nirantk/geneticsQA-train huggingface dataset:
Question: How many and which are the different isoforms for the ryanodine receptor?

Context:
Skeletal (RyR1) and cardiac muscle (RyR2) isoforms of ryanodine receptor calcium channels
Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle. RyRs are the largest known ion channels (> 2MDa) and exist as three mammalian isoforms (RyR 1-3),
Ryanodine receptors (RyRs) are a family of intracellular calcium release channels that mediate calcium-induced calcium release from the endoplasmic reticulum. Among the three RyR isoforms, RyR3 is preferentially expressed in the brain especially in the hippocampus and striatum.
In excitable cells such as skeletal and cardiac myocytes excitation-contraction coupling is an important intermediate step between initiation of the action potential and induction of contraction. This process is predominantly controlled by Ca(2+) release from the sarcoplasmic reticulum via the ryanodine receptor. This very large protein (MW 560 kDa) exists as a homotetramer (~2.2 MDa) and is expressed in three isoforms: RyR1, expressed in skeletal muscle; RyR2, expressed in cardiac muscle; and RyR3, expressed in various cells at lower levels than the other isoforms. 
Generally, three ryanodine receptor isoforms (RyR1-RyR3) are known; 
Ryanodine receptor (RyR) is a Ca(2+) channel that mediates Ca(2+) release from intracellular stores.
There are three RyR isoforms,
Ryanodine receptors (RyRs) are intracellular Ca(2+) channels that mediate the release of calcium from internal stores and therefore play an important role in Ca(2+) signaling and homeostasis. Three RyR isoforms have been described thus far,
RyR1 and RyR2
RyR3
Three different isoforms of the SR Ca2+ release channels, or ryanodine receptors (RyRs), have been isolated (RyR1, RyR2, and RyR3).

Answer: 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.
Exact answer: Ryanodine Receptor type 1, RyR1, Ryanodine Receptor type 2, RyR2, Ryanodine Receptor type 3, RyR3
Question: What disease in Loxapine prominently used for?

Context:
To describe the frequency and trends in the use of antipsychotics for adults with schizophrenia in Canada from 2005 to 2009.
Antipsychotic recommendations were estimated using CDTI data in which schizophrenia was listed as the indication. RESULTS: First-generation antipsychotic (FGA) recommendations for adults with schizophrenia increased by 38% between 2005 and 2009, from 329 380 to 454 960 recommendations. There were notable increases in recommendations for chlorpromazine, loxapine, zuclopenthixol, and flupentixol.
Loxapine has been prescribed in France since 1980. Its pharmacological profile is close to that of clozapine: it has dopamine (D2), histamine (H1), serotonin (5-HT2) and adrenergic (alpha 1)-blocking activities. Its best indication seems to be paranoid schizophrenia, although some data suggest bipolar action.

Answer: The best indication of loxapine is paranoid schizophrenia.
Exact answer: schizophrenia
Question: Which calcium channels does ethosuximide target?

Context:
In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity.
In rats, intraplantar (i.pl.) administration of db-cAMP or PGE(2)  caused mechanical hyperalgesia, an effect suppressed by AKAPI, two distinct T-channel blockers, NNC 55-0396 and ethosuximide, or ZnCl(2) , known to inhibit Ca(v) 3.2 among T channels.
Theta rhythms remained disrupted during a subsequent week of withdrawal but were restored with the T-type channel blocker ethosuximide.
Given evidence that chemotherapy-induced neuropathic pain is blocked by ethosuximide, known to block T-type calcium channels, we examined if more selective T-type calcium channel blockers and also inhibitors of cystathionine-γ-lyase (CSE), a major H₂S-forming enzyme in the peripheral tissue, are capable of reversing the neuropathic pain evoked by paclitaxel, an anti-cancer drug.
The results demonstrate that both ethosuximide and the active metabolite of methsuximide, alpha-methyl-alpha-phenylsuccinimide (MPS), block human T-type channels in a state-dependent manner, with higher affinity for inactivated channels.
T-type channels display current at the end of long pulses (persistent current), and this current was especially sensitive to block (ethosuximide IC(50) = 0.6 mM).
We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor.
The antihyperalgesic effects of the T-type calcium channel blockers ethosuximide, trimethadione, and mibefradil.
Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison.
The Ca(v)3.2 channel is sensitive to ethosuximide, amlodipine and amiloride.
The purpose of the present study was to explore the analgesic effects of the low voltage-activated T-type Ca2+ channel blockers ethosuximide, trimethadione, and mibefradil in persistent and acute nociceptive tests.
We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor. 
We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. 
Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison. 

Answer: Ethosuximide blocks the T-type calcium channels.
Exact answer: T-type calcium channels
Question: Which is the vector of Louping ill virus?

