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: In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice.', 'We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level.', 'U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction.
Answer: Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood.

SOLUTION: Is low birth weight associated with adiposity , impaired skeletal muscle energetics and weight loss resistance in mice?

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-naive 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: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. Increased understanding of the pathogenesis is necessary. Amyloid-beta (Abeta), a major extracellular deposit in Alzheimer's disease plaques, has recently been found in drusen, the hallmark extracellular deposit in AMD. The goal of this study was to characterize the distribution and frequency of Abeta deposits in drusen from AMD and normal post mortem human retinas to gain additional insight about the potential role of Abeta in AMD patho genesis.", 'Immunocytochemistry was performed with three Abeta antibodies on sections from 9 normal and 9 AMD (3 early, 3 geographic atrophy, 3 exudative AMD) retinas. Five sections from each eye were evaluated. Abeta positive deposits in drusen were identified using epifluorescence and confocal microscopy. Antibodies were pre-adsorbed with Abeta peptide to verify specificity. Some sections were stained with PAS-hematoxylin to aid in evaluation of morphology.', "To test and optimize immunocytochemistry, Abeta was detected in amyloid plaques from Alzheimer's brains. Abeta label was blocked by pre-adsorption of antibody with Abeta peptide, verifying specificity. Four of the 9 AMD retinas and none of the 9 normal retinas had Abeta positive drusen. Two of the early AMD eyes had a few A[beta] positive drusen, each with a few Abeta-containing vesicles, and 2 of the geographic atrophy (GA) eyes had many Abeta positive drusen with many Abeta containing vesicles.
Answer: Abeta was present in 4 of 9 AMD eyes. Within these eyes, Abeta localized to a subset of drusen. None of the 9 normal eyes surveyed, some of which had small drusen, were A beta positive. Abetapositive vesicles were most numerous in GA eyes at the edges of atrophy, the region at risk for further degeneration. These results suggest that Abeta in drusen correlates with the location of degenerating photoreceptors and retinal pigment epithelium (RPE) cells. Further work will be necessary to determine whether Abeta deposition in drusen may contribute to or result from retinal degeneration.

SOLUTION:
Is amyloid-beta found in drusen from some age-related macular degeneration retinas , but not in drusen from normal retinas?