nirantk/geneticsQA-train huggingface dataset:
Question: Can siRNA affect response to afatinib treatment?

Context:
On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab)
These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR
Among the anti-EGFR agents tested, the strongest biological effect was observed when afatinib was combined with T790M-specific-siRNAs
The combination of a potent, irreversible kinase inhibitor such as afatinib, with T790M-specific-siRNAs should be further investigated as a new strategy in the treatment of lung cancer containing the resistant T790M mutation.
The strongest biological effect was observed when afatinib was combined with an EGFR-specific siRNA
The addition of EGFR siRNA to either TKIs or cetuximab additively enhanced growth inhibition and induction of apoptosis in all five cell lines, independent of the EGFR mutation status (wild-type or sensitizing mutation or resistant mutation).
The combination of a potent, irreversible kinase inhibitor such as afatinib, with EGFR-specific siRNAs should be further investigated as a new strategy in the treatment of lung cancer and other EGFR dependent cancers, including those with downstream resistance mutations.

Answer: When afatinib was combined with an EGFR-specific siRNA there was a strong biological effect on growth inhibition and induction of apoptosis.
Exact answer: yes
Question: What are some common congenital anomalies associated with Mowat-Wilson syndrome, including hypospadias, agenesis of the corpus callosum, and what else?

Context:
 genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. ", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). ", "Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). ", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. ", "However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.", "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).", "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. "]

Answer: Congenital anomalies commonly associated with Mowat-Wilson syndrome include hypospadias, agenesis of the corpus callosum, genitourinary anomalies, congenital heart defects, Hirschsprung disease, and microcephaly.
Question: What is DNAshape?

Context:
DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale.
We present 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/.

Answer: 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/.
Question: Which is the most common genetic lesion among patients with Joubert Syndrome and a cerebello-oculo-renal phenotype?

Context:
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
Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.
Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion
Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. 
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.
Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. We present a Cep290 gene trap mouse model of JBTS that displays the kidney, eye, and brain abnormalities that define the syndrome.
Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.

Answer: 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.
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
Question: What is the mode of action of Hsp90 inhibitors?

Context:
In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose- and time-dependent manner.
In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth.
Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism.
Dicoumarol, a long-established oral anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/Securin gene expression and provokes apoptosis through a complex trait involving both intrinsic and extrinsic pathways.
Dicoumarol activity as an Hsp90 inhibitor is confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of in vivo heat shock luciferase activity recovery assays.
Likewise, established Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress PTTG1/Securin gene expression. 
However, effects on PTTG1/Securin could be partially ascribed to inhibition of the Ras/Raf/extracellular signal-regulated kinase pathway.
To document this field, we have studied two Hsp90 inhibitors (radicicol and geldanamycin), known to interact with the ATP-binding site of Hsp90 (the Bergerat fold),
One of these is the novel agent 17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone. Treatment of four human colon cancer cell lines with iso-effective concentrations of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal transduction.
The expression of hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and caveolin-1 were deregulated following treatment.

Answer: 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.
Question: How does lncRNA Gomafu respond to neuronal activation and what is its role in schizophrenia-related alternative splicing, given its interaction with splicing factors QKI and SRSF1 and its downregulation in post-mortem cortical gray matter from the superior temporal gyrus in SZ?

Context:
The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.
Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.
Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes.
The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing
Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. 
Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. 
The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.

Answer: The long non-coding RNA Gomafu is acutely downregulated in response to neuronal activation. It is involved in schizophrenia-associated alternative splicing by binding directly to the splicing factors QKI and SRSF1. Dysregulation of Gomafu leads to alternative splicing patterns similar to those observed in schizophrenia for genes DISC1 and ERBB4. Additionally, Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in schizophrenia.
Question: What are Degrons?

