nirantk/geneticsQA-train huggingface dataset:
Question: What are the side effects of Nalmefene?

Context:
Adverse experiences included nausea, dizziness, and insomnia.
Side effects to nalmefene were of greater duration and intensity in the subjects receiving 10 mg of nalmefene vs. those receiving 6 or 2 mg. These included most notably fatigue, lightheadedness, nausea and vomiting.
The nalmefene treated group ate 22% less, both in terms of absolute weight and caloric intake, of a standardised buffet-meal than did the placebo group. 
Thus the apparent nutrient specificity of nalmefene appeared to be an indirect consequence of its effect on palatability. Nalmefene also caused slight increases in self-rated alertness, and decreases in ratings of tiredness and elation, although it was thought unlikely that these accounted for observed changes in eating behaviour.
In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.
 In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. 
Doses of nalmefene as large as 0.4 mg/kg, IV, produced only minor side effects. These side effects included some passage of semifluid fecal material, intermittent penile relaxation, and mild sedation. Treated horses responded normally to external stimuli, retained their appetites, and performed appropriately when ridden. Sedation wore off during the course of prolonged infusions. 
The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness.

Answer: 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.
Exact answer: nausea
dizziness / lightheadedness
insomnia
fatigue
vomiting
reduced caloric intake / apetite
increased self-rated alertness
decreased tiredness
(horses) some passage of semifluid fecal material
(horses) intermittent penile relaxation
(horses) mild sedation
Question: What is the role of thymidine phosphorylase inhibitor in TAS-102, a novel nucleoside antitumor agent?

Context:
PURPOSE: Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor).
TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models.
TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5. 
PURPOSE: TAS-102 is an orally administered anticancer agent composed of α,α,α-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). 
Novel DNA synthesis inhibitors for the treatment of gastrointestinal malignancies include a combination of the antimetabolite TAS-102, which consists of trifluorothymidine with a thymidine phosphorylase inhibitor, and a novel micellar formulation of cisplatin NC-6004 that uses a nanotechnology-based drug delivery system. 
Repeated oral dosing of TAS-102 confers high trifluridine incorporation into DNA and sustained antitumor activity in mouse models.
TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine (FTD) and tipiracil hydrochloride (TPI).

Answer: The thymidine phosphorylase inhibitor in TAS-102, a novel nucleoside antitumor agent, is designed to inhibit the enzyme thymidine phosphorylase, which helps increase the concentration of trifluridine in the tumor cells by preventing its breakdown. This leads to enhanced antitumor activity.
Question: 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?

Context:
he Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling.
In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase.
Signaling pathways have become a major source of targets for novel therapies in hepatocellular carcinoma (HCC). Survival benefits achieved with sorafenib, a multikinase inhibitor, are unprecedented and underscore the importance of improving our understanding of how signaling networks interact in transformed cells.
Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease
(PSEN1) is the major locus for mutations causing familial Alzheimer's disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and many other signalling pathways and protein cleavage events including production of the Amyloidβ (Aβ) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN (APP
As beta-APP and Notch are both processed by gamma-secretase, we analyzed expression of the Notch signaling pathway in the adult DS brain and in a model system for DS, human trisomy 21 fibroblasts by quantitative PCR. In adult DS cortex we found that Notch1, Dll1 and Hes1 expression is up-regulated. Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes
A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging
Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Answer: 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.
Exact answer: yes
Question: What organism causes tularemia?

Context:
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
Tularemia is a zoonosis caused by Francisella tularensis that can be transmitted by several ways to human being and cause different clinical manifestations
Tularemia is a bacterial zoonotic disease that is caused by Francisella tularensis and among the infectious reasons that cause fever of unknown origin (FUO) in children
The bacterium Francisella tularensis causes the vector-borne zoonotic disease tularemia, and may infect a wide range of hosts including invertebrates, mammals and birds
Francisella tularensis, the Gram-negative bacterium that causes tularemia, is considered a potential bioterrorism threat due to its low infectivity dose and the high morbidity and mortality from respiratory disease
Francisella tularensis causes disease (tularemia) in a large number of mammals, including man
The tularemia-causing bacterium Francisella tularensis is a facultative intracellular organism with a complex intracellular lifecycle that ensures its survival and proliferation in a variety of mammalian cell types, including professional phagocytes.
Francisella tularensis is a highly virulent bacterium that causes tularemia, a disease that is often fatal if untreated.
Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease.
Tularemia, caused by the bacterium Francisella tularensis, where F.

Answer: 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. 
francisella tularensis, the agent of tularemia, is a gram-negative coccobacillus primarily pathogen for animals and occasionally for humans.
Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. 
Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans.
Exact answer: Francisella tularensis
Question: Describe clinical manifestation of the Mal de debarquement syndrome.

Context:
Mal de debarquement (MdD) is a subjective perception of self-motion after exposure to passive motion, in most cases sea travel, hence the name. Mal de debarquement occurs quite frequently in otherwise healthy individuals for a short period of time (several hours). However, in some people symptoms remain for a longer period of time or even persist and this is then called mal de debarquement syndrome (MdDS).
OBJECTIVE: Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. 
Mal de debarquement syndrome (MdDS) is a rare and poorly understood condition of perceived continual motion.
BACKGROUND: 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. 
It is characterized by abnormal sensation of motion/balance reported after travel by air, land, and sea; being reexposed to motion/activity relieves it. Symptoms may last from minutes to years. 
Persistent mal de debarquement syndrome: a motion-induced subjective disorder of balance.
Mal de debarquement syndrome (MdDS) is a disorder of phantom perception of self-motion of unknown cause. 
Mal de debarquement (MDD) is a common, benign, and self-limited syndrome suffered by many people after disembarkation from an oceangoing vessel.
Persistent mal de debarquement syndrome: a motion-induced subjective disorder of balance.

Answer: 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.
Question: Does amiodarone affect thyroid hormone receptors in the myocardium?

Context:
AM and 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 and, interestingly, AM increased TRalpha 1.
n the apex, AM also increased TRalpha 2.
Both in treated and untreated mice, TRalpha2 mRNA had the highest density in mouse heart, whereas TRbeta2 mRNA had the lowest density. Amiodarone dose-dependently downregulated the levels of TRalpha1 and beta1 mRNA in comparison to the control.
amiodarone subtype selectively downregulates the TR mRNA levels in mouse myocardium in a dose-dependent manner.
Western blot analysis revealed no change in the expression of the ThR protein.
Amiodarone and T3, respectively, downregulated T3R alpha 1, T3R beta 1, T3R beta 2 (p < 0.05), but did not affect the levels of T3R alpha 2. Amiodarone and T3, added together, upregulated T3R alpha 2 and T3R beta 1 (p < 0.05) as compared to amiodarone or T3 alone.

Answer: Yes
Exact answer: yes
Question: How does ranolazine affect kinase signaling activation in the heart?

Context:
support of this view, CaMKII activity was also increased in hearts of transgenic mice overexpressing a gain-of-function Na(v)1.5 mutant (N(1325)S). The effects of both ATX-II and the N(1325)S mutation were reversed by either I(NaL) inhibition (with ranolazine or tetrodotoxin) or CaMKII inhibition (with KN93 or autocamtide 2-related inhibitory peptide).
Such changes were related to enhanced Ca(2+)/calmodulin kinase II (CaMKII) activity and increased phosphorylation of its targets. Ranolazine at therapeutic concentrations partially reversed the HCM-related cellular abnormalities via I(NaL) inhibition, with negligible effects in controls. By shortening the action potential duration in HCM cardiomyocytes, ranolazine reduced the occurrence of early and delayed afterdepolarizations. Finally, as a result of the faster kinetics of Ca(2+)(i) transients and the lower diastolic Ca(2+)(i), ranolazine accelerated the contraction-relaxation cycle of HCM trabeculae, ameliorating diastolic function.

Answer: Ranolazine inhibits Ca(2+)/calmodulin kinase II (CaMKII) activity
Question: What is the minimal genome build?

Context:
As a key focus of synthetic biology, building a minimal artificial cell has given rise to many discussions. A synthetic minimal cell will provide an appropriate chassis to integrate functional synthetic parts, devices and systems with functions that cannot generally be found in nature. The design and construction of a functional minimal genome is a key step while building such a cell/chassis since all the cell functions can be traced back to the genome. 
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. 
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. 
Minimal bacterial gene set comprises the genetic elements needed for survival of engineered bacterium on a rich medium. This set is estimated to include 300-350 protein-coding genes. One way of simplifying an organism with such a minimal genome even further is to constrain the amino acid content of its proteins. 
A central undertaking in synthetic biology (SB) is the quest for the 'minimal genome'. However, 'minimal sets' of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack of consensus in the field as to what attributes make a gene truly essential adds another aspect of variation. Thus, a universal minimal genome remains elusive.
The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the last universal common ancestor, as few genes trace back to this hypothetical ancestral state. 

Answer: 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.
Question: What is the indication of Daonil (Glibenclamide)?