Context:
Deer are the key hosts of the vector (Ixodes ricinus) that transmits LIV to red grouse Lagopus lagopus scoticus, causing high mortality.
n Europe the primary arthropod vectors of zoonotic diseases are ticks, which transmit Borrelia burgdorferi sensu lato (the agent of Lyme disease), tick-borne encephalitis virus and louping ill virus between humans, livestock and wildlife. Ixodes ricinus ticks and reported tick-borne disease cases are currently increasing in the UK
Many vector-borne pathogens whose primary vectors are generalists, such as Ixodid ticks, can infect a wide range of host species and are often zoonotic.
Tick-borne encephalitis virus (TBEV) and Louping ill virus (LIV) are viruses in the Mammalian tick-borne virus group/genus Flavivirus, causing central nervous system disease.
The complex pathogen-host-vector system of the tick-borne louping-ill virus causes economic losses to sheep and red grouse in upland United Kingdom.
For pathogens transmitted by biting vectors, one of the fundamental assumptions is often that vector bites are the sole or main route of host infection. Here, we demonstrate experimentally a transmission route whereby hosts (red grouse, Lagopus lagopus scoticus) became infected with a member of the tick-borne encephalitis virus complex, louping ill virus, after eating the infected tick vector.
We used Susceptible Infected Recovered (SIR) models parameterized for the tick-borne louping ill virus (LIV) system.
This study has examined the efficacy following intramuscular administration of a recombinant Semliki Forest virus (rSFV) vaccine, encoding the prME and NS1 proteins of louping ill virus (LIV), in sheep.
Since the recognition that louping-ill, known for well over 100 years as an epizootic disease of sheep in Scotland, was caused by a virus transmitted by arthropods, many other arthropod-borne viruses capable of causing encephalitis in domestic animals or man have been discovered.

Answer: 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.
Deer are the key hosts of the vector (Ixodes ricinus) that transmits LIV to red grouse Lagopus lagopus scoticus, causing high mortality. (PMID: 22939093)
Exact answer: Ixodes ricinus
Question: Are circRNAs associated with diseases and traits?

Context:
Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits.
Circular RNAs 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.
Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated
Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases
In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated.
Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes.

Answer: 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.
Exact answer: yes
Question: Are there any urine biomarkers for chronic kidney disease?

Context:
Kidney and urine proteomic biomarkers are considered as promising diagnostic tools to predict CKD progression early in diabetic nephropathy, facilitating timely and selective intervention that may reduce the related health-care expenditures.
Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes.
Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress.
There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality.
Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper.
Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease.

Answer: 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.
Yes, there is a number of urine biomarkers used for early detection of chronic kidney disease.
Exact answer: yes
Question: Which compound is a specific inhibitor for Nox1 and Nox4?

Context:
The efficacy of the Nox1/Nox4 inhibitor GKT137831 on the manifestations of DN was studied in OVE26 mice, a model of type 1 diabetes. 
At both doses, GKT137831 inhibited NADPH oxidase activity, superoxide generation, and hydrogen peroxide production in the renal cortex from diabetic mice without affecting Nox1 or Nox4 protein expression
GKT136901, a specific inhibitor of Nox1- and Nox4-containing NADPH oxidase activity, attenuated ROS generation and atherosclerosis and decreased CD44 and HA expression in atherosclerotic lesions. 
Basal NAD(P)H oxidase activity was blocked by GKT136901 (Nox1/4 inhibitor) and by Nox1 siRNA in WKY cells and by siNOX1 and siNOX2 in SHR.
GKT136901, a specific inhibitor of Nox1- and Nox4-containing NADPH oxidase activity, attenuated ROS generation and atherosclerosis and decreased CD44 and HA expression in atherosclerotic lesions
Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion
The efficacy of the Nox1/Nox4 inhibitor GKT137831 on the manifestations of DN was studied in OVE26 mice, a model of type 1 diabetes
Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion. 

Answer: GKT136901 is a specific inhibitor of Nox1 and Nox4.
Exact answer: GKT136901
Question: How do high-risk HPVE6 proteins affect Ubc9 and host sumoylation in rat intervertebral disc cells?

Context:
 protein sumoylation.", "We report that the high risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO conjugation enzyme, Ubc9, concomitant with decreased host sumoylation.", "We observed steady-state expression of SUMO1-3, SUMO-conjugated enzyme-UBC9 and deSUMOylating enzymes - SENPs, throughout normal gestation.", "As the sole E2 enzyme for SUMOylation, Ubc9 is predominantly nuclear.", "Expression of small ubiquitin-like modifier (SUMO) molecules, SUMO E1 activating enzymes SAE1 and SAE2, SUMO E2 conjugating enzyme UBC9, and de-sumoylation enzyme sentrin/SUMO-specific proteases (SENP)1 was immunolocalized in rat intervertebral disc (IVD) cells."]
 protein sumoylation.", "We report that the high risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO conjugation enzyme, Ubc9, concomitant with decreased host sumoylation.", "We observed steady-state expression of SUMO1-3, SUMO-conjugated enzyme-UBC9 and deSUMOylating enzymes - SENPs, throughout normal gestation.", "As the sole E2 enzyme for SUMOylation, Ubc9 is predominantly nuclear.", "Expression of small ubiquitin-like modifier (SUMO) molecules, SUMO E1 activating enzymes SAE1 and SAE2, SUMO E2 conjugating enzyme UBC9, and de-sumoylation enzyme sentrin/SUMO-specific proteases (SENP)1 was immunolocalized in rat intervertebral disc (IVD) cells."]

