instruction:
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.
question:
Context: Our previous studies suggested that brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) axis inhibited cardiomyocyte apoptosis in myocardial infarction (MI). However, the relationship between BDNF and microRNA (miRNA) in cardiomyocytes are unclear. The present study was performed to investigate the role of miR-195 and the interplay between BDNF and miR-195 in ischemic cardiomyocyte apoptosis.', 'Male Wistar rats were subjected to coronary artery ligation, and primary neonatal rat ventricular myocytes were treated with hypoxia or hydrogen peroxide (H2O2). BDNF level in rat ventricles was measured by enzyme linked immunosorbent assay (ELISA). miR-195 mimic, inhibitor or negative control was transfected into the cardiomyocytes. Cell viability and apoptosis were detected by MTT assay and TdT-mediated dUTP nick end labeling (TUNEL) staining, respectively. Cardiac function and apoptosis were detected in MI rats intravenously injected with antagomiR-195. Luciferase assay, Western blot and Real-time RT-PCR were employed to clarify the interplay between miR-195 and BDNF.', 'miR-195 level was dynamically regulated in response to MI and significantly increased in ischemic regions 24 h post-MI as well as in hypoxic or H2O2-treated cardiomyocytes. Meanwhile, BDNF protein level was rapidly increased in MI rats and H2O2-treated cardiomyocytes. Apoptosis in both hypoxic and H2O2-treated cardiomyocytes were markedly reduced and cell viability was increased by miR-195 inhibitor. Moreover, inhibition of miR-195 significantly improved cardiac function of MI rats. Bcl-2 but not BDNF was validated as the direct target of miR-195. Furthermore, BDNF abolished the pro-apoptotic role of miR-195, which was reversed by its scavenger TrkB-Fc.
Answer: Up-regulation of miR-195 in ischemic cardiomyocytes promotes ischemic apoptosis by targeting Bcl-2. BDNF mitigated the pro-apoptotic effect of miR-195 in rat cardiomyocytes. These findings may provide better understanding of the pro-apoptotic role of miR-195 in MI and suggest that BDNF/miR-195/Bcl-2 axis may be beneficial for limiting myocardial ischemic injury.
answer:
Does bDNF-mediates Down-regulation of MicroRNA-195 inhibit Ischemic Cardiac Apoptosis in Rats?


question:
Context: Is weight-training exercise intervention harmful to women with or at risk of breast cancer-related lymphoedema?', 'Systematic review with meta-analysis of randomised trials.', 'Women with or at risk of breast cancer-related lymphoedema.', 'Progressive weight-training exercise.', 'The primary outcomes were severity (volume difference) and incidence of arm lymphoedema. Secondary outcomes included muscle strength of the upper and lower limbs, quality of life and body mass index.', 'Eleven studies from eight trials involving 1091 women were included. Weight-training exercise of low to moderate intensity with relatively slow progression significantly improved the upper limb strength (SMD 0.93, 95% CI 0.73 to 1.12) and lower limb strength (SMD 0.75, 95% CI 0.47 to 1.04) without increasing the arm volume (SMD -0.09, 95% CI -0.23 to 0.05) or incidence of breast cancer-related lymphoedema (RR 0.77, 95% CI 0.52 to 1.15). No significant effects were noted for body mass index (SMD -0.10, 95% -0.31 to 0.11). Some aspects of quality of life may improve with weight training. PARTICIPANTS in all trials used pressure garments and received supervision; no trials used high-intensity weight training.
Answer: Weight training appears to be safe and beneficial in improving limb strength and physical components of quality of life in women with or at risk of lymphoedema. Pressure garments, supervision and limiting the intensity of the weight training may each be important, but this could not be confirmed with this review.
answer:
Is weight training harmful for women with breast cancer-related lymphoedema : a systematic review?


question:
Context: To characterize the functional consequences of disease-associated mutations in the CNGB3 (B3) subunit of human cone photoreceptor cyclic nucleotide-gated channels in order to gain insight into disease mechanisms.', 'Three separate disease-associated mutations were generated in CNGB3: F525N, R403Q, and T383fsX. These mutant subunits were then heterologously expressed in Xenopus oocytes in combination with wild type CNGA3 (A3) subunits, and characterized by patch-clamp recording in the inside-out configuration.', 'Co-expression of A3 and B3F525N, A3 and B3R403Q, or A3 and B3R403Q and B3T383fsX subunits resulted in channels that exhibited an increase in ligand sensitivity without a reduction in current density compared to wild-type heteromeric channels. Each simulated disease state produced channels that exhibited greater sensitivity to block by L-cis-diltiazem than homomeric CNGA3 channels, confirming that the mutant CNGB3 subunits were competent to form functional heteromeric channels. Each combination of subunits displayed an increase in apparent affinity for cGMP relative to wild-type heteromeric channels. However, F525N enhanced cGMP apparent affinity to a significantly greater extent than the other two modeled disease states.
Answer: We have examined the gating effects of two previously uncharacterized disease-associated mutations in the CNGB3 subunit and found that in each case, the mutations resulted in a gain of function molecular phenotype. Furthermore, the magnitude of the effect on channel function correlated with the severity of the associated disease. The complete achromatopsia-associated F525N mutation resulted in more pronounced alterations in channel function than the mutation combinations linked to macular degeneration or progressive cone dystrophy.
answer:

Do disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels?