TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: Allopregnanolone (ALLO) is a physiologically relevant neurosteroid modulator of GABA(A) receptors, and it exhibits a psychopharmacological profile that closely resembles the post-ingestive effects of ethanol. The 5alpha-reductase inhibitor finasteride (FIN), which inhibits biosynthesis of ALLO and structurally related neurosteroids, was previously demonstrated to reduce the maintenance of limited-access ethanol consumption. The primary aim of the current work was to determine whether FIN would reduce the acquisition of drinking in ethanol-naïve mice.', 'Male C57BL/6J (B6) mice were acclimated to a reverse light/dark schedule, and were provided ad libitum access to chow and water. Following habituation to vehicle injections (VEH; 20% w/v beta-cyclodextrin; i.p.) administered 22-hour prior to drinking sessions with water only, mice were divided into 3 treatment groups: vehicle control (VEH), 50 mg/kg FIN (FIN-50), and 100 mg/kg FIN (FIN-100). Twenty-two hours after the first treatment, mice were permitted the inaugural 2-hour limited access to a 10% v/v ethanol solution (10E) and water. The acquisition of 10E consumption and underlying drinking patterns were assessed during FIN treatment (7 days) and subsequent FIN withdrawal (13 days) phases.', 'FIN dose-dependently blocked the acquisition of 10E drinking and prevented the development of ethanol preference, thereby suggesting that the GABAergic neurosteroids may be important in the establishment of stable drinking patterns. FIN-elicited reductions in 10E intake were primarily attributable to selective and marked reductions in bout frequency, as no changes were observed in bout size, duration, or lick rates following FIN treatment. FIN-treated mice continued to exhibit attenuated ethanol consumption after 2 weeks post-treatment, despite a full recovery in brain ALLO levels. A second study confirmed the rightward and downward shift in the acquisition of ethanol intake following 7 daily FIN injections. While there were no significant group differences in brain ALLO levels following the seventh day of ethanol drinking, ALLO levels were decreased by 28% in the FIN-50 group.
Answer: Although the exact mechanism is unclear, FIN and other pharmacological interventions that modulate the GABAergic system may prove useful in curbing ethanol intake acquisition in at-risk individuals.

SOLUTION: Does inhibition of 5alpha-reduced steroid biosynthesis impede acquisition of ethanol drinking in male C57BL/6J mice?

PROBLEM: Context: The orphan G protein-coupled receptor (GPR) 39 was originally identified as the receptor of obestatin. In this study, the effects and mechanisms of GPR39 on cell proliferation and differentiation were investigated in cultured porcine intramuscular preadipocytes.', 'Morphology of preadipocytes and accumulated lipid droplets within cells were identified by an inverted microscope. After transfected with constructed pCMV-GPR39 plasmid, cell proliferation was measured by using methyl thiazolyl tetrazolium method, mRNA expression of GPR39, CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), Caspase-9 and adipocyte determination and differentiation factor-1 (ADD1) was determined by RNA preparation and reverse transcription polymerase chain reaction, protein expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1, phosphorylated glycogen synthase kinase 3 (pGSK3), total Akt and phosphorylated Akt (pAkt) was analyzed by Western blot.', 'It found that GPR39 mRNA and protein were expressed in porcine intramuscular preadipocytes and its expression was significantly up-regulated after treatment with Zn(2+) whose function is found to be mediated by GPR39. Furthermore, over-expression of GPR39 further promoted the optical density value of cells, enhanced mRNA expression of PPARγ, C/EBPα and ADD1, and inhibited mRNA expression of Caspase-9. Protein expression of pGSK3 and pAkt was also increased by GPR39 stimulation. In addition, GPR39-induced proliferation and differentiation of porcine intramuscular preadipocytes was partially blocked by the Akt inhibitor (PDTC) and the PI3K inhibitor (LY294002).
Answer: It indicated that GPR39 was a transducer of Zn(2+), and enhanced proliferation and differentiation of porcine intramuscular preadipocytes through activation of the PI3K/Akt signaling pathway.

SOLUTION: Does gPR39 activate proliferation and differentiation of porcine intramuscular preadipocytes through targeting the PI3K/AKT cell signaling pathway?

PROBLEM: Context: Annual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses.', "It has been shown elsewhere that mutations introduced in the non-coding region of influenza genome segments can upregulate protein expression. Our objective was to assess a virus based on the laboratory strain A/PR/8/34 (PR8) containing a modified 3' non-coding region of RNA segment 4 (haemagglutinin).", 'NIBRG-93 was generated using reverse genetics. HA protein expression and growth properties were assessed. The virus phenotype suggested that it could be a candidate for use as a live attenuated vaccine, so in vivo studies were performed to assess its suitability.', "NIBRG-93 virus has enhanced haemagglutinin production and is significantly attenuated. Electron microscopy (EM) shows that the modified virus produces a large proportion of 'virus-like particles' that consist of budded cell membrane covered in HA but lacking M1 protein. The virus was shown to be attenuated in mice and offered complete protection against lethal challenge.
Answer: We demonstrate that NIBRG-93 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.

SOLUTION:
Does a promoter mutation in the haemagglutinin segment of influenza A virus generate an effective candidate live attenuated vaccine?