Answer: The high-risk HPVE6 proteins reduce the intracellular quantity of the sole SUMO conjugation enzyme, Ubc9, concomitant with decreased host sumoylation in rat intervertebral disc cells.
Question: How does dronedarone affect thyroid hormone signaling in the heart?

Context:
Administration of debutyl-dronedarone (DBD), a TRα1 antagonist abolished the T3-limiting effect on reperfusion injury:
Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%.
In the LVW, AM and Dron decreased TRbeta 1
Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1),
dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism.
The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.
Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals.

Answer: Dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor and selectively mimicks hypothyroidism.
Dronedarone  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.
Question: What is the enzymatic activity of PARL?

Context:
Here we demonstrate that the mitochondrial protease presenilin-associated rhomboid-like (PARL) can affect the proteolytic processing of PINK1 and that normal PINK1 localization and stability requires PARL's catalytic activity. 
The mitochondrial rhomboid protease Parl governs apoptosis, morphology, metabolism and might be implicated in Parkinson's disease, but the structural basis of its activity and complex regulation remain unknown.
. In this study, we evaluated the mRNA levels of presenilins-associated rhomboid-like protein (PARL) and mitochondrial content and enzyme activity from skeletal muscle isolated from insulin-resistant rats.
Rhomboids are a recently discovered family of widely distributed intramembrane serine proteases. 

Answer: the mitochondrial protease presenilin-associated rhomboid-like (PARL). Rhomboids are a recently discovered family of widely distributed intramembrane serine proteases.
Exact answer: PARL are serine proteases
Question: Does thyroid hormone signaling affect microRNAs expression in the heart?

Context:
e show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a.
On the other hand, T₃ treatment increased miR-350 expression.
Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor β1 (TRβ1), which negatively regulates β-MHC transcription, as a target of miR-27a
hese findings suggested that miR-27a regulates β-MHC gene expression by targeting TRβ1 in cardiomyocytes.
We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism.
Moreover, miR-27a was demonstrated to modulate β-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with β-MHC gene upregulation.

Answer: YES
Exact answer: yes
Question: What are the current treatments for generalised anxiety disorder in teenagers?

Context:
49.3% of the youths with depression had comorbid conditions: anxiety disorders in 23.37% of cases
To evaluate the feasibility and effectiveness of a school-based group cognitive-behavioral treatment (CBT) for anxiety disorders with African-American adolescents. METHODS: Twelve adolescents (mean age = 15.6 years) with anxiety disorders were randomly assigned to CBT (n = 6) or a group attention-support control condition
At posttreatment and among those who attended more than one treatment session, 3/4 adolescents in CBT no longer met diagnostic criteria for their primary anxiety disorder, compared with 1/5 in AS-Control. Clinician ratings of impairment and self-report levels of overall anxiety were significantly lower at posttreatment in CBT compared with AS-Control
The present study compares an individual versus a group format in the delivery of manualised cognitive-behavioural therapy (FRIENDS) for children with anxiety disorders. Clinically referred children (aged 8 to 12) diagnosed with Separation Anxiety Disorder (n = 52), Generalised Anxiety Disorder (n = 37), Social Phobia (n = 22) or Specific Phobia (n = 16) were randomly assigned to individual (n = 65) or group (n = 62) treatment.
Forty-eight percent of the children in the individual versus 41% in the group treatment were free of any anxiety disorder at post-treatment; 62% versus 54% were free of their primary anxiety disorder. Regression analyses showed no significant difference in outcome between individual and group treatment
Children improved in both conditions. Choice between treatments could be based on pragmatic considerations such as therapeutic resources, referral rates, and the preference of the parents and the child.
All child anxiety disorders were associated with several forms of anxiety disorder in the mother. Some specificity in the form of anxiety disorder in the child and the mother was apparent for social phobia and separation anxiety disorder. The findings have implications for the management of child anxiety.

Answer: Cognitive-behavioral treatment (CBT) - both in individual and in group treatment
Randomised, placebo controlled trials have found Sertraline efficacious for GAD in adults, children and adolescents.
While both CBT and SSRIs are beneficial, some evidence suggests that the effects of CBT may be more long lasting.
Exact answer: Cognitive-behavioral treatment (CBT)
CBT
group treatment
manualised cognitive-behavioural therapy, FRIENDS
Sertraline
SSRI
Question: Is exome sequencing efficient for the detection of germline mutations?

Context:
Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas
Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations.
These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology.
We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor.
whole-exome sequencing has been widely applied in the identification of germline mutations underlying Mendelian disorders, somatic mutations in various cancers and de novo mutations in neurodevelopmental disorders.

Answer: Exome sequencing is an efficient, sensitive, rapid and relatively cheap method for detection of germline mutations.
Exact answer: yes