected in the breast milk of nursing mothers. although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant." }, { "input": "Can therapeutic levels of Vedolizumab be found in the breast milk of nursing mothers following treatment for Inflammatory bowel disease?", "output": "Vedolizumab is barely detectable in the breast milk of nursing mothers. measurements in breast milk after an infusion of the drug showed that levels did not surpass 480 ng/ml, which was roughly 1/100 of the comparable serum levels." }, { "input": "Can therapeutic levels of Vedolizumab be found in the breast milk of nursing mothers following treatment for Inflammatory bowel disease?", "output": "Vedolizumab can be detected in the breast milk of nursing mothers .\nAlthough more data are imperative , the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant ." }, { "input": "Can therapeutic levels of Vedolizumab be found in the breast milk of nursing mothers following treatment for Inflammatory bowel disease?", "output": "Vedolizumab can be detected in the breast milk of nursing mothers. Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant." }, { "input": "What is predicted using SURFY?", "output": "surfaceome predictor SURFY, based on machine learning." }, { "input": "Which was the first adeno-associated virus vector gene therapy product approved in the United States?", "output": "The first adeno-associated virus vector gene therapy product in the United States was Luxturna." }, { "input": "What is known about the gene MIR140?", "output": "Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling.\nOur findings showed the novel transcriptional role of miR140-5p in the expression of Nrf2 and miR-140-5p protected against Cisplatin induced oxidative stress by activating Nrf2-dependent antioxidant pathway, providing a potentially therapeutic target in acute kidney injury." }, { "input": "Which gene therapy treatment is FDA approved for retinal dystrophy?", "output": "Luxturna is approved by the Food and Drug Administration (FDA) for the treatment of inherited retinal dystrophy." }, { "input": "Salivary Cortisol is a biomarker for what disease/syndrome/condition?", "output": "Salivary cortisone , as a biomarker for psychosocial stress , is associated with state anxiety and heart rate .\nortisol as a stress biomarker" }, { "input": "Salivary Cortisol is a biomarker for what disease/syndrome/condition?", "output": "Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate." }, { "input": "Salivary Cortisol is a biomarker for what disease/syndrome/condition?", "output": "Salivary Cortisol is a biomarker for stress" }, { "input": "Salivary Cortisol is a biomarker for what disease/syndrome/condition?", "output": "These results suggest that the saliva cortisol level is therefore a useful biomarker to evaluate the stress in AD patients." }, { "input": "What is the function of the cGAS pathway?", "output": "The cGAS-STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity." }, { "input": "Does RUNX2 inhibit astrocyte differentiation?", "output": "No, RUNX2 promostes astrocyte differentiation." }, { "input": "What are 5 key questions in human performance modeling?", "output": "There are five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are." }, { "input": "What are 5 key questions in human performance modeling?", "output": "the five key questions of human performance modeling: 1) why we build models of human performance; 2) what the expectations of a good human performance model are; 3) what the procedures and requirements in building and verifying a human performance model are; 4) how we integrate a human performance model with system design; and 5) what the possible future directions of human performance modeling research are." }, { "input": "What are 5 key questions in human performance modeling?", "output": "the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are." }, { "input": "What are 5 key questions in human performance modeling?", "output": "the five key questions of human performance modeling: 1) Why we build models of human performance; 2) What the expectations of a good human performance model are; 3) What the procedures and requirements in building and verifying a human performance model are; 4) How we integrate a human performance model with system design; and 5) What the possible future directions of human performance modeling research are" }, { "input": "What is the mode of action of the Tc toxins?", "output": "The toxin complex (tc) genes of bacteria comprise a large and growing family whose mode of action remains obscure. Tc toxins are widely distributed among different gram-negative and gram-positive bacteria, where they act as pathogenicity factors. Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood." }, { "input": "What does RUNX2 stand for?", "output": "Runt related factor-2" }, { "input": "Where, in the body, would the Cobb-Stainsby excision arthroplasty be performed?", "output": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy ( Stainsby ) with extensor tendon transfer to the metatarsal head ( Cobb ) ." }, { "input": "Where, in the body, would the Cobb-Stainsby excision arthroplasty be performed?", "output": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb)" }, { "input": "Where, in the body, would the Cobb-Stainsby excision arthroplasty be performed?", "output": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb)." }, { "input": "Where, in the body, would the Cobb-Stainsby excision arthroplasty be performed?", "output": "The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer" }, { "input": "Are cardenolides inhibitors of Na+/K+ ATPase?", "output": "Yes,\nCardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells." }, { "input": "Can antisense threapy be used for Huntington's disease?", "output": "Yes, antisense oligonucleotide therapy has been shown to lower Huntingtin mRNA levels and be beneficial against Huntington's disease." }, { "input": "What are acoustic reported genes used to detect?", "output": "Acoustic reporter genes are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound." }, { "input": "What are acoustic reported genes used to detect?", "output": "acoustic reporter genes , which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound ," }, { "input": "What are acoustic reported genes used to detect?", "output": "Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound" }, { "input": "What are acoustic reported genes used to detect?", "output": "Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound," }, { "input": "What are acoustic reported genes used to detect?", "output": "acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound," }, { "input": "What is a lipin 1 protein doing?", "output": "As a lipin family founding member, lipin1 exerts dual functions as a phosphatidate phosphatase enzyme and/or a co-transcriptional regulator in lipid metabolism. In fact, it is also involved in many other cell processes." }, { "input": "Which company produces patisiran?", "output": "Patisiran has been developed by Alnylam Pharmaceuticals." }, { "input": "What protein is recruited by Crumbs to regulate tracheal development?", "output": "In Drosophila, stellate-shaped tracheal terminal cells make seamless tubes, Early endocytosis maintains normal steady-state levels of Crumbs, which recruits apical phosphorylated (active) Moesin (Moe), which in turn regulates seamless tube shape in the development of the trachea." }, { "input": "Is collagen matrix of human articular cartilage changing with disease?", "output": "No,\nThe collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease." }, { "input": "Is ustekinumab a polyclonal antibody?", "output": "Ustekinumab is a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23." }, { "input": "Where in the body, is ghrelin secreted?", "output": "Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa." }, { "input": "Where in the body, is ghrelin secreted?", "output": "Ghrelin , an orexigenic peptide , is secreted from endocrine cells in the gastric mucosa ." }, { "input": "Where in the body, is ghrelin secreted?", "output": "BACKGROUND: Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa." }, { "input": "Where in the body, is ghrelin secreted?", "output": "ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa." }, { "input": "List the ERM proteins.", "output": "ezrin\nradixin\nmoesin" }, { "input": "What is epitranscriptomics?", "output": "Epitranscriptomics is the fast expanding area of RNA modifications." }, { "input": "What is resistin?", "output": "The adipocyte-secreting adipokine, resistin, may play a critical role in the modulation of inflammatory diseases." }, { "input": "What is resistin?", "output": "Resistin, a pro-inflammatory cytokine," }, { "input": "Is Pim-1 a protein phosphatase?", "output": "No,\nPim-1 is a kinase and not a phosphatase." }, { "input": "Name three binding partners of cofilin 2.", "output": "Cofilin 2 can bind miR-201a, the protein 14-3-3, and ATP/ADP-Pi-actin filaments." }, { "input": "What is the function of GvpA?", "output": "The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC, and" }, { "input": "What is the function of GvpA?", "output": "The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC, and seven additional accessory proteins are also involved." }, { "input": "What is the function of GvpA?", "output": "Gas vesicles are proteinaceous, gas-filled nanostructures produced by some bacteria and archaea. The hydrophobic major structural protein GvpA forms the ribbed gas vesicle wall." }, { "input": "What is the function of GvpA?", "output": "The gas vesicle wall is solely formed of proteins with the two major components, GvpA and GvpC," }, { "input": "What is the function of GvpA?", "output": "the gas vesicle wall is solely formed of proteins with the two major components, gvpa and gvpc," }, { "input": "What is a SMR based BCI?", "output": "Many Brain Computer Interface (BCI) and neurofeedback studies have investigated the impact of sensorimotor rhythm (SMR)" }, { "input": "What is a SMR based BCI?", "output": "An SMR based BCI is a SensoriMotor Rhythm Based brain-Computer Interface (BCI). It is an alternative communication system between the human brain and an output device and is controlled by a sensorimotor rhythm (SMR), a type of brain wave." }, { "input": "Is myc a tumour suppressor gene?", "output": "No,\r\nMyc is a proto-oncogene." }, { "input": "Which syndrome is associated to SAMHD1 gene mutations?", "output": "Mutations in the SAMHD1 gene that cause the severe autoimmune disease, Aicardi-Goutieres syndrome (AGS)." }, { "input": "List proteins with RING domain.", "output": "RING1\nTRIM proteins\nTRAF6 \nUHRF1\nMARCH7\nSINA\nBRCA1" }, { "input": "What conditions are associated with mutations in the gene FAAH?", "output": "Human FAAH gene mutations are associated with increased body weight and obesity. Results suggest that genetic mutations in FAAH may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence.\nresearch on the genetic modulation of pain has already identified variants in these genes, relative to pain, which may facilitate the pharmacogenetic assessments of new analgesics." }, { "input": "What is the results of mutations in the gene autoimmune regulator?", "output": "Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene (AIRE)" }, { "input": "Is CD63 an exosomal marker?", "output": "Yes,\nCD63 is a exosomal marker" }, { "input": "Is subdural empyema a complication of sinusitis?", "output": "Yes, subdural empyema can be a complication of sinusitis" }, { "input": "What is aphasia?", "output": "Aphasia is an inability to comprehend or formulate language because of damage to specific brain regions." }, { "input": "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium, yes or no", "output": "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium and causes anaplasmosis" }, { "input": "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium, yes or no", "output": "The genus Anaplasma belonging to the Anaplasmataceae family (order Rickettsiales) comprises obligate intracellular Gram-negative bacteria of veterinary and public health importance. nov." }, { "input": "What is the role of Acyl-Homoserine Lactone in bacteria?", "output": "A number of bacteria use a class of chemical compounds called acyl-homoserine lactones (AHLs) as quorum sensing (QS) signals to coordinate their behavior at the population level, including pathogens like Pseudomonas aeruginosa." }, { "input": "What is the role of Acyl-Homoserine Lactone in bacteria?", "output": "Some bacteria use a class of chemical compounds called acyl-homoserine lactones (AHLs) as quorum sensing (QS) signals to coordinate their behavior at the population level." }, { "input": "What is the role of Acyl-Homoserine Lactone in bacteria?", "output": "tructural analogues of acyl homoserine lactones with Quorum Sensing antagonist activity." }, { "input": "List 3 indications for rituximab.", "output": "Rituximab is used to treat rheumatoid arthritis as well as poly- and dermatomyositis, chronic lymphocytic leukemia, juvenile idiopathic arthritis, and Pemphigus foliaceus (PF)." }, { "input": "Is the crystal structure of Pim-1 available?", "output": "Yes,\nThe crystal structures of Pim1 in apo form and bound with AMPPNP have been solved" }, { "input": "Do tumour-associated macrophages have a prognostic role in gliomas?", "output": "M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment." }, { "input": "Is TNF-\u03b1 an activator of pancreatic stellate cells?", "output": "Yes,\nTNF-\u03b1 is the prime factor responsible for the activation of pancreatic stellate cells." }, { "input": "Can mitochondria transfer from cell to cell?", "output": "Yes,\nthe recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago." }, { "input": "Can Enlimomab improve stroke outcomes?", "output": "No. Anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke and, indeed, may significantly worsen stroke outcome." }, { "input": "What is the Triad of Alport Syndrome?", "output": "Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations." }, { "input": "Does GRHL2 over-expression lead to EMT?", "output": "Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. Grhl2 antagonizes transforming growth factor-b (TGFb)-induced EMT" }, { "input": "Does GRHL2 over-expression lead to EMT?", "output": "The transcription factor--Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype. Grhl2 is a suppressor of EMT. Grhl2 antagonizes transforming growth factor-b (TGFb)-induced EMT." }, { "input": "Does GRHL2 over-expression lead to EMT?", "output": "The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes Grhl2 antagonizes transforming growth factor-b (TGFb)-induced EMT" }, { "input": "What is Intanza?", "output": "Intanza(r) 9 ug (sanofi pasteur) is a microneedle-delivered intradermal trivalent inactivated influenza vaccine approved in 2009 for the prevention of seasonal influenza in adults 18 to 59 years of age. The microneedle system reliably and reproducibly delivers the vaccine to the dermis. Clinical studies show that Intanza 9 ug is as immunogenic and as well tolerated in working-age adults as a reference intramuscular trivalent inactivated vaccine. Local reactions to Intanza 9 ug, mainly erythema, are transient, mostly mild or moderate, and do not affect acceptability. Intanza 9 ug is considered satisfactory by at least 95% of both vaccinees and prescribers, especially because of the short needle and rapid administration." }, { "input": "Is the Fluzone intradermal and the Fluzone intradermal quadrivalent vaccine produced by different companies?", "output": "No, the Fluzone Intradermal vaccine and the Fluzone Intradermal Quadrivalent vaccine are produced by Sanofi Pasteur." }, { "input": "What is the purpose of the Barricaid annular closure device?", "output": "Barricaid annular closure device can improve outcome after lumbar discectomy by reducing the risk of recurrent disc herniation of the same level." }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "mutations in the methyl-cpg-binding protein-2 gene (mecp2) are commonly associated with rett syndrome" }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "Mutations in the MECP2 transcription factor, which codes for the transcription factor ECE1, have been found to be associated with Rett syndrome." }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "Mutations in the methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome. Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT)." }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "Mutations in the methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome." }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT)." }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome" }, { "input": "What disease is associated with mutations in the MECP2 transcription factor?", "output": "Mutations in the MECP2 transcription factor, which encodes the cellular iron exporter ferroportin, are associated with Rett syndrome." }, { "input": "Is endotrophin derived from collagen?", "output": "Yes,\nEndotrophin is released from COL VI." }, { "input": "Which receptor is inhibited by bimagrumab?", "output": "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators." }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "Ty3 is preferentially inserted in genes encoding transfer RNA genes." }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "The retrovirus-like element Ty3 of Saccharomyces cerevisiae integrates at the transcription initiation region of RNA polymerase III genes and is preferentially inserted in transfer RNA genes." }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "Ty3 integrates within the region of RNA polymerase III transcription initiation. Thus, genomic insertions of Ty3 in a particular orientation are apparently specified by the target, while the actual position of the insertion relative to the tRNA-coding sequence can vary slightly." }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "The retrovirus-like element Ty3 of Saccharomyces cerevisiae integrates at the transcription initiation region of RNA polymerase III" }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "The yeast transpozable element Ty3 is preferentially located in the promoter region of genes encoding ribosomal proteins." }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "rna polymerase iii" }, { "input": "Where is the yeast transpozable element Ty3 preferentially inserted?", "output": "Ty3 inserts at transcription initiation sites of genomic tRNA genes and plasmid-borne 5S and U6 RNA genes transcribed by RNA polymerase III." }, { "input": "List features of the Currarino triad.", "output": "Currarino syndrome is a congenital malformation syndrome typically characterized by sacral agenesis, anorectal malformation, and presence of a pre-sacral mass." }, { "input": "When was Afrezza approved by the FDA?", "output": "Afrezza was approved by the FDA in June 2014." }, { "input": "What are invasomes", "output": "invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems for dermatological applications." }, { "input": "What are invasomes", "output": "Ultra-flexible vesicles, e.g. invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems" }, { "input": "What are invasomes", "output": "Invasomes are novel vesicular systems that exhibit improved transdermal penetration compared to conventional liposomes." }, { "input": "Which T-UCRs have been implicated in lung cancer?", "output": "Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding capacity. The clinicopathologic significance and regulatory mechanism of T-UCRs in lung cancer (LC) remain largely unknown. Uc.454 is downregulated in both non-small-cell LC (NSCLC) tissues and LC cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages. Transfection with uc.454 markedly induces apoptosis and inhibites cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Thus uc.454 potentially plays a suppressive role in LC. Transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels." }, { "input": "Can Daptacel be used instead of IPOL?", "output": "No, Daptacel is a diphtheria, tetanus, 5-component acellular pertussis vaccine, while IPOL is an inactivated poliovirus vaccine." }, { "input": "Is ACE2 expressed on cell surfaces?", "output": "Yes,\nACE2 is a type 1 integral membrane protein and contains a catalytically active ectodomain that can be shed from the cell surface into the extracellular space." }, { "input": "List symptoms of the One-and-a-half syndrome.", "output": "One-and-a-half syndrome is defined by conjugated horizontal gaze palsy and internuclear ophthalmoplegia." }, { "input": "When was Fluzone Intradermal replaced with Fluzone Intradermal Quadrivalent?", "output": "Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine in advance of the 2015-2016 season." }, { "input": "List the cancers that are associated with SBLA syndrome.", "output": "Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as the SBLA cancer syndrome (sarcoma, breast, leukemia, and adrenal). Li-Fraumeni syndrome (LFS) is characterized by a pleth" }, { "input": "List the cancers that are associated with SBLA syndrome.", "output": "SBLA cancer syndrome (sarcoma, breast, leukemia, and adrenal)." }, { "input": "List the cancers that are associated with SBLA syndrome.", "output": "Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as the SBLA cancer syndrome (sarcoma, breast, brain, lung, lymphoma, leukemia, laryngeal and adrenal)." }, { "input": "Can leuprorelin acetate be used as androgen deprivation therapy?", "output": "Yes, leuprorelin acetate is being used as androgen deprivation therapy." }, { "input": "Which factors are included in the the APPEND score?", "output": "APPEND score components are anorexia, migratory Pain, local Peritonism, Elevated C-reactive protein, Neutrophilia and male gender (Dude). It is an acute appendicitis clinical prediction rule." }, { "input": "What is the function of the SSX proteins?", "output": "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors" }, { "input": "What is the function of the SSX proteins?", "output": "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Together, we conclude that the SS18-SSX2 fusion protein may act as a so-called transcriptional \"activator-repressor,\" which induces downstream target gene deregulation through epigenetic mechanisms. The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation. Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus." }, { "input": "What is the function of the SSX proteins?", "output": "transcriptional co-activator" }, { "input": "What is the function of the SSX proteins?", "output": "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus." }, { "input": "What is the function of the SSX proteins?", "output": "The SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus." }, { "input": "What is the function of the SSX proteins?", "output": "The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Taken together, these results led us to conclude that the SSX moiety, especially the most C-terminal 34 amino acids, of the SYT-SSX fusion proteins is crucial for aberrant spatial targeting and transcriptional control within the nucleus. The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation." }, { "input": "Are astrocytes part of the blood brain barrier?", "output": "Yes\nThe blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation." }, { "input": "What is Invaplex 50?", "output": "The Shigella flexneri Invaplex 50 is a macromolecular complex containing IpaB, IpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. It is used against shigellosis, a leading cause of diarrhea worldwide. The Invaplex 50 nasal vaccine was safe with encouraging mucosal immune responses." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "Lupus-like symptoms of systemic lupus erythematosus (SLE) are caused by X-linked mutations in the genes Tlr7 and Y." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration)." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "Tlr7 and Y chromosome abnormalities present lupus-like symptoms with considerable phenotypic overlap." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "X-chromosome abnormalities (Tlr7 and Y) present lupus-like symptoms." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "the accelerated development of systemic lupus erythematosus (sle) in male bxsb mice is associated with the genetic abnormality in its y chromosome" }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome. The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration)." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration) but additional contributions from other duplicated genes in the translocated X chromosome also exist" }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration)." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "X-chromosomal abnormalities in patients with SLE present lupus-like symptoms. X-chromatin abnormality on X chromosome 14q11.2, which encodes X-linked leiomyosarcoma, is the most common chromosomal abnormality in SLE. There is also a publication that links X- chromosome abnormalities to lupUS disease with synostosis." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "The accelerated development of systemic lupus erythematosus (SLE) in male BXSB mice is associated with the genetic abnormality in its Y chromosome, designated Yaa (Y-linked autoimmune acceleration). Yaa-mediated acceleration of SLE as well as various Yaa-linked cellular traits cannot be explained by the Tlr7 gene duplication alone, and suggest additional contributions from other duplicated genes in the translocated X chromosome." }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "yaa" }, { "input": "Which X chromosome abnormalities present lupus-like symptoms?", "output": "Lupus-like symptoms are present due to X-chromosomal abnormalities such as X-linked leiomyosarcoma, polycystic kidney disease, myelodysplastic syndrome (MDS), and X- linked hypogonadotropic hypomyelitis." }, { "input": "Which lncRNAS are regulated by SAM68?", "output": "Hotair, Mir155hg, as well as SR-lncRNA-1 and SR-lncRNA-2 are regulated by Sam68, and contained consensus Sam68 binding sites." }, { "input": "How many proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM)?", "output": "Over 5,000 proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM)." }, { "input": "How many proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM)?", "output": "5,000 proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM)." }, { "input": "How many proteins have been queried for protein partners by the Drosophila protein interaction map (DPiM)?", "output": "Defining protein-protein interactions in protein complexes, and establishing the when, what and where of potential interactions, is crucial to understanding the cellular function of any protein-especially those that have not been well studied by traditional molecular genetic approaches. In the Drosophila protein interaction map (DPiM) protein partners of nearly 5,000 Drosophila melanogaster proteins have been identified." }, { "input": "What is known about the orphan receptor GPR151?", "output": "Gpr151 is an orphan GPCR whose function is unknown. The restricted pattern of neuronal expression in the habenula, dorsal horn of the spinal cord and dorsal root ganglion plus homology with the galanin family of receptors imply a role in nociception. \nOur data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development." }, { "input": "Is Li\u2013Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "output": "Li-Fraumeni syndrome is a rare, autosomal DOMINANT, hereditary disorder that predisposes carriers to cancer development." }, { "input": "Is Li\u2013Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "output": "Yes, Li-Fraumeni syndrome is a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development." }, { "input": "Is Li\u2013Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "output": "li-fraumeni syndrome is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab is a fully human monoclonal antibody directed against BAFF. Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately approved by the United States Food and Drug Administration (FDA) in March 2011 for active autoantibody patients with systemic lupus erythematosus (SLE) despite standard therapy." }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "blys" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "The main therapeutic target of belimumab is BLyS" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an inv" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab is an anti-BAFF monoclonal antibody. BAFF is also known as BLyS (B-lymphocyte stimulator)." }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an investigational B-lymphocyte stimulator (BLyS) inhibitor." }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), a B-cell survival factor, was licensed in 2011 for the treatment of autoantibody-positive SLE" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab is a fully human anti-BLyS monoclonal antibody with specificity for BLyS. It is approved for SLE treatment." }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus Belimumab, an anti-BAFF monoclonal antibody" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), a B-cell survival factor, was licensed in 2011 for the treatment of autoantibody-positive SLE" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus To review the efficacy, safety, dosing, drug interactions, as well as economic and therapeutic considerations of belimumab, an investigational B-lymphocyte stimulator (BLyS) inhibitor. Belimumab, an anti-BAFF monoclonal antibody" }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (BLyS), was licensed in 2011 for the treatment of autoantibodies to Systemic Lupus Erythematosus." }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus." }, { "input": "Which is the target of belimumab in Systemic Lupus Erythematosus treatment?", "output": "belimumab is a blys-specificsor for systemic lupus erythematos" }, { "input": "Salzburg EEG criteria are used to diagnose which disorder?", "output": "Salzburg EEG criteria are used to diagnose Nonconvulsive Status Epilepticus." }, { "input": "List the components of the COMPASS complex", "output": "MLL4\nMLL3\nWDR5\nRBBP5\nASH2\nSET1" }, { "input": "Has the drug Afrezza been approved by the FDA?", "output": "Yes, Afrezza has been approved by the FDA." }, { "input": "Central Vein Sign is characteristic to which disease?", "output": "Central vein sign on FLAIR* magnetic resonance imaging is highly specific and sensitive for multiple sclerosis." }, { "input": "Which is the catalytic activity of the protein encoded by the gene KMT2C? ", "output": "The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers." }, { "input": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "output": "The LMNA gene is the most mutated gene in dilated cardiomyopathy (DCM) and affects approximately 25% of the patients." }, { "input": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "output": "Mutations in the gene encoding lamin A/C (LMNA) cause dilated cardiomyopathy" }, { "input": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "output": "lamin a/c gene (lmna)" }, { "input": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "output": "The most mutated gene in dilated cardiomyopathy (DCM) is the lamin A/C gene. Mutations in this gene are responsible for the most common form of DCM and result in a recessive form of cardiac hypertrophy. A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes dilatedCardiac b-myosin heavy chain gene (LMNA) to be mutated in 25% of patients with DCM." }, { "input": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "output": "Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy)" }, { "input": "Which is the most mutated gene in dilated cardiomyopathy (DCM)?", "output": "The most mutated gene in dilated cardiomyopathy (DCM) is the LMO2-binding protein (LMNA) gene. Mutations in the LMNA gene underlie both adult-onset and juvenile forms of DCM and result in very severe cardiac dysfunction." }, { "input": "List psychiatric diseases that are associated with Synaptosome Associated Protein 25 (snap25).", "output": "attention-deficit/hyperactivity disorder\nbipolar\nschizophrenia" }, { "input": "Which type of cells protect Haematopoietic stem and progenitor cells (HSPCs) from ultraviolet-light-induced DNA damage in aquatic vertebrates?", "output": "Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment to grow and are protected from ultraviolet-light-induced DNA damages by melanocytes. Mutations that lack melanocytes have normal steady-state haem atopoiesis under standard laboratory conditions while melanocytes above the stem cell niche protect HSPCs against ultraviolet- light-induced damage." }, { "input": "Which type of cells protect Haematopoietic stem and progenitor cells (HSPCs) from ultraviolet-light-induced DNA damage in aquatic vertebrates?", "output": "Melanocytes protect Haematopoietic stem and progenitor cells (HSPCs) from ultraviolet-light-induced DNA damages in aquatic vertebrates." }, { "input": "Which type of cells protect Haematopoietic stem and progenitor cells (HSPCs) from ultraviolet-light-induced DNA damage in aquatic vertebrates?", "output": "Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour. A melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. The melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche." }, { "input": "Which is the primary interacting protein of BLK?", "output": "The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling." }, { "input": "Which is the primary interacting protein of BLK?", "output": "Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK." }, { "input": "Which is the primary interacting protein of BLK?", "output": "BLK interacts with at least two of the three kinases in the B-cell/proteasome pathway, namely the transcription factor BANK1 and the chromatin-associated transcription factor 1 (CACGT1)." }, { "input": "Which is the primary interacting protein of BLK?", "output": "Primary interacting protein of BLK (also known as BANK1)" }, { "input": "Which is the primary interacting protein of BLK?", "output": "Primary interacting protein of BLK is Cdk1-binding protein 1 (Bik1/Nbk1)." }, { "input": "Which is the primary interacting protein of BLK?", "output": "The genes BANK1 and BLK were recently described as associated with SLE a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically." }, { "input": "Which is the primary interacting protein of BLK?", "output": "BLK activity is regulated by two interacting proteins, BANK1 and BANK2." }, { "input": "Which is the primary interacting protein of BLK?", "output": "a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically." }, { "input": "Which is the primary interacting protein of BLK?", "output": "Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK. a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically." }, { "input": "Which is the primary interacting protein of BLK?", "output": "A The genes BANK1 and BLK were recently described as associated with SLE" }, { "input": "Which is the primary interacting protein of BLK?", "output": "Autophagy-related gene 5 (ATG5), ATG7, B-lymphoid tyrosine kinase (BLK) and B-cell scaffold protein with ankyrin repeats 1 (BANK1) are involved in B-cell signaling;" }, { "input": "Which is the primary interacting protein of BLK?", "output": "bank1" }, { "input": "Is Protoporphyrinogen oxidase localized to the mitochondrium?", "output": "Yes,\nMitochondrial targeting of human protoporphyrinogen oxidase." }, { "input": "How many doses of vaxchora are required?", "output": "Vaxchora is a single-dose vaccine." }, { "input": "What is the SLC25A20 protein transporting?", "output": "The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport reaction allowing entry of acyl moieties in the form of acylcarnitines into the mitochondrial matrix and exit of free carnitine." }, { "input": "List the vaccine strains contained in Fluvirin.", "output": "Fluvirin contains 18 mg of haemagglutinin per H1N1 vaccine strain, 17 mg of haemagglutinin per H3N2 vaccine strain, and 15 mg of haemagglutinin per B vaccine strain." }, { "input": "Do de novo truncating mutations in WASF1 cause cancer?", "output": "No, de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability." }, { "input": "List the attenuated live viruses contained in the Fluzone intradermal quadrivalent vaccine.", "output": "The Fluzone Intradermal Quadrivalent vaccine contains 9 ug hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata)." }, { "input": "Which kinases are inhibited by Pyrotinib?", "output": "Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer." }, { "input": "Which bacteria causes rat bite fever?", "output": "Rat bite fever is caused by Streptobacillus moniliformis. Infection induces typical but not pathognomonic clinical signs, such as local purulent wound infection followed by maculopapular exanthema, myalgia as well as purulent joint infections." }, { "input": "What is the role of Gata3 in Th2 cells?", "output": "RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression." }, { "input": "What is the role of Gata3 in Th2 cells?", "output": "Gata3 coordinates the progression of H3K9me2/H3K27me3 by mediating histone deacetylation and chromatin remodeling in Th2 cells. Gata3 plays an important role in this process by repressing the expression of histone H3 in Th1 cells and by promoting chromatin condensation during DNA damage-induced DNA damage." }, { "input": "What is the role of Gata3 in Th2 cells?", "output": "RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes. posttranslational modifications of Gata3 that control the regulation of IFNg expression in memory Th2 cells." }, { "input": "What is the role of Gata3 in Th2 cells?", "output": "GATA3 is responsible for induction of T(h)2 differentiation and represses T(h)1 differentiation. Posttranslational modifications of Gata3 control the regulation of IFNg expression in memory Th2 cells." }, { "input": "Describe the Disambiguate algorithm and its application in next generation sequencing data", "output": "Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate." }, { "input": "Describe the Disambiguate algorithm and its application in next generation sequencing data", "output": "Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate." }, { "input": "Describe the Disambiguate algorithm and its application in next generation sequencing data", "output": "Disambiguate is an open-source application for disambiguating two species in next generation sequencing data from grafted samples. The method is based on an iterative Bayesian approach which uses sequence alignment information from germline genotype data to identify putative cis-regulatory elements which may be involved in the regulation of gene expression. The input to the method is a set of sequence elements known to be of interest to the genomics research community, and the outputs are calls for inclusion of putative regulatory elements such as enhancers, transcription factor binding sites, enhancers and enhancers" }, { "input": "Describe the Disambiguate algorithm and its application in next generation sequencing data", "output": "Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples." }, { "input": "Describe the Disambiguate algorithm and its application in next generation sequencing data", "output": "Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at https://github.com/AstraZeneca-NGS/disambiguate." }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance," }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": " Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance," }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "Yes, ICAMS, Intracellular Adhesion Molecules, are part of the immunoglobulin superfamily." }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "yes, Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance," }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "Yes, Intracellular Adhesion Molecules (ICAMS) are part of the immunoglobulin superfamily." }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "Intercellular adhesion molecules (ICAMs) are members of the immunoglobulin super-family which are present on the surface of endothelial cells." }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "Yes, ICAMs (Intracellular Adhesion Molecules) are a subset of the immunoglobulin superfamily." }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "Yes, Intracellular Adhesion Molecules (ICAMs) are part of the immunoglobulin superfamily." }, { "input": "Are ICAMS, Intracellular Adhesion Molecules, part of the immunoglobulin superfamily?", "output": "It has now been shown that adhesion molecules, particularly those of the immunoglobulin super family (e.g. ICAM-1, VCAM-1 and PECAM-1), Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance," }, { "input": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "output": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatmen" }, { "input": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "output": "Yes, there is evidence to suggest that traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment." }, { "input": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "output": "Yes, traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment, as determined by studies in humans and in animal models." }, { "input": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "output": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment" }, { "input": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "output": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment." }, { "input": "What receptor is associated with the protein encoded by the Sp\u00e4tzle gene?", "output": "Currently, as a ligand for the Toll-1 receptor, only Spatzle (Spz) has been identified and characterized." }, { "input": "What receptor is associated with the protein encoded by the Sp\u00e4tzle gene?", "output": "Currently Spatzle (Spz) has been identified and characterized as a ligand for the Toll-1 receptor" }, { "input": "What receptor is associated with the protein encoded by the Sp\u00e4tzle gene?", "output": "Spatzle (Spz) is the toll-1 receptor gene encoding a protein subunit of a multisubunit membrane protein complex that plays a central role in the remodeling of the cytoskeleton and its association with the membrane." }, { "input": "What receptor is associated with the protein encoded by the Sp\u00e4tzle gene?", "output": "The Drosophila Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the Toll-1 receptor, only Spatzle ( Spz) has been identified and characterized." }, { "input": "List targeted genome editing methodologies", "output": "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome. The choice of genome editing tool should be determined by the desired genome editing outcome. Such a rational approach is likely to benefit research outputs for groups working in fields as diverse as modification of cell lines, to animal models for disease studies, or gene therapy strategies." }, { "input": "List targeted genome editing methodologies", "output": "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome. Targeted genome editing (TALEN) was recently introduced as a method to manipulate eukaryotic genomes in a targeted manner with high efficiency and specificity." }, { "input": "List targeted genome editing methodologies", "output": "Genome editors such as CRISPR/Cas9 and TALENs are at the forefront of research into methodologies for targeted modification of the mammalian genome." }, { "input": "Is PTEN a tumour suppressor?", "output": "Yes" }, { "input": "Which is the function of the PRDM9 protein in mammals?", "output": "PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice." }, { "input": "Which is the function of the PRDM9 protein in mammals?", "output": "Here, we demonstrate that a major player for hotspot specification is the Prdm9 gene. In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 ( PRDM9). In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Developmental progress of germ cells through meiotic phases is closely tied to ongoing meiotic recombination." }, { "input": "Which is the function of the PRDM9 protein in mammals?", "output": "In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination." }, { "input": "Which is the function of the PRDM9 protein in mammals?", "output": "Developmental progress of germ cells through meiotic phases is closely tied to ongoing meiotic recombination. In mammals, recombination preferentially occurs in genomic regions known as hotspots; the protein that activates these hotspots is PRDM9,. In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots." }, { "input": "Which is the function of the PRDM9 protein in mammals?", "output": "in mammals , recombination preferentially occurs in genomic regions known as hotspots. the protein that activates these hotspots is prdm9" }, { "input": "Which is the function of the PRDM9 protein in mammals?", "output": "meiotic recombination" }, { "input": "Which graph database is used by the Reactome graph database?", "output": "Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery." }, { "input": "Which graph database is used by the Reactome graph database?", "output": "The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%." }, { "input": "Which graph database is used by the Reactome graph database?", "output": "The Reactome graph database organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic biomolecular pathways and presents them using a powerful web-based graphical interface. The data are stored in a relational database, Neo4j, which is updated regularly with the addition of new data and corrections to previous data." }, { "input": "Which graph database is used by the Reactome graph database?", "output": "The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage." }, { "input": "What is the route of administration of vaxchora?", "output": "Vaxchora is an oral vaccine." }, { "input": "What is the target of the drug remdesivir?", "output": "remdesivir is a polymerase inhibitor" }, { "input": "What is known about EphA2 in drug resistance?", "output": "ligand- and tyrosine kinase-independent EphA2 signaling (the noncanonical pathway) promotes tumor survival and metastasis and controls acquired drug resistance and maintenance of cancer stem cell-like properties.\nFindings confirm EPHA2 as an actionable drug target, provide a rational basis for drug combination approaches, and indicate that chemical proteomics is broadly applicable for the discovery of kinase inhibitor resistance." }, { "input": "How is Slc22a3 imprinted?", "output": "Two novel imprinted genes, Slc22a2 and Slc22a3 are described here that lie 110 and 155 kb 3' to Igf2r and that are not overlapped by the Air transcript but are regulated by the Igf2r-ICE, as previously shown for Igf2r. A bidirectional silencer for a 400-kilobase region that contains three imprinted, maternally expressed protein-coding genes (Igf2r/Slc22a2/Slc22a3) has been shown by targeted deletion to be located in a sequence of 3.7 kilobases, which also contains the promoter for the imprinted, paternally expressed non-coding Air RNA. Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA" }, { "input": "How is Slc22a3 imprinted?", "output": "cis expression of the air rna" }, { "input": "How is Slc22a3 imprinted?", "output": "Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA." }, { "input": "How is Slc22a3 imprinted?", "output": "Epigenetic mechanisms restrict the expression of imprinted genes to one parental allele in diploid cells. At the Igf2r/Air imprinted cluster on mouse chromosome 17, paternal-specific expression of the Air noncoding RNA has been shown to silence three genes in cis: Igf2r, Slc22a2, and Slc22a3. " }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Furthermore, recruitment of dimers on accumulating wild- type Tau increases its steady- state levels ostensibly by occluding access to proteases in a phosphorylated-dependent manner." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "The 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and mutant Tau proteins." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "14-3-3 dimers have two contrasting effects on Tau phosphorylation: (i) they increase the rate of Tau is phosphorylated by cAMP-dependent protein kinase and (ii) they prevent the relaxation of the autophagic state of Tau." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "Neurodegenerative dementias collectively known as Tauopathies involve aberrant phosphorylation and aggregation of the neuronal protein Tau. The largely neuronal 14-3-3 proteins are also elevated in the central nervous system (CNS) and cerebrospinal fluid of Tauopathy patients, suggesting functional linkage. Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner. In contrast, the R406W mutant, which lacks a putative 14-3-3 binding site, responds differentially to elevation of each 14-3-3 isoform. Although excess 14-3-3z stabilizes the mutant protein, elevated D14-3-3e has a destabilizing effect probably because of altered 14-3-3 dimer composition." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant. Moreover, 14-3-3 elevation itself is not pathogenic, but recruitment of dimers on accumulating wild-type Tau increases its steady-state levels ostensibly by occluding access to proteases in a phosphorylation-dependent manner. In contrast, the R406W mutant, which lacks a putative 14-3-3 binding site, responds differentially to elevation of each 14-3-3 isoform. Although excess 14-3-3z stabilizes the mutant protein, elevated D14-3-3e has a destabilizing effect probably because of altered 14-3-3 dimer composition." }, { "input": "What are the effects of 14-3-3 dimers on Tau phosphorylation?", "output": "Proteomic, biochemical and genetic evidence demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type and mutant Tau on multiple sites irrespective of their phosphorylation state. 14-3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W mutant Tau, but they are not essential for toxicity of either variant." }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice. Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant." }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Yes, Bruton's tyrosine kinase (BTK) is implicated in autoimmunity." }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Bt" }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant. Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity" }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "yes, BTK Signaling in B Cell Differentiation and Autoimmunity" }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity." }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant." }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Yes, variants of the tyrosine kinase BTK may be implicated in autoimmunity." }, { "input": "Is the tyrosine kinase BTK implicated in autoimmunity?", "output": "Yes, tyrosine kinase BTK is implicated in autoimmunity." }, { "input": "What is the BioPlex network?", "output": "Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. BioPlex contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors." }, { "input": "What is the BioPlex network?", "output": "BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors." }, { "input": "Which algorithm has been developed for detecting expansions of tandem repeats?", "output": "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. For that purpose, ExpansionHunter has been developed as a software tool that, using PCR-free WGS short- read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length." }, { "input": "Which algorithm has been developed for detecting expansions of tandem repeats?", "output": "Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. ExpansionHunter has been developed as a tool which using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions." }, { "input": "Which clotting factor is in the Andexxa?", "output": "Andexxa(r) is a first-in-class recombinant modified factor Xa protein. It is available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban." }, { "input": "How are nucleosome posisitions correlated with sites of 5'-methyl-cytosine (5mC) or 5-hydroxy-methyl-cytosine (5hmC)?", "output": "We find that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy. outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes we have investigated nucleosome organization around hypomethylated regions (HMRs)" }, { "input": "How are nucleosome posisitions correlated with sites of 5'-methyl-cytosine (5mC) or 5-hydroxy-methyl-cytosine (5hmC)?", "output": "Nucleosomes are enriched at hypomethylated region (HMR) boundaries. The mostly unmethylated CpG islands have reduced nucleosome occupancy. Outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes." }, { "input": "How are nucleosome posisitions correlated with sites of 5'-methyl-cytosine (5mC) or 5-hydroxy-methyl-cytosine (5hmC)?", "output": "Using this global approach, we observe the dependency of nucleosome positioning upon the 5'-methyl-cytosine (5mC) methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. Using a novel bioinformatics pipeline, we show a striking anti-correlation between nucleosomic positioning and 5-hydroxymethylation at CTCF regions that is not present at promoters. Transcription, histone modifications, and DNA methylation alter this \"ground state\"" }, { "input": "How are nucleosome posisitions correlated with sites of 5'-methyl-cytosine (5mC) or 5-hydroxy-methyl-cytosine (5hmC)?", "output": "outside of CpG islands most CpGs are methylated, and the average methylation density oscillates so that it is highest in the linker region between nucleosomes" }, { "input": "Which drugs are included in the drug LONSURF?", "output": "Lonsurf includes trifluridine and tipiracil. It is a novel oral anti-tumor agent combining an anti-neoplastic thymidine-based nucleoside analogue (trifluridine) with a thymidine phosphorylase inhibitor (tipiracil hydrochloride) presents a new treatment option for metastatic colorectal cancer patients refractory or intolerant to standard therapies." }, { "input": "What is 23andMe?", "output": "We first take a look at how personal genomics services, exemplified by the company 23andMe," }, { "input": "What is 23andMe?", "output": "23andMe is a genetic testing company which offers personal genetic services." }, { "input": "Is induction of interferon by TLR7 higher in males?", "output": "Yes. TLR7 activation correlates with induction of interferon more strongly in males." }, { "input": "Is induction of interferon by TLR7 higher in males?", "output": "Yes. TLR7 induction of interferon is higher in males than in females." }, { "input": "Is induction of interferon by TLR7 higher in males?", "output": "variations of tlr7 impair the immune response to hcv and imply a gender-specific effect" }, { "input": "Is induction of interferon by TLR7 higher in males?", "output": "Variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy." }, { "input": "Cushing's disease is associated with a tumor in what part of the body?", "output": "Cushing's disease is associated with a tumor in the pituitary gland" }, { "input": "Cushing's disease is associated with a tumor in what part of the body?", "output": "Cushing's disease is associated with a tumor in the pituitary gland." }, { "input": "Cushing's disease is associated with a tumor in what part of the body?", "output": "Cushing's disease (CD) is a rare endocrine disorder associated with increased serum levels of cortisol secreted due to an underlying tumour in pituitary." }, { "input": "Cushing's disease is associated with a tumor in what part of the body?", "output": "Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma," }, { "input": "Which was the first genetically modified organism (GMO) to be used as vaccine?", "output": "The first genetically modified organism to be used as vaccine was the live oral cholera vaccine CVD 103-HgR or vaxchora." }, { "input": "How does PRDM9 recognize the specific DNA motifs for meiotic recombination?", "output": "The PRDM9 gene encodes a protein with a highly variable tandem-repeat zinc finger (ZF) DNA-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence." }, { "input": "How does PRDM9 recognize the specific DNA motifs for meiotic recombination?", "output": "The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence." }, { "input": "How does PRDM9 recognize the specific DNA motifs for meiotic recombination?", "output": " In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9), a long-array zinc-finger and chromatin-modifier protein." }, { "input": "Which micro-RNAs (miR) are associated with the human cycloxygenase-2 (COX-2) gene promoter?", "output": "MicroRNA-16, miRNA-128, miR-26b, icroRNA-26a, MicroRNA-146b-3p, microRNA-137, mi R-146a, mir-143-5p,microRNA-101, microRNAs-142-3 p, mi r-146p, mir-128 and miR -128 were found to be associated with the human cycloxygenase-2 (COX-2) gene promoter." }, { "input": "Which micro-RNAs (miR) are associated with the human cycloxygenase-2 (COX-2) gene promoter?", "output": "miR-146a, miR-203, miRNA-124a, microRNA-155, miRS-146b, miS-146c, miG-145, miRP-148a, let-7b, siRNA-181, miRNAs-152, miN-182, mir-223, myosin heavy chain, are associated with the human cycloxygenase-2 (COX-2) gene promoter We also report the following miRNA associations with the COX- 2 gene promoters: miCENP-1," }, { "input": "Which micro-RNAs (miR) are associated with the human cycloxygenase-2 (COX-2) gene promoter?", "output": "Recently, the human cycloxygenase-2 (COX-2) gene promoter has a microRNA (miR) promoter region that is highly expressed in non-cancer cells and is associated with the cell cycle. MicroRNA-16, miRNA-128, microRNA-26a, miRNAs-142-3p, miR-144, mi R-146b-3 p, mir-146a, icroRNA- 26a, -26b,microRNA-137, mi r-146 a, mir-143-5p," }, { "input": "Which micro-RNAs (miR) are associated with the human cycloxygenase-2 (COX-2) gene promoter?", "output": "miR-16 was shown to bind the COX-2 3'-UTR and inhibit COX-2 expression by promoting rapid mRNA decay. miR-143-5p directly targets COX-2. The NF-kB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2-3'-UTR. microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells. MicroRNA-144 is regulated by CP2 and decreases COX-2 expression and PGE2 production in mouse ovarian granulosa cells. The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling. MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2. Altered expression of miR-146b-3p is closely related to the progression and development of DCMI mediating the RAF/P38MAPK/COX-2 signal transduction pathway. MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma." }, { "input": "Which micro-RNAs (miR) are associated with the human cycloxygenase-2 (COX-2) gene promoter?", "output": "The following micro-RNAs (miRNAs) have been associated with the human cycloxygenase-2 (COX-2) gene promoter: microRNA-16, miRNA-128, micro RNA-26a, miR-142-3p, mir-144, mi r-146b-3 p, mir-16), mir-26b, icroRNA-26 a, MicroRNA-146 b-3P, mir-146a, mir -143-5p, mir microRNA-137, mir--MicroRNA" }, { "input": "What percentage of patients of nasopharyngeal carcinoma (NPC) develop recurrent disease?", "output": "1.04% of patients with nasopharyngeal carcinoma develop recurrent disease. The overall recurrence rate is 75%." }, { "input": "What percentage of patients of nasopharyngeal carcinoma (NPC) develop recurrent disease?", "output": "The overall recurrence rate was 75% in HPV negative patients and 11% in HPV positive ones. Disease recurred in a spared parotid gland in three patients (1.04%)." }, { "input": "What classes of drugs does Retapamulin belong to?", "output": "Retapamulin is a member of the pleuromutilin family of antibiotics." }, { "input": "What classes of drugs does Retapamulin belong to?", "output": "Pleuromutilins have a potential to be developed as a new class of antibiotics for use in humans. This class includes valnemulin, tiamulin, and retapamulin." }, { "input": "What classes of drugs does Retapamulin belong to?", "output": "Retapamulin belongs to the class of gentamycin-resistant antibiotics." }, { "input": "What is the mechanism of action of ozanimod?", "output": "Ozanimod is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis." }, { "input": "What are Syndecans?", "output": "Syndecans are transmembrane proteoglycans with heparan and chondroitin sulfate chains attached to their extracellular domain. Like many proteoglycans, they interact with a large number of ligands, such as growth factors, adhesion receptors, soluble small molecules, proteinases, and other extracellular matrix proteins to initiate downstream signaling pathways. Syndecans play a major role in inflammation, mainly by regulating leukocyte extravasation and cytokine function." }, { "input": "What are Syndecans?", "output": "Syndecans are important mediators of signalling by transmitting external stimuli into the cells. Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. " }, { "input": "What are Syndecans?", "output": "Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. " }, { "input": "What is chemokinesis?", "output": "Chemokinesis is chemically prompted kinesis, a motile response of unicellular prokaryotic or eukaryotic organisms to chemicals that cause the cell to make some kind of change in their migratory/swimming behaviour." }, { "input": "What cellular process is JAK/STAT involved in?", "output": "The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and function of both innate and adaptive immunity." }, { "input": "What cellular process is JAK/STAT involved in?", "output": "The serine/threonine kinase JAK/STAT is a major regulator of Janus kinase activity and plays a critical role in regulating the ubiquitin/proinflammatory signaling pathway." }, { "input": "What cellular process is JAK/STAT involved in?", "output": "JAK/STAT is a master regulator of immunity" }, { "input": "What cellular process is JAK/STAT involved in?", "output": "JAK/STAT is involved in the regulation of immunity" }, { "input": "What is the link between dental x-ray and brain tumor risk?", "output": "There is data to suggest that dental x-ray can be associated with significantly increased risk of meningiomas and gliomas. However, some studies failed to demonstrate an association between dental x-rays and brain tumor risk." }, { "input": "Is there a vaccine for rotavirus?", "output": "Effectiveness of rotavirus pentavalent vaccine rotavirus pentavalent vaccine (RotaTeq(r)) as a sole vaccine" }, { "input": "Is there a vaccine for rotavirus?", "output": "safety and immunogenicity of pentavalent rotavirus vaccine (rv5 )" }, { "input": "Is there a vaccine for rotavirus?", "output": "Yes, there is a vaccine against rotavirus infection that is approved for Europe, Canada and Australia." }, { "input": "Is there a vaccine for rotavirus?", "output": "Yes, there is a human neonatal rotavirus vaccine against serogroup B Rotavirus." }, { "input": "Is there a vaccine for rotavirus?", "output": "Yes, there is a 4-component vaccine against capsular rotavirus vaccine." }, { "input": "Is there a vaccine for rotavirus?", "output": "Effectiveness of rotavirus pentavalent vaccine" }, { "input": "Is there a vaccine for rotavirus?", "output": "Yes, there is a human neonatal rotavirus vaccine." }, { "input": "Is there a vaccine for rotavirus?", "output": "Yes, there is a pentavalent vaccine for Rotavirus" }, { "input": "Is there a vaccine for rotavirus?", "output": "yes, rotavirus pentavalent vaccine (RotaTeq(r)) as a sole vaccine" }, { "input": "Is there a vaccine for rotavirus?", "output": "High effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country." }, { "input": "Is there a vaccine for rotavirus?", "output": " rotavirus pentavalent vaccine (RotaTeq(r)) as a sole vaccine" }, { "input": "Which T-UCR has been implicated in prostate cancer?", "output": "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer ( CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance." }, { "input": "Which T-UCR has been implicated in prostate cancer?", "output": "The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. Overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020)." }, { "input": "Is BNN20 involved in Parkinson's disease?", "output": "Yes. Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). BNN-20 has been suggested as an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway, mimicking the action of the endogenous neurotrophin BDNF. Thus BNN-20 could be proposed for treatment of PD." }, { "input": "Is BNN20 involved in Parkinson's disease?", "output": "Yes. BNN20 is an important neuroprotective agent acting through the TrkB neurotrophin receptor pathway that has been implicated in numerous pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis and Parkinson's disease." }, { "input": "Is BNN20 involved in Parkinson's disease?", "output": "Yes. BNN20 is involved in the development of Parkinson's disease. It is a member of the intramembrane-tumor necrosis factor-a (ITF-a) family of transcription factors that are dysregulated in several neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal degeneration, axonal injury, late-onset cerebellar ataxia, and multiple sclerosis." }, { "input": "Is BNN20 involved in Parkinson's disease?", "output": "Yes. BNN20 could be proposed as a therapeutic for PD. BNN-20 administration to Weaver/NGL mice induced a strong NF-kB-dependent transcriptional response in the brain as detected by bioluminescence imaging, which was abolished by co-administration of the TrkB inhibitor ANA-12" }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail" }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated" }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "MOZ/MYST3 complex associates with histone H3 with high affinity and specificity. Both proteins share a PHD finger domain." }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification." }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries. The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification" }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "MOZ/MYST3 complex associates with histone H3 with PHD finger domain." }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A." }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated" }, { "input": "Which domain of the MOZ/MYST3 protein complex associates with histone H3?", "output": "In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries. The double PHD finger domain of MOZ/MYST3 induces a-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification ere we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A." }, { "input": "Which company sells the drug Afrezza since 2015?", "output": "Afrezza has been marketed by Sanofi since February 2015." }, { "input": "Is there a role for MRPL53 in cancer?", "output": "No. MRPL53 is a new candidate gene for orofacial clefting identified using an eQTL approach." }, { "input": "Does Uc.63+ promote sensitivity to treatment in prostate cancer?", "output": "No. Overexpression of Uc.63+ increases the expression of AR and its downstream molecule PSA and promotes resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients is higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis indicates that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020)." }, { "input": "Does Uc.63+ promote sensitivity to treatment in prostate cancer?", "output": "No. Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. Moreover, high expression of serum Uc63+ correlated with a worse prognosis (P = 0.020) in patients treated with copropane versus placebo." }, { "input": "Does Uc.63+ promote sensitivity to treatment in prostate cancer?", "output": "No. Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. In contrast, Uc-63+ enhances sensitivity to treatment in other types of prostate cancer" }, { "input": "What is the gene PTENP?", "output": "PTEN pseudogene (PTENp) acts as an endogenous RNA, which regulates its parental gene by competitively binding to the 3' UTR of PTEN gene in the human." }, { "input": "Rachmilewitz Index is used for which diseases?", "output": "Rachmilewitz Index is used for assessment of endoscopic disease activity of patients with ulcerative colitis." }, { "input": "List angiotensin-converting-enzyme inhibitors.", "output": "captopril\nenalapril\nlisinopril\nramipril" }, { "input": "How does androgen deprivation therapy affect pain perception?", "output": "There were no significant changes in pain thresholds, ratings, or other response to quantitative sensory tests over the 6-month course of the study. Clinical pain did not differ between test and control groups, and no changes from baseline were observed in their group." }, { "input": "What is OAC CHV?", "output": "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), which contains health-related terms used by lay consumers," }, { "input": "What is OAC CHV?", "output": "The Open Access and Collaborative Consumer Health Vocabulary (OAC CHV), contains health-related terms used by lay consumers." }, { "input": "What is known about autosomal dominant Alzheimer\u2019s disease?", "output": "The first autosomal dominant mutation in the amyloid precursor protein (APP) gene was described in 1991. Later, AD was also associated with mutated early-onset (presenilin 1/2, PSEN1/2 and APP) and late-onset (apolipoprotein E, ApoE) genes. Genome-wide association and linkage analysis studies with identified multiple genomic areas have implications for the treatment of AD.\nThe Dominantly Inherited Alzheimer Network, an international family-clustered registry to study autosomal dominant Alzheimer disease which is a rare form of Alzheimer disease caused by mutations in any of the three genes including the amyloid precursor protein, presenilin 1 and presenilin 2." }, { "input": "List characteristic features of the Revesz syndrome.", "output": "Revesz syndrome is characterized by retinopathy, aplastic anemia, nail dystrophy, and cerebellar hypoplasia." }, { "input": "Does BNN27 promote memory loss?", "output": "No. The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats." }, { "input": "Are genomic regulatory blocks (GRBs) any different than TADs?", "output": "No, clusters of CNEs (GRBs) strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years." }, { "input": "Are Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in neurofibromatosis patients?", "output": "Spinal intradural primary malignant peripheral nerve sheath tumors (MPNST) are rare in patients without neurofibromatosis." }, { "input": "Are Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in neurofibromatosis patients?", "output": "No, Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in patients without neurofibromatosis." }, { "input": "Are Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in neurofibromatosis patients?", "output": "yes, Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in patients without a history of neurofibromatosis; only 18 cases have been reported in the English-language literature to this point." }, { "input": "What does MVA85A stand for?", "output": "MVA85A is the Modified Vaccinia virus Ankara expressing Antigen 85A." }, { "input": "Can MVA85A confer immunity against smallpox?", "output": "No MVA85A is a candidate tuberculosis vaccine." }, { "input": "Is MLL3 part of the ASCOM complex?", "output": "Yes" }, { "input": "What are the effects of CAMK4 inhibition?", "output": " Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator a (CREM-a) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation. CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling" }, { "input": "What are the effects of CAMK4 inhibition?", "output": "CaMK4 inhibition has potential as a therapeutic strategy for Th17-driven autoimmune diseases." }, { "input": "What are the effects of CAMK4 inhibition?", "output": "CaMK4-dependent activation of AKT/mTOR and CREM-a underlies autoimmunity-associated Th17 imbalance Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator a (CREM-a) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation." }, { "input": "What are the effects of CAMK4 inhibition?", "output": "Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator a (CREM-a) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation." }, { "input": "List cohesinopathies", "output": "Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), Warsaw Breakage Syndrome (WABS) and Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome." }, { "input": "Which protein is mutated in Erythropoietic Protoporphyria?", "output": "Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients." }, { "input": "Is marimastat effective for small-cell lung cancer?", "output": "No. Marimastat is not effective for small-cell lung cancer." }, { "input": "Which part of the TNFR2 gene is genetically associated with Systemic Lupus Erythematosus?", "output": "There is a TNFR2 3' flanking region polymorphism in systemic lupus erythematosus." }, { "input": "Which part of the TNFR2 gene is genetically associated with Systemic Lupus Erythematosus?", "output": "A TNFR2 3' flanking region polymorphism in systemic lupus erythematosus." }, { "input": "Which part of the TNFR2 gene is genetically associated with Systemic Lupus Erythematosus?", "output": "A tnfr2 3' flanking region polymorphism in systemic lupus erythematosus has been shown to be significantly associated with selenocytoplasmic lupus erythematotosus. No transmission distortion was observed for tnpr2-196r allele." }, { "input": "What is VISMapper?", "output": "VISMapper is a vector integration site analysis web server to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org." }, { "input": "What is VISMapper?", "output": "The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use. VISMapper is a vector integration site analysis web server to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org." }, { "input": "What is Taupathy?", "output": "Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau protein." }, { "input": "What is Taupathy?", "output": "Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau" }, { "input": "What is Taupathy?", "output": "Taupathy is a progressive neurodegenerative disease of the central nervous system caused by autosomal recessive mutations in the Tau (amyloid precursor protein 1) gene." }, { "input": "What is Taupathy?", "output": "Taupathy is an autosomal-dominant neurodegenerative disease characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and is characterized by loss of motor, sensory, and sensory function." }, { "input": "Is Figitumumab effective for non-small cell lung cancer?", "output": "No. Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit. Adding figitumumab to standard chemotherapy also failed to increase overall survival in patients with advanced nonadenocarcinoma NSCLC." }, { "input": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "output": "The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset measures changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs." }, { "input": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "output": "yes, The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big data provide gene expression profiles induced by over 10 000 compounds, shRNAs, and kinase inhibitors using the L1000 platform." }, { "input": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "output": "TheLINCS L1000 data set contains gene expression data for drug treated human cells, yes" }, { "input": "What is a cytokine storm?", "output": "A cytokine storm is an undesirable elevation of cytokine levels, as may occur in response to a drug or a device, may lead to severe side effects such as systemic inflammatory response syndrome." }, { "input": "What is a cytokine storm?", "output": "Cytokine storm is a poorly explained clinical entity caused by an undesired and aggrandized immune system response leading to unregulated activation of the proinflammatory cascade, often contributing to multisystem organ failure and even death" }, { "input": "What is a cytokine storm?", "output": "Cytokine storm is a poorly understood clinical entity caused by an undesired and ag grandized immune system response leading to unregulated activation of the proinflammatory cascade, often contributing to multisystem organ failure and even death." }, { "input": "Which database exists that contains regulatory SNPs which affect predicted transcription factor binding site affinity?", "output": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor." }, { "input": "Which database exists that contains regulatory SNPs which affect predicted transcription factor binding site affinity?", "output": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites." }, { "input": "Which database exists that contains regulatory SNPs which affect predicted transcription factor binding site affinity?", "output": "SN2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor." }, { "input": "Which database exists that contains regulatory SNPs which affect predicted transcription factor binding site affinity?", "output": "SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs." }, { "input": "Which R package has been developed for MS-based label-free phosphoproteomics?", "output": "Phosphonormalizer is an R package for normalization of MS-based label-free phosphoproteomics." }, { "input": "Which R package has been developed for MS-based label-free phosphoproteomics?", "output": "Phosphonormalizer is a commonly used normalization approach in mass spectrometry-based label-free proteomics. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples." }, { "input": "Which R package has been developed for MS-based label-free phosphoproteomics?", "output": "Global centering-based normalization is a commonly used normalization approach in mass spectrometry-based label-free proteomics. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples. However, especially in phosphoproteomics, this assumption can introduce bias, as the samples are enriched during sample preparation which can mask the underlying biological changes. To address this possible bias, phosphopeptides quantified in both enriched and non-enriched samples can be used to calculate factors that mitigate the bias. Phosphonormalizer is an R package for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics." }, { "input": "Which R package has been developed for MS-based label-free phosphoproteomics?", "output": "Phosphonormalizer is an R package for MS-based label-free phosphoproteomics based on mass spectrometry-based normalization. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples." }, { "input": "Is there a vaccine for peanut allergy?", "output": "Yes, there is a vaccine for peanut allergy." }, { "input": "Is there a vaccine for peanut allergy?", "output": "yes, there is currently a vaccine being tested for peanut allergies." }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "The virus that causes FIP, Feline Infectious Peritonitis belongs to the family coronavirus." }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline coronavirus (fcov) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (fip)." }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP)" }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline Infectious Peritonitis (FIP) belongs to the family of coronavirus." }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats." }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats" }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline Infectious Peritonitis virus (FIP) belongs to the coronavirus family of the genus Flavivirus which cause central nervous system disease." }, { "input": "The virus that causes FIP, Feline Infectious Peritonitis belongs to what family?", "output": "Feline infectious peritonitis (FIP) is a cat virus caused by a member of the coronavirus family coronaviruses." }, { "input": "What is a \"cytokine storm\"?", "output": "During infectious processes, the production of inflammatory cytokines including tumor necrosis factor (TNF), interleukin-1b (IL-1b), gamma interferon (IFNg) and chemokines orchestrates the anti-infectious innate immune response. However, an overzealous production, leading up to a cytokine storm, can be deleterious and contributes to mortality consecutive to sepsis or toxic shock syndrome." }, { "input": "Is golimumab effective for sarcoidosis?", "output": "No, golimumab is not effective for treatment of sarcoidosis." }, { "input": "Is SARS virus interacting with ACE2 encoded protein?", "output": "Yes,\nThe infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)." }, { "input": "What is Soluvia?", "output": "Soluvia(tm) by Becton Dickinson is a microinjection system for intradermal delivery of vaccines." }, { "input": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "output": "yes, Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection." }, { "input": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "output": "Yes. The FIP virus is a mutated strain of the Feline enteric Coronavirus (FECV) causing infectious peritonitis and neoplasia" }, { "input": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "output": " Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection." }, { "input": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "output": " Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection." }, { "input": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "output": "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection." }, { "input": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "output": "Yes. The FIP virus is a mutated strain of the Feline enteric coronavirus (FECV) infects cats, and is thought to be a newly identified strain with heterozygous mutations that create a K27M amino acid substitution." }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": "SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters." }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression" }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": "High level expression of the Xlr nuclear protein in immature thymocytes and colocalization with the matrix-associated region-binding SATB1 protein Its onset preceded the rearrangement of TCR genes, as Xlr expression was conserved in thymus cells from RAG1(0/0) mice. An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters." }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": " SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes." }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development." }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": " Its onset preceded the rearrangement of TCR genes, as Xlr expression was conserved in thymus cells from RAG1(0/0) mice. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters." }, { "input": "Does SATB1 regulate the RAG1 and RAG2 genes?", "output": "An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters." }, { "input": "What is the main difference between nascent and mature chromatin?", "output": "Nascent chromatin is created after transcription and is mostly lacking histone modifications and H1, which makes it more prone to digestion by DNaseI." }, { "input": "What is the main difference between nascent and mature chromatin?", "output": " Like normal nascent chromatin, chromatin labeled for brief periods (0.5-1 min) in the presence of butyrate was more sensitive to digestion with DNase I and micrococcal nuclease than control bulk chromatin. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin)." }, { "input": "What is the main difference between nascent and mature chromatin?", "output": "The nascent and mature forms of chromatin differ in two aspects of their histone modifications: polycistronic messengers are expressed as a sequence of individual nucleosomes only in mature chromatin, and the nucleosome is involved in both transcription and repair processes." }, { "input": "What is the main difference between nascent and mature chromatin?", "output": " The second class of nascent DNA is distinguished from the nucleosomal component by its insolubility, lack of discernible nucleosomal organization, and dependence on protein synthesis to attain typical subunit structure Like normal nascent chromatin, chromatin labeled for brief periods (0.5-1 min) in the presence of butyrate was more sensitive to digestion with DNase I and micrococcal nuclease than control bulk chromatin. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin). Incubation of mature chromatin in butyrate for 1 h did not induce DNase I sensitivity: therefore, the presence of sodium butyrate was required during replication to preserve the increased digestibility of nascent chromatin DNA In a previous study (Perry and Annunziato, Nucleic Acids Res. Within 10 min of DNA synthesis, the spacing of mature chromatin is established; the spacing maturation can occur in the absence of protein synthesis. this class of nascent chromatin exhibits a shortened repeat length of approximately 165 bp, as opposed to the 288-bp repeat of bulk chromatin." }, { "input": "What is the main difference between nascent and mature chromatin?", "output": "Mature and nascent chromatin differ in two aspects of their histone modifications: polycistronic messengers are expressed as a sequence of individual nucleosomes only in mature cells, and they are preferentially expressed in the later stages of cell development." }, { "input": "What is the main difference between nascent and mature chromatin?", "output": "In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin)." }, { "input": "Is CTCF bound at nucleosome free regions?", "output": "yes, robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites" }, { "input": "Is CTCF bound at nucleosome free regions?", "output": "nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin." }, { "input": "Is CTCF bound at nucleosome free regions?", "output": "robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites" }, { "input": "Is CTCF bound at nucleosome free regions?", "output": "Nucleosome occupancy at nucleosome-free regions (nfrs), many of which are located at sites occupied by the multivalent factors ctcf and cohesin. This general architectural change correlate with enhanced binding of ct cf and more pronounced insulation across chromatin boundaries in lineage-committed cells." }, { "input": "Is CTCF bound at nucleosome free regions?", "output": "Nucleosome occupancy is reduced at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors CTCF and cohesin. Robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites" }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. Proteasome inhibitor bortezomib" }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "Yes, bortezomib is a Proteasome inhibitor." }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "Yes, bortezomib is a potent and specific reversible ubiquitin/proteasome inhibitor." }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "yes, The proteasome-inhibitor bortezomib" }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "Yes bortezomib is a Proteasome inhibitor." }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "proteasome inhibitor bortezomib" }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for gbm." }, { "input": "Is bortezomib a Proteasome inhibitor?", "output": "Proteasome inhibitor bortezomib" }, { "input": "Is PRDM9 essential for meiosis?", "output": "PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis." }, { "input": "Is PRDM9 essential for meiosis?", "output": "In aggregate, our data indicate that domains typically involved in regulation of gene expression do not serve that role in PRDM9, but are likely involved in setting the proper chromatin environment for initiation and completion of homologous recombination. PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites." }, { "input": "Is PRDM9 essential for meiosis?", "output": "yes, Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis" }, { "input": "Is PRDM9 essential for meiosis?", "output": "Prdm9, is a meiosis-specific protein that trimethylates h3k4 and controls the activation of recombination hot spots. It is an essential enzyme in the progression of early meiotic prophase." }, { "input": "Is PRDM9 essential for meiosis?", "output": "Yes. PRDM9 is an evolutionarily conserved protein that is essential for meiosis." }, { "input": "Is PRDM9 essential for meiosis?", "output": "In many eukaryotes, sites of meiotic recombination, also called hotspots, are regions of accessible chromatin, but in many vertebrates, their location follows a distinct pattern and is specified by PR domain-containing protein 9 (PRDM9). PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites." }, { "input": "Is PRDM9 essential for meiosis?", "output": "Yes, PRDM9 is essential for meiosis." }, { "input": "Is PRDM9 essential for meiosis?", "output": "Yes. PRDM9 is an RNA-binding protein that is essential for meiosis." }, { "input": "Is PRDM9 essential for meiosis?", "output": "Yes. PRDM9 is an essential factor for meiosis." }, { "input": "Is PRDM9 essential for meiosis?", "output": "PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites." }, { "input": "Is PRDM9 essential for meiosis?", "output": "PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. PRDM9 (PR domain-containing protein 9) is a meiosis-specific protein that trimethylates H3K4 and controls the activation of recombination hot spots." }, { "input": "What is particular about the mouse Fxy gene's chromosomal position?", "output": "We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species." }, { "input": "What is particular about the mouse Fxy gene's chromosomal position?", "output": "The gene Fxy (also known as MID1 [7]) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes" }, { "input": "What is particular about the mouse Fxy gene's chromosomal position?", "output": "We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. " }, { "input": "What is particular about the mouse Fxy gene's chromosomal position?", "output": "The mouse fxy gene spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the x chromosome, but the remainder is located on both x and y chromosomes." }, { "input": "What is particular about the mouse Fxy gene's chromosomal position?", "output": "The gene Fxy (also known as MID1) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes." }, { "input": "What is particular about the mouse Fxy gene's chromosomal position?", "output": "The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22" }, { "input": "Should Pentoxifylline be used for treatment of amyotrophic lateral sclerosis?", "output": "No. Pentoxifylline is not beneficial in amyotrophic lateral sclerosis and should be avoided in patients treated with riluzole." }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron Excitation Tomography (PET) is a simple, reliable, and valid method of assessing brain activity in patients with Parkinson's disease (PD)." }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron emission tomography pet (pet) is used to measure changes in regional brain glucose metabolism. It is used for the quantitative measurement of regional cerebral flow in awake rats." }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron emission tomography (PET) allows the quantitative measurement of regional cerebral flow (rCBF) in humans in quantitative terms" }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron Excitation Tomography (PET) is a method that uses photoreactive nucleotides (Percutaneous Transluminal Angioplasty) to detect structural changes in the central nervous system (CNS) following ischemic injury." }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron emission tomography (PET) is used to measure differences in metabolism in different tissues." }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron Excitation Tomography (PET) is a method that allows for quantitative assessment of brain injury conditions such as multiple system atrophy." }, { "input": "What does a PET (Positron Excitation Tomography) measure?", "output": "Positron emission tomography (PET) with [(18)F]2-fluoro-2-deoxy-D-glucose was used to measure changes in regional brain glucose metabolism" }, { "input": "Is the CADM2 gene associated with differences in information processing speed?", "output": "Yes, genetic variation in the CADM2 gene is associated with individual differences in information processing speed." }, { "input": "Is the CADM2 gene associated with differences in information processing speed?", "output": "Yes. Genetic variation in the CADM2 gene is associated with individual differences in information processing speed." }, { "input": "Is the CADM2 gene associated with differences in information processing speed?", "output": "Yes, changes in the CADM2 gene have been associated with differences in information processing speed." }, { "input": "What is GeneCodeq?", "output": "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy." }, { "input": "What is GeneCodeq?", "output": "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy." }, { "input": "What is GeneCodeq?", "output": "The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. GeneCodeq is a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. The method leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods." }, { "input": "Is Nivolumab (Opdivo) a PD-L1 inhibitor?", "output": "No, Nivolumab (Opdivo) is a PD-1 inhibitor." }, { "input": "Is Nivolumab (Opdivo) a PD-L1 inhibitor?", "output": "Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab" }, { "input": "Does clinical trial data support the use of minocycline for amyotrophic lateral sclerosis?", "output": "No. Available clinical trial data suggest that minocycline does not improve prognosis and functional status, and has a harmful effect on patients with amyotrophic lateral sclerosis." }, { "input": "What are apoptotic bodies?", "output": "Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular space by almost all types of cells. EVs can cross the physiological barriers, and a variety of biological fluids are enriched in them. EVs are a heterogeneous population of vesicles, including exosomes, microvesicles, and apoptotic bodies.\nApoptotic bodies are generated on apoptotic cell shrinkage and death." }, { "input": "Is the drug Exubera currently (March 2020) available?", "output": "No, Exubera has been discontinued due to suboptimal market acceptance." }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "eviction of h1" }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "Chd1 and chd1 atp-dependent chromatin remodelers compete to set nucleosome spacing in vivo." }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo. CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing." }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing." }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo" }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin" }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing" }, { "input": "What is the function of the ISW1 and CHD1 remodellers in yeast chromatin?", "output": "The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing" }, { "input": "Are breaks in double stranded DNA associated with ionizing radiation?", "output": "Yes, double-strand breaks in double stranded DNA may be associated with ionizing radiation risk." }, { "input": "Are breaks in double stranded DNA associated with ionizing radiation?", "output": "Yes, breaks in double stranded DNA are associated with ionizing radiation." }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "Ionizing radiation is commonly associated with lung cancer, prostate cancer, breast cancer, cervical intraepithelial neoplasia and oral squamous cell carcinoma." }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "Exposure to ionizing radiation increases the risk for thyroid and breast cancer and leukemia as well as others such as osteosarcoma." }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "Breast cancer, multiple myeloma, leukaemia and osteosarcoma are commonly associated with ionizing radiation." }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "Breast cancer, multiple myeloma, leukaemia and osteosarcoma are examples of cancers that are commonly associated with ionizing radiation." }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "Because latency period for different nosological forms of radiation-induced malignant tumors varies widely, profound attention in further studies should be drawn not only to thyroid, breast cancers and leukemia, but also to malignancies with longer latent period: lung, stomach, colon, ovary, urinary bladder, kidney cancer and multiple myeloma." }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "By contrast, osteosarcoma may be caused by external or internal ionizing radiation," }, { "input": "As of 2019, what type of cancer is commonly associated with ionizing radiation", "output": "radiation- induced breast cancer" }, { "input": "Is KAT2A involved in Acute myeloid leukemia (AML)?", "output": "Yes. The KAT2A gene encodes a receptor tyrosine kinase that is frequently mutated in human acute myeloid leukemia (AML). Activating mutations in Kat2A in response to aberrations in TRAIL can lead to TRAIL-1 activation, resulting in the up-regulation of key AML genes, such as TGFb1, NF-kB, Akt, IKK-1, FOXO1, ERK1/2 and c-Myc." }, { "input": "Is KAT2A involved in Acute myeloid leukemia (AML)?", "output": "Yes, KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells." }, { "input": "What is Idiopathic toe walking?", "output": "Idiopathic toe walking is a pathological gait pattern in which children older than 3 years walk on their tip toes with no contact between the heels and the ground." }, { "input": "Is NicVAX vaccine effective for smoking cessation?", "output": "No. NicVAX vaccine failed to meet the primary endpoint in two large phase III studies, although the correlation of higher abstinence rates in subjects with higher immunity to nicotine was observed. The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support." }, { "input": "Does natalizumab improve disease course of secondary progressive multiple sclerosis?", "output": "No. Atalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component." }, { "input": "Before 2019, what neurologic diseases are associated with the tau protein?", "output": "Tau proteins are involved in the pathogenesis of multiple sclerosis and amyotrophic lateral sclerosis." }, { "input": "Before 2019, what neurologic diseases are associated with the tau protein?", "output": "Both Alzheimer's Disease and Multiple Sclerosis are associated with tau protein" }, { "input": "What is the difference between Daptacel and Pentacel?", "output": "Pentacel is a combination vaccine equivalent to the combination of Daptacel, IPOL and ActHIB vaccines." }, { "input": "AhR ligands are attractive drug targets for pharmaceutical development due to their induction of Cyp1a1, yes or no?", "output": "Yes, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines." }, { "input": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "output": "H2A.Z probably helps RSC in keeping the gene nucleosome-free." }, { "input": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "output": "H2A.Z probably helps RSC in keeping the gene nucleosome-fre" }, { "input": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "output": "Yes, the chromatin remodeling complex, RSC, uses H2A. Z nucleosomes to remodel chromatin." }, { "input": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "output": "yes, Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation." }, { "input": "Does the chromatin remodeling complex, RSC target H2A.Z nucleosomes?", "output": "H2A.Z probably helps RSC in keeping the gene nucleosome-fre Accordingly, the absence of SWR-C or histone H2A.Z results in compromised chromatin remodeling and impaired gene expression in the absence of RSC and H3K4 methylation." }, { "input": "List radioprotection agents.", "output": "Amifostine\nCAPE\nMelanin\nMelatonin\nMetformin\nTea polyphenols \nalpha-2-macroglobulin" }, { "input": "What is the effect of Satb1 knock-out in mice?", "output": "inhibited cell viability and migration" }, { "input": "What is the effect of Satb1 knock-out in mice?", "output": "While T cell growth in vitro, Satb1 knockdown was found to be effective in vivo by inhibiting T cell proliferation and activating apoptosis in a subset of T cells" }, { "input": "What is the effect of Satb1 knock-out in mice?", "output": "knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis." }, { "input": "What is the effect of Satb1 knock-out in mice?", "output": "SATB1 is essential for maintaining TCR responsiveness during the induction and effector phases and may provide a novel therapeutic target for T cell-mediated autoimmune diseases. knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis." }, { "input": "What is the effect of Satb1 knock-out in mice?", "output": "Knock-out of Satb1 significantly inhibited cell viability and migration, and promoted Schwann cells apoptosis." }, { "input": "Has ZP-PTH been tested in a phase II clinical trial?", "output": "Yes, ZP-PTH was successfully tested in a phase II clinical trial for the treatment of post-menopausal women with osteoporosis." }, { "input": "PH motifs in which genes endow breast cancer growth?", "output": "Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Signal-binding motifs in PAR1&2 are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes." }, { "input": "What is herd immunity?", "output": "Vaccines are very effective in providing individual and community (herd) immunity against a range of diseases.\nWe argue that individuals who have access to vaccines and for whom vaccination is not medically contraindicated have a moral obligation to contribute to the realisation of herd immunity by being vaccinated." }, { "input": "Are multipotent adult progenitor cells effective for treatment of stroke?", "output": "No. There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90. Further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned." }, { "input": "List the stages/types of Multiple Sclerosis.", "output": "Multiple sclerosis presents with different phenotypes, most commonly a relapsing-remitting course and, less frequently, a progressive accumulation of disability from disease onset (primary progressive multiple sclerosis). The majority of people with relapsing-remitting multiple sclerosis, after a variable time, switch to a stage characterised by gradual neurological worsening known as secondary progressive multiple sclerosis." }, { "input": "List the stages/types of Multiple Sclerosis.", "output": "Multiple Sclerosis (MS) is divided into three stages: primary progressive, relapsing-remitting, relapping-Remitting MS, and secondary progressive MS." }, { "input": "List the stages/types of Multiple Sclerosis.", "output": "Multiple Sclerosis can be classified into four different stages (A to C), with different types of neurodegenerative disorders such as primary, chronic, relapsing-remitting and progressive forms." }, { "input": "List the stages/types of Multiple Sclerosis.", "output": "Multiple Sclerosis (MS) is a multisystem disorder, which can be classified into primary progressive, relapsing-remitting, relapping-remoting and non-progressive stages." }, { "input": "What is known about Opicinumab for multiple sclerosis?", "output": "Opicinumab is a new Anti lingo 1 monoclonal antibody that is tested in relapsing remitting multiple sclerosis. The anti-LINGO-1 trial showed that the drug is safe and tolerable. A future phase II trial will provide more insights regarding the compound." }, { "input": "What is the target of Inebilizumab?", "output": "Inebilizumab is an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in multiple sclerosis and neuromyelitis optica." }, { "input": "Is eculizumab effective for Guillain-Barr\u00e9 syndrome?", "output": "In a clinical trial eculizumab did not achieve primary outcome for Guillain-Barre syndrome. However, because this was a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials." }, { "input": "List Mcl-1 inhibitors.", "output": "A-1210477\nS63845" }, { "input": "Autophagy is the process where a virus obtains nutrients from it's host, yes or no?", "output": "No, autophagy is important in cellular homeostasis for the cell survival mechanism and is involved apoptosis." }, { "input": "Autophagy is the process where a virus obtains nutrients from it's host, yes or no?", "output": "Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles." }, { "input": "Autophagy is the process where a virus obtains nutrients from it's host, yes or no?", "output": "Autophagy is important in cellular homeostasis for the cell survival mechanism." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "MPE-seq (methidiumpropyl-EDTA sequencing) is a new method for the genome-wide characterization of chromatin that involves the digestion of nuclei with MPE-Fe(II) followed by massively parallel sequencing of the whole genome. Like micrococcal nuclease (MNase), MNase preferentially cleaves the linker DNA between nucleosomes. However, there are differences in the cleavage of nuclear chromatin by MP e-seq relative to MNase. Moreover, unlike MNase, MPe-seq cleaves nuclear DNA" }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "Methidiumpropyl-EDTA sequencing (MPE-seq) is a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq unlike MNase-seq cleaves nuclear DNA with little sequence bias and thus provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "digestion of nuclei withmpe-fe(ii)" }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "Methidiumpropyl-edta sequencing is a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withmpe-fe (ii) followed by massively parallel sequencing. Mpe-seq provides a unique and straightforward means for theome-wide analysis of chromat structure with minimal dna sequence bias." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "The methidiumpropyl-EDTA sequencing (MPE-seq) method uses a GpC methyltransferase (M. CviPI) and next generation sequencing to generate a high resolution footprint of nucleosome structure using less than 1 million cells while retaining endogenous DNA fragments from the same DNA strand." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": " methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": " methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing." }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. " }, { "input": "What is the basis of the methidiumpropyl-EDTA sequencing (MPE-seq) method?", "output": "methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias." }, { "input": "Name two rotavirus vaccines.", "output": "Two rotavirus vaccines licensed for global use are RotaTeq and Rotarix." }, { "input": "Does CXorf21 escape X chromosome inactivation?", "output": "CXORF21 belongs to a set of X-linked differentially expressed genes that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function." }, { "input": "Does CXorf21 escape X chromosome inactivation?", "output": "Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function." }, { "input": "Does CXorf21 escape X chromosome inactivation?", "output": "yes, Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function." }, { "input": "Which programming language has been used for implementing GWAR?", "output": "Stata" }, { "input": "Describe f-scLVM", "output": "Single-cell RNA-sequencing (scRNA-seq) allows studying heterogeneity in gene expression in large cell populations. Such heterogeneity can arise due to technical or biological factors, making decomposing sources of variation difficult. F-scLVM (factorial single-cell latent variable model) is a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity. The model jointly estimates the relevance of individual factors, refines gene set annotations, and infers factors without annotation. F-scLVM robustly decomposes scRNA-seq datasets into interpretable components, thereby facilitating the identification of novel subpopulations." }, { "input": "Describe f-scLVM", "output": "f-scLVM (factorial single-cell latent variable model) is a method based on factor analysis that uses pathway annotations to guide the inference of interpretable factors underpinning the heterogeneity. It jointly estimates the relevance of individual factors, refines gene set annotations, and infers factors without annotation. In applications to multiple scRNA-seq datasets, f-SCLVM robustly decomposes scRNA -seq datasets into interpretable components, thereby facilitating the identification of novel subpopulations." }, { "input": "Does promoter shape vary across populations?", "output": "Yes. Promoter shape varies across populations and affects promoter evolution and expression noise. This is accompanied by differences in the expression levels of different genes, which may reflect differences in their regulatory mechanisms." }, { "input": "Does promoter shape vary across populations?", "output": "Yes. Promoter shape varies across populations and affects promoter evolution and expression noise." }, { "input": "Does promoter shape vary across populations?", "output": "Yes. Promoter shape varies across populations and affects promoter evolution and expression noise. In some populations, promoter shape is more or less consistent across populations, while in other populations it varies little." }, { "input": "How large is a lncRNAs?", "output": "lncRNAs are defined as RNA transcripts longer than 200 nucleotides that are not transcribed into proteins" }, { "input": "What is MLE4901?", "output": "MLE4901 is an oral neurikinin 3 receptor antagonist that has been shown to safely and effectively relieve hot flush symptoms in menopausal women without the need for oestrogen exposure." }, { "input": "What is the drug chloroquine or hydroxychloroquine used for?", "output": "Chloroquine (CQ) has been used for decades as the primary chemotherapeutic drug for the treatment of malaria.\nHydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA).\nChloroquine is a potent inhibitor of SARS coronavirus infection and spread." }, { "input": "Does xaliproden improve prognosis of amyotrophic lateral sclerosis?", "output": "No. There is not sufficient high quality evidence that xaliproden significantly improves prognosis of amyotrophic lateral sclerosis patients." }, { "input": "What is Telangiectasia?", "output": "Telangiectasia (macroscopically visible dilated skin vessels)" }, { "input": "What is Telangiectasia?", "output": "Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles" }, { "input": "What is Telangiectasia?", "output": "Telangiectasias are prominent small vessels (venules, capillaries or arterioles) that are visible as small red-purple focal lesions in the skin and mucous membranes." }, { "input": "What is Telangiectasia?", "output": "Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles Telangiectasia (macroscopically visible dilated skin vessels)" }, { "input": "Is cathepsin L active in endosomes?", "output": "yes,\nCathepsin L is found in the Late Endosome/Lysosome." }, { "input": "Which tissues express the ACE2 protein?", "output": "Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes" }, { "input": "In which chromosome are transgenes inserted in the case of the LiPS-A3S line?", "output": "Transgenesis of human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. While in recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. One cell line/clone, LiPS-A3, has an integration site in chromosome 15 maintaining robust expression without silencing. Different transgenes can be inserted therein rapidly and efficiently through recombinase-mediated cassette exchange (RMCE). The LiPS-A3 line can greatly facilitate the insertion of reporter and other genes in hPSCs. Targeting transgenes in the LiPS-A3S genomic locus can find broad applications in stem cell research and possibly cell and gene therapy." }, { "input": "In which chromosome are transgenes inserted in the case of the LiPS-A3S line?", "output": "The LiPS-A3S line of human pluripotent stem cells is inserted via transgenesis from chromosome 15." }, { "input": "In which chromosome are transgenes inserted in the case of the LiPS-A3S line?", "output": "The LiPS-A3S line of human pluripotent stem cells is inserted into chromosome 15." }, { "input": "In which chromosome are transgenes inserted in the case of the LiPS-A3S line?", "output": "Human pluripotent stem cells (hPSCs) can enable and empower a variety of studies in stem cell research, including lineage tracing and functional genetics studies. In recent years much progress has been made in the development of tools for gene targeting, little attention has been given to the identification of sites in the human genome where transgenes can be inserted and reliably expressed. The LiPS-A3S line of chromosome 15 is one of the few genes with an integration site in chromosome 15." }, { "input": "What is a J pouch?", "output": "The j pouch is a colonic j-pouch with anastomosis to the rectal stump. It is an accepted form of reconstruction after low anterior resection (lar) for rectal carcinoma." }, { "input": "What is a J pouch?", "output": "Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR) for rectal carcinoma total proctocolectomy with outcomes after ileal J-pouch anal anastomosis (IPAA) at a single institution" }, { "input": "What is a J pouch?", "output": "After a proctocolectomy or surgery for ulcerative colitis or rectal carcinoma, a ileal J-pouch anal anastomosis (IPAA) or J pouch. Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR)." }, { "input": "What is the function of the protein encoded by the gene NKCC2?", "output": "The protein function as an Na-K-Cl cotransporter." }, { "input": "Is celecoxib effective for amyotrophic lateral sclerosis?", "output": "No. In a clinical trial, celecoxib did not have a beneficial effect on patients with amyotrophic lateral sclerosis." }, { "input": "Is the protein MCL-1 anti-apoptotic?", "output": "Yes, MCL-1 is an anti-apoptotic protein." }, { "input": "Describe the mechanism of action of Trilaciclib.", "output": "Trilaciclib is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, which act by inhibiting progression from the G1 to S phases of the cell cycle." }, { "input": "How is ZP-PTH delivered to patients?", "output": "ZP-PTH uses a transdermal drug-coated microneedle patch system." }, { "input": "Which disease is ZP-PTH used for?", "output": "ZP-PTH is used for the treatment of osteoporosis." }, { "input": "Which gene is mutated in the classic Bartter's syndrome?", "output": "Classic Bartter's syndrome has been demonstrated to result from defective chloride transport across the basolateral membrane in the distal nephron due to mutations in the chloride channel gene CLCNKB." }, { "input": "What is the purpose of the Unique Connectivity of Uncharged Compounds (UC2) search tool?", "output": "The Unique Connectivity of Uncharged Compounds (UC2) search tool uses unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics." }, { "input": "What is the purpose of the Unique Connectivity of Uncharged Compounds (UC2) search tool?", "output": "The Unique Connectivity of Uncharged Compounds (UC2) search tool uses unique connectivity of uncharged compounds for metabolite annotation by database searching in mass spectrometry-based metabolomics. The UC2 search tool is available at http://unc.bioqrator.org/UC2/." }, { "input": "What is the purpose of the Unique Connectivity of Uncharged Compounds (UC2) search tool?", "output": "The Unique Connectivity of Uncharged Compounds (UC2) search tool is used for metabolite annotation by database searching in mass spectrometry-based metabolomics." }, { "input": "What is the purpose of the Unique Connectivity of Uncharged Compounds (UC2) search tool?", "output": "For metabolite annotation in metabolomics, variations in the registered states of compounds (charged molecules and multiple components, such as salts) and their redundancy among compound databases could be the cause of misannotations and hamper immediate recognition of the uniqueness of metabolites while searching by mass values measured using mass spectrometry. The search system named UC2 (Unique Connectivity of Uncharged Compounds) has been developed where compounds are tentatively neutralized into uncharged states and stored on the basis of their unique connectivity of atoms after removing their stereochemical information using the first block in the hash of the IUPAC International Chemical Identifier, by which false-positive hits are remarkably reduced, both charged and uncharged compounds are properly searched in a single query and records having a unique connectivity are compiled in a single search result." }, { "input": "Name a selective NK3R agonist.", "output": "Senktide is a highly potent and selective NK3R agonist." }, { "input": "What is the target of the drug Olmesartan?", "output": "Olmesartan (OL) is the pharmacologically active metabolite of Olmesartan medoxomil (OM), an FDA-approved angiotensin II receptor antagonist for administrating cardiovascular diseases" }, { "input": "In which cells does TLR7 escape X-chromosome inactivation?", "output": "The tlr7 gene encodes by an x chromosome locus. Tlr7 is encoded by an x-chromosome inactivation in immune cells from women and klinefelter syndrome patients." }, { "input": "In which cells does TLR7 escape X-chromosome inactivation?", "output": "TLR7 evades silencing by X chromosome inactivation in immune cells." }, { "input": "In which cells does TLR7 escape X-chromosome inactivation?", "output": "TLR7 escape X-chromosome inactivation by RNA polymerase II (ChIP-seq) DNA methylation to produce active TLR7 in immune cells" }, { "input": "In which cells does TLR7 escape X-chromosome inactivation?", "output": "TLR7 escape X-chromosome inactivation by becoming activated in response to DNA damage caused by biallelic loss-of-function mutations on the X chromosome. In addition, TLR7 expression can also be observed in a dose-dependent manner in immune cells, such as epithelial cells, monocytes and macrophages." }, { "input": "In which cells does TLR7 escape X-chromosome inactivation?", "output": "immune cells" }, { "input": "In which cells does TLR7 escape X-chromosome inactivation?", "output": "TLR7 is encoded by an X chromosome locus, and we examined here whether the TLR7 gene evades silencing by X chromosome inactivation in immune cells from women and Klinefelter syndrome males" }, { "input": "Which tool has been developed for prediction of single-cell DNA methylation states using deep learning?", "output": "DeepCpG is a computational approach based on deep neural networks to predict methylation states in single cells. By evaluating DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols it turns out that DeepCpG yields substantially more accurate predictions than previous methods." }, { "input": "Which tool has been developed for prediction of single-cell DNA methylation states using deep learning?", "output": "DeepCpG is a computational approach based on deep neural networks to predict single-cell DNA methylation states in single cells." }, { "input": "When was vaxchora first licensed by the FDA?", "output": "Vaxchora was licensed by the FDA on June 10 2016." }, { "input": "What is the active ingredient of Eligard?", "output": "The active ingredient of Eligard is leuprorelin acetate." }, { "input": "Which company produces Eligard?", "output": "Eligard is produced by Astellas Pharma GmbH." }, { "input": "Which type of distance is used in the R-package XenofilteR?", "output": "The R-package XenofilteR separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome." }, { "input": "Which type of distance is used in the R-package XenofilteR?", "output": "XenofilteR separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": " Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": " Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "20" }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the emergence of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "In the elephant genome, TP53 is encoded by 20 copies." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage." }, { "input": "How many copies of TP53 does the elephant genome contain?", "output": "The elephant genome encodes 20 copies of the tumor suppressor gene tp53 and that the evolution of large body sizes, the evolves of extreme sensitivity to genotoxic stress, and a hyperactive tp53 signaling pathway in the elephant (proboscidean) lineage have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction." }, { "input": "Which company originally developed the drug Afrezza?", "output": "The inhaled insulin Technosphere, also known as Afrezza is produced by the MannKind Corporation." }, { "input": "Which tool exist for predicting drug synergy with deep learning?", "output": "Deep Learning has had an impact in many research areas by achieving new state-of-the-art model performance. DeepSynergy has been developed as a tool that uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies." }, { "input": "Which tool exist for predicting drug synergy with deep learning?", "output": "DeepSynergy is an online tool for predicting drug synergy with deep learning. It is a method for predicting anti-cancer drug synergy based on a semi-supervised learning algorithm that is trained on a corpus of k-nearest neighbor data and combines pharmacological, structural and pharmacological features extracted from a large variety of biological datasets." }, { "input": "Is ozanezumab effective for amyotrophic lateral sclerosis?", "output": "No. Ozanezumab did not show efficacy compared with placebo in patients with amyotrophic lateral sclerosis. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS." }, { "input": "Is Dexmecamylamine effective for depression?", "output": "No. Antidepressant effect of Dexmecamylamine (TC-5214) was not observed in clinical trials." }, { "input": "Which cloud-based platform has been developed for comparing GWAS?", "output": "EasyGWAS is a cloud-based platform for comparing the results of Genome-Wide Association Studies (GWAS)." }, { "input": "Which cloud-based platform has been developed for comparing GWAS?", "output": "The ever- growing availability of high-quality genotypes for a multitude of species has enabled researchers to explore the underlying genetic architecture of complex phenotypes at an unprecedented level of detail using genome-wide association studies (GWAS). The systematic comparison of results obtained from GWAS of different traits opens up new possibilities, including the analysis of pleiotropic effects. In order to facilitate the simple comparison of GWAS results, easyGWAS has been developed as a powerful, species-independent online resource for computing, storing, sharing, annotating, and comparing GWAS." }, { "input": "Can CMB305 be used against sarcomas?", "output": "Yes, the CMB205 vaccine is aimed at synovial sarcoma and myxoid/round cell liposarcoma patients." }, { "input": "What is Quadracel?", "output": "Quadracel (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, Sanofi Pasteur Inc.) is a new vaccination developed to condense the last dose of both DTaP and IPV so they do not have to be given separately, thus reducing the total number of vaccinations required. In a randomized, controlled, phase 3, pivotal trial, Quadracel proved to be as efficacious and safe as Daptacel (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated, Sanofi Pasteur Inc.), given separately, to children between the ages of 4 and 6 years." }, { "input": "What delivery system is used for the Fluzone Intradermal vaccine?", "output": "Fluzone was the first influenza vaccine licensed in the USA that uses a new microinjection system for intradermal delivery of vaccines (Soluvia(tm), Becton Dickinson)." }, { "input": "Name two inhalable insulin products.", "output": "Despite discontinuation of the first inhalable insulin, Exubera(r), due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza(r)." }, { "input": "How is the mouse Fxy gene evolving?", "output": " Here, we report that the rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique." }, { "input": "How is the mouse Fxy gene evolving?", "output": "The rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique." }, { "input": "How long in bp is the human pseudoautosomal region 2 (PAR2)?", "output": "The human pseudoautosomal region 2 (PAR2), which is located in the long arm of chromosome 9 (LTR6B) and consists of 32 exons, is320-kb long." }, { "input": "How long in bp is the human pseudoautosomal region 2 (PAR2)?", "output": "The 320-kb human pseudoautosomal region 2 (PAR2) at the tips of the long arms of the X and Y chromosomes is thought to have been duplicated onto the Y chromosome recently in primate evolution" }, { "input": "How long in bp is the human pseudoautosomal region 2 (PAR2)?", "output": "The human pseudoautosomal region 2 (PAR2) is 320-kb long." }, { "input": "Does teplizumab hold promise for diabetes prevention?", "output": "Yes, teplizumab is promising for diabetes prevention." }, { "input": "What is another name for acid sphingomyelinase deficiency (ASMD)?", "output": "Acid sphingomyelinase deficiency(ASMD) is also known as Niemann-Pick disease type A and type B." }, { "input": "What is another name for acid sphingomyelinase deficiency (ASMD)?", "output": "Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). The clinical spectrum distinguishes a severe infantile neurological form (type A), a non-neurological visceral form (type B) and a rare intermediate neurovisceral form." }, { "input": "What is another name for acid sphingomyelinase deficiency (ASMD)?", "output": "Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B)" }, { "input": "What is another name for acid sphingomyelinase deficiency (ASMD)?", "output": "niemann-pick disease" }, { "input": "What rare disease is associated with a mutation in the GPC6 gene on chromosome 13?", "output": " The proband had normal molecular analysis of the glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia" }, { "input": "What rare disease is associated with a mutation in the GPC6 gene on chromosome 13?", "output": "The proband had normal molecular analysis of the glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia" }, { "input": "What rare disease is associated with a mutation in the GPC6 gene on chromosome 13?", "output": "The glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia." }, { "input": "What rare disease is associated with a mutation in the GPC6 gene on chromosome 13?", "output": "Omodysplasia is a rare autosomal recessive disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in the GPC6 gene on chromosome 13." }, { "input": "What are 3 symptoms of Waardenburg Syndrome?", "output": "Waardenburg syndrome is a rare genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation." }, { "input": "What are 3 symptoms of Waardenburg Syndrome?", "output": "Waardenburg syndrome (WS) is a rare autosomal dominant disorder characterized by dystopia canthorum, auditory, pigmentary abnormalities, and sensorineural deafness." }, { "input": "What are 3 symptoms of Waardenburg Syndrome?", "output": "Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation." }, { "input": "Does ProSavin use an adenoviral vector?", "output": "No, ProSavin is a lentiviral vector based gene therapy." }, { "input": "Does radiation for tinea capitis increases brain tumor risk?", "output": "Yes, radiation therapy for tinea capitis is associated with increased risk of meningiomas and gliomas." }, { "input": "What gene is mutated in Huntington's Disease patients?", "output": "Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene HTT encoding the Huntingtin protein on chromosome 4." }, { "input": "What gene is mutated in Huntington's Disease patients?", "output": "Huntington's disease (HD; OMIM 143100), a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ) motif in the huntingtin gene." }, { "input": "What gene is mutated in Huntington's Disease patients?", "output": "(HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene." }, { "input": "What gene is mutated in Huntington's Disease patients?", "output": "Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene." }, { "input": "List types of cancer where Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved", "output": "Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved in the development of pancreatic cancer, glioblastoma and breast cancer." }, { "input": "List types of cancer where Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved", "output": "Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) has been implicated in various types of cancer such as glioblastoma, breast cancer and pancreatic cancer." }, { "input": "List types of cancer where Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved", "output": "Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) is involved in several types of cancer including pancreatic cancer, glioblastoma and breast cancer." }, { "input": "Is pimavanserin a typical antipsychotic?", "output": "No, pimavanserin is an atypical antipsychotic." }, { "input": "Can Flotillin be used as exosomal marker?", "output": "Yes,\nFlotillin 1 is a known exosomal marker protein." }, { "input": "How many genes belong to the KRAB-ZNF family in the human genome?", "output": "The KRAB-ZNF family is a multisubunit protein family comprised of 70 co-regulated genes, denoted KLR1-ZNF15, that is represented by multigene families in the human genome." }, { "input": "How many genes belong to the KRAB-ZNF family in the human genome?", "output": "There are 70 human KRAB-ZNFs." }, { "input": "Which molecule is targeted by Asciminib?", "output": "Asciminib is an orally administered allosteric inhibitor of the BCR-ABL tyrosine kinase." }, { "input": "Please list 2 human diseases caused by a coronavirus.", "output": "Middle East respiratory syndrome (MERS) and SARS are diseases caused by a coronavirus." }, { "input": "Please list 2 human diseases caused by a coronavirus.", "output": "MERS and SARS are 2 human diseases caused by coronaviruses" }, { "input": "What is characteristic to Fitz-Hugh\u2013Curtis syndrome?", "output": "Fitz-Hugh-Curtis syndrome is a rare complication of pelvic inflammatory disease that involves liver capsule inflammation associated with genital tract infection, which is usually caused by Neisseria gonorrhoea and Chlamydia trachomatis." }, { "input": "What is the trade name of sildenafil?", "output": "The trade name of sildenafil is Viagra." }, { "input": "How large is the SARS-CoV proteome?", "output": "The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products." }, { "input": "Is Apremilast effective for Beh\u00e7et\u2019s Syndrome?", "output": "Yes, Apremilast is effective for Behcet's Syndrome" }, { "input": "Is Rad4/XPC a DNA damage sensing protein?", "output": "Yes,\r\nDNA damage recognition is achieved by the Rad4/XPC nucleotide excision repair complex." }, { "input": "List symptoms of the Hakim Triad?", "output": "Triad of Hakim is well known for normal pressure hydrocephalus (NPH) and includes dementia, gait disturbances and urinary incontinence." }, { "input": "Is the protein ABCG2 transmembrane?", "output": "Yes,\nthe protein ABCG2 is transmembrane." }, { "input": "Can radiotherapy cause radiation induced osteosarcoma?", "output": "Yes, Radiation-induced osteosarcomas are a recognized complication of radiation therapy." }, { "input": "What are manifestations of the Saint's Triad?", "output": "Saint's Triad includes hiatus hernia, gallstones, and diverticulosis coli." }, { "input": "What is the mechanism of action of Erdafitinib?", "output": "Erdafitinib is an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor." }, { "input": "Are male or female persons more prone to autoimmunity?", "output": "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. Examples of this autoimmune dimorphism include (but are not limited to) lupus, rheumatoid arthritis and multiple sclerosis with the two former more prevalent in females than males and the latter more severe during pregnancy. Most recently, sex chromosome abnormalities and skewed X chromosome inactivation have been suggested as novel players, particularly in later-onset diseases." }, { "input": "Are male or female persons more prone to autoimmunity?", "output": "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. Most recently, sex chromosome abnormalities and skewed X chromosome inactivation have been suggested as novel players, particularly in later-onset diseases." }, { "input": "Are male or female persons more prone to autoimmunity?", "output": "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases." }, { "input": "Are male or female persons more prone to autoimmunity?", "output": "females" }, { "input": "Are male or female persons more prone to autoimmunity?", "output": "Sex hormones have long been implicated in autoimmune diseases because women account for 80% of cases. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation." }, { "input": "Which is the phenotype of the disease fibrodysplasia ossificans progressiva?", "output": "Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "gene repression" }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "The nuclear lamina contributes to the regulation of gene expression and to chromatin organization. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "No, lamina-associated domains (LADs) are involved in transcriptional silencing and chromatin compaction." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. The nuclear lamina contributes to the regulation of gene expression and to chromatin organization." }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "Lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression" }, { "input": "Are lamina-associated domains (LADs) associated with transcriptional activation?", "output": "Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. The nuclear lamina contributes to the regulation of gene expression and to chromatin organization." }, { "input": "Is Hemochromatosis type 4 is caused by a mutation in a recessive gene?", "output": "No, Hemochromatosis type 4 is caused by an autosomal dominant gene" }, { "input": "Is Hemochromatosis type 4 is caused by a mutation in a recessive gene?", "output": "type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations." }, { "input": "Is Hemochromatosis type 4 is caused by a mutation in a recessive gene?", "output": "Hemochromatosis type 4, also known as ferroportin disease, is an autosomal dominant genetic disorder caused by pathogenic mutations in the SLC40A1 gene, which encodes ferroportin 1 (FPN1)" }, { "input": "What is the purpose of the LINCS Project?", "output": "The Library of Integrated Network-Based Cellular Signatures (LINCS) project aims to create a network-based understanding of biology by cataloging changes in gene expression and signal transduction that occur when cells are exposed to a variety of perturbations." }, { "input": "What is the purpose of the LINCS Project?", "output": "The functional annotation of the mammalian genome using sequencing (LINCS) project aims to systematically map all mammalian cell-type-specific transcriptomes with wide applications in biomedical research. TheLINCS annotation system, consisting of automated computational prediction, manual curation, and final expert curations, facilitated the comprehensive characterization of the human transcriptome, and could be applied to the transcriptomes of other species." }, { "input": "What is the purpose of the LINCS Project?", "output": "The library of Integrated Cellular Signatures Project (LINCS) is an international effort for creating an annotated transcriptome and translating science into improved health care to benefit patients. TheLINCS aims to systematically map all human transcriptomes, chromosome by chromosome, in a gene-dependent manner through dedicated efforts from national and international teams." }, { "input": "What is the purpose of the LINCS Project?", "output": "The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations." }, { "input": "Can Patient-derived organoids (PDOs) recapitulate patient responses in the clinic?", "output": "Yes. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. In summary, PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs." }, { "input": "Can Patient-derived organoids (PDOs) recapitulate patient responses in the clinic?", "output": "Yes. Patient-derived organoids (PDOs) can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs." }, { "input": "What is Fuchs' Uveitis?", "output": " Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation, which is associated with a gradual onset of decreased visual acuity." }, { "input": "What is Fuchs' Uveitis?", "output": " Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. " }, { "input": "What is Fuchs' Uveitis?", "output": "Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation, which is associated with a gradual onset of decreased visual acuity." }, { "input": "What is Fuchs' Uveitis?", "output": "Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation, which is associated with a gradual onset of decreased visual acuity. " }, { "input": "What is Fuchs' Uveitis?", "output": "Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation," }, { "input": "What is Fuchs' Uveitis?", "output": " Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous." }, { "input": "What is Fuchs' Uveitis?", "output": "Fuchs' Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous." }, { "input": "Is overexpression of LY6K associated with better prognosis for non-small cell lung cancer patients?", "output": "No, LY6K overexpression is associated with poor prognosis for patients with NSCLC." }, { "input": "Is overexpression of LY6K associated with better prognosis for non-small cell lung cancer patients?", "output": "No, overexpression of LY6K has been found to be associated with poor prognosis for non-small cell lung cancer patients." }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kruppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1." }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Here, using a reporter system, we show that TRIM28/ KRAB- ZNFs alter DNA methylation patterns in addition to H3 K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB- ZNFs ( ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes." }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kruppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes" }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Kruppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes" }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene" }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1. Using several expression datasets, we identified KRAB- ZNFs ( ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene" }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "The proteins encoded by KRAB-ZNF genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation." }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming." }, { "input": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "output": "Yes, the members of the KRAB-ZNF gene family are involved in gene repression." }, { "input": "What does the boxed warning of pimavanserin say?", "output": "Pimavanserin bears a boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia." }, { "input": "List Cdk targets that are dephosphorylated during cytokinesis", "output": "Aip1, Ede1 and Inn1 are Cdk targets that are dephosphorylated during cytokinesis." }, { "input": "List Cdk targets that are dephosphorylated during cytokinesis", "output": "The final event of the eukaryotic cell cycle is cytokinesis, when two new daughter cells are born. How the timing and execution of cytokinesis is controlled is poorly understood. A phosphoproteome analysis has identified Aip1, Ede1 and Inn1 as cytokinetic regulators. It seems that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes." }, { "input": "List Cdk targets that are dephosphorylated during cytokinesis", "output": "Downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. Aip1, Ede1 and Inn1 are Cdk targets that are dephosphorylated at the time of cytoklesis." }, { "input": "What is dystopia canthorum?", "output": "Dystopia canthorum is defined as a prominent broad nasal root with increased intercanthal distance." }, { "input": "Is the protein ABCG2 (ATP-Binding Cassette, subfamily G, member 2, transporter) excreting uric acid?", "output": "Yes,\r\nABCG2 plays a central role on extra-renal uric acid excretion" }, { "input": "What is Heterochromia Iridis?", "output": "Heterochromia Iridis is a condition where the affected person has differences in the color of the iris." }, { "input": "What is Heterochromia Iridis?", "output": "Heterochromia iridis is a rare autosomal recessive disorder of the iris, characterized by a heterochromatic pattern of inheritance, variable expressivity, and partial or total absence of iris and/or blonde hair." }, { "input": "What is Heterochromia Iridis?", "output": "Heterochromia Iridis is a rare autosomal dominant disorder of melanocyte development characterized by heterochromatosis of the coronal, sagittal, and lambdoid sutures." }, { "input": "How is transcriptional elongation affected by nucleosome positioning?", "output": "In order to elongate their products, both DNA and RNA polymerases must be able to overcome the inhibition presented by chromatin. Nucleosome arrays inhibit both initiation and elongation of transcripts." }, { "input": "How many annotated conserved human lncRNAs come from ancestral protein-coding genes?", "output": "~ 55" }, { "input": "How many annotated conserved human lncRNAs come from ancestral protein-coding genes?", "output": "~ 55 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs. Some lncRNAs inherited regulatory elements influencing transcription and translation from their protein-coding ancestors and those elements can influence the expression breadth and functionality of these lncRNAs." }, { "input": "Is modified vaccinia Ankara effective for smallpox?", "output": "Yes, modified vaccinia Ankara is effective for smallpox." }, { "input": "Does nintedanib hold promise for lung disease associated with systemic sclerosis?", "output": "Yes, nintedanib holds promise for lung disease associated with systemic sclerosis. It is being tested in a clinical trial." }, { "input": "What is the LINCS Program?", "output": "The Library of Integrated Network-based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations." }, { "input": "What is the LINCS Program?", "output": "The National Institutes of Health library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource." }, { "input": "What is the LINCS Program?", "output": "To fill this gap, recently, the LINCS program generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level" }, { "input": "What is the LINCS Program?", "output": "The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource. To fill this gap, recently, the LINCS program generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines" }, { "input": "What is the LINCS Program?", "output": "The library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data tools to improve our understanding of human diseases at the systems level." }, { "input": "What is the LINCS Program?", "output": "The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level. It has generated almost 1.3 million profiles for over 40,000 drug and genetic perturbations for over 70 different human cell types, including meta information about the experimental conditions and cell lines." }, { "input": "What is the LINCS Program?", "output": "The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level" }, { "input": "Is PF-05190457 an inverse agonist of the ghrelin receptor?", "output": "Yes, PF-05190457 is an inverse agonist of the ghrelin receptor." }, { "input": "Is Ubrogepant effective for migraine?", "output": "Yes, Ubrogepant is effective for treatment of migraine." }, { "input": "Is Selinexor effective for multiple myeloma?", "output": "Yes, Selinexor is effective for multiple myeloma." }, { "input": "What is the protein product of the gene GBA2?", "output": "The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose." }, { "input": "Are there lncRNAs that control the extent of neuronal outgrowth?", "output": "Yes. there are lncRNAs which regulate the extent of neuronal outgrowth." }, { "input": "Are there lncRNAs that control the extent of neuronal outgrowth?", "output": "Yes. LncRNAs are involved in a variety of biological processes, including the epigenetic control of gene expression, post-transcriptional regulation of mRNA, and neuronal outgrowth." }, { "input": "Can the radiation of cellphones be dangerous?", "output": "two sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Dr. Lennart Hardell. The recent studies reach very different conclusions. With four exceptions the industry-funded Interphone studies found no increased risk of brain tumors from cellphone use, while the Swedish studies, independent of industry funding, reported numerous findings of significant increased brain tumor risk from cellphone and cordless phone use." }, { "input": "Does metformin has as an antitumor effect?", "output": "Yes, \tThe anti-tumor effect of metformin is widely known." }, { "input": "Can radiation induced meningiomas be treated with radiosurgery?", "output": "Yes, radiation induced meningiomas be treated with radiosurgery. Radiosurgery provides satisfactory control of radiation induced meningiomas." }, { "input": "What is known about ROS production in relation to UVR?", "output": "Skin exposure to ultraviolet radiation (UVR) may induce the production of reactive oxygen species (ROS) which cause oxidative stress, DNA damage, and alteration of fibroblasts and collagen responsible for skin photoaging." }, { "input": "Which drugs used in the treatment of Systemic Lupus Erythematosus are targeting granulocytes?", "output": "Epratuzumab, a humanized monoclonal antibody against disialoganglioside, is the only officially approved treatment for the treatment of Systemic Lupus Erythematosus.Food and Drug Administration approval of SLE treatment with rituximab; however, more research is required before a large-scale application for clinical decision-making can be recommended." }, { "input": "Which drugs used in the treatment of Systemic Lupus Erythematosus are targeting granulocytes?", "output": "Systems responded to rituximab and cyclophosphamide." }, { "input": "Which drugs used in the treatment of Systemic Lupus Erythematosus are targeting granulocytes?", "output": "Cyclophosphamide and rituximab are used in the treatment of Systemic Lupus Erythematosus. GLPG-0634 and INCB18424 are other drugs that target and neutralize granulocytes." }, { "input": "What is PWMScan?", "output": "Transcription factors regulate gene expression by binding to specific short DNA sequences of 5-20 bp to regulate the rate of transcription of genetic information from DNA to messenger RNA. PWMScan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database." }, { "input": "Is there a BRCA mutation analysis in the Greek population?", "output": "Yes. Molecular analysis of the BRCA1 and BRCA2 genes in 898 Greek families was performed using Sanger sequencing or Next Generation Sequencing for the detection of small insertion/deletion frameshift, nonsynonymous, truncating and splice-site alterations and MLPA for the detection of large genomic rearrangements. In total, a pathogenic mutation was identified in 12.9% of 898 families analyzed. Of the 116 mutations identified in total 9% were novel and 14.7% were large genomic rearrangements." }, { "input": "What is the basis of the DamID experimental protocol?", "output": " Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts. This inducible system will help to generate genome-wide profiles of chromatin proteins in given cell types and tissues with no need to dissect tissues from organs or separate cells from tissues, which is achieved by using specific regulatory DNA elements and due to the high sensitivity of the method. DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. Recently, a novel methylation-based tagging technique, termed DamID (DNA adenine methyltransferase identification), has emerged as a powerful tool to decipher transcriptional networks, to study chromatin-associated proteins, and to monitor higher-order chromatin organization on a genome-wide scale. We show here that the in vivo methylation-based tagging technique DamID (DNA adenine methyltransferase identification) can be used for studies of DNA-protein interactions or chromatin profiling in plants DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible. " }, { "input": "What is the basis of the DamID experimental protocol?", "output": "Recently, a novel methylation-based tagging technique, termed DamID (DNA adenine methyltransferase identification), has emerged as a powerful tool to decipher transcriptional networks, to study chromatin-associated proteins, and to monitor higher-order chromatin organization on a genome-wide scale. We show here that the in vivo methylation-based tagging technique DamID (DNA adenine methyltransferase identification) can be used for studies of DNA-protein interactions or chromatin profiling in plants Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible." }, { "input": "What is the basis of the DamID experimental protocol?", "output": " Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts. It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible." }, { "input": "What is the basis of the DamID experimental protocol?", "output": "DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites." }, { "input": "What is the basis of the DamID experimental protocol?", "output": "This inducible system will help to generate genome-wide profiles of chromatin proteins in given cell types and tissues with no need to dissect tissues from organs or separate cells from tissues, which is achieved by using specific regulatory DNA elements and due to the high sensitivity of the method. DNA adenine methyltransferase identification (DamID) has emerged as one of the most comprehensive and versatile methods available for profiling protein-DNA interactions on a genomic scale. DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible." }, { "input": "What is the basis of the DamID experimental protocol?", "output": "DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible." }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Binding of elongation factor Spt6 to Iws1 provides an effective means for coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I. Spt6 (suppressor of Ty6) has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression." }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. Spt6 is a highly conserved factor required for normal transcription and chromatin structure." }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression." }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Binding of elongation factor Spt6 to Iws1 provides an effective means for coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I. Spt6 (suppressor of Ty6) has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression. Previous characterization of the Saccharomyces cerevisiae Spt4, Spt5, and Spt6 proteins suggested that these proteins act as transcription factors that modify chromatin structure. The SPT4, SPT5, and SPT6 gene products define a class of transcriptional repressors in Saccharomyces cerevisiae that are thought to function through their effects on chromatin assembly or stability. The SPT4, SPT5 and SPT6 genes of Saccharomyces cerevisiae were identified originally by mutations that suppress delta insertion mutations at HIS4 and LYS2. Taken together, these genetic and biochemical results indicate that SPT4, SPT5 and SPT6 function together in a transcriptional process that is essential for viability in yeast. Next, we showed that CK2 interacts with the major histone chaperone Spt6, and phosphorylates it in vivo and in vitro. CK2 phosphorylation of Spt6 is required for its cellular levels " }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. A transcriptional elongation factor, Spt6 is essential for rRNA Synthesis by RNA Polymerase I. Spt6 is the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression." }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression." }, { "input": "What is the function of the Spt6 gene in yeast?", "output": "These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Spt6 is a highly conserved factor required for normal transcription and chromatin structure. Two lines of evidence suggest that Spt6 also plays a role in rRNA synthesis. We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during transcriptional repression." }, { "input": "What has pimavanserin been approved for by the FDA (2018)?", "output": "Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis." }, { "input": "List the members of a network of noncoding regulatory RNAs that play a role in the mammalian brain", "output": "In mice, the long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7-targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network." }, { "input": "Has ProSavin undergone phase IV clinical trials by 2018?", "output": "No, ProSavin has undergone a dose escalation, open-label, phase 1/2 trial." }, { "input": "List approved radioprotective compounds", "output": "Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy." }, { "input": "Does deletion of cohesin change gene expression?", "output": " The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements." }, { "input": "Does deletion of cohesin change gene expression?", "output": "Yes. Deletion of cohesin inhibits gene expression at multiple points within the genome and in different genomic regions." }, { "input": "Does deletion of cohesin change gene expression?", "output": "The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements." }, { "input": "Does deletion of cohesin change gene expression?", "output": "We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\". The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements." }, { "input": "Does deletion of cohesin change gene expression?", "output": "Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter \"connections\" and \"insulation.\"" }, { "input": "Does deletion of cohesin change gene expression?", "output": "Yes. Numerous studies have demonstrated that deletion of cohesin reduces gene expression at multiple points within the genome." }, { "input": "Do MAIT cells have a role in multiple myeloma?", "output": "Yes, MAIT cells may represent new immunotherapeutic targets for treatment of Multiple Myeloma and other malignancies" }, { "input": "Do MAIT cells have a role in multiple myeloma?", "output": "Yes, MAIT cells have a role in multiple myeloma." }, { "input": "Do MAIT cells have a role in multiple myeloma?", "output": "Yes. Mucosal-associated invariant T cells (MAIT cells) play a key role in the pathogenesis of multiple myeloma." }, { "input": "What is ProSavin?", "output": "ProSavin, a lentiviral vector based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease. It has been shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. Moderate improvements in motor behavior over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow-up." }, { "input": "Are stretch enhancers transcribed more than super-enhancers?", "output": "No. Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers." }, { "input": "Are stretch enhancers transcribed more than super-enhancers?", "output": "No. Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers. Importantly, most of the stretch enhancers that are distinct from super-enhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers." }, { "input": "What is Q-SYMBIO?", "output": "Q-SYMBIO is a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality] that assessed coenzyme Q10 as adjunctive treatment of chronic heart failure. METHOD: Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis. CONCLUSION: Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events." }, { "input": "What is the function of the NIPBL factor in genome conformation?", "output": "The NIPBL protein stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes.. NIPBL recruits histone deacetylases to mediate local chromatin modifications." }, { "input": "What is the function of the NIPBL factor in genome conformation?", "output": "NIPBL loads cohesin onto chromatin. The NIPBL protein is required for the loading of cohesin onto chromatin. A cohesin-loading factor (NIPBL) is one of important regulatory factors in the maintenance of 3D genome organization and function, by interacting with a large number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex component. The mechanism of this gene regulation remains unclear, but NIPBL and cohesin have been reported to affect long-range chromosomal interactions, both independently and through interactions with CTCF." }, { "input": "What is the function of the NIPBL factor in genome conformation?", "output": "The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications." }, { "input": "Is mesothelioma caused by asbestos exposure?", "output": "Yes, mesothelioma is caused by asbestos exposure." }, { "input": "Is mesothelioma caused by asbestos exposure?", "output": "Yes, mesothelioma is a hard to treat malignant neoplasia caused by asbestos exposure." }, { "input": "Is mesothelioma caused by asbestos exposure?", "output": "Yes, mesothelioma is a type of malignant mesothelial cancer caused by asbestos exposure." }, { "input": "Is mesothelioma caused by asbestos exposure?", "output": "Yes, mesothelioma is caused by exposure to asbestos." }, { "input": "Is mesothelioma caused by asbestos exposure?", "output": "Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure." }, { "input": "Which diagnostic test is approved for coronavirus infection screening?", "output": "Real-time reverse transcription-PCR (rRT-PCR) is mostly used as the lab test for screening coronaviral infection." }, { "input": "What is Xanamem?", "output": "UE2343 was identified as a potent, orally bioavailable, brain-penetrant 11b-HSD1 inhibitor and selected for clinical studies. Reducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol-regenerating enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has emerged as a therapeutic strategy to treat cognitive impairment in early Alzheimer's disease (AD). UE2343 is safe, well tolerated and reaches the brain at concentrations predicted to inhibit 11b-HSD1. UE2343 is therefore a suitable candidate to test the hypothesis that 11b-HSD1 inhibition in brain improves memory in patients with AD." }, { "input": "Can nrf2 activation lead to resistance to radiotherapy?", "output": "Resistance to chemoradiotherapy is a major obstacle to successful treatment of glioblastoma. Recently, the role of NF-E2-related factor 2 (Nrf2) in enhancing chemoradiation sensitivity has been reported in several types of cancers. Blocking Nrf2 activation may be a promising method enhancing chemoradiation sensitivity of glioblastoma cells." }, { "input": "Are there interactions between short and long noncoding RNAs?", "output": "Yes. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions." }, { "input": "Are there interactions between short and long noncoding RNAs?", "output": "It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi-interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation." }, { "input": "Are there interactions between short and long noncoding RNAs?", "output": "Yes. Short RNAs and long noncoding RNAs interact with each other with reciprocal consequences for their fates and functions." }, { "input": "Which molecule is inhibited by encorafenib?", "output": "Encorafenib is a BRAF inhibitor. It is a promising therapy for metastatic or inoperable melanoma with a BRAF mutation." }, { "input": "What is the basis of the capture Hi-C experimental protocol?", "output": "Capture Hi-C (CHi-C) allows high-resolution analysis of targeted regions of the genome by incorporating a sequence capture step into a Hi-C protocol. Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads" }, { "input": "What is the basis of the capture Hi-C experimental protocol?", "output": "Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts." }, { "input": "What is the basis of the capture Hi-C experimental protocol?", "output": "Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. To address this, Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas7,8 Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. " }, { "input": "What is the basis of the capture Hi-C experimental protocol?", "output": "Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. Here we develop a capture Hi-C (cHi-C) approach to allow an agnostic characterization of these physical interactions on a genome-wide scale. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types." }, { "input": "What is the basis of the capture Hi-C experimental protocol?", "output": "Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. Here we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the long-range interactions of almost 22,000 promoters in 2 human blood cell types. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas7,8 To address this, Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of biologically significant chromatin interactions compared to conventional Hi-C, for an equivalent number of sequence reads We developed Promoter Capture Hi-C (PCHi-C) to enable the genome-wide detection of distal promoter-interacting regions (PIRs), for all promoters in a single experiment. Here, we use Capture Hi-C (CHi-C) to annotate 63 loci; we identify 110 putative target genes at 33 loci." }, { "input": "What is the role of Scc2/Nipbl?", "output": "Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes. Scc2 also binds dynamically to chromatin, principally through an association with cohesin. Scc2's movement within chromatin is consistent with a 'stop-and-go' or 'hopping' motion. A low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading." }, { "input": "What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?", "output": "Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder resulting in advanced vascular atherosclerosis and premature death, primarily from coronary artery disease. The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19" }, { "input": "What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?", "output": "Mutations in the LDLr gene (LDLR), which is located on chromosome 19, cause familial hypercholesterolemia" }, { "input": "What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?", "output": "The chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia is chromosome 19q13.3." }, { "input": "What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?", "output": "Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder resulting in advanced vascular atherosclerosis and premature death, primarily from coronary artery disease. The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19." }, { "input": "What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?", "output": "The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19." }, { "input": "Can brain derived exosomes carry APP molecules?", "output": "Yes,\nsmall lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP" }, { "input": "List the most common cancers after a radiation exposure?", "output": "well-known increase in leukaemia, increases in solid cancer such as cancers of the lung, breast, stomach and thyroid have also been demonstrated." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "MBF/SBF is the major transcriptional repressor of G1/S genes in Saccharomyces cerevisiae." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "The G(1)/S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "MBF and SBF are two members of bHLH-PAS-containing family of transcription factors that represent theG1/S transcription factors in Saccharomyces cerevisiae" }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1- S transcription factor DSC1/ MBF. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair." }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. The G(1)/S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe" }, { "input": "Which are the main G1/S transcription factors in yeast?", "output": "In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair. MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively." }, { "input": "What is Hemochromatosis?", "output": "Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy." }, { "input": "What is Hemochromatosis?", "output": "Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload." }, { "input": "What molecules are the multidrug transporter MDR3 targeting?", "output": "Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator." }, { "input": "What is the role of the Hof1-Cyk3 interaction in yeast?", "output": "In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. There is also evidence that they interact physically." }, { "input": "What is the role of the Hof1-Cyk3 interaction in yeast?", "output": "In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. Hof1 and Cyk3 interact physically and the interaction 1) is mediated by a direct binding of the Hof1 SH3 domain to a proline-rich motif in Cyk3; 2) occurs specifically at the time of cytokinesis but is independent of the (hyper)phosphorylation of both proteins that occurs at about the same time; 3) is dispensable for the normal localization of both proteins; 4) is essential for normal primary-septum formation and a normal rate of cleavage-furrow ingression; and 5) becomes critical for growth when either Inn1 or the type II myosin Myo1 (a key component of the contractile actomyosin ring) is absent. The similarity in phenotype between cyk3[?] mutants and mutants specifically lacking the Hof1-Cyk3 interaction suggests that the interaction is particularly important for Cyk3 function, but it may be important for Hof1 function as well." }, { "input": "List features of the SAM syndrome.", "output": "SAM syndrome is characterized by severe dermatitis, multiple allergies and metabolic wasting. It is caused by mutations in the desmoglein 1 gene (DSG1)." }, { "input": "What does the Smith\u2013Waterman algorithm do?", "output": "The Smith-Waterman algorithm performs local sequence alignments. " }, { "input": "Is SATB1 positioned close to AT-rich sequences?", "output": "Yes, SATB1 is preferentially located at the start of an AT-rich sequence and is associated with other, more diffuse AT- rich sequences in the genome." }, { "input": "Is SATB1 positioned close to AT-rich sequences?", "output": "Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand. SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs)." }, { "input": "Is SATB1 positioned close to AT-rich sequences?", "output": "Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand." }, { "input": "Is SATB1 positioned close to AT-rich sequences?", "output": "We have purified and identified one of the core factors as the matrix attachment region (MAR) binding protein, SATB1, which is known to bind to AT-rich sequences with a high propensity to unwind" }, { "input": "Describe the Java Adverse Drug Event (JADE) tool", "output": "The Java Adverse Drug event (Jade) is a tool for medical researchers to explore adverse drug events using health insurance plans and drug-drug interactions." }, { "input": "Describe the Java Adverse Drug Event (JADE) tool", "output": "The Java Adverse Drug Event (JADE) tool enables the analysis of prescribed drugs in connection with diagnoses from hospital stays. It can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information." }, { "input": "Which drugs were tested in the CheckMate 227 clinical trial?", "output": "CheckMate-227 clinical trial tested ipilimumab plus nivolumab for the treatment of non-small cell lung cancer." }, { "input": "What is known about PAI-1 in longevity in humans?", "output": "Plasminogen activator inhibitor-1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However, the role of PAI-1 in human longevity remains unclear.\n, in centenarians there was a significantly higher frequency of the 4G allele and of the homozygous 4G4G genotype associated with high PAI-1 levels. Since high PAI-1 is considered a predictor of recurrent myocardial infarction in young men, it is intriguing that the corresponding genetic marker is more frequent in centenarians who have escaped major age-related atherothrombotic disease and reached the extreme limits of human life. Homozygosity for the 4G allele, despite its association with impaired fibrinolysis, is compatible with successful aging." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Yes. Metformin has been shown to decrease frequency of atherosclerosis-associated adverse effects in statin-intolerant patients and to slow the pathogenesis of type 2 diabetes mellitus." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Yes. Metformin has been shown to decrease frequency of atherosclerosis-associated adverse effects in statin-intolerant patients and to slow the pathogenesis of type 2 diabetes." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Coupled with their proven good safety profile these findings could translate into a significant clinical benefit. Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses Our results suggest that metformin impeded the progression of atherosclerosis, possibly by suppressing macrophage infiltration and inflammatory responses." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Yes. Metformin has been shown in a number of clinical trial to prevent and attenuate atherosclerosis." }, { "input": "Does metformin alleviate atherosclerosis?", "output": "Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease. Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory response." }, { "input": "List side effects of radiation therapy?", "output": "radiation-induced tumors\nradiation necrosis\nmicroangiopathy\nprogressive leukencephalopathy\npneumonitis\ndisturbance of the blood-brain barrier\nradionecrosis of brain tissue\nradiogenic liver damage\nmucositis\ncolitis\nosteitis\nosteoradionecrosis\nmyositis\nRadiation-induced fibrosis\nAcute skin reactions" }, { "input": "Are CD8+ (cytotoxic) T cells and CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?", "output": "Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, These two cell types are derived from common precursors in the thymus." }, { "input": "Are CD8+ (cytotoxic) T cells and CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?", "output": "no, CD8+ (cytotoxic) T cells, like CD4+ Helper T cells, are generated in the thymus not the thyroid and express the T-cell receptor." }, { "input": "Are CD8+ (cytotoxic) T cells and CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?", "output": "The CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent model to study binary fate decision processes. These two cell types are derived from common precursors in the thymus." }, { "input": "What bacteria is associated with Gastric cancer and peptic ulcers?", "output": "Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterial pathogen that colonizes the stomachs of more than half of all humans, is linked to chronic gastritis, peptic ulcers and gastric cancer." }, { "input": "What bacteria is associated with Gastric cancer and peptic ulcers?", "output": "Peptic ulcer and gastric cancer are caused by the same bacteria, Helicobacter pylori." }, { "input": "Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?", "output": "No, Huntington's disease is caused by expansion of a CAG repeat (not CTG) in the HTT gene on Chromosome 4." }, { "input": "Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?", "output": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT)." }, { "input": "Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?", "output": "Huntington disease (HD) is a dominantly inherited disorder caused by a CAG expansion mutation in the huntingtin (HTT) gene," }, { "input": "What is the purpose of the 123 dihydrorhodamine assay?", "output": "detection of inheritance pattern in thirty-three mexican males with chronic granulomatous disease" }, { "input": "What is the purpose of the 123 dihydrorhodamine assay?", "output": "Dihydrorhodamine assays measure oxidative bursts and are used to quantify cell activation via respiratory bursts. Nitroblue-tetrazolium dye reduction test and 123 dihydro-rhodamine assay by flow cytometry are the screening tests for Chronic Granulomatous Disease." }, { "input": "What is the purpose of the 123 dihydrorhodamine assay?", "output": "Dihydrorhodamine assay (DRB) is a simple, reliable, and valid method for studying oxidative stress, in particular oxidative stress and reactive oxygen species." }, { "input": "What is the purpose of the 123 dihydrorhodamine assay?", "output": "We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. Detection of inheritance pattern in thirty-three Mexican males with chronic granulomatous disease through 123 dihydrorhodamine assay." }, { "input": "What is the mode of action of filgotinib?", "output": "Filgotinib is an oral selective Janus kinase 1 (JAK1) inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be effective." }, { "input": "What is the mode of action of filgotinib?", "output": "Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease." }, { "input": "What is the mode of action of filgotinib?", "output": "Filgotinib is an oral selective JAK inhibitor. It works by inhibiting JAK1." }, { "input": "What is the mode of action of filgotinib?", "output": "Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1)." }, { "input": "What is the mode of action of filgotinib?", "output": "Filgotinib (GS-6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohn's disease. Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes." }, { "input": "What is the mode of action of filgotinib?", "output": "Filgotinib is an oral selective JAK1 inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be safe and efficacious." }, { "input": "What is the mode of action of filgotinib?", "output": "Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor," }, { "input": "What is the mode of action of filgotinib?", "output": "Selective inhibition of JAK-1 with filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies. The selectivity of filgotinib for JAK1 may have theoretical advantages in terms of limiting toxicity." }, { "input": "Is Huntington's disease caused by a dominate or recessive gene?", "output": "Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease" }, { "input": "Is Huntington's disease caused by a dominate or recessive gene?", "output": "Huntington's disease is caused by an autosomal dominant gene." }, { "input": "Is Huntington's disease caused by a dominate or recessive gene?", "output": "Huntington's disease (HD) is an inherited NDD caused by autosomal-dominant expanded CAG trinucleotide repeat mutation in the gene coding for Huntingtin (Htt)." }, { "input": "What is RiboTag profiling?", "output": "RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures." }, { "input": "What is RiboTag profiling?", "output": "Ribo tag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell types and organisms. It is a simple, sensitive, rapid and relatively cheap method for integrative epigenomic profiling. The method can be used to identify endogenous and ectopically expressed ribosomal RNAs (RP), which are then analyzed using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of ubiquitously expressed proteins." }, { "input": "What is RiboTag profiling?", "output": "RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures. RiboTag immunoprecipitation is capable of recovering high integrity RNA from small numbers of transfected cells that can then be interrogated by a variety of methods (e.g., RT-qPCR, PCR array, RNA-Seq) and compared with basal RNA expression of the entire culture. Co-transfection of RiboTag with small hairpin RNA (shRNA) constructs can validate and accurately assess the degree of gene expression knockdown." }, { "input": "Is there an increased risk of meningiomas in atomic bomb survivors?", "output": "Yes, the incidence of meningiomas is increased in atomic bomb survivors." }, { "input": "What is foliglurax?", "output": "Foliglurax is a positive allosteric modulator of the metabotropic glutamate receptor 4. Foliglurax induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced dyskinesia. It was the first compound of its class to enter phase IIa clinical trials." }, { "input": "What is the genetic basis for Cornelia de Lange's syndrome?", "output": "Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified." }, { "input": "What is the genetic basis for Cornelia de Lange's syndrome?", "output": "Approximately 60% of Cornelia de Lange Syndrome (CdLS) cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3. Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified." }, { "input": "What is the genetic basis for Cornelia de Lange's syndrome?", "output": "Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified. 60% of CdLS cases are due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one proband was found to carry a mutation in SMC3." }, { "input": "Are gut microbiota profiles altered by irradiation?", "output": "Yes, \tIrradiation profoundly impacted gut microbiota profiles" }, { "input": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "output": "Yes. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation." }, { "input": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "output": "Yes, TIM-3 has shown promising results in early phases of trials in NSCLC patients and can be a target for cancer immunotherapy." }, { "input": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "output": "Yes, TIM-3 has emerged as an important target of cancer immunotherapy because of its preferential expression in NSCLC cell lines and its presence in 90% of tumors. (PMID: 21494614) We have developed a cancer vaccine in whichtim-3 is fused with dendritic cells resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. This (CT)n element has been shown to induce poly(ADP-ribose) polymerase activation, and it has also been suggested thatTim-3 may act as a tumor suppressor gene, thus making it a potential therapeutic target of CDKN2A/PD-" }, { "input": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "output": " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation." }, { "input": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "output": "Implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients." }, { "input": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "output": " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients. Cytometric profiling identified an immunologically \"hot\" cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically \"cold\" cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers" }, { "input": "How does LB-100 affect the DDR proteins (BRCA1, Chk2, and \u03b3H2AX)?", "output": "LB100 induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gH2AX)." }, { "input": "What particles is Hadron therapy using?", "output": "Hadron therapy is using proton beams." }, { "input": "Does an interferon (IFN) signature exist for SLE patients?", "output": "Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. An IFN-I score (positive or negative), as a measure of IFN-I activation, is assessed using the expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)." }, { "input": "Is AND-1/Ctf4 essential for proliferation?", "output": "Yes. AND-1 fork protection function prevents fork resection and is essential for proliferation." }, { "input": "Is AND-1/Ctf4 essential for proliferation?", "output": "Yes. AND-1/Ctf4 bridges the CMG helicase and DNA polymerase alpha, facilitating replication. AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint. Replication without AND-1 causes fork speed slow-down and accumulation of long single-stranded DNA (ssDNA) gaps at the replication fork junction, with these regions being converted to DNA double strand breaks (DSBs) in G2." }, { "input": "Does the BRAFV600E mutation have an effect on clinical response to radioiodine therapy?", "output": "Yes, it has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis." }, { "input": "Which phosphatase is inhibited by LB-100?", "output": "LB-100 is a phosphatase 2A inhibitor" }, { "input": "What are the most common side effects of amantadine ER?", "output": "The most common side effects of amantadine ER are hallucination, dizziness, orthostatic hypotension and pedal edema." }, { "input": "Which symptoms comprise Abdominal aortic aneurysm rupture Triad?", "output": "Classic triad of Abdominal aortic aneurysm rupture include shock, acute abdominal pain, and pulsatile abdominal mass." }, { "input": "List symptoms of Allgrove syndrome.", "output": "The classical clinical triad of the Allgrove syndrome includes alacrima, achalasia and adrenal insufficiency. It can be also associated with progressive peripheral neuropathy." }, { "input": "What is water radiolysis?", "output": "Water radiolysis involves chemical decomposition of the water molecule into free radicals after exposure to ionizing radiation. These free radicals have deleterious effects on normal cell physiology." }, { "input": "How do the plasma concentrations of amantadine extended release and amantadine immediate release compare?", "output": "When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release." }, { "input": "How do the plasma concentrations of amantadine extended release and amantadine immediate release compare?", "output": "When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release. PK modeling suggested the recommended daily ADS-5102 dosage (274 mg qhs) resulted in 1.4- to 2.0-fold higher amantadine plasma concentrations during the day versus amantadine IR." }, { "input": "Is the BAGEL algorithm used for arrayed CRISPR screens?", "output": "No. BAGEL (Bayesian Analysis of Gene EssentiaLity) is a supervised learning method for analyzing pooled library gene knockout screens. It offers significantly greater sensitivity than current methods, while computational optimizations reduce runtime by an order of magnitude." }, { "input": "What is included in the LACE Index?", "output": "The LACE index is a simple tool that includes 4 parameters: Length of stay, Acuity of admission, Comorbidity, and Emergency visits in the previous 6 months. It is used to predict early re-admission after hospital discharge." }, { "input": "Which drugs are included in GI cocktail?", "output": "\"GI cocktail\" is a mixture of liquid antacid, viscous lidocaine, and an anticholinergic." }, { "input": "Is AZD5153 active in prostate cancer?", "output": "Yes, AZD5153 was shown to be effective in treatment of prostate cancer." }, { "input": "Is AZD5153 active in prostate cancer?", "output": "Yes. AZD5153, a novel BRD4 inhibitor, inhibits prostate cancer cell growth in vitro and in vivo. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells." }, { "input": "Is GRG5 involved only in late embryonic mouse development?", "output": "No. Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in both early and late embryonic mouse development." }, { "input": "Are astronauts in higher risk for developing cancer?", "output": "No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation." }, { "input": "Describe the mechanism of action of a drug Elagolix.", "output": "Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist. It is in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids." }, { "input": "Describe mechanism of action of volanesorsen.", "output": "Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. It has been shown to decrease TGs by 70-80%." }, { "input": "What is the cyberknife used for?", "output": "CyberKnife(r) is a robotic stereotactic radiotherapy system" }, { "input": "Is Niraparib effective for ovarian cancer?", "output": "Yes. Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is approved by the United States Food and Drug Administration and the European Medicines Agency for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy." }, { "input": "Which portal has been developed to explore protein-protein interactions in cancer cell lines?", "output": "The OncoPPi Portal has been developed as an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of protein-protein interactions (PPIs) experimentally detected in cancer cell lines. To facilitate prioritization of PPIs for further biological studies, this resource combines network connectivity analysis, mutual exclusivity analysis of genomic alterations, cellular co-localization of interacting proteins and domain-domain interactions. Estimates of PPI essentiality allow users to evaluate the functional impact of PPI disruption on cancer cell proliferation. Furthermore, connecting the OncoPPi network with the approved drugs and compounds in clinical trials enables discovery of new tumor dependencies to inform strategies to interrogate undruggable targets like tumor suppressors. The OncoPPi Portal serves as a resource for the cancer research community to facilitate discovery of cancer targets and therapeutic development." }, { "input": "Are genes that escape X-chromosome inactivation related to mental impairment?", "output": "Yes. Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving." }, { "input": "Are genes that escape X-chromosome inactivation related to mental impairment?", "output": "Yes, most of the X-chromosome inactivation genes shown to be associated with mental retardation are those encoding transcription factors involved in intellectual disability, such as X-linked Na(+) /H(+) exchanger 2 (NHE2), Sox 10, Endothelin-3 (EDN3) and SOX10. Some X- chromosome inactivation gene variants are associated with intellectual disability but not others." }, { "input": "Are genes that escape X-chromosome inactivation related to mental impairment?", "output": "Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving. The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes." }, { "input": "Which biological process takes place in nuclear speckles?", "output": "Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. They serve as splicing factor storage sites and play important roles in regulation of pre-mRNA splicing." }, { "input": "What is the effect of HMGB2 loss on CTCF clustering?", "output": "Depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF. Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects." }, { "input": "Has LB-100 been tested in clinical trials?", "output": "Yes, a phase I trial has been performed to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors." }, { "input": "Which algorithms have been developed for analysing CRISPR/Cas9 knockout screens data?", "output": "HiTSelect and MAGeCK (Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout)" }, { "input": "Which cells are affected in radiation-induced leukemias?", "output": "Hemopoietic stem cells, the possible target cells for radiation-induced leukemias." }, { "input": "PDQ39 questionnaires is design for which disease?", "output": "PDQ39 is Parkinson's Disease Questionnaire that is used for assessment of quality of life in patients with Parkinson's Disease." }, { "input": "Is palbociclib effective for glioblastoma?", "output": "No. In a clinical trial palbociclib monotherapy was not an effective treatment for recurrent glioblastoma." }, { "input": "List five proteins with antioxidant properties?", "output": "thioredoxin 1 (Trx1), \nperoxiredoxin 1 (Prx1), \nGSH reductase (GSR),\nphosphatase and tensin homolog (PTEN)\nsuperoxide dismutase (SOD)" }, { "input": "Does the Mcm2-Ctf4-Pol\u03b1 axis play a role in transfer of histones to leading strand DNA at the replication forks?", "output": "No, the Mcm2-Ctf4-Pola axis facilitates parental histone H3-H4 transfer to lagging strands." }, { "input": "What is Scalp cirsoid aneurysms?", "output": "Cirsoid aneurysms are rare arteriovenous malformations of the scalp, which are usually of congenital etiology. They often present as an enlarging pulsatile scalp mass." }, { "input": "Which gene is frequently involved in autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)?", "output": "Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene." }, { "input": "What is the radiation-induced CD8 lymphocyte apoptosis (RILA) assay used for?", "output": "Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy." }, { "input": "What are the puQTLs (promoter-usage Quantitative Trait Loci)?", "output": "The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs) have been mapped from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals. There are five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, puQTL effects are either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters." }, { "input": "Which is the main epigenetic difference between poised and constitutive enhancers?", "output": "We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone." }, { "input": "Which is the main epigenetic difference between poised and constitutive enhancers?", "output": "Histone H3K27ac separates active from poised enhancers and predicts developmental state." }, { "input": "Which is the main epigenetic difference between poised and constitutive enhancers?", "output": ". The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation.. Histone H3K27ac separates active from poised enhancers and predicts developmental state.. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.. These chromatin domains, mostly constitutive, may have been used as genomic niches where novel regulations could evolve due to both the preexistence of a structural backbone poised to integrate novel regulatory inputs, and a highly adaptive transcriptional readout. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes" }, { "input": "Which is the main epigenetic difference between poised and constitutive enhancers?", "output": "Histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone." }, { "input": "What is PRL3-zumab?", "output": "PRL3-zumab is a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. PRL3-zumab specifically blocked PRL-3+, but not PRL-3-, orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3+ tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become \"extracellular oncotargets\" that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells." }, { "input": "What is PRL3-zumab?", "output": "PRL3-zumab is a humanized monoclonal antibody specific for the epithelial-cell-associated phosphatase 3 (PRL-3) protein. It is approved for treatment of non-small cell lung carcinoma, adenocarcinoma of the stomach and gastroesophageal Junction, and recurrent glioblastoma." }, { "input": "Which receptor is inhibited by Tivozanib?", "output": "Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 tyrosine kinases." }, { "input": "Can discharge destinations be accurately predicted using the Risk Assessment and Prediction Tool (RAPT)?", "output": "Yes. The Risk Assessment and Prediction Tool (RAPT) appears to be a valuable predictor of discharge destination after orthopedic surgery and neurosurgical procedures." }, { "input": "What is Perturb-seq?", "output": "Perturb-seq is a technique that combines single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and their genetic interactions. By decomposing many high content measurements into the effects of perturbations, their interactions, and diverse cell metadata, Perturb-seq dramatically increases the scope of pooled genomic assays." }, { "input": "What is the content of the REPAIRtoire database?", "output": "The REPAIRtoire database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases." }, { "input": "Has amantadine ER been approved by the FDA?", "output": "Yes, amantadine ER is an US FDA-approved treatment." }, { "input": "Can PRL3-zumab inhibit PRL3+ cancer cells in vitro and in vivo?", "output": "PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro." }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "Circulating tumour cells (CTCs) are significantly rare entity in the blood of patients with non-small cell lung cancer (NSCLC) patients as well as in other types of cancer. Small-cell lung cancer cells are typically quiescent, whereas CTCs can be up-regulated in response to radiation or chemical agents and may contribute to tumorigenesis as an endogenous red cell marker." }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "extremely low" }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge." }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. However, selective capture and quantification of CTCs from whole blood was still full of challenge due to the extremely scare number of CTCs." }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "We have focused on breast cancer as most clinical studies on CTC detection so far have been done in these patients. However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge." }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "CTCs are of extremely low number (as low as 1 in 10(9) hematologic cells) in the blood of patients." }, { "input": "How rare are CTCs (circulating tumour cells) in the plasma of patients?", "output": "However, largely because of the extremely low number of CTCs (as low as 1 in 10(9) hematologic cells) in the blood of patients, effective detection and separation of the rare cells remain a tremendous challenge. This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs), a rare cell species in blood circulation." }, { "input": "What is gamma sterilization used for?", "output": "Gamma sterilization of bone allografts is used as a gold standard method to provide safety against disease transmission. Also, gamma (g)-sterilization has been commonly employed for wide range of products as indicated by the pharmacopoeias." }, { "input": "Does Estrogen lead to forkhead FoxA1 activation?", "output": "The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA." }, { "input": "Does Estrogen lead to forkhead FoxA1 activation?", "output": "Yes, induction of forkhead FoxA1 activation by estrogen seems to result in increased expression of the ERK2/ERK1 pathway in breast cancer cells. (PMID: 21494614) We also find that the testis-specific variant of the FOXA1 gene, which encodes the triggering receptor encoded by exon 9 on estrogen, is recruited to kinetochores and contributes to estrogen-induced silencing of NF-kappaB activation at the mating-type locus. ( PMID: 20160027)" }, { "input": "Does Estrogen lead to forkhead FoxA1 activation?", "output": "The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA" }, { "input": "Does Estrogen lead to forkhead FoxA1 activation?", "output": "Yes, estrogen-induced transcriptional activation of FoxA1 is tightly regulated by estrogen receptor tyrosine kinase and enhances Forkhead protein expression." }, { "input": "Does Estrogen lead to forkhead FoxA1 activation?", "output": "We showed that CTCF acts upstream of the \"pioneer\" factor FOXA1 in determining the genomic response to estrogen." }, { "input": "What is detected by the UV-damaged DNA-binding protein (UV-DDB) complex?", "output": "Upon UV irradiation of primate cells, UV-DDB associates tightly with chromatin and is involved in global genomic nucleotide excision repair (NER) in mammalian cells." }, { "input": "What is the current regulation of eye lens radiation exposure?", "output": "The reduction of the dose limit for eye lens from 150 to 20 mSv yr-1 must be implemented by EU member states by February 2018. Consequently, there is a requirement for all employers engaged with work with ionising radiation to have appropriate monitoring arrangements in place by this date to demonstrate that they can meet this new limit for all workers. Eye lens dose is conventionally monitored by specific dosemeters worn near the eye.\nThe yearly ocular lens dose, particularly for interventionists dealing with complex interventions, could cross the permitted yearly limit set by the new Euratom directive. Therefore, X-ray safety glasses would become mandatory for complex radiological vascular interventions." }, { "input": "Does association with the nuclear pore promote gene silencing?", "output": "MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. The nucleoporin Nup358 plays an important role in this process" }, { "input": "Which methods are used for genome segmentation of gene expression data?", "output": "Most of the used methods are variations of Markov Models such as Markov Chain Monte Carlo (MCMC) or Combinatorial methods." }, { "input": "Which methods are used for genome segmentation of gene expression data?", "output": "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome." }, { "input": "Which methods are used for genome segmentation of gene expression data?", "output": "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome. We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier. Our method is based on a combinatorial genome segmentation solely using information on combinations of epigenetic marks." }, { "input": "Which methods are used for genome segmentation of gene expression data?", "output": ". We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier.. Our method is based on a combinatorial genome segmentation solely using information on combinations of epigenetic marks.. We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome." }, { "input": "Which methods are used for genome segmentation of gene expression data?", "output": "reversible jump markov chain monte carlo (rjmcmc) method" }, { "input": "Which methods are used for genome segmentation of gene expression data?", "output": "We use piecewise constant intensity models with varying number of pieces, and show how a reversible jump Markov Chain Monte Carlo (RJMCMC) method can be used to obtain a posteriori distribution on the intensity of the patterns along the genome. We introduce Markov models for segmentation of symbolic sequences, extending a segmentation procedure based on the Jensen-Shannon divergence that has been introduced earlier." }, { "input": "Which receptor is inhibited by Teprotumumab?", "output": "Teprotumumab is a monoclonal inhibitory antibody targeting IGF-1 receptor." }, { "input": "What is the cause of the disease Xeroderma Pigmentosum?", "output": "Mutations in the ERCC1 or ERCC4 genes cause a remarkable array of rare inherited human disorders including specific forms of xeroderma pigmentosum. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration." }, { "input": "List Alkaptonuria Triad.", "output": "Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis." }, { "input": "Can LB-100 sensitize ovarian carcinoma to cisplatin?", "output": "Yes, LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity." }, { "input": "List T-UCRs that have been implicated in breast cancer", "output": "Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no protein-coding capacity. Transcribed ultraconserved regions (T-UCRs) are a type of lncRNA and are conserved among human, chick, dog, mouse and rat genomes. These sequences are involved in cancer biology and tumourigenesis. Overexpression of one specific T-UCRs named uc.63 is associated with bad outcome in luminal A subtype of breast cancer patients. Uc.38 negatively regulates the expression of the pre-B-cell leukaemia homeobox 1 (PBX1) protein and subsequently affects the expression of Bcl-2 family members, ultimately inducing breast cancer cell apoptosis." }, { "input": "How many different miRNAs can be upregulated by LB-100?", "output": "LB-100 has been reported to upregulate one miRNA, namely miR-181b-1." }, { "input": "Which T-UCRs have been implicated in gastric cancer?", "output": "Uc.160 is significantly down-regulated in gastric carcinomas and can inhibit the tumor growth both in vitro and in vivo, suggesting that uc.160 may be used as a diagnostic marker and therapeutic target of gastric malignancies. Uc.416+A is overexpressed in GC and is associated with cell growth through the regulation of IGFBP6 (insulin-like growth factor-binding protein 6) in gastric cancer (GC)." }, { "input": "Which disease can be treated with Anifrolumab?", "output": "Anifrolumab is a type I interferon (IFN) receptor antagonist that has been shown to be effective for moderate-to-severe systemic lupus erythematosus (SLE)." }, { "input": "Which de novo mutation in FGFR cause achondroplasia?", "output": "Recurrent missense mutations in a CpG doublet of the transmembrane domain of the FGFR3 protein (glycine substituted with arginine at residue 380, G380R)." }, { "input": "List types of DNA lesions caused by UV light.", "output": "cyclobutane pyrimidine dimers\npyrimidine pyrimidone photoproducts\n8-oxo-7,8-dihydroguanine" }, { "input": "Has istadefylline been considered as a treatment for Parkinson's disease?", "output": "Yes, istradefylline is a new drug developed for the treatment of Parkinson's disease." }, { "input": "In which cellular compartment do stress granules localize?", "output": "cytoplasm" }, { "input": "In which cellular compartment do stress granules localize?", "output": "Stress granules (SGs) are cytoplasmic granules that are formed in cells when stress occurs." }, { "input": "In which cellular compartment do stress granules localize?", "output": "Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins" }, { "input": "In which cellular compartment do stress granules localize?", "output": "Stress granules (SGs) are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and are characteristic to eukaryotic cells." }, { "input": "In which cellular compartment do stress granules localize?", "output": "Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. Here, we show that Rbfox2 is a novel constituent of cytoplasmic stress granules, the translational silencing machinery assembled in response to cellular stress." }, { "input": "Which software are used for the detection of selective sweeps?", "output": "Four open-source software releases (SweeD, SweepFinder, SweepFinder2, and OmegaPlus) are able to detect selective sweeps accurately. RAiSD (Raised Accuracy in Sweep Detection), an open-source software implements a parameter-free detection mechanism that relies on multiple signatures of a selective sweep via the enumeration of SNP vectors." }, { "input": "Which organs are primarily damaged in SLE?", "output": "The patients with SLE are mostly affected by renal, peripheral vascular, musculoskeletal and neurological damage. The skin and heart are also damaged very frequently." }, { "input": "Which organs are primarily damaged in SLE?", "output": "In systemic lupus erythematosus (SLE), brain and kidney are the most frequently damaged organs. The heart is one of the most commonly damaged organs in SLE. Any part of the heart can be affected, including the pericardium, myocardium, coronary arteries, valves, and the conduction system" }, { "input": "What is Amyand hernia?", "output": "An Amyand hernia is a rare disease where the appendix is found within an inguinal hernia sac, which may or may not contain other abdominal contents or pathologic inflammatory changes." }, { "input": "What is the Lupus Severity Index (LSI)?", "output": "It is a simple systemic lupus erythematosus (SLE) severity index that requires knowledge of only American College of Rheumatology (ACR) criteria and subcriteria." }, { "input": "What is the Lupus Severity Index (LSI)?", "output": "The Lupus Severity Index (LSI) is a simple, reliable, and valid measure of disease severity in patients with systemic lupus erythematosus." }, { "input": "What is the Lupus Severity Index (LSI)?", "output": "The Lupus Severity Index (LSI) is a simple, reliable, and valid measure of disease severity in patients with systemic lupus erythematosus. The index can be used to identify patients at risk for acute exacerbations of Lupus nephritis. Based on the score, patients were classified into five different groups, one with the most severe, the other with the worst prognosis, and the others with the best prognosis." }, { "input": "Is amantadine ER the first approved treatment for akinesia?", "output": "No, extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia." }, { "input": "Which disease is Dasatinib used to treat?", "output": "Patients with chronic myeloid leukemia" }, { "input": "Which disease is Dasatinib used to treat?", "output": "Dasatinib is a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib. A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood." }, { "input": "Which disease is Dasatinib used to treat?", "output": "Dasatinib is a pan receptor tyrosine kinase inhibitor (RTK) used in the treatment of chronic myelogenous leukemia (CML)." }, { "input": "Which disease is Dasatinib used to treat?", "output": "chronic myeloid leukemia" }, { "input": "Which disease is Dasatinib used to treat?", "output": "Dasatinib is a small molecule covalently binding and inhibiting BCR-ABL receptor. It is used for treatment of chronic myelogenous leukemia (CML) by targeting the integrins avb3 and avb5 over-expressed on B cells." }, { "input": "Is g-H2AX a marker for double strand breaks?", "output": "Yes,\nThe specific phosphorylation of histone H2AX on serine residue 139, described as g-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs)." }, { "input": "Which algorithm has been developed for finding conserved non-coding elements (CNEs)?", "output": "CNEFinder is a tool for identifying CNEs between two given DNA sequences with user-defined criteria." }, { "input": "Which algorithm has been developed for finding conserved non-coding elements (CNEs)?", "output": "CNEFinder is an algorithm which has been developed for finding conserved non-coding elements (CNEs)." }, { "input": "What type of antagonist is istradefylline?", "output": "Istradefylline is a selective adenosine A2A receptor antagonist." }, { "input": "What are the advantages of liquid biopsy in NSCLC?", "output": "Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure." }, { "input": "What are the advantages of liquid biopsy in NSCLC?", "output": ". These plasma-isolated exosomes can be used as a non-invasive and repeatable way for the detection and follow-up of these biomarkers.. We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact.. In summary, the panel concluded that liquid biopsy approaches have significant potential to improve patient care, and immediate implementation in the clinic is justified in a number of therapeutic settings relevant to NSCLC.. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution.. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status." }, { "input": "What are the advantages of liquid biopsy in NSCLC?", "output": "Mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status. Plasma-isolated exosomes can be used as a non-invasive and repeatable way for the detection and follow-up of these biomarkers. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. Complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution." }, { "input": "What is the 4D-CHAINS algorithm?", "output": "The 4D-CHAINS/autoNOE-Rosetta is a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta." }, { "input": "Which disorders are caused by de novo mutations in ZSWIM6?", "output": "Mutations in the ZSWIM6 gene, which encodes the cellular iron exporter ZEB6, are the cause of de novo autosomal recessive acromelic frontonasal dysostosis and Leber's hereditary optic neuropathy and/or dystonia." }, { "input": "Which disorders are caused by de novo mutations in ZSWIM6?", "output": "A recurrent de novo nonsense variant in ZSWIM6 results in severe intellectual disability without frontonasal or limb malformations. Also, a recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 has previously been reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect." }, { "input": "Which disorders are caused by de novo mutations in ZSWIM6?", "output": "Mutations in the solute carrier family 9, subfamily A member 6 (SLC9A6) gene, encoding the endosomal ZSWIM6 protein, are the cause of autosomal recessive acromelic frontonasal dysostosis and Leber's hereditary optic neuropathy and/or dystonia." }, { "input": "Describe ChromoTrace", "output": "Recent advances of super-resolution microscopy in principle enable the mapping of specific molecular features with nanometer precision inside cells. Combined with highly specific, sensitive and multiplexed fluorescence labeling of DNA sequences this opens up the possibility of mapping the 3D path of the genome sequence in situ. ChromoTrace is a computational methodology to reconstruct the sequence configuration of all human chromosomes in the nucleus from a super-resolution image of a set of fluorescent in situ probes hybridized to the genome in a cell. ChromoTrace uses suffix trees to assign a known linear ordering of in situ probes on the genome to an unknown set of 3D in-situ probe positions in the nucleus from super-resolved images using the known genomic probe spacing as a set of physical distance constraints between probes. The algorithm can assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences." }, { "input": "Describe ChromoTrace", "output": "ChromoTrace is a computational tool to reconstruct the sequence configuration of all human chromosomes in the nucleus from a super-resolution image of a set of fluorescent in situ probes hybridized to the genome in a cell. It can be used to assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences. By simulating appropriate spatial resolution, label multiplexing and noise scenarios it is possible to assess the algorithms performance." }, { "input": "What is the aim of iodine prophylaxis?", "output": "Due to high volatility and environmental mobility, radioactive isotopes of iodine pose a serious risk in the acute phases of a nuclear accident. The critical organ for iodine is the thyroid. A number of studies dealing with thyroid protection from exposure to radioiodine have shown that radioiodine uptake by the thyroid can be effectively blocked by administration of stable iodine, usually in the form of potassium iodide (KI) pills." }, { "input": "Through which molecular pathway does LB-100 reduce hepatic steatosis?", "output": "PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway." }, { "input": "Which drugs are included in PolyIran?", "output": "PolyIran polypill is composed of acetylsalicylic acid, hydrochlorothiazide, enalapril, and atorvastatin, whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials." }, { "input": "Are tumour specific antigens originating from known protein coding genes?", "output": "Heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP. Tumour antigens are mostly of weak immunogenicity, because the vast majority are tumour-associated differentiation antigens already 'seen' by the patient's immune system." }, { "input": "Are tumour specific antigens originating from known protein coding genes?", "output": "heat-shock proteins (hsps)" }, { "input": "Are tumour specific antigens originating from known protein coding genes?", "output": "The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP." }, { "input": "Are tumour specific antigens originating from known protein coding genes?", "output": "It is well established that MHC class I molecules present peptides from endogenous proteins, such as virus or tumour antigens, to CD8+ T lymphocytes. So far, human tumour specific antigens that can be presented by HLA molecules have not been identified on the molecular level. The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP." }, { "input": "Are tumour specific antigens originating from known protein coding genes?", "output": "D" }, { "input": "Mutations in which gene form the genetic basis of the DOORS syndrome?", "output": "Mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes. Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations. More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24." }, { "input": "What is the aim of the \"Radiogenomics Consortium\"?", "output": "A major aim of research in radiogenomics is the development of a predictive instrument to enable identification of people who are at greatest risk for adverse effects resulting from cancer treatment using radiation. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics." }, { "input": "Who should wear dosimeters?", "output": "Nuclear medicine technologists rely on a single dosimeter to measure their work-related dose. Dosimetry for the study of medical radiation workers." }, { "input": "What kind of molecule is AZD8601?", "output": "AZD8601 is a modified mRNA." }, { "input": "Which disease category is LB-100 mostly assessed for?", "output": "LB-100 is designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. It is assessed for its therapeutic potential against cancer." }, { "input": "Which disease can be classified using the Koos Classification?", "output": "The Koos classification is used from vestibular schwannomas. It is designed to stratify tumors based on extrameatal extension and compression of the brainstem." }, { "input": "What is circulating free DNA ( cfDNA)?", "output": "Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden, and mechanisms of progression and drug resistance." }, { "input": "What is circulating free DNA ( cfDNA)?", "output": "Cell-free DNA (cfDNA) and cell-free RNA (cfRNA), RNA associated to platelets and circulating tumor cells (CTCs) are some of the materials that can be derived from the blood of cancer patients." }, { "input": "What are the in vivo effects of AZD8601?", "output": "AZD8601 administration in vivo results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing." }, { "input": "Which receptor does amantadine antagonize?", "output": "Amantadine is an N-methyl-D-aspartic acid or N-methyl-D-aspartate (NMDA) receptor antagonist." }, { "input": "Which characteristics are used in the SLEDAI index for SLE patients?", "output": "The SLEDAi is a \"weighted\" index of 9 organ systems for disease activity in SLE which includes: 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic." }, { "input": "Which characteristics are used in the SLEDAI index for SLE patients?", "output": "Twenty-four variables were identified as important factors in a disease activity index. This generated a \"weighted\" index of 9 organ systems for disease activity in SLE, the SLEDAI 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic." }, { "input": "Which medication are included in the Polycap polypill?", "output": "Polycap polypil contains aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; and simvastatin, 20 mg. It is taken as two capsules once daily." }, { "input": "Describe the mechanism of action of Luspatercept.", "output": "Luspatercept is a recombinant soluble activin type-II receptor-IgG-Fc fusion protein that blocks transforming growth factor beta (TGF b) superfamily inhibitors of erythropoiesis. Luspatercept is tested for the treatment of various types of anemias." }, { "input": "Which method has been developed for mapping of Transcription Start Sites (TSS) starting from nanograms of RNA?", "output": "SLIC-CAGE has been developed as a method to identify transcriptome-wide the binding sites of transcription start sites (TSSs) using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of DNA-binding proteins, transcription, individual nucleosomes and transcriptional starting sites." }, { "input": "Which method has been developed for mapping of Transcription Start Sites (TSS) starting from nanograms of RNA?", "output": "Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5' ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. SLIC-CAGE is a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA." }, { "input": "Which method has been developed for mapping of Transcription Start Sites (TSS) starting from nanograms of RNA?", "output": "SLIC-CAGE has been developed as a method to identify transcriptome-wide the binding sites of transcription start sites (TSSs) using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of DNA-binding sites, transcription, mRNA, and nucleosomes." }, { "input": "What are the molecular and cellular effects of LB-100 on ovarian carcinoma cells following cisplatin treatment?", "output": "LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites." }, { "input": "Can LB-100 downregulate miR-33?", "output": "No, LB-100 has been reported to modulate (upregulate) only miR-181b-1." }, { "input": "What is molecular radiotherapy?", "output": "Molecular radiotherapy is working through tumor-targeted radionuclides." }, { "input": "Which mRNAs are sequestered in stress granules?", "output": "Stress granules are higher order assemblies of nontranslating mRNAs and proteins that form when translation initiation is inhibited. \nThis subset of mRNAs is characterized by extended length and adenylate-uridylate (AU)-rich motifs, is highly enriched with genes critical for cell survival and proliferation. mRNA accumulation in stress granules correlates with longer coding and UTR regions and poor translatability" }, { "input": "Which are the problems associated with the use of PD-L1 as immunotherapy biomarker?", "output": "The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells" }, { "input": "Which are the problems associated with the use of PD-L1 as immunotherapy biomarker?", "output": "The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells." }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "Yes. Poliosis circumscripta is another term for a white or unpigmented patch of hair or skin." }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "Yes, poliosis circumscripta, or \"white forelock,\" is defined as a localized patch of white hair in a group of hair follicles." }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "poliosis circumscripta is a \" localized patch of white hair in a group of hair foll white forelock \" circumscripta was defined as a \"" }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "yes, \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle" }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "Yes, poliosis circumscripta is another term for a white or unpigmented patch of hair or skin." }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle" }, { "input": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "output": "white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle" }, { "input": "How are SAHFS created?", "output": "Cellular senescence-associated heterochromatic foci (SAHFS) are a novel type of chromatin condensation involving alterations of linker histone H1 and linker DNA-binding proteins. SAHFS can be formed by a variety of cell types, but their mechanism of action remains unclear." }, { "input": "How are SAHFS created?", "output": "Senescent cells have a distinct gene expression profile, which is often accompanied by the spatial redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs). Their creation goes through the senescence stimulated depletion of LMNB1, which facilitates the nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers which characterize senescence-associated heterochromatic foci (SAHF)." }, { "input": "What is another name for AZD0530?", "output": "AZD0530 is also known as saracatinib." }, { "input": "Which is the effect of the HP1a protein on chromatin?", "output": "Heterochromatin Protein 1 (HP1a) is a well-known conserved protein that is involved in heterochromatin formation and gene silencing through the reading of the heterochromatin mark methylation of histone H3 lysine 9 (H3K9me) in different species including humans." }, { "input": "Which is the effect of the HP1a protein on chromatin?", "output": "Heterochromatin-associated protein 1 (HP1a) mediates silencing and switching at the mating-type loci and is essential for pluripotency in Drosophila. HP1a belongs to a homologous family of histone-deacetyltransferases that mediate chromatin organization through the binding of histones to chromatin. The ATP-dependent chromatin-remodelling activity of HP1A is mediated, in part, by its interaction with histone H3 methyltransferase 3 (H3K9me2/3)." }, { "input": "Is Selumetinib effective for low-grade glioma?", "output": "Selumetinib has promising antitumor activity in children with LGG." }, { "input": "What is Nextflow?", "output": "Reproducing routine bioinformatics analysis is challenging owing to a combination of factors hard to control for. Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines. Third party pipelines can be ported into Nextflow with minimum re-coding." }, { "input": "What is Nextflow?", "output": "Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines." }, { "input": "What is Nextflow?", "output": "Reproducing routine bioinformatics analysis is challenging owing to a combination of factors hard to control for. Nextflow is a flow management framework that uses container technology to insure efficient deployment and reproducibility of computational analysis pipelines." }, { "input": "What is Nextflow?", "output": "Nextflow is a flow management framework that uses container technology to ensure efficient deployment and reproducibility of computational analysis pipelines." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAZViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny. Furthermore, BioPAXViz supports the display of hierarchical trees that allow efficient navigation through sets of variants of a single reference pathway. Thus, BioPAXViz can significantly facilitate, and contribute to, the study of metabolic pathway evolution and engineering." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application providing a comprehensive framework for metabolic pathway visualization. The application provides a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application providing a comprehensive framework for metabolic pathway visualization." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application for the visual exploration of metabolic pathway evolution. The software is distributed under the MIT License and is accompanied by example files and data. Additional documentation is available at the aforementioned repository." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny." }, { "input": "Which application is the backbone of BioPAXViz?", "output": "BioPAXViz is a Cytoscape (version 3) application, providing a comprehensive framework for metabolic pathway visualization. Beyond the basic parsing, viewing and browsing roles, the main novel function that BioPAXViz provides is a visual comparative analysis of metabolic pathway topologies across pre-computed pathway phylogenomic profiles given a species phylogeny. Furthermore, BioPAXViz supports the display of hierarchical trees that allow efficient navigation through sets of variants of a single reference pathway. Thus, BioPAXViz can significantly facilitate, and contribute to, the study of metabolic pathway evolution and engineering.Availability and Implementation: BioPAXViz has been developed as a Cytoscape app and is available at: https://github.com/CGU-CERTH/BioPAX.Viz." }, { "input": "What is SpatialDE?", "output": "SpatialDE is a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data. SpatialDE also implements ' automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology." }, { "input": "What is SpatialDE?", "output": "Technological advances have made it possible to measure spatially resolved gene expression at high throughput. However, methods to analyze these data are not established. SpatialDE is a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data. SpatialDE also implements 'automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology." }, { "input": "What is the Match BAM to VCF method?", "output": "MBV (Match BAM to VCF) is a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias." }, { "input": "What is the Match BAM to VCF method?", "output": "Large genomic datasets combining genotype and sequence data, such as for expression quantitative trait loci (eQTL) detection, require perfect matching between both data types. MBV (Match BAM to VCF) is a method to quickly solve sample mislabeling and detect cross-sample contamination and PCR amplification bias. MBV is implemented in C ++ as an independent component of the QTLtools software package, the binary and source codes are freely available at https://qtltools.github.io/qtltools/." }, { "input": "Describe MAGNIMS criteria.", "output": "Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS)." }, { "input": "Is SATB1 expressed in thymocytes?", "output": "A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes. SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. In this study we show that special AT-rich binding protein 1 (SATB1), a T lineage-enriched chromatin organizer and regulator, is induced in response to TCR signaling during early thymocyte development" }, { "input": "Is SATB1 expressed in thymocytes?", "output": "Yes, SATB1 is expressed in thymocytes and has a major role in the regulation of cell differentiation." }, { "input": "Is SATB1 expressed in thymocytes?", "output": "yes, This was shown by fluorescence in situ hybridization on wild-type and Satb1-null thymocytes using in vivo SATB1-bound sequences as probes. " }, { "input": "Is SATB1 expressed in thymocytes?", "output": "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. " }, { "input": "Is SATB1 expressed in thymocytes?", "output": "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes." }, { "input": "Is SATB1 expressed in thymocytes?", "output": "SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. SATB1 is a cell-type specific nuclear protein that recruits chromatin-remodeling factors and regulates numerous genes during thymocyte differentiation." }, { "input": "Is SATB1 expressed in thymocytes?", "output": "A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes." }, { "input": "Which company produces ORMD-0801?", "output": "ORMD-0801 is produced by Oramed Pharmaceuticals." }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "saf-a/hnrnp u is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region dna" }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "SAF-A/hnRNP U is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs. Scaffold attachment factor A (SAF-A) participates in the regulation of gene expression by organizing chromatin into transcriptionally active domains and by interacting directly with RNA polymerase II." }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "Scaffold attachment factor B (SAF-B) is a nuclear matrix-associated protein. It is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs." }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "TheSAF-A protein is localized to the nuclear matrix" }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "SAF-A/hnRNP U is an abundant nuclear protein that interacts specifically with nuclear matrix attachment region DNA (MAR) and RNA as a component of hnRNPs. " }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "The SAF-A protein localizes to the nucleus where it promotes ribosome biogenesis" }, { "input": "In which cell organelle is the SAF-A protein localized?", "output": "SAF-A is localized to the nucleus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth." }, { "input": "Describe Twiddler Syndrome.", "output": "Twiddler syndrome is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices." }, { "input": "What are Drosophila's balancer chromosomes?", "output": "genetic reagents" }, { "input": "What are Drosophila's balancer chromosomes?", "output": "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens." }, { "input": "What are Drosophila's balancer chromosomes?", "output": "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. This problem is of particular importance when the mutant allele has been maintained with a balancer chromosome. From four isogenic lines of Drosophila melanogaster, four sets of recombinant extracted lines were constructed using standard balancer-chromosome techniques" }, { "input": "What are Drosophila's balancer chromosomes?", "output": "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. This problem is of particular importance when the mutant allele has been maintained with a balancer chromosome." }, { "input": "What are Drosophila's balancer chromosomes?", "output": "balancer chromosomes are genetic reagents used for stock maintenance and mutagenesis screens" }, { "input": "What is iodine thyroid blocking?", "output": "High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later." }, { "input": "Does gavestinel improve outcomes of stroke patients?", "output": "No. In a randomized clinical trial, treatment with gavestinel within 6 hours of acute ischaemic stroke did not improve outcome." }, { "input": "Can Systemic Lupus Erythematosus cause seizures?", "output": "In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE)" }, { "input": "Can Systemic Lupus Erythematosus cause seizures?", "output": "Yes, Systemic Lupus Erythematosus s an autosomal recessive disorder can cause seizures." }, { "input": "Can Systemic Lupus Erythematosus cause seizures?", "output": "Yes, Seizure can be caused by Systemic Lupus Erythematosus." }, { "input": "What disease is associated with a Malar rash?", "output": "Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash;" }, { "input": "What disease is associated with a Malar rash?", "output": "Malar rash is associated with a disease of the skin called Systemic lupus erythematosis." }, { "input": "What disease is associated with a Malar rash?", "output": "Malar rash is a systemic lupus erythematosus (SLE) syndrome characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and chronic course." }, { "input": "What disease is associated with a Malar rash?", "output": "The malar or butterfly rash is seen on the face and is associated with systemic Lupus erythematosus" }, { "input": "What disease is associated with a Malar rash?", "output": " Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash;" }, { "input": "What disease is associated with a Malar rash?", "output": "the cutaneous effects of sle are frequently the presenting symptoms. typically noted in the classic malar \"butterfly \" rash" }, { "input": "What disease is associated with a Malar rash?", "output": "Malar rash is associated with a Systemic lupus erythematosus." }, { "input": "What disease is associated with a Malar rash?", "output": " Cutaneous manifestations of SLE are frequently the presenting symptoms, typically noted in the classic malar \"butterfly\" rash; " }, { "input": "What is the mechanism of action of rogaratinib?", "output": "Rogaratinib is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "H3K27me3 is the major histone methyltransferase activity of PRC2." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "The Polycomb Repressive Complex 2 (PRC2) has been identified as a key regulator of epigenetic mark H3K27me3." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "There are data showing coordinate regulation between DNAme and H3K27me3, which are both involved in the establishment and maintenance of epigenetic gene silencing. We found that the Polycomb Repressive Complex 2 (PRC2), which is responsible for di- and trimethylation of H3K27 (H3K27me2/me3), binds to its own site of methylation." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "H3K27me3 is the endogenous epigenetic mark deposited by PRC2." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "H3K27me3 is an epigenetic mark deposited by PRC2 (Polycomb repressive complex 2)." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "polycomb repressive complex 2 (prc2 ) mediates trimethylation of lysine 27 on histone h3" }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, which establishes H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs." }, { "input": "Which epigenetic mark is deposited by PRC2?", "output": "PRC2 is H3K27me3 ubiquitously-associated and acts as an epigenetic mark deposition mechanism." }, { "input": "Is Impetigo a viral infection that affects the skin?", "output": "No, impetigo is a highly contagious bacterial skin infection" }, { "input": "List diseases that are caused by the Meningococcus B?", "output": "The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus" }, { "input": "List diseases that are caused by the Meningococcus B?", "output": "Both bacterial meningitis and septicemia can be caused by Meningococcus B" }, { "input": "List diseases that are caused by the Meningococcus B?", "output": "the prevention of paediatric bacterial meningitis and septicaemia has entered a new era with the availability of two vaccines against capsular group b meningoco" }, { "input": "Should Lubeluzole be used for treatment of ischemic stroke?", "output": "No. Lubeluzole failed to consistently show an efficacy in the treatment of acute stroke and should not be used." }, { "input": "What is vivotif?", "output": "Vivotif(r) is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe. It is indicated for adults and children from 5 years of age upwards. Specifically, in the most developed countries, vaccination is suggested for highrisk population groups and particularly for international travellers to destinations where the risk of contracting typhoid fever is high. Vivotif(r) appears to be a powerful means of disease prevention, the importance of which is highlighted by the spread of antibiotic-resistant strains of Salmonella typhy (S. typhi)." }, { "input": "List types of cancer where TBC1 domain family member 16 (TBC1D16) is involved", "output": "TBC1D16 is a predictive marker for favorable prognosis of Epithelial ovarian cancer (EOC). In addition, a short isoform of TBC1D16 (TBC1D16-47KD) exacerbates melanoma growth and metastasis both in vitro and in vivo." }, { "input": "List types of cancer where TBC1 domain family member 16 (TBC1D16) is involved", "output": "TBC1 domain family member 16 (Tbc1D16) is involved in several types of cancer. These include epithelial ovarian cancer, gastric cancer, breast cancer, cervical cancer, adenocarcinoma, colorectal cancer, Hodgkin lymphoma, nasopharyngeal carcinoma and oral squamous cell carcinoma." }, { "input": "What does osanetant and talnetant have in common?", "output": "Osanetant and talnetant are selective NK3 antagonists. Preclinical and Phase II clinical results of osanetant and talnetant in schizophrenic patients have indicated that NK(3) antagonists may provide significant improvement of the positive symptoms and cognitive impairment associated with this disorder." }, { "input": "List SLC25A46-related pathologies", "output": "SLC25A46-related pathologies include Charcot-Marie-Tooth disease type 2, Leigh syndrome, progressive myoclonic ataxia, lethal congenital pontocerebellar hypoplasia, autosomal dominant optic atrophy, Menkes disease, hyper-IgM with immunodeficiency syndrome (HIGM), and anterior pituitary aplasia." }, { "input": "List SLC25A46-related pathologies", "output": "The mitochondrial protein SLC25A46 has been identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia, lethal congenital pontocerebellar hypoplasia and lethal neuropathology" }, { "input": "List SLC25A46-related pathologies", "output": "The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital pontocerebellar hypoplasia." }, { "input": "List SLC25A46-related pathologies", "output": "SLC25A46-related pathologies include optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital ptacerebellar hypoplasia." }, { "input": "What is the target of galcanezumab?", "output": "Galcanezumab is a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention." }, { "input": "Which disease was studied in the CADISS trial?", "output": "CADISS was a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection." }, { "input": "What is the human RCA locus size in bps?", "output": "The human RCA locus is located on chromosome 1 (CA1) and consists of approximately 750 kb." }, { "input": "What is the human RCA locus size in bps?", "output": "Genome and expressed sequence tag information of Xenopus tropicalis suggested that short-consensus repeat (SCR)-containing proteins are encoded by three genes that are mapped within a 300-kb downstream of PFKFB2, which is a marker gene for the regulator of complement activation (RCA) loci in human and chicken" }, { "input": "What is the human RCA locus size in bps?", "output": "The locus containing the ribosomal protein A (RCA) gene is located at a perinuclear structure 3 kb from the left end and 610 kb in bps, leaving a footprint of 7.4 kb on chromosome 1." }, { "input": "What is the human RCA locus size in bps?", "output": "The human RCA locus is located on chromosome 1q21-32 and measures approximately 2-3 kb in bps." }, { "input": "What is the human RCA locus size in bps?", "output": "The human RCA locus is located on chromosome 1q21-32 and consists of approximately 150 tandemly repeated copies of a 9.1 kb locus." }, { "input": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "output": "Yes. Tet2-TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. TETs are ubiquitously expressed and play diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. Depletion of Tet2 and its ligand, Tet3, from mouse CD4CD8 double-positive thymus-derived cardiomyocytes (iNKT) resulted in dysregulated development and proliferation, with increased expression of tumour suppressor genes and decreased" }, { "input": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "output": "Yes. TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)." }, { "input": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "output": "Yes. Tet2-Tet3 double-knocked-out (DKO) iNKT cells displayed pronounced skew toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPok. Moreover, simultaneous deletion of Tet2 and Tet3 in mouse CD4CD8 double-positive thymocytes resulted in dysregulated development and proliferation of the non-classical major histocomponent complex (MHC) CD1d, which presents lipid antigens to T-cell-derived" }, { "input": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "output": "Yes. Tet2-Tet3 proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. Indeed, deletion of Tet2 and Tet3 in mouse CD4CD8 double-positive thymus cells resulted in dysregulated development and proliferation of the non-classical major histocompromised T cell antigen receptor (MHC) protein CD1d, which presents lipid antigens to iNKB-derived cells. Moreover, overexpression of TET1 and TET3 in Drosophila melanogaster T cells (iN" }, { "input": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "output": "Yes. Tet2-Tet3 double-knockout (DKO) cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Mutations in exon 2 interfere with the synthesis of the full-length isoform of Tet2 and lead to the production of a shortened isoform, Tet2s. These mutations have been found in human natural killer T cells (iNKTs), the most common type of innate immune cells." }, { "input": "What is the purpose of the Sunnybrook Facial Grading System?", "output": "The Sunnybrook facial grading system is applied to evaluate facial function in patients with facial palsy." }, { "input": "What is the function of the PDZ domain in SATB1?", "output": "N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1." }, { "input": "What is the function of the PDZ domain in SATB1?", "output": "N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. Binding studies using HD-lacking SATB1 and binding target with increased spacer between the two half-sites led us to propose a model for SATB1-DNA complex in which the HDs bind in an antiparallel fashion to the palindromic consensus element via minor groove, bridged by the PDZ-like dimerization domain SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins. We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. " }, { "input": "What is the function of the PDZ domain in SATB1?", "output": "PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1." }, { "input": "What is the function of the PDZ domain in SATB1?", "output": "We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis. PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1. Binding studies using HD-lacking SATB1 and binding target with increased spacer between the two half-sites led us to propose a model for SATB1-DNA complex in which the HDs bind in an antiparallel fashion to the palindromic consensus element via minor groove, bridged by the PDZ-like dimerization domain N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins." }, { "input": "What is the function of the PDZ domain in SATB1?", "output": "We found this dimerization region to have sequence similarity to PDZ domains, which have been previously shown to be involved in signaling by conferring protein-protein interactions. SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis." }, { "input": "What is the function of the PDZ domain in SATB1?", "output": "The PDZ domain is a cytoplasmic protein domain found in histone H3 lysine 27 and it is essential for PDZ-mediated ubiquitination of SATB1." }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Clathrin is a central regulator of endocytosis in all eukaryotes that plays a role in bacterial and plastid differentiation" }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes). while clathrin mediated endocytosis w" }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Clathrin is a central regulator of endocytosis in all eukaryotes that plays a critical role in the maintenance of cellular homeostasis" }, { "input": "What cellular process is the protein clathrin involved in?", "output": "while clathrin mediated endocytosis w. Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes)." }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes)" }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Clathrin plays a critical role in endocytosis and in doing so is crucial for maintaining cellular homeostasis" }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Receptor-mediated endocytosis proceeds by transfer of receptor-ligand complexes from clathrin-coated pits at the cell surface to uncoated endocytic vesicles termed receptosomes (or endosomes)." }, { "input": "What cellular process is the protein clathrin involved in?", "output": "Clathrin plays a critical role in endocytosis and in many other cellular processes" }, { "input": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "output": "No, Thymoquinone has been found to be effective against radiation induced enteritis" }, { "input": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "output": "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. " }, { "input": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "output": "thymoquinone (tq ) could mitigate intestinal damages induced by irradiation" }, { "input": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "output": "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation." }, { "input": "Which are the databases for intrinsic protein disorders?", "output": "Intrinsic disorder (ID), i.e. the lack of a unique folded conformation at physiological conditions, is a common feature for many proteins, which requires specialized biochemical experiments that are not high-throughput. DisProt and MobiDB are databases for intrinsic protein disorders." }, { "input": "List the 5 different human immunoglobulin heavy chains.", "output": "The 5 human immunoglobulin heavy chains are Alpha, Delta Epsilon, Gamma and Mu" }, { "input": "List the 5 different human immunoglobulin heavy chains.", "output": "using heavy chain specific gamma, alpha, mu, delta and epsilon" }, { "input": "Has the Spanich flu virus been reconstructed?", "output": "Tes,\nReconstruction of the 1918 influenza virus has facilitated considerable advancements in our understanding of this extraordinary pandemic virus." }, { "input": "What is the basis of the BLISS technique?", "output": "Here we present Breaks Labeling In Situ and Sequencing (BLISS), a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks." }, { "input": "What is the basis of the BLISS technique?", "output": "Breaks Labeling In Situ and Sequencing (BLISS) is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks." }, { "input": "What is the basis of the BLISS technique?", "output": "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. A recent method, BLISS, uses photoreactive nucleotides to crosslink RBPs to target RNAs in cells prior to immunoprecipitation." }, { "input": "What is the basis of the BLISS technique?", "output": "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks." }, { "input": "What is the basis of the BLISS technique?", "output": "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. Recently, we have further expanded the quantitative nature, applicability, and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing (BLISS). Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing." }, { "input": "What is the basis of the BLISS technique?", "output": "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing." }, { "input": "What is the basis of the BLISS technique?", "output": "bliss is a versatile and quantitative method for genome-wide profiling of dna double-strand breaks" }, { "input": "What is the basis of the BLISS technique?", "output": "BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. Recently, we have further expanded the quantitative nature, applicability, and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing (BLISS)" }, { "input": "What is the basis of the BLISS technique?", "output": "BLISS (Breaks Labeling In Situ and Sequencing) is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks (DSBs). It uses a novel Bayesian approach which represents continuous allele frequencies for both the endogenous and endogenous DSBs, while leveraging the endogenous Cpf1 methyltransferase activity of the zinc cluster as a template." }, { "input": "List 3 NK3R antagonists.", "output": "NK3 receptor antagonists include MLE4901 (also known as AZD4901), SB222200 and ESN364." }, { "input": "Is Verubecestat effective for Alzheimer's Disease?", "output": "No. Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events." }, { "input": "Is Aptiganel effective for treatment of stroke?", "output": "No. Aptiganel is not efficacious in patients with acute ischemic stroke and may be harmful." }, { "input": "Is indinavir effective for treatment of amyotrophic lateral sclerosis?", "output": "No, indinavir is not effective for treatment of amyotrophic lateral sclerosis." }, { "input": "Is there an increased risk for meningiomas in childhood leukemia survivors?", "output": "Yes, the risk of meningiomas is higher in children treated with cranial irradiation for leukemia." }, { "input": "List the clinical characteristics of the Smith-Kingsmore syndrome (SKS)", "output": "Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features." }, { "input": "List the clinical characteristics of the Smith-Kingsmore syndrome (SKS)", "output": "Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. " }, { "input": "What is ORMD-0801?", "output": "ORMD-0801 is an oral insulin capsule. Treatment with ORMD-0801 was associated with a significant 24.4% reduction in the frequencies of glucose readings >200 mg/dL (60.1 +- 7.9% pretreatment vs. 45.4 +- 4.9% during ORMD-0801 treatment; p = 0.023) and a significant mean 16.6% decrease in glucose area under the curve (AUC) (66055 +- 5547 mg/dL/24 hours vs. 55060 +- 3068 mg/dL/24 hours, p = 0.023), with a greater decrease during the early evening hours. When used in conjunction with subcutaneous insulin injections, ORMD-0801 was well tolerated and effectively reduced glycemia throughout the day." }, { "input": "Does saracatinib promote oncogenesis?", "output": "No, saracatinib has antitumor activity." }, { "input": "Is BCL11B involved in schizophrenia?", "output": "Yes, BCL11B is associated with attention, memory, executive function and antipsychotic-induced schizophrenia." }, { "input": "Is BCL11B involved in schizophrenia?", "output": "Yes. SATB2 is associated with schizophrenia and is an important transcription factor regulating neocortical organization and circuitry. Rare mutations in SATB2 cause a syndrome that includes developmental delay, and mouse studies identify an important role for SATB2 in learning and memory. Interacting partners BCL11B and GATAD2A are also schizophrenia risk genes." }, { "input": "Is BCL11B involved in schizophrenia?", "output": "Yes. Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with schizophrenia, including BCL11B, a master regulator of cortical development, in patients with schizophrenia. BCL 11B is involved in the development of the central nervous system, and its deficiency or pharmacological neutralization may contribute to the onset of schizophrenia." }, { "input": "Is BCL11B involved in schizophrenia?", "output": "Yes. BCL11B is a transcriptional repressor essential for schizophrenia." }, { "input": "Is BCL11B involved in schizophrenia?", "output": "Yes. BCL11B is associated with early as well as with late onset schizophrenia." }, { "input": "What is Synucleinopathy?", "output": "Synucleinopathy is an autosomal-dominant disease characterised by misfolding of presynaptic synuclein and the formation of Lewy bodies with ubiquitin-ligase activity." }, { "input": "What is Synucleinopathy?", "output": "Synucleinopathies (also called a-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells." }, { "input": "What is Synucleinopathy?", "output": "Synucleinopathy is an autosomal recessive neurodegenerative disease characterized by the degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy neurites in central nervous system" }, { "input": "What is Synucleinopathy?", "output": "Synucleinopathy is an autosomal recessive neurodegenerative disease characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies in a proportion of the remaining neurones." }, { "input": "What is Synucleinopathy?", "output": "The accumulation of abnormal a-synuclein is the major histopathological feature of Lewy body disease and multiple system atrophy (MSA), which are referred to as synucleinopathies." }, { "input": "Which receptor is modulated with Siponimod?", "output": "Siponimod is a functional sphingosine-1-phosphate (S1P) antagonist." }, { "input": "What is a zoonotic virus?", "output": "A zoonotic disease is a disease that can be passed from animals to humans. Zoonotic viruses may adapt to a human host eventually becoming endemic in humans, but before doing so punctuated outbreaks of the zoonotic virus may be observed." }, { "input": "Which drug is the first oral ghrelin receptor inverse agonist to be profiled in healthy subjects?", "output": "PF-05190457 is the first oral ghrelin receptor inverse agonist to be profiled in healthy subjects." }, { "input": "What is the function of BRD4?", "output": "As a member of the bromodomain and extraterminal (BET) family, BRD4 (bromodomain containing 4) can bind to acetylated histones and transcription factors, and is also able to recruit various transcriptional regulators. As transcriptional coactivator, BRD4 represses autophagy and lysosomal function." }, { "input": "What is the function of BRD4?", "output": "Our recent study revealed that autophagy programs are transcriptionally suppressed by the BET family protein BRD4." }, { "input": "What is the protective efficacy of vaxchora against moderate to severe cholera?", "output": "The protective efficacy of vaxchora against moderate to severe cholera is 80-100%." }, { "input": "What is minodixil approved for?", "output": "Minoxidil is the only topical drug approved for the treatment of both female and male pattern hair loss. In the US, minoxidil is approved over-the-counter (OTC) at a maximum concentration of 5%." }, { "input": "Are Chernobyl survivors at increased risk for breast cancer?", "output": "Yes, Chernobyl survivors are at increased risk for breast cancer." }, { "input": "What is AZD0530 an inhibitor of?", "output": "AZD0530 is a highly selective, dual Src/Abl kinase inhibitor." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Yes. SATB1 is an essential factor for the regulation of T-cell maturation." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. the transcription factor SATB1 that regulates the T-cell maturation SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Yes, SATB1 is necessary for T-cell maturation." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Yes. SATB1 is an essential regulator of T-cell maturation." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Yes, SATB1 is required for T-cell maturation." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Yes. SATB1 is associated with the late-M-to-early-G1 phase of T-cell maturation and its activation correlates with histone H3 hyperacetylation, DNA methylation, and chromatin reorganization at the transcriptional level, while it is involved in the early stages of T cell differentiation into the erythroid lineage." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "yes, SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. " }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. the transcription factor SATB1 that regulates the T-cell maturation" }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "the transcription factor SATB1 that regulates the T-cell maturation. SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling." }, { "input": "Is SATB1 necessary for T-cell maturation?", "output": "the transcription factor SATB1 that regulates the T-cell maturation Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling." }, { "input": "For how long do Drosophila embryos use maternal genome mRNA?", "output": "mitoses before interphase 14 run on maternal products and occur in metasynchronous waves" }, { "input": "For how long do Drosophila embryos use maternal genome mRNA?", "output": "before interphase 14" }, { "input": "For how long do Drosophila embryos use maternal genome mRNA?", "output": "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves. In many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus." }, { "input": "For how long do Drosophila embryos use maternal genome mRNA?", "output": "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves." }, { "input": "For how long do Drosophila embryos use maternal genome mRNA?", "output": "In Drosophila embryogenesis mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves." }, { "input": "For how long do Drosophila embryos use maternal genome mRNA?", "output": "Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves. An exceptional case of Nos-independent regulation by Pum has been described-repression of maternal bicoid (bcd) m RNA at the anterior pole of the early embryo, dependent on both Pum and conserved Pum binding sites in the 3'- UTR of the m RNA" }, { "input": "What is the use of erenumab?", "output": "Erenumab is a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist-for the prevention of migraine. CGRP is a vasodilatory neuropeptide implicated in the pathophysiology of migraine and treatment with erenumab was associated with significant reductions in migraine frequency in phase II and III clinical trials. Based on these positive results erenumab was recently approved in the US for the preventive treatment of migraine in adults and has received a positive opinion in the EU for the prophylaxis of migraines in adults who have at least 4 migraine days per month.\n\nConclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use." }, { "input": "What is the function of a viral peplomer?", "output": "The coronavirus peplomer protein S is responsible for attachment and fusion during viral entry as well as for the induction of cell to cell fusion.\nSince tissue affinities are a function of the viral peplomer-mediated attachment of virus to cells and are often directly related to pathogenicity," }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Yes, toll-like receptor 2 activators (TLR2) have been found in food." }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Yes, Toll-like receptor 2 activators (TLR2) have been found in food." }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Yes, Toll-like receptor 2 (TLR2) activators have been found in food." }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "toll-like receptor 2 (tlr2) ) is a widely expressed pattern recognition receptor critical for innate immunity. tlr2 activators are found in many common foods" }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Yes, Toll-like receptor 2 activators have been found in food." }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease and they are found in many common foods. " }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Toll-like receptor 2 ( TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods," }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "yes, Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods," }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods," }, { "input": "Have toll-like receptor 2 activators been found in food?", "output": "TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods," }, { "input": "Describe the Open Targets platform", "output": "The Open Targets platform is a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org." }, { "input": "Does radiotherapy for Hodgkin disease increases risk for lung cancer?", "output": "Yes, radiotherapy for Hodgkin disease is associated with increased risk for lung cancer." }, { "input": "Does radiotherapy for prostate cancer increase bladder cancer risk?", "output": "Yes, radiotherapy for prostate cancer is associated with increased bladder cancer risk." }, { "input": "What is ESN364?", "output": "systemic administration of an NK3R antagonist (ESN364) prolongs the LH interpulse interval in ovarectomized ewes and significantly lowers plasma LH and FSH concentrations in castrated nonhuman primates (Macaca fascicularis). Moreover, daily oral dosing of ESN364 throughout the menstrual cycle in M fascicularis lowered plasma estradiol levels in a dose-dependent manner, although nadir levels of estradiol were maintained well above menopausal levels. Nevertheless, estradiol levels during the follicular phase were sufficiently inhibited at all doses to preclude the triggering of ovulation as evidenced by the absence of the LH surge and failure of a subsequent luteal phase rise in plasma progesterone concentrations, consistent with the absence of normal cycle changes in the uterus. Apart from the point at surge, FSH levels were not altered over the course of the menstrual cycle. These effects of ESN364 were reversible upon cessation of drug treatment.\n\nESN364 was well-tolerated and rapidly bioavailable with linear pharmacokinetics and no drug accumulation with repeated, daily oral administration. Drug treatment dose-dependently decreased basal LH, but not FSH, and consequently decreased estradiol and progesterone (in women) as well as testosterone (in men). The hormonal changes in women corresponded to delayed ovulation, decreased endometrial thickening, impeded follicular maturation, and prolongation of the menstrual cycle. Drug effects were rapidly reversible. Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women. These results suggest that ESN364 may offer therapeutic benefit in the treatment of women's health disorders with a mitigated risk of menopausal-like adverse events." }, { "input": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "output": "No, genes with monoallelic expression contribute disproportionately to genetic diversity in humans." }, { "input": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "output": "No. Genes with monoallelic expression contribute disproportionately to genetic diversity in humans." }, { "input": "Has MLE4901 been tested in phase III clinical trials?", "output": "No, MLE4901 has been tested in phase 2, randomised, double-blind, placebo-controlled trial." }, { "input": "Does ESN364 activate the hypothalamic-pituitary-gonadal axis?", "output": "No, the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion" }, { "input": "Which type of variants can be called by the VarDict algorithm?", "output": "VarDict is a novel and versatile variant caller for both DNA- and RNA-sequencing data. It simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation." }, { "input": "Which type of variants can be called by the VarDict algorithm?", "output": "VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood." }, { "input": "Which type of variants can be called by the VarDict algorithm?", "output": "VarDict is a novel and versatile variant caller for both DNA- and RNA-sequencing data. It calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors." }, { "input": "Which type of variants can be called by the VarDict algorithm?", "output": "VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors." }, { "input": "Has ORMD-0801 been tested in patients?", "output": "Yes, ORMD-0801 has been tested in patients." }, { "input": "Was vivotif licensed in Europe and the US at the same time?", "output": "No, vivotif was licensed in Europe in 1983 and in the US in 1989." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "Yes, stem cell transplantation is becoming the treatment of choice for complicated acute kidney injury." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "Yes, stem cell transplantation is being used for treatment of acute kidney injury." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "Yes, stem cell transplants are being used for treatment of acute kidney injury." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "Yes, stem cell transplants are being used for acute kidney injury treatment." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "Yes, stem cell transplants are being used to treat acute kidney injury." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "Yes, Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration." }, { "input": "Are stem cell transplants used to treat acute kidney injury?", "output": "D" }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. " }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin." }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes." }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head. Pds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction." }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head" }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "we propose that wapl and pds5 directly modulate conformational changes of cohesin to make it competent for dissolving from chromatin during prophase" }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin" }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction." }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin " }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin along DNA. the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head" }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": " the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction." }, { "input": "What is the interaction between WAPL and PDS5 proteins?", "output": "We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding. the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. ds5 and Wapl, but not Brca2, limit the distance that cohesin extends from origins, thereby determining which active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B and cohesin, largely in the same direction." }, { "input": "Is deletion at 6q24.2-26 associated with shorter survival for ovarian cancer patients?", "output": "No, the 6q24.2-26 deletion is an independent marker of favorable outcome in high-grade serous ovarian carcinoma (HGSOC) patients with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life." }, { "input": "Is deletion at 6q24.2-26 associated with shorter survival for ovarian cancer patients?", "output": "No, deletion at 6q24.2-26 predicts longer survival of high-grade serous ovarian cancer patients." }, { "input": "What is the function of a protein kinase?", "output": "Protein kinases are enzymes that add a phosphate (PO4) group to a protein, and can modulate its function." }, { "input": "Which was the first cholera vaccine approved in the US?", "output": "Vaxchora is the first vaccine approved by the Food and Drug Administration for the prophylaxis of cholera infection." }, { "input": "List 3 PD-L1 inhibitors on the market as of 2018.", "output": "Atezolizumab (Tecentriq), Avelumab (Bavencio), and Durvalumab (Imfinzi) are PD-L1 inhibitors" }, { "input": "Are there negative enhancers?", "output": "Yes, negative enhancers are also called gene silencers." }, { "input": "Are there negative enhancers?", "output": "Yes, there are. There is a gene called the CANP mL gene, which is responsible for muscle type regulation. It is a negative enhancer." }, { "input": "Are there negative enhancers?", "output": "Yes, they are genomic regions that are dense in negative regulatory elements." }, { "input": "Are there negative enhancers?", "output": "Yes. Negative enhancers are enhancers that negatively regulate gene expression by physically blocking transcription of a subset of genes, often immobilizing transcriptional machinery." }, { "input": "Are there negative enhancers?", "output": "Yes. Numerous studies suggest that negative enhancers are present in eukaryotic genomes and play key roles in gene expression." }, { "input": "Are there negative enhancers?", "output": "Yes, there are. There is a gene called the CANP mL gene, which is responsible for muscle type regulation. It has a positive and a negative enhancer. The positive enhancer gene controls muscle type, while the negative one controls muscle growth." }, { "input": "Are there negative enhancers?", "output": "Yes. There are numerous studies of gene regulation in which enhancers are found to be negative enhancers, either because they negatively regulate transcription, or are absent or have a limited function." }, { "input": "What is the function of WAPL protein on cohesin?", "output": "Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase We show that the human ortholog of Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase." }, { "input": "What is the function of WAPL protein on cohesin?", "output": "Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase.It promotes the release of cohesin from chromosomes during both interphase and mitosis." }, { "input": "What is the function of WAPL protein on cohesin?", "output": "Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. We show that the human ortholog of Wapl is a cohesin-binding protein that facilitates cohesin's timely release from chromosome arms during prophase." }, { "input": "What is romiplostim targeting?", "output": "Romiplostim (ROM) is a thrombopoietin (TPO)-receptor-agonist approved for treatment of adults with chronic immune thrombocytopenia (ITP)." }, { "input": "Please list 3 drugs that have EGFR as their primary target.", "output": "There are a number of drugs that target EGFR. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib)" }, { "input": "Please list 3 drugs that have EGFR as their primary target.", "output": "Cetuximab, erlotinib and gefitinib are 3 drugs that have EGFR as their primary target." }, { "input": "Please list 3 drugs that have EGFR as their primary target.", "output": "The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib)" }, { "input": "What is the role of STAG1/STAG2 proteins in differentiation?", "output": "STAG1/STAG2 proteins are tumour suppressor proteins that suppress cell proliferation and are essential for differentiation." }, { "input": "What is the role of STAG1/STAG2 proteins in differentiation?", "output": "involved in the g2-m transition" }, { "input": "What is the role of STAG1/STAG2 proteins in differentiation?", "output": "STAG1/STAG2 proteins are tumour suppressor proteins that suppress cell proliferation and differentiation." }, { "input": "What is the role of STAG1/STAG2 proteins in differentiation?", "output": "The expression of STAG1 mRNA was induced in response to various genotoxic stresses in a p53-dependent manner; moreover, enforced expression of STAG1 led to apoptosis in several additional cancer cell lines. The simultaneous blocking of STAG1 and STAG2 significantly reduces cell proliferation. STAG1 preferentially contributes to the stabilization of topologically associating domain boundaries together with CTCF, whereas STAG2 promotes cell-type-specific contacts between enhancers and promoters independently of CTCF." }, { "input": "What can we measure with the TSA-Seq method?", "output": "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler. TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling." }, { "input": "What can we measure with the TSA-Seq method?", "output": "TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler. " }, { "input": "What can we measure with the TSA-Seq method?", "output": "TSA-Seq is a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling." }, { "input": "What can we measure with the TSA-Seq method?", "output": "mean chromosomal distances" }, { "input": "Which method is behind HipMCL?", "output": "HipMCL is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands." }, { "input": "Which method is behind HipMCL?", "output": "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. HipMCL is based on MPI and OpenMP and is freely available under a modified BSD license." }, { "input": "Which method is behind HipMCL?", "output": "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands. High-performance MCL (HipMCL) offers a parallel implementation of the original MCL algorithm that can run on distributed-memory computers. By exploiting distributed-memory environments, HipMCL clusters large-scale networks several orders of magnitude faster than MCL and enables clustering of even bigger networks. HipMCL is based on MPI and OpenMP and is freely available under a modified BSD license." }, { "input": "Which method is behind HipMCL?", "output": "While various clustering algorithms have been proposed to find highly connected regions, Markov Clustering (MCL) has been one of the most successful approaches to cluster sequence similarity or expression networks. Despite its popularity, MCL's scalability to cluster large datasets still remains a bottleneck due to high running times and memory demands. HipMCL is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks." }, { "input": "Which method is behind HipMCL?", "output": "HipMCL (HipClustering) is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks." }, { "input": "Which method is behind HipMCL?", "output": "HipMCL is a high-performance parallel implementation of the Markov clustering algorithm for large-scale networks." }, { "input": "What is the function of CR elements in B-cells?", "output": " After addition of culture supernatant from BCG-activated macrophages CR- B cells cooperate with both unprimed and primed T helper cells." }, { "input": "What is the function of CR elements in B-cells?", "output": "The SR/CR mouse phenotype, first described in 1999 in BALB/c and later bred into C57BL/6 mice, is resistant to cancer formation following high doses of cancer cells administered intraperitoneally." }, { "input": "What is the function of CR elements in B-cells?", "output": "CR elements are subtelomeric protein complexes that repress translation of a subset of RNAs in response to abiotic stress and can mediate diverse physiological and developmental processes in B- cells." }, { "input": "What is drug target for olaparib?", "output": "Olaparib(Lynparza) is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair." }, { "input": "What is drug target for olaparib?", "output": "Olaparib is a Poly(ADP-ribose) Polymerase (PARP) Inhibitor" }, { "input": "What virus is the Gardisil vaccine used for?", "output": "Gardisil is a quadrivalent HPV vaccine would have been useful in the prevention of infections with human papillomavirus." }, { "input": "What virus is the Gardisil vaccine used for?", "output": "Gardisil is a 4-component vaccine against capsular HPV 16 (4C HPV16), which has recently been licensed in Europe, Canada and Australia." }, { "input": "What virus is the Gardisil vaccine used for?", "output": "Gordisil is a 4-component vaccine against capsular Meningococcus serogroup B (4CMenB), which has recently been licensed in Europe, Canada and Australia." }, { "input": "What virus is the Gardisil vaccine used for?", "output": "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections " }, { "input": "What virus is the Gardisil vaccine used for?", "output": "Gardisil is a 16-component vaccine against human papillomavirus (HPV), which has recently been licensed in Europe, Canada and Australia." }, { "input": "What virus is the Gardisil vaccine used for?", "output": "Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections" }, { "input": "Which cells mature in the human thymus?", "output": "Thymus progenitor cells mature in the human thymus through differentiation into cardiomyocytes and fibroblasts." }, { "input": "Which cells mature in the human thymus?", "output": "Late stages of T cell maturation in the thymus involve NF-kB and tonic type I interferon signaling. NF-kB and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells." }, { "input": "Which cells mature in the human thymus?", "output": "late stages of t cell maturation in the thymus involve nf-kb and tonic type i interferon signals" }, { "input": "Which cells mature in the human thymus?", "output": "NF-kB and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells." }, { "input": "Which cells mature in the human thymus?", "output": "The mammalian thymus is an important post-translational organ that plays a pivotal role in the development of the human immune system. Thymocytes, which represent 50% of the cells in the human body, mature into cardiomyocytes and T cells." }, { "input": "Which cells mature in the human thymus?", "output": "T cells mature in the human thymus; in particular, type T cells." }, { "input": "What are the eRNA-producing centers (EPCs)?", "output": "Active enhancers in mammals produce enhancer RNAs (eRNAs) that are bidirectionally transcribed, unspliced, and unstable. Enhancer regions are also enriched with long noncoding RNA (lncRNA) transcripts, which are typically spliced and substantially more stable. DNase hypersensitive sites with evidence of bidirectional transcription are called eRNA-producing centers (EPCs). EPCs found very close to transcription start sites of lncRNAs exhibit attributes of both enhancers and promoters, including distinctive DNA motifs and a characteristic chromatin landscape. These EPCs are associated with higher enhancer activity, driven at least in part by the presence of conserved, directional splicing signals that promote lncRNA production, pointing at a causal role of lncRNA processing in enhancer activity." }, { "input": "Describe Brain Radiation Information Data Exchange (BRIDE) approach", "output": "BRIDE (Brain Radiation Information Data Exchange) is a data integration platform that acts as a knowledge broker for LDIR researchers to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics." }, { "input": "When was vivotif first licenced in Europe?", "output": "The vaccine vivotif was first licensed in Europe in 1983." }, { "input": "What is herceptin?", "output": "Herceptin is a second generation tyrosine kinase inhibitor, that serves as an effective and approved oral therapy for patients with HER2-positive breast cancer." }, { "input": "What is herceptin?", "output": "Herceptin is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that binds to HER2 and inhibits HER2 activation. It is approved for the treatment of breast cancer." }, { "input": "What is herceptin?", "output": "Trastuzumab (Herceptin(r) [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer." }, { "input": "What is herceptin?", "output": "trastuzumab is the standard of care for her2-positive breast cancer" }, { "input": "What is herceptin?", "output": "Trastuzumab (Herceptin(r) [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. " }, { "input": "What is herceptin?", "output": "Herceptin is a tyrosine-kinase inhibitor that targets the HER2 receptor oncogene with high affinity and activity. It is approved for treatment of breast cancer." }, { "input": "Has saracatinib been tested in clinical trials?", "output": "Yes, saracatinib has been tested in multiple clinical trials." }, { "input": "What animal is thought to be the host for the Coronavirus causing MERS?", "output": "The animal thought to be the host for the Coronavirus causing MERS is camels." }, { "input": "What animal is thought to be the host for the Coronavirus causing MERS?", "output": "The Virus causing MERS is though to have originated in dromedary camels" }, { "input": "Which molecules are inhibited by Gilteritinib?", "output": "Gilteritinib is a novel, dual FLT3/AXL inhibitor with promising early phase trial data for acute myeloid leukemia." }, { "input": "Is \u03b1CGRP a member of the CGRP family?", "output": "Yes, aCGRP, a 37-residue-long peptide hormone, is a novel amyloidogenic member of the CGRP family." }, { "input": "Is \u03b1CGRP a member of the CGRP family?", "output": "Yes. aCGRP is a member of the CGRP family." }, { "input": "Is \u03b1CGRP a member of the CGRP family?", "output": "Yes, aCGRP is a member of the CGRP family." }, { "input": "Which is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Loss-of-function nuclear factor kB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans." }, { "input": "Which is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of common variable immunodeficiency (CVID), which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells" }, { "input": "Which is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Loss-of-function nuclear factor kB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans." }, { "input": "Which is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of common variable immunodeficiency (CVID), which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells." }, { "input": "Which is the most common monogenic cause of common variable immunodeficiency (CVID) in Europeans?", "output": "Heterozygous loss-of-function nuclear factor kB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells." }, { "input": "List 3 human diseases caused by viruses in the family Paramyxoviridae.", "output": "Measles, mumps and encephalitis are diseases caused by viruses in the family Paramyxoviridae." }, { "input": "List 3 human diseases caused by viruses in the family Paramyxoviridae.", "output": "Viruses in the family Paramyxoviridae can cuase , measles, mumps and encephalitis as well as respiratory illness in humans." }, { "input": "Which disease is caused by de novo VPS4A mutations?", "output": "Mutations in the VPS4A gene, which encodes the alpha-subunit of the lysosomal sorting enzyme, beta-N-acetylhexosaminidase 4, are the cause of multisystem disease type 4 or Ferroportin disease." }, { "input": "Which disease is caused by de novo VPS4A mutations?", "output": "De novo mutations in the gene encoding for endosomal sorting enzyme VPS4A (Val4A) cause multisystem disease" }, { "input": "Which disease is caused by de novo VPS4A mutations?", "output": "De \u03bdovo VPS4A mutations cause multisystem disease with abnormal neurodevelopment." }, { "input": "What is the target of a drug pidilizumab?", "output": "Pidilizumab is a a humanised monoclonal antibody that targets programmed death-1 pathway." }, { "input": "List the proteins defining the triple negative breast cancer.", "output": "The so called \"Triple Negative Breast Cancer\" (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene." }, { "input": "Han Wistar and Sprague Dawley are breeds of what laboratory animal?", "output": "Han-Wistar and Sprague-Dawley rats" }, { "input": "Han Wistar and Sprague Dawley are breeds of what laboratory animal?", "output": "Han Wistar and Sprague Dawley are breeds of Rats" }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor (RHG)." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE. IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins, thus being involved in the pathogenesis of SLE." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "IFIT1 is a newly discovered systemic lupus erythematosus related up-regulated gene. IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "The IFIT1 gene, encoding the syntaxin binding protein 1, is highly expressed in Systemic Lupus Erythematosis (SLE) and its expression is downregulated significantly in cases of SLE. Loss of IFit1 expression is correlated with SLE disease activity and leads to activation of transcriptional mediator Gli2, with consequent inhibition of I\u03baB kinase activity, resulting in dysfunction of myeloid cell growth and transformation to a malignant state.IFIT1 (interferon regulatory factor 1) is an interferon-binding protein that" }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factors." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor (RHC)." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "The IFIT1 gene, originally identified as a telomere-binding factor in yeast, is now recognized to play a critical role in the pathogenesis of Systemic Lupus Erythematosus (SLE) disease. IFit1 overexpression generates an inflammatory response via activation of transcriptional mediator NF-kappaB and leads to activation of the nuclear factor \u03baB signaling pathway, with consequent inhibition of I\u03baB kinase and nuclear factor-\u03baB activation." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor (RH/RAC)." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor . IfIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE . Ifit1 may regulate the activation of Rho and Rac proteins, thus being involved in the pathogenesis of the disease ." }, { "input": "Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) is caused by a protein called interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). IFIT1 is the first gene described as a candidate gene for SLE, and may function activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor." }, { "input": "Has tocilizumab been assessed against Covid-19?", "output": "Preliminary clinical results have indicated that tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile." }, { "input": "Variants in which genes cause nonsyndromic retinal degeneration?", "output": "Variants in DYNC2H1, IFT81, USH2A and ABHD12 can cause nonsyndromic retinal degeneration." }, { "input": "Describe the mechanism of action of Omecamtiv Mecarbil.", "output": "Omecamtiv mecarbil is a novel, selective cardiac myosin activator that has been shown to improve cardiac function and to decrease ventricular volumes, heart rate, and N-terminal pro-B-type natriuretic peptide in patients with heart failure." }, { "input": "List the types of defensins expressed in humans.", "output": "Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express \u03b1- and \u03b2-defensins, which are known for their antiviral and antibacterial activities." }, { "input": "What do HA and NA stand for with respect to the flue virus, e.g. H1N1?", "output": "VaxArray assays for influenza hemagglutinin (HA) and neuraminidase (NA) have been developed to address this need." }, { "input": "What do HA and NA stand for with respect to the flue virus, e.g. H1N1?", "output": "HA and NA stand for hemagglutinin (HA) and neuraminidase (NA), two components of the flue virus genome." }, { "input": "What do HA and NA stand for with respect to the flue virus, e.g. H1N1?", "output": "HA and NA, (sometimes H or N) refer to influenza surface proteins neuraminidase (NA) and hemagglutinin (HA)." }, { "input": "Is the TFR1 gene dispensable for erythropoiesis?", "output": "Yes. The TFR1 gene is a key part of the mechanism by which the body delivers iron to the red blood cells. It is not dispensable for erythropoiesis." }, { "input": "Is the TFR1 gene dispensable for erythropoiesis?", "output": "No, the TFR1 gene, which encodes the triggering receptor encoded in myeloid cells of the erythropoietin receptor 1 (TFR1), is an essential regulator of hematopoietic stem and progenitor cells that is defective in several forms of myeloma." }, { "input": "Is the TFR1 gene dispensable for erythropoiesis?", "output": "No, the TFR1 gene, due to the presence of two promoters (Tf1 and Tf2) in its 5' flanking region, is required for erythropoiesis." }, { "input": "Is the TFR1 gene dispensable for erythropoiesis?", "output": "Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis." }, { "input": "Is the TFR1 gene dispensable for erythropoiesis?", "output": "Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake." }, { "input": "Is the TFR1 gene dispensable for erythropoiesis?", "output": "No, the TFR1 gene, due to the presence of two promoters (TFR1 and TFR2) in its 5' flanking region, is required for erythropoiesis but not for granulocytopenia." }, { "input": "Which are the predominant rotavirus genotypes around the world?", "output": "The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes." }, { "input": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "output": "Multiple TREX mRNA export complex subunits, e.g. THOC1, THOC2, THOC5, THOC6, THOC7, have been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer." }, { "input": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "output": "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in NDD's." }, { "input": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "output": "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have also been implicated." }, { "input": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "output": "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in NDDs." }, { "input": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "output": "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in NDDs and cancer, respectively." }, { "input": "Which TREX mRNA export complex subunits have been implicated in neurodevelopmental disorders?", "output": "THOC1, THOC2 and THOC5 have been implicated in neurodegeneration and cancer. THOC6, THO7 and THO8 have been shown to be implicated in cancer." }, { "input": "What is the use of the Liverpool Elbow Score?", "output": "The Liverpool Elbow Score (LES) is a newly developed, validated elbow-specific score. It has been widely used to assess the outcomes of total elbow replacement in various conditions." }, { "input": "Is Bcl-2-like protein 1 an pro apoptotic protein?", "output": "No,\nit is an anti-apoptotic protein." }, { "input": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "output": "Yes, there is evidence that glucoraphanin from broccoli can help reduce obesity." }, { "input": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "output": "Yes, glucoraphanin from vegetables can help reduce obesity." }, { "input": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "output": "Glucoraphanin: a broccoli sprout extract can ameliorate obesity-induced inflammation and insulin resistance" }, { "input": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "output": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance." }, { "input": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "output": "Yes, Glucoraphanin from vegetables can help reduce obesity." }, { "input": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "output": "Yes, it has been documented that glucoraphanin from broccoli can reduce obesity." }, { "input": "What is the function of the zelda transcription factor in D. melanogaster?", "output": "The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility." }, { "input": "What does tsDMARD stand for?", "output": "tsDMARDs are targeted synthetic disease-modifying antirheumatic drugs." }, { "input": "Which conditions are manifested by TRIM8 mutations?", "output": "TRIM8 mutations are associated with epilepsy, epileptic encephalopathy, developmental delay and intellectual disability." }, { "input": "Which conditions are manifested by TRIM8 mutations?", "output": "Mutations in the TRIM8 gene, which encodes the triggering receptor encoded in myeloid cells 8 (TRIM8) are associated with epilepsy, epileptic encephalopathy, developmental delay and intellectual disability." }, { "input": "Which conditions are manifested by TRIM8 mutations?", "output": "Focal segmental glomerulosclerosis, severe developmental delay, intellectual disability and epilepsy." }, { "input": "Which conditions are manifested by TRIM8 mutations?", "output": "Mutations in TRIM8 gene have been described in patients with severe developmental delay, epileptic encephalopathy, developmental delay and intellectual disability." }, { "input": "What is LY-CoV555?", "output": "LY-CoV555 is an anti-spike neutralizing antibody targeting the SARS-CoV-2 that has been tested for patients with Covid-19." }, { "input": "List blood marker for Non-Hodgkin lymphoma.", "output": "Soluble interleukin-2 receptor-\u03b1, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes.\nGALECTIN-3 AS A PROGNOSTIC BIOMARKER IN PATIENTS WITH NON-HODGKIN LYMPHOMA." }, { "input": "Are bacteria in the genus Clostridium facultative anaerobes?", "output": "Clostridia belong to those bacteria which are considered as obligate anaerobe, e.g. oxygen is harmful or lethal to these bacteria." }, { "input": "Are bacteria in the genus Clostridium facultative anaerobes?", "output": "No, bacteria in the genus Clostridium are obligate anaerobes" }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "No, nematodes do not contain architectural proteins such as CTCF." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "No. Most nematodes do not contain architectural proteins like CTCF." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "No, nematodes do not contain architectural proteins like CTCF." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. \u03a4he insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans." }, { "input": "Do nematodes contain architectural proteins like CTCF?", "output": "No, nematodes contain architectural proteins such as CTCF." }, { "input": "What is the primary indication of tocilizumab?", "output": "Tocilizumab is considered first-line treatment for rheumatoid arthritis." }, { "input": "Describe efforts on Sarcoma from the 100,000 Genomes Project", "output": "The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5\u2009years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. A specialist sarcoma centre recruited close to 1000 patients to the project. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant-calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design." }, { "input": "Describe efforts on Sarcoma from the 100,000 Genomes Project", "output": "The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5\u2009years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. The number of informative genomes produced was reduced further by a PCR amplification step." }, { "input": "What is the goal of the RadRAT calculator?", "output": "Radiation risk assessment tool (RadRAT) can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history. The calculator can be used to estimate lifetime cancer risk from both uniform and non-uniform doses that are acute or chronic. It is most appropriate for low-LET radiation doses < 1 Gy, and for individuals with life-expectancy and cancer rates similar to the general population in the US." }, { "input": "List the deadliest viruses in the world.", "output": "The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are among the deadliest viruses that cause disease in humans, with reported case fatality rates of up to 90% in some outbreaks.\r\nWHO ranks HIV as one of the deadliest diseases.\r\nInfluenza virus" }, { "input": "What monoclonal antibody drugs are used to treat late stage melanoma?", "output": "Nivolumab, ipilimumab, vemurafenib, and dabrafenib are used to treat late stage melanoma" }, { "input": "What monoclonal antibody drugs are used to treat late stage melanoma?", "output": "Dabrafenib, ipilimumab and vemurafenib are monoclonal antibodies that are used to treat late stage melanoma." }, { "input": "What monoclonal antibody drugs are used to treat late stage melanoma?", "output": "Dabrafenib, ipilimumab and vemurafenib are monoclonal antibodies used to treat late-stage melanoma." }, { "input": "What monoclonal antibody drugs are used to treat late stage melanoma?", "output": "Dabrafenib, ipilimumab and vemurafenib are monoclonal antibodies that are used to treat late-stage melanoma." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "The Notch/Hes axis represses a cohort of transcription factor genes . In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which shut off achaete-scute transcription . The molecular details of how Hes and Hey proteins control transcription are still poorly understood ." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "Hes genes encode factors that mediate many of the activities of the Notch pathway. Hes genes are functionally classified into two groups: those that are regulated by Notch and those that are not." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway. HES transcriptional repressors are important components of the Notch pathway that regulates neurogenesis from Drosophila to vertebrates." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which interact with the Groucho protein to shut off achaete-scute transcription." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "HES transcriptional repressors are important components of the Notch pathway that regulates neurogenesis from Drosophila to vertebrates. Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction" }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "The Notch/Hes axis represses a cohort of transcription factor genes . The molecular details of how Hes and Hey proteins control transcription are still poorly understood . In Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES) genes, which act as negative regulators in this process ." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction" }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. Based on these data, we propose a model in which Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts." }, { "input": "Which transcription factor controls Drosophila's Hes genes?", "output": "Mammalian Hes genes encode transcriptional factors that mediate many of the activities of the Notch pathway . Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling . The Notch-Hes1 pathway regulates ovarian somatic cell development, which is necessary for oocyte survival and maturation ." }, { "input": "Is tocilizumab a tumor necrosis factor inhibitor?", "output": "No, tocilizumab, is a non-TNFi DMARD." }, { "input": "Describe manifestations of KIF1A-related disorders in children", "output": "KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. A study identified twelve individuals from 10 families. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent-but sometimes progressive-changes in white matter on MRI. Epilepsy was common among the more severely affected children." }, { "input": "Describe manifestations of KIF1A-related disorders in children", "output": "KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress." }, { "input": "Describe the mechanism of action of pitolisant.", "output": "Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. It is used for treatment of narcolepsy." }, { "input": "What is endoplasmic reticulum stress?", "output": "Endoplasmic reticulum stress,\" an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen, has been implicated in rheumatoid arthritis and other inflammatory and metabolic diseases.\nEndoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative stress, cytoplasmic inclusion body formation, and apoptosis in hepatocytes.\nThe endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases." }, { "input": "What is endoplasmic reticulum stress?", "output": "Endoplasmic reticulum stress is an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen." }, { "input": "What is an operon?", "output": "An operon is a group of genes linked together in a linear fashion and producing polycistronic mRNA." }, { "input": "What is an operon?", "output": "genes are contained in operons, multigene clusters controlled by a single promoter. s. An operon is a group of genes linked together in a linear fashion and producing a polycistronic mRNA." }, { "input": "What is an operon?", "output": "An operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter." }, { "input": "Do circular exons increase gene expression?", "output": "circRNAs might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. They can thus lead to both over- and under-expression of mRNAs." }, { "input": "What does CMB305 contain?", "output": "CMB305 includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A." }, { "input": "What kind of mutations cause GRK1 associated Oguchi disease?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Hutchinson-Gilford disease as well as congenital stationary night blindness in around 90% of patients." }, { "input": "What kind of mutations cause GRK1 associated Oguchi disease?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)." }, { "input": "What kind of mutations cause GRK1 associated Oguchi disease?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare autosomal recessive disorder characterized by congenital stationary night blindness (CSNB)." }, { "input": "What kind of mutations cause GRK1 associated Oguchi disease?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)" }, { "input": "What kind of mutations cause GRK1 associated Oguchi disease?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 cause Oguchi disease. Oguchi disease is a rare subtype of congenital stationary night blindness." }, { "input": "Is MAGE-A3 immunotherapeutic effective for non-small-cell lung cancer?", "output": "No. In a randomized, double-blind, placebo-controlled, phase 3 trial (MAGE-A3-positive non-small-cell lung cancer; MAGRIT), adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected non-small-cell lung cancer. Based on these results, further development of the MAGE-A3 immunotherapeutic for use in non-small-cell lung cancer has been stopped." }, { "input": "Does protein ALEX1 contain armadillo repeats?", "output": "Yes,\nALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains." }, { "input": "What disease is associated with Anticitrullinated peptide antibodies (ACPAs)?", "output": "nticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA)" }, { "input": "What disease is associated with Anticitrullinated peptide antibodies (ACPAs)?", "output": "Anticitrullinated peptide antibodies (ACPAs) are associated with rheumatoid arthritis." }, { "input": "What disease is associated with Anticitrullinated peptide antibodies (ACPAs)?", "output": "Anticitrullinated peptide antibodies (ACPAs) have been shown to be associated with rheumatoid arthritis" }, { "input": "What disease is associated with Anticitrullinated peptide antibodies (ACPAs)?", "output": "The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis." }, { "input": "What disease is associated with Anticitrullinated peptide antibodies (ACPAs)?", "output": "Anticitrullinated protein antibodies are found in patients with rheumatoid arthritis" }, { "input": "What is the function of emergency granulopoiesis?", "output": "ARIH2 encodes TRIAD1, an E3 ubiquitin ligase required for termination of emergency granulopoiesis and leukemia suppressor function in AML . The Interferon Consensus Sequence Binding Protein (Icsbp/Irf8) Is Required for Termination of Emergency GranulopOiesis . Emergency granulopsis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells (HSPCs) upon infection ." }, { "input": "What is the function of emergency granulopoiesis?", "output": "Emergency granulopoiesis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells upon infection . It is widely considered a homoeostatic mechanism for replacing exhausted leukocytes . ARIH2 encodes TRIAD1, an E3 ubiquitin ligase required for termination of emergency granulopsis and leukemia suppressor function in MLL1 ." }, { "input": "What is the function of emergency granulopoiesis?", "output": "During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors . Granulopoiesis is tightly regulated to meet host demands during both \"steady-state\" and \"emergency\" situations, such as infection . It promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance ." }, { "input": "What is the function of emergency granulopoiesis?", "output": "Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Emergency granulopoiesis is a component of the innate immune response that is induced in response to infectious or inflammatory challenge. During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors." }, { "input": "What is the function of emergency granulopoiesis?", "output": "The function of granulopoiesis is to increase the number of neutrophils in the bone marrow to fight an infection. It's not a function, it's a function of the immune system." }, { "input": "What was the predominant rotavirus genotype in the pre-vaccine era, in Australia?", "output": "G1P[8] was the dominant genotype in Australia in the prevaccine era (1995-2006)." }, { "input": "Missense mutations in which genes cause X-linked developmental and epileptic encephalopathy?", "output": "GRIA3 missense mutation is cause of an x-linked developmental and epileptic encephalopathy. Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 also cause an X-linked developmental and epileptic encephalopathy." }, { "input": "Does radiotherapy for cervical cancer increases risk of colon cancer?", "output": "Yes, there is epidemiological evidence to suggest that radiotherapy for cervical cancer increases risk for colon cancer." }, { "input": "List human antibody isotypes.", "output": "IgA\nIgE\nIgG\nIgM\nIgD" }, { "input": "What is CRAO in the context of the eye?", "output": "central retinal artery occlusion (CRAO) is an ophthalmological emergency, the retinal analog of a stroke." }, { "input": "What is CRAO in the context of the eye?", "output": "Central retinal artery occlusion (CRAO) is the most common central retinal artery occlusion." }, { "input": "What is CRAO in the context of the eye?", "output": "CRAO is the abbreviation for central retinal artery occlusion." }, { "input": "What is CRAO in the context of the eye?", "output": "central retinal artery occlusion (CRAO)" }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "The chromatin configuration is altered into an accessible state within 290\u2009bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation . We investigated the mechanisms by which chromatin is reconstituted ." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Histone Chaperone Asf1 is required for the establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression . Chromatin is reconstituted in the fission yeast Schizoaccharombe pombefbp1 gene, which is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions ." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Yes. transcription factors in Saccharomyces cerevisiae fbp1 and fbp2 are involved in the response to glucose starvation stress." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK)" }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Yes. In Saccharomyces cerevisiae, fbp1 expression is affected by glucose starvation and is increased under glucose starvation stress." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "The Schizosaccharomyces pombe fbp1 gene is robustly induced upon glucose starvation but tightly repressed under glucose-rich conditions. The Schizosaccharomyces pombe fbp1 gene encodes fructose-1,6-bisphosphatase." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK)." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Yes. In Saccharomyces cerevisiae, transcriptional responses to glucose starvation are mediated by the F-box protein fbp1. Ace1 mediates glucose-induced gene expression in cells exposed to stressful levels of glucose, whereas fBP1 activates a subset of genes under glucose-free conditions." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Yes. The yeast fbp1 gene, which encodes fructose-1,6,bis-bis-phosphatase, is transcriptionally repressed by the CAMP-dependent protein kinase (PKA) and transcriptionally suppressed by the mitogen-activated Protein Kinase (MAPK). It is not affected by glucose starvation stress, but it is affected by the stress of starvation." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Yes. In Saccharomyces cerevisiae, transcriptional responses to glucose starvation are mediated by two distal enhancer elements, fbp1 and fbp2." }, { "input": "Is yeast fbp1 affected by glucose starvation stress?", "output": "Yes. transcription of yeast fbp1 is increased in response to glucose starvation stress." }, { "input": "What does csDMARD stand for?", "output": "csDMARDS are conventional synthetic disease-modifying antirheumatic drugs." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Scube2 (-/-) caused defective endochondral bone formation and impaired Ihh-mediated chondrocyte differentiation and proliferation as well as osteoblast differentiation of -/- bone-marrow mesenchymal stromal-cell cultures." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation of -/--marrow cells cultures." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Loss-of-function of SCUBE2 causes loss of osteoblast differentiation, bone formation and endochondral bone formation. Loss of the hedgehog signaling pathway plays an important role in skeletal development." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Loss-of-function mutations of SCUBE2 lead to premature differentiation of osteoblast differentiation, bone formation and endochondral bone formation. Down-regulation of hedgehog signaling promotes the formation of osteoblasts, adipogenesis." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation of -/- marrow-marrow." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation of -/--marrow." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Loss-of-function of SCUBE2 causes loss of function, disruption of osteoblast differentiation, bone formation and endochondral bone formation." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation as well as osteoblast differentiation." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Scube2 plays a key regulatory role in IH-dependent endochondral bone formation. It is a key regulator of IH in coordinating skeletogenesis, and the loss of function of SCUBE2 (-/-) caused defective IHH-mediated Ihh-mediated cell differentiation and proliferation." }, { "input": "What is caused by SCUBE2 loss-of-function?", "output": "Loss-of-function mutations of SCUBE2 cause loss of osteoblast differentiation, bone formation and endochondral bone formation. Loss of hedgehog activity leads to premature differentiation of mesenchymal stem cells and induces apoptosis of chondrocyte precursor cells." }, { "input": "Is Semagacestat effective for Alzheimer's Disease?", "output": "No. In a placebo controlled clinical trial, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. The trial was terminated due to unexpected aggravation of cognitive deficits and side effects." }, { "input": "List enzymes that removes histone modifications.", "output": "Histone deacetylases\nLysine Specific Demethylases" }, { "input": "Roughly how many base pairs are in the human mitochondrial genome or mtDNA?", "output": "The mitochondrial genome, mtDNA, is 16569 base pairs." }, { "input": "Roughly how many base pairs are in the human mitochondrial genome or mtDNA?", "output": "The number of base pairs in the human mitochondrial genome (mhl) is currently estimated at 16569." }, { "input": "Do nematodes contain a CTCF gene?", "output": "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans." }, { "input": "Do nematodes contain a CTCF gene?", "output": "Insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans . The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode yeast . Our findings show that C.TCF and possibly chromatin insulation are present in basal nemathews ." }, { "input": "Do nematodes contain a CTCF gene?", "output": "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes." }, { "input": "Do nematodes contain a CTCF gene?", "output": "We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode." }, { "input": "Do nematodes contain a CTCF gene?", "output": "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode." }, { "input": "Is tocilizumab a csDMARD?", "output": "No, tocilizumab is a biological DMARD (bDMARD)." }, { "input": "What is caused by heterozygous lamin B1 and lamin B2 variants?", "output": "Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy." }, { "input": "What is caused by heterozygous lamin B1 and lamin B2 variants?", "output": "Heterozygous lamin B1 and Lamin B2 variants cause primary microcephaly and define a novel laminopathy." }, { "input": "What is caused by heterozygous lamin B1 and lamin B2 variants?", "output": "Microcephaly is a rare autosomal recessive disorder caused by heterozygous lamin B1 and Lamin B2 variants." }, { "input": "What is caused by heterozygous lamin B1 and lamin B2 variants?", "output": "Heterozygous lamin B1 and Lamin B2 variants cause primary microcephaly and define a novel laminopathy" }, { "input": "What is caused by heterozygous lamin B1 and lamin B2 variants?", "output": "Heterozygous lamin B1 and laminB2 variants cause primary microcephaly and define a novel laminopathy." }, { "input": "What is the risk for secondary cancer after proton beam therapy?", "output": "Proton beam therapy is associated with lower risk of secondary cancer when compared to other radiation therapy approaches. It allows excellent dose localization by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. Therefore it is more commonly used in children." }, { "input": "List the essential aminoacids.", "output": "Leucine\r\nIsoleucine\r\nValine \r\nTryptophan\r\nCysteine\r\nMethionine\r\nLysine\r\nPhenylalanine" }, { "input": "What does Retapamulin treat?", "output": "Retapamulin is a small molecule covalently binding and inhibiting the bacterium Staphylococcus aureus (MRSA)." }, { "input": "What does Retapamulin treat?", "output": "Retapamulin is used to treat topical bacterial infections with both methicillin-susceptible and resistant S. aureus and streptococcus infections." }, { "input": "What does Retapamulin treat?", "output": "Retapamulin is an antiviral medication used in the treatment of methicillin-resistant Staphylococcus aureus." }, { "input": "Which histone mark distinguishes active from inactive enhancers?", "output": "Histone H3K27ac separates active from poised enhancers and predicts developmental state . In contrast, elements of the second class 'poised enhancers' are linked to genes inactive in hESCs . They are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation ." }, { "input": "Which histone mark distinguishes active from inactive enhancers?", "output": "Enhancers cause a high level of transcription and activation of chromatin structure at target genes . Individual chromatin marks, such as H3K27ac, have been identified to distinguish active from inactive enhancers . In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H327ac and enrichment of histone H3 lysine 27 trimethylation ." }, { "input": "Which histone mark distinguishes active from inactive enhancers?", "output": "Conversion of inactive enhancers to an active state is marked by accumulation of H3K4me1 and H3K27ac histone marks." }, { "input": "Which histone mark distinguishes active from inactive enhancers?", "output": "Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances . In contrast, elements of the second class 'poised enhancers' are distinguished by the absence of H3K27ac and enrichment of histone H3 lysine 27 trimethylation . They are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation and mesoderm formation ." }, { "input": "Which histone mark distinguishes active from inactive enhancers?", "output": "Monomethylation of histone H3 on Lys 27 (H3K27) is associated with active and inactive enhancers, respectively. An enhancer chromatin state signature associated withactive enhancers may be defined by high levels of H3 K27 acetylation, nucleosome displacement, hypersensitivity to sonication, and strong suppression of enhancer activity by DNase I." }, { "input": "Which histone mark distinguishes active from inactive enhancers?", "output": "We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an \"active enhancer landscape\" and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac." }, { "input": "What does DMARD stand for?", "output": "DMARD stands for disease-modifying antirheumatic drug." }, { "input": "Can SMAD6 variants cause craniosynostosis?", "output": "Yes, SMAD6 variants can cause craniosynostosis." }, { "input": "Can SMAD6 variants cause craniosynostosis?", "output": "Yes. Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure." }, { "input": "What is targeted by Pexidartinib?", "output": "Pexidartinib is a selective tyrosine kinase inhibitor against CSF1R." }, { "input": "What is the microgenderome?", "output": "The sexually dimorphic microbiome has been termed the 'microgenderome'." }, { "input": "What causes yellowing of the skin and eyes, also known as jaundice, in patients with liver failure?", "output": "Jaundice refers to yellow coloration of the skin and the sclera (white of the eyes) of newborn babies that result from the accumulation of bilirubin in the skin and mucous membranes." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Tcf3 is a component of the Wnt/\u03b2-catenin and Notch signaling pathways." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "TCF3, a novel positive regulator of osteogenesis, plays a crucial role in modulating the diverse effect of canonical Wnt signaling. We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "A terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3) co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog . Overexpression of TCF3 (transcription factor 3) attenuated the effect of miR-17 on modulating Wnt signaling ." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It's a family of transcription factors that regulate the growth of cells." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It regulates the growth and differentiation of cells." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is associated with the Wnt pathway." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It's a family of transcription factors that regulate the growth and differentiation of cells." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "A terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog . The noncanonical Wnt signaling pathway, through actions of Tcf3, can antagonize the canonical pathway ." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes. Tcf3 is associated with the Wnt/\u03b2-catenin pathway." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is associated with the WNT pathway. The Wnt pathway is a part of the pluripotency regulator Oct4 and Nanog. It's a family of transcription factors that regulate the growth and differentiation of pluripotent cells." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, TCF3 is a key transcription factor of the canonical Wnt pathway." }, { "input": "Is Tcf3 associated with the Wnt pathway?", "output": "Yes, Tcf3 is involved in the activation of the Wnt pathway." }, { "input": "Have the rotavirus vaccines changed the predominant rotavirus genotypes?", "output": "The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Dysfunction of the ciliary ARMC9/TOGARAM1 protein causes Joubert syndrome." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Joubert syndrome (JBTS) is a recessive neurodevelopmental disorder caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. All known JBTS genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Joubert syndrome is a rare autosomal recessive disorder caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy characterized by a pathognomonic hindbrain malformation." }, { "input": "Which syndrome is caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein?", "output": "Joubert syndrome (JBTS) is a rare autosomal recessive disorder caused by dysfunction of the ciliary ARMC9/TOGARAM1 protein." }, { "input": "Does head ct increase brain tumor risk?", "output": "Yes, there appears to be a small but higher than expected lifetime risk of secondary brain tumors in persons who underwent CT scans during childhood." }, { "input": "Which main viral protein is targeted by the drug remdesivir?", "output": "Viral Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease." }, { "input": "What can be isolated from Pleurotus mutilus?", "output": "Pleuromutilins are antibiotics, isolated from the fungus, Pleurotus mutilus, that selectively inhibit bacterial translation and are semisynthetic derivatives of the naturally occurring tricyclic diterpenoid pleuromutilins." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency. Otx2 and Oct4 drive early activation during embryonic stem cell transition from naive pluripotency." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the mesendoderm-to-neural fate switch by suppressing BMP4 and FGf2." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells. Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the Mesendoderm to Neuron fate switch." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the mesendoderm-to-neural fate switch by suppressing BMP4 and FGf2. The transcription factor OTX2 acts as a negative switch in the regulation of transition from naive to primed pluripotency." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "Otx2 is required to maintain the ESC metastable state by antagonizing ground state pluripotency and promoting commitment to differentiation. Furthermore, Otx2 is required for ESC transition into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4 and Fgf2. Otx2 is a novel intrinsic determinant controlling the functional integrity of ESCs and EpiSCs. Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency." }, { "input": "Which type of pluripotency is Otx2 associated with?", "output": "Otx2 is an intrinsic determinant of the embryonic stem cell state and is required to stabilize the EpiSC state by suppressing the mesendoderm-to-neural fate switch." }, { "input": "Can AGY be used as antidiuretic replacement therapy?", "output": "No, AGY is an oral egg yolk anti-gliadin antibody used to neutralize gluten. It is used in patients with celiac disease." }, { "input": "What is caused by de novo sox6 variants?", "output": "SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. De novo variants of the SOX6 gene have been identified in a large family with a complex phenotype variably associating attention-deficit/hyperactivity disorder (ADHD) with craniosynostosis, hearing impairment, developmental delay and carpal and tarsal fusions." }, { "input": "What is caused by de novo sox6 variants?", "output": "De novo SOX6 variants cause a neurodevelopmental syndrome associated with ADHD, Craniosynostosis, and Osteochondromas." }, { "input": "Can secondary glioblastoma be caused by brain irradiation?", "output": "Yes, brain irradiation can cause secondary glioblastoma." }, { "input": "Is aggrephagy a variant of autophagy?", "output": "Yes,\nthe selective branch of autophagy that deals with identification, capture and degradation of protein aggregates is called aggrephagy." }, { "input": "List the blood group antigens, associated with blood type", "output": "ABO antigens are highly abundant in many human cell types, including platelets, vascular endotheliums, and red blood cells." }, { "input": "List the blood group antigens, associated with blood type", "output": "The blood group antigens, associated with blood type, are: ab, von willebrand factor, o, a, de ritis, rhesus, b, factor viii, rresus d, platelets and abo." }, { "input": "List the blood group antigens, associated with blood type", "output": "ABO antigens are highly abundant in many human cell types, including platelets, vascular endothelium, and red blood cells." }, { "input": "List the blood group antigens, associated with blood type", "output": "The blood group antigens, associated with blood type, are: ab, von willebrand factor, o, a, de ritis, rhesus, b, factor vii, platelets." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "The expression of genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR) Targeted deletion of 5'HS1 and 5\u2019HS4 of the beta-globin locus Control region reveals additive activity of the sites . The LCR is composed of a series of 5 DNase . sites (5'HSs), that form in the nucleus of erythroid precursors ." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals. The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "Mammalian beta-globin loci is composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated . Globin gene expression is regulated by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR) The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals ." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "The expression of genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR) The LCR is composed of a series of 5 DNase . sites (5'HSs), that form in the nucleus of erythroid precursors . In the chromatin of the epsilon globin gene, four DNase. sites that are located 6-18kb 5' of the . epsilon, Ggamma, Agamma, delta, beta ." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "Mammalian beta-globin expression is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, termed 5'HS1-5, located 6-22 Kb upstream of the epsilon-globin gene, each of which is highly homologous among humans, mice, and other mammals." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. Globin gene expression is regulated, in part, by the locus control region, which physically consists of five DNaseI-hypersensitive sites located 6-22 Kb upstream of the epsilon -globin gene." }, { "input": "How many DNaseI hypersensitive sites (DHS) mark the murine beta globin locus region?", "output": "In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18kb 5' of the epsilon globin gene . Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by a linked 15-kilobase region ." }, { "input": "What is the outcome of COVID-19 patients treated with tocilizumab?", "output": "Preliminary clinical results have indicated that tocilizumab can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile." }, { "input": "Which loss-of-function ABCC8 mutation is associated with Pulmonary Arterial Hypertension (PAH)?", "output": "A de novo novel heterozygous predicted deleterious missense variant c.G2873A (p.R958H) in ABCC8 in a child with idiopathic PAH." }, { "input": "Which disease is rated using the Fahn-Tolosa-Marin scale?", "output": "The Fahn-Tolosa-Marin clinical tremor rating scale is used for essential tremor." }, { "input": "List the core SNARE complex proteins.", "output": "VAMP2\nSyntaxin\nSNAP25" }, { "input": "What is septicemia?", "output": "Septicemia occurs when a bacterial infection elsewhere in the body, such as the lungs or skin, enters the bloodstream." }, { "input": "Which is the master oncogenic transcription factor in T-cell acute lymphoblastic leukemia?", "output": "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-Cell Acute lymphoblastic Leukemia (T-ALL) cells." }, { "input": "Which is the master oncogenic transcription factor in T-cell acute lymphoblastic leukemia?", "output": "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells." }, { "input": "Which is the master oncogenic transcription factor in T-cell acute lymphoblastic leukemia?", "output": "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell Acute lymphoblastic Leukemia (T-ALL) cells. It's not the master transcription factor, it's the oncogene." }, { "input": "Which is the master oncogenic transcription factor in T-cell acute lymphoblastic leukemia?", "output": "The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell Acute lymphoblastic Leukemia (T-ALL) cells." }, { "input": "List as many European influenza vaccines as possible.", "output": "Three split-virion vaccines (Vaxigrip, Begrivac, and Influsplit/Fluarix) and three subunit vaccines containing only viral surface glycoproteins (Influvac, Agrippal, and Fluvirin)." }, { "input": "What is canSAR?", "output": "canSAR (http://cansar.icr.ac.uk) is a public integrative cancer-focused knowledgebase for the support of cancer translational research and drug discovery. Through the integration of biological, pharmacological, chemical, structural biology and protein network data, it provides a single information portal to answer complex multidisciplinary questions including--among many others--and what is known about a protein, in which cancers is it expressed or mutated, and what chemical tools and cell line models can be used to experimentally probe its activity." }, { "input": "What is canSAR?", "output": "canSAR (http://cansar.icr.ac.uk) is a freely available, multidisciplinary, cancer-focused knowledgebase developed to support cancer translational research and drug discovery . It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessments ." }, { "input": "What is canSAR?", "output": "canSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowlegebase. canSAR informs researchers to help solve key bottlenecks in cancer translation and drug discovery. It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessments. canSAR is widely used internationally by academia and industry." }, { "input": "What is canSAR?", "output": "CanSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowledgebase. It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessment. canSAR is widely used worldwide by professors, biologists and scientists interested in the molecular biology of cancer, in particular with regard to translation-dependent and -independent pathways of cancer progression." }, { "input": "What is the mechanism of action of magrolimab?", "output": "Magrolimab is an anti-CD47 antibody with promising results for myelodysplastic syndromes and acute myeloid leukemia." }, { "input": "List types of mutations.", "output": "point mutations\ndeletions\ninsertions\ninversions\ntranslocations" }, { "input": "HER-2 belongs to what family of proteins?", "output": "Her-2 belongs to the family of the human epidermal growth factor receptors (EGFRs)." }, { "input": "HER-2 belongs to what family of proteins?", "output": "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER3, HER4, HER5, and HER6." }, { "input": "HER-2 belongs to what family of proteins?", "output": "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, HER6, and HER8." }, { "input": "HER-2 belongs to what family of proteins?", "output": "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, and HER6." }, { "input": "HER-2 belongs to what family of proteins?", "output": "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, HER6, HER7, HER8, and HER9." }, { "input": "HER-2 belongs to what family of proteins?", "output": "HER-2 is also known as human epidermal growth factor receptor 2 and is a member of the Epidermal growth factor receptor (EGFR) family, members of which are: EGFR, HER2, HER3, and HER4." }, { "input": "HER-2 belongs to what family of proteins?", "output": "HER-2 belongs to the human epidermal growth factor receptor family, which is a family of proteins that also includes EGF, EGF1, HER2, HER3, HER4, HER5, HER6, HER7, and HER8." }, { "input": "HER-2 belongs to what family of proteins?", "output": "Her-2 belongs to the human epidermal growth factor receptor 2 (EGF) family of proteins." }, { "input": "HER-2 belongs to what family of proteins?", "output": "Herceptin-2 belongs to the human epidermal growth factor receptor 2 (HER2) family of proteins." }, { "input": "What is the chemical structure of Etanercept (ETN)?", "output": "Etanercept (ETN) is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites, which form a complex with the plasma membrane protein Enbrel. Etanercept has been tested for treatment of solid cancers, including glioblastoma and neuroblastoma, and liver fibrosis." }, { "input": "What is the chemical structure of Etanercept (ETN)?", "output": "Etanercept (ETN) is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites. Etanercept has the ability to bind to TNF-\u03b1 and TGF-\u03b2, and thus is a potential novel therapeutic option for the treatment of cancer." }, { "input": "What is the chemical structure of Etanercept (ETN)?", "output": "Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites." }, { "input": "What is the chemical structure of Etanercept (ETN)?", "output": "Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis. Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains multiple N- and O-glycosylation sites." }, { "input": "What is the chemical structure of Etanercept (ETN)?", "output": "Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis. Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains multiple N- and O-glycosylation sites. Etanercept is a TNF\u03b1 receptor Fc fusion protein used for the treatment of rheumatic disease and psoriasis. Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1." }, { "input": "What is the chemical structure of Etanercept (ETN)?", "output": "Etanercept has the best retention rate in rheumatic diseases, but is less effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis . It possesses three N- and 13 O-glycosylation sites, with multiple N-and-IgG1-N-G sites . It is a fusion protein, composed of the Fc portion of IgG1 and the extracellular domain of the TNF receptor ." }, { "input": "What does bDMARD stand for?", "output": "bDMARDs are biologic disease-modifying antirheumatic drugs." }, { "input": "Is there any role of genotoxic pks + E. coli in cancer?", "output": "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cancer." }, { "input": "Is there any role of genotoxic pks + E. coli in cancer?", "output": "Yes. A distinct mutational signature in colorectal cancer was described which implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island." }, { "input": "Is there any role of genotoxic pks + E. coli in cancer?", "output": "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cell death." }, { "input": "Is there any role of genotoxic pks + E. coli in cancer?", "output": "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cell death and cell death." }, { "input": "Is there any role of genotoxic pks + E. coli in cancer?", "output": "Yes. Genotoxic pks and E. Coli are known to cause mutations in the DNA of cells, which can lead to cell death and cancer." }, { "input": "Should tirilazad be used for treatment of ischemic stroke?", "output": "No. Tirilazad should not be used for treatment of stroke because it does not improve disease outcomes, but may increase death and disability." }, { "input": "List the major families of Histones.", "output": "Five histone families (H1, H2A, H2B, H3, and H4)." }, { "input": "Is the Paramyxovirus geneome segmented, negative-sense RNA?", "output": "The paramyxovirus family has a genome consisting of a SINGLE STRAND of negative sense RNA" }, { "input": "Is the Paramyxovirus geneome segmented, negative-sense RNA?", "output": "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA." }, { "input": "Is the Paramyxovirus geneome segmented, negative-sense RNA?", "output": "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA" }, { "input": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "output": "The total number of genes contained in the X chromosome's non- pseudoautosomal region (PAR) is 783." }, { "input": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "output": "There are 783 non-pseudoautosomal region (PAR) X-chromosome genes." }, { "input": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "output": "Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes harbored loss-of-function mutations more frequently in males." }, { "input": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "output": "There are 783 non-pseudoautosomal region X-chromosome genes harbored loss-of-function mutations more frequently in males." }, { "input": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "output": "The number of genes contained in the X chromosome's non-pseudoautosomal region (non-PAR) is 783." }, { "input": "Approximately how many genes are contained in the X chromosome's non-pseudoautosomal region (non-PAR)?", "output": "The number of genes contained in the non- pseudo-autosomal region (PAR) X chromosome is 783." }, { "input": "Does the use of bDMARDs during pregnancy impact neonatal development?", "output": "Exposure to bDMARDs during pregnancy does not seem to interfere with post-natal development up to infancy." }, { "input": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "output": "No. The KMT2D missense variants do not cause KS1, they cause a different type of malformations disorder distinct from Kabuki syndrome." }, { "input": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "output": "No. The KMT2D missense variants do not cause KS1, they cause a different type of malformations disorder distinct from Kabuki Syndrome." }, { "input": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "output": "No. The KMT2D missense variants do not cause KS1. They cause a multiple malformations disorder distinct from Kabuki syndrome." }, { "input": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "output": "No. The KMT2D missense variants do not cause KS1. They cause a different type of malformations disorder distinct from Kabuki Syndrome." }, { "input": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "output": "No. The KMT2D missense variants do not cause KS1. They cause a multiple malformations disorder distinct from Kabuki Syndrome." }, { "input": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "output": "No. KMT2D missense variants (MVs) located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome type 1 (KS1). Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism." }, { "input": "The NoSAS Score can be used for screening of which disorders?", "output": "The NoSAS score can be used for screening of obstructive sleep apnea syndrome, Sleep-Disordered Breathing and obstructive sleep apnea-hypopnea syndrome." }, { "input": "What is the chromosomal abnormality associated with Klinefelter Syndrome", "output": "About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY" }, { "input": "What is the chromosomal abnormality associated with Klinefelter Syndrome", "output": "About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome)" }, { "input": "What distinguishes RIDLs from other transpozable elements?", "output": "Here, we link these two concepts by proposing that exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs)." }, { "input": "What distinguishes RIDLs from other transpozable elements?", "output": "One class of sequence elements that is enriched in lncRNA is represented by transposable elements (TEs), repetitive mobile genetic sequences that have contributed to genome evolution through a process termed exaptation. We term such elements Repeat insertion domains of LncRNAs (RIDLs)." }, { "input": "What distinguishes RIDLs from other transpozable elements?", "output": "Repeat Insertion Domains of LncRNAs (RIDLs) are exonic TEs that are essential for lncRNA function." }, { "input": "What distinguishes RIDLs from other transpozable elements?", "output": "Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs . A growing number of RIDLs have been experimentally defined, where TE-derived fragments of lncRNA act as RNA-, DNA-, and protein-binding domains . We term such elements Repeat Insertion Domains of LncRNAs (RIDL)" }, { "input": "What distinguishes RIDLs from other transpozable elements?", "output": "Exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs)" }, { "input": "What indication has FTY720 been approved for by the FDA?", "output": "FTY720 has been pproved (September 2010) by the U.S. FDA as a new treatment for multiple sclerosis (MS)." }, { "input": "Is fingolimod a drug or a pro-drug?", "output": "FTY720 is a prodrug." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Mutations in the HFE gene, encoding the syntaxin binding protein HFE1, are the cause of hereditary hemochromatosis." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Hereditary hemochromatosis is an autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage . The vast majority of HH patients are homozygous for the C282Y HFE mutation in HFE . The study was to establish a reliable, cost-effective molecular diagnostic service for this potentially lethal disorder in South Africa . The authors suggest lymphocytes from HH patients may have an increased capacity to respond to DEB-induced chromosome breakage ." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage. The vast majority of HH patients are homozygous for the C282Y mutation in HFE." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Mutations in the HFE gene cause hereditary hemochromatosis, an iron overload disorder that is hallmarked by excessive accumulation of iron in parenchymal organs." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Hereditary hemochromatosis (HH) is common among Caucasians. Hereditary hemochromatosis patients homozygous for the C282Y HFE mutation." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage. The vast majority of HH patients are homozygous for the C282Y mutation in HFE. HFE mutation can possess the risk of AD in transferrin-, APOE- and APP-normal patients." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Mutations in HFE, a gene encoding a putative lysosomal trafficking protein, cause hereditary hemochromatosis." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "The mechanisms by which the hereditary hemochromatosis protein, HFE, decreases transferrin-mediated iron uptake were examined Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "Mutations in HFE, a gene encoding a putative lysosomal trafficking protein, are the cause of hereditary hemochromatosis." }, { "input": "Which conditions is caused by mutations in HFE?", "output": "HFE, a gene encoding a putative lysosomal trafficking protein, is involved in the pathogenesis of hereditary hemochromatosis." }, { "input": "What is the reason for the abundance of operons in the genome of C. elegans?", "output": "Our data shows that transcription proceeds in some ways as if operons were composed of multiple adjacent single genes. Recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of machinery during recovery from growth arrested states." }, { "input": "What is the reason for the abundance of operons in the genome of C. elegans?", "output": "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans . A recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states . Our data suggest operons and \"spliced leader\" trans-splicing predate the radiation of the nematode phylum ." }, { "input": "What is the reason for the abundance of operons in the genome of C. elegans?", "output": "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans, and a recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states. The operons contain primarily genes required for rapid growth, including genes whose products are needed for mitochondrial function and the basic machinery of gene expression. Recent evidence suggests that RNA polymerase is poised at the promoters of growth genes, and operons allow more efficient recovery from growth-arrested states, resulting in reduction in the need for this cache of inactive RNA polymerase." }, { "input": "What is the reason for the abundance of operons in the genome of C. elegans?", "output": "Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans. A recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states. C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do." }, { "input": "What is the reason for the abundance of operons in the genome of C. elegans?", "output": "Our data shows that transcription proceeds in some ways as if operons were composed of multiple adjacent single genes. Previous work has proposed that germline expression drives operon organization in Caenorhabditis elegans, and a recent hypothesis proposes that operons provide an evolutionary advantage via the conservation of transcriptional machinery during recovery from growth arrested states." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The TLR7 locus acts in vivo as a tumor suppressor gene and is located on chromosome X (X chromosome)." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The TLR7 locus acts on the X chromosome in humans and is located on chromosome 9 (XC7)" }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC) The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The X chromosome. TLR7 is encoded on X chromosome Xp22." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC) In this review we will discuss the role of the X chromosome encoded toll-like receptor 7 (TLR7) and interferon gamma (IFN\u03b3) in the development of autoimmunity." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "TLR7 (located on the X chromosome). Since the TLR7 gene is localized on the chromosome X, the allelic frequency of the Gln11Leu polymorphism was analyzed separately in males and females. TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC). The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production. Xp22 harbours the TLR7 and TLR8 genes." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The X chromosome. TLR7 is encoded on X chromosome XP22." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production . The major candidate gene for causation of the Yaa-associated autoimmune phenotypes has been TLR7 . The Toll like receptor 7 gene is encoded by a gene on the X chromosome gene, denoted TLR 7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells ." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "The X chromosome. TLR7 is encoded by a gene on X chromosome Xp22." }, { "input": "Which chromosome contains the TLR7 locus in the human genome?", "output": "TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse. X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR 7-mediated IFN-\u03b1 production of plasmacytoid dendritic cells from women." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "DNaseI hypersensitive sites correspond to regions along genomic regulatory regions where transcription starts and stops." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "Hypersensitive sites are chromosomal regions up to 2kb distant to known genomic regulatory regions and 5 kb from known regulatory regions." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "DNaseI hypersensitive sites correspond to regions of the genome that have recently been isolated as well as specific genomic regulatory regions." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "DNaseI hypersensitive sites are chromosomal regions up to 2kb distant to known genomic regulatory regions and 5 kb from known regulatory regions." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "DNAaseI hypersensitive sites consist of covalent domains that are hypersensitive to DNA polymerase I and are generally found in genomic regulatory regions where transcription starts and stops at these regions." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "Mapping DNaseI hypersensitive sites is commonly used to identify regulatory regions in the genome." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "In genetics, DNase I hypersensitive sites (DHSs) are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it accessible." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "Yes, DNaseI hypersensitive sites have been shown to be markers for all types of active cis-acting regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "DNA hypomethylation and the presence of DNaseI hypersensitive sites correlate with transcriptional activity of P1.1. Mapping sites within the genome that are hypersensitive to digestion withDNaseI is an important method for identifying DNA elements that regulate transcription." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements in regions of open chromatin." }, { "input": "What is marked by DNaseI hypersensitive sites?", "output": "Mapping sites within the genome that are hypersensitive to digestion with DNaseI is an important method for identifying DNA elements that regulate transcription . The identification of cis-regulatory elements is central to understanding gene transcription . Of two promoter-like duplications in each spacer, only the most upstream copy is associated with hypersensitivity to DNAaseI ." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "Yes. The polycomb group proteins (PcG) mediate the formation of chromatin loops by facilitating co-localization of heterochromatin loops." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "Polycomb action at a distance can be organized by local chromatin topology." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response element (PRE) and a distal promoter Polycomb action at a distance can be organized by local chromatin topology" }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "Yes. The polycomb group proteins (PcG) mediate the formation of chromatin loops." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "Yes, polycomb group proteins (PcG) play a critical role in the formation of chromatin loops." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response element (PRE) and a distal promoter Polycomb action at a distance can be organized by local chromatin topology Polycomb repressive complex 2 is recruited through the interaction of CTCF" }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb Response element (Pre) and a distal promoter Polycomb action at a distance can be organized by local chromatin topology Polycomb repressive complex 2 is recruited through the interaction of CTCF." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "Yes, the polycomb group proteins (PcG) play a critical role in the formation and/or maintenance of chromatin loops." }, { "input": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "output": "Yes. Chromatin-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of exons of genes, such as PcG. The polycomb group proteins (PcG) mediate the formation of chromatin loops by binding to nuclear-insoluble structures at late-M-to-early-G1 on histone H3 lysine 27. Depending on what residue is mutated and the degree of transcription, polycomb loop formation is linked to either transcriptionally active or silent chromatin." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "DeSeq2 is a software for differential gene expression analysis of RNA sequencing data." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "Both TMM and DESeq2 are widely used for differential gene expression analysis." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "DeSeq2 performed differential gene expression analysis of paired-end tag sequencing data." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "DeSeq2 supports differential gene expression analysis by combining multiple sources of evidence." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "DeSeq2 enables differential gene expression analysis of multiple cellular origins." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "DesSeq2 is widely used for differential gene expression analysis." }, { "input": "Which type of analysis does DeSeq2 perform?", "output": "DESeq2 is a method for differential analysis of count data. It is used for the calculation of fold change and dispersion of RNA-seq data." }, { "input": "What is the function of a protein degron?", "output": "Protein degrons are part of the DNA damage response triggered by dysfunctional transcription factors. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine residues that targets them to the proteolytic machinery. Disruption of one degron by a RNA-binding protein causes it to become ubiquitinated, dimerizes and translocates to the nucleus." }, { "input": "What is the function of a protein degron?", "output": "A protein degron is a protein that is attached to the N-terminus of a protein of interest. The N-degron then targets itself and the attached protein for rapid proteasomal degradation." }, { "input": "What is the function of a protein degron?", "output": "A N-degron can be attached to the N-terminus of a protein of interest. Upon expression of a site-specific protease, the dormant N-degron becomes deprotected. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through the N-end rule pathway." }, { "input": "What is the function of a protein degron?", "output": "A protein degron is a protein that is attached to the N-terminus of a protein of interest. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through a N-end rule pathway." }, { "input": "What is the function of a protein degron?", "output": "The N-degron protein degradation strategy for investigating the function of essential genes We developed a dormant N-degron that can be attached to the N-terminus of a protein of interest. Upon expression of a site-specific protease, the dormant N-degron becomes deprotected." }, { "input": "What is the function of a protein degron?", "output": "Protein degrons are artificial short peptides which specifically bind to defined functional domains, track, and inhibit a given target molecule with high affinity and specificity. They represent a remarkable alternative to antibodies in many applications." }, { "input": "What is the function of a protein degron?", "output": "A protein degron is a protein that is attached to the N-terminus of a protein of interest. The N-degron then targets itself and the attached protein for rapid proteasomal degradation through a N-end rule pathway. The degradation pathway is a pathway in which proteins are fused to a degron that removes itself in an absence of drug, resulting in an untamable protein." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "The computational methods which are used for the definition of synteny are:1) multisyn, 2) poff, 3) orthocluster, 4) phyldiag, 5) synblast, 6) cinteny, 7) domain team, 8)mcscanx and 9) run Orthoclusterdb and 10) view synteny." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "Computational methods used for the definition of synteny include multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainmanagement, domainweekly, domainScanx, run orthocluster, orthClusterdb and view synteny." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "Computational methods used for the definition of synteny include multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainmanagement, domainScanx, run orthoclustereddb, view synteny and others." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "The automated and fast detection of syntenic domain teams is implemented in the DomainTeam software. Here we present the SynBlast pipeline that is designed to construct and evaluate local synteny information. Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances. OrthoClusterDB is a new online platform for the identification and visualization of synteny blocks. OrthoClusterDB consists of two key web pages: Run OrthoCluster and View Synteny. MCScan is an algorithm able to scan multiple genomes or subgenomes in order to identify putative homologous chromosomal regions, and align these regions using genes as anchors. PoFF is an extension for the standalone tool Proteinortho, which enhances orthology detection by combining clustering, sequence similarity, and synteny. MultiSyn: A Webtool for Multiple Synteny Detection and Visualization of User's Sequence of Interest Compared to Public Plant Species." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection. Here we present the SynBlast pipeline that is designed to construct and evaluate local synteny information. PoFF is an extension for the standalone tool Proteinortho, which enhances orthology detection by combining clustering, sequence similarity, and synteny." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "Computational methods used for the definition of synteny include multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainmanagement, electrophobicity, run orthoclustereddb, mcScan and view synteny." }, { "input": "Which computational methods are used for the definition of synteny?", "output": "The computational methods that are used for the definition of synteny are: multisyn, poff, orthocluster, phyldiag, synblast, cinteny, domainteam, mcscanx and run orthoclustersdb." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Single-cell ATAC-seq detects open chromatin in individual cells." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Yes. When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Single-cell ATAC-seq: strength in numbers. When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Yes. The method can be also employed in single-cell mode, allowing the analysis of cell-based epigenetic changes only." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Yes, ATAC-seq can be employed in single-cell mode." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Yes, single-cell ATAC-seq can be used to detect genome-wide the binding sites of RNA binding proteins in individual cells." }, { "input": "Can ATAC-Seq be employed in single-cell mode?", "output": "Yes. ATAC-seq can be used as a primary method for analyzing genome-wide open chromatin structure within single-cell populations." }, { "input": "How can B-cells transdifferentiate into macrophages?", "output": "Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis . Vascular endothelial growth factor modified macrophage transdifferentiates into endothelial-like cells and decrease foam cell formation . Human cancer cells can be induced by C/EBP\u03b1 to transdifferentiated into seemingly normal cells at high frequencies ." }, { "input": "How can B-cells transdifferentiate into macrophages?", "output": "Through the ectopic over-expression of the CCAAT/enhancer binding protein-\u03b1 (C/EBP\u03b1), which induces transdifferentiation of B cells into macrophages at high efficiencies." }, { "input": "How can B-cells transdifferentiate into macrophages?", "output": "C/EBP\u03b2-expressing B cells produced granulocyte-macrophage progenitor progenitors when subjected to selective pressure to eliminate lymphoid cells . The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells . Tet2 helps CEBP\u03b1 rapidly derepress myeloid genes during conversion of pre-B cells ." }, { "input": "How can B-cells transdifferentiate into macrophages?", "output": "C/EBP\u03b2-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells. Tet2 helps CEBP\u03b1 rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages." }, { "input": "How can B-cells transdifferentiate into macrophages?", "output": "Human cancer cells can be induced by C/EBP\u03b1 to transdifferentiate into seemingly normal cells at high frequencies . This provides a proof of principle for a potential new therapeutic strategy for treating B cell malignancies . Inflammatory macrophages\u00a0transdifferentiate\u00a0into myofibroblasts\u00a0during renal fibrosis ." }, { "input": "What is the function of the chromHMM software?", "output": "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark . It uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment . Chromatin states are learned, annotations are produced, and enrichments are computed within 1 d ." }, { "input": "What is the function of the chromHMM software?", "output": "The ChromHMM software is a tool for learning chromatin-state signatures. It allows you to learn chromatin states, and then use that knowledge to make an annotated chromatin state for each cell type." }, { "input": "What is the function of the chromHMM software?", "output": "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark. ChromHMM uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment. ChromHMM helps to annotate the noncoding genome using epigenomic information across one or multiple cell types. It combines multiple genome-wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer a complete annotation for each cell type" }, { "input": "What is the function of the chromHMM software?", "output": "ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark. It uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment." }, { "input": "What is the function of the chromHMM software?", "output": "The ChromHMM software is a tool for learning chromatin-state signatures. It allows you to learn chromatin states, and then use that knowledge to make an annotated chromatin state for a cell type." }, { "input": "What is FeatureCounts used for?", "output": "featureCounts is a general purpose program for assigning sequence reads to genomic features. It is a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments." }, { "input": "What is FeatureCounts used for?", "output": "featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments" }, { "input": "What is FeatureCounts used for?", "output": "featureCounts can be used to quantify reads generated from either RNA or DNA sequencing technologies in terms of any type of genomic feature. It implements chromosome hashing, feature blocking and other strategies to assign reads to features with high efficiency." }, { "input": "What is FeatureCounts used for?", "output": "Featurecounts is a system that uses a novel Bayesian approach to calculate informative metrics at each depth required to inform a broad range of functional and evolutionary studies. The database is optimized to support fast interactive performance with the RNA-Seq platform." }, { "input": "What is FeatureCounts used for?", "output": "featureCounts: an efficient general purpose program for assigning sequence reads to genomic features." }, { "input": "What is FeatureCounts used for?", "output": "We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments." }, { "input": "Which is the main difference in the roles of Otx2 and Nanog during development?", "output": "Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition . The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells . OTX2-mediated Nanog regulation contributes to the integrity of the ESC state and cell lineage specification in preimplantation development ." }, { "input": "Which is the main difference in the roles of Otx2 and Nanog during development?", "output": "There is a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. Through mutual antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs and individually predispose them for optimal response to naive or primed inducing factors. More specifically OTX2 impedes self-renewal of iPS cells through downregulation of NANOG expression." }, { "input": "Are super enhancers structurally insulated in chromatin loops?", "output": "Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements. CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target." }, { "input": "Are super enhancers structurally insulated in chromatin loops?", "output": "Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements." }, { "input": "Are super enhancers structurally insulated in chromatin loops?", "output": "Dissecting super-enhancer hierarchy based on chromatin interactions Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements." }, { "input": "Are super enhancers structurally insulated in chromatin loops?", "output": "We also demonstrate that the Wap super-enhancer, which is built on STAT5 and other common transcription factors, retains its exquisite mammary specificity when placed into globally permissive chromatin, suggesting a limited role of chromatin in controlling cell specificity. CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target." }, { "input": "Does IL18 signaling have a role in thymus?", "output": "Yes. IL18 signaling promotes homing of mature Tregs into the thymus." }, { "input": "Does IL18 signaling have a role in thymus?", "output": "Yes. IL18 signaling plays a key role in thymus regulation and differentiation." }, { "input": "Does IL18 signaling have a role in thymus?", "output": "Yes. IL18 signaling plays a key role in the regulation of thymus function." }, { "input": "Does IL18 signaling have a role in thymus?", "output": "Yes. IL18 signaling plays a crucial role in thymus regulation and differentiation." }, { "input": "Does an antiphlogistic promotes inflammation?", "output": "Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity." }, { "input": "Does an antiphlogistic promotes inflammation?", "output": "An antiphlogistic drug counteracts inflammation" }, { "input": "Which interleukin receptors are targeted with rilonacept?", "output": "Rilonacept inhibits interleukin-1\u03b1 and interleukin-1\u03b2. It has a role for treatment of pericarditis." }, { "input": "Which deep learning framework has been developed for cancer molecular subtype classification?", "output": "Molecular subtyping of cancer is a critical step towards more individualized therapy and provides important biological insights into cancer heterogeneity. Although gene expression signature-based classification has been widely demonstrated to be an effective approach in the last decade, the widespread implementation has long been limited by platform differences, batch effects, and the difficulty to classify individual patient samples. DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. It is platform independent, robust to missing data, and can be used for single sample prediction facilitating clinical implementation of cancer molecular subtyping." }, { "input": "Which deep learning framework has been developed for cancer molecular subtype classification?", "output": "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. It is based on deep learning of functional spectra quantifying activities of biological pathways. In two case studies about colorectal and breast cancer classification, DeepCC classifiers and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy." }, { "input": "Which deep learning framework has been developed for cancer molecular subtype classification?", "output": "The DeepCC framework is a novel deep learning-based framework for cancer molecular subtype classification." }, { "input": "Which deep learning framework has been developed for cancer molecular subtype classification?", "output": "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification." }, { "input": "Which deep learning framework has been developed for cancer molecular subtype classification?", "output": "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. In two case studies about colorectal and breast cancer classification, DeepCC classifier and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy compared with other widely used classification methods such as random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), and multinomial logistic regression algorithms." }, { "input": "Which deep learning framework has been developed for cancer molecular subtype classification?", "output": "DeepCC is a novel deep learning-based framework for cancer molecular subtype classification. DeepCC is platform independent, robust to missing data, and can be used for single sample prediction." }, { "input": "What class of drugs have been given a black box warning for suicide?", "output": "In 2004, the European and American authorities released a black-box warning on antidepressants indicating an association with an increased risk of suicidality (suicidal ideation and behavior) in young people" }, { "input": "What class of drugs have been given a black box warning for suicide?", "output": "In 2004, the US Food and Drug Administration (FDA) controversially issued a black box warning that antidepressants were associated with an increased risk of suicidal thoughts and behaviours in people aged under 18 years." }, { "input": "What class of drugs have been given a black box warning for suicide?", "output": "The U.S Food and Drug Administration issued a Black box warning in October 2004 after placebo-controlled trials of antidepressant medications found an increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications relative to placebo." }, { "input": "What nerve is affected in Carpel Tunnel syndrome?", "output": "Carpel tunnel syndrome (CTS) is a condition in which median nerve compression results in paresthesias and pain in the wrist and hand." }, { "input": "What nerve is affected in Carpel Tunnel syndrome?", "output": "Carpel tunnel syndrome is a common compression neuropathy of the median nerve causing pain, numbness and functional dysfunction of the hand." }, { "input": "What nerve is affected in Carpel Tunnel syndrome?", "output": "Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel." }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an oral interleukin-1 receptor antagonist that is used to treat rheumatoid arthritis." }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an anti-IL-1RA targeting IL-1beta with a central role in the occurrence of auto-inflammatory diseases." }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that binds to and inactivates the interleukin-1 receptor (IL1R) signaling pathway and is used to treat rheumatoid arthritis" }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases." }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an orally administered interleukin-1 receptor antagonist that is used to treat rheumatoid arthritis." }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases like rheumatoid arthritis." }, { "input": "What drug, used to treat rheumatoid arthritis, is an interleukin-1 receptor antagonist?", "output": "Anakinra is an anti-IL-1RA targeting IL-1\u03b2 with a central role in the occurrence of auto-inflammatory diseases" }, { "input": "Herpes viruses have what type of genome?", "output": "The Herpesviridae are a family of viruses which have a large genome of linear, double-stranded DNA (> 120 kb)" }, { "input": "Herpes viruses have what type of genome?", "output": "The genome of Herpes viruses is composed of linear, double-stranded DNA." }, { "input": "Herpes viruses have what type of genome?", "output": "Herpes simplex virus 1 (HSV-1) and HSV-2 are nuclear-replicating viruses composed of a double-stranded DNA genome" }, { "input": "Herpes viruses have what type of genome?", "output": "Herpes simplex virus 1 (HSV-1) has a double-stranded linear DNA genome that is approximately 152 kbp in length." }, { "input": "Herpes viruses have what type of genome?", "output": "Herpesviridae are a family of viruses which have a large genome of linear, double-stranded DNA." }, { "input": "Herpes viruses have what type of genome?", "output": "Herpes viruses have a linear, double-stranded DNA genome." }, { "input": "Is liraglutide effective for weight reduction?", "output": "Yes, liraglutide is effective and approved for weight reduction." }, { "input": "Is lorcaserin associated with increased cancer risk?", "output": "The US Food and Drug Administration (FDA) reported an increased risk of cancer with lorcaserin in the follow-up of the CAMELLIA-TIMI 61 trial. However, subsequent meta-analysis did not confirm the increased risk of cancer with lorcaserin but suggests a trend in this direction, with a greater incidence of some subtypes such as lung and pancreas." }, { "input": "Is Eflornithine and Sulindac are effective for prevention of progression in Familial Adenomatous Polyposis?", "output": "No. In a clinical trial, the incidence of progression in Familial Adenomatous Polyposis was not significantly lower with the combination of eflornithine and sulindac than with either drug alone." }, { "input": "Which cancer can be treated with Darolutamide?", "output": "Darolutamide is used for treatment of nonmetastatic castration-resistant prostate cancer." }, { "input": "Which cancers can be treated with Selpercatinib?", "output": "Selpercatinib was recently approved by the US FDA for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer." }, { "input": "What is the target of Volanesorsen?", "output": "Volanesorsen is a second-generation antisense oligonucleotide inhibiting apoC-III (apolipoprotein C-III) transcription/translation that has been recently approved in Europe for Familial Chylomicronemia Syndrome (FCS) treatment." }, { "input": "Roflumilast Cream is effective for which disease?", "output": "Roflumilast Cream has been shown to be effective for psoriasis." }, { "input": "Describe the mechanism of action of Givosiran.", "output": "Givosiran is an aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA (siRNA) covalently linked to a ligand to enable specific delivery of the siRNA to hepatocytes. This results in downregulation of ALAS1 mRNA and prevents accumulation of neurotoxic \u03b4-aminolevulinic acid and porphobilinogen levels that are associated with acute porphyria attacks." }, { "input": "Is Olaparib effective for prostate cancer?", "output": "Yes, olaparib was shown to be effective for treatment of prostate cancer. Olaparib led to stable disease or tumor regressions of prostate cancer patients." }, { "input": "Is Olaparib effective for prostate cancer?", "output": "Yes. Olaparib has antitumour activity against metastatic castration-resistant prostate cancer with DDR gene aberrations." }, { "input": "Is Olaparib effective for prostate cancer?", "output": "Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate." }, { "input": "What is Corkscrew Esophagus?", "output": "Corkscrew esophagus is a classic finding of diffuse esophageal spasm in barium studies reflecting abnormal contractions, leading to compartmentalization and curling of the esophagus, ultimately giving an appearance similar to a corkscrew or rosary beads." }, { "input": "List 3 conventional synthetic DMARDs.", "output": "Three conventional synthetic (cs) DMARDs include methotrexate (MTX), leflunomide, and sulfasalazine." }, { "input": "Is isradipine effective for Parkinson's disease?", "output": "No. Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage Parkinson's disease." }, { "input": "Is MK-1602 a CGRP antagonist?", "output": "Yes, MK-1602 is a CGRP antagonist." }, { "input": "Which company developed eptinezumab?", "output": "Eptinezumab was developed by Lundbeck Seattle BioPharmaceuticals." }, { "input": "What are the features of the AESOP syndrome?", "output": "Adenopathy and Extensive Skin Patch Overlying a Plasmacytoma is defined as the AESOP Syndrome." }, { "input": "Which drugs are included in the VIFUP regimen for breast cancer?", "output": "ViFuP includes vinorelbine, cisplatin and continuous infusion of 5-fluorouracil." }, { "input": "Which drugs are included in the EE-4A regimen for Wilm's tumor?", "output": "EE-4A regimen includes dactinomycin and vincristine." }, { "input": "Does inactivation of CYLD help in colorectal cancer?", "output": "\u039d\u03bf. Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis." }, { "input": "Which network analysis method can you use for prioritization of metabolic disease genes?", "output": "metPropagate is a network-guided propagation of metabolomic information for prioritization of metabolic disease genes. metPropagate was able to prioritize at least one causative gene in the top 20th percentile of candidate genes for 92% of patients with known IEMs." }, { "input": "Which network analysis method can you use for prioritization of metabolic disease genes?", "output": "Many inborn errors of metabolism (IEMs) are amenable to treatment, therefore early diagnosis is imperative. Whole-exome sequencing (WES) variant prioritization coupled with phenotype-guided clinical and bioinformatics expertise is typically used to identify disease-causing variants; however, it can be challenging to identify the causal candidate gene when a large number of rare and potentially pathogenic variants are detected. MetPropagate is a network-based approach that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs." }, { "input": "Which network analysis method can you use for prioritization of metabolic disease genes?", "output": "MetPropagate is a network-guided propagation of metabolomic information for prioritization of metabolic disease genes. Basically, you take a single patient and a group of controls, and compare their metabolomic data to the data of other patients with IEMs. If you find a gene that is in the top 20% of the population, you rank it higher in the network. If not, you don't rank it at all." }, { "input": "Which network analysis method can you use for prioritization of metabolic disease genes?", "output": "Met Propagate is a network-based approach that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs." }, { "input": "Which network analysis method can you use for prioritization of metabolic disease genes?", "output": "MetPropagate is a network-guided propagation of metabolomic information for prioritization of metabolic disease genes. Basically, you take a single patient and a group of controls, and compare their metabolomic data to the data of other patients with IEMs. If you find a gene that is in the top 20% of the population, you rank it higher than the other genes in the population. If not, you don't." }, { "input": "Which drugs are included in the IROX regimen for colorectal cancer?", "output": "IROX regimen for colorectal cancer includes irinotecan and oxaliplatin." }, { "input": "What are the targets of pemigatinib?", "output": "Pemigatinib is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) 1, FGFR2 and FGFR3, received accelerated approval for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma and a FGFR2 fusion or other rearrangement, as detected by a US FDA-approved test." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. There are high levels of nucleotide diversity in this species and research suggests that the recent invasions of Europe and the continental United States are independent demographic events." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Yes, there is high nucleotide diversity in the Drosophila suzukii species. There is a lot of genetic diversity in this species, and it is thought that the recent expansion of the species into Europe and the continental United States are independent demographic events. This means that there is a high level of diversity within the species." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Yes, there is high nucleotide diversity in the Drosophila suzukii species. There is a lot of genetic diversity in this species, and it is thought that the recent expansion of the species into Europe and the Americas are independent demographic events." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Yes. There is high nucleotide diversity within the Drosophila suzukii species." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Yes. There is high nucleotide diversity within and between populations of Drosophila suzukii, as shown by the presence of 12.1% single-nucleotide variants and 43.6% double-stranded DNA." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Yes. There is high nucleotide diversity within and between populations of Drosophila suzukii, across all developmental stages examined from only one genome." }, { "input": "Is there high nucleotide diversity in the Drosophila suzukii species?", "output": "Yes. There is high nucleotide diversity within and between populations of Drosophila suzukii, manifesting both in gene expression patterns and genomic locations." }, { "input": "Which tools have been developed for identifying and visualising ncRNA promoters?", "output": "Epd, ncpro-ml and ucsc genome browser are tools that have been developed for identifying and visualising ncRNA promoters." }, { "input": "Which tools have been developed for identifying and visualising ncRNA promoters?", "output": "The Eukaryotic Promoter Database (EPD) and ncPro-ML" }, { "input": "What is the mode of administration of AZD8601?", "output": "AZD8601 is administered intradermally." }, { "input": "What is SAR425899?", "output": "SAR425899 ia a dual glucagon-like peptide-1 receptor/glucagon receptor agonist." }, { "input": "Which class of disorders are caused by AMPA receptor GluA2 subunit defects?", "output": "Mutations in the AMPA receptor GluA2 subunit cause a variety of neurodevelopmental disorders including autism spectrum disorder." }, { "input": "Which class of disorders are caused by AMPA receptor GluA2 subunit defects?", "output": "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Mutations lead to a decrease in agonist-evoked current mediated by mutant subunits." }, { "input": "Which class of disorders are caused by AMPA receptor GluA2 subunit defects?", "output": "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes." }, { "input": "Which class of disorders are caused by AMPA receptor GluA2 subunit defects?", "output": "AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. De-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission." }, { "input": "Which class of disorders are caused by AMPA receptor GluA2 subunit defects?", "output": "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders." }, { "input": "Is Hunter's disease is associated with the X Chromosome?", "output": "Yes, Hunter's disease is associated with the X Chromosome." }, { "input": "Is Hunter's disease is associated with the X Chromosome?", "output": "Yes, the X Chromosome is associated with the X chromosome." }, { "input": "Is Hunter's disease is associated with the X Chromosome?", "output": "Hunter's disease is associated with the X chromosome." }, { "input": "Where are integrins localized in a cell?", "output": "Integrins are transmembrane glycoproteins that are broadly distributed in living organisms." }, { "input": "What is a bacteriocin?", "output": "Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives.\nOne such strategy involves using narrow-spectrum protein antibiotics (so-called bacteriocins), which diverse bacteria use to compete against closely related species." }, { "input": "What protein complex is altered in \"Coffin-Siris syndrome\"?", "output": "he genes causative of CSS mainly encode the SWI/SNF complex, which contributes to chromatin remodeling and regulates the access of transcriptional factors to specific gene sites." }, { "input": "What protein complex is altered in \"Coffin-Siris syndrome\"?", "output": "Report. Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome. Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome." }, { "input": "What is Aortitis?", "output": "Aortitis is the inflammation of the aorta due to various causes, such as the manifestation of an underlying infectious or noninfectious disease process." }, { "input": "What is Aortitis?", "output": "Aortitis is an inflammation of the aorta due to various causes. It can be a symptom of an underlying infectious or non-infectious disease process." }, { "input": "What is Aortitis?", "output": "Aortitis is inflammation of the aorta due to various causes. It can be caused by an underlying infectious or non-infectious disease process." }, { "input": "What is Aortitis?", "output": "Aortitis is the inflammation of the aorta due to various causes. Aortitis is classified as non-infectious or infectious." }, { "input": "What is Aortitis?", "output": "Aortitis includes conditions with infectious or non-infectious etiology, characterized by inflammatory changes in one or more layers in aortic wall." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "The syndromes that are part of Castleman's disease AKA TAFRO are:1) organomegaly, 2) anasarca, 3) myelofibrosis, 4) thrombocytopenia and 5) reticulin fibrosis." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "TAFRO (or Castleman-Kojima) syndrome has been gradually recognized in recent years. It is a systemic inflammatory disease characterized by thrombocytopenia (T), anasarca (A), myelofibrosis/fever (F), renal dysfunction/reticulin fibrosis (R), and organomegaly (O)." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "TAFRO syndrome is defined as CD with thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "The syndromes that are part of Castleman's disease AKA TAFRO are organomegaly, anasarca, myelofibrosis, thrombocytopenia, reticulin fibrosis and renal dysfunction." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "The syndromes that are part of Castleman's disease AKA TAFRO are organomegaly, anasarca, myelofibrosis, thrombocytopenia and reticulin fibrosis. There is also renal dysfunction." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly)." }, { "input": "Please list the syndromes that are part of Castleman's disease AKA TAFRO", "output": "TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) is an atypical manifestation of multicentric Castleman's disease." }, { "input": "What is known about the protein Curli?", "output": "A major component of bacterial biofilms is curli amyloid fibrils secreted by the curli biogenesis system.\nCurli is a bacterial \u03b1-synuclein (\u03b1Syn) which is deposited first in the enteric nervous system and amyloid deposits are propagated in a prion like manner to the central nervous system.\ncurli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid \u03b1-synuclein (\u03b1Syn), we reveal that colonization with curli-producing Escherichia coli promotes \u03b1Syn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate \u03b1Syn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate \u03b1Syn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities." }, { "input": "List the core lung matrisome proteins.", "output": "LGALS7, \nASPN, \nHSP90AA1, \nHSP90AB1,\nCOL1A1, \nSCGB1A1, \nTAGLN, \nPSEN2, \nTSPAN1, \nCTSB, \nAGR2, \nCSPG2,\nSERPINB3,\nfibronectin,\nemilin-1,\nversican,\ndecorin" }, { "input": "Can Freund's complete adjuvant induce arthritis?", "output": "Yes, Rheumatoid arthritis (RA) was induced by Freund's Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil), injected subcutaneously on days 0, 30 and 40" }, { "input": "Can saponins be used as adjuvant?", "output": "Yes,\nsaponin is an ideal adjuvant candidate." }, { "input": "Is erabutoxin b usually found in plants?", "output": "Erabutoxin b is a short-chain neurotoxic peptide purified from the venom of the sea snake Laticauda semifasciata." }, { "input": "Is erabutoxin b usually found in plants?", "output": "No, erabutoxin b is not found in plants, it is a transmembrane toxin" }, { "input": "Are Toll-like receptors (TLRs) induced by microbes?", "output": "Yes,\nGram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-\u03b1 and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1\u03b2 into its mature form." }, { "input": "What is a decoy exosome?", "output": "exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity." }, { "input": "Can you summarize Myasthenia Gravis?", "output": "Myasthenia gravis (MG) is a neuromuscular disease which affects the central nervous system, dorsal root ganglia of the spinal cord, heart and in certain cases the pancreas. Two thirds of MG cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them." }, { "input": "Can you summarize Myasthenia Gravis?", "output": "Myasthenia gravis (MG) is a neuromuscular disease resulting from a disorder of the central nervous system. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. MG can be symptomatic of focal cortical malformation, in which there is intraepithelial (usually intraepidermal) infiltration by neoplastic cells showing glandular differentiation. Clinical symptoms occur first after an age of approximately 30\u00a0years. Main manifestations include cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral" }, { "input": "Can you summarize Myasthenia Gravis?", "output": "Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles. The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction, the nicotinic acetylcholine receptor." }, { "input": "Can you summarize Myasthenia Gravis?", "output": "Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles. The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction, the nicotinic acetylcholine receptor. Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse." }, { "input": "Can you summarize Myasthenia Gravis?", "output": "Myasthenia gravis (MG) is a neuromuscular disease resulting from a disorder of the extrapyramidal system. Pathogenesis is still unknown and temporal lobe has been thought to take part in the pathogenesis. MG can be symptomatic of focal cortical malformation, and few cases were reported. Clinical symptoms occur first after an age of approximately 30\u00a0years. Main manifestations include central nervous system (CNS) and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeoch" }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "McKusick-Kaufman syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children. It is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect." }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "Clinical symptoms of Kaufman-McKusick syndrome (KM) include postaxial polydactyly, hydrometrocolpos, and congenital heart disease." }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "Mekusick-Kusick syndrome is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease." }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "McKusick-Kaufman Syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children. It is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect." }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "MKKS) is one of rare syndromes which presents as polydactyly, hydrometrocolpos (HMC) and cardiac anomalies." }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "McKusick-Kaufman syndrome (MKKS) is a rare, recessively inherited syndrome reported mainly in young children and is characterised by vaginal atresia with hydrometrocolpos, postaxial polydactyly, and congenital heart defect." }, { "input": "What 3 disorders are commonly associated with Kaufman-McKusick syndrome?", "output": "The Kaufman-McKusick syndrome (MK 23670) AKA McKusik-Kaufman syndrome, is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease" }, { "input": "Is Ixodes a species of tick?", "output": "Ixodes is a family of hard ticks." }, { "input": "Is Ixodes a species of tick?", "output": "tick, Ixodes ricinus" }, { "input": "Is Ixodes a species of tick?", "output": "Yes, Ixodes is a species of tick." }, { "input": "Is Ixodes a species of tick?", "output": "ixodid ticks hard ticks (family Ixodidae)" }, { "input": "What is the active ingredient in the most common hand sanitizer?", "output": "Evaluation of a benzalkonium chloride hand sanitizer in reducing transient Staphylococcus aureus bacterial skin contamination in health care workers." }, { "input": "What is the active ingredient in the most common hand sanitizer?", "output": "The active ingredient in the most common hand sanitizer is ethanol, benzalkonium chloride, isopropanol, alcohol, bzk, 70% ethanol." }, { "input": "What is the active ingredient in the most common hand sanitizer?", "output": "The active ingredients in most hand sanitizers include ethanol, benzalkonium chloride, isopropanol, alcohol, bzk, 70% ethanol and soap." }, { "input": "What is the active ingredient in the most common hand sanitizer?", "output": "The active ingredient is isopropyl alcohol, which is an alcohol-based hand sanitizer." }, { "input": "What is the active ingredient in the most common hand sanitizer?", "output": "While there is a new commercially available hand sanitizer using 0.12% benzalkonium chloride (BZK) as the active ingredient in hand sanitizer, most hand sanitizers are 70-80% ethanol-based or 75% isopropanol" }, { "input": "Which was the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA)?", "output": "FTY720 (Fingolimod) was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010." }, { "input": "Which S1P receptors does fingolimod bind to?", "output": "Pharmacologically, fingolimod has been characterized as a non-selective agonist of all of the S1P receptors (S1PR), with the exception of S1P2." }, { "input": "What was fingolimod synthesized from?", "output": "FTY720 (fingolimod, Gilenya\u00ae) was synthesized from myriocin, one of the metabolites of the fungus Isaria sinclairii known from traditional Chinese medicine for its antibacterial and energy boosting effect." }, { "input": "What does fingolimod do to the grey matter of the brain?", "output": "Fingolimod has been shown to reduce/prevent both focal and diffuse grey matter (GM) damage in active multiple sclerosis. The percentage of patients with new cortical lesions (CL) (13.5 vs. 89%, p\u2009<\u20090.001) and the percentage of GM volume change was lower in the fingolimod treated group (p\u2009<\u20090.001). The regional analysis revealed that the treated group had also less volume loss in thalamus, caudatus, globus pallidus, cingulate cortex, and hippocampus (p\u2009<\u20090.001), as well as in, cerebellum, superior frontal gyrus, and insular-long gyrus (p\u2009<\u20090.05)." }, { "input": "What doses of fingolimod were administered during the FREEDOMS trial?", "output": "In the FREEDOMS trial fingolimod was administered at 0.5mg or 1.25mg doses." }, { "input": "How many patients were enrolled in the FREEDOMS clinical trial?", "output": "FREEDOMS study, a randomised, double-blind study included 1272 patients with relapsing-remitting MS." }, { "input": "What is blepharospasm?", "output": "The neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood." }, { "input": "What is blepharospasm?", "output": "Yes, blepharospasm is an adult-onset dystonia typically present at rest and exacerbated by bright light, stress and voluntary movements of eyes and eyelids." }, { "input": "What is blepharospasm?", "output": "Blepharospasm is a type of focal dystonia depicted by periodic and spontaneous closure of the orbicularis oculi and surrounding muscles." }, { "input": "What is blepharospasm?", "output": "Blepharospasm (BL) is characterized by involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle." }, { "input": "What is blepharospasm?", "output": "Blepharospasm is a type of focal dystonia. It is a movement disorder characterized by periodic and spontaneous closure of the orbicularis oculi muscle and surrounding muscles." }, { "input": "What is blepharospasm?", "output": "Blepharospasm is a type of focal dystonia. It's a movement disorder characterized by periodic and spontaneous closure of the orbicularis oculi muscle and surrounding muscles." }, { "input": "What is blepharospasm?", "output": "Blepharospasm is a type of focal dystonia. It's a movement disorder characterized by periodic and spontaneous closure of the orbicularis oculi and surrounding muscles." }, { "input": "What is blepharospasm?", "output": "Blepharospasm means involuntary twitching, blinking or closure of the eyelids resulting from any cause." }, { "input": "Explain the action of Balovaptan.", "output": "Balovaptan is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks Vasopressin-1a. It is approved for the treatment of autism spectrum disorders (ASD)." }, { "input": "Explain the action of Balovaptan.", "output": "Balovaptan is an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction." }, { "input": "Explain the action of Balovaptan.", "output": "Balovaptan, an orally administered selective vasopressin V1a receptor antagonist which can penetrate the blood brain barrier." }, { "input": "Explain the action of Balovaptan.", "output": "Yes, Balovaptan, an investigational vasopressin 1a receptor antagonist that has been evaluated for improvement of social communication and interaction." }, { "input": "Explain the action of Balovaptan.", "output": "Balovaptan is an orally administered selective vasopressin V1a receptor antagonis. Balovaptan has been evaluated for improvement of social communication and interaction." }, { "input": "Explain the action of Balovaptan.", "output": "Balovaptan is an orally administered small molecule that binds to mTORC1 and inhibits activation of the mTOR signalling pathway. It is approved for treatment of children with autism spectrum disorders." }, { "input": "Explain the action of Balovaptan.", "output": "Balovaptan is a low-molecular-weight, orally active, hydrophilic non-peptide dual antagonist of both the V1a and V2a receptors that is approved for the treatment of autism spectrum disorders (ASD) in children and adults with intellectual disability." }, { "input": "what is the effect of Bisphenol A in the body?", "output": "Bisphenol A (BPA) is an endocrine-disruptor compound that exhibits estrogenic activit" }, { "input": "what is the effect of Bisphenol A in the body?", "output": "BPA is considered an endocrine disruptor and several studies have proposed a relationship between exposure to BPA and the appearance of adverse health effects, such as cancer, infertility, diabetes, and obesity, among others." }, { "input": "what is the effect of Bisphenol A in the body?", "output": "Bisphenol A is an endocrine-disruptor compound, that exhibits estrogenic activity, can affect male fertility, and can modulate the immune response to infections. It is also associated with increased risk of obesity and diabetes." }, { "input": "what is the effect of Bisphenol A in the body?", "output": "Bisphenol A (BPA) is an endocrine disruptor that modulates the immune response to infections." }, { "input": "List the main proteins found in human saliva.", "output": "Amylases\nCystatins\nImmunoglobulins\nMucins" }, { "input": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "output": "No. The HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes mellitus, although not a perfect one. It is associated with high morbidity and mortality, and is not an ideal biomarker for assessment of well-controlled diabetes." }, { "input": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "output": "No. HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates." }, { "input": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "output": "No, HbA1c is not an ideal biomarker of well-controlled diabetes." }, { "input": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "output": "No. The HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes mellitus, although not a perfect one. It is associated with poor prognosis in patients with type 2 diabetes and is an ideal biomarker for the diagnosis of Type 2 diabetes." }, { "input": "Which tool has been developed for microRNA-target enrichment and network-based analysis?", "output": "MIENTURNET (MicroRNA ENrichment TURned NETwork) is a web tool that receives in input a list of miRNAs or mRNAs and tackles the problem of prioritizing miRNA-target interactions by performing a statistical analysis followed by a fully featured network-based visualization and analysis. The statistics is used to assess the significance of an over-representation of miRNA-target interactions and then MIENTURNET filters based on the statistical significance associated with each miRNA-target interaction. In addition, the holistic approach of the network theory is used to infer possible evidences of miRNA regulation by capturing emergent properties of the miRNA-target regulatory network that would be not evident through a pairwise analysis of the individual components." }, { "input": "Which tool has been developed for microRNA-target enrichment and network-based analysis?", "output": "MIENTURNET (MicroRNA ENrichment TURned NETwork) is an interactive web tool for microRNA-target enrichment and network-based analysis." }, { "input": "Which tool has been developed for microRNA-target enrichment and network-based analysis?", "output": "MIENTURNET is a web tool for microRNA-target enrichment and network-based analysis. MIENTURNET offers the possibility to consistently perform both statistical and network-based analyses." }, { "input": "List example genes that SWIM tool has identified and which are down-regulated in glioblastoma", "output": "SWIM is a software able to unveil a small pool of genes - called switch genes - critically associated with drastic changes in cell phenotype. Applying SWIM to the expression profiling of glioblastoma stem-like cells and conventional glioma cell lines identifies switch genes related to stem-like phenotype. SWIM identifies 171 switch genes that are all down-regulated in glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways." }, { "input": "List example genes that SWIM tool has identified and which are down-regulated in glioblastoma", "output": "This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways." }, { "input": "List example genes that SWIM tool has identified and which are down-regulated in glioblastoma", "output": "SWIM tool has identified and which genes are down-regulated in glioblastoma. These include the genes: itga3, hmmr, sox2, cav1, itga5, thbs1, sdc1, col6a3, col5a1 and sall2." }, { "input": "List example genes that SWIM tool has identified and which are down-regulated in glioblastoma", "output": "SWIM tool has identified and which genes are down-regulated in glioblastoma and which are important for tumorigenesis: met, vegfc, flnb, itga3, hmmr, sox2, cav1, itGA5, thbs1, sdc1, col6a3, col5a1 and sall2." }, { "input": "List example genes that SWIM tool has identified and which are down-regulated in glioblastoma", "output": "SWIM identifies 171 switch genes that are all down-regulated in glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in \"ECM-receptor interaction\" and \"focal adhesion\" pathways" }, { "input": "Describe SWItchMiner (SWIM)", "output": "SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called \"fight-club hubs\", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called \"switch genes\", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance." }, { "input": "Describe SWItchMiner (SWIM)", "output": "SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. SWIM allows unearthing the existence of a new class of hubs, called \"fight-club hubs\", characterized by a marked negative correlation with their first nearest neighbors." }, { "input": "What promotes amyloid-peptide beta 42 (A\u03b242) accumulation in neuroblastoma cells?", "output": "The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients' brain. A specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (A\u03b242) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis." }, { "input": "What promotes amyloid-peptide beta 42 (A\u03b242) accumulation in neuroblastoma cells?", "output": "The amyloid-peptide beta 42 (A\u03b242) accumulates in neuroblastoma cells due to a protein called apoE4-165, which is an apolipoprotein (APOE4). This protein is the most common protein responsible for late-onset Alzheimer disease." }, { "input": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "output": "EpiMethylTag is a fast, low- input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "output": "EpiMethyl tag is a method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "output": "Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. EpiMethylTag is a fast, low-input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "output": "EpiMethyl tag is a fast, low- input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "output": "EpiMethylTag is a fast, low- input, low sequencing depth method that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "Which method has been developed for detection of ATAC-seq or ChIP-seq signals with DNA methylation?", "output": "EpiMethyl tag is a technology that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "Which protein is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks?", "output": "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks." }, { "input": "Which protein is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks?", "output": "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks. Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in enhancer connectivity." }, { "input": "Which protein is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks?", "output": "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancers networks." }, { "input": "Which protein is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks?", "output": "KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood." }, { "input": "Which protein is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks?", "output": "KLF4 is involved in the organization and regulation of pluripotency-associated enhancer networks. How transcription factors orchestrate the complex molecular changes around their target gene loci remains incompletely understood." }, { "input": "Where is the agouti-related peptide expressed?", "output": "Function. Agouti-related protein is expressed primarily in the adrenal gland, subthalamic nucleus, and hypothalamus, with lower levels of expression in the testis, kidneys, and lungs." }, { "input": "Where is the agouti-related peptide expressed?", "output": "The agouti-related peptide is expressed in neurons in the hypothalamus." }, { "input": "What is the function of ketohexokinase-A?", "output": "The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C." }, { "input": "Are the major royal jelly proteins similar to the yellow proteins?", "output": "Yes,\nMajor royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family." }, { "input": "Which R packages have been developed for studying TADs?", "output": "TADCompare is an R Package for differential and temporal analysis of Topologically Associated Domains. SpectralTAD is an R package for defining a hierarchy of topologically associated domains using spectral clustering." }, { "input": "Which R packages have been developed for studying TADs?", "output": "TADCompare is a method for differential analysis of boundaries of interacting domains between two or more Hi-C datasets. SpectralTAD is a method for defining a hierarchy of topologically associated domains using spectral clustering." }, { "input": "Which bioconductor tool has been developed for accessing bacterial regulatory networks?", "output": "The Regutools R package to facilitates programmatic access to RegulonDB data in computational biology. regutools gives researchers the possibility of writing reproducible workflows with automated queries to RegulonDB. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages." }, { "input": "Which bioconductor tool has been developed for accessing bacterial regulatory networks?", "output": "RegulonDB has collected, harmonized and centralized data from hundreds of experiments for nearly two decades and is considered a point of reference for transcriptional regulation in Escherichia coli K12. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages." }, { "input": "Is the Apis mellifera genome available?", "output": "Yes,\nthe Apis mellifera genome is available since 2006." }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The gene encoding clcn1, mBNl1, gcic-1, scn4a, clc-1 and dmpk are implicated in myotonic goats and other nondystrophic myotonias." }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The following genes are implicated in myotonic goats and other nondystrophic myotonias: clcn1 (also known as mbnl1), gcic-1, scn4a, clc-1 and dmpk." }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The genes that are implicated in myotonic goats and other nondystrophic myotonias are clcn1, mbnl1, gcic-1, scn4a, clc-1 and dmpk." }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "Myotonic goats and other Nondystrophic myotonic myotonias are caused by mutations in either the CLCN1 gene or the SCN4A gene." }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The gene encoding clcn1 (also known as clc-1), gcic-1, scn4a, and dmpk is implicated in myotonic goats and other nondystrophic myotonias" }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. In goats, the gCIC-1 protein encoded by the CLCN1 gene, is affected ." }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene" }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "The gene encoding clcn1, mphanl1, gcic-1, scn4a, clc-1 and dmpk are implicated in myotonic goats and other nondystrophic myotonias" }, { "input": "What genes is implicated in myotonic goats and other nondystrophic myotonias?", "output": "Myotonic goats and other Nondystrophic Myotonias are caused by mutations in either the CLCN1 gene in Myotonia congenita or in the SCN4A gene in S4A." }, { "input": "Has the olive tree pollen proteome been studied?", "output": "Yes,\nOlive pollen is a major allergenic source worldwide due to its extensive cultivation. We have combined available genomics data with a comprehensive proteomics approach to get the annotated olive tree (Olea europaea L.) pollen proteome and define its complex allergenome." }, { "input": "Is cadherin a plasma membrane marker?", "output": "Yes,\ncadherin is a plasma membrane protein marker." }, { "input": "What impacts stability of genomic imprinting in mouse pluripotent stem cells?", "output": "A susceptibility locus on chromosome 13 profoundly impacts the stability of genomic imprinting in mouse pluripotent stem cells." }, { "input": "What are the end products of the shikimate pathway?", "output": "The shikimate pathway responsible for the generation of aromatic amino acids" }, { "input": "What are the uber-operons?", "output": "Uber-operons are groups of functionally or transcriptionally related operons, whose gene sets are conserved across multiple reference genomes. Many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments." }, { "input": "Which key gene is involved in syndromic obesity phenotype of patients with 1p21.3 microdeletions?", "output": "MIR137 is the key gene mediator of the syndromic obesity phenotype of patients with 1p21. 3 microdeletions." }, { "input": "Which key gene is involved in syndromic obesity phenotype of patients with 1p21.3 microdeletions?", "output": "MIR137 is the key gene mediator of the syndromic obesity phenotype of patients with 1p21.3 microdeletions." }, { "input": "Which key gene is involved in syndromic obesity phenotype of patients with 1p21.3 microdeletions?", "output": "The MIR137 gene. It is the one that is responsible for the obesity phenotype of patients with 1p21.3 microdeletions." }, { "input": "Which key gene is involved in syndromic obesity phenotype of patients with 1p21.3 microdeletions?", "output": "The MIR137 gene. It is the one that is responsible for the obesity phenotype of patients carrying 1p21.3 microdeletions." }, { "input": "Which key gene is involved in syndromic obesity phenotype of patients with 1p21.3 microdeletions?", "output": "Deletions in the long arm of chromosome 1 have been described in patients with a phenotype consisting primarily of obesity, intellectual disability and autism-spectrum disorder. MIR137 is suggested as the mediator of the obesity phenotype of patients carrying 1p21.3 microdeletions." }, { "input": "Is cabergoline used for treatment of the Nelson's syndrome ?", "output": "Yes, cabergoline has been shown to be effective for treatment of the Nelson's syndrome." }, { "input": "Are mucins glycosylated proteins?", "output": "Yes,\nMany members of the mucin family are evolutionarily conserved and are often aberrantly expressed and glycosylated in various benign and malignant pathologies leading to tumor invasion, metastasis, and immune evasion." }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy in humans." }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome (CTS) is a type of nerve entrapment due to compression of the nerve root extraforaminally between the wrist and the wrist at the carpal tunnel." }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand." }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis." }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome (CTS) is a focal compressive neuropathy of the central nervous system causing hemorrhage-prone multiple lumen vascular malformation and very severe neurological consequences" }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes" }, { "input": "Is carpal tunnel syndrome a type of nerve entrapment?", "output": "Carpal tunnel syndrome (CTS) is a type of nerve entrapment due to compression of the nerve root ganglion as it travels through the wrist at the carpal tunnel." }, { "input": "What is the main manifestation of Liebenberg syndrome?", "output": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly." }, { "input": "What is the main manifestation of Liebenberg syndrome?", "output": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly . It is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics ." }, { "input": "What is the main manifestation of Liebenberg syndrome?", "output": "People who are affected by Liebenberg Syndrome suffer from three main symptoms: Dysplasia (improper formation) of the bony components of the elbow. Abnormal shape of carpal bones. Brachydactyly, a symptom where the fingers and toes are shorter than normal." }, { "input": "What is the main manifestation of Liebenberg syndrome?", "output": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition . It is characterized by dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly . We speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds ." }, { "input": "What is the main manifestation of Liebenberg syndrome?", "output": "Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly" }, { "input": "Which IDH inhibitors by Agios Pharmaceuticals have been approved by the FDA?", "output": "Enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration" }, { "input": "What is RADICL-seq?", "output": "Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq) is a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure." }, { "input": "What is RADICL-seq?", "output": "RADICL-seq is a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. It identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA- chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure." }, { "input": "What is RADICL-seq?", "output": "RADICL-seq is a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. It is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL -seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA- chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure." }, { "input": "Which disease is treated with Anti\u2013Siglec-8 Antibody?", "output": "Anti-Siglec-8 Antibody was shown to be effective for Eosinophilic Gastritis and Duodenitis. It is also undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases." }, { "input": "What is known about mammalian melatonin receptors?", "output": "Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals.\nThe melatonin receptor family is a small group of receptors within the G protein-coupled receptor (GPCR) superfamily. The group comprises of three subtypes which bind melatonin and one member, the melatonin related receptor (MRR), that shares >40% sequence identity with the other melatonin receptors but does not bind melatonin." }, { "input": "What is holoprosencephaly?", "output": "Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis . The most common developmental defect is characterized by inadequate or absent midline division of the forebrain into cerebral hemispheres with concomitant midline facial defects in the majority of cases ." }, { "input": "What is holoprosencephaly?", "output": "Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis." }, { "input": "What is holoprosencephaly?", "output": "Holoprosencephaly is a congenital defect of the brain, median structures, and face resulting from incomplete incomplete cleavage of the primitive brain during early embryogenesis." }, { "input": "What is holoprosencephaly?", "output": " Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis." }, { "input": "What is the effect of notch in the division of neural progenitor cells in Drosophila?", "output": "The Notch pathway mediates the differentiation of neural progenitor cells in Drosophila. It's an important part of the development of neural stem cells, which are the cells that make up the brain. Notch/HES signaling and MIR-9 signaling are very important for the homeostasis of neural cells. It is thought that notch activation is responsible for the growth of neurons." }, { "input": "What is the effect of notch in the division of neural progenitor cells in Drosophila?", "output": "Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates. In the adult mammalian brain niches for neural stem cells are maintained, which enable a steady-state neurogenesis. This process is tightly regulated by multiple niche factors, including Notch and NF-\u03baB signaling. As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells." }, { "input": "What is the effect of notch in the division of neural progenitor cells in Drosophila?", "output": "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Disruption of Notch signaling causes neuronal progenitor cell self-renewal, a hallmark of systemic lupus erythematosus (SLE), and leads to premature differentiation of them into the erythroid lineage." }, { "input": "What is the effect of notch in the division of neural progenitor cells in Drosophila?", "output": "Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates In the adult mammalian brain niches for neural stem cells are maintained, which enable a steady-state neurogenesis. This process is tightly regulated by multiple niche factors, including Notch and NF-?B signaling. As a result of Notch activation, neuronal differentiation is inhibited in neighboring cells and they remain neural progenitor cells." }, { "input": "What is the effect of notch in the division of neural progenitor cells in Drosophila?", "output": "The Notch pathway mediates the differentiation of neural progenitor cells in Drosophila. It's an important part of the development of neural stem cells, which are the cells that make up the brain. Notch/HES signaling and MIR-9 signaling are very important for the homeostasis of neural cells." }, { "input": "In what clinical trials has SAR425899 been tested?", "output": "Subcutaneous administrations of SAR425899 were tested in two randomized, placebo-controlled, double-blind clinical trials. In the first trial, healthy overweight volunteers (body mass index [BMI] 25-30\u2009kg/m2 ; n\u2009=\u200932) received single-ascending doses (0.01-0.1 mg) of SAR425899 or placebo. In the second, a multiple-ascending-dose trial (NCT02411825), healthy normal- to overweight volunteers (BMI 20-30\u2009kg/m2 ; n\u2009=\u200940) and overweight/obese patients with T2D (BMI 28-42\u2009kg/m2 ; n\u2009=\u200936) received daily doses of SAR425899 or placebo over 21 or 28\u2009days, respectively." }, { "input": "Is there a link between rare variants in PPARG and type 1 diabetes?", "output": "No. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes." }, { "input": "Is there a link between rare variants in PPARG and type 1 diabetes?", "output": "No. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes" }, { "input": "What is the mechanisms of action of pexidartinib?", "output": "Pexidartinib is small-molecule tyrosine kinase inhibitor that has strong selectivity against colony-stimulating factor 1 receptor." }, { "input": "List pore forming toxins.", "output": "cytolysin A\n\u03b1-hemolysin\nStreptolysin O\npneumolysin\nlisteriolysin\nleukocidin\nGlabralysin" }, { "input": "What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D?", "output": "Mutations in lysine methyltransferase 2D (KMT2D) cause Kabuko syndrome." }, { "input": "What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D?", "output": "Mutations in lysine methyltransferase 2D (KMT2D) gene, which encodes the catalytic core of a multisubunit chromatin remodeling enzyme, are responsible for the neurodegenerative disorder Kabuki syndrome." }, { "input": "What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D?", "output": "Kabuki syndrome is a rare autosomal dominant disorder caused by mutations in the lysine methyltransferase 2D (KMT2D) gene." }, { "input": "What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D?", "output": "Kabuki syndrome (KS) is commonly caused by mutations in the histone-modifying enzyme lysine methyltransferase 2D (KMT2D)." }, { "input": "What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D?", "output": "Mutations in the lysine methyltransferase 2D (KMT2D) gene, which encodes the alpha-subunit of the kappaB gene, are associated with the autosomal dominant hemophagocytic syndrome type 4 or Ferroportin syndrome." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "Yes, steroid 5A-reductase deficiency can lead to hermaphroditism." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "5\u03b1 steroid reductase deficiency (5\u03b1SRD) is an autosomal recessive enzymatic deficiency and mutations in the 5\u03b1 steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis. The diagnosis of steroid-5-alpha-reductase deficiency is rarely considered by the paediatrician." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "Yes, steroid 5A-reductase deficiency is a rare autosomal recessive disorder." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "Yes, steroid 5A-Reductase deficiency is associated with hermaphroditism." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "5\u03b1 steroid reductase deficiency (5\u03b1SRD) is an autosomal recessive enzymatic deficiency and mutations in the 5\u03b1 steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "Male pseudo hermaphroditism caused by steroid 5 alpha reductase deficiency is a rare autosomal recessive disorder. This enzyme catalyses the conversion of testosterone to dihydrotestosterone (DHT) in genital tissue." }, { "input": "Does steroid 5A-Reductase deficiency lead to hermaphroditism?", "output": "Yes, steroid 5A-reductase deficiency is associated with hermaphroditism." }, { "input": "Has ubrogepant entered clinical phase III trials?", "output": "Yes, ubrogepant has entered phase III trials." }, { "input": "How many nucleotides long is the HOTAIR CNE?", "output": "The HOTAIR CNE is a 32-nucleotide long conserved noncoding element" }, { "input": "How many nucleotides long is the HOTAIR CNE?", "output": "HOTAIR was proposed to regulate either HoxD cluster genes in trans or HoxC cluster genes in cis, a mechanism that remains unclear. A 32-nucleotide conserved noncoding element (CNE) was identified as HOTAIR ancient sequence that likely originated at the root of vertebrate." }, { "input": "How many nucleotides long is the HOTAIR CNE?", "output": "The HOTAIR element is a 32-nucleotide conserved noncoding element" }, { "input": "What symptoms are included in the narcolepsy pentad?", "output": "Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep." }, { "input": "What is the function of osteolectin?", "output": "C-type lectin domain family 11 member A (Clec11a), also known as stem cell growth factor (SCGF), C-type lectin superfamily member 3 (CLECSF3), or osteolectin was initially identified as a growth factor for hematopoietic progenitor cells." }, { "input": "What is ECMO?", "output": "Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF)" }, { "input": "What is ECMO?", "output": "The method of extracorporeal membrane oxygenation (VA-ECMO) has developed from being used as a 'rescue therapy' to become an accepted treatment option for patients with acute lung failure." }, { "input": "What is ECMO?", "output": "Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF) and is used to treat severe symptoms of Covid-19 as well as other cases of severe respiratory and/or circulatory failure over periods of several days to several weeks" }, { "input": "What is ECMO?", "output": "Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF)." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. It has also been shown to be associated with various autoimmune conditions such as lupus-like syndrome, collagen induced arthrits and glomerulonephritis." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus, maids, rheumatoid arthritis, arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, and lupUS-like nephitis." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "The Yaa gene-mediated acceleration of murine lupus: Yaa- T cells from non-autoimmune mice collaborate with Yaa+ B cells to produce Lupus autoantibodies in vivo." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus,maids, rheumatoid arthritis, arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, lUPus-like nephitis and other inflammatory bowel diseases." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus,maids, rheumatoid arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, lUPus and lupUS-like nephitis." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa." }, { "input": "Which diseases are associated with the Yaa gene?", "output": " Yaa is a Y-chromosome-linked gene that accelerates autoimmune diseases in some autoimmune-prone strains of mice The role of the Yaa gene in lupus syndrome The Y chromosome-linked \"autoimmune accelerating\" yaa gene suppresses collagen-induced arthritis" }, { "input": "Which diseases are associated with the Yaa gene?", "output": "Yaa is a Y-chromosome-linked gene that accelerates autoimmune diseases in some autoimmune-prone strains of mice . BXSB mice spontaneously develop a lupus-like syndrome that is accelerated by the Yaa gene . Yaa mice bearing the NZB chromosome 13 locus displayed increased serum gp70 production, but not glomerulonephritis ." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus, maids, rheumatoid arthritis, arthritis, l upus nephritis, murine acquired immunodeficiency syndrome, and lUPus-like nephitis." }, { "input": "Which diseases are associated with the Yaa gene?", "output": "Diseases associated with the Yaa gene include aids, systemic lupus erythematosus,maids, rheumatoid arthritis, l upus nephritis and murine acquired immunodeficiency syndrome." }, { "input": "Which receptors does bimagrumab block?", "output": "Bimagrumab blocks the activin type II receptors." }, { "input": "Are PDXK mutations linked to polyneuropathy?", "output": "Yes, PDXK mutations are linked to polyneuropathy." }, { "input": "Are PDXK mutations linked to polyneuropathy?", "output": "Yes, PDXK mutations are associated with autosomal recessive polyneuropathy." }, { "input": "Are PDXK mutations linked to polyneuropathy?", "output": "Yes. PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation." }, { "input": "Are PDXK mutations linked to polyneuropathy?", "output": "Yes, PDXK mutations are associated with delayed polyneuropathy." }, { "input": "Are PDXK mutations linked to polyneuropathy?", "output": "Yes, point mutations in PDXK gene may be associated with peripheral neuropathy." }, { "input": "Is avelumab effective for urothelial carcinoma?", "output": "Yes. Avelumab is an anti-programmed death-ligand 1 monoclonal antibody that is approved for the treatment of urothelial carcinoma." }, { "input": "What tissues have been studied by circadian proteomics?", "output": "Retina\nLiver" }, { "input": "Is MIS-C or Multisystem Inflammatory syndrome in children a complication of Covid-19?", "output": "Is MIS-C or Multisystem Inflammatory Syndrome in children a complication of Covid-19? Yes, it is." }, { "input": "Is MIS-C or Multisystem Inflammatory syndrome in children a complication of Covid-19?", "output": "Multisystem Inflammatory syndrome AKA MIS-C is a complication of Covid-19 infection in children." }, { "input": "Is MIS-C or Multisystem Inflammatory syndrome in children a complication of Covid-19?", "output": "Multisystem inflammatory syndrome in children (MIS-C) is a complication of Covid-19, clinically characterized by severe chronic inflammation in the central nervous system of children and adolescents." }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Analogously to mRNAs, the non-protein-encoding enhancer RNAs are synthesized by RNA Pol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail." }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Enhancers are bound by sequence-specific transcription factors, which in turn facilitate the cooperative binding of chromatin remodeling enzymes, histone modifying enzymes, other co-factors, and ultimately the RNA polymerase II complex (RNA pol II). Both the target genes and the enhancers are transcribed by RNA pol II." }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Analogously to mRNAs, the non-protein-encoding enhancer RNAs are synthesized by RNA Pol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail. Recent evidence indicates that miRNA genes are transcribed by RNA polymerase II (Pol II)" }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Enhancer RNAs (eRNAs) are a group of lncRNAs transcribed from enhancers by RNA Polymerase II." }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Analogously to mRNAs, the non-protein-encoding enhancers are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail. Recent evidence indicates that miRNA genes are transcribed by RNA Pol II (Pol II)" }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Because the transcripts of most enhancer genes are the products of type-II RNA polymerase, enhancer RNA Pol II (Pol II) has a poly(A) tail and appears in expressed sequence tags (EST). Analogously to mRNAs, the non-protein-encoding enhancer RNAs (ncRNAs) are synthesized by RNAPol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tails." }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "Because the transcripts of most enhancers are the products of type-II RNA polymerase, enhancer RNA Pol II (Pol II) has a poly(A) tail and appears in expressed sequence tags (EST). Analogously to mRNAs, the non-protein-encoding enhancer RNAs are synthesized by RNAPol II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly ( A) tail." }, { "input": "Which RNA polymerase transcribes enhancer RNAs?", "output": "The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP." }, { "input": "Name the three phase 3, randomized, double-blind, placebo-controlled that assessed galcanezumab?", "output": "Galcanezumab has been assessed in the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2 and REGAIN studies." }, { "input": "Is co-loss of BRCA2-RB1 associated with better prognosis for prostate cancer patients?", "output": "No. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype." }, { "input": "Which drugs were investigated in the ALPHEUS trial?", "output": "ALPHEUS study examined if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective percutaneous coronary intervention (PCI)." }, { "input": "Which cell secretes the enzyme tryptase?", "output": "Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines." }, { "input": "What disease does BCG immunotherapy used to treat?", "output": "Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy is used for treatment of bladder cancer." }, { "input": "What disease does BCG immunotherapy used to treat?", "output": "Bacillus Calmette- Gu\u00e9rin (BCG) immunotherapy is used for treatment of bladder cancer." }, { "input": "What disease does BCG immunotherapy used to treat?", "output": "Bacillus Calmette- Gu\u00e9rin (BCG) immunotherapy is used in the treatment of bladder cancer." }, { "input": "What disease does BCG immunotherapy used to treat?", "output": "BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer (NMIBC) after transurethral resection." }, { "input": "What disease does BCG immunotherapy used to treat?", "output": "BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer." }, { "input": "What disease does BCG immunotherapy used to treat?", "output": "Bacillus Calmette-gu\u00e9rin (BCG) immunotherapy is used in the treatment of bladder cancer." }, { "input": "Which epigenetic marks are deposited by PRC1?", "output": "PRC2 induces histone H3 lysine 27 (H3K27) trimethylation (H3K27me3), which is subsequently read by PRC1 that further catalyzes H2A monoubiquitination (H2Aub1), creating a transcriptional silent chromatin conformation." }, { "input": "Which epigenetic marks are deposited by PRC1?", "output": "H2A monoubiquitination (H2Aub1), catalyzed by Polycomb-Repressive Complex1 (PRC1) is a key epigenetic mark in Polycomb silencing . Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase ." }, { "input": "Which epigenetic marks are deposited by PRC1?", "output": "Histone H2A monoubiquitination (H2Aub1), catalyzed by Polycomb-Repressive Complex1 (PRC1), is a key epigenetic mark in Polycomb silencing . Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase ." }, { "input": "Does erenumab target the calcitonin gene-related peptide?", "output": "No, erenumab targets the calcitonin gene-related peptide receptor." }, { "input": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "output": "Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. ARID1B is the key gene behind 6q microdeletion syndrome." }, { "input": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "output": "Interstitial 6q25 microdeletion syndrome (ICS) is a rare autosomal dominant disorder characterized by loss-of-function mutations of the ARID1B gene and severe intrauterine and post-natal growth retardation" }, { "input": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "output": "The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14." }, { "input": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "output": "Interstitial 6q25 microdeletion syndrome (IL-6q25) is a rare autosomal dominant disorder caused by mutations in the ARID1B gene, which encodes a major regulator of heme oxygenase 1 (HMOX1), resulting in a loss of a ubiquitously expressed protein, gigaxonin." }, { "input": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "output": "Interstitial 6q25 microdeletion syndrome (IPS) is a rare autosomal dominant disorder characterized by loss-of-function mutations in the ARID1B gene, which encodes a major regulator of heme oxygenase 1 (HMOX1), and many other genes involved in heme catabolism." }, { "input": "Which key gene is involved in interstitial 6q25 microdeletion syndrome?", "output": "Interstitial 6q25 microdeletion syndrome (ICS) is a rare autosomal recessive genetic disorder characterized by loss-of-function mutations in the ARID1B gene, which encodes a major regulator of heme oxygenase activity." }, { "input": "Brensocatib was tested for treatment of which disease?", "output": "Brensocatib was tested for bronchiectasis. Brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes." }, { "input": "What is the function of the protein Cuf1?", "output": "Cuf1 is a copper-sensing transcription factor." }, { "input": "How many groups of viruses exist in the Baltimore Classification?", "output": "There are seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction." }, { "input": "How many groups of viruses exist in the Baltimore Classification?", "output": "seven \"Baltimore classes\" (BCs) that define the major features of virus reproduction" }, { "input": "How many groups of viruses exist in the Baltimore Classification?", "output": "The Baltimore Classification system consists of seven classes (A, B, C, D, E, F, G, C and D) that are classified into seven different regions based on sequence similarity." }, { "input": "What is the effect of Dkk1 in Wnt signaling?", "output": "Transcriptional silencing of the Wnt-antagonist DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis." }, { "input": "What is the effect of Dkk1 in Wnt signaling?", "output": "DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis." }, { "input": "What is the effect of Dkk1 in Wnt signaling?", "output": "DKK1 is a secreted protein that inhibits WNT signaling and plays essential roles in vertebrate embryogenesis." }, { "input": "What is the effect of Dkk1 in Wnt signaling?", "output": "DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis including head induction, skeletal development, and limb patterning." }, { "input": "What is bimagrumab", "output": "Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators." }, { "input": "List orally bioavailable MPS1 kinase inhibitors", "output": "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazalo,bos172722 and cct251455." }, { "input": "List orally bioavailable MPS1 kinase inhibitors", "output": "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazolo, bos172722, cCT251455." }, { "input": "List orally bioavailable MPS1 kinase inhibitors", "output": "MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. CCT251455, BOS172722, CCT271850, 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides and NMS-P715 are orally bioavailable MPS1 kinase inhibitors." }, { "input": "List orally bioavailable MPS1 kinase inhibitors", "output": "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazolo, bos172722 and cct251455 are orally bioavailable MPS1 kinase inhibitors." }, { "input": "List orally bioavailable MPS1 kinase inhibitors", "output": "1 h-pyrrolo [3,2-c] pyridine, cct271850, nms-p715, 4-aminopyrazola,bos172722 and cct251455 are orally bioavailable MPS1 kinase inhibitors." }, { "input": "Can radiosurgery be used for the DNET tumors?", "output": "Yes, radiosurgery is used for the DNET (Dysembryoplastic neuroepithelial) tumors. However, the level of evidence is limited." }, { "input": "What are commensal bacteria?", "output": "The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria. Maintenance of the commensal bacteria that comprise the gut microbiome is essential to both gut and systemic health." }, { "input": "What disease is associate with defects in both the KDM6A (lysine specific demethylase 6A) and KMT2D (lysine methyltransferase 2D)", "output": "Over the last 20 years, mutations in five key COMPASS complex genes have been linked to three human congenital syndromes: Kabuki syndrome (type 1 [KMT2D] and 2 [KDM6A]" }, { "input": "What disease is associate with defects in both the KDM6A (lysine specific demethylase 6A) and KMT2D (lysine methyltransferase 2D)", "output": "Kabuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in the differentiation and proliferation of hematopoietic stem cells." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPalpha is required are unknown . 'Steady-state' granulopsis is absolutely dependent on the C/ EBPalpha transcription factor ." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in the differentiation and proliferation of hematopoietic stem cells. It is a transcription factor required for emergency granulopoiesis." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "Differentiation and proliferation of hematopoietic stem cells are regulated by C/EBP\u03b2, a transcription factor required for emergency granulopoiesis. Granulopoiesis during emergency situations, such as infection, is dependent on C/EBP\u03b2." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) plays critical roles in the differentiation and proliferation of hematopoietic stem cells. There is no definitive role of the transcription factor in emergency granulopoiesis." }, { "input": "Which transcription factor regulates emergency granulopoiesis?", "output": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) regulates the differentiation and proliferation of hematopoietic stem cells." }, { "input": "When did eptinezumab get its first FDA approval?", "output": "In February 2020, eptinezumab was approved in the USA for the preventive treatment of migraine in adults." }, { "input": "Which database exists that contains regulatory sites for splicing in human basal ganglia?", "output": "Braineacv2 has been identified as a database that contains regulatory sites for splicing in human basal ganglia." }, { "input": "Which database exists that contains regulatory sites for splicing in human basal ganglia?", "output": "Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. Disease-relevant regulatory loci were identified, finding that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through http://braineacv2.inf.um.es/." }, { "input": "Which database exists that contains regulatory sites for splicing in human basal ganglia?", "output": "Braineacv2 is a database that contains regulatory sites for splicing in human basal ganglia." }, { "input": "Should minocycline be used for mild Alzheimer disease?", "output": "No. Minocycline did not delay the progress of cognitive or functional impairment in people with mild Alzheimer disease during a 2-year period." }, { "input": "What is pyroptosis?", "output": "Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1\u03b2. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules." }, { "input": "What is a HapMap", "output": "HapMap is a international effort for creating an annotated haplotype map of the world\u2019s most commonhaplotype sequences." }, { "input": "What is a HapMap", "output": "HapMap provides linkage disequilibrium information on a sample of 3.7 million SNPs that can be used for tag SNP selection in whole-genome association studies." }, { "input": "What is a HapMap", "output": "A haplotype map (HapMap)is aimed at describing these variation patterns across the entire genome and has been recently developed by the International HapMap Consortium. HapMap characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed." }, { "input": "What is a HapMap", "output": "The \"HapMap\" project is now underway to characterize patterns of LD in the human genome." }, { "input": "What is a HapMap", "output": "The HapMap haplotype map project aims to systematically map all human haplotypes, chromosome by chromosome, in a gene-dependent manner through dedicated efforts from national and international teams." }, { "input": "What is a HapMap", "output": "The HapMap haplotype map project aims to systematically map all human haplotypes, chromosome by chromosome, in a gene-rich manner through dedicated efforts from national and international teams." }, { "input": "What is a HapMap", "output": "The International Haplotype Map Project (HapMap) is an international effort for creating an annotated haplotype map of the human genome using protein sequences and other genomic data." }, { "input": "What is a HapMap", "output": "A HapMap is a map of the human genome. It's a 3.1 million human single nucleotide polymorphisms (SNPs) that can be genotyped and mapped." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1, are observed in ~\\n10% of all human cancers, including gastric, non-small cell lung, breast ductal carcinoma, nonsmall cell lung cancer, prostate cancer, ovarian cancer, breast tumor, papillary thyroid cancer, and gastric cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, lung cancer, and skin cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, lung cancer, and lung cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "TWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. STAT3 mediates TGF-\u03b21-induced TWIST1 expression and prostate cancer invasion. Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. The Transcription Factor ETV5 Mediates BRAFV600E-Induced Proliferation and TWIST1 Expression in Papillary Thyroid Cancer Cells." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, and lung cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Cancer is caused by uncontrolled cell division. Mutations in TWIST1 are associated with breast cancer, prostate cancer, lung cancer, and prostate cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1 (PRC1), are observed in ~\\n10% of patients with gastric, non-small cell lung, breast ductal carcinomas, nonsmall cell lung cancer, prostate cancer, ovarian cancer, breast tumor, papillary thyroid cancer, and gastric cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1 (PRC1), are observed in ~\\n10% of patients with gastric, non-small cell lung, breast ductal carcinomas, nonsmall cell lung cancer, prostate cancer, female breast cancer, ovarian cancer, breast tumor, papillary thyroid cancer, and gastric cancer." }, { "input": "Which cancer types are associated with mutations in the TWIST1 gene?", "output": "Loss-of-function mutations of TWIST1, a catalytic component of polycomb repressive complex 1 (PRC1), are observed in ~\\n10% of patients with gastric, non-small cell lung, breast ductal carcinomas, nonsmall cell lung cancer, prostate cancer, ovarian cancer, breast tumor, papillary thyroid cancer, cervical cancer, adenoid cystic carcinoma, salivary gland neoplasms." }, { "input": "What did the RESILIENT study investigate?", "output": "A global, randomized, double-blind placebo-controlled study was conducted to confirm that BYM338 (bimagrumab), an anti-activin type II receptor antibody, improves motor function in patients with sporadic inclusion body myositis after 52 weeks' treatment consisting of intravenous administration every 4 weeks at doses of 10, 3, and 1\u2005mg/kg." }, { "input": "List features of the Thrombotic Thrombocytopenic Purpura pentad.", "output": "Thrombotic thrombocytopenic purpura (TTP) is typically characterized by the symptomatic pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, and renal failure." }, { "input": "What are organoids?", "output": "Organoids are 3D physiological in vitro structures that recapitulate morphological and functional features of in vivo tissues and offer significant advantages over traditional cell culture methods." }, { "input": "List 3 therapeutic uses for botulism toxin.", "output": "Botulinum toxin injections are effective in relieving focal spasticity resulting from upper motor neuron injuries, migraine headaches, over active bladder and to relieve pain in the Sacroiliac Joint." }, { "input": "What is the role of Tcf3 in the maintenance of pluripotency?", "output": "The maintenance of pluripotency in mouse embryonic stem cells relies on a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3 . We uncover a key role for post-translational regulation in the maintenance of pliospotency ." }, { "input": "What is the role of Tcf3 in the maintenance of pluripotency?", "output": "The maintenance of pluripotency in mouse embryonic stem cells relies on a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3 . A recent report shows that \u03b2-catenin modulates the effect of TERRA in mESC maintenance ." }, { "input": "What is the role of Tcf3 in the maintenance of pluripotency?", "output": "The maintenance of pluripotency in mouse embryonic stem cells relies on a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3 . We found that down-regulation of Tlf3, a member of the Tcf/Lef family, represents a specific response to Wnt activation in ESCs . Further studies revealed that T cell factor 3 ( TCF3) is a potential downstream target of TERRA ." }, { "input": "What is the role of Tcf3 in the maintenance of pluripotency?", "output": "Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Tcf3 co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Tcf3 down-regulation modulates the lineage differentiation potential of mouse embryonic stem cells through Wnt signaling. Tcf3 down-regulation is a necessary step towards Wnt-mediated suppression of differentiation. Depletion of Tcf3 enables the maintenance of undifferentiated mouse ESCs." }, { "input": "What pathological condition is MK-1602 used for?", "output": "MK-1602 has been assessed in clinical trials for the acute treatment of migraine." }, { "input": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "output": "Yes. Genome-wide analyses indicate a association between mutations in ACVR1 and ulcerative colitis due to loss-of-function mutations in ADCY7." }, { "input": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "output": "Yes. Sequencing analysis showed an association between mutations in ADCY7 and ulcerative colitis patients and high psychopathic traits." }, { "input": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "output": "Yes. Genome-wide analyses indicate an association of alterations in ADCY7 and ulcerative colitis. Mutations in exon 2 interfere with the synthesis of the full-length isoform of CDKN2A and lead to the production of a shortened isoform, with significant morbidity and mortality." }, { "input": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "output": "Yes, there is an association of alterations in ADCY7 and ulcerative colitis." }, { "input": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "output": "To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, whole genomes of 4,280 patients were sequenced at low coverage and compared to 3,652 previously sequenced population controls across 73.5 million variants. A 0.6% frequency missense variant in ADCY7 was discovered that doubles the risk of ulcerative colitis." }, { "input": "What is the mechanism of action of satralizumab?", "output": "Satralizumab is a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody that has been approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD)." }, { "input": "Are mucin overexpression associated with disease?", "output": "Yes,\nmucins are overexpressed in various malignancies and inflammations." }, { "input": "What are the 4 types of holoprosencephaly?", "output": "Holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the forebrain structures at various levels or to various degrees . Depending on the degree of involvement, it is classified into 4 types: Alobar, Semilobar, Lobar, and Middle interhemispheric fusion variant ." }, { "input": "What are the 4 types of holoprosencephaly?", "output": "Holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the forebrain structures at various levels or to various degrees. Depending on the degree of involvement, it is classified into 4 types: Alobar, Semilobar, Lobar and Middle interhemispheric fusion variant." }, { "input": "What are the 4 types of holoprosencephaly?", "output": "The 4 types of holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the foremost structures at various levels or to varying degrees. Depending on the degree of involvement, it is divided into 4 types: Alobar, Halilobar, Lobar and Middle interhemispheric fusion variant." }, { "input": "What are the 4 types of holoprosencephaly?", "output": "4 types of holoprosencephaly have been described: lobar, alobar, interhemispheric, sacral, and cerebellar." }, { "input": "What are the 4 types of holoprosencephaly?", "output": "The 4 types of holoprosencephaly is a rare congenital disorder which results from failure of cleavage or incomplete differentiation of the foremost structures at various levels or to varying degrees. Depending on the degree of involvement, it is broken down into 4 types: Alobar, Halilobar, Lobar and Middle interhemispheric fusion variant." }, { "input": "What are the 4 types of holoprosencephaly?", "output": "Four types of holoprosencephaly have been described: lobar, alobar, interhemispheric, and sacral. (PMID: 22990134)" }, { "input": "Which yeast genes encode for condensin?", "output": "Smc2-Smc4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction . Both SMC2 and SMC4 are essential for chromosome transmission in anaphase . Smc 2-8 suppresses catenanes accumulation, mitotic arrest and growth defects induced by histone depletion at semi-permissive temperature ." }, { "input": "Which yeast genes encode for condensin?", "output": "Smc2/4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction" }, { "input": "Which yeast genes encode for condensin?", "output": "Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic. Here, we probe the topology of Smc2-Smc4 dimers of the S. cerevisiae condensin complex with high-speed atomic force microscopy (AFM) in liquid Interestingly, SAC activation is suppressed by the absence of Top2 and Smc2, an essential component of condensin." }, { "input": "What is another name for the drug AMG334?", "output": "AMG334 is also called erenumab." }, { "input": "Describe the genetic determinants of common epilepsies", "output": "Genetic determinants of common epilepsies are defined as the interaction of mutations in one of two unlinked genes, SCN1 and SCN2, which code for the proteins hamartin and epilepticin, respectively. Disruption of these genes has been found to be associated with epileptic encephalopathies, but it is not entirely clear if this translates directly to the increased risk for epilepsy or via epigenetic changes." }, { "input": "Describe the genetic determinants of common epilepsies", "output": "The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. Meta-analysis of an all-epilepsy cohort identified loci at 2q24.3 (p=8\u00b771\u2008\u00d7\u200810(-10)), implicating SCN1A, and at 4p15.1 (p=5\u00b744\u2008\u00d7\u200810(-9)), harbouring PCDH7, which encodes a protocadherin molecule. For the cohort of genetic generalised epilepsy, a single signal at 2p16.1 (p=9\u00b799\u2008\u00d7\u200810(-9)), implicating VRK2 or FANCL was noted. Data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype." }, { "input": "Should nerinetide be used for treatment of ischaemic stroke?", "output": "Nerinetide did not improve the proportion of ischemic stroke patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo." }, { "input": "What is the role of alcohol acyl transferases in fruit aroma?", "output": "Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT).\nThe expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene." }, { "input": "What is Hikikomori syndrome?", "output": "The 'Hikikomori' syndrome (HS) consists of prolonged and severe social withdrawal." }, { "input": "What is Hikikomori syndrome?", "output": "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social withdrawal in Japan. It is a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis." }, { "input": "What is Hikikomori syndrome?", "output": "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social problem in Japan. It is a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis." }, { "input": "What is Hikikomori syndrome?", "output": "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social problem in Japan. It's a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis." }, { "input": "What is Hikikomori syndrome?", "output": "Hikikomori is a clinical condition in which a subject locks himself/herself into his/her own house for more than 6 months." }, { "input": "What is Hikikomori syndrome?", "output": "Hikikomori syndrome is a Japanese culture-bound syndrome and a serious social withdrawal in Japan. It's a condition in which a subject locks himself/self into a house for a prolonged period of time for the period of 6 months or more, with no evident psychosis." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally . It is caused by cytogenetic deletions or mutations of the TWIST1 gene . Of the 37 patients with classic features of the syndrome, the overall detection rate for TWIST mutations was 68% . Increased risk for developmental delay is associated with TWIST deletions ." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome is an autosomalomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1 . The majority of patients have mutations in TWIST gene, which codes for a basic helx-loix-loge transcription factor ." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome (SCS), one of the most common forms of syndromic craniosynostosis (premature fusion of the cranial sutures), results from haploinsufficiency of TWIST1, caused by deletions of the entire gene or loss-of-function variants within the coding region." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype. Mutations of the TWIST gene in the Saethre-Chotzen syndrome." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "It is caused by cytogenetic deletions or mutations of the TWIST1 gene. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Autosomal dominant mutations in the gene encoding the basic helix-loop-helix transcription factor Twist1 are associated with limb and craniofacial defects in humans with Saethre-Chotzen syndrome." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "It is caused by cytogenetic deletions or mutations of the TWIST1 gene." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Mutations in the TWIST1 gene, encoding the syntaxin binding protein 1, have been described as the cause of the Saethre-Chotzen syndrome." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1 . The majority of patients have mutations in TWIST gene on chromosome 7p21 . The most common cause of the syndrome is loss-of-function mutations in a genetic mutation in the TWIST 1 gene . The patient is a heterozygous carrier of the pathogenic variant c.415C>A ." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome (SCS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the TWIST1 gene (transcription factor Xa, also known as T-box-binding protein 1)." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1 . The majority of patients with the syndrome have mutations in TWIST gene . In 55 patients with features of the syndrome, 11% detected to have deletions by real-time gene dosage analysis ." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome is a craniosynostosis syndrome that is rarely diagnosed prenatally. It is caused by cytogenetic deletions or mutations of the TWIST1 gene. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype." }, { "input": "Which gene is primarily associated with the Saethre-Chotzen syndrome?", "output": "Saethre-Chotzen syndrome (SCS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the TWIST1 gene." }, { "input": "List 4 targeted synthetic DMARDs that are JAK inhibitors.", "output": "Targeted synthetic (ts) DMARDs that are Janus kinase (JAK) inhibitors include tofacitinib, baricitinib, filgotinib, upadacitinib." }, { "input": "Which microRNAs are involved in targeting CYLD in triple negative breast cancer?", "output": "Mir-182 and miR-301b are involved in targeting CYLD in triple negative breast cancer." }, { "input": "Which microRNAs are involved in targeting CYLD in triple negative breast cancer?", "output": "MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD. Knockdown of miR-182 up-regulates the expression of cylindromatosis (CYLD) deubiquitinase, which promotes the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-\u03b1-treated BT-549 cells." }, { "input": "Which drugs were tested in the candor trial?", "output": "CANDOR trial investigated carfilzomib, dexamethasone, and daratumumab for patients with relapsed or refractory multiple myeloma." }, { "input": "Which are the parts of a flaggelum?", "output": "The bacterial flagellum is a supramolecular motility machine consisting of the basal body, the hook, and the filament.\nThe axial structure of the flagellum consists of the rod, hook, junction, filament, and cap." }, { "input": "Why are male calico cats rare?", "output": "The tortoiseshell coat color is characteristic to female cats, and its occurrence in tomcats is very rare and associated with the presence of an additional copy of X chromosome." }, { "input": "Why are male calico cats rare?", "output": "The tortoishell coat colour is characteristic to female cats, and its occurrence in tom cats is very rare and associated with chromosome abnormalities." }, { "input": "Which master regulator drives liver development?", "output": "Hepatocyte nuclear factor (HNF)4\u03b1 regulates fetal liver development." }, { "input": "Which master regulator drives liver development?", "output": "The HNF4\u03b1 plays a major role in liver development, but it's not the only factor. There's a lot of other factors that play a role, but that's the big one." }, { "input": "Are there small molecule CGRPs under development for the treatment of migraine?", "output": "Yes, there are several small molecule CGRPs under development for the treatment of migraine." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. Five novel genetic variants influencing the volumes of the putamen and caudate nucleus were identified. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08\u2009\u00d7\u200910(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen and caudate nucleus, where a novel intergenic locus with replicative influence on volume and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohort." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945330; P = 1.08 \u00d7 10(-33); 0.52% variance explained. In caudate nucleus scientists have identified five novel genetic variants influenced the volumes of putamen and caudated nucleus." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "The putamen is the most affected by common genetic variants. It is the subcortical brain structure responsible for learning, memory and motivation." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "The putamen is the most influenced by common genetic variants. It is the subcortical brain structure responsible for learning, memory and motivation." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945280; P = 1.08 \u00d7 10(-33); 0.52% variance explained) showed evidence of altering the expression of theKTN1 gene in both brain and blood tissue. Variants affecting putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "The putamen is the most influenced by common genetic variants. It is the subcortical brain structure responsible for learning and memory consolidation." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "Common genetic variants influence human subcortical brain structures. The strongest effects are found for the putamen and caudate nucleus, where a novel intergenic locus with replicable influence on volume and intracranial volume have been identified." }, { "input": "Which subcortical brain structure is influenced the most by common genetic variants?", "output": "The putamen is the most affected by common genetic variants. It is the subcortical brain structure responsible for learning and memory consolidation." }, { "input": "Givosiran is used for treatment of which disease?", "output": "Givosiran is approved for treatment of porphyria." }, { "input": "List mediators that are released from mast cells?", "output": "tryptase\nhistamine\nheparin proteoglycan\nchymase\ncytokines\n2,3-dinor-11\u03b2-PGF2\u03b1\nleukotriene (LT)E4" }, { "input": "What is Exencephaly?", "output": "Exencephaly is a type of cephalic disorder wherein the brain is located outside of the skull" }, { "input": "What is Exencephaly?", "output": "exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly. ." }, { "input": "What is Exencephaly?", "output": "exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly." }, { "input": "What is the role of TNF in obesity?", "output": "The role of TNF in obesity is not fully understood, but it is thought to play a major role in adipose tissue formation and fat storage. TNF-alpha is a protein that has been shown to increase fat storage in fat cells. It is also thought to have a role in insulin resistance." }, { "input": "What is the role of TNF in obesity?", "output": "The role of TNF in obesity is not fully understood, but it is thought to play a major role in adipose tissue formation and fat storage. TNF-alpha is a protein that has been shown to increase fat storage in fat cells. It also has a role in insulin resistance, which is a major factor in obesity." }, { "input": "What is the role of TNF in obesity?", "output": "TNF, acting via its receptors, is a major contributor to obesity-associated insulin resistance." }, { "input": "What is the role of TNF in obesity?", "output": "Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity." }, { "input": "What is the role of TNF in obesity?", "output": "TNFalpha gene overexpression induces insulin resistance. TNF-alpha is associated with obesity" }, { "input": "Is eptinezumab a small molecule?", "output": "No, eptinezumab is a humanized monoclonal antibody." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers" }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The ENIGMA Consortium is a global team science effort, now including over 800 scientists spread across 340 institutions in 35 countries, with the shared goal of understanding disease and genetic influences on the brain." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The Enhancing NeuroImaging genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,189 individuals have been provided by the Charcot-Marie-Tooth [CMT] Consortium for replication of findings, in a total of 24,997 subjects." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, they have detected factors that affect the brain that no individual site could detect on their own, and that require larger numbers of subjects than any individual study has currently collected." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, the consortium has detected factors that affect the brain that no individual site could detect on its own." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, they have detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual study has currently collected." }, { "input": "Describe the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium", "output": "The ENIGMA Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, EnIGMA studies have analyzed neuroimaging data from over 12,826 subjects. By meta-analyzing results from many sites, they have detected factors that affect the brain that no individual site could detect on their own." }, { "input": "Inhaled Molgramostim can be used for treatment of which disease?", "output": "Inhaled Molgramostim was shown to be effective for Autoimmune Pulmonary Alveolar Proteinosis." }, { "input": "Which are the main functions of the annexin family?", "output": "Annexins are required for membrane organization and membrane transport events required for the establishment/maintenance of epithelial polarity. \nAn association of annexins with ion channels, as membrane-guiding auxiliary proteins or modulators of channel activity. \nLast but not least, some annexins seem to work as extracellular autocrine modulators of receptor function under different physiological conditions." }, { "input": "Please list the 2 vaccines for herpes zoster(shingles)", "output": "live attenuated zoster vaccine (Zostavax\u00ae) and live attenuates herpes zoster (Shingles) are effective for treatment of infections with herpesZoster(shingles)." }, { "input": "Please list the 2 vaccines for herpes zoster(shingles)", "output": "live attenuated zoster vaccine (Zostavax; also known as shingles vaccine) is effective for prevention of infections with herpes zoster virus (VZV)." }, { "input": "Please list the 2 vaccines for herpes zoster(shingles)", "output": "Shingrix is a recombinant adjuvant subunit vaccine." }, { "input": "Please list the 2 vaccines for herpes zoster(shingles)", "output": "The are 2 vaccines for herpes zoster, adjuvated recombinant vaccines and a live attenuated vaccine." }, { "input": "What is a likely origin of intronless genes?", "output": "More than half of SEGs identified in most of the species have at least one ortholog multiple exon gene in the same genome, which provides insight to their possible origin by retrotransposition" }, { "input": "What is a likely origin of intronless genes?", "output": "There is strong support for the idea that retrotransposition followed by tandem duplications is the most probable event that can explain the expansion of intronless or single-exon genes (SEG) in eukaryotic organisms. More than half of SEGs identified in most of the species have at least one ortholog multiple exon gene in the same genome, which provides insight to their possible origin by retrotransposition." }, { "input": "What is a likely origin of intronless genes?", "output": "The origin of intronless genes is most likely retrotransposition" }, { "input": "What is a likely origin of intronless genes?", "output": "Intronless genes (IGs) constitute approximately 3% of the human genome. Their origin is likely to be retrotransposition due to loss-of-function mutations or duplication." }, { "input": "What is a likely origin of intronless genes?", "output": "Genes without introns are a characteristic feature of prokaryotes, but there are still a number of intronless genes in eukaryotes. Most of these genes may have originated from retrotransposition rather than lineage-specific expansions of repeat elements." }, { "input": "Which company developed ivosidenib?", "output": "Ivosidenib has been developed by Agios Pharmaceuticals." }, { "input": "Is the apilimod inhibitor effective against SARS-CoV-2?", "output": "To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules were profiled. In a study the identification of 30 known drugs that inhibit viral replication was reportedd. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment." }, { "input": "Is the apilimod inhibitor effective against SARS-CoV-2?", "output": "Yes, apilimod inhibition is effective for treatment of SARS-CoV-2." }, { "input": "Is Lanabecestat effective for Alzheimer's disease?", "output": "No. Treatment with lanabecestat was well tolerated and did not slow cognitive or functional decline of Alzheimer's disease patients." }, { "input": "How is the STING protein activated?", "output": "During DNA virus infections, detection of cytosolic DNA by the cGAS-STING pathway leads to activation of IFN-\u03b2." }, { "input": "Explain the use of Radio Frequency Ablation as a treatment", "output": "Radio-frequency ablation (RFA) is a promising minimal-invasive treatment option for treatment of, cancer, pain, tissue hyperplasia and cardiac arrhythmias cancer, triggering tissue necrosis and results in reduced tumor volumes." }, { "input": "Explain the use of Radio Frequency Ablation as a treatment", "output": "Radiofrequency ablation is a simple, safe, and effective treatment option for the treatment of castration-resistant ovarian cancer." }, { "input": "Explain the use of Radio Frequency Ablation as a treatment", "output": "Radio frequency ablation is used in the treatment of infertility." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s basically a measure of how active a patient is in regards to how active they are in relation to the DAS28. The 28 joint DAS (28 joints) is a way to measure how active the patient is compared to other people with the same disease." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": "DAS28 is a subjective Disease Activity Score in Rheumatoid Arthritis patients that checks 28 individual joints." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": " In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s a measure of how active a patient is in regards to how active they are in relation to the DAS28. The 28 joint DAS (28 joints) is the highest score." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": "In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s basically a measure of how active a patient is in regards to how active they are in relation to the DAS28. The 28 joint DAS (28 joints) is a way to measure how active the patient is compared to other patients with the same disease." }, { "input": "What does \"28\" stand for in the Disease Activity Score DAS28?", "output": "It stands for the Disease Activity Score 28 Joint Index (DAS28). It\u2019s a measure of how active a patient is in regards to how active they are in relation to the DAS28." }, { "input": "What is EPICCURE?", "output": "EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30%-50%) undergoing elective coronary artery bypass surgery. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887)." }, { "input": "List updates for JASPAR 2020", "output": "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles." }, { "input": "List updates for JASPAR 2020", "output": "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, a Q&A forum was created to ease the communication between the user community and JASPAR curators. Finally, the genomic tracks, inference tool, and TF-binding profile similarity clusters were updated." }, { "input": "List updates for JASPAR 2020", "output": "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles." }, { "input": "List updates for JASPAR 2020", "output": "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release." }, { "input": "List updates for JASPAR 2020", "output": "JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature." }, { "input": "Was golimumab tested for diabetes?", "output": "Yes, among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo." }, { "input": "Is G3BP1 found in stress granules?", "output": "Yes,\nRAS GTPase-activating protein-binding protein (G3BP1) is an RNA-binding protein that is essential for assembling stress granules." }, { "input": "What is Progeria?", "output": "Hutchinson-Gilford progeria syndrome is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction." }, { "input": "What is Progeria?", "output": "Progeria is a rare genetic premature ageing disorder." }, { "input": "What is Progeria?", "output": "Progeria is a rare genetic disorder that causes premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke)." }, { "input": "What is Progeria?", "output": "Progeria is a rare genetic disorder, characterized by premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke)." }, { "input": "What is Progeria?", "output": "Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C . In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24 ." }, { "input": "What is Progeria?", "output": "Hirschford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction." }, { "input": "What is Progeria?", "output": "Progeria is a rare genetic disorder, characterized by progressive premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke)." }, { "input": "What is Progeria?", "output": "Progeria is a genetic disorder that causes premature aging and early death in the first or second decade of life, usually secondary cardiovascular events (myocardial infarction and stroke)." }, { "input": "What is Progeria?", "output": "Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction" }, { "input": "Describe CrossICC", "output": "CrossICC is an R package designed for the unsupervised clustering of gene expression data from multiple datasets/platforms without the requirement of batch effect adjustment. CrossICC utilizes an iterative strategy to derive the optimal gene signature and cluster numbers from a consensus similarity matrix generated by consensus clustering." }, { "input": "Describe CrossICC", "output": "CrossICC is an R package designed for the unsupervised clustering of gene expression data from multiple datasets/platforms without the requirement of batch effect adjustment. CrossICC utilizes an iterative strategy to derive the optimal gene signature and cluster numbers from a consensus similarity matrix generated by consensus clustering. The package also provides abundant functions to visualize the identified subtypes and evaluate subtyping performance. The package is implemented in R and available at GitHub (https://github.com/bioinformatist/CrossICC) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/CrossICC.html) under the GPL v3 License." }, { "input": "Which receptor is blocked by Finerenone?", "output": "Finerenone is a nonsteroidal mineralocorticoid receptor antagonist." }, { "input": "Is colistin an antibiotic?", "output": "Yes,\ncolistin is an antibiotic." }, { "input": "Is Tocilizumab (Actemra) used to block/antagonize the IL-6 receptor?", "output": "yes, tocilizumab (actemra) is used to block/antagonize the il-6 receptor." }, { "input": "Is Tocilizumab (Actemra) used to block/antagonize the IL-6 receptor?", "output": "Yes. Tocilizumab (Actemra) is an anti-IL-6 receptor antagonist. It is a monoclonal antibody against the receptor." }, { "input": "Is Tocilizumab (Actemra) used to block/antagonize the IL-6 receptor?", "output": "Tocilizumab is an IL-6 receptor antagonist." }, { "input": "Is Tocilizumab (Actemra) used to block/antagonize the IL-6 receptor?", "output": "yes, tocilizumab (actemra) is an approved humanized monoclonal antibody that blocks the il-6 receptor." }, { "input": "Is the process of DNA loop-extrusion independent of ATP?", "output": "The process of DNA loop-extrusion is not independent of ATP. It is dependent on the energy of ATP hydrolysis." }, { "input": "Is the process of DNA loop-extrusion independent of ATP?", "output": "Yes, a single condensin complex is able to extrude tens of kilobase pairs of DNA, using the energy of ATP hydrolysis." }, { "input": "Is the process of DNA loop-extrusion independent of ATP?", "output": "The DNA-organizing mechanism of condensin depends on the energy of ATP hydrolysis but how this activity specifically promotes proper compaction and segregation of chromosomes during mitosis remains poorly understood." }, { "input": "What is the effect of carbamazepine on CYP3A4?", "output": "Carbamazepine is an inducer of CYP3A4." }, { "input": "Is there an upper limit on the functional fraction of the human genome?", "output": "Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower." }, { "input": "Is there an upper limit on the functional fraction of the human genome?", "output": "yes, there is an upper limit on the functional fraction of the human genome." }, { "input": "What is Couvelaire Uterus?", "output": "Couvelaire uterus is hematic infiltration uterine myometrium due to the formation of a massive hematoma. It is charecterised by dark purple patches with ecchymosis and indurations." }, { "input": "What protein is Otof gene encoding?", "output": "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs)" }, { "input": "What protein is Otof gene encoding?", "output": "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs). In the absence of otoferlin, signal transmission of IHCs fails due to impaired release of synaptic vesicles at the IHC synapse." }, { "input": "What protein is Otof gene encoding?", "output": "The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs)." }, { "input": "What is hypercapnia?", "output": "Hypercapnia is also known as High CO2 retention." }, { "input": "What is TSA-Seq used for?", "output": "TSA-Seq provides a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling." }, { "input": "What is TSA-Seq used for?", "output": "TSA-Seq is a new mapping method capable of providing a \"cytological ruler\" for estimating mean mean distance distances from nuclear speckles genome-wide and for predicting several MbP chromosome trajectories between nuclear compartments." }, { "input": "What is TSA-Seq used for?", "output": "TSA-Seq is used as a cytological ruler to calculate relative distances between nuclear elements in 3D genome organization maps." }, { "input": "What is TSA-Seq used for?", "output": "yes, tsa-seq is a new mapping method capable of providing a cytological ruler for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling." }, { "input": "What is TSA-Seq used for?", "output": "tsa-seq is a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling." }, { "input": "What is TSA-Seq used for?", "output": "we describe TSA-Seq, a new mapping method capable of providing a \"cytological ruler\" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling" }, { "input": "Does the HercepTest use a polycloncal or monoclonal antibody?", "output": "The HercepTest uses a polyclonal antibody." }, { "input": "Describe participants' experiences from the 100,000 genomes project", "output": "Interviewees' decisions to participate in 100\u202fkG\u202fP were based on interpersonal and institutional trust in the NHS, and on an investment in improving care for the future. Interviewees relied upon receiving good ongoing NHS care for managing their own or their child's rare disease, but they worried about what their relationships with NHS healthcare professionals would be like in future. A few participants worried about whether Genomics England's biorepository would remain protected and an asset of the NHS." }, { "input": "What is the role of elagolix in treatment of uterine fibroids?", "output": "Elagolix is approved for the treatment of moderate to severe pain caused by endometriosis. Elagolix is also effective for heavy bleeding caused by uterine fibroids." }, { "input": "Where is the organ of Corti located?", "output": "The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the cochlear spiral is the organ of Corti, a highly derived and rigorously patterned sensory epithelium that acts to convert auditory stimuli into neural impulses." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis Infectious uveitis accounted for 37% of posterior uveitis cases of which toxoplasmosis was the most common cause. Toxoplasmosis was the most common cause of posterior uveitis (60%)" }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "A large percentage of posterior and infectious uveitis is associate with toxoplasmosis. Retinochoroiditis is associated with congenital toxoplasmosis." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "the most frequent manifestation of congenital toxoplasmosis is retinochoroiditis." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis" }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "yes, ocular toxoplasmosis is associated with retinochoroiditis." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Toxoplasmosis was the most common cause of posterior uveitis (60%) Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis Infectious uveitis accounted for 37% of posterior uveitis cases of which toxoplasmosis was the most common cause." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "The eye disease(s) associated with ocular toxoplasmosis are:1) ocular syphthalmia, 2) retinochoroiditis, 3) juvenile idiopathic arthritis and4) chorioretinitis." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Toxoplasmosis was the most common cause of posterior uveitis (60%) for infectious uveritis, herpetic iridocyclitis, ocular toxoplasmosa, and bacterial endophthalmitis increased in patients with congenital tasma." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Diseases associated with ocular toxoplasmosis are ocular syphilis, retinochoroiditis, juvenile idiopathic arthritis and chorioretinitis." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Diseases associated with ocular toxoplasmosis are:1) ocular syphilis, 2) retinochoroiditis, 3) juvenile idiopathic arthritis and4) chorioretinitis." }, { "input": "What eye disease(s) are associated with ocular toxoplasmosis?", "output": "Ocular toxoplasmosis (OTS) is a rare but life threatening complication of ocular syphilis, which is followed by retinochoroiditis, juvenile idiopathic arthritis and chorioretinitis." }, { "input": "Which eukaryote genomes contain operons?", "output": "Genes in nematode and ascidian genomes frequently occur in operons such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis We find that birth-death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes and generate predictions about the number of monocistronic, nonoperon genes that likely participate in the birth-death process" }, { "input": "Which eukaryote genomes contain operons?", "output": "The eukaryote genomes contain operons, which can be classified into boader families based, particularly, on the presence of other types of genes. Operons have been found to be present in the following genomes: caenorhabditis elegans, ciona, c. elegans, trichinella spiralis, trichuris muris and ciona intestinalis. Operons have also been reported to exist in the non-coding regions of the human and plant genomes." }, { "input": "Which eukaryote genomes contain operons?", "output": "Genes in nematode and ascidian genomes frequently occur in operons. Such genes comprise 15-20% of the coding genome for Caenorhabditis elegans and Ciona intestinalis. The organization of genes into operons, clusters of genes that are co-transcribed to produce polycistronic pre-mRNAs, is a trait found in a wide range of eukaryotic groups, including multiple animal phyla." }, { "input": "Which eukaryote genomes contain operons?", "output": "Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans" }, { "input": "Which eukaryote genomes contain operons?", "output": "Operons are widespread in prokaryotes, but are uncommon in eukaryotes, except nematode worms, where approximately 15% of genes reside in over 1100 operons in the model organism Caenorhabditis elegans. Birth-death models of operon evolution reasonably describe the relative abundance of operons of different sizes in the C. elegans and Ciona genomes" }, { "input": "What has capmatinib received FDA approval for in 2020?", "output": "In May 2020, oral capmatinib received its first global approval in the USA for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test." }, { "input": "Is SLIC-CAGE used for quantification of translation?", "output": "No. Cap analysis of gene expression (CAGE) is a method used for single-nucleotide resolution detection of RNA polymerase II transcription start sites (TSSs). Accurate detection of TSSs enhances identification and discovery of core promoters. In addition, active enhancers can be detected through signatures of bidirectional transcription initiation. Described here is a protocol for performing super-low input carrier-CAGE (SLIC-CAGE). The SLIC adaptation of the CAGE protocol minimizes RNA losses by artificially increasing the RNA amount through use of an in vitro transcribed RNA carrier mix that is added to the sample of interest, thus enabling library preparation from nanogram-amounts of total RNA (i.e., thousands of cells)." }, { "input": "Is SLIC-CAGE used for quantification of translation?", "output": "No, the super-low input carrier-CAGE (SLIC-Cage) is not used for quantification of translation." }, { "input": "Does hypofractionated radiotherapy offers any benefit for DIPG?", "output": "No. Hypofractionated radiotherapy does not offers benefit when compared to conventional fractionated radiation therapy for DIPG." }, { "input": "What is the function of the stard10 protein?", "output": "STARD10, a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) protein family, is highly expressed in the liver and has been shown to transfer phosphatidylcholine." }, { "input": "Is progeria caused by an autosomal recessive gene?", "output": "Yes. Progeria is caused by an autosomal recessive gene." }, { "input": "Is progeria caused by an autosomal recessive gene?", "output": "yes, progeria is caused by an autosomal recessive gene." }, { "input": "What is the target of adalimumab?", "output": "adalimumab is an anti-tumour necrosis factor (tf)-\u03b1 antibody." }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy. Targeted drugs against key pathogenetic molecules such as TNF-alpha have significantly improved outcomes in rheumatoid arthritis (RA). They are widely used in clinical practice and drug registries give us information to support their use." }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a fully human anti-TNF-alpha IgG1-\u03ba monoclonal antibody." }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a fully human monoclonal antibody against TNF-alpha." }, { "input": "What is the target of adalimumab?", "output": "The objective of this study was to assess the relative importance of local versus systemic interactions between adalimumab and tumour necrosis factor (TNF)-\u03b1 in rheumatoid arthritis (RA), identify localization of the site of adalimumab action and assess the efficacy of local (intra-articular) versus systemic adalimumab administration for treatment of RA" }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a monoclonal antibody that targets TNF-alpha, a central cytokine in the immune response in psoriasis that has been linked to autoimmune disease." }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a fully human anti-TNF-alpha monoclonal antibody." }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy." }, { "input": "What is the target of adalimumab?", "output": "Adalimumab is a human anti-TNF\u03b1 monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation. The major pathway of TNF\u03b1 elimination from the synovial fluid (\u223c77% for subcutaneous administration, and \u223c72% for intravenous and intra-articular administration of adgalimumab 40 mg) is interaction with adalumumab, which reaches the joints following local or systemic administration." }, { "input": "Which gene is implicated in the metabolism of codeine, and its polymorphisms in the mother can pose a risk to breastfeeding children?", "output": "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine." }, { "input": "Describe the role of epidermal CYLD inactivation in sebaceous and basaloid skin tumors", "output": "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors. Epidermal cyld inactivation also inhibits the growth of epidermal cell lines, leading to development of skin tumors in the early phase of the disease." }, { "input": "Describe the role of epidermal CYLD inactivation in sebaceous and basaloid skin tumors", "output": "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors. The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDm-syndrome)." }, { "input": "Describe the role of epidermal CYLD inactivation in sebaceous and basaloid skin tumors", "output": "Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors." }, { "input": "Describe the role of epidermal CYLD inactivation in sebaceous and basaloid skin tumors", "output": "The deubiquitinase-encoding CYLDM gene is a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDM-Syndrome). It's a dominant gene in the basaloid and sebaceous regions of the epidermis, which is the outermost layer of the skin. When it's mutated, it can lead to a variety of skin tumors." }, { "input": "Describe the role of epidermal CYLD inactivation in sebaceous and basaloid skin tumors", "output": "The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDm-syndrome). Despite recent advances, little is understood about the molecular mechanisms responsible for this painful and difficult-to-treat skin disease. Epidermal CYLD inactivation sensitizes mice to the development of sebaceous and basaloid skin tumors." }, { "input": "Describe the mechanism of action of Lisocabtagene maraleucel.", "output": "Lisocabtagene maraleucel is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product." }, { "input": "What is the cause of the Kleefstra syndrome?", "output": "Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a rare form of intellectual disability (ID) with strong autistic traits and sensory processing deficits." }, { "input": "Is acupotomy used to treat muscle stiffness?", "output": "Yes. Acupotomy has been widely used to treat nerve entrapment syndrome. URL_0" }, { "input": "Is acupotomy used to treat muscle stiffness?", "output": "Acupotomy has been used to treat frozen shoulder, cervical spondylosis, third lumbar vertebrae transverse process syndrome, trigger finger, knee osteoarthritis, and lumbar spinal stenosis." }, { "input": "Which is the role of mediator in genome organization?", "output": "Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly." }, { "input": "Which is the role of mediator in genome organization?", "output": "Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4. Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement." }, { "input": "Which is the role of mediator in genome organization?", "output": "mediator binds to boundaries of chromosomal interaction domains and to proteins involved in dna looping, rna metabolism, chromatin remodeling, and actin assembly.. mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to rna polymerase ii in eukaryotes." }, { "input": "Which is the role of mediator in genome organization?", "output": "Mediator plays a significant role in higher-order genome organization. Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4" }, { "input": "Which two antibodies directed towards the CGRP ligand, were approved by the FDA in September 2018.", "output": "Two antibodies, fremanezumab and galcanezumab, directed towards the CGRP ligand, were approved by the FDA in September 2018." }, { "input": "Describe LowMACA", "output": "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver mutations through the identification of their mutational hotspots. Low MACA is an R package available at http://www.bioconductor.org/packages/release/bioc/html/LowMCCC.html." }, { "input": "Describe LowMACA", "output": "LowMACA is a software for the identification of gain-of-function mutations in putative oncogenic families, increasing the amount of information on functional domains and their possible role in cancer. In this context LowMACA emphasizes the role of genes mutated at low frequency otherwise undetectable by classical single gene analysis." }, { "input": "Describe LowMACA", "output": "LowMACA is a computational tool for the analysis and visualization of somatic mutation data in cancer." }, { "input": "Describe LowMACA", "output": "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a software for the identification of gain-of-function mutations in putative oncogenic families, increasing the amount of information on functional domains and their possible role in cancer. In this context LowMACA emphasizes the role of genes mutated at low frequency otherwise undetectable by classical single gene analysis. LowMACA is an R package available at http://www.bioconductor.org/packages/release/bioc/html/LowMACA.html. It is also available as a GUI standalone downloadable at: https://cgsb.genomics.iit.it/wiki/projects/LowMACA." }, { "input": "Describe LowMACA", "output": "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver mutations through the identification of their mutational hotspots." }, { "input": "Describe LowMACA", "output": "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is exploiting protein family analysis for the identification of rare driver mutations in cancer." }, { "input": "Describe LowMACA", "output": "LowMACA (Low frequency Mutations Analysis via Consensus Alignment) is a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver genes through the identification of their mutational hotspots. It is an R package available at http://www.bioconductor.org/packages/release/bioc/html/ lowMACA.html." }, { "input": "Describe LowMACA", "output": "LowMACA is designed to visualize and statistically assess potential driver genes through the identification of their mutational hotspots." }, { "input": "Describe LowMACA", "output": "LowMACA is a software that combines the mutations of various proteins sharing the same domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments." }, { "input": "Is ofatumumab effective for multiple sclerosis?", "output": "Ofatumumab, a fully human anti-CD20 monoclonal antibody, is effective for relapsing forms of multiple sclerosis." }, { "input": "List proteins that promotes calcification.", "output": "tissue nonspecific alkaline phosphatase (TNAP)\nmatrix Gla protein (MGP)\nfibroblast growth factor-23 (FGF-23)\nmatrix metalloproteinases" }, { "input": "Please list 3 small molecule CGRP-Receptor antagonists for migraine", "output": "Rimegepant and ubrogepant have been developed for acute migraine treatment, while atogepant is studied for migraine prophylaxis." }, { "input": "What are the two types of duplicated genes in the yeast S. cerevisiae?", "output": "Yeast genes are duplicated both via the whole genome duplication and via smaller scale duplications. The genome of the budding yeast contains 50% of protein-coding genes that are paralogs, including 457 pairs of duplicated genes coming probably from an ancient whole genome duplication." }, { "input": "What are the two types of duplicated genes in the yeast S. cerevisiae?", "output": "The mechanism of duplication matters, with whole-genome duplicates being more transcriptionally altered than small-scale duplicates." }, { "input": "Why is fingolimod considered a prodrug?", "output": "FTY720/fingolimod, is considered a prodrug because it requires in vivo phosphorylation to its active phosphorylated form." }, { "input": "Is there a role for Dickkopf-1 (DKK1) in prostate cancer?", "output": "Yes. Dickkopf-1 (DKK1) expression is increased in double-negative prostate cancer (DNPC) relative to prostate-specific antigen (PSA)-expressing Metastatic castration-resistant prostate cancer (mCRPC)." }, { "input": "Is there a role for Dickkopf-1 (DKK1) in prostate cancer?", "output": "Yes, Dickkopf-1 (DKK-1) stimulated prostate cancer growth and metastasis and inhibited bone formation in osteoblastic bone metastases." }, { "input": "What is Hemophilic Pseudotumor?", "output": "Hemophilic Pseudotumor is a rare complication of hemophilia. It is an encapsulated haematoma in patients with haemophilia which has a tendency to progress and produce clinical symptoms related to its anatomical location. The lesion most frequently occurs in the long bones, pelvis, small bones of the hands and feet, or rarely in the maxillofacial region." }, { "input": "What is the aim of the TRAP method?", "output": "The translating ribosome affinity purification (TRAP) method is used to obtain obtain translatome data." }, { "input": "The Shingrix vaccine is used to prevent what disease?", "output": "The Shingrix vaccine is used for prevention of herpes zoster." }, { "input": "The Shingrix vaccine is used to prevent what disease?", "output": "Shingrix is a 4-component vaccine against capsular herpes zoster (4CZV), which has recently been licensed in Europe, Canada and Australia." }, { "input": "The Shingrix vaccine is used to prevent what disease?", "output": "the shingrix vaccine is used for the prevention of herpes zoster and postherpetic neuralgia." }, { "input": "The Shingrix vaccine is used to prevent what disease?", "output": "The Shingrix vaccine prevents Postherpetic neuralgia, also known as Shingles, which is caused by herpes zoster (HZ)" }, { "input": "The Shingrix vaccine is used to prevent what disease?", "output": "Shingrix vaccine is used for prevention of herpes zoster." }, { "input": "What is the function of HP1a in the nucleus?", "output": "Heterochromatin protein 1 (HP1) is an abundant component of heterochromatin, a highly condensed compartment of the nucleus that comprises a major fraction of complex genomes." }, { "input": "What is the function of HP1a in the nucleus?", "output": "Drosophila heterochromatin-associated protein 1 (HP1) is an abundant component of heterochromatin, a highly condensed compartment of the nucleus that comprises a major fraction of complex genomes." }, { "input": "What is the function of HP1a in the nucleus?", "output": "Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as a heterochromatin associated protein required for epigenetic gene silencing." }, { "input": "Has AZD9668 been tested in clinical trials?", "output": "Yes, AZD9668 has been tested in clinical trials." }, { "input": "Which class of genomic elements was assessed as part of the FANTOM6 project?", "output": "Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, the expression of 285 lncRNAs was systematically knocked down in human dermal fibroblasts. Cellular growth, morphological changes, and transcriptomic responses were quantified using Capped Analysis of Gene Expression (CAGE)." }, { "input": "Which class of genomic elements was assessed as part of the FANTOM6 project?", "output": "The functional annotation of the mammalian genome 6 (FANTOM6) project aims to systematically map all human long noncoding RNAs (lncRNAs) in a gene-dependent manner through dedicated efforts from national and international teams" }, { "input": "Which molecule is targeted by Camrelizumab?", "output": "Camrelizumab is a humanised antibody that targets programmed death-1 (PD-1) ligand." }, { "input": "Which molecule is targeted by Camrelizumab?", "output": "Camrelizumab is PD-1 (programmed cell death-1 receptor) inhibitor that is used for treatment of cancer." }, { "input": "What is a foam cell?", "output": "Foam cell, a hallmark of atherosclerosis, is prominently derived from monocyte-differentiated macrophage, and vascular smooth muscle cells (VSMCs) through unlimitedly phagocytizing oxidized low-density lipoprotein (oxLDL). Therefore, the inhibition of monocyte adhesion to endothelium and uptake of oxLDL might be a breakthrough point for retarding atherosclerosis." }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": " Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis." }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": "3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors (statins) are generally well tolerated, with statin-associated muscle symptoms (SAMS) the most common side effect (~10%) seen in statin users." }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": "The most commonly experienced side-effect of statin medication is muscle pain" }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": "A class of drug called a statin. It's a drug that works by reducing the amount of cholesterol in the body, which is what causes muscle fatigue." }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": "statins are generally well tolerated, with statin-associated muscle symptoms (sams) the most common side effect (~10%) seen in statin users." }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": "Statin use has been associated with an increased risk of glucocorticoid-induced rhabdomyolysis as well as with adverse effects such as mysositis and hypercholesterolemia." }, { "input": "What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect?", "output": "3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors, a class of drugs called statins are generally well tolerated, with statin-associated muscle symptoms (SAMS) such as muscle pain, myositis, and rarely rhabdomyolysis, the most common side effect (~10%) seen in statin users." }, { "input": "Which cytokine molecule activates SMADs?", "output": "SMADs are activated by Transforming growth factor beta (TGF beta)" }, { "input": "Which cytokine molecule activates SMADs?", "output": "smads are activated by transforming growth factor-\u03b2 (tgf-\u03b2)." }, { "input": "Which cytokine molecule activates SMADs?", "output": "SMADs are activated by Transforming growth factor beta (TGF-\u03b2)" }, { "input": "Which cytokine molecule activates SMADs?", "output": "TGF-\u03b21 effects appear to be mediated through the canonical Smad pathway." }, { "input": "Which cytokine molecule activates SMADs?", "output": "SMADs are activated by Transforming growth factor beta (TGF beta)." }, { "input": "Which cytokine molecule activates SMADs?", "output": "In an NEC animal model, oral administration of the isoform TGF-\u03b21 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence Transcription factor specificity protein 1 modulates TGF\u03b21/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P." }, { "input": "Which cytokine molecule activates SMADs?", "output": "The protein expression of TGF\u2011\u03b21/mothers against decapentaplegic homolog (Smad) and phosphoinositide 3\u2011kinase (PI3K)/protein kinase B (AKT) signaling pathways was evaluated by western blotting regulates the ERK/MAPK pathway independent of the SMAD pathway" }, { "input": "Which cytokine molecule activates SMADs?", "output": "Activated SMADs are phosphorylated by TGF-\u03b2 superfamily type I receptors at two serine residues at an S-M/V-S motif at their extreme C-terminus. Once phosphorylated, activated R-SMADs form complexes with SMAD4, which accumulate in the nucleus where they activate or repress transcription." }, { "input": "What is the Oncomine Dx Target test?", "output": "The Oncomine Dx Target Test (ODxTT) is a next-generation sequencing-based companion diagnostic test, that could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC." }, { "input": "What are common variants at 12q14 and 12q24 associated with?", "output": "Common variants at 12q14 and 12q24 are associated with hippocampal volume. Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors." }, { "input": "What are common variants at 12q14 and 12q24 associated with?", "output": "Common variants at 12q14 and 12q24 are associated with hippocampal volume. As we age, our hippocampus (the part of the brain that is responsible for memory and cognition) becomes less and less efficient at storing information. As a result, the volume of the hippocampus shrinks." }, { "input": "What are common variants at 12q14 and 12q24 associated with?", "output": "Common variants at 12q14 and 12q24 are associated with hippocampal volume." }, { "input": "What are common variants at 12q14 and 12q24 associated with?", "output": "Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Common variants at 12q14 and 12q24 are associated with hippocampal volume." }, { "input": "Which mutation is targeted by Sotorasib?", "output": "Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C." }, { "input": "When is DELE1 exiting the mitochondrion?", "output": "Mitochondrial stress stimulates OMA1-dependent cleavage of DELE1 and leads to the accumulation of DELE1 in the cytosol." }, { "input": "What is a ciliopathy?", "output": "A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function" }, { "input": "What is a ciliopathy?", "output": "Ciliopathy is a rare disorder of the central nervous system characterized by defects in ciliary motility, endocytosis, and photoreceptors." }, { "input": "What is a ciliopathy?", "output": "ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking." }, { "input": "What is a ciliopathy?", "output": "Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking." }, { "input": "Which histone mark is recognized by HP1?", "output": "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins--a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure." }, { "input": "Which histone mark is recognized by HP1?", "output": "h3k9me3 is the major histone mark that is recognized by hp1." }, { "input": "Which histone mark is recognized by HP1?", "output": "Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins." }, { "input": "Which histone mark is recognized by HP1?", "output": "Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression." }, { "input": "Which histone mark is recognized by HP1?", "output": "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species." }, { "input": "Which histone mark is recognized by HP1?", "output": "HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4. Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression." }, { "input": "Which histone mark is recognized by HP1?", "output": "Histone H3 at lysine 9 (H3K9me3)" }, { "input": "Which histone mark is recognized by HP1?", "output": "Histone H3 at lysine 9 trimethylation (H3K9me3)" }, { "input": "What is AZD8601?", "output": "AZD8601 is a modified mRNA encoding vascular endothelial growth factor A (VEGF-A). Sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing." }, { "input": "List critical regions for 7p22.1 microduplication syndrome", "output": "7p22.1 microduplication syndrome is mainly characterized by developmental and speech delay, craniofacial dysmorphism and skeletal abnormalities. The minimal critical region includes two OMIM genes: ACTB and RNF216." }, { "input": "List critical regions for 7p22.1 microduplication syndrome", "output": "7p22.1 microduplication syndrome is mainly characterized by developmental and speech delay, craniofacial dysmorphisms and skeletal abnormalities. The minimal critical region includes two OMIM genes: ACTB and RNF216." }, { "input": "Which molecules are targeted by Trastuzumab Deruxtecan?", "output": "Trastuzumab deruxtecan is a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate being developed for the treatment of HER2-expressing solid tumours, including breast cancer, gastric cancer, colorectal cancer and non-small cell lung cancer" }, { "input": "What is the function of the HSJ1 proteins?", "output": "HSJ1 is a neuronal enriched member of the HSP40/DNAJ co-chaperone family." }, { "input": "What is the indication for zolmitriptan?", "output": "Development of a novel zolmitriptan intracutaneous microneedle system (Qtrypta\u2122) for the acute treatment of migraine" }, { "input": "What is the indication for zolmitriptan?", "output": "Zolmitriptan is an effective medicine used in the treatment of migraine." }, { "input": "What is the indication for zolmitriptan?", "output": "zolmitriptan is approved for the treatment of migraine." }, { "input": "What is the indication for zolmitriptan?", "output": "zolmitriptan is approved for migraine treatment." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Approximately 15% of the genes in C. elegans are operons." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Both methods indicate that the pre-mRNAs of about 70% of Caenorhabditis elegans genes are trans-spliced and as many as a quarter are transcribed in these operons." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "about 15% of genes in Caenorhabditis elegans, a model organism belonging to Nematoda, reside in operons (Blumenthal et al. 2002; Blumenthal and Gleason 2003). For two reasons, nematode and prokaryotic operons are believed to have separate origins." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Our data indicate that 15% of the genes in C. elegans reside in operons." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Approximately 15% of the genes in C. elegans are located in operons, of which at least 15% are known to date." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Nearly 15% of the ~20,000 C. elegans genes are contained in operons, multigene clusters controlled by a single promoter. Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Because operons account for about 15% of the genes in C. elegans, this lower duplication frequency might place a large constraint on the plasticity of the genome." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Approximately 15% of the genes in C. elegans are located in operons." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "About 15% of all C. elegans genes reside in operons. URL_0 > Nearly 15 percent of the ~20,000 C. Elegans genes are contained in operon, multigene clusters controlled by a single promoter." }, { "input": "What percentage of C. elegans genes reside in operons?", "output": "Evidence indicates that the genome of C. elegans contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes." }, { "input": "What is the most advanced phase of clinical trial that fingolimod has entered?", "output": "Fingolimod has been assessed in phase IV clinical trials." }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism, which is the most common and curable form of arterial hypertension." }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. " }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. The leukodystrophy of Glialcam, which is encoded in the gene, is associated with dysregulated extracellular ion homeostasis, and abnormal RPE cell function." }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "Primary aldosteronism is a rare autosomal dominant disorder caused by gain-of-function mutations in CLCN2 and clinically characterized by severe intrauterine and post-natal growth retardation" }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism." }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "Primary aldosteronism is an autosomal dominant disorder caused by gain-of-function mutations in CLCN2." }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Primary aldosteronism is the most common and curable form of secondary arterial hypertension." }, { "input": "What is caused by a gain-of-function mutation in CLCN2?", "output": "Primary aldosteronism is the most common and curable form of secondary arterial hypertension. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism." }, { "input": "Which treatments were compared in the UNBLOCS trial?", "output": "The UNBLOCS trial compared thulium laser transurethral vaporesection of the prostate versus transurethral resection of the prostate for men with lower urinary tract symptoms or urinary retention." }, { "input": "Which are the ligands of the Roundabout (Robo) receptors?", "output": "Roundabouts comprise a family of single-pass transmembrane receptors facilitating this process upon interaction with the soluble extracellular ligand Slit protein family emanating from the midline." }, { "input": "What is the function of kisspeptin in the brain?", "output": "Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis. It is the most potent factor known to induce GnRH release. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus" }, { "input": "What is the function of kisspeptin in the brain?", "output": "kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus and human neuronal cell line." }, { "input": "What is the function of kisspeptin in the brain?", "output": " Kisspeptin is the most potent factor known to induce GnRH release. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus" }, { "input": "What is the function of kisspeptin in the brain?", "output": "Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis. Kisspeptin also preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain." }, { "input": "What is the function of kisspeptin in the brain?", "output": " Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis" }, { "input": "What is the function of kisspeptin in the brain?", "output": "The function of kisspeptin in the brain is not really known, but it plays an integral role in the regulation of hunger, sex, and reproduction. Kisspeptin is the most potent factor known to induce GnRH release in Mice. URL_0" }, { "input": "What is the function of kisspeptin in the brain?", "output": " Kisspeptin is the most potent factor known to induce GnRH release. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis Intraperitoneal Treatment of Kisspeptin Suppresses Appetite and Energy Expenditure and Alters Gastrointestinal Hormones in Mice." }, { "input": "What is the function of kisspeptin in the brain?", "output": "Kisspeptin is a leptin-like protein that exerts important effects on the regulation of food intake and energy expenditure by interacting with the glucocorticoid receptor in the brain." }, { "input": "What is the function of kisspeptin in the brain?", "output": "Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis." }, { "input": "Is Nanog repressed in pluripotent stem cells?", "output": "The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm." }, { "input": "Is Nanog repressed in pluripotent stem cells?", "output": "No. The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm." }, { "input": "Is Nanog repressed in pluripotent stem cells?", "output": "Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm." }, { "input": "What is the mode of administration of Ubrogepant?", "output": "Ubrogepant (MK-1602) is administered orally." }, { "input": "Are synonymous sites in primates and rodents functionally constrained?", "output": "No. Synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. In primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally." }, { "input": "Which animal bite can cause Capnocytophaga canimorsus infection?", "output": "Capnocytophaga canimorsus infection is typically associated with dog bites, especially in asplenic or immunocompromised patients, and typically manifest as sepsis and/or bacteremia." }, { "input": "What is the function of lysozyme?", "output": "Lysozymes are an ancient group of antimicrobial enzymes of the innate immune system. Lysozyme activity is a marker of Paneth cell function." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band syndrome (ABS) is a rare congenital disease with variable manifestations ranging from simple constriction rings at the extremities to major defects such as exencephaly." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts in fibrous amniotic bands." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band syndrome is a rare congenital disorder characterized by the association of bilateral microtia, aplasia or hypoplasia of the upper aerodigestive tract, and severe pre- and postnatal growth retardation." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band syndrome, also known as constriction ring syndrome, happens when fibrous bands of the amniotic sac (the lining inside the uterus that contains a fetus) get tangled around a developing fetus. In rare cases, the bands wrap around the fetus' head or umbilical cord." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band sequence (ABS) is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero that presents with complex multisystem anomalies." }, { "input": "Explain amniotic band syndrome.", "output": "yes, amniotic band syndrome is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions." }, { "input": "Explain amniotic band syndrome.", "output": "Amniotic band syndrome is a rare congenital disorder characterized by the association of bilateral microtia, aplasia or hypoplasia of the collagen fibers of the fascia of the palm, and severe pre- and postnatal growth retardation." }, { "input": "Explain amniotic band syndrome.", "output": "abs is an uncommon and heterogeneous congenital disorder caused by entrapment of fetal parts by fibrous amniotic bands, causing distinctive structural abnormalities involving limbs, trunk, and craniofacial regions. the incidence ranges between 1/1200 and 1/15,000 live births, but is higher in stillbirths and previable fetuses." }, { "input": "Which are the main advantages of kallisto against similar methodologies?", "output": "Kallisto is a pseudo-alignment algorithm, which is a way of quantifying RNA-sequencing. It's used in RNA-seq because it's much faster and more efficient than other methodologies." }, { "input": "Which are the main advantages of kallisto against similar methodologies?", "output": "Kallisto is two orders of magnitude faster than similar methodologies. It uses a novel efficient approach to perform this analysis and to calculate informative metrics at each depth required to inform a broad range of functional and evolutionary studies. It improves performance and speed of RNA sequencing analysis of large data sets." }, { "input": "Which are the main advantages of kallisto against similar methodologies?", "output": "kallisto, an RNA-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy." }, { "input": "Which are the main advantages of kallisto against similar methodologies?", "output": "kallisto is an RNA-seq quantification program that is two orders of magnitude faster than previous approaches and achieves similar accuracy. Kallisto pseudoaligns reads to a reference, producing a list of transcripts that are compatible with each read while avoiding alignment of individual bases." }, { "input": "What methodology does the HercepTest use?", "output": "The HercepTest is immunohistochemistry based." }, { "input": "Which R/Bioconductor package has been developed for gene expression signature searching?", "output": "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (ESE) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results." }, { "input": "Which R/Bioconductor package has been developed for gene expression signature searching?", "output": "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (ESE) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. To identify which processes are predominantly modulated in the GESS results, FEA methods are combined with drug-target network visualization tools. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types" }, { "input": "Which R/Bioconductor package has been developed for gene expression signature searching?", "output": "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results." }, { "input": "Which R/Bioconductor package has been developed for gene expression signature searching?", "output": "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types." }, { "input": "Which R/Bioconductor package has been developed for gene expression signature searching?", "output": "SignatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (ANS) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results." }, { "input": "Which molecule is targeted by Upadacitinib?", "output": "Upadacitinib is a Janus kinase 1 inhibitor developed for treatment of moderate to severe rheumatoid arthritis." }, { "input": "Which molecule is targeted by Upadacitinib?", "output": "Upadacitinib is a Janus kinase 1 inhibitor under development for the treatment of several inflammatory disorders including rheumatoid arthritis." }, { "input": "What is known about natriuretic peptide receptor A?", "output": "Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure.\nThe natriuretic peptide receptor A (NPRA), also known as NPR1 or guanylyl cyclase A, binds ANP and BNP to initiate transmembrane signal transduction by elevating the intracellular levels of cyclic guanosine monophosphate." }, { "input": "What is the mode of action of dexamethasone?", "output": "Glucocorticoids like Dexamethasone have a number of modes of action. While these drugs are used to reduce inflammation, Dexamethasone can also induce apoptosis thru initiation of autophagy, activate glucocorticoid receptors in the treatment of uveitic edema, alter gene expression in allergic asthma prevent tachycardia-induced ionic remodeling by reduction of atrial sodium current I(Na), increase gut permeability and suppress inflammation. in addition, Dexamethasone (Dex) can enhance BMP-2-induced osteoblast differentiation and can differentially modulated dendritic cell maturation and TREM1 signaling pathways in GM-CSF-treated and M-CSF-treated monocytes. Dexamethasone can be used for pain management" }, { "input": "What is the mode of action of dexamethasone?", "output": "yes, dexamethasone is used to treat acute graft-versus-host disease (agvhd) due to its immunosuppressive activity." }, { "input": "What is the mode of action of dexamethasone?", "output": "Dexamethasone (Dex), a synthetic glucocorticoid (GC), in feed has been shown to increase gut permeabilit" }, { "input": "What is the phenomenon described as \"complex coacervation\"?", "output": "Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. Impact of macromolecular crowding on RNA/spermine complex coacervation and oligonucleotide compartmentalization. The addition of PEG decreased both the amount of spermine required for phase separation and the coacervation temperature (TC)." }, { "input": "What is the phenomenon described as \"complex coacervation\"?", "output": " Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. Impact of macromolecular crowding on RNA/spermine complex coacervation and oligonucleotide compartmentalization. The addition of PEG decreased both the amount of spermine required for phase separation and the coacervation temperature (TC)." }, { "input": "What is the phenomenon described as \"complex coacervation\"?", "output": "Charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. The addition of PEG decreased both the amount of spermine required for phase separation and the coacoration temperature (TC)." }, { "input": "What is the phenomenon described as \"complex coacervation\"?", "output": " Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules." }, { "input": "What is the phenomenon described as \"complex coacervation\"?", "output": "Recently, we reported a unique and nearly ubiquitous phenomenon of inducing simple and complex coacervation in solutions of a broad variety of individual and mixed amphiphiles and over a wide range of concentrations and mole fractions. Complex coacoration is an emerging liquid/liquid phase separation (LLPS) phenomenon that behaves as a membrane-less organelle in living cells." }, { "input": "What is the phenomenon described as \"complex coacervation\"?", "output": "Complex coacervation is a phase separation process that is mediated by the charges of the components involved." }, { "input": "Which proteins does RG-7992 target?", "output": "BFKB8488A is a bispecific antibody against FGFR1 and KLB." }, { "input": "Is there a role for TFII-I in megakaryopoiesis?", "output": "Yes. TFII-I acts as a repressor of \u03b2-globin gene transcription and is implicated in the differentiation of erythrocytes into megakaryopoiesis. Mutations in exon 2 interfere with the synthesis of the full-length isoform of TF II-I and lead to the production of a shortened isoform, TFII, in erythroid cells. TF2-I has a role in embryonic development and differentiation of all eukaryotes but its physiological function is still unclear." }, { "input": "Is there a role for TFII-I in megakaryopoiesis?", "output": "Yes. TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. TFII-I acts as a repressor of \u03b2-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells." }, { "input": "Is there a role for TFII-I in megakaryopoiesis?", "output": "Yes. The data show that TFII-I acts as a repressor of \u03b2-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells." }, { "input": "Is there a role for TFII-I in megakaryopoiesis?", "output": "Yes. TFII-I acts as a repressor of \u03b2-globin gene transcription and it is implicated in the differentiation of erythrocytes and megakaryopoiesis. In fact, upregulation of TF II-I expression in mesenchymal stem cells increases both survival and angiogenesis and may therefore represent a novel and efficient therapeutic approach for modulating cell proliferation and differentiation." }, { "input": "Which drugs are included in the VAC regiment for Ewing's sarcoma?", "output": "VAC regiment for Ewing's sarcoma includes vincristine, actinomycin, cyclophosphamide." }, { "input": "Is YKL-40 used as a biomarker for Alzheimer's disease?", "output": "Yes,\ncerebrospinal fluid (CSF) YKL-40 levels were reported to be a promising candidate biomarker of glial inflammation in Alzheimer's disease (AD)." }, { "input": "On what chromosome is the gene for \"SILVER\" coat color found for the domestic cat?", "output": "Linkage mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87-99.21 Mb) on chromosome D2 in the domestic cat." }, { "input": "On what chromosome is the gene for \"SILVER\" coat color found for the domestic cat?", "output": "the gene for \"silver\" coat color found for the domestic cat is located on chromosome d2." }, { "input": "Which lncRNAs are induced by heatshock?", "output": "Malat1, papas, long noncoding rnas, circrna, neat1, and mirna are induced by heat shock." }, { "input": "Which lncRNAs are induced by heatshock?", "output": "Malat1, papas, long noncoding rnas, circrna, neat1 and mirna are induced by heathock." }, { "input": "Which lncRNAs are induced by heatshock?", "output": "The Malat1 long non-coding RNA is upregulated by signalling through the PERK axis of unfolded protein response during flavivirus infection. Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA. The long non-coding RNA NEAT1 and nuclear paraspeckles are upregulated by the transcription factor HSF1 in the heat shock response" }, { "input": "What is the prevalence of poor metabolizers of CYP2C19 among Southern Asians compared to East Asians?", "output": "Southeast Asians exhibit a higher prevalence of CYP2C19-poor metabolisers compared with Caucasians and East Asians." }, { "input": "Which R/Bioconductor package has been developed for network-based differential expression analysis?", "output": "INDEED is an R/Bioconductor package for network based differential expression analysis. INDEED allows users to construct a sparse network based on partial correlation, and to identify biomolecules that have significant changes both at individual expression and pairwise interaction levels." }, { "input": "Can propofol cause green urine?", "output": "Yes, propofol can cause green discoloration of urine. It is a rare and benign condition, which occurs when clearance of propofol exceeds the hepatic and extrahepatic elimination." }, { "input": "Are Gram positive bacteria able to release extracellular vesicles?", "output": "Yes, Gram-negative and Gram-positive bacteria release a variety of membrane vesicles through different formation routes." }, { "input": "Describe a cytokine release syndrome.", "output": "The major factor responsible for acute respiratory distress syndrome is the so-called \"cytokine storm,\" which is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines." }, { "input": "Describe a cytokine release syndrome.", "output": "Cytokine release syndrome is defined by the release of cytokines from sarcoplasmic reticulum (SR) and is associated with retinal vein occlusions, fatigue and dyspnea." }, { "input": "Describe a cytokine release syndrome.", "output": "Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction that is associated with chimeric antigen receptor (CAR)-T cell therapy, therapeutic antibodies, and haploidentical allogeneic transplantation." }, { "input": "Describe a cytokine release syndrome.", "output": "cytokine storm is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines." }, { "input": "Describe a cytokine release syndrome.", "output": "Cytokine release syndrome is characterized by the release of cytokines from the cytosol into the cerebrospinal fluid (CSF) and cytokine production from the sarcoplasmic reticulum (SR)." }, { "input": "Describe a cytokine release syndrome.", "output": "the so-called \"cytokine storm,\" which is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines." }, { "input": "Describe a cytokine release syndrome.", "output": "\"Cytokine storm,\" is an aberrant response from the host immune system that induces an exaggerated release of proinflammatory cytokines/chemokines. I" }, { "input": "Describe a cytokine release syndrome.", "output": "A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS)." }, { "input": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "output": "The genes involved in primitive endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, p dgfr\u03b1, gATA6, nanog, pDgfralpha, egam1 and dab2." }, { "input": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "output": "Fgf receptor/Erk signalling is known to be required for specification of the primitive endoderm. Platelet derived growth factor receptor alpha (Pdgfr\u03b1) as an early-expressed protein that is also a marker of the later primitive endoderm lineage. ES cells expressing exogenous EGAM1 preferentially differentiate into extra-embryonic primitive endoderm. Lrp2 is a novel PrE precursor (pre-PrE) marker by using a microarray strategy that combines a transcriptome analysis of three stem cell lines and early embryos." }, { "input": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "output": "The genes which are the main markers of primitive Endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, pDgfr\u03b1, gATA6, nanog, p dgfralpha, egam1 and dab2." }, { "input": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "output": "The main markers of primitive Endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, p dgfr\u03b1, gATA6, nanog, pDgfralpha, egam1 and dab2." }, { "input": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "output": "The main markers of primitive Endoderm (prEN) formation are fgf4, lrp2, gata4, pdgfra, pDgfr\u03b1, gATA6, nanog, p dgfralpha, egam1 and dab2." }, { "input": "Which genes are the main markers of primitive Endoderm (prEN) formation?", "output": "The markers of primitive endoderm (prEN) formation are the transcriptional activators fgf4 and its ligand, lrp2, gata4, pdgfra, p dgfr\u03b1, gATA6, nanog, pDgfralpha, egam1 and dab2." }, { "input": "What are the EMA and FDA recommendations regarding pharmacogenetic testing for abacavir?", "output": "Abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir. Accordingly to these results the abacavir label has been modified: the European Medicines Agency (EMA) and the FDA recommend/suggested that the administration of abacavir must be preceded by a specific genotyping test. The HLA locus is extremely polymorphic, exhibiting many closely related alleles, making it difficult to discriminate HLA-B*57:01 from other related alleles, and a number of different molecular techniques have been developed recently to detect the presence of HLA-B*57:01." }, { "input": "Describe PWMScan", "output": "PWMScan is used to scan a position weight matrix (PWM) against a genome or, in general, a large set of DNA sequences. The PWM is the most commonly used mathematical model to describe the DNA binding specificity of a transcription factor (TF). " }, { "input": "Describe PWMScan", "output": "PWMScan is a fast web-based tool to scan server- resident genomes for matches to a user-suppressor PWM or transcription factor binding site model from a public database." }, { "input": "Describe PWMScan", "output": "pwmscan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied pwm or transcription factor binding site model from a public database." }, { "input": "Describe PWMScan", "output": "PWMScan is a fast web-based tool to scan server- resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database." }, { "input": "Describe PWMScan", "output": "pwmscan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied pw or transcription factor binding site model from a public database." }, { "input": "Describe PWMScan", "output": "PWMScan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database. It is available for pre-assembled copies of the original PWM/TF binding model." }, { "input": "Describe PWMScan", "output": "Transcription factors regulate gene expression by binding to specific short DNA sequences of 5-20 bp to regulate the rate of transcription of genetic information from DNA to messenger RNA. PWMScan is a fast web-based tool to scan server-resident genomes for matches to a user-supplied PWM or transcription factor binding site model from a public database." }, { "input": "Describe PWMScan", "output": "PWMScan is a fast web-based tool to scan server- resident genomes for matches to a user-suppressor PWM or transcription factor binding site model from a Public database." }, { "input": "Describe PWMScan", "output": "PWMScan is a fast web-based tool for scanning entire genomes with a position-specific weight matrix. It's a fast and cheap way to scan a large portion of an entire genome with a small amount of time." }, { "input": "Is vocimagene amiretrorepvec effective for glioblastoma?", "output": "No. Treatment with vocimagene amiretrorepvec did not improve survival of glioblastoma patients." }, { "input": "List the major royal jelly proteins in Apis mellifera.", "output": "The genome of the western honeybee (Apis mellifera) harbors nine transcribed major royal jelly protein genes (mrjp1-9) which originate from a single-copy precursor via gene duplication." }, { "input": "What is BEL(Biological Expression Language) used for?", "output": "Biological Expression Language (BEL) is a novel method for the statistical extraction of causal relation relationships from large biomedical literature datasets." }, { "input": "What is BEL(Biological Expression Language) used for?", "output": "Biological expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships." }, { "input": "What is BEL(Biological Expression Language) used for?", "output": "Biological expression language (BEL) is a syntax representation allowing for the structured representation of a broad range of biological relationships. It is used in various situations to extract such knowledge and transform it into BEL networks." }, { "input": "What is BEL(Biological Expression Language) used for?", "output": "Biological Expression Language (BEL) is a novel method for the automatic extraction of causal relation networks from biomedical literature." }, { "input": "What is BEL(Biological Expression Language) used for?", "output": "Biological Expression Language (BEL) is a novel method for statistical extraction of causal relation networks from biomedical literature." }, { "input": "What is BEL(Biological Expression Language) used for?", "output": "Biological Expression Language (BEL) is a literature-based method for the statistical estimation of causal relation relationships among entities (e.g. species, populations, populations) and temporal relationships among them." }, { "input": "Which database contains gene expression data for yeast?", "output": "We developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays." }, { "input": "Which database contains gene expression data for yeast?", "output": "The MOPED database (http://arep.med.har. Edu/ expressDB) provides access to extensive gene expression data from yeast genomes." }, { "input": "Which database contains gene expression data for yeast?", "output": "We developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays. MOPED (Multi-Omics Profiling Expression Database; http://moped.proteinspire.org) has transitioned from solely a protein expression database to a multi-omics resource for human and model organisms." }, { "input": "Which database contains gene expression data for yeast?", "output": "The ExpressDB database is a database for yeast RNA expression data. The FED database is for fungal gene expression data for yeast." }, { "input": "Which CYP gene polymorphism is a well-known predictor of efavirenz disposition?", "output": "Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response, playing an important role in the regulation of cell differentiation." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response, playing an important role in the regulation of cell proliferation and differentiation." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum and ER-associated degradation (ERAD)." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfold protein response." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response. The pathway is indispensable for the development of secretory cells by facilitating protein folding and enhancing secretory capacity." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation." }, { "input": "What is the role of the IRE1a-XBP1 pathway?", "output": "The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response. It is indispensable for the development of secretory cells by facilitating protein folding and enhancing secretory capacity." }, { "input": "Can Panitumumab cause trichomegaly?", "output": "Yes. Panitumumab is EGFR inhibitor that is associated with eyelash trichomegaly." }, { "input": "List proteins that are contained in atherosclerotic plaques?", "output": "extracellular matrix proteins\nbiglycan\nLumican\nApolipoprotein A-I" }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "yes, developmental and epileptic encephalopathies (dees) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Clinical characteristics of Developmental and Epileptic Encephalopathies include global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Clinical characteristics of Developmental and Epileptic Encephalopathies (DEEs) include global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing, resulting in deterioration in developmental, cognitive, and motor functions." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "developmental and epileptic encephalopathies (dees) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Developmental and epileptic encephalopathies (DEEs) are a group of severe neurological disorders characterized by global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Developmental and epileptic encephalopathies (DEEs) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": " Developmental epileptic encephalopathies (DEEs) are genetically heterogeneous severe childhood-onset epilepsies with developmental delay or cognitive deficits." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Clinical characteristics of Developmental and Epileptic Encephalopathies (DEEs) include global developmental delay, contractures, refractory seizures, intractable seizures, epilepsy, facial dysmorphism, macrocephaly, cognitive deficits, autism, seizures, cerebellar dysgenesis, developmental delayed, behavioral abilities, developmental impairment or regression, intellectual disability, and brain anomalies." }, { "input": "List characteristics of Developmental and Epileptic Encephalopathies (DEEs).", "output": "Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that have poor prognosis. DEEs are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression." }, { "input": "Which methods exist for efficient calculation of Elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs)?", "output": "EFM-Ta is a novel algorithm that uses a linear programming-based tree search and efficiently enumerates a subset of EFMs in genome-scale metabolic networks (GSMNs). The stand-alone software TreeEFM is implemented in C++ and interacts with the open-source linear solver COIN-OR Linear program Solver (CLP)." }, { "input": "Which methods exist for efficient calculation of Elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs)?", "output": "The efficient calculation of elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs) is still a challenge. EFM-ta and treeefm are two different algorithms that use linear programming-based tree search and efficiently enumerates a subset of EFMs in GSMNs." }, { "input": "Which methods exist for efficient calculation of Elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs)?", "output": "Elementary flux modes (EFMs) are a key tool for analyzing genome-scale metabolic networks, and several methods have been proposed to compute them. Among them, those based on solving linear programming (LP) problems like TreeEFM and EFM-Ta are known to be very efficient if the main interest lies in computing large enough sets of EFMs." }, { "input": "Which methods exist for efficient calculation of Elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs)?", "output": "The efficient calculation of elementary flux modes (EFMs) in genome-scale metabolic networks (GSMNs) is a challenge. Two methods for this task have been developed, eFM-ta and treeefm." }, { "input": "What is the mechanism of action of vosoritide?", "output": "Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification." }, { "input": "What is the \"flight-or-fight response\"?", "output": "This is also known as \" flight-or- fight response\" and is defined as an individual's response to a stimulus such as stress, that includes loss of sleep, anxiety, shortness of breath, muscle and joint pain." }, { "input": "What is the \"flight-or-fight response\"?", "output": "The cAMP intracellular signaling pathway is an important system for signal transmission responsible for the ancestral 'flight or fight' response and involved in the control of critical functions including frequency and strength of heart contraction, energy metabolism and gene transcription." }, { "input": "How is Burke-Fahn-Marsden Dystonia scale used?", "output": "Burck-Fahn-Marsden Dystonia scale (BBS) is a simple, reliable, and valid measure of disease severity in patients with dystonia." }, { "input": "How is Burke-Fahn-Marsden Dystonia scale used?", "output": "Motor responses and disease severity in conditions such as cerebral palsy or other dystonias can be measured with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). This scale can be use to track surgery or treatment response." }, { "input": "How is Burke-Fahn-Marsden Dystonia scale used?", "output": "The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) including the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing." }, { "input": "How is Burke-Fahn-Marsden Dystonia scale used?", "output": "Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) includes the movement and disability scales was used to evaluate the dystonia severity of the eyes, the mouth, speech, and swallowing." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Yes, methotrexate is effective for the treatment of Rheumatoid Arthritis. MTX can be administered in combination with other chemotherapeutic agents or as mono-therapy. Response rate to MTX is more than 90%. MTX therapy is associated with improved survival of RA patients." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Yes, methotrexate is effective for the treatment of Rheumatoid Arthritis." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Methotrexate (MTX) is clearly effective in the treatment of rheumatoid arthritis. MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Yes, methotrexate is used for the treatment of Rheumatoid Arthritis." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Methotrexate is a cornerstone in the treatment of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatic arthritis. It is considered a second-line disease modifying agent." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis. Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis" }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Yes. MTX is a folic acid antagonist that is approved for the management of severe active RA in patients who have had an insufficient therapeutic response to or are intolerant of an adequate trial of first-line therapy, including full-dose NSAIDs." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "The use of methotrexate in rheumatoid arthritis. Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Yes. Methotrexate is used for the treatment of Rheumatoid Arthritis (RA) and other rheumatic diseases." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Yes, methotrexate is a promising treatment option for the treatment of rheumatoid arthritis." }, { "input": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "output": "Methotrexate (MTX) has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions." }, { "input": "What methodology does the FoundationOne CDx test use?", "output": "FoundationOne CDx is a next generation sequencing (NGS) based test." }, { "input": "Which R/bioconductor package exists for discovery of intergenic transcripts?", "output": "To increase the power of transcript discovery from large collection of RNA-seq data sets, a novel '1-Step' approach named pooling RNA-Seq and Assembling Models (PRAM) has been developed that build transcript models from pooled RNA- sequencing data sets. PRAM is implemented as an R/Bioconductor package." }, { "input": "Which R/bioconductor package exists for discovery of intergenic transcripts?", "output": "PRAM is a novel pooling approach for discoveries of intergenic transcripts from large-scale RNA sequencing experiments." }, { "input": "Which R/bioconductor package exists for discovery of intergenic transcripts?", "output": "PRAM is a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments. PRAM is implemented as an R/Bioconductor package. It covers raw reads alignment, RNA methylation site detection, motif discovery and functional analysis. More than 50% of reconstructed transcripts represent novel transcriptome elements, including 8,343 novel exons and exon extensions of annotated coding genes, 11,217 novel antisense transcripts and 29,541 novel intergenic transcript or their fragments showing canonical features of long non-coding RNAs (lncRNAs)." }, { "input": "Which R/bioconductor package exists for discovery of intergenic transcripts?", "output": "Pooling RNA-seq and Assembling Models (PRAM) is a novel approach for discovering intergenic transcripts from large-scale RNA sequencing experiments. Applying PRAM to 30 human ENCODE RNA-seq data sets identified unannotated transcripts with epigenetic signatures similar to those of recently annotated transcripts." }, { "input": "Which R/bioconductor package exists for discovery of intergenic transcripts?", "output": "PRAM (Pooling RNA-seq and Assembling Models) is a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments." }, { "input": "What is the mechanism of action of idasanutlin?", "output": "Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53." }, { "input": "Where is corticosterone synthesized?", "output": "Following a stressful event, the hypothalamus-pituitary-adrenal axis mediates the release of the stress hormone cortisol (corticosterone in rodents; CORT)." }, { "input": "Where is the klotho protein primarily expressed in the body", "output": "The klotho protein is primarily expressed in the lungs, kidney, lens, cerebellum, trpc6, renal cells and the brain." }, { "input": "Where is the klotho protein primarily expressed in the body", "output": "Klotho is primarily expressed in the kidney but also in the brain, lens of the eye, and heart." }, { "input": "Where is the klotho protein primarily expressed in the body", "output": "Klotho is primarily expressed in the lungs, kidney, lens, cerebellum, trpc6, renal cells and the brain." }, { "input": "Which particular intersex phenotype is related to steroid reductase?", "output": "Steroid reductase mutations are associated with both sex-determining and non-syndromic hypospadias" }, { "input": "Which particular intersex phenotype is related to steroid reductase?", "output": "Virilization of the external genitalia in the male fetus requires testosterone and dihydrotestosterone (DHT), which is formed from testosterone by the action of the enzyme, 5alpha-reductase type 2 (5alphaR-2). Numerous cases of male pseudohermaphroditism due to 5 alpha reductase-2 deficiency have been identified." }, { "input": "Which particular intersex phenotype is related to steroid reductase?", "output": "Mutations in the steroid 5 alpha-reductase 2 gene are the cause of 5 alpha reductase deficiency. In the 20 yr since it was established that impairment of dihydrotestosterone formation is a cause of a rare form of human intersex, a wealth of information has accumulated about the genetics, endocrinology, and variable phenotypic manifestations." }, { "input": "Which particular intersex phenotype is related to steroid reductase?", "output": "Hypospadias is a rare form of intersex due to reduced activity of steroid reductase 5 alpha-reductase." }, { "input": "Is atenolol metabolized by CYP2D6?", "output": "No, atenolol is metabolized in a CYP2D6-independent manner." }, { "input": "Describe DeepTRIAGE", "output": "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, placing all luminal samples along a continuum of severity." }, { "input": "Describe DeepTRIAGE", "output": "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture, which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, placed all luminal samples along a continuum of severity." }, { "input": "Describe DeepTRIAGE", "output": "Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. DeepTRIAGE uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample." }, { "input": "Describe DeepTRIAGE", "output": "Breast cancer is a collection of multiple tissue pathologies, each with a distinct molecular signature that correlates with patient prognosis and response to therapy. Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. Although this problem has been addressed using machine learning methods in the past, there remains unexplained heterogeneity within the established sub-types that cannot be resolved by the commonly used classification algorithms. DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is novel deep learning architecture which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample." }, { "input": "Describe DeepTRIAGE", "output": "DeepTRIAGE is an algorithm that uses machine learning to classify breast cancer sub-types. Basically, it takes a bunch of different subtypes of breast cancer, each with a distinct molecular signature that correlates with patient prognosis, and gives a score that describes how important each gene is in predicting the sub-type for each sample." }, { "input": "Describe DeepTRIAGE", "output": "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture, which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, determining all luminal samples along a continuum of severity." }, { "input": "Describe DeepTRIAGE", "output": "DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression) is a novel deep learning architecture, which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. DeepTRIAge simultaneously reveals heterogeneity within the luminal A biomarker score that significantly associate with tumour stage, place all luminal samples along a continuum of severity, and assess whether the major principal axis associate with known clinical phenotypes." }, { "input": "What is Pseudomelanosis duodeni?", "output": "Pseudomelanosis duodeni is a rare incidental finding seen on endoscopy and has the characteristic appearance of flat, black-speckled pigmented mucosa that can be associated with gastrointestinal bleeding, hypertension, chronic heart failure, chronic renal failure and consumption of different drugs." }, { "input": "Is the glucocorticoid receptor a transcription factor?", "output": "Yes,\nThe glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci." }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension." }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors. These factors include obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension." }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension" }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome is the concurrent presentation of multiple cardiovascular factors, including obesity, insulin resistance, type 1 diabetes, type 2 diabetes, and hypertension." }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome is a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels." }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome (MetS) is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, insulin resistance, hypertension, dyslipidemia and hyperglycemia." }, { "input": "What are the five traits associated with metabolic syndrome?", "output": "Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, insulin resistance, hypertension, dyslipidemia and hyperglycemia." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "Liebenberg syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. Patients present with prominent neurological, medical, and behavioral symptoms." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "We discuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5" }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "We re-define the phenotype of Liebenberg syndrome as a transformation of the upper limbs to reflect lower limb characteristics. We speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "Liebenberg syndrome is caused by genetic changes near the PITX1 gene. The protein produced from this gene plays a critical role in lower limb development by controlling the activity of other genes involved in limb development, directing the shape and structure of bones and other tissues in the legs and feet." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "Liebenberg syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "Liebenberg syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeodomain complex 1 (PITX1) gene." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics The deleted region is upstream to the PITX1 gene." }, { "input": "Which gene is responsible for the Liebenberg syndrome?", "output": "Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics" }, { "input": "Which pharmacogenetic test is recommended prior to administering carbamazepine and why?", "output": "HLA-B\u221715:02 is known as a biomarker for carbamazepine (CBZ) induced Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) in some Asian populations. Hence United States Federal Drug Administration (USFDA) recommends HLA-B\u221715:02 screening for Asian and other populations with a high prevalence of HLA-B\u221715:02, prior to the administration of carbamazepine." }, { "input": "Are there sex differences in oncogenic mutational processes?", "output": "Yes. Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. There are sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes." }, { "input": "Are there sex differences in oncogenic mutational processes?", "output": "Yes. There are sex differences in oncogenic mutational processes." }, { "input": "Which drugs are included in the MAID chemotherapy regimen for sarcoma?", "output": "MAID chemotherapy regimen for sarcomas include mesna, adriamycin, ifosfamide and dacarbazine." }, { "input": "Which is the main ligand for the glucocorticoid receptor?", "output": "Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans)." }, { "input": "Who received the Nobel prize for development of CRISPR?", "output": "The 2020 Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna. Charpentier and Doudna pioneered the site-specific CRISPR gene-editing technology that has revolutionized cancer research and treatment." }, { "input": "Who received the Nobel prize for development of CRISPR?", "output": "Emmanuelle Charpentier, PhD, and Jennifer Doudna, PhD, who pioneered the site-specific CRISPR gene-editing technology that has revolutionized cancer research and treatment, were awarded the 2020 Nobel Prize in Chemistry." }, { "input": "Who received the Nobel prize for development of CRISPR?", "output": "CRISPR has finally won a Nobel Prize. Jennifer Doudna and Emmanuelle Charpentier have been awarded the ultimate science prize for their breakthrough research on CRISPR technology." }, { "input": "Who received the Nobel prize for development of CRISPR?", "output": "The 2020 Nobel Prize in Chemistry was awarded to CRISPR-Cas pioneers Emmanuelle Charpentier and Jennifer Doudna, who developed the CRISPR-Cas system to precisely edit genomic DNA." }, { "input": "Who received the Nobel prize for development of CRISPR?", "output": "020 Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer Doudna for their discovery of the CRISPR/Cas9 genetic scissors that have revolutionized genome editing." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers are defined as genomic regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers are defined as genomic regions spanned by highly conserved non-coding elements (HCNEs), which include enhancers, transcription factor binding sites that can activate or repress gene expression by multiple mechanisms." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity. Super-enhancers are large clusters of transcriptional enhancers regarded as having essential roles in driving the expression of genes that control cell identity during development and tumorigenesis." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers (SEs) are large clusters of enhancers that drive expression of genes controlling cell identity. Super-enhancers are important for controlling and defining the expression of cell-specific genes." }, { "input": "How are super enhancers defined?", "output": "Super enhancers are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as enhancers of one target gene in the region." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers are defined as genomic regions spanned by highly conserved non-coding elements (HCNEs), which include both syntenic and nonsyntenic regions, that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of many genes, including those encoding major transcription factors." }, { "input": "How are super enhancers defined?", "output": "The super enhancers are important for defining cell identity in mammalian developmental processes and human diseases. They are defined as genomic regions containing clusters of multiple enhancers, which regulate cell-identity genes and oncogenes. The enhancers can be identified by ChIP sequencing (ChIP-seq) to identify domains enriched for the histone marks histone H3 lysine 4 trimethylation (H3K4me3, H3k4me1, and H3K27ac) and define, for the first time, the super enhancementancers and typical enhancers active in primary human cor" }, { "input": "How are super enhancers defined?", "output": "Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity." }, { "input": "How are super enhancers defined?", "output": "Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive expression of genes controlling cell identity. They recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac)." }, { "input": "Is metoprolol metabolized by CYP2D6?", "output": "Yes, metoprolol is metabolized by CYP2D6." }, { "input": "List versions of ExpansionHunter", "output": "ExpansionHunter and ExpansionHunter Denovo" }, { "input": "List versions of ExpansionHunter", "output": "ExpansionHunter Denovo is an efficient catalog-free method for genome-wide repeat expansion detection. ExpansionHunter is a sequence-graph-based tool to analyze variation in short tandem repeat regions." }, { "input": "What are the uses of Nirsevimab?", "output": "A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants." }, { "input": "What is the proteoglycan Tsukushi?", "output": "Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan (SLRP) family, plays multifunctional roles by interacting with signaling molecules during development.\nIn lung cancer cells, TSK is expressed more highly than the other SLRPs family members, and regulates the EMT and proliferation. Thus, TSK may be a key coordinator of multiple pathways and an important structural element in the lung cancer microenvironment.\nGain- and loss-of-function analyses showed that the small leucine-rich proteoglycan, tsukushi, contributes to vitamin K2-mediated enhancement of collagen accumulation." }, { "input": "Does Curare function by stimulating the acetylcholine receptor?", "output": "No. Curare function does not stimulate the acetylcholine receptor." }, { "input": "Does Curare function by stimulating the acetylcholine receptor?", "output": "Usual clinical concentrations of curare cause competitive inhibition of muscle nicotinic acetylcholine receptors." }, { "input": "Does Curare function by stimulating the acetylcholine receptor?", "output": "No, curare is an inhibitor of acetylcholine-induced currents that only blocks the N-terminal glutamine-rich channel." }, { "input": "Does Curare function by stimulating the acetylcholine receptor?", "output": "No, curare is an antagonist of acetylcholine-induced currents that binds to the choline receptor." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Yes, somatic mutations are more preferentially located at the nuclear periphery than at the core." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Yes, somatic mutations are preferentially located in the lamina-associated regions of the genome." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Yes, somatic mutations are more preferentially situated at the nuclear periphery." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nucle core. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nucle periphery. At day 4, GOF, its carrier chromosome territory 13 and the non-carrier homolog had moved back toward the nucleus." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Yes, somatic mutations are more preferentially located in the nuclear periphery than in the core." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Mutational signatures differ between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nucle core. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, are more enriched in the nucle periphery. The distribution of retrogenes in the Drosophila melanogaster genome can be explained by an insertion bias toward chromosome domains containing testis-biased genes that are located at the nucleus in somatic cells." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery." }, { "input": "Are somatic mutations positioned towards the nuclear periphery?", "output": "Yes, somatic mutations are preferentially located in the chromatin near the nuclear periphery." }, { "input": "Which biological drugs are EMA approved for pediatric psoriasis?", "output": "Currently there are three European Medicines Agency (EMA)-approved biological treatment options for pediatric psoriasis: etanercept, ustekinumab, and adalimumab." }, { "input": "What is the role of Adamts18 in hormone receptor signaling?", "output": "Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation." }, { "input": "What is the role of Adamts18 in hormone receptor signaling?", "output": "The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts with the basal membrane-specific proteoglycan, Col18a1." }, { "input": "What is the role of Adamts18 in hormone receptor signaling?", "output": "Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. Both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation." }, { "input": "What is the role of Adamts18 in hormone receptor signaling?", "output": "Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche." }, { "input": "What is the role of Adamts18 in hormone receptor signaling?", "output": "In vitro, ADAMTS18 cleaves fibronectin; in vivo, it causes increased collagen deposition during adolescence, which results in impaired Hippo signaling and reduced Fgfr2 expression both in vitro and in vivo. Importantly, it is required for stem cell activation, has multiple binding partners in the basement membrane, and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the caveolae of stem cells as part of the stem cell niche." }, { "input": "Is belimumab effective for the lupus nephritis?", "output": "Yes, belimumab appears to effective for the lupus nephritis." }, { "input": "Which are the lactate isomers?", "output": "Lactate contains a chiral carbon and thus has two optical isomers-d-lactate and l-lactate." }, { "input": "What is the function of the Eyeless associated gene in Drosophila?", "output": "Eyeless (ey) also known as Pax6, is one of the most critical transcription factors for initiating the entire eye development in Drosophila." }, { "input": "What is the function of the Eyeless associated gene in Drosophila?", "output": "Theeye-associated Pax6 gene controls neuronal navigation in Drosophila." }, { "input": "What is the function of the Eyeless associated gene in Drosophila?", "output": "Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila. Two Pax6 genes are in Drosophila: eyeless (ey) and twin of eyeless (toy)" }, { "input": "What is the function of the Eyeless associated gene in Drosophila?", "output": "Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila." }, { "input": "Are enhancers directional in their targeting of gene promoters?", "output": "Promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously. Most enhancers are able to regulate promoters on either side." }, { "input": "Are enhancers directional in their targeting of gene promoters?", "output": "These promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously." }, { "input": "Are enhancers directional in their targeting of gene promoters?", "output": "Bi-directional duplex promoters (BDDP) were constructed by placing two identical core promoters divergently on both upstream and downstream sides of their duplicated enhancer elements. These promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously." }, { "input": "Has dupilumab been FDA approved for atopic dermatitis?", "output": "Yes, dupilumab has been approved by FDA for atopic dermatitis." }, { "input": "Describe ReactomeGSA", "output": "ReactiveomeGSA is a novel resource for comparative pathway analyses of multi-omics datasets. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAt Atlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. reactomegSA greatly reduces the technical barrier for multi-CSF, cross-species, and Comparative Pathways analysis." }, { "input": "Describe ReactomeGSA", "output": "Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge. ReactomeGSA performs comparative pathway analyses of multi-omics datasets. It can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses." }, { "input": "Describe ReactomeGSA", "output": "ReactiveomeGSA is a novel R Bioconductor package for comparative pathway analyses of multi-omics datasets. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAt Atlas can be directly integrated in the analysis. ReactomeGsa greatly reduces the technical barrier for multi-seq, cross-species, comparative pathway analysis." }, { "input": "Describe ReactomeGSA", "output": "Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge. ReactomeGSA is a resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses." }, { "input": "Describe ReactomeGSA", "output": "ReactomeGSA is a new pathway analysis tool integrated into the Reactome ecosystem. Its main feature is that it performs quantitative pathway analyses (so-called gene set analyses). This increases the statistical power of the differential expression analysis, which is directly performed on the pathway level." }, { "input": "Describe ReactomeGSA", "output": "ReactiveomeGSA is a novel resource for comparative pathway analyses of multi-omics datasets." }, { "input": "What is the role of phenylbutyrate\u2013taurursodiol for amyotrophic lateral sclerosis?", "output": "Treatment of amyotrophic lateral sclerosis patients with phenylbutyrate\u2013taurursodiol was associated with both functional and survival benefits." }, { "input": "What is known about growth arrest-specific 6 protein?", "output": "Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and receptors of the TAM (Tyro3, Axl, and Mer) family may be involved in the pathogenesis of obesity, systemic inflammation, and insulin resistance." }, { "input": "What is Leptomeningeal disease?", "output": "Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells." }, { "input": "What is Leptomeningeal disease?", "output": "Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells. LMD represents infiltration of the leptomeninges by tumor cells." }, { "input": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "output": "These therapies are, however, expensive and 30% of patients fail to respond." }, { "input": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "output": "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response." }, { "input": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "output": "Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with RA, showing beneficial effects in approximately 25% of the patients." }, { "input": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "output": "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. By contrast, those patients who had failed to respond to 2 or more anti-TNF agents had a 72.5% lower probability of achieving a moderate to good EULAR response." }, { "input": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "output": "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond" }, { "input": "What percent of Rheumatoid Arthritis (RA) patients are not responding to anti-TNF therapy?", "output": "Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond." }, { "input": "Which recombinant antibody therapeutics were granted marketing approval in 2014?", "output": "Six recombinant antibody therapeutics (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted their first marketing approvals in 2014." }, { "input": "What is caused by BACH2-related immunodeficiency?", "output": "Affected subjects of a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation." }, { "input": "Should cerebrolysin be used for aneurysmal subarachnoid hemorrhage?", "output": "No. Randomized clinical trial did not find any superior effects of cerebrolysin for patients with aneurysmal subarachnoid hemorrhage." }, { "input": "Do bacteria release extracellular vesicles?", "output": "Yes, Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites." }, { "input": "What is the effect of the venom of the cone snail, Conus tulipa?", "output": "Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-, \u03b4-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins." }, { "input": "What is the effect of the venom of the cone snail, Conus tulipa?", "output": "Conus tulipa venom comprised both paralytic (putative ion channel modulating \u03b1-, \u03c9-, \u03bc-, \u03b4-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins." }, { "input": "Which component of the Influenza A Virus affects mRNA transcription termination?", "output": "Defective Pol II termination occurs independently of the ability of the viral NS1 protein to interfere with host mRNA processing. Instead, this termination defect is a common effect of diverse cellular stresses and underlies the production of previously reported downstream-of-gene transcripts (DoGs)." }, { "input": "Which component of the Influenza A Virus affects mRNA transcription termination?", "output": "Influenza A virus (IAV) infection induces global transcriptional defects at the 3' ends of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions. This phenomenon occurs with multiple strains of IAV, is dependent on influenza NS1 protein, and can be modulated by SUMOylation of an intrinsically disordered region (IDR) of NS1 expressed by the 1918 pandemic IAV strain" }, { "input": "Which two genes are predominantly considered by warfarin initial dosing algorithms?", "output": "Polymorphisms in CYP2C9 and VKORC1 are taken into consideration by warfarin initial dosing algorithms." }, { "input": "Describe MSstatsTMT", "output": "MSstatsTMT is a general statistical approach for relative protein quantification in MS- based experiments with TMT labeling." }, { "input": "Is Tranexamic acid effective for intracerebral haemorrhage?", "output": "No. According to clinical trial data tranexamic acid does not improve outcomes of patients with intracerebral haemorrhage." }, { "input": "Are interferons defensive proteins?", "output": "Yes,\nThe innate immune system, in particular the type I interferon (IFN) response, is a powerful defence against virus infections." }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) is a sulfur-based nutritional supplement that is purported to have pain and inflammation-reducing effects." }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) is an anti-inflammatory drug with anti-proinflammatory activity" }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) exerts anti-inflammatory effects in animal models of inflammation" }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "These findings indicate that MSM may protect against inflammation in the heart" }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) is an anti-inflammatory agent that acts by inhibiting inflammatory cytokine production and epithelial cell proliferation and differentiation." }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) exerts anti-inflammatory activity in the body" }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) is a naturally occurring compound that demonstrates anti-inflammatory effects in humans and various animal and cell culture models." }, { "input": "What effect does Methylsulfonylmethane (MSM) have on inflammation?", "output": "Methylsulfonylmethane (MSM) is a sulfur-based compound that is purported to have anti-inflammatory and inflammation-reducing effects. URL_0" }, { "input": "What is particular about the 3D structure of the inactive X chromosome?", "output": "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. This specific bipartite organization of the inactive X chromosome that probably plays an important role in maintenance of gene silencing." }, { "input": "What is particular about the 3D structure of the inactive X chromosome?", "output": "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Despite the importance of X chromosome inactivation, little is known about this 3D conformation. The inactive X chromosomes are the best examples of XCI in females, originally discovered as a compact 3D structure at the nuclear periphery known as the Barr body." }, { "input": "What is particular about the 3D structure of the inactive X chromosome?", "output": "The inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region that is enriched in histone H3 lysine 27." }, { "input": "What is particular about the 3D structure of the inactive X chromosome?", "output": "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region." }, { "input": "What is particular about the 3D structure of the inactive X chromosome?", "output": "The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomain differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. Genes that escape X inactivation do not cluster but are located near a periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase." }, { "input": "Why mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding?", "output": "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called Thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). Rtpca can be used for high-throughput intracellular monitoring of protein complex dynamics." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). Rtpca was reported to be able to integrate downloaded protein/protein interaction information from different online databases with private data to construct new and personalized interaction networks." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA)." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA). It offers user-friendly tools to explore datasets for their protein-protein interaction predictive performance and easily integrates with available R packages." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA)" }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package for differential thermal proximity coaggregation analysis. It is based on a model of thermal proximity (TFD) analysis performed by combining multiple layers of TSSs with TSSS (TSC) and TSSF (TSS-FANCA) data." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called Thermal proximity coaggregation (TPCA). It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implemented methods for inferring protein-protein interactions (PPIs) based on Thermal proteome profiling experiments or in a differential setting via an approach called Thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages." }, { "input": "Which R package can infer protein-protein interactions via thermal proximity coaggregation (TPCA)?", "output": "Rtpca is an R package implementing methods for inferring protein-protein interactions based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation (TPCA) It offers user-friendly tools to explore datasets for their protein-protein interaction predictive performance and easily integrates with available R packages." }, { "input": "What is the mechanisms of action of Evinacumab?", "output": "Evinacumab is angiopoietin-like protein 3 (ANGPTL3) monoclonal antibody that was shown to substantially reduce low-density lipoprotein cholesterol concentration." }, { "input": "Do honey contain diastases/amylases?", "output": "Yes\nhoney contain the protein amylase." }, { "input": "What year was the first successful human heart transplant performed?", "output": "The first human heart transplant in 1967 was performed using a deceased donor heart," }, { "input": "What year was the first successful human heart transplant performed?", "output": "the first human heart transplant in 1967 was performed using a deceased donor heart," }, { "input": "Which disease is monitored in the BIOCURA cohort?", "output": "Rheumatoid Arthritis (RA) is one of the diseases that is monitored in the BIOCURA cohort. There are other diseases that are monitored as well, such as breast cancer, ovarian cancer, and thyroid cancer." }, { "input": "Which disease is monitored in the BIOCURA cohort?", "output": "BiOCura cohort is used to monitor rheumatoid arthritis." }, { "input": "Which disease is monitored in the BIOCURA cohort?", "output": "The BiOCURA registry includes patient with Rheumatoid Arthritis (RA) with the aim of defining their response profile to different RA treatments." }, { "input": "Which disease is monitored in the BIOCURA cohort?", "output": "BiOCura cohort is used for clinical monitoring of rheumatoid arthritis." }, { "input": "Which gene is associated with response to abacavir?", "output": "Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir." }, { "input": "Is adenosine signaling prognostic for cancer outcome?", "output": "Yes, adenosine signaling has been shown to be prognostic for cancer outcome." }, { "input": "Is adenosine signaling prognostic for cancer outcome?", "output": "Yes, adenosine signaling is prognostic for cancer outcome." }, { "input": "Is adenosine signaling prognostic for cancer outcome?", "output": "Yes. Adenosine signaling is prognostic for cancer outcome and has predictive utility for immunotherapeutic response." }, { "input": "Which drugs are included in the CNIC polypill?", "output": "CNIC polypill includes atorvastatin 40mg, ramipril 10mg and aspirin 100mg." }, { "input": "Which human tissue synthesize CRP?", "output": "CRP is predominantly produced in the liver in a native pentameric form (nCRP)." }, { "input": "What is the relationship between the X chromosome and a neutrophil drumstick?", "output": "In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome." }, { "input": "What is the relationship between the X chromosome and a neutrophil drumstick?", "output": "In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome" }, { "input": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "output": "MAP3K8 (Tpl2) regulates the formation of inflammatory molecule IL-1\u03b2" }, { "input": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "output": "MAP3K8 (Tpl2) regulates the formation of IL-1\u03b2 by masking its inflammatory function." }, { "input": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "output": "MAP3K8 (also known as Map3k8) regulates the formation of IL-1\u03b2" }, { "input": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "output": "IL-1\u03b2 formation is regulated by MAP3K8 (TPL2)" }, { "input": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "output": "Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1beta production and optimal host defense." }, { "input": "The formation of which inflammatory molecule is regulated by MAP3K8 (TPL2)?", "output": "MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1\u03b2 and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance." }, { "input": "Which company produces the Oncomine Dx target test?", "output": "The Oncomine Dx Target Test Panel is produced by Thermo Fisher Scientific." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is a computational tool to infer mRNA synthesis, processing and degradation dynamics from RNA- and 4sU-seq time course experiments." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. INSPEcT provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. INSPECT provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. In addition, it provides gene-level quantification of these rates, and a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation." }, { "input": "Describe the INSPEcT R package", "output": "InSPEcT is an R package for the integrative analysis of RNA-seq data to study the dynamics of transcriptional regulation." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. To graphically inspect the resulting networks, the package contains a visualization tool, which allows for the direct network manipulation and access of node and link information. INSPecT-GUI is freely available within the R/Bioconductor package INSPECT at http://bioconductor.org/packages/INSPECAT/." }, { "input": "Describe the INSPEcT R package", "output": "INSPEcT is an R package for the integrative analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional regulation. In particular, it provides a modeling framework to identify which of these regulatory processes are most likely to explain the observed mRNA and pre-mRNA concentrations. Software performance is tested on a synthetic dataset, instrumental to guide the choice of the modeling parameters and the experimental design." }, { "input": "Which molecule is targeted by Teprotumumab?", "output": "Teprotumumab is a human monoclonal antibody that targets IGF-1R. It can be used for treatment of thyroid eye disease." }, { "input": "Which protein is encoded by the protein APOBEC3C?", "output": "The gene APOBEC3C codes for: apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C" }, { "input": "Does AZD3759 cross the blood brain barrier?", "output": "AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier." }, { "input": "Does AZD3759 cross the blood brain barrier?", "output": "AZD3759 is an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration." }, { "input": "Does AZD3759 cross the blood brain barrier?", "output": "Yes, AZD3759 cross the blood brain barrier." }, { "input": "What is the major sequence determinant for nucleosome positioning?", "output": "G+C content is the primary determinant of MNase-derived nucleosome occupancy." }, { "input": "Which is the primary enzyme metabolizing esomeprazole?", "output": "Esomeprazole is primarily metabolized by CYP2C19." }, { "input": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "output": "Somalatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease, particularly atrial fibrillation and dysregulation of transcphenne muscular dystrophy, as well as other genetic variation, in the early phase of disease." }, { "input": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "output": "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease." }, { "input": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "output": "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (VEO-IBD)." }, { "input": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "output": "Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease. Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders." }, { "input": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "output": "Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Somatic mosaicism and common genetic variation contribute to the risk of this disease." }, { "input": "Which factors contribute to the risk of very-early-onset inflammatory bowel disease?", "output": "Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders including Crohn's disease, depression and cocaine addiction. Somatic mosaicism and common genetic variation contribute to the risk of IBD." }, { "input": "What disease is treated with BIVV001?", "output": "BIVV001 fusion protein has been developed as Factor VIII replacement therapy for hemophilia A" }, { "input": "What is the mode of action of Thiazovivin?", "output": "Thiazovivin is a selective small molecule that directly targets Rho-associated kinase (ROCK) and increases expression of pluripotency factors." }, { "input": "Explain the association between Barr bodies (nuclear inclusions) and the X chromosome?", "output": "Barr body is an inactivated X chromosome in the normal female somatic cell." }, { "input": "Explain the association between Barr bodies (nuclear inclusions) and the X chromosome?", "output": "A Barr body (named after discoverer Murray Barr) is an inactive X chromosome in a cell with more than one X chromosome, rendered inactive in a process called lyonization, in species with XY sex-determination (including humans)." }, { "input": "Explain the association between Barr bodies (nuclear inclusions) and the X chromosome?", "output": "Transcriptional inactivation of one X chromosome in mammalian female somatic cells leads to condensation of the inactive X chromosome into the heterochromatic sex chromatin, or Barr body." }, { "input": "Explain the association between Barr bodies (nuclear inclusions) and the X chromosome?", "output": "Barr body is an inactivated X chromosome in the normal female somatic cell" }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "During developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome. Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation. Early enhancers are characterized by an intrinsically high nucleosome barrier. Zelda tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of zelda(zld) motifs." }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "Yes, it is known as a chromatin remodeling factor." }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "Yes, the zebrafish transcription factor Zelda is a chromatin remodeling factor." }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "Yes, it is known as a transcription factor for a chromatin remodeling factor." }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "Yes, the zelda transcription factor is a chromatin remodller." }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Zelda is essential for hundreds of regions of open chromatin. Zelda binds cis-regulatory elements (TAGteam heptamers), making chromatin accessible for gene transcription." }, { "input": "Is the zelda transcription factor a chromatin remodeller?", "output": "This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression." }, { "input": "What is the effect of the alleles CYP2C19*2 and CYP2C19*3 on CYP2C19 function?", "output": "The CYP2C19*2 and CYP2C19*3 alleles of CYP2C19 are associated with loss-of-function (LOF)." }, { "input": "Describe Full Spectrum of Intolerance to Loss-of-function (FUSIL)", "output": "Full Spectrum of Intolerance to Loss-of-function (FUSIL) is a cross-species gene classification across the full spectrum of mutations in genes of unknown function. FUSIL has been proposed as a method to identify potentially pathogenic variants in genes not previously associated with rare diseases." }, { "input": "Describe Full Spectrum of Intolerance to Loss-of-function (FUSIL)", "output": "The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. By integrating measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines, a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) was proposed. Genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development." }, { "input": "Describe Full Spectrum of Intolerance to Loss-of-function (FUSIL)", "output": "The FUSIL is the Full Spectrum of Intolerance to Loss-of-function (FUSIL). It's the full spectrum of genes that are not essential for cell survival, but essential for organism development." }, { "input": "Describe Full Spectrum of Intolerance to Loss-of-function (FUSIL)", "output": "Full Spectrum of Intolerance to Loss-of-function (FUSIL) is a cross-species gene classification across the full spectrum of genes in five mutually exclusive categories have differing biological properties. FUSIL is proposed as an efficient approach for disease gene discovery." }, { "input": "Describe Full Spectrum of Intolerance to Loss-of-function (FUSIL)", "output": "Full Spectrum of Intolerance to Loss-of-function (FUSIL) is a cross-species gene classification across the full spectrum of essential and non-essential genes. FUSIL is an efficient approach for disease gene discovery." }, { "input": "Is capmatinib effective for glioblastoma?", "output": "No. Combination of capmatinib buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma." }, { "input": "Are there antimicrobial proteins in royal jelly?", "output": "Yes,\nJelleines, isolated as novel antibacterial peptides from the Royal Jelly (RJ) of bees, exhibit broad-spectrum protection against microbial infections." }, { "input": "What are the years of the initiation and completion of the Human Genome project?", "output": "The Human Genome Project was initiated in 1990 and completed in 2003." }, { "input": "What are the years of the initiation and completion of the Human Genome project?", "output": "The Human Genome Project (HGP) was initiated in 1990, and the completion of the genome project was in 2003." }, { "input": "Which methods infer 3D genome structure without proximity ligation?", "output": "SPRITE is a method that enables genome-wide detection of higher-order interactions within the nucleus.\nTransposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility.\nGenome architecture mapping (GAM) can be used for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections." }, { "input": "Which methods infer 3D genome structure without proximity ligation?", "output": "To investigate three-dimensional (3D) genome organization in prokaryotic and eukaryotic cells, three main strategies are employed, namely nuclear proximity ligation-based methods, imaging tools (such as fluorescence in situ hybridization (FISH) and its derivatives), and computational/visualization methods." }, { "input": "Which methods infer 3D genome structure without proximity ligation?", "output": "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype. By combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide interactions within topological domains and global genome structure as a whole. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We describe a genome architecture assay, tethered multiple 3C (TM3C), that maps genome-wide chromatin contacts via a simple protocol of restriction enzyme digestion and religation of fragments upon agarose gel beads followed by paired-end sequencing. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We now report transposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility." }, { "input": "Which methods infer 3D genome structure without proximity ligation?", "output": "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype. By combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide interactions within topological domains and global genome structure as a whole. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We describe a genome architecture assay, tethered multiple 3C (TM3C), that maps genome-wide chromatin contacts via a simple protocol of restriction enzyme digestion and religation of fragments upon agarose gel beads followed by paired-end sequencing. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles." }, { "input": "How many genes are screened by the FoundationOne companion diagnostic?", "output": "FoundationOne CDx comprises a 324-gene panel." }, { "input": "Interaction of WDR5 with which gene has a critical role in pancreatic cancer?", "output": "Mechanistically, WDR5 functions to sustain proper execution of DNA replication in pancreatic ductal adenocarcinoma (PDAC) cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. It was indeed demonstrated that interaction with c-Myc is critical for this function." }, { "input": "Interaction of WDR5 with which gene has a critical role in pancreatic cancer?", "output": "WDR5 is a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1-4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR" }, { "input": "Interaction of WDR5 with which gene has a critical role in pancreatic cancer?", "output": "WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc. Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance. The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation" }, { "input": "Interaction of WDR5 with which gene has a critical role in pancreatic cancer?", "output": "Interaction of WDR5 with WDR4 and c-Myc is critical for the development of pancreatic cancer." }, { "input": "Can thiotepa be recommended for treatment of osteosarcoma?", "output": "No. Thiotepa did not improve survival of patients with osteosarcoma and therefore can not be recommended for treatment of osteosarcoma." }, { "input": "What is known about aberrant proteolytic activity in disease?", "output": "Research into Alzheimer's disease pathology and treatment has often focused on presenilin proteins. These proteins provide the key catalytic activity of the \u03b3-secretase complex in the cleavage of amyloid-\u03b2 precursor protein and resultant amyloid tangle deposition. Over the last 25 years, screening novel drugs to control this aberrant proteolytic activity has yet to identify effective treatments for the disease.\nOthers are human skin disorders where proteolytic pathways are dysregulated." }, { "input": "Does a comet assay measure radiation induced mutations?", "output": "Yes. The comet assay is frequently used to measure DNA damage in individual cells." }, { "input": "Does a comet assay measure radiation induced mutations?", "output": "Evaluation of primary DNA-damage is one way to identify potential genotoxic agents and for this purpose the Comet assay has, for the last decades, been used to monitor DNA single strand and double strand breaks in individual cells" }, { "input": "Does a comet assay measure radiation induced mutations?", "output": "The comet assay is frequently used to measure DNA damage in individual cells following exposure to mutagens such as ionizing radiation." }, { "input": "Does a comet assay measure radiation induced mutations?", "output": "Yes, a comet assay measures radiation-induced mutations in DNA." }, { "input": "What is formative pluripotency?", "output": "Formative pluripotency features a gene regulatory network switch from the nave state. Two phases of pluripotency, called nave and primed, have previously been described." }, { "input": "What is formative pluripotency?", "output": "Two phases of pluripotency, called na\u00efve and primed, have previously been described. The transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that is called formative pluripotency." }, { "input": "What is formative pluripotency?", "output": "Formative pluripotency features a gene regulatory network switch from the na ve state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification." }, { "input": "What is formative pluripotency?", "output": "Formative pluripotency is an intermediate stage in the developmental continuum. It's a bit of a misnomer. The term \"formative\" comes from the word \"formal\" which is used to refer to an intermediate state that isn't fully formed." }, { "input": "What is formative pluripotency?", "output": "Formative pluripotency features a gene regulatory network switch from the na\u00efve state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification. Here, we discuss an intermediate stage of pluripotency that we term \"formative\". Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency. In this Hypothesis article, a third phase, called formative pluripotency, is proposed to exist as part of a developmental continuum between the na\u00efve and primed phases. Two phases of pluripotency, called na\u00efve and primed, have previously been described." }, { "input": "What is formative pluripotency?", "output": "Formative pluripotency is an intermediate state of differentiation that we call \"formative\". It is proposed to exist as part of a developmental continuum between the na\u00efve and primed phases. It consists of a gene regulatory network switch from the na\u00efve state to the formative epiblast-like cells of EpiLCs." }, { "input": "Has the companion diagnostic HercepTest received FDA approval?", "output": "Yes, the HercepTest has received FDA approval." }, { "input": "Which R/Bioconductor package has been developed for visualizing differential amino acid group usage in proteomics?", "output": "DagLogo is an R/Bioconductor package for identifying and visualizing differential amino acid group usage in proteomics data. DagLogo allows various formats for input sets and provides comprehensive options to build optimal background models. It implements different reduced AA alphabets to group AAs of similar properties. Furthermore, dagLogo provides statistical and visual solutions for differential AA (or AA group) usage analysis of both large and small data sets. Case studies showed that dagLogo can better identify and visualize conserved protein sequence patterns from different types of inputs and can potentially reveal the biological patterns that could be missed by other logo generators." }, { "input": "Which R/Bioconductor package has been developed for visualizing differential amino acid group usage in proteomics?", "output": "dagLogo is an R/Bioconductor package for identifying and visualizing differential amino acid group usage in data. dagLogo allows various formats for input sets and provides comprehensive options to build optimal background models." }, { "input": "Which R/Bioconductor package has been developed for visualizing differential amino acid group usage in proteomics?", "output": "DagLogo is an R/Bioconductor package for identifying and visualizing differential amino acid group usage in proteomics data." }, { "input": "Dasatinib and Blinatumomab are used for treatment of which disease?", "output": "Dasatinib and Blinatumomab produces molecular responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia." }, { "input": "Is phosphoenolpyruvate carboxykinase 1 (PCK1) the rate-limiting enzyme in gluconeogenesis?", "output": "Yes, Pck1 is a rate-limiting gluconeogenic enzyme, where its deficiency or mutation contributes to serious clinical situations as neonatal hypoglycemia and liver failure." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": "Scouring collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": "The scratch collapse test (SCT) is a clinical examination maneuver that has been reported as a reliable and reproducible test to diagnose carpal tunnel syndrome (CTS) cubital tunnel syndrome and other compressive upper limb neuropathies." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": "Scales collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": "Scratch collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": "Evaluation of the Scratch Collapse Test for Carpal and Cubital Tunnel Syndrome-A Prospective, Blinded Study." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": "Scrap collapse test is used for the diagnosis of cts, cubital tunnel syndrome and carpal tunnel syndrome." }, { "input": "What conditions are diagnosed using the scratch collapse test?", "output": " A diagnostic maneuver known as the \"scratch-collapse test\" (SCT), to aid in the diagnosis of compressive upper limb neuropathies such as carpal tunnel syndrome (CTS)," }, { "input": "Which is the main gene signature in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) has a type I interferon (IFN) gene signature." }, { "input": "Which is the main gene signature in Systemic Lupus Erythematosus (SLE)?", "output": "SLE is characterized by a type-I interferon gene signature." }, { "input": "Which is the main gene signature in Systemic Lupus Erythematosus (SLE)?", "output": "Systemic Lupus Erythematosus (SLE) is a type I interferon (IFN) disease. The main gene signature is a 4-gene expression of 4 genes." }, { "input": "Which is the main gene signature in Systemic Lupus Erythematosus (SLE)?", "output": "SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE." }, { "input": "Which is the main gene signature in Systemic Lupus Erythematosus (SLE)?", "output": "A role for interferon (IFN) in systemic lupus erythematosus (SLE) pathogenesis is inferred from the prominent IFN gene signature (IGS), but the major IFN species and its relationship to disease activity are unknown." }, { "input": "Has FTY720 been considered for the treatment of stroke?", "output": "Yes, FTY720 is a strong candidate for stroke treatment." }, { "input": "List R packages for lipidomics", "output": "R packages for lipidomics: lipidomics, masspix, lipidms, lipidr and lipid mini-on." }, { "input": "List R packages for lipidomics", "output": "R packages for lipidomics include: lipidr, masspix, lipidms, lipidr and lipid mini-on." }, { "input": "List R packages for lipidomics", "output": "Lipidomics, masspix, lipidms, lipidr and lipid mini-on are R packages for lipidomics." }, { "input": "List R packages for lipidomics", "output": "Lipid Mini-On, lipidr, LipidMS and massPix" }, { "input": "Which disease can be treated with Relugolix.", "output": "Relugolix has a role in treatment of prostate cancer, uterine fibroids, endometriosis and uterine myomas." }, { "input": "What is the effect of Carbendazim on bees?", "output": "Carbendazim is an environmental risk factor that likely weakens bee colonies, partially due to reduced expression of major royal jelly proteins, which may be potential causes of colony collapse disorder." }, { "input": "What 3 organs are the sphincter of Oddi associated with?", "output": "Sphincter of Oddi is associated with the pancreatic duct, duodenum and gallbladder." }, { "input": "What 3 organs are the sphincter of Oddi associated with?", "output": "The sphincter of Oddi is associated with the pancreatic duct, the duodenal crypts and gallbladder." }, { "input": "What 3 organs are the sphincter of Oddi associated with?", "output": "Sphincter of Oddi (SO) is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum." }, { "input": "What 3 organs are the sphincter of Oddi associated with?", "output": "The sphincter of oddsi is associated with the pancreatic duct, the duodenal crypts and the gallbladder." }, { "input": "What 3 organs are the sphincter of Oddi associated with?", "output": "The sphincter ofoddi is associated with the pancreatic duct, the duodenal crypts and gallbladder." }, { "input": "What 3 organs are the sphincter of Oddi associated with?", "output": "The sphincter of Oddi is a dynamic structure located strategically at the confluence of the bile duct, the pancreatic duct and the duodenum." }, { "input": "List clinical phenotypes and molecular genetic features of patients with KMT2B-related disorders", "output": "Atypical patterns of dystonia evolution and a subgroup of patients presents with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features there seem to be co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies." }, { "input": "List clinical phenotypes and molecular genetic features of patients with KMT2B-related disorders", "output": "KMT2B-related disorders result in significant improvement in motor function and disability at 6 months, 1 year, and again at 1 year after stimulation. The greatest improvements are seen for trunk and cervical dystonia, with less clinical impact on laryngeal or transternal dystonias. Patients with chromosomal deletions and protein truncating variants have a higher burden of systemic disease than those with missense variants." }, { "input": "What is the use of Atogepant?", "output": "Atogepant is used for preventive treatment of migraine." }, { "input": "Is SMOC2 expressed during wound healing?", "output": "Yes,\nSMOC2 response to wounding." }, { "input": "What is a potential alternate uses(repositioning) for Primaquine", "output": "Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization. PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity" }, { "input": "What is a potential alternate uses(repositioning) for Primaquine", "output": "Primaquine could be used as a novel drug for vascular leakage by maintaining endothelial integrity and for" }, { "input": "What is a potential alternate uses(repositioning) for Primaquine", "output": "Primaquine Diphosphate, a known Antimalarial Drug, blocks Vascular Leakage through Junction Stabilization. This is a potential alternate uses." }, { "input": "Does daily atemoya juice intake change the pharmacokinetics of CYP1A2 substrates?", "output": "No, atemoya juice does not change the pharmacokinetics of CYP1A2 substrates." }, { "input": "What is caused by gain-of-function variants in SYK?", "output": "Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice." }, { "input": "What is caused by gain-of-function variants in SYK?", "output": "SYK gain-of-function variants cause immune dysregulation and systemic inflammation in humans and mice." }, { "input": "Is Cabotegravir effective for HIV prevention?", "output": "Yes, Cabotegravir is effective for HIV prevention." }, { "input": "What is the function of the protein SERT?", "output": "SERT is a Serotonin transporter." }, { "input": "Are G-quadruplexes(G4) possible drug targets for glioblastoma?", "output": "The 2H2-6M(4)-oxazole telomestatin derivative (6OTD) targets Glioma stem cells through G4 stabilization and promotion of DNA damage responses. Therefore, G4s are promising therapeutic targets for glioblastoma." }, { "input": "Are G-quadruplexes(G4) possible drug targets for glioblastoma?", "output": "G-quadruplex DNA structures (G4 DNA) are a promising therapeutic target for glioblastoma because of their ability to stabilize DNA damage and promote DNA damage response in response to 6-oxazole 6-methyl-CoA reductase inhibitors (6OTD)." }, { "input": "Is RUNX1T1 associate with obesity?", "output": "Yes, the rs34269950 SNP of the RUNX1T1 gene was significantly associated with obesity risk and metabolic abnormalities. Specifically, compared to AA genotype, rs34269950 del/del genotype was associated with a 1.47 [95% confidence interval (CI): 1.01-2.14, P\u2009=\u20090.042] fold higher rate of obesity risk." }, { "input": "Is Adamts18 deficiency associated with cancer?", "output": "Yes. ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/\u03b2-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model." }, { "input": "What causes Ocular Thelaziasis?", "output": "Ocular Thelaziasis is caused by Thelazia callipaeda." }, { "input": "What is the role of cytidine deaminase in healthy cells?", "output": "Activation-induced cytidine deaminase (AID) catalyses the deamination of deoxycytidines to deoxyuracils within immunoglobulin genes to induce somatic hypermutation and class-switch recombination." }, { "input": "Summarize the cause of autosomal dominant Spinocerebellar Ataxia type 3.", "output": "Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3." }, { "input": "Summarize the cause of autosomal dominant Spinocerebellar Ataxia type 3.", "output": "Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3." }, { "input": "Through which pathway does the FTO-guided demethylation of GADD46 drive myogenesis?", "output": "FTO-mediated demethylation of GADD45B promotes myogenesis through the activation of p38 MAPK pathway." }, { "input": "What are the key characteristics of the syndrome caused by ANKRD17 loss-of-function variants?", "output": "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphia." }, { "input": "What are the key characteristics of the syndrome caused by ANKRD17 loss-of-function variants?", "output": "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism." }, { "input": "What are the key characteristics of the syndrome caused by ANKRD17 loss-of-function variants?", "output": "Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism, as well as growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy, and/or abnormal EEG, and predisposition to recurrent infections." }, { "input": "Is Ozanimod effective for Ulcerative Colitis?", "output": "Yes, Ozanimod is effective for Ulcerative Colitis." }, { "input": "What is the function of the protein PIEZO1?", "output": "Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca2+ influx, which in turn regulates cytoskeletal remodeling and stress alterations." }, { "input": "Please list 3 biologic(monoclonal antibody) drugs used to treat migraine headaches.", "output": " Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use." }, { "input": "Please list 3 biologic(monoclonal antibody) drugs used to treat migraine headaches.", "output": "Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use." }, { "input": "What is the most common N6-methyladenosine (m6A) methylation modification site of RUNX1T1?", "output": "The RRACH motif is the most common N6-methyladenosine (m6A) methylation modification site of RUNX1T1." }, { "input": "Describe GREEKC", "output": "The COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together experts from all over the world working on various steps in the knowledge management process that focuses on understanding gene regulatory mechanisms." }, { "input": "Describe GREEKC", "output": "As computational modeling becomes more essential to analyze and understand biological regulatory mechanisms, governance of the many databases and knowledge bases that support this domain is crucial to guarantee reliability and interoperability of resources. To address this, the COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together a wide range of experts from all over the world working on various steps in the knowledge management process that focuses on understanding gene regulatory mechanisms. The discussions between ontologists, curators, text miners, biologists, bioinformaticians, philosophers and computational scientists spawned a host of activities aimed to standardize and update existing knowledge management workflows and involve end-users in the process of designing the Gene Regulation Knowledge Commons (GRKC)." }, { "input": "Which receptors are targeted by Tirzepatide?", "output": "Tirzepatide is dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide." }, { "input": "Is esophageal adenocarcinoma associated with aberrant glycosylation?", "output": "Yes,\nAltered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown." }, { "input": "What is the function of a chaperonin?", "output": "Molecular chaperones promote the correct folding of proteins in aggregation-prone cellular environments by stabilizing nascent polypeptide chains and providing appropriate folding conditions. They are involved in the development of pathological processes, including--atherosclerosis and coronary heart disease." }, { "input": "What is the function of a chaperonin?", "output": "Chaperonins assist in the acquisition of native protein structure in the cell by providing a shielded environment for a folding polypeptide chain, generated by the interior surface of their cylindrical structure." }, { "input": "What is the function of a chaperonin?", "output": "Molecular chaperones promote the correct folding of proteins in aggregation-prone cellular environments by stabilizing nascent polypeptide chains and providing appropriate folding conditions." }, { "input": "Can FTO promote pancreatic cancer development?", "output": "No, the m6A demethylase FTO suppresses pancreatic cancer tumorigenesis." }, { "input": "Which disorder is caused by biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1)?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)." }, { "input": "Which disorder is caused by biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1)?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB)" }, { "input": "Which disorder is caused by biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1)?", "output": "Biallelic mutations in G-Protein coupled receptor kinase 1 (GRK1) cause Oguchi disease, a rare subtype of congenital stationary night blindness (CSNB), which is caused by a protein-coupled receptor-protein interaction." }, { "input": "Which disease is treated with Tebentafusp?", "output": "Tebentafusp is used for treatment of Metastatic Uveal Melanoma." }, { "input": "Is Lysozyme abundant in human tears?", "output": "Yes,\nlysozyme is the most prevalent protein in tear fluid." }, { "input": "What is Neuromedin U (NmU)", "output": "Neuromedin U (NmU) is a highly conserved neuropeptide and has multiple physiological and pathophysiological roles detected, ranging from smooth muscle contraction, feeding, energy balance to tumorigenesis, stress responses, and inflammation." }, { "input": "What is Neuromedin U (NmU)", "output": "Neuromedin U (NmU) is a bioactive neuropeptide that is highly distributed in the central nervous system and the gastrointestinal tract. It has a number of physiological and pathophysiological roles, ranging from feeding behavior, energy metabolism, stress responses, circadian rhythmicity and inflammation." }, { "input": "Is FTY720 FDA approved?", "output": "Yes, FTY720 was approved by the US Food and Drug Administration (FDA) in 2010." }, { "input": "Describe SPar-K", "output": "SPar-K is a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other kinds of functional sites. This method efficiently deals with problems of data heterogeneity, limited misalignment of anchor points and unknown orientation of asymmetric patterns." }, { "input": "Describe SPar-K", "output": "SPar-K (Signal Partitioning with K-means) is a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other kinds of functional sites. This method efficiently deals with problems of data heterogeneity, limited misalignment of anchor points and unknown orientation of asymmetric patterns." }, { "input": "Describe SPar-K", "output": "SPar-K (Signal Partitioning with K-means) is a method to search for archetypical chromatin architectures by partitioning a set of genomic regions characterized by chromatin signal profiles around ChIP-seq peaks and other functional sites." }, { "input": "What is the mechanism of action of donanemab?", "output": "Donanemab is a new monoclonal antibody that uniquely targets A\u03b2(p3-42), a pyroglutamate form of Amyloid-\u03b2 (A\u03b2) exclusively found in plaques." }, { "input": "Is cytokeratin a tumor marker?", "output": "Yes,\ncytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a tumor marker." }, { "input": "What are TAMs in cancer therapy?", "output": "TAMs are Tumor Associated Macrophages and are important in Cancer therapy." }, { "input": "What is the relationship between RUNX1T1 and FTO?", "output": "FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. The effect of FTO on adipogenesis appears to be mediated via enhanced expression of the pro-adipogenic short isoform of RUNX1T1." }, { "input": "Which java utility has been developed for class hidden markov models?", "output": "JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols, and is used for biological sequence analysis and class hidden markov models in Java EE 8 and Java EE 9." }, { "input": "Which java utility has been developed for class hidden markov models?", "output": "JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols." }, { "input": "Which java utility has been developed for class hidden markov models?", "output": "JUCHMME is an open-source software package in Java designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols." }, { "input": "What is the mechanism of action of Etesevimab?", "output": "Etesevimab is a neutralizing antibody indicated for treatment of coronavirus disease 2019 (COVID-19) in patients with early mild or moderate disease." }, { "input": "List known pseudokinases.", "output": "TRIB1\nTRIB2\nTRIB3\nMLKL\nULK4\nHER3\nCASK" }, { "input": "Where is the body would the Peyer's patches be found", "output": "Peyer's patches (PPs) play a major role in intestinal mucosal immunity and are located in the gut." }, { "input": "Is tofacitinib a JAK inhibitor?", "output": "Yes, tofacitinib is a small JAK inhibitor." }, { "input": "Describe the GenomeAsia 100K Project", "output": "The GenomeAsia 100K Project (GenomeAsia100K Project) aims to identify and catalogue genetic variation, population structure, disease associations and founder effects in populations across Asia and worldwide. It includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia, as well as a population-wide association dataset." }, { "input": "Describe the GenomeAsia 100K Project", "output": "The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world's population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. The pilot phase of the GenomeAsia 100K Project includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia." }, { "input": "Which disease is treated with Risdiplam?", "output": "Risdiplam is approved for spinal muscular atrophy." }, { "input": "What is protein palmitoylation?", "output": "Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16\u2011carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization." }, { "input": "\u0391re plants from the genus Strychnos the original source of curare?", "output": "Species of plants from the genus Strychnos are the source of curare." }, { "input": "When was galcanezumab approved by FDA?", "output": "Galcanezumab was approved by the FDA in September 2018." }, { "input": "Are variants in FHF2 (also known as FGF13) associated with encephalopathy?", "output": "Yes. FHF2 (also known as FGF13) variants are a cause of infantile-onset developmental and epileptic encephalopathy." }, { "input": "Tofersen has been developed for treatment of which disease?", "output": "Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis is being studied for the treatment of amyotrophic lateral sclerosis due to SOD1 mutations." }, { "input": "What is the cause of lactose intolerance?", "output": "Lactose intolerance is a common condition caused by lactase deficiency and may result in symptoms of lactose malabsorption (bloating, flatulence, abdominal discomfort, and change in bowel habits).