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: Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic side effects. Plasma levels of the vasoconstrictor peptide endothelin-1 are increased after cyclosporine administration, and endothelin-1 has been shown to cause renal vasoconstriction. In this study we used in vivo microscopy to investigate the role of endothelin-1 in cyclosporine-induced vasoconstriction.', 'Hydronephrotic kidneys in decerebrate rats were suspended in an environmentally controlled tissue bath with neurovascular supply intact. Interlobular, afferent, and efferent arteriolar diameters and flow were measured by videomicroscopy and Doppler velocimetry. Cyclosporine was added to the tissue bath, and measurements were repeated for 60 minutes. In study groups endogenous endothelin-1 was blocked by infusion of either specific endothelin antiserum or an endothelin-1 receptor antagonist.', 'Cyclosporine caused constriction of the interlobular artery by 20% +/- 2% and a corresponding decrease in blood flow by 66% +/- 4%. The afferent and efferent arterioles constricted to a similar degree. This vasoconstriction was entirely prevented by infusion of either the endothelin antiserum or the receptor antagonist. The antagonist reagents alone had no effect on hemodynamic parameters or renal microvessel diameters.
Answer: The acute renal vasoconstriction induced by cyclosporine is mediated by endothelin-1. Endogenous endothelin-1 has little role in maintaining basal vascular tone.

SOLUTION: Is acute cyclosporine-induced renal vasoconstriction mediated by endothelin-1?

PROBLEM: Context: Is the activity of sirtuin 3 (SIRT3) altered in granulosa and cumulus cells from young women with reduced ovarian reserve or women of advanced maternal age?
Answer: SIRT3 mRNA and active protein in granulosa and cumulus cells were decreased in women with reduced ovarian reserve and advanced maternal age.

SOLUTION: Are mitochondrial SIRT3 and its target glutamate dehydrogenase altered in follicular cells of women with reduced ovarian reserve or advanced maternal age?

PROBLEM: Context: MicroRNAs play an important role in cardiac remodeling. MicroRNA 499 (miR499) is highly enriched in cardiomyocytes and targets the gene for Calcineurin A (CnA), which is associated with mitochondrial fission and apoptosis. The mechanism regulating miR499 in stretched cardiomyocytes and in volume overloaded heart is unclear. We sought to investigate the mechanism regulating miR499 and CnA in stretched cardiomyocytes and in volume overload-induced heart failure.', 'Rat cardiomyocytes grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of volume overload with aorta-caval shunt in adult rats was used to study miR499 expression. Mechanical stretch downregulated miR499 expression, and enhanced the expression of CnA protein and mRNA after 12 hours of stretch. Expression of CnA and calcineurin activity was suppressed with miR499 overexpression; whereas, expression of dephosphorylated dynamin-related protein 1 (Drp1) was suppressed with miR499 overexpression and CnA siRNA. Adding p53 siRNA reversed the downregulation of miR499 when stretched. A gel shift assay and promoter-activity assay demonstrated that stretch increased p53 DNA binding activity but decreased miR499 promoter activity. When the miR499 promoter p53-binding site was mutated, the inhibition of miR499 promoter activity with stretch was reversed. The in vivo aorta-caval shunt also showed downregulated myocardial miR499 and overexpression of miR499 suppressed CnA and cellular apoptosis.
Answer: The miR499-controlled apoptotic pathway involving CnA and Drp1 in stretched cardiomyocytes may be regulated by p53 through the transcriptional regulation of miR499.

SOLUTION:
Does mechanical Stretch inhibit MicroRNA499 via p53 to Regulate Calcineurin-A Expression in Rat Cardiomyocytes?