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.

Input: Consider Input: Context: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8\xa0wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention.', 'Volunteers were supplemented daily with 36\xa0mg/kg body weight (BW) of GAA for the first 4\xa0wk of the intervention; afterward GAA dosage was titrated ≤60\xa0mg/kg BW of GAA daily. At baseline, 4, and 8\xa0wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity.', 'Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4\xa0wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P\xa0<\xa00.05). Thalamus creatine levels decreased after 4\xa0wk for 6.5% (P\xa0=\xa00.02), and increased nonsignificantly after 8\xa0wk for 8% (P\xa0=\xa00.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P\xa0<\xa00.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention.
Answer: Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.

Output: Does dietary guanidinoacetic acid increase brain creatine levels in healthy men?


Input: Consider Input: Context: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.', 'To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.', 'Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.', 'Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.', 'Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.
Answer: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.

Output: Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways?


Input: Consider Input: Context: Only 2\xa0% of the human genome code for proteins. Among the remaining 98\xa0%, transposable elements (TEs) represent millions of sequences. TEs have an impact on genome evolution by promoting mutations. Especially, TEs possess their own regulatory sequences and can alter the expression pattern of neighboring genes. Since they can potentially be harmful, TE activity is regulated by epigenetic mechanisms. These mechanisms participate in the modulation of gene expression and can be associated with some human diseases resulting from gene expression deregulation. The fact that the TE silencing can be removed in cancer could explain a part of the changes in gene expression. Indeed, epigenetic modifications associated locally with TE sequences could impact neighboring genes since these modifications can spread to adjacent sequences.', 'We compared the histone enrichment, TE neighborhood, and expression divergence of human genes between a normal and a cancer conditions. We show that the presence of TEs near genes is associated with greater changes in histone enrichment and that differentially expressed genes harbor larger histone enrichment variation related to the presence of particular TEs.
Answer: Taken together, these results suggest that the presence of TEs near genes could favor important variation in gene expression when the cell environment is modified.


Output: Is the transposable element environment of human genes associated with histone and expression changes in cancer?