\nFour clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance." }, { "input": "What is Etizolam?", "output": "Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India as an anxiolytic drug with a pharmacologic profile similar to that of the classic benzodiazepines. Neurochemical research suggests that etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (ie, alpha1, beta2, gamma2)." }, { "input": "What is Etizolam?", "output": "Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABAA receptors." }, { "input": "Is AZD9668 a VEGF mRNA drug?", "output": "AZD9668 is a reversible and selective inhibitor of neutrophil elastase." }, { "input": "What is caused by de novo VPS4A mutations?", "output": "De novo VPS4A mutations cause multisystem disease with abnormal neurodevelopment. VPS4A normal function is required for multiple human developmental and cellular processes." }, { "input": "What is caused by de novo VPS4A mutations?", "output": "De-novo VPS4A mutations cause multisystem disease with abnormal neurodevelopment, including dyskinesias, dyslipidemia, and dysplastic skin and cartilaginous neoplasia, as well as an inability to control intracranial temperature." }, { "input": "What is the use of pegcetacoplan?", "output": "Pegcetacoplan is promising for paroxysmal nocturnal haemoglobinuria and Geographic Atrophy." }, { "input": "What is the activity of a Oligosaccharyltransferases ?", "output": "oligosaccharyltransferases (OSTs), which catalyze the attachment of glycans to specific amino acid residues in target proteins" }, { "input": "On what chromosome would the MKKS gene for McKusick-Kaufman(AKA Kaufman-McKusick) syndrome be found?", "output": "The MKKS gene is mapped to chromosome 20" }, { "input": "Which maternal CYP2D6 related phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding?", "output": "Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine." }, { "input": "Describe the web application VICTOR", "output": "VICTOR is a free, dependency-free visual analytics web application that allows the visual comparison of the results of various clustering algorithms. It can handle multiple cluster set results simultaneously and compare them using ten different metrics. Clustering results can be filtered and compared with the use of data tables or interactive heatmaps, bar plots, correlation networks, sankey and circos plots." }, { "input": "Describe the web application VICTOR", "output": "VICTOR is a visual analytics web application which allows the visual comparison of the results of various clustering algorithms." }, { "input": "Describe the web application VICTOR", "output": "VICTOR is the first fully interactive and dependency-free visual analytics web application which allows the visual comparison of the results of various clustering algorithms. VICTOR can handle multiple cluster set results simultaneously and compare them using ten different metrics. Clustering results can be filtered and compared to each other with the use of data tables or interactive heatmaps, bar plots, correlation networks, sankey and circos plots." }, { "input": "What is GLS-5700?", "output": "GLS-5700 is a synthetic, consensus DNA vaccine encoding the ZIKV premembrane and envelope proteins that was tested for Zika virus disease." }, { "input": "Is histone variant H3.3K27M associated with gliomas?", "output": "Yes,\nDiffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation." }, { "input": "What is another name for keratomileusis?", "output": "Report the outcomes of laser in situ keratomileusis (LASIK) for high myopia correction after long-term follow-up" }, { "input": "What is another name for keratomileusis?", "output": "['Report the outcomes of laser in situ keratomileusis (LASIK) for high myopia correction after long-term follow-up.']" }, { "input": "What is another name for keratomileusis?", "output": "Laser in situ keratomileusis is also known as LASIK" }, { "input": "What is another name for keratomileusis?", "output": "Laser in situ keratomileusis (LASIK)" }, { "input": "In which motif of the RUNX1T1 protein is the rs34269950 SNP located?", "output": "The rs34269950 SNP of RUNX1T1 is located in the 'RRACH' motif." }, { "input": "What is caused by SCUBE3 loss of function?", "output": "SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling." }, { "input": "What is caused by SCUBE3 loss of function?", "output": "SCUBE3 is a BMP2/BMP4 co-receptor. It is responsible for the development of bone and teeth. When it is not functioning properly, it inhibits the growth and development of these tissues." }, { "input": "What is caused by SCUBE3 loss of function?", "output": "SCUBE3 loss-of-function results in a human disease caused by defective function of a member of the SCUBE family that is associated with a previously unrecognized syndromic disorder. The disorder is characterized by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. It is also associated with dysregulating bone morphogenetic protein signaling." }, { "input": "Which drugs are included in the CAPOX chemotherapy regimen for colorectal cancer?", "output": "CAPOX chemotherapy regimen for colorectal cancer includes capecitabine plus oxaliplatin." }, { "input": "Is FKBP52 encoding a chaperone ?", "output": "Yes,\nFKBP52 is a co-chaperone." }, { "input": "Isotocin is an homolog of what hormone?", "output": "Isotocin is a homolog of oxytocin." }, { "input": "Fingolimod is a selective antagonist for which molecule?", "output": "Fingolimod is a selective S1P1 functional antagonist by induction of irreversible S1P1 internalization and degradation." }, { "input": "Does \u03b1CGRP have amyloidogenic properties?", "output": "Yes. \u03b1CGRP, a 37-residue-long peptide hormone, is a novel amyloidogenic member of the CGRP family" }, { "input": "Does \u03b1CGRP have amyloidogenic properties?", "output": "Yes, it has amyloidogenic properties. It is a member of the CGRP family." }, { "input": "Is istiratumab effective for pancreatic cancer?", "output": "No. In clinical trial, istiratumab failed to improve efficacy of standard of care for pancreatic cancer." }, { "input": "What is the human proteoform project?", "output": "Top-down proteomics is emerging as a preferred approach to investigate biological systems, with objectives ranging from the detailed assessment of a single protein therapeutic, to the complete characterization of every possible protein including their modifications, which define the human proteoform." }, { "input": "Telomestatin is derived from what organism?", "output": "Telomestatin is a natural macrocyclic compound derived from Streptomyces anulatus 3533-SV4" }, { "input": "Which plant is khellin extracted from?", "output": "Khellin is extracted from the seeds of the plant Ammi visnaga." }, { "input": "Describe ANTISOMA", "output": "The ANTISOMA method is a computerized pipeline for the reduction of the aggregation tendency of monoclonal antibodies (mAbs) based on an automated amino acid substitution approach. The method is available online at http://bioinformatics.biol.uoa.gr/antisoma." }, { "input": "Describe ANTISOMA", "output": "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability." }, { "input": "Describe ANTISOMA", "output": "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach." }, { "input": "Describe ANTISOMA", "output": "ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability. The method is available online at http://bioinformatics.biol.uoa.gr/ANTISOMA ." }, { "input": "Which factors are inhibited by Abelacimab?", "output": "Abelacimab is a novel dual inhibitor of Factor XI and Factor XIa." }, { "input": "What is vesiduction?", "output": "'Vesiduction' as a fourth mode of intercellular DNA transfer." }, { "input": "What is the route of administration of eptinezumab?", "output": "Eptinezumab is administered intravenously." }, { "input": "What kind of approaches you need to combine in order to manage Familial spontaneous pneumothorax?", "output": "Clinical, radiological and genetic approaches" }, { "input": "What kind of approaches you need to combine in order to manage Familial spontaneous pneumothorax?", "output": "Combining clinical, radiological and genetic approaches to pneumothorax management is a critical step in managing family history and family history-based causes of spontaneous pneumothorsic disease (FPSD) in children and adults who have a family history of FPSD and are at high risk for the disease because of family history." }, { "input": "What is the mechanism of action of Vericiguat?", "output": "Vericiguat is a stimulator of soluble guanylate cyclase. It was developed for treatment of chronic heart failure with reduced ejection fraction." }, { "input": "What is the origin of HEp-2 cells?", "output": "human larynx epidermoid carcinoma cell line (HEp-2)" }, { "input": "Does bleomycin cause lung toxicity?", "output": "Pulmonary toxicity is a devastating complication of bleomycin chemotherapy." }, { "input": "What is another name for bimagrumab", "output": "Bimagrumab also goes by the name BYM338." }, { "input": "What is STATegra?", "output": "STATegra is a comprehensive multi-omics dataset of B-cell differentiation in mouse. It includes measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation." }, { "input": "What is STATegra?", "output": "It's a multi-omics dataset that combines measurements from up to 10 different omics technologies, namely pre-B-cell differentiation." }, { "input": "What is STATegra?", "output": "Stategra is a multi-omics dataset that includes measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. It includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and is complemented with single-cell data." }, { "input": "What is STATegra?", "output": "STATegra is a comprehensive multi-omics dataset of B-cell differentiation in mouse. It combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data." }, { "input": "What is the generic name of the Xofluza?", "output": "Baloxavir marboxi is the generic name of Xofluza. It is approved for influenza." }, { "input": "Is Keutel syndrome a common genetic disorder?", "output": "No, Keutel syndrome (OMIM 245150) is a very rare syndrome" }, { "input": "Is fusobacterium associated with Lemierre's syndrome?", "output": "Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum." }, { "input": "Is fusobacterium associated with Lemierre's syndrome?", "output": "Yes. Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum." }, { "input": "Is fusobacterium associated with Lemierre's syndrome?", "output": "Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum" }, { "input": "Is fusobacterium associated with Lemierre's syndrome?", "output": "Lemierre's syndrome is a rare condition that results from oropharyngeal infection, usually with the gram-negative, anaerobic Fusobacterium necrophorum." }, { "input": "What is the synonym of MK-1602?", "output": "MK-1602 is also named Ubrogepant." }, { "input": "How many families did the 100,000 Genomes Pilot enrol?", "output": "The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. A pilot study was conducted involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present." }, { "input": "How many families did the 100,000 Genomes Pilot enrol?", "output": "The 100,000 Genomes Project is a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present." }, { "input": "What is CIS43LS?", "output": "CIS43LS is an antimalarial monoclonal antibody with an extended half-life against infection with Plasmodium falciparum." }, { "input": "List the main salt-inducible kinases.", "output": "SIK1\nSIK2\nSIK3\nHDAC4\nHDAC5" }, { "input": "Unlike DNA, RNA is not methylated, yes or no?", "output": "In addition to DNA methylation, reversible epigenetic modification occurring in RNA has been discovered recently. The most abundant type of RNA methylation is N6-methyladenosine (m6A) modification, which is dynamically regulated by methylases (\"writers\"), demethylases (\"erasers\") and m6A-binding proteins (\"readers\")" }, { "input": "Unlike DNA, RNA is not methylated, yes or no?", "output": "N6-methyladenosine (m6A) is the most abundant internal modification on messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in eukaryotes" }, { "input": "What methodology does the Oncomine Dx target test use?", "output": "The Oncomine Dx target test uses the next generation sequencing methodology." }, { "input": "Describe the application of whole genome sequencing in the diagnosis of primary ciliary dyskinesia (PCD)", "output": "Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery." }, { "input": "Describe the application of whole genome sequencing in the diagnosis of primary ciliary dyskinesia (PCD)", "output": "Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. In these cases it may detect SVs and is a powerful tool for novel gene discovery. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants." }, { "input": "Describe the application of whole genome sequencing in the diagnosis of primary ciliary dyskinesia (PCD)", "output": "WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants." }, { "input": "Which CD38 antibody has been shown to be effective for Lupus Erythematosus?", "output": "Daratumumab, a human monoclonal antibody that targets CD38, has been used to treat Lupus Erythematosus." }, { "input": "What is a circRNA?", "output": "Circular RNAs (circRNAs) are a new class of non-coding RNA with a stable structure formed by special loop splicing." }, { "input": "Summarize Fanconi's anemia", "output": "Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer." }, { "input": "Which one of the CYP450 enzymes is the second most frequently implicated in the metabolism of the drugs currently available on the market?", "output": "CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively." }, { "input": "Describe SBGNview", "output": "SBGNview is a tool set for pathway based data visalization" }, { "input": "Describe SBGNview", "output": "Pathway analysis is widely used in genomics and omics research, but the data visualization has been highly limited in function, pathway coverage and data format. SBGNview is a comprehensive R package to address these needs." }, { "input": "Which diseases can be treated with Itepekimab?", "output": "Itepekimab, a monoclonal antibody targeting IL-33, demonstrated clinical activity in asthma, with potential in chronic obstructive pulmonary disease (COPD)." }, { "input": "What is the msDNA?", "output": "msDNA is actually a complex of DNA, RNA, and probably protein. It is composed of a small, single-stranded DNA, linked to a small, single-stranded RNA molecule. The 5' end of the DNA molecule is joined to an internal guanosine residue of the RNA molecule by a unique 2'-5' phosphodiester bond. msDNA is produced in many hundreds of copies per cell, but its function remains unknown." }, { "input": "Are Epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 epoxygenases from arachidonic acid?", "output": "Epoxyeicosatrienoic acids (EETs) are fatty acid signaling molecules synthesized by cytochrome P450 epoxygenases from arachidonic acid" }, { "input": "Are Epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 epoxygenases from arachidonic acid?", "output": "Yes. Epoxyeicosatrienoic acids (EETs) are synthesized by cytochrome P450 epoxygenases from arachidonic acid." }, { "input": "Are Epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 epoxygenases from arachidonic acid?", "output": "Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells." }, { "input": "What percentage of currently available drugs are metabolized by CYP3A4?", "output": "CYP3A4 metabolizes approximately 50% of the drugs available today on the market." }, { "input": "What is caused by bi-allelic loss-of-function variants in IPO8?", "output": "Bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes." }, { "input": "What is caused by bi-allelic loss-of-function variants in IPO8?", "output": "Importin, a member of the importin-\u03b2 protein family, is a protein that translocates cargo molecules, proteins, and ribonucleoprotein complexes into the nucleus in RanGTP-dependent manner. Bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm." }, { "input": "What is caused by bi-allelic loss-of-function variants in IPO8?", "output": "Syndromic thoracic aortic aneurysm" }, { "input": "What is the mechanism of action of Evinacumab?", "output": "Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) that has been shown to reduce low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia." }, { "input": "Which glands in the bee secretes royal jelly?", "output": "hypopharyngeal glands" }, { "input": "List the common retinal diseases associated with circRNAs.", "output": "Circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for retinal degeneration, diabetic retinopathy, proliferative diabetic retinopathy (PDR) and Retinopathy of prematurity (ROP)" }, { "input": "How do CYP1A2 polymorphisms affect the habitual coffee consumption effect on apetite?", "output": "The CYP1A2 polymorphism -163C\u2009>\u2009A (rs762551) polymorphism renders carriers: rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers.\nHigh coffee consumption was more prevalent in rapid compared to slow metabolizers (P\u2009=\u20090.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption\u2009=\u20090.002 and 0.048, respectively)." }, { "input": "What is the role of SDE2?", "output": "SDE2 is a previously uncharacterized essential gene required for ribosome biogenesis and the regulation of alternative splicing." }, { "input": "What is the role of SDE2?", "output": "The role of SDE2 is to regulate RNA splicing and ribosome biogenesis." }, { "input": "What is the role of SDE2?", "output": "SDE2 is required for ribosome biogenesis and the regulation of alternative splicing" }, { "input": "What is the role of SDE2?", "output": "Silencing Defective 2 (SDE2) is an essential gene required for ribosome biogenesis and the regulation of alternative splicing. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability." }, { "input": "What is the role of SDE2?", "output": "SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing." }, { "input": "Which drugs are included in the CABENUVA pill?", "output": "Cabenuva contains cabotegravir and rilpivirine. It is used for treatment of HIV." }, { "input": "What is Shone's complex?", "output": "Shone's syndrome is a rare congenital heart disease that includes 4 cardiovascular anomalies: supravalvular mitral ring, parachute mitral valve, subaortic stenosis, and coarctation of the aorta." }, { "input": "What methods are used to diagnose bowel endometriosis?", "output": "Double-contrast barium enema (DCBE), transrectal endoscopic ultrasonography (REU), multidetector computerized tomography enema (MDCT-e), and computed tomography colonoscopy (CTC) have been successfully used for the diagnosis of bowel endometriosis." }, { "input": "When did FDA approve the first B-cell maturation antigen-targeted CAR-T cell therapy?", "output": "FDA approved the first B-cell maturation antigen-targeted CAR-T cell therapy on March 26, 2021." }, { "input": "Describe the N6-methyladenosine RNA modification in AML", "output": "The N6-methyladenosine RNA modification in AML is a nucleotide that is not normally found in the DNA of cancer cells. This nucleotide has been shown to have an effect on the cell's ability to divide." }, { "input": "Describe the N6-methyladenosine RNA modification in AML", "output": "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells. Similar observations were made with the demethylases fat mass and obesity-associated protein and AlkB homologue 5 RNA demethylase. Of importance, loss of any of these genes has little to no effect on normal hemopoietic stem cells, suggesting therapeutic potential." }, { "input": "Describe the N6-methyladenosine RNA modification in AML", "output": "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells." }, { "input": "Describe the N6-methyladenosine RNA modification in AML", "output": "the N6-methyladenosine (m6A) modification of RNA has been shown to play an important role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs)" }, { "input": "Describe the N6-methyladenosine RNA modification in AML", "output": "The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells. Similar observations were made with the demethylases fat mass and obesity-associated protein and AlkB homologue 5 RNA demethylase." }, { "input": "Does trimetazidine protect from myocardial injury after percutaneous coronary intervention?", "output": "Oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice." }, { "input": "When is the drug Ivermectin used?", "output": "Ivermectin (IVM) has been well known for its role in the treatment of parasitic diseases, due to its effect on glutamate-gated chloride channels. These same channels are also present in the mosquito vector, and thus, research has focused on the insecticidal effects of this drug." }, { "input": "What is the function of a DEAD box protein?", "output": "DEAD-box helicases are ubiquitous in RNA-mediated processes and function by coupling cycles of ATP binding and hydrolysis to changes in affinity for single-stranded RNA." }, { "input": "What is the function of a DEAD box protein?", "output": "DEAD-box helicase proteins perform ATP-dependent rearrangements of structured RNAs" }, { "input": "What is the function of a DEAD box protein?", "output": "DEAD-box (DDX) proteins belong to the largest subfamily of RNA helicase SF2, which contributes to all biological processes of RNA metabolism" }, { "input": "What is the function of a DEAD box protein?", "output": "DEAD-box proteins catalyze the ATP-dependent unwinding of RNA duplexes and accompany RNA molecules throughout their cellular life." }, { "input": "What is the effect of rHDL-apoE3 on vascular permeability?", "output": "rHDL-apoE3 markedly improves vascular permeability as demonstrated by the reduced concentration of Evans Blue dye in tissues such as the stomach, the tongue and the urinary bladder and ameliorated hypercholesterolemia." }, { "input": "What is inhibited by TH1579?", "output": "TH1579 is a best-in-class MTH1 inhibitor." }, { "input": "What is inhibited by TH1579?", "output": "MTH1" }, { "input": "What is inhibited by TH1579?", "output": "TH1579 inhibits the MTH1 protein, which is the protein that cancer cells rely on to make their DNA." }, { "input": "What is the mechanism of action of Gemogenovatucel-T?", "output": "Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-\u03b21 and TGF-\u03b22." }, { "input": "What is the Versene Solution used for?", "output": "the Versene Solution is used for the detachment of stem cell sheets." }, { "input": "Are circRNAs susceptible to degradation by RNase R?", "output": "Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation." }, { "input": "Are circRNAs susceptible to degradation by RNase R?", "output": "Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs." }, { "input": "Are circRNAs susceptible to degradation by RNase R?", "output": "Yes. Circular RNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation." }, { "input": "Does atemoya juice inhibit tye CYP3A4 enzyme?", "output": "No, atemoya juice does not inhibit CYP3A4." }, { "input": "Which processes are affected by pathogenic SPTBN1 variants?", "output": "SPTBN1 variants lead to effects that affect \u03b2II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics." }, { "input": "Describe the role of bevacizumab in radiosurgery for arteriovenous malformation.", "output": "Bevacizumab is used for the treatment of severe, refractory perilesional edema due to an arteriovenous malformation treated with stereotactic radiosurgery." }, { "input": "Is Mycobacterium abscessus a human pathogen?", "output": "Yes,\nMycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates." }, { "input": "What is the indication for Favipiravir?", "output": "Favipiravir (FVP) has been used for treatment of COVID-19 in many countries." }, { "input": "Is MEDI2228 a bispecific antibody?", "output": "No, MEDI2228 is an antibody drug conjugate (ADC)." }, { "input": "Which syndrome is caused by pathogenic COL4A3-COL4A5 variants?", "output": "Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis. The population frequencies for Alport syndrome are suggested by the frequencies of predicted pathogenic COL4A3-COL4A5 variants, but must be adjusted for the disease penetrance of individual variants and for the likelihood of already diagnosed disease and non-Gly substitutions." }, { "input": "Which syndrome is caused by pathogenic COL4A3-COL4A5 variants?", "output": "Pathogenic variants in the genes in Alport Syndrome (COL4A3-C4A5) are found in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), and 20% with familial immunoglobulin A (IGA) Glomerulonephritis. The population frequencies for Alport syndrome are suggested to be higher than the frequencies of predicted pathogenic variants, but must be adjusted for the disease penetrance individual variants and for the likelihood of already diagnosed disease and non-Gly substitutions." }, { "input": "Which syndrome is caused by pathogenic COL4A3-COL4A5 variants?", "output": "Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis." }, { "input": "Is proton beam therapy used for treatment of craniopharyngioma?", "output": "Yes, proton beam therapy is used for treatment of craniopharyngioma." }, { "input": "What are the phases of hair follicle cycle?", "output": "Hair follicle cycle phases (anagen, catagen and telogen)" }, { "input": "What is the cause of Bow Hunter's syndrome?", "output": "Bow hunter's syndrome (BHS) is caused by posterior circulation insufficiency that results from the occlusion or compression of the vertebral artery (VA) during neck rotation." }, { "input": "What is the cause of Bow Hunter's syndrome?", "output": "Bow Hunter's Syndrome (BHS) is caused by the occlusion of the vertebral artery with head rotation leading to ischemia and sometimes stroke." }, { "input": "What types of anti-tumor therapeutic antibodies are available?", "output": "Anti-tumor therapeutic antibodies include single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs)." }, { "input": "Which disease do pathogenic NR2F1 variants cause?", "output": "Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal-dominant disorder characterized by optic atrophy and intellectual disability caused by loss-of-function mutations in NR2F1." }, { "input": "Which disease do pathogenic NR2F1 variants cause?", "output": "Bosch-Boonstra-Schaaf optic atrophy syndrome" }, { "input": "Which disease do pathogenic NR2F1 variants cause?", "output": "Bosch-Boonstra-Schaaf Optic Atrophy Syndrome" }, { "input": "Which mutation is targeted by Tepotinib?", "output": "MET Exon 14 Skipping Mutation is targeted by Tepotinib that is used for patients with non-small-cell lung cancer." }, { "input": "List second messengers.", "output": "Cyclic adenosine monophosphate\nCeramide\nCyclic diguanylate\nNitric oxide\nCalcium\nDiacylglycerol" }, { "input": "Is there a genetic cause of craniostenosis?", "output": "9There a a number of different genetic mutations or syndromes(Saethre-Chotzen, Aperts, Crouzon, Pfeiffer) associated with craniostenosis." }, { "input": "Is there a genetic cause of craniostenosis?", "output": "Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities" }, { "input": "Can bergapten cross the blood-brain barrier?", "output": "Yes, bergapten can cross the blood-brain barrier." }, { "input": "Does TIMELESS-TIPIN participate in replisome disassembly?", "output": "Yes. TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans." }, { "input": "Nemolizumab has been shown to be effective for which disease?", "output": "Nemolizumab has been shown to be effective for atopic dermatitis." }, { "input": "Is hemoglobin antimicrobial?", "output": "Yes,\nBeyond its physiological activity, hemoglobins are able to inhibit the growth of several microorganisms." }, { "input": "What is the mammalian version of arginine vasotocin?", "output": "Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP)" }, { "input": "What is the mammalian version of arginine vasotocin?", "output": "Arginine vasopressin (AVP) is the mammalian homolog of arginine vasotocin (AVT)." }, { "input": "Which kinase does PD98059 inhibit?", "output": "PD98059 is a specific, reversible MEK inhibitor." }, { "input": "What is caused by loss-of-function variants in BCAS3?", "output": "Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder. BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis." }, { "input": "What is caused by loss-of-function variants in BCAS3?", "output": "Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder." }, { "input": "What is caused by loss-of-function variants in BCAS3?", "output": "BCAS3 microtubule-associated migration factor (BCAS3) is a large, highly tuned cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in the growth of tumors. It has been linked to a syndromic neurodevelopmental disorder." }, { "input": "What is caused by loss-of-function variants in BCAS3?", "output": "BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis. Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder." }, { "input": "Which transporter is inhibited by Sotagliflozin?", "output": "Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2." }, { "input": "What is the main use of ETD fragmentation?", "output": "Electron-based fragmentation methods have revolutionized biomolecular mass spectrometry, in particular native and top-down protein analysis." }, { "input": "What is the Bartter syndrome?", "output": "Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney. Its clinical features are renal salt wasting, hypokalemic metabolic alkalosis, elevated renin and aldosterone levels with normal or low blood pressure, polyuria, hypercalciuria and malnutrition." }, { "input": "What is the Bartter syndrome?", "output": "Bartter syndrome is a rare hereditary salt-losing tubulopathy caused by mutations of several genes in the thick ascending limb of Henle's loop, characterized by polyuria, hypokalemic metabolic alkalosis, growth retardation and normal blood pressure." }, { "input": "What is the Bartter syndrome?", "output": "Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney." }, { "input": "What is the Bartter syndrome?", "output": "Bartter syndrome is a syndrome associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis" }, { "input": "Can bergapten cause phototoxicity?", "output": "Yes, phototoxicity is a side effect of bergapten." }, { "input": "Which syndromes are caused by LAMA1 mutations?", "output": "Poretti-Boltshauser and Joubert syndromes" }, { "input": "Which syndromes are caused by LAMA1 mutations?", "output": "Poretti\u2013Boltshauser syndrome, Joubert syndrome" }, { "input": "What is the use of Lactin-V?", "output": "Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis and can be used for bacterial vaginosis. Lactin-V after treatment for cystitis was associated with a reduction in recurrent UTI." }, { "input": "What is Congo red agar plates used for?", "output": "Congo red agar plates are used as a canonical indicator of biofilm-formation ability. Culture on Congo red agar plates in which slime-producing strains form black colonies, while nonslime-forming ones develop red colonies." }, { "input": "What is the protein that is truncated to produce progerin?", "output": "The truncated lamin A protein produced \"progerin" }, { "input": "What is the protein that is truncated to produce progerin?", "output": "Hutchinson Gilford progeria syndrome (HGPS) is a devastating accelerated aging disease caused by LMNA gene mutation. The truncated lamin A protein produced \"progerin\"" }, { "input": "What are the effects of ibrutinib on CART cell production?", "output": "CART cell generation in the presence of ibrutinib resulted in increased cell viability and expansion of CLL patient-derived CART cells. Furthermore, ibrutinib enriched CART cells with less-differentiated na\u00efve-like phenotype and decreased expression of exhaustion markers including PD-1, TIM-3 and LAG-3. In addition, ibrutinib increased the cytokine release capacity of CLL patient-derived CART cells. In summary, BTK/ITK inhibition with ibrutinib during CART cell culture can improve yield and function of CLL patient-derived CART cell products." }, { "input": "What is the role of miR-193b in prostate cancer?", "output": "Overexpression of miR-193b led to the inhibition of the majority of the 41 genes in prostate cancer cell lines." }, { "input": "What is the role of miR-193b in prostate cancer?", "output": "Overexpression of miR-193b in prostate cancer cell lines inhibited invasion and induced apoptosis. A majority of the top 150 genes downregulated when miR-193b was overexpressed in liposarcoma are overexpressed in metastatic prostate cancer and 41 miR-193b target genes overlapped with the 86 genes in the aggressive prostate cancer subtype 1 (PCS1) signature. Overexpression of miR-193b led to the inhibition of the majority of the 41 genes in prostate cancer cell lines. High expression of the 41 genes was correlated with recurrence of prostate cancer. Knockdown of miR-193b targets FOXM1 and RRM2 in prostate cancer cells phenocopied overexpression of miR-193b. Dual treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors decreased miR-193b promoter methylation and restored inhibition of FOXM1 and RRM2." }, { "input": "What is the role of miR-193b in prostate cancer?", "output": "Overexpression of miR-193b in prostate cancer cell lines inhibited invasion and induced apoptosis." }, { "input": "What treatment was studied in the KEYNOTE-522 trial?", "output": "KEYNOTE-522 trial studied adjuvant pembrolizumab for patients with triple-negative breast cancer." }, { "input": "Which disease is associated with DNAJB1-PRKACA fusion gene?", "output": "Fibrolamellar carcinoma is distinctive at clinical and histologic levels. A novel DNAJB1-PRKACA fusion gene characterizes almost all cases." }, { "input": "What is NTI, Nerve Tissue Contrast Index", "output": "The Nerve Tissue Index NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a ultrasound image." }, { "input": "What is NTI, Nerve Tissue Contrast Index", "output": "The NTI is a ratio between the brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image." }, { "input": "What is NTI, Nerve Tissue Contrast Index", "output": "The NTI is a ratio of average brightness levels of surrounding tissue and the median nerve used in the diagnostic of Carpal Tunnel Syndrome." }, { "input": "What is NTI, Nerve Tissue Contrast Index", "output": "The NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image." }, { "input": "When was dupilumab approved by EMA?", "output": "Dupilumab was approved fby the EMA in 2017." }, { "input": "Describe bigPint", "output": "BigPint is a data visualization package available on Bioconductor under the GPL-3 license (https://bioconductor.org/packages/release/bioc/html/bigPint.html). This software introduces new visualization technology that enables independent layers of interactivity using Plotly in R, which aids in the exploration of large biological datasets. The bigPint package presents modernized versions of scatterplot matrices, volcano plots, and litre plots through the implementation of layered interactivity. These graphics have detected normalization issues, differential expression designation problems, and common analysis errors in public RNA-sequencing datasets. Researchers can apply bigPint graphics to their data by following recommended pipelines written in reproducible code in the user manual." }, { "input": "Aducanumab can be used for treatment of which disease?", "output": "Aducanumab is approved for treatment of Alzheimer's disease." }, { "input": "Can IFNg induce the expression of IDO?", "output": "Yes,\nIFNG-induce up-regulation of indoleamine 2,3-dioxygenase (IDO)" }, { "input": "Covid-19 is though to have arisen from what species?", "output": "COVID-19 caused by SARS-CoV-2 most likely originated in bats and transmitted to humans through a possible intermediate host." }, { "input": "Are TAMs good anticancer therapeutic targets?", "output": "Therapeutic strategies to target TAMs to complement conventional therapies has yielded promising results." }, { "input": "Describe meCLICK-Seq", "output": "MeCLICK-Seq is a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. The method hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA." }, { "input": "Describe meCLICK-Seq", "output": "meCLICK-Seq (methylation CLICK-degradation Sequencing) is a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. The method hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA." }, { "input": "Describe meCLICK-Seq", "output": "The meCLICK-Seq (methylation CLICK-degradation Sequencing) is a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. It hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA." }, { "input": "What is the mechanism of action of Lumasiran?", "output": "Lumasiran is a subcutaneously administered small interfering RNA targeting the mRNA for hydroxyacid oxidase 1 gene that is used for the treatment of primary hyperoxaluria type 1 (PH1). By silencing the gene encoding glycolate oxidase, lumasiran depletes glycolate oxidase and thereby inhibits the synthesis of oxalate, which is the toxic metabolite that is directly associated with the clinical manifestations of PH1." }, { "input": "Where are Goblet cells localized?", "output": "Goblet cells are found in the intestine, in the lungs, in the eyes etc. Goblet cells are localized in the epithelium." }, { "input": "What is OHRQoL?", "output": "The assessment of the oral health-related quality of life (OHRQoL) is possible with the Oral Health Impact Profile-14 (OHIP-14) questionnaire comprising 7 subdomains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap" }, { "input": "What is OHRQoL?", "output": "Diseases and disorders that damage the mouth and face can disturb well-being and his self-esteem. Oral health-related quality of life (OHRQOL) is a relatively new but rapidly growing concept and can be assessed using a number of different methods including standardized questionnaires. The OHRQoL is a concept that includes functional, social, emotional, and environmental issues. How patients perceive their oral health-related quality of life (OHRQoL) is important for health-care provider for understanding and planning in patient management." }, { "input": "Which VKORC1 genotypes are associated with a need for lower warfarin maintenance dose?", "output": "Patients with VKORC1-1639GA or AA required a lower warfarin maintenance dose." }, { "input": "Which R/bioconductor have been developed for copy number analysis?", "output": "CNVRanger, seqCNA, iGC, PLRS, SomatiCA, Copynumber, crlmm, KC-SMARTR are all R/bioconductor packages for copy number analysis" }, { "input": "Is gabapentin effective for chronic pelvic pain?", "output": "Based on data from multicentre, randomised, double-blind, placebo-controlled trial (GaPP2), treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo." }, { "input": "Does the royal jelly contain proteins?", "output": "Yes, main bioactive compounds of Royal Jelly, include proteins and peptides." }, { "input": "What is the brand name for erenumab?", "output": "Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine." }, { "input": "What is the brand name for erenumab?", "output": "Erenumab-aooe (erenumab, Aimovig\u00ae)-a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor-is approved for the prevention of migraine in adults in a number of countries" }, { "input": "Which protein does capmatinib bind?", "output": "Capmatinib binds MET." }, { "input": "Which neuropsychiatric disorders are associated with 16p13.11 genomic copy number variants?", "output": "schizophrenia, autism, mental retardation, ADHD, epilepsy" }, { "input": "Which neuropsychiatric disorders are associated with 16p13.11 genomic copy number variants?", "output": "16p13.11 genomic copy number variants are implicated in several neuropsychiatric disorders, such as schizophrenia, autism, mental retardation, ADHD and epilepsy." }, { "input": "Which neuropsychiatric disorders are associated with 16p13.11 genomic copy number variants?", "output": "schizophrenia, autism, mental retardation, ADHD and epilepsy" }, { "input": "What is carcinoma en cuirasse?", "output": "Breast carcinoma en cuirasse is an extremely rare form of cutaneous metastases of breast cancer, characterized by diffuse sclerodermoid induration of the skin." }, { "input": "What is carboxyglutamate?", "output": "One of the important glutamic acid modifications is post-translationally modified 4-carboxyglutamate." }, { "input": "What is Morton's Neuroma?", "output": "Morton's neuroma (MN) is a neuralgia involving the common plantar digital nerves of the metatarsal region." }, { "input": "What is Morton's Neuroma?", "output": "Morton's neuromas are abnormalities of the common digital nerve branch located between the lesser metatarsal heads and is a common cause of foot pain." }, { "input": "Which company produces the HercepTest?", "output": "DAKO is the company producing the companion diagnostic HercepTest." }, { "input": "Does UBE4B promote renal cancer?", "output": "Yes. UBE4B might act as an oncogene in regulating renal cancer development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of renal cancer patients." }, { "input": "Does addition of valproic acid improve survival of patients with diffuse intrinsic pontine glioma?", "output": "No. Addition of valproic acid and bevacizumab to radiation was well tolerated but did not appear to improve survival in children with diffuse intrinsic pontine glioma." }, { "input": "List the main protein families found in human tears?", "output": "Lipocalin\nCystatin S (CST4), \ncalcyclin (S100A6),\ncalgranulin A (S100A8) \nmatrix metalloproteinase 9 (MMP9)\nLTF, \nLYZ, \nZAG,\nDNAJC3" }, { "input": "In what year did Gregor Mendel die?", "output": "The life and personality of Johann Gregor Mendel (1822-1884)" }, { "input": "In what year did Gregor Mendel die?", "output": "Gregor Mendel, OSA (1822-1884), founder of scientific genetics." }, { "input": "In what year did Gregor Mendel die?", "output": "Johann Gregor Mendel 1822-1884" }, { "input": "List 4 monoclonal antibodies in development for the prevention of migraine.", "output": "Four monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab)" }, { "input": "Is there a role for CADM1 in Myelodysplastic syndrome (MDS)?", "output": "Yes, CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies with deletion of the long arm of chromosome 11." }, { "input": "Is there a role for CADM1 in Myelodysplastic syndrome (MDS)?", "output": "Yes. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11." }, { "input": "Is there a role for CADM1 in Myelodysplastic syndrome (MDS)?", "output": "Yes. Together with the frequent simultaneous deletions of KMT2A, ATM and CBL and mutations of ASXL1, SF3B1 and CBL, CADM1 may be important in the physiopathology of the del(11q) MDS." }, { "input": "Which drugs are in the Segluromet combination pill?", "output": "Segluromet includes combinations of ertugliflozin and metformin. It has recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM." }, { "input": "Where is the protein \"Single-stranded DNA-binding protein\" found?", "output": "In the mitochondrion (mitochondrial single-stranded DNA binding protein, mtSSB) and its role is the regulation of mitochondrial DNA replication initiation in mammalian mitochondria." }, { "input": "Is periampullary carcinoma (PAC) a relatively rare genitourinary malignancy", "output": "Periampullary carcinoma (PAC) a relatively rare gastrointestinal malignancy and includes Pancreaticobiliary as a subtype of Periampullary carcinoma" }, { "input": "For which indication has inotersen been approved?", "output": "Inoteresen has been approved for patients in stage 1 and stage 2 hereditary transthyretin amyloidosis polyneuropathy." }, { "input": "Do SETD1A mutations predispose to schizophrenia?", "output": "Yes. There is a mutation in the gene that codes for a protein called SetD1A. This protein is involved in the development of schizophrenia." }, { "input": "Do SETD1A mutations predispose to schizophrenia?", "output": "Yes. SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits." }, { "input": "Is Sotatercept effective for Pulmonary Arterial Hypertension?", "output": "Sotatercept was shown to be effective for Pulmonary Arterial Hypertension." }, { "input": "Which disease is caused by mutations in the gene CALR?", "output": "Somatic mutations of calreticulin (CALR) have been identified as a main disease driver of myeloproliferative neoplasms," }, { "input": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "output": "Conclusion. The German-SNOT-22 validated here matches the original SNOT-22. It is a reliable, valid and responsive questionnaire to assess symptoms, HRQOL and treatment-response in CRS-patients." }, { "input": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "output": "The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS)" }, { "input": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "output": "The SNOT-22 is a reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS)." }, { "input": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "output": "Yes, the 22-item sino-nasal outcome test (SNOT-22) is a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)." }, { "input": "Is the 22-item sino-nasal outcome test (SNOT-22) a widely used measure for Health-Related Quality-of-Life (HRQOL) associated with chronic rhinosinusitis (CRS)?", "output": "The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS)." }, { "input": "Is pRETRO-SUPER an adenoviral vector?", "output": "No, pRETRO-SUPER is a retroviral vector." }, { "input": "Which tool has been developed for annotation of G\u03b1, G\u03b2 and G\u03b3 subunits of G-proteins?", "output": "GprotPRED is an online tool that uses profile Hidden Markov Models (pHMMs) and application to proteomes. The sensitivity and specificity for all pHMMs were equal to 100% with the exception of the G\u03b2 case, where sensitivity equals to 100%, while specificity is 99.993%." }, { "input": "Which tool has been developed for annotation of G\u03b1, G\u03b2 and G\u03b3 subunits of G-proteins?", "output": "GprotPRED is a tool that has been developed for annotation of G\u03b1, G\u03b2 and G\u03b3 subunits of G-proteins using profile Hidden Markov Models (pHMMs)." }, { "input": "Describe applications of the CHALICE rule?", "output": "The children's head injury algorithm for the prediction of important clinical events (CHALICE) is one of the strongest clinical prediction rules for the management of children with head injuries. It can be used to predict death, need for neurosurgical intervention or CT abnormality in children with head trauma." }, { "input": "What is the KDEL retention signal?", "output": "the -KDEL retention signal sequence is characteristic of many proteins localized to the ER." }, { "input": "What are the diagnostic criteria for hemophagocytic lymphohistiocytosis?", "output": "Hemophagocytic syndrome (HS) is a severe hyper inflammatory condition whose cardinal symptoms are prolonged fever, cytopenia, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages." }, { "input": "What are the diagnostic criteria for hemophagocytic lymphohistiocytosis?", "output": "Hemophagocytic lymphohistiocytosis (HLH), diagnosis is based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis)." }, { "input": "When was Vitravene approved in Brazil?", "output": "Vitravene was approved in Brazil in the summer of 1999." }, { "input": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "output": "No. There is independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning" }, { "input": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "output": "No. There is evidence for the independence of chromatin organization and dorsoventral gene expression in Drosophila. Tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active." }, { "input": "Is vocimagene amiretrorepvec effective for recurrent high-grade glioma?", "output": "No. Despite initially promising results in a randomized, open-label phase 2/3 trial, among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC did not improve overall survival or other efficacy end points." }, { "input": "Which proteins are markers of myositis?", "output": "Blood tests showed significantly increased CK and aldolase values in patients with myositis (p < 0.001 and p < 0.0001)." }, { "input": "What is the association between maternal and fetal alloantigens and RANTES production?", "output": "Induction of maternal tolerance to fetal alloantigens by RANTES production." }, { "input": "What is the association between maternal and fetal alloantigens and RANTES production?", "output": "Maternal tolerance to fetal alloantigens may be induced by RANTES production." }, { "input": "What is Tagsedi?", "output": "Tagsedi is a second-generation antisense oligonucleotide with 2'-O-methoxyethyl modification designed to bind to the 3' untranslated region of the transthyretin mRNA in the nucleus of the liver cells." }, { "input": "Should perampanel be used for amyotrophic lateral sclerosis?", "output": "No. Perampanel should not be used for amyotrophic lateral sclerosis." }, { "input": "Is Satb1 a transcription factor?", "output": "Yes,\ntranscription factor Satb1." }, { "input": "What is PPROM?", "output": "Preterm premature(Prelabor) rupture of fetal membranes is often abbreviated as PPROM, and is defined as rupture of membranes before the onset of labor at < 37 weeks' gestation, affects approximately 3% of all pregnancies" }, { "input": "What is PPROM?", "output": "Preterm prelabor rupture of fetal membranes (PPROM) is defined as rupture of membranes before the onset of labor at 37 weeks' gestation, affects approximately 3% of all pregnancies." }, { "input": "What is PPROM?", "output": "spontaneous preterm premature rupture of fetal membranes (PPROM)." }, { "input": "What is the half-life of epimutations across generations of C. elegans?", "output": "In C. elegans, epimutations typically have short half-lives of two to three generations. Nevertheless, some epimutations last at least ten generations." }, { "input": "What drugs are included in the Avandamet pill?", "output": "The combination of metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes." }, { "input": "What does temsirolimus inhibit?", "output": "Temsirolimus is a mTOR inhibitor" }, { "input": "Are circular RNAs implicated in diseases of the eye?", "output": "Circular RNA (circRNA) are associated with several eye diseases." }, { "input": "What happens to the expression levels of piRNAs in the case of intracranial aneurysm rupture?", "output": "piRNAs showed a substantial decrease in RNA abundance that was sustained after IA rupture." }, { "input": "Lucio\u2019s Phenomenon is characteristic to which disease?", "output": "Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy." }, { "input": "Where are the complexins expressed?", "output": "Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane." }, { "input": "Please list the tests used to diagnose Allergic Rhinitis.", "output": "Diagnosis of allergic rhinitis is made by a combination of medical history, physical examination, positive methacholine challenge result or bronchodilator responsiveness, determination of IgE-mediated sensitization, and specific inhalation challenge tests as the gold standard, specific IgE screening tests include Skin prick test (SPT), Phadiatop, and nasal provocation test (NPT)." }, { "input": "Can epigenetic modifications be heritable?", "output": "Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift." }, { "input": "What is the role of the AIMS65 score?", "output": "AIMS65 score is used to predict outcomes after upper GI bleeding." }, { "input": "What is the gene ABCG1 encoding?", "output": "ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues." }, { "input": "Febrifugine could be repositioned for what diseases?", "output": "Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug." }, { "input": "Febrifugine could be repositioned for what diseases?", "output": "Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug. In addition, Prolyl-tRNA synthetase (PRS) drives protein translation in cells and are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against Plasmodium falciparum and Toxoplasma gondii. Febrifugine analogues have potential as Leishmania donovani trypanothione reductase inhibitors" }, { "input": "When was Volanesorsen approved in the EU?", "output": "In May 2019, volanesorsen was approved in the EU for the treatment of adult patients with familial chylomicronemia syndrome." }, { "input": "Is Belimumab used for lupus nephritis?", "output": "Yes, Belimumab can be used for lupus nephritis." }, { "input": "Is SOX10 expressed in melanoma cells?", "output": "Yes,\nThe most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10" }, { "input": "How many copies of LBX are found in teleosts?", "output": "In teleosts, that have undergone an additional genome duplication, 8 Lbx paralogons (three of which retain Lbx genes) were found." }, { "input": "How many copies of LBX are found in teleosts?", "output": "URL_0 > In teleosts, that have undergone an additional genome duplication, 8 LBx paralogons (three of which retain Lbx genes) were found." }, { "input": "Which organizations approved Tagsedi in 2018?", "output": "In 2018 Tagsedi was approved by the United States Food and Drug Agency, Health Canada, and European Commission." }, { "input": "What is the use of the CAHP score?", "output": "CAHP (cardiac arrest hospital prognosis) score is used to evaluate prognosis after cardiac arrest." }, { "input": "What is the drug Aduhelm approved for?", "output": "he Food and Drug Administration (FDA) granted approval for Aduhelm (aducanumab) for the treatment of Alzheimer's disease under its accelerated approval program" }, { "input": "What are the 4 histological types of lung cancer?", "output": "Lung cancer is broadly subclassified on the basis of histological features into squamous cell carcinoma, adenocarcinoma, large cell carcinoma and small cell carcinoma." }, { "input": "What are the 4 histological types of lung cancer?", "output": "There are 4 histological classes of lung cancer, small cell carcinoma and 3 non small cell lung cancer (NSCLC) types, adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma." }, { "input": "What is F105-P?", "output": "F105-P is a protamine-antibody fusion protein designed to deliver siRNA to HIV-infected or envelope-transfected cells. In specific, it was designed with the protamine coding sequence linked to the C terminus of the heavy chain Fab fragment of an HIV-1 envelope antibody." }, { "input": "Should edasalonexent be used for Duchenne muscular dystrophy patients?", "output": "No. In phase 3 clinical trial edasalonexent did not achieve statistical significance for improvement in primary and secondary functional endpoints for assessment of Duchenne muscular dystrophy. However, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age." }, { "input": "What disease is presenilin involved in?", "output": "Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD)." }, { "input": "In what part of the body is the masseter muscle located?", "output": "In human anatomy, the masseter is one of the muscles of mastication and is located in the jaw." }, { "input": "Which endothelial cell migration pathways were modulated at the gene expression level by rHDL-apoE3?", "output": "The most pronounced effect was observed for EC migration, with 42/198 genes being involved in the following EC migration-related pathways: 1) MEK/ERK, 2) PI3K/AKT/eNOS-MMP2/9, 3) RHO-GTPases, and 4) integrin." }, { "input": "Is tivantinib effective for MET-high hepatocellular carcinoma?", "output": "No. In phase 3 clinical trials Tivantinib did not improve overall survival compared with placebo in patients with MET-high hepatocellular carcinoma despite promising phase 2 trial results." }, { "input": "What is the function of the protein SLC26A5?", "output": "SLC26A5 transporter prestin is fundamental for the higher hearing sensitivity and frequency selectivity of mammals. Prestin is a voltage-dependent transporter found in the cochlear outer hair cells responsible for their electromotility." }, { "input": "Is EuroQol 5-Dimension Health Assessment (EQ-5D) [a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease] a 5 question assessment?", "output": "The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease." }, { "input": "Is EuroQol 5-Dimension Health Assessment (EQ-5D) [a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease] a 5 question assessment?", "output": "The EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease. It is a 6 question assessment." }, { "input": "What are piRNAs?", "output": "PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi-piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs)." }, { "input": "Bimekizumab is used for treatment of which disease?", "output": "Bimekizumab is used for psoriasis." }, { "input": "What is the white mutation in Drosophila affecting?", "output": "\u0392eyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance." }, { "input": "Austrian syndrome is a rare entity characterized by Osler's triad. Please list the 3 components of Osler's triad.", "output": "Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae" }, { "input": "Austrian syndrome is a rare entity characterized by Osler's triad. Please list the 3 components of Osler's triad.", "output": "Austrian syndrome, which is also known as Osler's triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae." }, { "input": "Austrian syndrome is a rare entity characterized by Osler's triad. Please list the 3 components of Osler's triad.", "output": "Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by Streptococcus pneumoniae" }, { "input": "What is the rate of epimutations in C. elegans?", "output": "In C. elegans epimutations arise spontaneously at a rate approximately 25 times greater than DNA sequence changes." }, { "input": "Is sacituzumab govitecan effective for breast cancer?", "output": "Yes. Sacituzumab Govitecan is a new and available treatment for metastatic triple-negative breast cancer." }, { "input": "What is Upadacitinib?", "output": "Upadacitinib is an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA) and recently approved by the European Medicines Agency for the treatment of psoriatic arthritis (PsA)." }, { "input": "Please list the difference between Pyoderma gangrenosum versus chronic venous ulceration?", "output": "Even when other body sites are affected, pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and feet. (2) Pyoderma gangrenosum can be associated with systemic diseases, especially inflammatory bowel disease. (4) Crater-like holes or cribriform scarring is commonly seen in pyoderma gangrenosum but not in chronic venous ulcers." }, { "input": "Please list the difference between Pyoderma gangrenosum versus chronic venous ulceration?", "output": "Diagnosis of Pyoderma gangrenosum(PG) especially when trying to differentiate it from chronic venous ulceration(CVU) requires a number of clinical observations. 1. Pyoderma gangrenosum usually affects the upper and lower legs and feet or peristomal sites compared with chronic venous ulcers that are limited to the lower legs and feet. (2) Pyoderma gangrenosum can be associated with systemic diseases, especially inflammatory bowel disease. (3) Pustules and purulent discharge are features of pyoderma gangrenosum but not of chronic venous ulcers. (4) Crater-like holes or cribriform scarring is commonly seen in pyoderma gangrenosum but not in chronic venous ulcers. (5) Pathergy is a specific but not sensitive finding of pyoderma gangrenosum" }, { "input": "What is Mobilome-seq?", "output": "Mobilome-seq is a method for selectively amplifying and sequencing eccDNAs. It relies on linear digestion of genomic DNA followed by rolling circle amplification of circular DNA. Both active DNA transposons and retrotransposons can be identified using this technique." }, { "input": "Which variables are included in the ALT-70 Score for cellulitis?", "output": "ALT-70 cellulitis score includes: Asymmetry (3 points), Leukocytosis (1 point), Tachycardia (1 point), and age \u226570 (2 points)." }, { "input": "List biomarkers for sepsis.", "output": "HCK, PRKCD, SIRPA, DOK3, ITGAM, LTB4R, MAPK14, MALT1, NLRC3, LCK\nC-Reactive Protein (CRP), Procalcitonin (PCT) and Interleukin 6 (IL-6)\nsTM" }, { "input": "Is Acute Necrotizing Encephalopathy (ANE) which typically affects young, healthy children usually triggered by exposure to air pollution?", "output": "Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection" }, { "input": "Is Acute Necrotizing Encephalopathy (ANE) which typically affects young, healthy children usually triggered by exposure to air pollution?", "output": "Acute Necrotizing Encephalopathy (ANE) usually occurs in children under 4 years old after a viral infection" }, { "input": "Is Acute Necrotizing Encephalopathy (ANE) which typically affects young, healthy children usually triggered by exposure to air pollution?", "output": "Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection" }, { "input": "What is Waylivra?", "output": "Volanesorsen (Waylivra\u00ae), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL)." }, { "input": "Which disease can be prevented with PfSPZ Vaccine?", "output": "PfSPZ Vaccine is used for prevention of malaria." }, { "input": "Is Phospholemman a membrane protein?", "output": "Yes, FXYD1 (encoding phospholemman) is a transmembrane protein." }, { "input": "What is MACE in the context of cardiotoxicity?", "output": "MACE is an acronym for Major Adverse Cardiovascular Events." }, { "input": "What is MACE in the context of cardiotoxicity?", "output": "major adverse cardiac events (MACE)" }, { "input": "Which clinical trials led to the first approval of Volanesorsen by the EU?", "output": "The approval of Volanesorsen by the EU was based on the positive results from the multinational, phase III APPROACH and COMPASS studies." }, { "input": "Can Isradipine slow progression of Early Parkinson Disease?", "output": "No. In a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial Isradipine did not slow progression of Early Parkinson Disease." }, { "input": "Is neurofilament light marker for disease?", "output": "Yes,\nSerum neurofilament light chain (sNfL) is a marker of neuroaxonal injury leading to numerous diseases such as frontotemporal dementia (FTD) and Multiple sclerosis (MS)." }, { "input": "Is resistance training usually associated with increasing muscle hypertrophy?", "output": "Traditional resistance exercises have been widely used to promote muscle strength and hypertrophy." }, { "input": "Is resistance training usually associated with increasing muscle hypertrophy?", "output": "Is resistance training usually associated with increasing muscle hypertrophy? Yes." }, { "input": "Is resistance training usually associated with increasing muscle hypertrophy?", "output": "While traditional resistance exercises have been widely used to promote muscle strength and hypertrophy in the elderly" }, { "input": "Which company developed Waylivra?", "output": "Waylivra is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics." }, { "input": "Is nerinetide effective for ischaemic stroke?", "output": "No. Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo." }, { "input": "What is known about FANK1?", "output": "Fank1 encodes a protein containing a fibronectin type III domain in the amino terminus and five ankyrin repeats in its carboxyl terminus. FANK1 displays a high degree of sequence conservation in 11 vertebrate species during evolution. Bioinformatic and experimental analyses revealed that Fank1 was exclusively expressed in the testis in both mice and humans.\nConsistent with its nuclear localization, a gene ontology analysis suggests that FANK1 has a DNA binding activity and thus may function as a transcription factor." }, { "input": "Please list the drugs associated with Drug-Induced Hypophosphatemia.", "output": "Drug induced hypophosphatemia can occur with iron therapy as well a treatment with ferric carboxymaltose, elotuzumab, cemiplimab, Temsirolimus, capecitabine, panobinostat, bendamustine, ofatumumab, carboplatin and etoposide (BOCE)" }, { "input": "Is Algenpantucel-L effective for pancreatic cancer?", "output": "No. In phase 3 clinical trial Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable pancreatic cancer receiving SOC neoadjuvant chemotherapy and chemoradiation." }, { "input": "Is Mical an oxidoreductase?", "output": "Yes,\nMICAL is an oxidoreductase" }, { "input": "What is the most frequent evolution (next stage) when Aortic intramural hematoma (IMH) is not treated?", "output": "Aortic intramural hematoma (IMH) evolves very dynamically in the short-term to regression, dissection, or aortic rupture" }, { "input": "What is the most frequent evolution (next stage) when Aortic intramural hematoma (IMH) is not treated?", "output": "Intramural hematoma IMH may progress to classic dissection, frank rupture, or aneurysmal dilation." }, { "input": "Which drugs are included in the Qtern pill?", "output": "Qtern pill includes saxagliptin and dapagliflozin. It is indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus." }, { "input": "List SLE-related autoantibodies.", "output": "Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies).\nDiagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected." }, { "input": "What is nephropathic cystinosis?", "output": "Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by abnormal accumulation of intracellular cystine in various tissues including the brain, kidneys, bones, and eyes." }, { "input": "What is nephropathic cystinosis?", "output": "Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein." }, { "input": "What is nephropathic cystinosis?", "output": "Cystinosis is an autosomal recessive lysosomal storage disorder. It is caused by mutations in the CTNS gene, which encodes the cystinosin protein. In cases of cystinoin deficiency, free cystine accumulates in lyssomes and forms toxic crystals." }, { "input": "Which drugs are included in the Contrave pill?", "output": "Contrave\u00ae is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX)." }, { "input": "When is lorlatinib used?", "output": "Lorlatinib is a third-generation ALK inhibitor that can overcome the largest number of acquired ALK resistance mutations, including the solvent-front mutation G1202R." }, { "input": "Ladybird homeobox (Lbx) transcription factors regulate the development of what body systems/organs?", "output": "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals" }, { "input": "Ladybird homeobox (Lbx) transcription factors regulate the development of what body systems/organs?", "output": "Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals." }, { "input": "Should istiratumab be used for Pancreatic Cancer?", "output": "No. In a clinical trial Istiratumab failed to improve the efficacy of standard of care chemotherapy in metastatic pancreatic cancer patients." }, { "input": "When is the protein OAS1 activated?", "output": "OAS1 is a IFN-stimulated gene. Antiviral response." }, { "input": "Does Amblyopia affect the eye?", "output": "Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to process inputs from one eye and over time favors the other eye. It results in decreased vision in an eye that otherwise typically appears normal" }, { "input": "Which drugs are included in the Lonsurf combination pill?", "output": "Lonsurf is an oral fixed dose combination of trifluridine and tipiracil that is used for cancer treatment." }, { "input": "What is the correlation of Cathepsin L and COVID-19?", "output": "Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection" }, { "input": "Is autism thought to be related to the Arginine Vasopressin Peptide (AVP)?", "output": "Differences in vasopressin levels in individuals suffering from the autism spectrum disorders have been demonstrated." }, { "input": "Is autism thought to be related to the Arginine Vasopressin Peptide (AVP)?", "output": "Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD." }, { "input": "Are there any tools that could predict protein structure considering amino acid sequence?", "output": "Yes. Tools such as Jpred, Jnet, Porter 4.0 and PSIPRED Workbench have been developed that predict protein structure based solely on its amino acid sequence, whereas the recently updated Jnet algorithm provides a three-state (alpha-helix, beta-strand and coil) prediction of secondary structure at an accuracy of 81.5%." }, { "input": "Are there any tools that could predict protein structure considering amino acid sequence?", "output": "AlphaFold, PredictProtein, PSIPRED, Jpred and Porter do all predict protein stucture from amino acid sequence." }, { "input": "Which proteins does p110\u03b1 interact with?", "output": "p110\u03b1 interacts with p85\u03b1 and RAS proteins." }, { "input": "Which proteins does p110\u03b1 interact with?", "output": "RAS interaction with PI3K p110\u03b1" }, { "input": "Which is the protein-membrane interface of the Cholesterol-regulated Start protein 4 protein (STARD4)?", "output": "L124 is the protein-membrane interface of the Cholesterol-regulated Start protein 4 protein (STARD4)." }, { "input": "Which is the protein-membrane interface of the Cholesterol-regulated Start protein 4 protein (STARD4)?", "output": "Our results show that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (\u03a91) loop, which covers the sterol binding pocket, attenuates sterol transfer activity." }, { "input": "What causes the \"worst headache\" of a patient's life?", "output": "This is a classic description of a subarachnoid hemorrhage (SAH). The gold standard for the diagnostic evaluation of a SAH remains non-contrast head computed tomography (CT) followed by lumbar puncture if the CT is negative." }, { "input": "What causes the \"worst headache\" of a patient's life?", "output": "Headache is the most common presenting symptom of subarachnoid hemorrhage (SAH), ranging from mild headache to the \"worst headache of my life\"" }, { "input": "What causes the \"worst headache\" of a patient's life?", "output": "Aneurysmal subarachnoid hemorrhage (SAH) is associated with a mortality of more than 30%. Acute, severe headache, typically described as the worst headache of the patient's life, and meningismus are the characteristic manifestations of SAH." }, { "input": "Which are the types of cancer that c-Myc is associated with?", "output": "The types of cancer that c-Myc is associates with are breast cancer, non-small-cell lung cancer and pancreatic ductal adenocarcinoma." }, { "input": "Which are the types of cancer that c-Myc is associated with?", "output": "c-Myc is known to be deregulated in a variety of tumors, including breast cancer, prostate cancer, non-small cell lung cancer (NSCLC), papillary thyroid cancer (PDA), ovarian cancer, cervical intraepithelial neoplasia, and gastric cancer." }, { "input": "Which pathways are involved in cellular senescence?", "output": "Cellular senescence requires signal transduction, and the two most important signaling pathways are the P16Ink4a/Rb (retinoblastoma protein) pathway and the P19Arf/P53/P21Cip1 pathway, which interact but independently regulate the process of the cells cycle." }, { "input": "Which disease phenotype has the worst prognosis in Duchenne Muscular Dystrophy?", "output": "A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented." }, { "input": "Which disease phenotype has the worst prognosis in Duchenne Muscular Dystrophy?", "output": " A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented." }, { "input": "Which disease phenotype has the worst prognosis in Duchenne Muscular Dystrophy?", "output": "Dp140 isoform is related to increased risk of cognitive impairment and thus worse prognosis." }, { "input": "Which disease phenotype has the worst prognosis in Duchenne Muscular Dystrophy?", "output": "A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found." }, { "input": "What links developmental pathways to ALS?", "output": "A direct link between developmental pathways and ALS is not described. However, cytoskeletal proteins such as KIF5A are implicated in ALS, and the cytoskeletal protein N-cadherin is involved in plasticity of the cerebral cortex. Development depends on connections of the sympathetic nervous system, involving mechanisms such as axon growth, neuron survival, and dendrite growth. BACE1, which is involved in Alzheimer's disease, is also implicated in axonal regeneration." }, { "input": "Is thalidomide used as an immunomodulatory drug nowadays?", "output": "Yes." }, { "input": "Is thalidomide used as an immunomodulatory drug nowadays?", "output": "Nowadays, thalidomide is being used as an immunomodulatory drug." }, { "input": "Does p85\u03b1 homodimerize?", "output": "p110\u03b1-free p85\u03b1 homodimerizes" }, { "input": "Does p85\u03b1 homodimerize?", "output": "Yew, p85\u03b1 forms homodimers" }, { "input": "Which are the components that evaluate druglikeness?", "output": "Lipinski's rule states that, in general, an orally active drug has no more than one violation of the following criteria:\nNo more than 5 hydrogen bond donors (the total number of nitrogen\u2013hydrogen and oxygen\u2013hydrogen bonds)\nNo more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)\nA molecular mass less than 500 daltons\nAn octanol-water partition coefficient (log P) that does not exceed 5" }, { "input": "Which are the components that evaluate druglikeness?", "output": "In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15)" }, { "input": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "output": "No. Patients receiving angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should continue treatment with these agents if there is no other reason for discontinuation. Despite speculation that patients with COVID-19 who are receiving these agents may be at increased risk for adverse outcomes, accumulating evidence does not support an association of ACE inhibitors and ARBs with more severe disease. In addition, stopping these agents in some patients can exacerbate comorbid cardiovascular or kidney disease and increase mortality." }, { "input": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "output": "ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death." }, { "input": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "output": "No. ACEIs and ARBs have not been shown to increase the likelihood of severe COVID-19 hospitalization." }, { "input": "Which small molecules inhibit the c-Myc/Max dimerization?", "output": "Mycros are the first inhibitors of c-Myc/Max dimerization, which have been demonstrated to inhibit DNA binding of c-Myc with preference over other dimeric transcription factors in vitroMost Myc inhibitors prevent the association between Myc and its obligate heterodimerization partner Max via their respective bHLH-ZIP domainsPreviously we showed that two c-Myc-Max inhibitors, 10058-F4 and 10074-G5, bound to distinct ID regions of the monomeric c-Myc bHLHZip domainWe tested the efficacy of Mycro3, a small-molecule inhibitor of Myc-Max dimerizationIn a fluorescence polarization screen for the MYC-MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kr\u00f6hnke pyridine libraryWe have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpressionWe developed a series of small-molecule MYC inhibitors that engage MYC inside cells, disrupt MYC/MAX dimers, and impair MYC-driven gene expression.Inhibition of MYC/MAX dimerization by a small-molecule antagonist (IIA6B17) has been shown to interfere with MYC-induced transformation of chick embryo fibroblasts, suggesting that the functional inhibitors of the MYC family of oncoproteins have potential as therapeutic agents." }, { "input": "Which small molecules inhibit the c-Myc/Max dimerization?", "output": "The small molecules that inhibit c-Myc/Max dimerization are Mycro1, Mycro2, Mycro3, IIA6B17, celastrol, 10058-F4, 10074-G5, JY-3-094, KJ-Pyr-9, MYCi361 and MYCi975" }, { "input": "Which models are used for predicting disease progression in Duchenne Muscular Dystrophy?", "output": "Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach." }, { "input": "Which models are used for predicting disease progression in Duchenne Muscular Dystrophy?", "output": "Models used to predict disease progression of Duchenne Muscular Dyystrophy are: cumulative distribution function using a non-linear mixed effects approach, ..." }, { "input": "Which models are used for predicting disease progression in Duchenne Muscular Dystrophy?", "output": "Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach. Longitudinal progression of Duchenne Muscular Dystrophy was also modeled using a weighted average probability method. Duchenne muscular dystrophy disease progression was modeled using the following models: linear progression function, logarithmological, multisubunit, linear multiple-parametry, and linear multiple sum" }, { "input": "Which models are used for predicting disease progression in Duchenne Muscular Dystrophy?", "output": "Modeling disease trajectory in Duchenne muscular dystrophy Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach." }, { "input": "What links muscle cellular pathways to ALS?", "output": "Changes to muscle cellular pathways may occur downstream of motor neuron pathology in ALS. Genetic changes to pathways that are important to muscle function may also be causal of the disease. In addition, changes to the muscle may be responsible for motor neuron death. Pathological changes occur in muscle before disease onset and independent from MN degeneration, and the muscle may release toxic elements, such as via extracellular vesicle secretion. Muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood, are all deregulated in ALS. There may also be a link between motor neuron death, the immune system, and muscle cells, as muscle-resident glial cells have been shown to activate upon nerve injury. Muscle-restricted expression of a localized insulin-like growth factor Igf-1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1(G93A) transgenic mice." }, { "input": "For what known mutations is KRAS gene considered to be oncogenic?", "output": "G12C, G12V, G12D and G12A are all observed mutations of the KRAS oncogene." }, { "input": "Which proteins does the p85\u03b1 interact with?", "output": "p85\u03b1 interacts with itself, with p110\u03b1 and with p110d" }, { "input": "Computational tools for predicting allosteric pathways in proteins", "output": "CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities." }, { "input": "Computational tools for predicting allosteric pathways in proteins", "output": "We find that CARDS captures allosteric communication between the two cAMP-Binding Domains (CBDs)Overall, it is demonstrated that the communication pathways could be multiple and intrinsically disposed, and the MC path generation approach provides an effective tool for the prediction of key residues that mediate the allosteric communication in an ensemble of pathways and functionally plausible residuesWe utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM)Here, we introduce the Correlation of All Rotameric and Dynamical States (CARDS) framework for quantifying correlations between both the structure and disorder of different regions of a proteinWe present a novel method, \"MutInf\", to identify statistically significant correlated motions from equilibrium molecular dynamics simulationsCorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities.Here, a Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths." }, { "input": "Computational tools for predicting allosteric pathways in proteins", "output": "Here, a Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths. Overall, it is demonstrated that the communication pathways could be multiple and intrinsically disposed, and the MC path generation approach provides an effective tool for the prediction of key residues that mediate the allosteric communication in an ensemble of pathways and functionally plausible residues We utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM)" }, { "input": "Computational tools for predicting allosteric pathways in proteins", "output": "A Monte Carlo (MC) path generation approach is proposed and implemented to define likely allosteric pathways through generating an ensemble of maximum probability paths. A novel method, \"MutInf\", to identify statistically significant correlated motions from equilibrium molecular dynamics simulations. CorrSite identifies potential alloster-binding sites based on motion correlation analyses between cavities. The Correlation of All Rotameric and Dynamical States (CARDS) framework for quantifying correlations between both the structure and disorder of different regions of a protein" }, { "input": "Computational tools for predicting allosteric pathways in proteins", "output": "Computational tools for predicting allosteric pathways in proteins include MCPath, MutInf, pySCA, CorrSite, and CARDS." }, { "input": "What are the classic signs of a basilar skull fracture?", "output": "Basilar skull fractures are fractures of the lower part of the skull. The four classic signs are:\n1. Periorbital ecchymosis (\u201craccoon eyes\u201d).\n2. Postauricular ecchymosis (Battle sign).\n3. CSF otorrhea or rhinorrhea (leakage of CSF, which is clear in appearance, from the ears or nose).\n4. Hemotympanum (blood behind the eardrum)." }, { "input": "What are the classic signs of a basilar skull fracture?", "output": "Possible clinical signs are the presence of cerebrospinal fluid rhinorrhea or otorrhea, periorbital ecchymosis (raccoon eyes), retroauricular ecchymosis (battle sign) and cranial nerve injuries" }, { "input": "Which biomarkers are currently used for Duchenne Muscular Dystrophy?", "output": "MRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD. malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy" }, { "input": "Which biomarkers are currently used for Duchenne Muscular Dystrophy?", "output": "MRI, fat fraction MRI, MRI mean T2, malate dehydrogenase 2 are some biomarkers that are used for DMD." }, { "input": "Which biomarkers are currently used for Duchenne Muscular Dystrophy?", "output": "malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophyMRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD." }, { "input": "Which biomarkers are currently used for Duchenne Muscular Dystrophy?", "output": "MRI measurements can be used as biomarkers of disease severity in ambulant patients with DMD." }, { "input": "What links lipid metabolism pathways to ALS?", "output": "Dysregulation of lipid metabolism is observed early in the spinal cord of the SOD1 ALS mouse model, and abnormal levels of cholesterol and other lipids are observed in the blood and CNS of ALS patients. In addition, higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing ALS." }, { "input": "What is the multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19?", "output": "Multisystem inflammatory syndrome in children (MIS-C) is a well described and documented condition that is associated with the active or recent COVID-19 infection. A similar presentation in adults is termed as Multisystem inflammatory syndrome in Adults (MIS-A). Multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has created a diagnostic challenge due to overlap with Kawasaki disease (KD) and KD shock syndrome. The majority of patients with MIS-C present with the involvement of at least four organ systems, and all have evidence of a marked inflammatory state. Most patients show an increase in the level of at least four inflammatory markers (C-reactive protein, neutrophil count, ferritin, procalcitonin, fibrinogen, interleukin-6, and triglycerides). Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most patients, even those with severe cardiovascular involvement, recover without sequelae. Since coronary aneurysms have been reported, echocardiographic follow-up is needed." }, { "input": "What is the multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19?", "output": "Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It shares clinical features with Kawasaki disease (KD) and KD shock syndrome. Clinical features include persistent fever, severe illness with involvement of multiple organ systems, and elevated inflammatory markers. Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most children with MIS-C, even those with severe cardiovascular involvement, recover without sequelae. A very similar syndrome has also been reported in adults in association with COVID-19 infection or exposure and is termed multisystem inflammatory syndrome in adults (MIS-A)." }, { "input": "What is the multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19?", "output": "Multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has created a diagnostic challenge due to overlap with Kawasaki disease (KD) and KD shock syndrome. The majority of patients with MIS-C present with the involvement of at least four organ systems, and all have evidence of a marked inflammatory state. Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most patients, even those with severe cardiovascular involvement, recover without sequela" }, { "input": "What datasets are available related to Duchenne Muscular Dystrophy?", "output": "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total)." }, { "input": "What datasets are available related to Duchenne Muscular Dystrophy?", "output": "MD STARnet, ImagingDMD and PRO-DMD-01 are some of the available DMD datasets." }, { "input": "What datasets are available related to Duchenne Muscular Dystrophy?", "output": "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total)." }, { "input": "What datasets are available related to Duchenne Muscular Dystrophy?", "output": "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)" }, { "input": "What datasets are available related to Duchenne Muscular Dystrophy?", "output": "Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study." }, { "input": "What datasets are available related to Duchenne Muscular Dystrophy?", "output": "Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total)." }, { "input": "What links immune response pathways to ALS?", "output": "Microglia, which are the primary immune cells of the central nervous system, are strongly implicated in ALS, their activation being correlated with various clinical features, and inflammatory microglial responses being correlated withe disease progression. The immune response may be implicated in other ways with ALS molecular pathology. such as through inflammatory regulation and circulating interleukins. It is possible the T cell receptor signalling and activation is involved. It is also possible that the innate / non-specific immune system is involved - i.e. immune protection against foreign substances, viruses, and bacteria." }, { "input": "Which vitamin deficiencies may present with neurologic signs or symptoms?", "output": "Many vitamin deficiencies have been described as a cause of neurologic signs and symptoms. For instance, vitamin B12 deficiency can cause several types of neurological manifestations, such as subacute combined degeneration of the spinal cord, ataxia, peripheral polyneuropathy, optic nerve neuropathy, and cognitive disorders. In addition, vitamin B1 (Thiamine) and B6 (Pyridoxine) deficiency can both cause peripheral neuropathy. Specifically, vitamin B1 deficiency can also cause confusion, ophthalmoplegia, nystagmus, and ataxia in the context of beriberi and Wernicke's encephalopathy. Finally, vitamin A deficiency has been described to cause retinal change-related visual defects and subsequent vision loss." }, { "input": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "output": "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy." }, { "input": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "output": "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy. The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations." }, { "input": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "output": "URL_0 > Deep learning of Ultrasound imaging for evaluation of Ambulatory Function of Individuals with Duchenne Muscular Dystrophy." }, { "input": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "output": "The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations." }, { "input": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "output": "Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy. The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations. Deep learning models are used to predict muscle function in DMD patients." }, { "input": "Which are the uses of deep learning models in Duchenne Muscular Dystrophy?", "output": "Deep learning models enable the evaluation of DMD patients using ultrasound images." }, { "input": "What is \"long-COVID\"?", "output": "\"Long-COVID\" is a complex condition where the affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, and the symptoms are not explained by an alternative diagnosis.\n\nPersistent physical symptoms following acute COVID-19 are common and typically include fatigue, dyspnea, chest pain, and cough. Headache, joint pain, myalgias, and loss of smell have also been reported. Common psychological and cognitive symptoms include poor concentration, cognitive impairment/confusion, insomnia, and overall reduced quality of life." }, { "input": "What is \"long-COVID\"?", "output": "\"Long COVID\" is the condition whereby affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, whether tested or not. Emerging aspects of the Covid-19 clinical presentation are its long-term effects, which are characteristic of the so-called \"long COVID\". The main symptoms associated with \"long COVID\" were headache, fatigue, muscle aches/myalgia, articular pains, cognitive impairment, loss of concentration, and loss of smell. Additionally, the subjects showed significant levels of insomnia (p < 0.05) and an overall reduced quality of life (p < 0.05). Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings." }, { "input": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "output": "North Star Ambulatory Assessment is practical and reliable. allow assessment of high-functioning boys with Duchenne muscular dystrophy." }, { "input": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "output": "Yes, functional tests are a good biomarker for Duchenne Muscular Dystrophy. \nNorth Star Ambulatory Assessment is practical and reliable. allow assessment of high-functioning boys with Duchenna muscular dystrophy \nFunctional tests are used for assessment of boys with muscular atrophy." }, { "input": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "output": "Functional tests such as North Star Ambulatory Assessment (NSAA) are good biomarkers for Duchenne Muscular Dystrophy." }, { "input": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "output": "North Star Ambulatory Assessment is practical and reliable." }, { "input": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "output": "allow assessment of high-functioning boys with Duchenne muscular dystrophy.North Star Ambulatory Assessment is practical and reliable." }, { "input": "What is the most sensitive test for the diagnosis of multiple sclerosis?", "output": "MRI is the most sensitive tool for the diagnosis of multiple sclerosis (MS). It can detect asymptomatic lesions in the white matter and is the most predictive test for diagnosing clinically definite multiple sclerosis (CDMS). It is also a reliable measure of the current disease activity. The presence of oligoclonal bands in the cerebrospinal fluid (CSF) provides supportive evidence for the diagnosis of MS." }, { "input": "What is the most sensitive test for the diagnosis of multiple sclerosis?", "output": "These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS." }, { "input": "What is the most sensitive test for the diagnosis of multiple sclerosis?", "output": "MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS. MRI also is a reliable measure of the extent of the MS process, serial MRI scans detect evidence of disease activity in MS not always disclosed by clinical evaluation. Results indicate that the presence of oligoclonal bands provides sensitive supporting evidence" }, { "input": "Define pseudotumor cerebri. How is it treated?", "output": "Benign intracranial hypertension (BIH) is characterized by an elevation of the intracranial pressure not associated with an intracranial process or hydrocephaly, and with normal cerebrospinal fluid (CSF) contents. The elevation of the intracranial pressure is isolated; therefore, diseases such as cerebral venous thrombosis or dural fistulas should not be considered as etiologies of BIH. The exact definition of BIH remains debated, and other terms such as \"pseudotumor cerebri\" or \"idiopathic intracranial hypertension\" are often used in the literature. The management of patients with BIH depends mainly on the presence and severity of ocular symptoms and signs on which the prognostic of the disease is based. Repeated lumbar punctures associated with acetazolamide and weight loss are usually efficient enough. However a surgical treatment (optic nerve sheath fenestration or lumboperitoneal shunt) is required when appropriate medical management does not prevent progressive alteration of vision (visual loss or visual field defect), or when the patients complains of severe, refractory headaches. Careful follow-up with repeated formal visual field testing may help preventing a devastating visual loss in these patients." }, { "input": "Define pseudotumor cerebri. How is it treated?", "output": "Pseudotumor cerebri is a condition characterized by an elevation of the intracranial pressure not associated with an intracranial process or hydrocephaly, and with normal cerebrospinal fluid (CSF) contents. It most often occurs in obese women of childbearing age. The management of patients with pseudotumor cerebri mainly depends on the presence and severity of ocular symptoms and signs on which the prognostic of the disease is based. Repeated lumbar punctures associated with acetazolamide and weight loss are usually efficient enough. However a surgical treatment (optic nerve sheath fenestration or lumboperitoneal shunt) is required when appropriate medical management does not prevent progressive alteration of vision (visual loss or visual field defect), or when the patients complains of severe, refractory headaches. Careful follow-up with repeated formal visual field testing may help preventing a devastating visual loss in these patients." }, { "input": "What is pseudodementia?", "output": "Depression can cause some clinical symptoms and signs of dementia, classically in older adults. This type of \"dementia\" is called pseudodementia and is typically reversible with treatment." }, { "input": "What is pseudodementia?", "output": "Pseudodementia is defined as an intellectual impairment in patients with a primary psychiatric disorder, in which the features of intellectual abnormality resemble, at least in part, those of a neuropathologically induced cognitive deficit. This neuropsychological impairment is reversible, and there is no apparent primary neuropathological process that leads to the genesis of this disturbance." }, { "input": "Should acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) be used when providing supportive care for COVID-19?", "output": "Nonsteroidal anti-inflammatory drugs (NSAIDs) have been theorized to cause harm in patients with COVID-19, but clinical data are limited. Given the uncertainty, acetaminophen is the preferred antipyretic agent for most patients rather than NSAIDs. If NSAIDs are needed, the lowest effective dose is recommended." }, { "input": "Should acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) be used when providing supportive care for COVID-19?", "output": "Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID-19 and case-reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID-19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID-19 patients until there are enough evidence." }, { "input": "Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, particularly influenza?", "output": "No, the clinical features of COVID-19 overlap substantially with influenza and other respiratory viral illnesses. There is no way to distinguish among them without testing." }, { "input": "Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, particularly influenza?", "output": "Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations)" }, { "input": "Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, particularly influenza?", "output": "Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations). At present, clinical workup of COVID-19 remains a hard task to accomplish." }, { "input": "What is the incubation period for COVID-19?", "output": "For COVID-19, the mean incubation period was 6.0\u00a0days globally but near 7.0\u00a0days in the mainland of China, which will help identify the time of infection and make disease control decisions. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain." }, { "input": "What is the incubation period for COVID-19?", "output": "The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately five to seven days after exposure. The incubation period also varies by viral variant. For example, the incubation period for the Delta variant (B.1.617.2) appears to be slightly shorter, with symptoms first appearing around four days after exposure." }, { "input": "What is Guillain-Barre syndrome (GBS)?", "output": "Guillain-Barr\u00e9 syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF). Recently, the heterogeneity of GBS has been noticed with definition of several GBS variants. The diagnosis of GBS includes clinical, electrophysiological and laboratory (CSF) criteria." }, { "input": "What is Guillain-Barre syndrome (GBS)?", "output": "Guillain-Barr syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF)." }, { "input": "What is Guillain-Barre syndrome (GBS)?", "output": "Guillain-Barre syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF)." }, { "input": "What is Guillain-Barre syndrome (GBS)?", "output": "Guillain-Barr\u00e9 syndrome (GBS) is an acute immune mediated neuropathy, polyradiculoneuritis, characterized by rapid onset of symmetric extremity muscle paralysis, areflexia and albuminocytological dissociation in the cerebrospinal fluid (CSF)." }, { "input": "Is lumbar puncture the first test that should be performed on a patient with increased intracranial pressure?", "output": "No. A lumbar puncture is contraindicated in any patient with signs of increased intracranial pressure because it may precipitate cerebral herniation and death. For this reason, a computed tomography (CT) or magnetic resonance imaging (MRI) scan is done first. When the findings of the scan are normal, a lumbar puncture can be performed, if needed." }, { "input": "Is lumbar puncture the first test that should be performed on a patient with increased intracranial pressure?", "output": "Lumbar puncture (LP) is usually contra-indicated in situations where the ICP is suspected to be high." }, { "input": "What laboratory abnormalities are commonly seen in patients with COVID-19?", "output": "Common laboratory abnormalities among patients with COVID-19 include:\n\n1. Elevated inflammatory markers (e.g., ferritin, C-reactive protein, and erythrocyte sedimentation rate).\n2. Elevated aminotransaminase levels (i.e., AST, ALT).\n3. Elevated lactate dehydrogenase (LDH) levels.\n4. Lymphopenia, leucocytosis.\n\nAbnormalities in coagulation testing (e.g., increased D-Dimers, decreased platelets), elevated procalcitonin levels, and elevated troponin levels have also been reported. The degree of these abnormalities tends to correlate with disease severity." }, { "input": "Do only changes in coding regions of MEF2C cause developmental disorders?", "output": "No. Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms." }, { "input": "Which factor is inhibited by Milvexian?", "output": "Milvexian is a small molecule, active-site inhibitor of factor XIa (FXIa) being developed to prevent and treat thrombotic events." }, { "input": "What is Granzyme B?", "output": "Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular immune response and can induce apoptosis." }, { "input": "Is CircRNA produced by back splicing of exon, intron or both, forming exon or intron circRNA?", "output": "Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA." }, { "input": "How does condensin affect the function of topoisomeraseII?", "output": "Condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation." }, { "input": "How does condensin affect the function of topoisomeraseII?", "output": "aids sister chromatid decatenation by topoisomerase II" }, { "input": "How does condensin affect the function of topoisomeraseII?", "output": "Condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation which are created by topoisomerase II. Condensin-dependent localisation of topoisomerase II to an axial chromosomal structure is required for sister chromatid resolution during mitosis." }, { "input": "How does condensin affect the function of topoisomeraseII?", "output": "aids sister chromatid decatenation" }, { "input": "How does condensin affect the function of topoisomeraseII?", "output": "Condensin interferes with the function of Topo II. It prevents catenanes from persisting between sister chromatids during mitosis." }, { "input": "How does condensin affect the function of topoisomeraseII?", "output": "Condensin aids sister chromatid decatenation by topoisomerase II and minimizes topoisomerase II-mediated entanglements of DNA in vivo" }, { "input": "Which signaling pathway does LY294002 inhibit?", "output": "LY294002, can block the PI3K/AKT signaling pathway." }, { "input": "Is METTL1 overexpression associated with better patient survival?", "output": "No. METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival." }, { "input": "List monoclonal antibodies included in the REGEN-COV.", "output": "REGEN-COV is a combination of the monoclonal antibodies casirivimab and imdevimab. It has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019." }, { "input": "Which disease is caused by mutations in the gene PRF1?", "output": "The presence of mutations in PRF1, UNC13D, STX11 and STXBP2 genes in homozygosis or compound heterozygosis results in immune deregulation. Most such cases lead to clinical manifestations of haemophagocytic lymphohistiocytosis (HLH)." }, { "input": "What protein is encoded by the GRN gene?", "output": "Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN), GRN, are one of the major genetic abnormalities involved in frontotemporal lobar degeneration." }, { "input": "What is the difference in the roles of Tcf1 and Tcf3 during development?", "output": "\u03a4here are opposing effects of Tcf3 and Tcf1 in the control of Wnt stimulation of embryonic stem cell self-renewal. In contrast to \u03b2-catenin-dependent functions described for Tcf1 the known embryonic functions for Tcf3 are consistent with \u03b2-catenin-independent repressor activity. Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling." }, { "input": "What is the difference in the roles of Tcf1 and Tcf3 during development?", "output": "Tcf3 antagonizes Wnt signaling, while Tcf1 enhances" }, { "input": "Why mix \u03b3-cyclodextrin with grapefruit juice?", "output": "Grapefruit (Citrus paradisi) juice enhances the oral bioavailability of drugs that are metabolized by intestinal cytochrome P450 3A4 (CYP3A4). Patients are advised to avoid drinking grapefruit juice to prevent this drug-grapefruit juice interaction. The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with \u03b3CD. The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with \u03b3CD. Similar attenuation effects by \u03b3CD were observed in the cases of BG and DHBG. Furthermore, BG and DHBG were suggested to be strongly encapsulated in the cavity of \u03b3CD.The encapsulation of BG and DHBG by \u03b3CD and the resulting attenuation of the inhibition of CYP3A activity by grapefruit juice may be applicable to juice processing for preventing drug-grapefruit juice interactions." }, { "input": "What is disrupted by ALS- and FTD-associated missense mutations in TBK1?", "output": "ALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy." }, { "input": "What is Morel\u2013Lavall\u00e9e lesion?", "output": "Morel-Lavall\u00e9e lesion is a closed degloving soft-tissue injury that results in the accumulation of a hemolymphatic fluid between the skin/superficial fascia and the deep fascia." }, { "input": "What is known about the protein patatin?", "output": "Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 \u03bcg/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects." }, { "input": "What is the mode of action of primaquine?", "output": "Primaquine (PQ) not only eliminates P. falciparum gametocytes but also kills liver dormant forms of P. vivax and P. ovale." }, { "input": "Which databases are devoted to 3D genome interactions?", "output": "3DIV is a 3D-genome Interaction Viewer and database. The 3D Genome Browser is a web-based browser for visualizing 3D genome organization and long-range chromatin interactions. GMOL is an Interactive Tool for 3D Genome Structure Visualization. 3Disease Browser is a Web server for integrating 3D genome and disease-associated chromosome rearrangement data. The 3DGD is a database of genome 3D structure, that currently holds Hi-C data on four species, for easy accessing and visualization of chromatin 3D structure data." }, { "input": "Where does REGN5458 bind to?", "output": "The bispecific antibody REGN5458 binds to B-cell maturation antigen (BCMA) and CD3." }, { "input": "Do mutations in KCNT2 only cause phenotypes with epilepsy?", "output": "No. There is a report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy." }, { "input": "Is there an association between pyostomatitis vegetans and Crohn's disease?", "output": "Yes. Pyostomatitis vegetans (PV) is a rare condition characterized by pustules that affect the oral mucosa. It is a highly specific marker for inflammatory bowel disease and its correct recognition may lead to the diagnosis of ulcerative colitis or Crohn's disease." }, { "input": "Is serotonin transported by platelets?", "output": "Yes,\nplatelets transport serotonin." }, { "input": "Proteins in the karyopherin family (Kaps) are associated with what cellular process?", "output": "Nuclear translocation of large proteins is mediated through specific protein carriers, collectively named karyopherins (importins, exportins and adaptor proteins)" }, { "input": "What percentage of human genes have no introns?", "output": "About 3% of human genes have no introns. URL_0" }, { "input": "What percentage of human genes have no introns?", "output": "Intronless genes (IGs) constitute approximately 3% of the human genome. Intronless genes (IGs) fraction varies between 2.7 and 97.7% in eukaryotic genomes." }, { "input": "What percentage of human genes have no introns?", "output": "3 percent of the human genome" }, { "input": "What percentage of human genes have no introns?", "output": "Intronless genes (IGs) constitute approximately 3% of the human genome." }, { "input": "What percentage of human genes have no introns?", "output": "Intronless genes (IGs) constitute approximately 3% of the human genome. Intronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function." }, { "input": "What percentage of human genes have no introns?", "output": "Intronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function." }, { "input": "What are the currently FDA approved monoclonal antibodies for myeloma?", "output": "The US Food and Drug Administration approved MoAbs, include belantamab mafodotin, daratumumab, elotuzumab, and isatuximab." }, { "input": "What is caused by biallelic variants in PCDHGC4?", "output": "Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies." }, { "input": "Is Sotrovimab effective for COVID-19?", "output": "Yes. Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression." }, { "input": "Is Otolin-1 a matrix protein?", "output": "Yes,\notolin-1 is a otoconia matrix protein." }, { "input": "List the drug targets of Faricimab?", "output": "Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2." }, { "input": "List the drug targets of Faricimab?", "output": "Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2" }, { "input": "What induces downstream of gene (DoG) readthrough transcription?", "output": "Stress-induced transcriptional readthrough generates very long downstream of gene containing transcripts (DoGs), which may explain up to 20% of intergenic transcription. Massive induction of transcriptional readthrough generates downstream of gene-containing transcripts (DoGs) in cells under stress condition. Ca2+ signaling mediates reduced transcription termination in response to certain stress conditions. This reduction allows readthrough transcription, generating a highly inducible and diverse class of downstream of gene containing transcripts (DoGs) that we have recently described." }, { "input": "What induces downstream of gene (DoG) readthrough transcription?", "output": "osmotic stress" }, { "input": "What induces downstream of gene (DoG) readthrough transcription?", "output": "DoGs are induced by osmotic stress at the level of transcription by a mechanism that depends on calcium release from the endoplasmic reticulum mediated by IP3 receptors." }, { "input": "What is the effect of rHDL-apoE3 on endothelial cell migration?", "output": "rHDL-apoE3 has been shown to promote endothelial cell migration." }, { "input": "Is AGO2 related to cytokinesis?", "output": "Yes. AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division." }, { "input": "Hampton\u2019s hump is characteristic to which disease?", "output": "Hampton\u2019s hump is characteristic to pulmonary embolism." }, { "input": "What is the activity of Indoleamine 2,3-dioxygenase 1.", "output": "Indoleamine 2,3-dioxygenase 1 (IDO1), a known immunosuppressive enzyme that catalyzes the rate-limiting step in the oxidation of tryptophan (Trp) to kynurenine (Kyn), has received increasing attention as an attractive immunotherapeutic target for cancer therapy." }, { "input": "What is the purpose of Macropinocytosis?", "output": "Macropinocytosis is an endocytic process, which involves the engulfment of extra-cellular content in vesicles known as macropinosomes." }, { "input": "Which was the first species in which a de novo gene emergence (\"gene birth\") was reported?", "output": "New genes can arise through duplication of a pre-existing gene or de novo from non-coding DNA, providing raw material for evolution of new functions in response to a changing environment. A prime example is the independent evolution of antifreeze glycoprotein genes (afgps) in the Arctic codfishes and Antarctic notothenioids to prevent freezing." }, { "input": "What are chromones?", "output": "The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up." }, { "input": "Which type of cancer has been suggested as a strategy for potential small-molecule inhibition of METTL3?", "output": "Small-molecule inhibition of METTL3 is a strategy against myeloid leukaemia. Targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy." }, { "input": "Which type of cancer has been suggested as a strategy for potential small-molecule inhibition of METTL3?", "output": "Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia." }, { "input": "What is the mechanism of action of Lanifibranor?", "output": "Lanifibranor is peroxisome proliferator-activated receptor (PPAR) agonist." }, { "input": "Is the protein HOXA11 associated with endometrial disease?", "output": "Yes,\nLow HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells" }, { "input": "Summarize the function of DEAH helicase DHX36 and its role in G-quadruplex-dependent processes.", "output": "DEAH-Box helicase 36 (DHX36), a member of the large DExD/H box helicase family, enzymatically unwinds both G4 DNA and G4 RNA. RNA helicases of the DEAH/RHA family form a large and conserved class of enzymes that remodel RNA protein complexes (RNPs) by translocating along the RNA" }, { "input": "What is the function of the YY1 transcriptional regulator?", "output": "The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation. YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. YY1 overexpression and/or activation is associated with unchecked cellular proliferation, resistance to apoptotic stimuli, tumorigenesis and metastatic potential. YY1, in addition to its regulatory roles in normal biologic processes, may possess the potential to act as an initiator of tumorigenesis and may thus serve as both a diagnostic and prognostic tumor marker; furthermore, it may provide an effective target for antitumor chemotherapy and/or immunotherapy." }, { "input": "What is the function of the YY1 transcriptional regulator?", "output": "The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation. YY1 exerts its effects on genes involved in these processes via its ability to initiate, activate, or repress transcription depending upon the context in which it binds. Mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes." }, { "input": "What is the function of the YY1 transcriptional regulator?", "output": "YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. We present evidence that YY1, a ubiquitously expressed DNA-binding protein, regulates the activity of the c-fos promoter primarily through an effect on DNA structure. the principal function of YY1 in this promoter is to bend DNA to regulate contact between other proteins. By using oligonucleotide competition and a specific antibody we demonstrated that the transcription factor YY1 is responsible for the formation of complex BIII. Also in this case, the transient expression of the YY1 cDNA in CHO cells resulted in an increased transcription from the FE65 minimal promoter. The absence of any co-operative effect when CHO cells were co-transfected with both YY1 and Pur alpha cDNA species suggests that two different transcription regulatory mechanisms could have a role in the regulation of the FE65 gene." }, { "input": "What is the function of the YY1 transcriptional regulator?", "output": "YY1 is a transcriptional regulator. It is a protein that binds to the C-fos promoter. The function of this protein is to bend DNA to allow it to contact with other proteins." }, { "input": "Which CYP genes' expression is decreased at the in vivo level following pomegranate juice consumption?", "output": "It was found that pomegranate juice consumption decreased total hepatic CYP content as well as the expression of CYP1A2 and CYP3A." }, { "input": "Class-defining mutations in which genes drive FLT3-ITD-mutant AML?", "output": "Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations frequently synergize with internal tandem duplications in FLT3 (FLT3-ITDs) to drive leukemogenesis." }, { "input": "Class-defining mutations in which genes drive FLT3-ITD-mutant AML?", "output": "Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA." }, { "input": "Class-defining mutations in which genes drive FLT3-ITD-mutant AML?", "output": "NPM1, MLL, and CEBPA" }, { "input": "Class-defining mutations in which genes drive FLT3-ITD-mutant AML?", "output": "NPM1, RUNX1, CEBPA, MLL" }, { "input": "Belzutifan has shown effectiveness for which diseases?", "output": "Belzutifan is the small-molecule HIF 2 alpha inhibitor that has demonstrated significant efficacy in the von Hippel-Lindau disease related renal cell carcinomas, hemangioblastomas, and pancreatic neuroendocrine tumors while demonstrating an acceptable safety profile" }, { "input": "Where are the PUX proteins found?", "output": "PUX proteins specifically associate with the nucleoskeleton underneath the INM." }, { "input": "Are Tregs CD4(+)CD25(+) regulatory T cells a positive regulator of the immune response?", "output": "CD4(+)CD25(+) regulatory T cells (Tregs) are negative regulators of the immune system that induce and maintain immune tolerance." }, { "input": "Is Mediator present at super enhancers?", "output": "Yes. Super enhancers are clusters of enhancers that are densely occupied by the master regulator and mediator." }, { "input": "Is Mediator present at super enhancers?", "output": "Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers." }, { "input": "Is Mediator present at super enhancers?", "output": "Super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator." }, { "input": "Is Mediator present at super enhancers?", "output": "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. Master transcription factors and mediator establish super-enhancers at key cell identity genes" }, { "input": "Is Mediator present at super enhancers?", "output": "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs)." }, { "input": "Is Mediator present at super enhancers?", "output": "Master transcription factors and mediator establish super-enhancers at key cell identity genes Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs)." }, { "input": "Is Mediator present at super enhancers?", "output": "clusters of enhancers that are densely occupied by the master regulators" }, { "input": "Is Mediator present at super enhancers?", "output": "Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator" }, { "input": "Is Mediator present at super enhancers?", "output": "yes" }, { "input": "Is Mediator present at super enhancers?", "output": "Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation." }, { "input": "Does atemoya juice inhibit the CYP1A2 enzyme?", "output": "Yes, atemoya juice inhibits the CYP1A2 enzyme." }, { "input": "What is caused by biallelic variants in SPATA5L1?", "output": "Biallelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss." }, { "input": "What is caused by biallelic variants in SPATA5L1?", "output": "Bi-allelic variants in SPATA5L1 lead to microcephaly, intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss." }, { "input": "A combination of which two drugs was tested in the IMbrave150 trial?", "output": "IMbrave150 trial tested a combination of atezolizumab and bevacizumab for advanced hepatocellular carcinoma." }, { "input": "Is ALS a heritable disease?", "output": "Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance." }, { "input": "What is ARNIL?", "output": "Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is involved in several human cancers." }, { "input": "What is the indication of CPX-351?", "output": "CPX-351 has been approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes." }, { "input": "List signs of patients with biallelic variants in KARS1", "output": "KARS1-associated signs are autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement." }, { "input": "List signs of patients with biallelic variants in KARS1", "output": "Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated in the knockout zebrafish." }, { "input": "Which substance use is associated with Brodifacoum poisoning?", "output": "Brodifacoum poisoning was linked to marijuana use." }, { "input": "What is Alphafold?", "output": "AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm." }, { "input": "List diseases that are repeat expansion disorders (REDs).", "output": "The expansion of Short tandem repeats underlies the pathogenesis of multiple neurological disorders, including Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, fragile X-associated tremor/ataxia syndrome, and myotonic dystrophies, known as repeat expansion disorders (REDs)." }, { "input": "List diseases that are repeat expansion disorders (REDs).", "output": "he Fragile-X related disorders (FXDs) are Repeat Expansion Diseases (REDs) that result from expansion of a CGG-repeat tract located at the 5' end of the FMR1 gene." }, { "input": "What is bb21217?", "output": "BB21217 is a chimeric antigen receptor (CAR)-modified T-cell therapy used to target B-cell maturation antigen (BCMA) in the treatment of multiple myeloma." }, { "input": "Describe the syndrome that is caused by biallelic variants in HPDL", "output": "Biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays." }, { "input": "Which receptor is targeted by Spesolimab?", "output": "Spesolimab is a novel anti-interleukin-36 receptor antibody." }, { "input": "Is NfL (neurofilament light chain) a biomarker of neurodegeneration?", "output": "Yes,\nNeurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD)." }, { "input": "Is Epistaxis associated with dental implant placement?", "output": "Epistaxis is a frequent complication associated with dental implant placement." }, { "input": "What is the effect of grapefruit juice on CYP3A4?", "output": "Grapefruit juice inhibits CYP3A4 activity." }, { "input": "Which is the major clinical feature observed in FDXR-associated disease?", "output": "FDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort." }, { "input": "Which is the major clinical feature observed in FDXR-associated disease?", "output": "Retinal dystrophy is a major clinical feature observed in FDXR-associated disease." }, { "input": "Is Daprodustat effective for anemia?", "output": "Yes. Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease." }, { "input": "Where is the the protein perforin localized?", "output": "Perforin are stored inside the leukocytes in secretory granules." }, { "input": "Is REGN5458 a single-targeted antibody?", "output": "No, REGN5458 is a bispecific antibody." }, { "input": "Which disease is associated with X-linked recessive TLR7 deficiency?", "output": "X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years." }, { "input": "Which disease is associated with X-linked recessive TLR7 deficiency?", "output": "COVID-19 pneumonia" }, { "input": "Which disease is associated with X-linked recessive TLR7 deficiency?", "output": "Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years." }, { "input": "Which disease is associated with X-linked recessive TLR7 deficiency?", "output": "COVID-19" }, { "input": "Is Benralizumab effective for Chronic Spontaneous Urticaria?", "output": "Yes, the anti-IL-5 antibody benralizumab has been reported to reduce Chronic Spontaneous Urticaria symptoms." }, { "input": "Do the proteins Talin and Amot interact?", "output": "Yes,\nAmot binds Talin" }, { "input": "Do RNA binding Proteins that bind to adenine uridine (AU)-rich elements (AREs) in the 5' untranslated region (UTR) of mRNAs (AU-RBPs) regulate the DNA Damage Response?", "output": "RNA Binding Proteins (RBPs) that bind to adenine uridine (AU)-rich elements (AREs) in the 3' untranslated region (UTR) of mRNAs (AU-RBPs) have emerged as key players in regulating the DNA Damage Response (DDR) and preserving genome integrity." }, { "input": "Do RNA binding Proteins that bind to adenine uridine (AU)-rich elements (AREs) in the 5' untranslated region (UTR) of mRNAs (AU-RBPs) regulate the DNA Damage Response?", "output": "We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA." }, { "input": "Has CPX-351 been approved by the FDA and the EMA?", "output": "Yes, CPX-351 has been approved by the US FDA and the EMA." }, { "input": "What is the role of KAT7 in AML?", "output": "KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements and more specifically driven by the MLL-X gene fusions." }, { "input": "What is the role of KAT7 in AML?", "output": "KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements." }, { "input": "Which drugs are included in the CAPIRI regimen?", "output": "CAPIRI regimen includes capecitabine plus irinotecan." }, { "input": "What is the p-crAssphage?", "output": "CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes." }, { "input": "What is the function of Circular RNA (circRNA)?", "output": "Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation as well as the pathogenesis of diseases. including cancer" }, { "input": "What is the function of Circular RNA (circRNA)?", "output": "Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation." }, { "input": "Which one was the first chromone in clinical use?", "output": "The first chromone in clinical use, khellin." }, { "input": "Which resource is used for visualisation of non-covalent contacts?", "output": "The Protein Contacts Atlas is an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information. The Protein Contacts Atlas is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe." }, { "input": "Which resource is used for visualisation of non-covalent contacts?", "output": "The Protein Contacts Atlas is an interactive resource of non-covalent contacts at different scales of organization: atoms, residues, secondary structures, secondary structure, subunits, and entire complexes." }, { "input": "Which disease is treated with Emapalumab?", "output": "Emapalumab is a human monoclonal antibody directed against interferon-\u03b3 (IFN-\u03b3) that was approved by the Food and Drug Administration for primary hemophagocytic lymphohistiocytosis (HLH)." }, { "input": "Do we find bacteriophages in the gut?", "output": "yes,\nBacterial viruses (bacteriophages, phages) of the gut have increasingly become a focus in microbiome studies, with an understanding that they are likely key players in health and disease." }, { "input": "What is the function of the protein encoded by PUMILIO1?", "output": "Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms." }, { "input": "What is the function of the protein encoded by PUMILIO1?", "output": "Pumilio is a member of the highly conserved PUF family of RNA-binding proteins that function as a developmental regulator in diverse animal species. Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms." }, { "input": "What is CPX-351", "output": "CPX-351 (United States: Vyxeos\u00ae; Europe: Vyxeos\u00ae Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes." }, { "input": "What is the prevalence of the inactivating AKT variant p.Pro50Thr in the Finnish population?", "output": "1.1% frequency" }, { "input": "What is the prevalence of the inactivating AKT variant p.Pro50Thr in the Finnish population?", "output": "The P.Pro50Thr allele is present at 1.1% frequency in Finns but virtually absent in other ancestries." }, { "input": "What is the prevalence of the inactivating AKT variant p.Pro50Thr in the Finnish population?", "output": "A study identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function." }, { "input": "Which mutations are inhibited by Ripretinib?", "output": "Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations." }, { "input": "What is known about the PYHIN proteins?", "output": "The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle.\nAbsent in melanoma 2 (AIM2) is a member of the PYHIN (pyrin and HIN domain-containing protein) family with important roles in sensing double-stranded DNA (dsDNA) and assembling the AIM2 inflammasome, which has wide-ranging, pro-inflammatory and pro-pyroptotic properties." }, { "input": "What class of drugs is commonly associated with Drug-induced interstitial lung disease (DIILD)?", "output": "[' Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity.']" }, { "input": "What class of drugs is commonly associated with Drug-induced interstitial lung disease (DIILD)?", "output": "Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity" }, { "input": "What class of drugs is commonly associated with Drug-induced interstitial lung disease (DIILD)?", "output": "Cytotoxic drugs are the most common cause of toxic lung disease." }, { "input": "What pathological phenotype could potentially concomitant pomegranate juice and rosuvastatin use cause?", "output": "Concomitant use of rosuvastatin and pomegranate juice has been hypothesized to be associated with the development of rhabdomyolysis in a case report." }, { "input": "Which tool has been developed to discover VNTR-associated deletions?", "output": "\u03a4rfermikit is a software tool designed to detect deletions larger than 50\u2009bp occurring in Variable Number Tandem Repeats (VNTRs) using Illumina DNA sequencing reads. In such regions, it achieves a better trade-off between sensitivity and false discovery than a state-of-the-art structural variation (SV) caller, Manta, and complements it by recovering a significant number of deletions that Manta missed. trfermikit is based upon the fermikit pipeline, which performs read assembly, maps the assembly to the reference genome, and calls variants from the alignment." }, { "input": "Is tirabrutinib effective for lymphoma?", "output": "Yes, tirabrutinib appears to be effective for lymphoma. It was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma." }, { "input": "Is covid-19 induced anosmia caused by disruption of nuclear architecture?", "output": "Yes. Disruption of nuclear architecture is a cause of COVID-19 induced anosmia." }, { "input": "What is the mechanism of action of Toripalimab?", "output": "Toripalimab is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy." }, { "input": "Is taxilin a cancer marker?", "output": "Yes,\n\u03b1-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker." }, { "input": "What are the symptoms of an incidental durotomy (ID).", "output": "Incidental durotomy can cause postural headaches, nausea, vomiting, dizziness, photophobia, tinnitus, and vertigo. Meningitis is a rare complication reported to occur with a frequency of 0.18%" }, { "input": "What are the symptoms of an incidental durotomy (ID).", "output": "Incidental durotomy can cause postural headaches, nausea, vomiting, dizziness, photophobia, tinnitus, and vertigo." }, { "input": "Is PCAT6 a microRNA?", "output": "No, PCAT6 is a long noncoding RNA." }, { "input": "Is HDAC1 required for GATA-1 transcriptional activity?", "output": "Yes. HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis." }, { "input": "Which enzyme is inhibited by Aramchol?", "output": "Arachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression." }, { "input": "What is the cause of the Diamond Blackfan Anemia?", "output": "Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency." }, { "input": "What are the functions of DNA and RNA G-quadruplexes?", "output": "G-Quadruplex, a unique secondary structure in nucleic acids found throughout human genome, elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, RNAs and telomere, G-Quadruplex structure regulates transcription, translation, splicing, etc" }, { "input": "What is the effect of epiregulin expression in tumors?", "output": "Epiregulin has elevated expression in a variety of human cancers. Epiregulin expression promotes tumor progression and metastasis and reduces patient survival." }, { "input": "Name scRNA-seq workflows which harness graph attention networks", "output": "SCDRHA and CellVGAE" }, { "input": "Which molecule is targeted by Fenebrutinib?", "output": "Fenebrutinib is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK)." }, { "input": "What is Cereblon?", "output": "Cereblon (CRBN) is a substrate recognition protein in the E3-ligase ubiquitin complex. The binding target of CRBN varies according to tissues and cells, and the protein regulates various biological functions by regulating tissue-specific targets." }, { "input": "What is Abbreviated Injury Scale (AIS) used to determine?", "output": "The Abbreviated Injury Scale (AIS) is an objective anatomically-based injury severity scoring system that classifies each injury by body region on a 6 point scale. AIS is the system used to determine the Injury Severity Score (ISS) of the multiply injured trauma patient.\n\nAIS CLASSIFICATIONS\nThe AIS classifies individual injuries by body region as follows:\nAIS 1 \u2013 Minor\nAIS 2 \u2013 Moderate\nAIS 3 \u2013 Serious\nAIS 4 \u2013 Severe\nAIS 5 \u2013 Critical\nAIS 6 \u2013 Maximal (currently untreatable)" }, { "input": "Which protein family is epiregulin a member of?", "output": "EREG (epiregulin), a member of the epidermal growth factor (EGF) family." }, { "input": "Describe Cap Trap RNA-seq", "output": "Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly,\u2009~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Cap Trap RNA-seq is a technology which combines cap trapping and long read MinION sequencing." }, { "input": "What is the use of the Canadian C-Spine Rule?", "output": "The Canadian C-spine rule clinically clears cervical spine fracture without imaging." }, { "input": "What is the Daughterless gene?", "output": "The daughterless (da) gene in Drosophila encodes a broadly expressed transcriptional regulator whose specific functions in the control of sex determination and neurogenesis have been extensively examined." }, { "input": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "output": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor and is used to treat cancer." }, { "input": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "output": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor." }, { "input": "What is amphiregulin a ligand of?", "output": "Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand." }, { "input": "Which genetic susceptibility loci are implicated in irritable bowel syndrome (IBS)?", "output": "There have been six genetic susceptibility loci identified and confirmed for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6." }, { "input": "Which genetic susceptibility loci are implicated in irritable bowel syndrome (IBS)?", "output": "Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6." }, { "input": "Is there an association between Guillain\u2013Barr\u00e9 syndrome and covid vaccine?", "output": "Yes. There series reporting Guillain\u2013Barr\u00e9 syndrome after COVID-19 vaccination." }, { "input": "What is the function of the protein calreticulin?", "output": "Calreticulin (CALR) is an endoplasmic reticulum (ER)-resident protein involved in a spectrum of cellular processes. In healthy cells, CALR operates as a chaperone and Ca2+ buffer to assist correct protein folding within the ER." }, { "input": "Atlanto-axial rotary instability (Fielding type 1) is common to what diseases?", "output": "Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes as well as infectious disease." }, { "input": "Atlanto-axial rotary instability (Fielding type 1) is common to what diseases?", "output": "Atlanto-axial instability (AAI) is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) syndromes, where it typically presents as a rotary subluxation due to incompetence of the alar ligament." }, { "input": "What is the effect of epiregulin on leptin secretion?", "output": "Epiregulin induces leptin secretion." }, { "input": "Which JASPAR release is JASPAR 2022?", "output": "JASPAR (http://jaspar.genereg.net/) is an open-access database containing manually curated, non-redundant transcription factor (TF) binding profiles for TFs across six taxonomic groups. In JASPAR 2022, JASPAR's 9th release, the CORE collection was expanded with 341 new profiles (148 for plants, 101 for vertebrates, 85 for urochordates, and 7 for insects), which corresponds to a 19% expansion over the previous release." }, { "input": "Is Erythropoietin effective for neuroprotection of Preterm Infants.", "output": "No. High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age." }, { "input": "What is the SPRTN protein function?", "output": "The protease SPRTN emerged as the essential enzyme for DNA-protein crosslink proteolysis repair." }, { "input": "What part of the body is associated with Cauda equina", "output": "The cauda equina is the sack of nerve roots (nerves that leave the spinal cord between spaces in the bones of the spine to connect to other parts of the body) at the lower end of the spinal cord." }, { "input": "What does RUNX1T1 stand for?", "output": "RUNX1T1 stands for runt-related transcription factor 1." }, { "input": "Describe InteractiveComplexHeatmap", "output": "InteractiveComplexHeatmap is designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one additional line of code." }, { "input": "Describe InteractiveComplexHeatmap", "output": "InteractiveComplexHeatmap is an R package that brings interactivity to the widely used ComplexHeatmap package. InteractiveComplexHeatmap is designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one additional line of code. InteractiveComplexHeatmap also provides flexible functionalities for integrating interactive heatmap widgets to build more complex and customized Shiny web applications." }, { "input": "What is the use of Brain Metastasis Velocity (BMV) Model?", "output": "Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery." }, { "input": "What is \"cell competition\"?", "output": "Cell competition is a social cellular phenomenon in which unfit cells are selectively eliminated to maintain tissue homeostasis.\nAt the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer." }, { "input": "What is IDD in relation to organ transplantation?", "output": "Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation after cardiac death" }, { "input": "What is IDD in relation to organ transplantation?", "output": "Imminent death donation (IDD) is a proposal to procure organs from patients prior to the withdrawal of life support, which is anticipated to lead to death" }, { "input": "What is IDD in relation to organ transplantation?", "output": "Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient." }, { "input": "Is METTL3 an m6A writer, reader or eraser?", "output": "The methyltransferase METTL3 is an m6A writer." }, { "input": "What is the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells." }, { "input": "What is the 4D nucleome project?", "output": "The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions." }, { "input": "What is the 4D nucleome project?", "output": "The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions." }, { "input": "Which drugs were included in the polypill that was tested in TIPS-3 trial?", "output": "Polypill tested in the TIPS-3 trial was comprised of atenolol, ramipril, hydrochlorothiazide, and a statin." }, { "input": "What is the drug gantenerumab targeting?", "output": "Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain." }, { "input": "Is Ameloblastoma (AB) a common benign tumor occurring in the brain?", "output": "Ameloblastoma (AM) is a slow growing and aggressive benign tumor with an odontogenic epithelial origin arising from the mandible or maxilla." }, { "input": "Is Ameloblastoma (AB) a common benign tumor occurring in the brain?", "output": "Ameloblastoma is a neoplasm arising in the craniofacial skeleton." }, { "input": "Is Ameloblastoma (AB) a common benign tumor occurring in the brain?", "output": "Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the mandible" }, { "input": "In which aspects of the immune response is m6A methylation implicated?", "output": "m6A is a novel regulator of immune system homeostasis and activation. m6A modifications and m6A modifying proteins play a critical role in pathogen recognition, immune cell activation, immune cell fate decisions, and immune reactions. These modifications modulate the fate decisions of innate and adaptive immune cells and regulate immune responses in immune-associated diseases, including viral infections and cancer." }, { "input": "Describe nextNEOpi", "output": "NextNEOpi is a comprehensive and fully-automated bioinformatic pipeline to predict tumor neoantigens from raw DNA and RNA sequencing data. In addition, nextNEOpi quantifies neoepitope- and patient-specific features associated with tumor immunogenicity and response to immunotherapy." }, { "input": "What is the use of the ATRIA score?", "output": "ATRIA score determines bleeding risk for patients on warfarin." }, { "input": "Which protein is targeted by Herceptin?", "output": "Her2 is targeted by Herceptin." }, { "input": "What are the main clinical components of the brain death exam?", "output": "The three essential findings in brain death are coma, absence of brain stem reflexes by neurologic exam including ancillary testing, and apnea. Studies can highlight the variability in practice in regard to the AT and supports the use of ancillary tests to determine BD in patients. Coma and brain stem reflexes can be determined by several ancillary tests Ancillary tests include electroencephalography, brainstem auditory evoked potentials, included somatosensory evoked potentials, transcranial Doppler ultrasonography, conventional cerebral angiography, and nuclear medicine flow study" }, { "input": "How does amphiregulin decrease the anti-proliferative effect of cetuximab?", "output": "In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (p\u2009<\u20090.05) via AKT and ERK activation." }, { "input": "Describe RCandy", "output": "RCandy is a platform-independent R package for rapid, simple, and flexible visualisation of recombination events in bacterial genomes." }, { "input": "What variables are included in the MuLBSTA score?", "output": "MuLBSTA score includes Multilobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age." }, { "input": "Which organisms are the focus of the Wormbase?", "output": "WormBase continues to advance its practices on data acquisition, curation and retrieval to most effectively deliver comprehensive knowledge about Caenorhabditis elegans, and genomic information about other nematodes and parasitic flatworms." }, { "input": "Is Ameloblastoma (AB) a benign tumor that never metastasizes?", "output": "Ameloblastomas are benign but locally invasive neoplasms which can be metastatic" }, { "input": "What does PCAT6 stand for?", "output": "PCAT6 stands for prostate cancer-associated transcript 6." }, { "input": "Is there any role of the 'Greek islands' in olfactory receptor choice?", "output": "Yes. 'Greek islands' first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression." }, { "input": "What is ASTRAL Score?", "output": "ASTRAL Score is used to predict prognosis of stroke patients." }, { "input": "Is paxillin affected by RANKL?", "output": "Yes,\nRANKL promotes paxillin serine and tyrosine phosphorylation." }, { "input": "What organ is associated with a Gleason pattern or Gleason Score?", "output": "The Gleason score is an important parameter for clinical outcome in prostate cancer patients" }, { "input": "What organ is associated with a Gleason pattern or Gleason Score?", "output": "The Gleason score is an important parameter for clinical outcome in prostate cancer patients." }, { "input": "How does FTO suppress pancreatic tumorigenesis?", "output": "Reduced expression of the m6A demethylase, fat mass and obesity-associated protein (FTO), was responsible for the high levels of m6A RNA modification in pancreatic cancer. Moreover, FTO demethylated the m6A modification of praja ring finger ubiquitin ligase 2 (PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells." }, { "input": "Which tool has been developed to identify the glycan shielding of glycosylated proteins?", "output": "GLYCO (GLYcan COverage) is an in silico approach to quantify the glycan shielding of a protein surface. The software provides insights into glycan-dense/sparse regions of the entire protein surface or a subset of the protein surface. GLYCO calculates glycan shielding from a single coordinate file or from multiple coordinate files, for instance, as obtained from molecular dynamics simulations or by nuclear magnetic resonance spectroscopy structure determination, enabling analysis of glycan dynamics." }, { "input": "Which tool has been developed to identify the glycan shielding of glycosylated proteins?", "output": "GLYCO calculates glycan shielding from a single coordinate file or from multiple coordinate files, for instance, as obtained from molecular dynamics simulations or by nuclear magnetic resonance spectroscopy structure determination, enabling analysis of glycan dynamics." }, { "input": "What are the targets of Tirbanibulin?", "output": "Tirbanibulin is Src kinase signaling inhibitor and tubulin polymerisation inhibitor that is being developed for the topical treatment of actinic keratosis, and psoriasis." }, { "input": "Is retinol binding protein 4 an adipokine?", "output": "Yes,\nRetinol-binding protein 4 (RBP4) is a prominent adipokine." }, { "input": "What is the function of BACH1", "output": "BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar" }, { "input": "What does the gene symbol EREG stand for?", "output": "The gene symbol EREG stands for the gene epiregulin." }, { "input": "Which tool has been developed for proteome-wide detection of membrane lipid-binding proteins?", "output": "MBPpred is a profile Hidden Markov Model based method capable of detecting Membrane Binding Proteins (MBPs) from information encoded in their amino acid sequence." }, { "input": "What disease can be treated with Avacopan?", "output": "Avacopan is effective for ANCA-associated vasculitis." }, { "input": "Is HYDIN (Hydrocephalus-inducing protein homolog) an axonemal protein?", "output": "Yes,\nHYDIN is a axonemal protein." }, { "input": "What disease is also known as Bechterew's Disease?", "output": "Ankylosing spondylitis (Bechterew's disease) is the most typical form of axial SpA whereby sacroiliitis can be found on X-rays of the SI joints." }, { "input": "Through which pathway does epiregulin promote leptin secretion?", "output": "EREG increased leptin production and secretion in a dose-dependent manner in iAb fat explants via the EGFR/MAPK pathway." }, { "input": "Are there any R packages that help with visualizing data on spirals?", "output": "Yes. Spiralize is an R package for visualizing data on spirals." }, { "input": "Was ALVAC-HIV effective for HIV prevention in the HVTN 702 trial?", "output": "No. The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity" }, { "input": "Do Afamin bind Vitamin E?", "output": "Yes,\nAfamin is a plasma vitamin E-binding glycoprotein." }, { "input": "Is disruption of immune regulation mechanisms associated with adverse pregnancy outcomes, including preeclampsia (PE)?", "output": "Inflammation and oxidative stress at the maternal-fetal interface characterize the placental dysfunction that underlies the pregnancy disorder preeclampsia." }, { "input": "Is disruption of immune regulation mechanisms associated with adverse pregnancy outcomes, including preeclampsia (PE)?", "output": "Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE)" }, { "input": "Can autophagy related lncRNAs be used for colorectal cancer prognosis?", "output": "Yes, a prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC." }, { "input": "Are there roles for cohesin mutations in AML?", "output": "Yes. Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression." }, { "input": "What is the target of Sotorasib?", "output": "Sotorasib is a KRASG12C inhibitor." }, { "input": "Is ASF1 phopshorylated by the Tousled-like kinases?", "output": "Yes,\nAsf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs)." }, { "input": "What is Luteolin?", "output": "Luteolin has been reviewed as a flavonoid possessing potential cardioprotective, anti-inflammatory, anti-cancer activities." }, { "input": "What is Luteolin?", "output": "Luteolin, a polyphenolic flavonoid, has potent anti-inflammatory properties." }, { "input": "Does sphingosine-1 phosphoate suppress epiregulin?", "output": "Sphingosine-1 phosphate induces epiregulin (EREG) gene expression." }, { "input": "Which is the literature-based database of phenotypes?", "output": "PheneBank is a Web-portal for retrieving human phenotype-disease associations that have been text-mined from the whole of Medline. This approach exploits state-of-the-art machine learning for concept identification by utilising an expert annotated rare disease corpus from the PMC Text Mining subset. Evaluation of the system for entities is conducted on a gold-standard corpus of rare disease sentences and for associations against the Monarch initiative data." }, { "input": "Which is the literature-based database of phenotypes?", "output": "PheneBank is a Web-portal for retrieving human phenotype-disease associations that have been text-mined from the whole of Medline." }, { "input": "Idecabtagene vicleucel can be used for treatment of which disease?", "output": "Idecabtagene vicleucel was shown to be effective for Relapsed and Refractory Multiple Myeloma." }, { "input": "LINC00339 is a diagnostic, prognostic and treatment efficacy biomarker for what disease?", "output": "LINC00339 as a cancer diagnostic, prognostic and treatment efficacy biomarker." }, { "input": "What is the role of PCAT6 in human cancers?", "output": "PCAT6, is a carcinogenic lncRNA. It is abnormally elevated in various human malignant tumors. PCAT6 has been found to sponge various miRNAs to activate the signaling pathways, which further affects tumor cell proliferation, migration, invasion, cycle, apoptosis, radioresistance, and chemoresistance. It is believed to have diagnostic and prognostic value and clinical applications in various human malignancies." }, { "input": "Can whole genome sequencing be used for diagnosis of mitochondrial disease?", "output": "Yes. Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments." }, { "input": "What are the targets of avapritinib?", "output": "Avapritinib is a novel inhibitor of KIT/PDGFRA. It is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors." }, { "input": "What is Jackhammer esophagus?", "output": "Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000 mm Hg.s.cm during high-resolution manometry (HRM)." }, { "input": "What is Jackhammer esophagus?", "output": "Jackhammer esophagus (JE) is a recently recognized esophageal motility disorder that is characterized by hypercontractile peristalsis." }, { "input": "Can METTL3 methylate long noncoding RNAs?", "output": "Yes, METTL3 can modulate methylation and expression of lncRNA." }, { "input": "Which disease is caused by repeat expansion in VWA1?", "output": "An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy." }, { "input": "What is the use of the Apfel Score?", "output": "The Apfel simplified risk score, developed in 1999, is the most widely used tool for risk stratification of postoperative nausea and vomiting." }, { "input": "Is PPROM a condition that occurs in males or females?", "output": "Preterm premature rupture of fetal membranes (PPROM) occurs in pregnant females." }, { "input": "What is EpiMethylTag?", "output": "EpiMethylTag is a fast, low-input, low sequencing depth method, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA." }, { "input": "What is the target of Sutimlimab?", "output": "Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s." }, { "input": "Can parasite infections by Schistosoma japonicum prevent or improve asthma?", "output": "A peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice." }, { "input": "Describe Multilocus Inherited Neoplasia Allele Syndrome (MINAS)", "output": "Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations." }, { "input": "Is erenumab effective for trigeminal neuralgia?", "output": "No. In a randomized clinical trial erenumab was not effective for treatment of trigeminal neuralgia." }, { "input": "What is the first indication for lurasidone?", "output": "Lurasidone's initial indication is the treatment of bipolar depression." }, { "input": "What is the first indication for lurasidone?", "output": "Lurasidone is an atypical antipsychotic drug that was initially developed for the treatment of schizophrenia and bipolar depression." }, { "input": "What is the first indication for lurasidone?", "output": "Lurasidone is an atypical antipsychotic drug that was initially developed for the treatment of schizophrenia" }, { "input": "What is the first indication for lurasidone?", "output": "The first indication for lurasidone is the treatment of schizophrenia." }, { "input": "Can other vaccines be given with COVID-19 vaccine?", "output": "Although there are no data regarding safety and efficacy when COVID-19 vaccines are co-administered with other vaccines, the Centers for Disease Control and Prevention (CDC) has stated that COVID-19 vaccines can be administered at any time in relation to other non-COVID-19 vaccines, and if needed, can be administered on the same day as other vaccines. This is based on the experience with non-COVID-19 vaccines, where the immunogenicity and adverse event profiles were generally similar when vaccines are administered simultaneously or alone.\n\nFurthermore, in a randomized trial, frequency of adverse effects and immunogenicity were largely similar when a COVID-19 vaccine (BNT162b2 or ChAdOx1) was given concomitantly with either an influenza vaccine or placebo." }, { "input": "What is Sublocade?", "output": "Sublocade\u00ae is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly." }, { "input": "Is music therapy effective for pain management in neonates?", "output": "No, although there are beneficial effects of music-based interventions, there are no clear evidence of their effectiveness on pain management in neonates." }, { "input": "What is the mechanisms of action of Gilteritinib?", "output": "The fms-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib is indicated for relapsed or refractory FLT3-mutated acute myeloid leukemia." }, { "input": "What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs?", "output": "Small interfering RNAs (siRNAs) with N-acetylgalactosamine (GalNAc) conjugation for improved liver uptake represent an emerging class of drugs to treat liver diseases." }, { "input": "What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs?", "output": "N-acetylgalactosamine (GalNAc) conjugation of siRNAs is the primary strategy for hepatocyte-targeted delivery, followed by conjugation to a targeting moiety for improved liver uptake." }, { "input": "What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs?", "output": "N-acetylgalactosamine (GalNAc) conjugation is used to improve liver uptake of siRNAs. It is a targeting moiety used to deliver siRNAs to liver hepatocytes. This strategy has been successful in the development of siRNA drugs that target various liver diseases" }, { "input": "What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs?", "output": "The reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs is to improve liver uptake and facilitate targeted delivery of siRNA to hepatocytes, which is the primary strategy for hepatocyte-targeted delivery. This conjugation induces robust RNAi-mediated gene silencing in the liver, owing to uptake mediated by the asialoglycoprotein receptor (ASGPR). GalNAc-siRNA conjugates also have a remarkable durability of activity that can persist for months in preclinical species and humans, making them an emerging class of drugs to treat liver diseases." }, { "input": "What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs?", "output": "N-acetylgalactosamine (GalNAc) conjugation of siRNAs is used to improve liver uptake and target hepatocytes. This strategy enhances the delivery and therapeutic potential of siRNA drugs for treating liver-related diseases" }, { "input": "What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs?", "output": "N-acetylgalactosamine (GalNAc) is used as a targeting moiety for Hepatocytes. Small interfering RNAs (siRNAs) with N-acetylgalactosamine (GalNAc) conjugation for improved liver uptake represent an emerging class of drugs to treat liver diseases and this has become a primary strategy for hepatocyte-targeted delivery," }, { "input": "What is synthetic lethality?", "output": "Two genes are synthetic lethal if mutation of either alone is compatible with viability but mutation of both leads to death. So, targeting a gene that is synthetic lethal to a cancer-relevant mutation should kill only cancer cells and spare normal cells. Synthetic lethality therefore provides a conceptual framework for the development of cancer-specific cytotoxic agents." }, { "input": "What is synthetic lethality?", "output": "Synthetic lethality is a phenomenon in which the simultaneous occurrence of two genetic mutations leads to cell death, while each mutation alone has no effect on cell viability. This concept has been extensively studied in cancer research, as it provides a potential therapeutic strategy for targeting cancer cells with minimal toxicity to normal cells. The idea is to identify pairs of genes that, when mutated together, result in synthetic lethality and then develop drugs that target one of these genes. For example, PARP inhibitors have been developed for the treatment of BRCA-mutated cancers because BRCA-deficient cells are sensitive to PARP inhibition due to synthetic lethality between these two genes. Synthetic lethality has also been explored in other areas such as infectious diseases and neurodegenerative disorders. Overall, understanding synthetic lethality can provide insights into disease mechanisms and lead to the development of novel therapies." }, { "input": "What is synthetic lethality?", "output": "Synthetic lethality is a genetic concept that occurs when the simultaneous disruption of two or more genes leads to cell death, while the individual disruption of each gene does not have a lethal effect. This phenomenon has gained significant attention in cancer research as it offers a promising therapeutic strategy for selectively targeting cancer cells with specific genetic alterations. By exploiting the unique vulnerabilities of cancer cells, synthetic lethality can be used to develop targeted therapies that minimize damage to healthy cells and reduce side effects. One well-known example of synthetic lethality in cancer therapy is the use of PARP inhibitors in BRCA1/2-mutated cancers, where the combined deficiency in DNA repair pathways results in cell death specifically in tumor cells." }, { "input": "What is synthetic lethality?", "output": "Synthetic lethality is a phenomenon in which two or more genetic mutations interact in a way that causes the death of an organism, even though each mutation alone would not be lethal. It is a form of genetic interaction that can be used to identify potential drug targets for cancer therapy." }, { "input": "What is synthetic lethality?", "output": "Synthetic lethality is a phenomenon in which the simultaneous inactivation of two or more genes leads to cell death, while the inactivation of either gene alone has no effect. It is a promising approach for cancer therapy, as it can be used to target cancer cells while leaving normal cells unaffected." }, { "input": "What is synthetic lethality?", "output": "Synthetic lethality occurs between two genes when the perturbation of either gene alone is viable but the perturbation of both genes simultaneously results in the loss of viability. So, two genes are synthetic lethal if mutation of either alone is compatible with viability but mutation of both leads to death. Targeting a gene that is synthetic lethal to a cancer-relevant mutation should kill only cancer cells and spare normal cells. Therefore, synthetic lethality provides a conceptual framework for the development of cancer-specific cytotoxic agents." }, { "input": "How many injections of CLS-TA did the patients participating in the PEACHTREE trial receive?", "output": "The patients participating in the PEACHTREE trial received two suprachoroidal injections of CLS-TA at 0 and 12 weeks." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "The most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy include genetic testing, electromyography (EMG), muscle biopsy, and serum creatine kinase (CK) levels." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "The newborns with retest positive result were recalled again for serum creatine kinase (CK) and multiplex ligation-dependent probe amplification (MLPA) test." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "The most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy include genetic testing, muscle biopsy, electromyography (EMG), and serum creatine kinase (CK) testing." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "The most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy are multiplex ligation-dependent probe amplification (MLPA), genetic sequencing, and creatine kinase (CK) testing." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "The most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy are multiple ligation-dependent probe amplification (MLPA), Whole-Exome Sequencing (WES) and Next Generation Sequencing (NGS)." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "The most commonly used diagnostic tests for Duchenne muscular dystrophy include multiplex ligation-dependent probe amplification (MLPA), DNA tests, sequencing analysis, whole-exome sequencing (WES), and serum creatine kinase (CK) tests." }, { "input": "What are the most commonly used diagnostic tests for the diagnosis of Duchenne muscular dystrophy?", "output": "Commonly used diagnostic tests for Duchenne muscular dystrophy include western blotting, immunohistochemical staining, multiplex polymerase chain reaction, multiplex ligase-dependent probe amplification, and complete sequence analysis. Additionally, genetic testing can also provide an accurate diagnosis of the disease when conventional methods fail." }, { "input": "Is there any association between Tripe palms and cancer?", "output": "Yes. Tripe palms sign is associated with cancer." }, { "input": "is prosopagnosia inherited or acquired?", "output": "Prosopagnosia can be inherited in an autosomal dominant mode of inheritance (congenital prosopagnosia) or acquired following a large unilateral right-hemispheric lesion in frontal (acquired prosopagnosia)." }, { "input": "is prosopagnosia inherited or acquired?", "output": "There is evidence that prosopagnosia can be inherited in an autosomal dominant mode of inheritance, suggesting that it is a genetic condition." }, { "input": "is prosopagnosia inherited or acquired?", "output": "Prosopagnosia can be both inherited and acquired" }, { "input": "is prosopagnosia inherited or acquired?", "output": "Prosopagnosia can be both inherited (congenital) and acquired. Congenital prosopagnosia is a genetic condition present from birth, while acquired prosopagnosia occurs due to brain damage or injury." }, { "input": "is prosopagnosia inherited or acquired?", "output": "Prosopagnosia is an acquired condition, usually caused by brain damage, although there is evidence of a genetic component in some cases." }, { "input": "is prosopagnosia inherited or acquired?", "output": "Prosopagnosia can be inherited in an autosomal dominant mode of inheritance." }, { "input": "Where are promoters typically found in DNA?", "output": "Promoters are typically found in the 5' region of a gene, upstream of the transcription start site. They are DNA sequences that bind transcription factors and RNA polymerase, and are necessary for the initiation of transcription." }, { "input": "Where are promoters typically found in DNA?", "output": "A promoter is a short region of DNA (100-1,000 bp) where transcription of a gene by RNA polymerase begins. It is typically located directly upstream or at the 5' end of the transcription initiation site." }, { "input": "Where are promoters typically found in DNA?", "output": "A promoter is an important regulatory element which marks the region that transcription of a gene by RNA polymerase begins. It is typically located directly upstream or at the 5' end of the transcription initiation site." }, { "input": "What was the duration of the follow-up period of patients in the PEACHTREE clinical trial?", "output": "The patient follow-up period in the PEACHTREE trial lasted 24 weeks (6 months)." }, { "input": "Which are some symptoms of FSHD?", "output": "The main symptoms of FSHD are facial weakness, proximal weakness of the upper limbs, lower limb weakness, truncal muscle weakness, periscapular weakness, foot dorsiflexor weakness, hip girdle weakness, and hearing loss. These symptoms are usually progressive and asymmetric." }, { "input": "Which are some symptoms of FSHD?", "output": "5 major FSHD symptoms: facial, periscapular, foot dorsiflexor, hip girdle weakness, and hearing loss." }, { "input": "Which are some symptoms of FSHD?", "output": "Some symptoms of FSHD include facial weakness, proximal upper limb weakness, lower limb weakness, truncal muscle weakness, and asymmetric weakness." }, { "input": "Which are some symptoms of FSHD?", "output": "-Progressive muscle weakness and wasting\n-Difficulty with facial expressions\n-Difficulty with eye movements\n-Difficulty with chewing and swallowing\n-Scoliosis\n-Joint contractures\n-Muscle cramps\n-Fatigue\n-Pain in the muscles and joints" }, { "input": "Which are some symptoms of FSHD?", "output": "The primary symptoms of Facioscapulohumeral muscular dystrophy (FSHD) include progressive muscle weakness and wasting of the face, shoulder blades, and upper arms. Other symptoms may include scapular winging, foot drop, difficulty with running and climbing stairs, and difficulty with facial expressions." }, { "input": "Which are some symptoms of FSHD?", "output": "Some symptoms of FSHD include facial and proximal weakness of the upper limbs, weakness of foot dorsiflexors, hip girdle weakness, periscapular weakness, and hearing loss. Weakness is progressive and frequently asymmetric, which is a hallmark of the disease." }, { "input": "Which are some symptoms of FSHD?", "output": "Some symptoms of FSHD include facial weakness, proximal upper limb weakness, lower limb weakness, truncal muscle weakness, and hearing loss." }, { "input": "Which are some symptoms of FSHD?", "output": "Some symptoms of FSHD are the following: asymmetric weakness, facial and proximal weakness of the upper limbs, and lower limb and truncal muscles weakness, facial, periscapular, foot dorsiflexor, hip girdle weakness, and hearing loss." }, { "input": "What is the mechanism of action of Adagrasib?", "output": "Adagrasib is a KRASG12C inhibitor that irreversibly and selectively binds KRASG12C, locking it in its inactive state." }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "Yes, mutations of the Super Oxide Dismutase 1 (SOD1) gene have been linked to some cases of Amyotrophic Lateral Sclerosis (ALS)." }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "Yes, mutations in the SOD1 gene can cause familial Amyotrophic Lateral Sclerosis (ALS)." }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "Yes, approximately 2% of ALS cases are caused by mutations in the SOD1 gene." }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "Amyotrophic Lateral Sclerosis (ALS) can be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene, in a small percentage of cases." }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "ALS can be associated with a mutation of the SOD1 gene" }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are caused by mutations in the super oxide dismutase 1 (SOD1) gene a ." }, { "input": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "output": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is associated with mutations in the super oxide dismutase 1 (SOD1) gene." }, { "input": "What are enhancers?", "output": "Enhancers are important cis-acting elements that can regulate gene transcription and cell fate alongside promoters by providing binding sites for transcription factors and their complexes. Unlike promoters, enhancers are not necessarily adjacent to target genes and can exert their functions regardless of enhancer orientations, positions and spatial segregations from target genes. In fact, because enhancers are highly cell/tissue specific, lack common motifs, and are far from the target gene, the systematic and precise identification of enhancer regions in DNA sequences is a big challenge. Despite that, many human cancers and diseases have been shown to be associated with the malfunction of enhancers." }, { "input": "What is the mode of delivery of the drug XIPERE?", "output": "XIPERE is administered via a microneedle-based device, the SCS Microinjector, in the suprachoroidal space." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common muscular dystrophies include the congenital muscular dystrophies (CMD) and the childhood and adult-onset muscular dystrophies. The CMD include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD. Childhood and adult-onset muscular dystrophies include dystrophinopathies, limb-girdle muscular dystrophies, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common muscular dystrophies include Duchenne muscular dystrophy, Becker muscular dystrophy, myotonic dystrophy, and facioscapulohumeral muscular dystrophy." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common muscular dystrophies are dystrophinopathies, limb-girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common muscular dystrophies are Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), myotonic dystrophy (DM), and congenital muscular dystrophy (CMD)." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common muscular dystrophies are Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common types of muscular dystrophies are dystrophinopathies, limb-girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, and myotonic dystrophy." }, { "input": "What are the most common muscular dystrophies?", "output": "The most common muscular dystrophies are Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, congenital muscular dystrophy, and distal muscular dystrophy." }, { "input": "Which disease is targeted by Fazirsiran?", "output": "Fazirsiran is an RNA interference therapeutic that was developed for Liver Disease Associated with Alpha1-Antitrypsin Deficiency." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "Brain natriuretic peptide (BNP) is a cardiac hormone that is secreted from the heart. It is synthesized in the heart and circulates in the blood." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "BNP usually originates from the ventricles of the heart." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "The Brain or B Type Natriuretic Peptide, BNP is usually derived from neurons within the walls of the left atrium and right auricle." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "Brain (or B type) Natriuretic Protein, BNP is produced mainly by the ventricles of the heart in response to increased wall stress." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "BNP usually originates from the left ventricle of the heart in response to volume overload." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "Stretching of cultured cardiomyocytes up-regulates the expression of brain natriuretic peptide (BNP)." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "BNP, or Brain (B-type) Natriuretic Protein, usually originates from the ventricles of the heart." }, { "input": "Where does Brain (or B type) Natriuretic Protein, BNP usually originate from?", "output": "cardiomyocyte stress up-regulates the expression of brain natriuretic peptide (BNP)." }, { "input": "Are any medications available to prevent COVID-19 following exposure?", "output": "Currently, no. Certain monoclonal antibodies had previously been demonstrated to prevent SARS-CoV-2 infection after exposure, but they mostly lack activity against circulating SARS-CoV-2 variants.\n\nOther agents (e.g., Hydroxychloroquine, Ivermectin, Tixagevimab/Cilgavimab) have not been shown to be effective." }, { "input": "Has RTA 408 received FDA approval?", "output": "Yes, RTA 408 is FDA approved." }, { "input": "Which are the types of myotonic dystrophy?", "output": "There are two types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2)." }, { "input": "Which are the types of myotonic dystrophy?", "output": "There are two types of myotonic dystrophy: type 1 (DM1) and type 2 (DM2)." }, { "input": "Which are the types of myotonic dystrophy?", "output": "There are two types of myotonic dystrophy: DM type 1 (DM1) and DM type 2 (DM2)." }, { "input": "Which are the types of myotonic dystrophy?", "output": "The two types of myotonic dystrophy are DM1 and DM2." }, { "input": "What are the active components of Opdualag?", "output": "Opdualag is a new dual anti-PD-1 (Nivolumab) and anti-LAG-3 (Relatimab) treatment approved as the first LAG-3 blocking antibody combination for unresectable or metastatic melanoma." }, { "input": "Where in the body would Schlemm's canal be found", "output": "Schlemm's canal can be found in the anterior chamber of the eye." }, { "input": "Where in the body would Schlemm's canal be found", "output": "Schlemm's canal is found in the eye." }, { "input": "Where in the body would Schlemm's canal be found", "output": "Schlemm's canal is in the eye" }, { "input": "Where in the body would Schlemm's canal be found", "output": "Schlemm's canal is found in the eye, specifically in the trabecular meshwork of the anterior chamber of the eye." }, { "input": "Can reinfection occur after SARS-CoV-2 infection?", "output": "Protective and detectable immune responses are induced after SARS-CoV-2 infection but it is not yet established to what degree and for how long protection against reinfection lasts. Evidence suggests that some of these responses can be detected for at least a year following infection.\n\nThe short-term risk of reinfection (e.g., within the first several months after initial infection) is low. Several studies estimated the risk of reinfection to be less than 1 percent in the subsequent 5-8 months following initial infection. The risk of reinfection may be greater with the Omicron variant." }, { "input": "What is the mode of inheritance of Friedreich\u2019s ataxia?", "output": "Friedreich's Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder." }, { "input": "What is the difference between Duchenne muscular Dystrophy and Becker muscular dystrophy?", "output": "DMD patients do not produce dystrophin whereas BMD patients produce 10-40% of the normal amount of dystrophin." }, { "input": "What is the difference between Duchenne muscular Dystrophy and Becker muscular dystrophy?", "output": "The main difference between Duchenne muscular dystrophy and Becker muscular dystrophy is the amount of dystrophin present in the patient. In DMD patients, dystrophin is virtually absent, while BMD patients have 10% to 40% of the normal amount. Additionally, the age of onset, severity of disease, and rate of progression can also differ between the two types." }, { "input": "What is Lance-Adams syndrome?", "output": "Lance-Adams syndrome is a rare complication of successful cardiopulmonary resuscitation, often accompanied by action myoclonus. Myoclonus may occur as generalized, focal, or multifocal movements and can include the face, trunk, and/or extremities." }, { "input": "What does mitapivat do?", "output": "Mitapivat is an oral drug that activates the pyruvate kinase enzyme, increasing ATP production and reducing levels of 2,3-diphosphoglycerate. It is used for the treatment of hereditary hemolytic anemias" }, { "input": "What does mitapivat do?", "output": "Mitapivat (AG-348) is a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. MitapivAT has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte Pyruvates (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphoglycerate." }, { "input": "What does mitapivat do?", "output": "Mitapivat is a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemia" }, { "input": "What does mitapivat do?", "output": "Mitapivat (AG-348) is a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. Mitapvat has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte Pyruvates kinase (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphoglycerate." }, { "input": "What does mitapivat do?", "output": "Mitapivat (AG-348) is a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. It has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte pyruve kinase (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphoglycerate." }, { "input": "What does mitapivat do?", "output": "Mitapivat is a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. It has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte pyruvate kinase (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphoglycerate. It has been used for the treatment of hereditary hemolytic anemias, and has been shown to increase the hemoglobin level in patients with pyruvate kinase deficiency." }, { "input": "What does mitapivat do?", "output": "Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells." }, { "input": "What does mitapivat do?", "output": "Mitapivat is an oral, first-in-class medication that activates the pyruvate kinase enzyme in red blood cells. This activation increases ATP production and reduces 2,3-diphosphoglycerate levels, ultimately helping to treat hereditary hemolytic anemias such as pyruvate kinase deficiency by increasing hemoglobin levels" }, { "input": "What does mitapivat do?", "output": "Mitapivat is an investigational drug that inhibits the activity of dihydroorotate dehydrogenase (DHODH), an enzyme involved in the de novo pyrimidine biosynthesis pathway. It is being studied as a potential treatment for pyruvate kinase deficiency, a rare inherited metabolic disorder." }, { "input": "In prokaryotes, functionally related genes are sometimes positioned adjacent to each other in the genome and can be under the control of the same regulatory machinery. What are these called?", "output": "In prokaryotes, functionally related genes are often organized into operons. Operons are clusters of adjacent genes that are transcribed together under the control of a single promoter, allowing for coordinated gene expression and efficient co-translation of proteins involved in the same cellular pathway. This organization is a fundamental element of how genetic information is arranged in prokaryotes and ensures that coregulated gene expression occurs through co-transcription. The arrangement of functionally-related genes in operons provides spatiotemporal control over cellular processes, contributing to the overall regulation and efficiency of prokaryotic gene expression." }, { "input": "In prokaryotes, functionally related genes are sometimes positioned adjacent to each other in the genome and can be under the control of the same regulatory machinery. What are these called?", "output": "In prokaryotes, functionally related genes that are positioned adjacent to each other in the genome and under the control of the same regulatory machinery are called operons. Operons are a unique feature of prokaryotic gene organization, allowing for coordinated expression of multiple genes involved in a specific metabolic pathway or cellular process. An operon typically consists of a promoter region, an operator site, and a cluster of functionally related genes. The promoter region is where RNA polymerase binds to initiate transcription, while the operator site serves as a binding location for regulatory proteins called repressors or activators. These regulatory proteins modulate gene expression by either inhibiting or promoting transcription based on environmental conditions or cellular needs. One well-known example of an operon is the lac operon in Escherichia coli, which regulates lactose metabolism in response to glucose availability. Overall, operons provide an efficient mechanism for prokaryotes to regulate gene expression and adapt to changing environments." }, { "input": "In prokaryotes, functionally related genes are sometimes positioned adjacent to each other in the genome and can be under the control of the same regulatory machinery. What are these called?", "output": "In prokaryotes, functionally related genes are often arranged in operons, which are polycistronic messages transcribed from a single promoter. This organization allows for coordinated gene expression and efficient cotranslation of proteins involved in the same pathway. Operons can be regulated by the same regulatory machinery, ensuring that all genes within an operon are coregulated. The clustering of functionally related genes in operons is a fundamental element of how genetic information is organized in prokaryotes and plays a crucial role in their ability to adapt to changing environments. Overall, operons provide a mechanism for spatiotemporal control of cellular processes and allow prokaryotes to efficiently coordinate gene expression." }, { "input": "In prokaryotes, functionally related genes are sometimes positioned adjacent to each other in the genome and can be under the control of the same regulatory machinery. What are these called?", "output": "Prokaryotes often have functionally-related genes joined together under the direction of a single promoter. These structures are called operons. Clustering of functionally-related genes in operons allows for coordinated gene expression and spatiotemporal control of cellular processes." }, { "input": "What is the active ingredient of Xipere?", "output": "The active ingredient of Xipere is triamcinolone acetonide." }, { "input": "What are the most common mutation locations in dystrophin gene in Duchenne muscular dystrophy?", "output": "The most common mutation locations in dystrophin gene in Duchenne muscular dystrophy are the distal hotspot exons, specifically exons 47, 48, and 50. Additionally, mutations in the proximal portion of the gene not involving Dp140 have been found to be less severe. Duplications spanning one or more exons are also a common cause of the disease." }, { "input": "What are the most common mutation locations in dystrophin gene in Duchenne muscular dystrophy?", "output": "The most common mutation locations in the dystrophin gene in Duchenne muscular dystrophy are exons 45-54, which constitute a hotspot for DMD mutations, and exons 3-9, which encompass a mutational hot spot. Distal hotspot exons 47, 48 and 50 are also commonly deleted." }, { "input": "What are the most common mutation locations in dystrophin gene in Duchenne muscular dystrophy?", "output": "The most common mutation locations in DMD gene are exons 3-9 and 45-55." }, { "input": "What are the most common mutation locations in dystrophin gene in Duchenne muscular dystrophy?", "output": "Distal hotspot exons 47, 48 and 50 were the commonly deleted exons. Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients We confirmed that del45-55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations." }, { "input": "Does mutation of ARTEMIS gene causes severe combined immunodeficiency?", "output": "Artemis mutation disrupts development of adaptive immunity and leads to severe combined immunodeficiency." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "No, Wilson's disease is an autosomal recessive disorder caused by a mutation in the ATP7B gene, which leads to an accumulation of copper in the body. It is not an iron storage disease." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "Wilson's disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "No, Wilson's disease is a copper storage disorder, not an iron storage disorder." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "No, Wilson's disease is not an iron storage disease. It is a copper storage disorder that affects the liver and brain." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "Yes. Wilson disease is a copper storage disease caused by mutations in ATP7B, which leads to excessive copper accumulation throughout the body. This excess metal results in damage to various organs such as the liver and brain, causing severe neurological problems and ultimately requiring lifelong chelation therapy." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "No, Wilson's disease is not described as an iron storage disease. It is an inherited disorder that affects the body's ability to regulate copper." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "Wilson's disease is a rare inherited disorder that causes copper to accumulate in your liver, brain and other vital organs." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "Wilson disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms." }, { "input": "Is Wilson's disease described as an iron storage disease?", "output": "Yes, Wilson's Disease is characterized by excessive accumulation of copper due to impaired transport or decreased metabolism of Cu2+. This results in disruption of vital organs such as the liver and brain leading to symptoms like neurological damage, pigment abnormalities, pancytopenia and even death if left untreated." }, { "input": "What are promoters?", "output": "A promoter is generally defined to be the sequence that directs the initiation of transcription. This simple definition belies a diverse and complex transcriptional module. There are two major types of core promoters - focused and dispersed. Focused promoters contain either a single transcription start site or a distinct cluster of start sites over several nucleotides, whereas dispersed promoters contain several start sites over 50-100 nucleotides.\n\nIn summary, promoters are short regions of DNA (100-1,000 bp) where transcription by RNA polymerase begins. They are typically located directly upstream or at the 5' end of the transcription initiation site." }, { "input": "What are promoters?", "output": "Promoters are short regions of DNA (100-1,000 bp) located upstream or at the 5' end of the transcription initiation site. They are responsible for directing the initiation of transcription by RNA polymerase II and can be either focused or dispersed. Focused promoters contain either a single transcription start site or a distinct cluster of start sites over several nucleotides, while dispersed promoters contain several start sites over 50-100 nucleotides and are typically found in CpG islands in vertebrates." }, { "input": "What are promoters?", "output": "Promoters are short regions of DNA, typically ranging from 100 to 1,000 base pairs, that play a crucial role in gene transcription by serving as the binding site for RNA polymerase. They are usually located directly upstream or at the 5' end of the transcription initiation site. The RNA polymerase II core promoter is responsible for directing the initiation of transcription and can be classified into two major types: focused and dispersed. Focused promoters contain either a single transcription start site or a distinct cluster of start sites spanning several nucleotides, while dispersed promoters feature multiple start sites spread across 50-100 nucleotides and are commonly found in CpG islands in vertebrates." }, { "input": "Is omaveloxolone an activator of NFkB?", "output": "No, omaveloxolone is an inhibitor of NF\u03baB." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "The most pain scale used to measure pain in children is FLACC (Face, leg, activity, cry, and consolability) score." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "The most commonly used pain scale for the measurement of pain in children is the Face, Legs, Activity, Cry, and Consolability (FLACC) scale." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "The most commonly used pain scale for measuring pain in children is the Faces, Legs, Activity, Cry, Consolability (FLACC) scale." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "The most commonly used pain scale for the measurement of pain in children is the Faces Pain Scale-Revised (FPS-R)." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "Face, leg, activity, cry, and consolability (FLACC) pain scale is used for postoperative pain assessment in children." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "The most commonly used pain scale for the measurement of pain in children is the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. This scale is reported to be used by 54% of pediatric intensive care units (PICUs) for daily assessment and documentation of pain." }, { "input": "What is the most commonly used pain scale for the measurement of pain in children?", "output": "The Faces Pain Scale (FPS) is one of the most commonly used scales for measuring pain in children." }, { "input": "What is the mechanism of action of daridorexant?", "output": "Daridorexant is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist that is being developed for the treatment of insomnia." }, { "input": "What is DILI-CAT used for?", "output": "DILI-CAT, ia a clinically intuitive, data-driven, computer-assisted scoring algorithm and is a useful tool for early detection of drug's hepatotoxicity in clinical drug development." }, { "input": "What is DILI-CAT used for?", "output": "DILI-CAT, a novel phenotype-based drug-induced liver injury causality assessment tool, is a useful tool for early detection of drug's hepatotoxicity in clinical drug development." }, { "input": "What is DILI-CAT used for?", "output": "DILI-CAT, a clinically intuitive, data-driven, computer-assisted scoring algorithm, is a useful tool for early detection of drug's hepatotoxicity in clinical drug development." }, { "input": "What is DILI-CAT used for?", "output": "DILI-CAT is a clinically intuitive, data-driven, computer-assisted scoring algorithm used for early detection of drug's hepatotoxicity in clinical drug development. It is a novel phenotype-based drug-induced liver injury causality assessment tool that allows for signal confirmation in early drug development." }, { "input": "What is DILI-CAT used for?", "output": "We utilised a novel DILI causality assessment tool (DILICAT) which uses drugspecific liver injury phenotypes to examine potential DILI in early phase ximelagatran clinical development.A novel p" }, { "input": "What is DILI-CAT used for?", "output": "DILI-CAT is a web-based tool used to assess the risk of drug-induced liver injury (DILI) in clinical trials. It uses a combination of clinical and laboratory parameters to predict the risk of DILI." }, { "input": "What is DILI-CAT used for?", "output": "The DILI-CAT is a novel computer-assisted drug induced liver injury causality assessment tool designed to help differentiate drugs causing severe liver injuries from those causing mild or moderate liver damage." }, { "input": "What is the significance of a persistently positive RT-PCR for weeks after illness?", "output": "Patients diagnosed with COVID-19 can have detectable SARS-CoV-2 RNA in upper respiratory tract specimens for weeks after the onset of symptoms. However, prolonged viral RNA detection does not necessarily indicate prolonged infectiousness. In particular, isolation of infectious virus more than 10 days after illness onset is rare in patients whose symptoms have resolved.\n\nPeople with COVID-19 are thus generally felt to have low infectiousness after about 10 days, particularly after mild to moderate disease and in the absence of immunocompromise, regardless of whether they continue to have a positive reverse-transcription polymerase chain reaction (RT-PCR) test." }, { "input": "What is the significance of a persistently positive RT-PCR for weeks after illness?", "output": "A persistently positive RT-PCR for weeks after illness does not necessarily correspond to infectiousness, as available viral culture data suggests shorter durations of shedding of viable virus. However, immunocompromised individuals may have prolonged shedding of viral RNA and viable virus, which can pose a challenge for managing such patients" }, { "input": "What is the significance of a persistently positive RT-PCR for weeks after illness?", "output": "A persistently positive RT-PCR for weeks after illness indicates the presence of viral RNA but may not necessarily correlate with infectivity. While detection of viral RNA can be prolonged, the actual shedding of viable virus typically lasts for a shorter duration, with infectivity highest at symptom onset and declining rapidly within 10-15 days" }, { "input": "What is the genetic cause of Freidreich's ataxia?", "output": "Friedreich ataxia is caused by hyperexpansion of the triplet repeat sequence GAA\u00b7TTC in the first intron of the FXN gene." }, { "input": "Which diagnostic tests are used for the diagnosis of FSHD?", "output": "The diagnosis of FSHD is mainly based on a DNA test using Southern Blotting and hybridization to a set of probes, but EMG and muscle biopsy can be used to rule out other diagnoses." }, { "input": "Which diagnostic tests are used for the diagnosis of FSHD?", "output": "For diagnosing FSHD, the main tests used are DNA testing with Southern Blotting and hybridization to a set of probes. When genetic confirmation is not possible, other investigations, such as EMG and muscle biopsy, are employed to rule out alternative diagnoses." }, { "input": "Which diagnostic tests are used for the diagnosis of FSHD?", "output": "FSHD is diagnosed with a Southern blot based DNA test. In the absence of genetic confirmation, other investigations, mainly EMG and muscle biopsy, are needed to rule out another diagnosis." }, { "input": "Can Efgartigimod be used for myasthenia gravis?", "output": "Yes. Efgartigimod is effective, approved and can be used for myasthenia gravis." }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Quercetin-biapigenin nanoparticles are effective to penetrate the blood-brain barrier." }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Yes, Quercetin-biapigenin nanoparticles have been shown to be effective in penetrating the blood-brain barrier in an in vitro BBB model." }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Yes, Quercetin-biapigenin nanoparticles have been shown to be effective in penetrating the blood-brain barrier." }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Yes, Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier" }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Yes, Quercetin-biapigenin loaded nanoparticles have been shown to effectively penetrate the blood-brain barrier in various studies." }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Yes, Quercetin-biapigenin loaded PCL-nanoparticles have previously been shown to be effective at crossing the blood-brain barrier in pre-clinical studies." }, { "input": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "output": "Yes, Quercetin-biapigenin nanoparticles are effective to penetrate the blood-brain barrier." }, { "input": "What process involves metabolite-sensing mRNAs to control gene expression?", "output": "The process involving metabolite-sensing mRNAs to control gene expression is known as riboswitch regulation. Riboswitches are structured RNA elements typically found in the 5' untranslated regions (UTRs) of mRNAs that can directly bind to small metabolites or ions. Upon binding, they undergo conformational changes that modulate gene expression by affecting transcription, translation, or mRNA stability. This mechanism allows cells to rapidly respond to fluctuations in the levels of specific metabolites, ensuring appropriate metabolic adaptation and homeostasis. Riboswitches have been identified in bacteria, archaea, and eukaryotes, with diverse ligands including purines, amino acids, coenzymes, and metal ions. They serve as an efficient means for cells to sense and regulate their internal environment without relying on protein factors such as transcription factors or regulatory enzymes." }, { "input": "What process involves metabolite-sensing mRNAs to control gene expression?", "output": "Metabolite-sensing mRNAs are involved in a process known as riboswitch-mediated gene regulation. Riboswitches are RNA elements that can bind small molecules, such as metabolites, and change their conformation to regulate gene expression. Metabolite-sensing mRNAs contain riboswitches in their untranslated regions (UTRs), which allow them to sense changes in intracellular metabolite concentrations and modulate the translation or stability of the mRNA. This mechanism is particularly important for regulating metabolic pathways, where the availability of specific metabolites can affect the expression of genes involved in those pathways. For example, in bacteria, riboswitches have been identified that control the expression of genes involved in amino acid biosynthesis, vitamin biosynthesis, and sugar metabolism. The discovery of riboswitches has opened up new avenues for understanding how cells respond to changes in their environment and has potential applications for developing novel antibiotics and other therapeutics that target these regulatory elements." }, { "input": "What process involves metabolite-sensing mRNAs to control gene expression?", "output": "Riboswitches are metabolite-sensing gene-control elements that are typically located in non-coding portions of mRNAs, where they selectively bind their target compound and subsequently modulate gene expression. In eukaryotes, a well-characterized riboswitch senses the vitamin B1 derivative TPP (thiamine pyro-phosphate)." }, { "input": "What is Concerta\u00ae?", "output": "Concerta\u00ae is a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD)." }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "The most common neuropsychiatric disorders associated with Duchenne muscular dystrophy are autism spectrum disorders (ASDs), epilepsy, attention-deficit hyperactivity disorder (ADHD), depression, anxiety disorders and obsessive-compulsive disorder (OCD)." }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "The most common neuropsychiatric disorders associated with Duchenne muscular dystrophy are autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder (OCD)." }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "To estimate the prevalence of neuropsychiatric disorders, including autism spectrum disorders (ASDs), attention-deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder (OCD), in populations with Duchenne muscular dystrophy (DMD)" }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "Neuropsychiatric phenotype associated to DMD gene mutations include now low IQ scores, epilepsy, autism, and attention deficit disorder. Increased rates of clinically significant internalizing disorders (obsessive compulsive disorder, anxiety, and depression) have been demonstrated in males with Duchenne muscular dystrophy, and a Duchenne muscular dystrophy neuropsychiatric syndrome has been suggested. Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms." }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "The most common neuropsychiatric disorders associated with Duchenne muscular dystrophy are autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder (OCD)." }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "The most common neuropsychiatric disorders associated with Duchenne muscular dystrophy include:\n\n1. Attention Deficit Hyperactivity Disorder (ADHD)\n2. Anxiety\n3. Depression\n4. Learning Disabilities\n5. Behavioral Problems\n6. Sleep Disturbances\n7. Autistic Spectrum Disorders\n8. Intellectual Disability" }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "The most common neuropsychiatric disorders associated with Duchenne muscular dystrophy are attention deficit hyperactivity disorder (ADHD), anxiety, depression, autism spectrum disorder, and sleep disturbances." }, { "input": "What are the most common neuropsychiatric disorders associated with Duchenne muscular dystrophy?", "output": "The most common neuropsychiatric disorders associated with Duchenne muscular dystrophy are autism spectrum disorders (ASDs), attention-deficit hyperactivity disorder (ADHD), anxiety disorders, obsessive-compulsive disorder (OCD), and depression. The prevalence rates for these disorders in the DMD population are 7.0%, 18.0%, 24.0%, 12.0%, and 11.0%, respectively. Clinically significant internalizing disorders have also been reported in males with DMD." }, { "input": "Which interleukins are affected by Dupilumab?", "output": "Dupilumab is a monoclonal antibody for adults and adolescents with moderate-to-severe atopic dermatitis, that inhibits interleukin-4 receptor alpha subunit (IL4-R\u03b1) and the signaling pathways activated by interleukin (IL)-4 and IL-13." }, { "input": "What cells are used to regenerate cartilage?", "output": "Chondrocytes and stem cells, including mesenchymal stem cells, are used to regenerate cartilage." }, { "input": "What cells are used to regenerate cartilage?", "output": "Chondrocytes and stem cells, particularly mesenchymal stem cells, are commonly used to regenerate cartilage." }, { "input": "What cells are used to regenerate cartilage?", "output": "Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors." }, { "input": "What cells are used to regenerate cartilage?", "output": "Chondrocytes, mesenchymal stem cells, and induced pluripotent stem cells are all used to regenerate cartilage." }, { "input": "What cells are used to regenerate cartilage?", "output": "Chondrocytes and stem cells are used to regenerate cartilage." }, { "input": "Is adenosine methylation an epigenetic modification?", "output": "Adenosine methylation is the most common mammalian epigenetic modification of mRNAs that is directed by a large methyltransferase complex containing Mettl3." }, { "input": "Which year was XIPERE approved by the FDA?", "output": "XIPERE was approved by the FDA in 2021." }, { "input": "Can breastfeeding be used to alleviate the procedural pain in neonates?", "output": "Yes, breastfeeding is effective in alleviating procedural pain in neonates." }, { "input": "Can breastfeeding be used to alleviate the procedural pain in neonates?", "output": "Yes, breastfeeding is effective for pain management in neonates." }, { "input": "Can breastfeeding be used to alleviate the procedural pain in neonates?", "output": "Yes, breastfeeding has been shown to reduce the pain response in neonates during medical procedures." }, { "input": "Can breastfeeding be used to alleviate the procedural pain in neonates?", "output": "The conclusion was that breastfeeding was effective in reducing pain caused by blood collection for newborn screening. Premature Infant Pain Profile scores were lower in the breastfeeding group when compared to the placebo and the group positioned in mother's arms, but were not different compared to the no-treatment and the glucose groups." }, { "input": "Can lenacapavir be used for HIV?", "output": "Yes, lenacapavir can be used for HIV." }, { "input": "What color light does the the inhibitory receptor halorhodopsin (eNpHR) respond to?", "output": "The inhibitory receptor halorhodopsin (eNpHR) responds to yellow light." }, { "input": "What color light does the the inhibitory receptor halorhodopsin (eNpHR) respond to?", "output": "Halorhodopsin (eNpHR) is an inhibitory receptor that responds to yellow-green light (wavelength of 590 nm)." }, { "input": "What color light does the the inhibitory receptor halorhodopsin (eNpHR) respond to?", "output": "Halorhodopsin responds to yellow light." }, { "input": "What color light does the the inhibitory receptor halorhodopsin (eNpHR) respond to?", "output": "The eNpHR is sensitive to yellow light." }, { "input": "What color light does the the inhibitory receptor halorhodopsin (eNpHR) respond to?", "output": "eNpHR responds to yellow light." }, { "input": "What regulatory element promotes RNA polymerase II binding as well as the binding of factors that facilitate the unwinding of DNA prior to translation?", "output": "Found in about 24% of human gene promoters, the TATA box is a critical regulatory element that is mostly found in genes transcribed by RNA polymerase II, and as such, recruits this enzyme to the promoter. Additionally, the TATA-binding protein aids in unwinding DNA." }, { "input": "What regulatory element promotes RNA polymerase II binding as well as the binding of factors that facilitate the unwinding of DNA prior to translation?", "output": "The TATA box is a critical regulatory element found in many promoters transcribed by RNA polymerase II. Located 25-30 nucleotides upstream of the transcription initiation site, it promotes RNA polymerase II binding and facilitates the unwinding of DNA prior to translation. The TATA-binding protein (TBP), a major component of the human TFIID multiprotein complex, plays an essential role in directing the initiation of RNA transcription at a site immediately downstream of the TATA sequence. Approximately 24% of human genes have a TATA-like element with AT-rich promoters, but only around 10% contain the canonical TATA box (TATAWAWR)." }, { "input": "How many patients with Friedreich's ataxia were included in each cohort of the phase I/II double-blind, comparator-controlled trial of RT001.", "output": "Each cohort of the phase I/II double-blind, comparator-controlled trial of RT001 involved 9 Friedreich's ataxia patients. In total nineteen patients enrolled in the trial, and 18 completed all safety and efficacy measurements." }, { "input": "What is the incidence of Facioscapulohumeral Muscular Dystrophy?", "output": "Facioscapulohumeral Muscular Dystrophy has and incidence of 1:8000 to 1:20000." }, { "input": "What is the incidence of Facioscapulohumeral Muscular Dystrophy?", "output": "The incidence of Facioscapulohumeral Muscular Dystrophy (FSHD) is approximately 1 in 8000 individuals." }, { "input": "What is the incidence of Facioscapulohumeral Muscular Dystrophy?", "output": "The incidence of Facioscapulohumeral Muscular Dystrophy is approximately 1 in 8,000." }, { "input": "What is the incidence of Facioscapulohumeral Muscular Dystrophy?", "output": "The incidence of Facioscapulohumeral Muscular Dystrophy is approximately 1 in 8000 people." }, { "input": "Risdiplam is used for treatment of which disease?", "output": "Risdiplam is approved for treatment of spinal muscular atrophy." }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "Neurofilament light chain (NfL) is a biomarker of neurodegeneration and is associated with many diseases such as MS, CKD, Ataxia telangiectasia, Langerhans cell histiocytosis (LCH) and acute and chronic inflammatory polyneuropathies" }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "Elevated plasma Neurofilament Light chain (NfL) levels have been associated with several diseases, including Multiple Sclerosis, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Huntington's Disease, Langerhans Cell Histiocytosis, Myotonic Dystrophy type 1, Chronic Kidney Disease, and Brain Metastases." }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "The disorders linked to increased levels of NfL include neurological conditions like Alzheimer\u2019s Disease (AD), Multiple Sclerosis (MS), Chronic Traumatic Encephalopathy (CTE), Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Other diseases where NfL levels have been reported to be altered include peripheral nervous system injuries and inflammatory responses." }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "The diseases associated with elevations in the plasma Neurofilament Light chain (NfL) include multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke, and spinal cord injury." }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "Plasma Neurofilament Light chain (NfL) has been associated with various diseases, including Multiple Sclerosis, Radiologically Isolated Syndrome, Progressive Multiple Sclerosis, Chronic Kidney Disease, Brain Metastases, Frontotemporal Dementia-Amyotrophic Lateral Sclerosis Spectrum, Ataxia Telangiectasia, Langerhans Cell Histiocytosis, Myotonic Dystrophy type 1, and Inflammatory Polyneuropathies." }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "The diseases associated with elevated levels of Plasma Neurofilament Light Chain (NfL) include Multiple Sclerosis (MS), Alzheimer's Disease (AD), Brain Trauma, Myasthenia Gravis (MG), Creutzfeldt-Jakob Disease (CJD), Amyotrophic Lateral Sclerosis (ALS), Progressive Supranuclear Palsy (PSP), Cerebral Amyloid Angiopathy (CAA), Demyelinating Lesions such as multiple sclerosis plaques and white matter hyperintensities seen on magnetic resonance imaging brain scans, Peripheral nervous system disorders including Guillain-Barre Syndrome (GBS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Paraproteinemia-related Demyelinating Polyneuropathy (PDN), Multifocal Motor Neuron Disorder (MMND), and others." }, { "input": "Please list the diseases associated with elevations in the plasma Neurofilament Light chain (NfL).", "output": "Elevations in the plasma Neurofilament Light chain (NfL) have been associated with multiple sclerosis (MS), radiologically isolated syndrome (RIS), progressive multiple sclerosis (MS), chronic kidney disease (CKD), brain metastases, frontotemporal dementia-amyotrophic lateral sclerosis spectrum (FAS), ataxia telangiectasia, myotonic dystrophy type 1 (DM1), and inflammatory polyneuropathies." }, { "input": "What are the most common assays to profile chromatin accessibility?", "output": "Recent advancements in next-generation sequencing technologies and accompanying reductions in cost have led to an explosion of techniques to examine chromatin accessibility genome-wide. Generally, accessible regions of chromatin are permissive for factor binding and are therefore hotspots for regulation of gene expression. Therefore, identification of these regions is critical for understanding regulatory mechanisms of gene expression associated with various biological processes in eukaryotes.\n\nCurrently, high-throughput methodologies, such as DNase-seq, ATAC-seq, FAIRE-seq, and MNase-seq have been widely applied in mapping open chromatin in various eukaryotic genomes." }, { "input": "What doses of RT001 were used in the phase I/II double-blind, comparator-controlled trial of Friedreich's ataxia patients?", "output": "In the phase I/II double-blind, comparator-controlled trial of RT001 in Friedreich's ataxia patients two doses of the drug were evaluated 1.8 or 9.0 g/day." }, { "input": "What are the most common pain scales used to measure pain in neonates?", "output": "The most common pain scales used to measure pain in neonates are the following: Premature Infant Pain Profile-Revised (PIPP), Premature Infant Pain Profile-Revised (PIPP-R), Neonatal Facial Coding System (NFCS), Neonatal Infant Pain Scale (NIPS), Neonatal Pain, Agitation, and Sedation Scale (NPASS), COMFORT and Douleur Aigu\u00eb du Nouveau-n\u00e9 (DAN)." }, { "input": "What are the most common pain scales used to measure pain in neonates?", "output": "The most common pain scales used to measure pain in neonates are the Neonatal Facial Coding System (NFCS), Douleur Aigu\u00eb du Nouveau-n\u00e9 (DAN) scale, Neonatal Infant Pain Scale (NIPS), and Premature Infant Pain Profile (PIPP)." }, { "input": "What are the most common pain scales used to measure pain in neonates?", "output": "The most common pain scales used to measure pain in neonates are the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) and the Neonatal Infant Pain Scale (NIPS). Other pain scales used in the article include PIPP, NFCS, and NPASS." }, { "input": "What are the most common pain scales used to measure pain in neonates?", "output": "1. Neonatal Facial Coding System (NFCS)\n2. Premature Infant Pain Profile (PIPP)\n3. Neonatal Infant Pain Scale (NIPS)\n4. CRIES Pain Scale\n5. COMFORT Scale\n6. FLACC Scale" } ] }