nirantk/geneticsQA-train huggingface dataset:
Question: What is the target of tanezumab?

Context:
Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model.
OBJECTIVE: To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials.
 Current research focuses on the development of new OA drugs (such as sprifermin/recombinant human fibroblast growth factor-18, tanezumab/monoclonal antibody against β-nerve growth factor), which aims for more effectiveness and less incidence of adverse effects than the traditional ones.
Areas covered: This manuscript is a review that examines both the pharmacological properties and clinical studies of tanezumab, the most widely studied antibody to NGF, for management of osteoarthritis (OA) and low back pain. 
OBJECTIVE: Evaluate efficacy and safety of tanezumab, a humanized monoclonal antibody against nerve growth factor, in neuropathic pain.
In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models.
Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions.
Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system.
In this randomized, double-blind, placebo controlled phase 2 study we investigated tanezumab, a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for interstitial cystitis pain.Patients with interstitial cystitis received a single intravenous dose of 200 μg/kg tanezumab or placebo
Nerve safety of tanezumab, a nerve growth factor inhibitor for pain treatment.
In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models.
Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions.
Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system..

Answer: Tanezumab is a humanized monoclonal antibody against nerve growth factor.
Exact answer: nerve growth factor, NGF
Question: Which currently known mitochondrial diseases have been attributed to POLG mutations?

Context:
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)
Mutations in the gene encoding mitochondrial DNA polymerase gamma (POLG), the enzyme that synthesises mitochondrial DNA (mtDNA), have been associated with a mitochondrial disease-autosomal dominant or recessive progressive external ophthalmoplegia-and multiple deletions of mtDNA.
About 150 mutations in the human POLG have been identified in patients with mitochondrial diseases such as Alpers syndrome, progressive external ophthalmoplegia, and ataxia-neuropathy syndromes.
Nineteen exhibited a cluster of three or more predefined clinical manifestations suggestive of POLG-related disease: progressive external ophthalmoplegia, seizures and/or an abnormal electroencephalogram, neuropathy, ataxia, liver function abnormalities, migraine or dysphagia/dysarthria. 
Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy.

Answer: 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).
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)
Exact answer: childhood Myocerebrohepatopathy Spectrum disorders (MCHS)
Alpers syndrome
Ataxia Neuropathy Spectrum (ANS) disorders
Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA)
autosomal recessive Progressive External Ophthalmoplegia (arPEO)
autosomal dominant Progressive External Ophthalmoplegia (adPEO)
Question: List functional roles of the FtsZ protein.

Context:
bacterial homologue FtsZ establishes the cytokinetic ring that constricts during cell division. 
In Escherichia coli, initial assembly of the Z ring for cell division requires FtsZ plus the essential Z ring-associated proteins FtsA and ZipA.
FtsZ is an essential cell division protein in Escherichia coli, and its localization, filamentation, and bundling at the mid-cell are required for Z-ring stability.
the bacterial division FtsZ protein
The GTPase-dependent polymerization/depolymerization dynamics of FtsZ regulate bacterial cell division in vivo. 
Bacterial cytokinesis depends upon the tubulin-like GTPase FtsZ, which polymerizes into an annular structure at midcell (the Z-ring) that defines the division site.
FtsZ is the first of the divisome proteins to accumulate at the division site and is widely thought to function as a force generator that constricts the cell envelope. 
the cell division protein FtsZ
FtsZ, the key protein of bacterial cell division was selected as a potent anti bacterial target. 
the cell-division protein FtsZ
 FtsZ and PG together function in orchestrating cell division and maintaining cell shape in almost all other bacteria.
 the tubulin-like protein of the division septum FtsZ
FtsZ is a widely distributed major cytoskeletal protein involved in the archaea and bacteria cell division. 
Four major roles of FtsZ have been characterized: cell elongation, GTPase, cell division, and bacterial cytoskeleton. 
Bacterial cell division involves a complex and dynamic sequence of events whereby polymers of the protein FtsZ assemble at the division plane and rearrange to achieve the goal of contracting the cell membrane at the site of cell division, thus dividing the parent cell into two daughter cells. 
the cell division protein FtsZ
FtsZ, the homolog of eukaryotic tubulin, is a GTPase that assembles into cytokinetic Z rings essential for cell division in prokaryotic cells

Answer: Four major roles of FtsZ have been characterized: cell elongation, GTPase, cell division, and bacterial cytoskeleton.
Exact answer: cell elongation, GTPase, cell division, bacterial cytoskeleton
Question: What role do gluten proteins play in the development of celiac disease?