Context:
Metformin and glibenclamide are now increasingly viewed as a rational alternative to insulin therapy--a treatment both preferred by the women and a less expensive one, during pregnancy and breastfeeding.
The effect of TFG on blood glucose were studied and the levels of lipid peroxidation [MDA (Malondialdehyde)] and antioxidant enzymes [SOD (Superoxide dismutase), GPx (Reduced Glutathione peroxidase)] were estimated and compared with standard drugs glibenclamide and insulin.
Treatment with TFG, insulin and glibenclamide resulted in significantly reduced blood glucose in LM (8.71%) and HM (3.87%) in comparison with normal controls.
Potency of TFG in restoring several parameters to normal values is comparable to glibenclamide, though not as efficient as insulin, an indication of its antihyperglycemic and antioxidant effect.
However, dietary supplementation with PB (6 g/kg extract for 4 weeks administered orally using an intragastric tube) ameliorated the alloxan-induced diabetes in a manner comparable with that of the reference antidiabetic drug glibenclamide
Moreover, the potassium-specific effects of both diazoxide and nicorandil on oxidative phosphorylation in skeletal muscle mitochondria were completely abolished by the antidiabetic sulfonylurea derivative glibenclamide, a well-known inhibitor of ATP-regulated potassium channels (K(ATP) channels).
In mild NIDDM, gliclazide, tolbutamide or acetohexamide is used, and in more severe NIDDM glibenclamide is used.
An improvement of the glucose tolerance could be observed up to 3 years, whereas after a 5-year glibenclamide therapy no certain influence on the glucose tolerance and insulin secretion could be proved.
In general the improvement of the glucose tolerance was not associated with an increased secretion of insulin, so that an extrapancreatic effect of glibenclamide (improvement of the peripheral insulin sensitivity?) seems to be possible.
From clinical and practical point of view the findings would support the opinion that normal weight persons with IGT, particularly in already decreased insulin secretion, have an indication for a glibenclamide therapy.

Answer: Glibenclamide is an antidiabetic and antiglycemic, used in severe NIDDM, and increasingly viewed as a rational alternative to insulin therapy.
Exact answer: Diabetes mellitus
Question: Where is the protein slitrk1 localized?

Context:
Slitrk1 is localized to excitatory synapses
 Slitrk1 is enriched in postsynaptic fractions and is localized to excitatory synapses.
 The porcine SLITRK1 gene is expressed exclusively in brain tissues.
Six family members exist (Slitrk1-6) and all are highly expressed in the central nervous system (CNS).

Answer: Slitrk1 is enriched in postsynaptic fractions and is localized to excitatory synapses.
Question: What is the oldest human sample analysed by paleontology proteomics?

Context:
Paleoproteomic study of the Iceman's brain tissue.
We report the first use of shotgun proteomics to detect the protein expression profile of buccal swabs and cloth samples from two 500-year-old Andean mummies.
Identification of ancient biological samples from the 1991-discovered and more than 5300-year-old Tyrolean mummy, also called iceman or Oetzi, is very difficult. T
To determine whether a 2,700-year-old tumor can be reliably diagnosed using microscopic and proteomic techniques 

Answer: The Tyrolean Iceman's brain is the oldest (5300 years old) human sample that has been studied by paleoproteomics.
Question: How do protein misfolding and aggregation contribute to neurodegenerative disorders like ALS, PD, and AD?

Context:
Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD).
Human Hsp70 Disaggregase Reverses Parkinson's-Linked α-Synuclein Amyloid Fibrils.
Disaggregases, molecular chaperones that resolubilize protein aggregates.
The structural basis by which Hsp104 dissolves disordered aggregates and prions is unknown.

Answer: Protein misfolding and aggregation contribute to neurodegenerative disorders like ALS, PD, and AD by causing common and fatal conditions that urgently require therapeutic agents. These disorders are linked to the misfolding and aggregation of proteins, leading to issues such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD).
Question: Are defects in recombination repair involved in carcinogenesis?

Context:
Inherited mutations in genes involved in HR are associated with gene rearrangement and may be a prerequisite for tumor development in some cancer-prone hereditary diseases like Bloom, Werner and Rothmund-Thomson syndromes. 
Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. 
Although alcohol consumption is related to increased cancer risk, its molecular mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA), the first product of ethanol metabolism, is believed to be responsible for DNA damage induced by alcohol. 
Although efficiency of these repair processes substantially decrease the efficacy of cancer chemotherapies that target DNA, compromised DNA repair contributes to mutagenesis and genomic instability leading to carcinogenesis.
damage response and repair pathways are important barriers to carcinogenesis. 
olymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely documented. For colorectal cancer, the loss of mismatch repair gene activity is a key genetic determinant. Nucleotide excision repair (NER), recombination repair (RR) and base excision repair (BER) pathways have critical roles in protection against other cancers, and we wished to investigate their role in colorectal cancer. 

Answer: Yes. The breast cancer-associated BRCA1 and BRCA2 proteins are strongly implicated in recombination repair.
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.
Carcinogenesis 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.
Exact answer: yes