Context:
Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system.
Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters. 
The N-degrons, a set of degradation signals recognized by the N-end rule pathway, comprise a protein's destabilizing N-terminal residue and an internal lysine residue.
The ubiquitin-proteasome system degrades an enormous variety of proteins that contain specific degradation signals, or 'degrons'.
Degron refers to an amino acid sequence that encodes a protein degradation signal, which is oftentimes a poly-ubiquitin chain that can be transferred to other proteins. 
Degradation signals (degrons) that are targeted by the N-end rule pathway include a set called N-degrons. The main determinant of an N-degron is a destabilizing N-terminal residue of a protein
The N-end rule pathway is a proteolytic system in which destabilizing N-terminal amino acids of short lived proteins are recognized by recognition components (N-recognins) as an essential element of degrons, called N-degrons
The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes
More than 25 years ago, the first degradation signal was discovered and defined as destabilizing N-terminal amino-acid residue (or N-degron) of protein substrates
A protein domain called "degron", which induces rapid proteolysis by the proteasome, can be used for this purpose. Degron-based technologies for the conditional depletion of POI--degron fusion proteins have been developed by exploiting various pathways leading to proteasomal degradation.

Answer: Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system.
Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters.
portable degradation sequences, or degrons, have the ability to bind to e3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters.
Question: What personality traits can be evaluated with the Ten Item Personality Inventory.

Context:
Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory.
The questionnaire measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism.
DESIGN: Adoptive mothers (N = 136) were surveyed for depressive symptoms using the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Edinburgh Postnatal Depression Scale (EPDS). Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory. 
Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory. 

Answer: The Ten Item Personality Inventory measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism.
Exact answer: openness, extroversion, conscientiousness, agreeableness, neuroticism
Question: How are G-quadruplex forming sequences associated with human mitochondrial DNA deletion breakpoints in disease?

Context:
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.
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. 
Currently, the multiple types of GQ sequences and their association with human mtDNA stability are unknown.<br><b>RESULTS</b>: Here, we show an association between human mtDNA deletion breakpoint locations (sites where DNA ends rejoin after deletion of a section) and sequences with G-quadruplex forming potential (QFP), and establish the ability of selected sequences to form GQ in vitro.
A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma.
DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.
Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints.

Answer: G-quadruplex forming sequences are associated with human mitochondrial DNA deletion breakpoints in disease by residing in close proximity (within 20 base pairs) to known deletion breakpoints. Circular dichroism and UV spectral analysis have shown that G-rich sequences near deletion breakpoints form G-quadruplex DNA structures. Nucleotide repeats flanking the deletions are also observed at most analyzed deletion breakpoints. The ability of selected sequences to form G-quadruplexes in vitro has been established, and these structures are inefficiently unwound by the mitochondrial replicative Twinkle helicase.
Question: Describe mechanism of action of PLX3397 drug.

Context:
Following the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia. 
.METHODS: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the autoinhibited conformation.
Treatment with PLX3397, a small molecule inhibitor of the CSF1 receptor CSF1R and related kinases, decreases microglial numbers by promoting microglial apoptosis in both CSF1 overexpressing and control mice.
Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs.
We hypothesized that PLX3397, which inhibits KIT and colony-stimulating-factor-1 receptor (CSF1R), would be more efficacious than imatinib in GIST by also depleting tumor-associated macrophages, which are generally thought to support tumor growth.
The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+) myeloid derived suppressor cells. 
The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397.
In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.
The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397.
In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.
The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. 

Answer: PLX3397 works by inhibiting colony-stimulating-factor-1 receptor (CSF1R).
Question: Which are the coactivators of the Yes-associated protein (yap)?

Context:
ndependent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads.
TEADs on their own are unable to activate transcription and they require the help of coactivators. Several TEAD-interacting coactivators are known and they can be classified into three groups: (1) YAP and its paralog TAZ;
YAP and TAZ are transcription coactivators and effectors of the Hippo pathway, which play a key role in organ size control. Through interaction with transcription factors such as TEADs, they activate gene transcription and thus promote cell proliferation, inhibit apoptosis, and regulate cell differentiation. 
The YAP/TAZ-TEAD complex also upregulates several other proliferation-promoting genes and also promotes anchorage-independent cell proliferation.
hree-dimensional structure of the YAP-TEAD complex

Answer: The Yap protein forms complex with Tead (TEA domain) transcription factors.
Exact answer: Tead (TEA domain) transcription factors.