Context:
Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. 
Celiac disease (CD) is an autoimmune enteropathy initiated and sustained by the ingestion of gluten in genetically susceptible individuals. It is caused by a dysregulated immune response toward both dietary antigens, the gluten proteins of wheat, rye, and barley, and autoantigens, the enzyme tissue transglutaminase (TG2)
Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies
Transglutaminase 2 (TG2) catalyzes cross-linking or deamidation of glutamine residues in peptides and proteins. The in vivo deamidation of gliadin peptides plays an important role in the immunopathogenesis of celiac disease (CD).
Tissue transglutaminase (TG2) modifies proteins and peptides by transamidation or deamidation of specific glutamine residues. TG2 also has a central role in the pathogenesis of celiac disease. The enzyme is both the target of disease-specific autoantibodies and generates deamidated gliadin peptides recognized by intestinal T cells from patients.

Answer: Gluten proteins from wheat, rye, and barley are dietary antigens that trigger a dysregulated immune response in genetically susceptible individuals, leading to the development of celiac disease. The immune response targets both gluten proteins and autoantigens like tissue transglutaminase 2 (TG2), contributing to the autoimmune enteropathy characteristic of the disease.
Question: Is skin color affected by variations of the SLC24A5 gene?

Context:
the alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) associated with light skin pigmentation in Eurasian populati
Associations between five single nucleotide polymorphisms (SNPs) known to play a role in pigmentation (rs1426654-SLC24A5, rs1042602-TYR, rs16891982-SLC45A2, rs6058017-ASIP, and rs642742-KITLG) and MI measures were tested using standard one-way analysis of variance (ANOVA) within each population.

Answer: Yes. The alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) are associated with light skin pigmentation in Eurasian population.
Exact answer: yes
Question: Which receptors are targeted by suvorexant?

Context:
Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, 1 (SB-649868), or suvorexant have shown promise for the treatment of insomnias and sleep disorders in several recent clinical trials in volunteers and primary insomnia patients. 
Several such compounds have entered into clinical development, including the dual orexin receptor antagonists, suvorexant and almorexant.
 Suvorexant (MK-4305) is an orexin receptor antagonist being developed for the treatment of insomnia. 
Indeed, phase III clinical trials were completed last year of suvorexant, a non-selective (dual) antagonist for orexin receptors, for the treatment of primary insomnia, and demonstrate promising results.
METHODS: We evaluated suvorexant, an orexin receptor antagonist, for treating patients with primary insomnia in a randomized, double-blind, placebo-controlled, 2-period (4 weeks per period) crossover polysomnography study.
Suvorexant is a dual orexin antagonist currently in Phase III clinical trials for the modulation of sleep and is being developed by Merck.
Merck's suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012. 
A concise, enantioselective synthesis of the potent dual orexin inhibitor suvorexant (1) is reported. 
Reaction development and mechanistic study of a ruthenium catalyzed intramolecular asymmetric reductive amination en route to the dual Orexin inhibitor Suvorexant (MK-4305).
The first example of an intramolecular asymmetric reductive amination of a dialkyl ketone with an aliphatic amine has been developed for the synthesis of Suvorexant (MK-4305), a potent dual Orexin antagonist under development for the treatment of sleep disorders. 
Suvorexant (MK-4305) is a potent, selective, and orally bioavailable antagonist of OX(1)R and OX(2)R currently under clinical investigation as a novel therapy for insomnia.
Suvorexant is a pharmacologically novel dual antagonist of orexin receptors OX1R and OX2R, which has an effect that promotes sleep by reducing arousal and wakefulness.
 Indeed, phase III clinical trials were completed last year of suvorexant, a non-selective (dual) antagonist for orexin receptors, for the treatment of primary insomnia, and demonstrate promising results.
 In order to understand the differential contribution of both receptors in regulating sleep/wakefulness states we compared the pharmacological effects of a newly developed OX2R antagonist (2-SORA), Compound 1 m (C1 m), with those of a dual orexin receptor antagonist (DORA), suvorexant, in C57BL/6J mice.
Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.

Answer: 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.
Exact answer: orexin 1, orexin 2
Question: Does thyroid hormone regulate calcium transient in the myocardium? 

Context:
3-iodothyronamine (T(1)AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect
In adult rat cardiomyocytes acute exposure to 20 microM T(1)AM decreased the amplitude and duration of the calcium transient.
In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium
The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine
hese results indicate that the thyroid state influences the time course of the calcium transient and are consistent with the abbreviation in the duration of contraction that is observed in the hyperthyroid state.

Answer: YES
Exact answer: yes
Question: Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?

Context:
This study reports the consequences of LT4 treatment over a prolonged period of time in 2 of the first patients with a heterozygous mutation in TRα1.
Here we show that the dysregulation of the pituitary-thyroid axis was worsened by the lack of TR alpha1 in TR betaPV mice, and severe impairment of postnatal growth was manifested in TR betaPV mice deficient in TR alpha1.
Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. 
The data demonstrate a novel array of effects mediated by a dominant negative TRalpha1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment.
No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality
These results demonstrate that 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. 

Answer: 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
Exact answer: yes
Question: With which complexes is the protein SUS1 associated?

Context:
The yeast DUBm comprises a catalytic subunit, Ubp8, and three additional subunits, Sgf11, Sus1 and Sgf73, all of which are required for DUBm activity.
the deubiquitination module (DUBm) of SAGA, which is composed of Ubp8, Sus1, Sgf11, and Sgf73.
The conserved Sac3:Thp1:Sem1:Sus1:Cdc31 (TREX2) complex binds to nuclear pore complexes (NPCs)
Sus1 (hENY2) participates in this coordination as part of two protein complexes: SAGA, a transcriptional co-activator; TREX-2, which functions in mRNA biogenesis and export.
The deubiquitinating module (DUBm) of the SAGA coactivator contains the Ubp8 isopeptidase, Sgf11, Sus1, and Sgf73, which form a highly interconnected complex. 
Sus1/ENY2, a component of the SAGA and TREX-2 complexes, is involved in both transcription and mRNA export
Sus1 is a component of both the SAGA transcriptional co-activator complex and the TREX-2 complex that binds to nuclear pore complexes.
 distinct subcomplex called the deubiquitinating module (DUBm), which contains the ubiquitin-specific protease Ubp8, bound to Sgf11, Sus1, and Sgf73.
The yeast deubiquitinase Ubp8 protein is recruited and activated by the SAGA complex and, together with Sgf11, Sus1, and Sgf73, forms a DUB module responsible for deubiquitinating histone H2B during gene expression. 
In the nucleus, Sus1 is associated to the transcriptional co-activator SAGA and to the NPC associated complex termed TREX2/THSC

Answer: Sus1/ENY2 is a component of the SAGA and TREX-2 complexes
Exact answer: SAGA complex, TREX-2 complex
Question: Is cystatin C or cystatin 3 used as a biomarker of kidney function?

Context:
to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes.
Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP.
This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. 
he primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)).
A number of recent reports have suggested that the cystatin C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in pediatric patients.
The CKD-EPI equation using cystatin C was the most precise method of renal function evaluation in patients with neurogenic bladder.
Serum cystatin C (CysC) is an endogenous marker of kidney function.
The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy.
Estimated kidney function based on serum cystatin C 
: Several formulas for glomerular filtration rate (GFR) estimation, based on serum creatinine or cystatin C, have been proposed. 
he highest and lowest eGFR levels corresponded to the cystatin C-based and MDRD-4 equations, respectively. 
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels.
Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease
Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. 
Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.
 Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.
 Cystatin C was recently reported to be an endogenous surrogate of kidney function, and a high level of cystatin C is reported to be a strong predictor of CVD;
Studies that have simultaneously compared measured GFR and estimated GFR (using endogenous filtration markers such as creatinine, or newer ones such as cystatin C or β-trace protein)

Answer: Yes, cystatin C (CysC) is a  novel biomarker of renal function.
Exact answer: yes
Question: Does Rad9 interact with Aft1 in S.cerevisiae?

Context:
Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae.
Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that 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.
Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast
Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. 
Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that 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.

Answer: 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.
Exact answer: yes
Question: Which is the cellular target of gefitinib?

Context:
Gefitinib, the specific inhibitor of the epidermal growth factor receptor (EGFR), may cause growth delay in cancer cell lines.
Gefitinib (Iressa) is a specific and effective epidermal growth factor receptor inhibitor.
Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) that causes growth delay in cancer cell lines and human tumor xenografts expressing high levels of EGFR.

Answer: The specific cellular target of Gefitinib (Iressa) is the epidermal growth factor receptor (EGFR).
Exact answer: Epidermal growth factor receptor (EGFR)