Given a passage, 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: We compare the effects of postinjury administration of allopregnanolone, a metabolite of progesterone, to progesterone in an animal model of transient middle cerebral artery occlusion.', 'Focal cerebral ischemia was induced in age-matched, adult, male, Sprague-Dawley rats by using an intraluminal filament and suture method to occlude the right middle cerebral artery. After 120 minutes of middle cerebral artery occlusion, the occluding filament was withdrawn to allow reperfusion. Laser-Doppler flowmetry was used to monitor cerebral blood flow for the entire 2-hour period of occlusion and for 5 minutes after reperfusion. Animals subjected to middle cerebral artery occlusion received injections of allopregnanolone (8 mg/kg, n=6), progesterone (8 mg/kg, n=6) and vehicle (2-hydroxypropyl-beta-cyclodextrin, n=7) at 2 hours (intraperitoneally 5 minutes before reperfusion) and 6 hours (subcutaneously) postocclusion. Brains were removed at 72 hours post-middle cerebral artery occlusion, sectioned into coronal slices, and stained with 2,3,5-triphenyltetrazolium chloride (TTC). In a blinded analysis, infarct volume was calculated by using computer-aided morphometry to measure brain areas not stained with TTC.', 'After progesterone or allopregnanolone treatment, stained sections revealed a significant reduction in cortical, caudate-putamen, and hemispheric infarct volumes (percentage of contralateral structure) compared with vehicle-injected controls. Cortical infarction (percentage of contralateral cortex) was 37.47%+/-10.57% (vehicle), 25.49%+/-7.38% (progesterone; P<.05 from vehicle), and 11.40%+/-7.09% (allopregnanolone; P<.05 from vehicle; P<.05 from progesterone). Caudate-putamen infarction (percentage of contralateral caudate-putamen) was 78.02%+/-22.81% (vehicle), 48.41%+/-22.44% (progesterone; P<.05 from vehicle), and 50.44%+/-10.90% (allopregnanolone; P<.05 from vehicle). Total hemispheric infarction (percentage of contralateral hemisphere) was 24.37%+/-6.69% (vehicle), 15.95%+/-3.59% (progesterone; P<.05 from vehicle), and 11.54%+/-3.71% (allopregnanolone; P<.05 from vehicle). No significant differences in cerebral blood flow between groups and time points during ischemia and early reperfusion were observed, suggesting that the relative ischemic insult was equivalent among all groups.

Output: Is allopregnanolone , a progesterone metabolite , more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion?


Input: Consider Input: Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes.', 'Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis.', 'We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects.

Output: Does endoplasmic reticulum stress contribute to beta cell apoptosis in type 2 diabetes?


Input: Consider Input: miR-155 is an oncogenic miRNA that is often overexpressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors, including RAD51, MLH1, and MSH6, and its overexpression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that overexpression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 overexpression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone nonhomologous end-joining pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 overexpression does not resemble that of a mismatch repair-deficient background. Further investigation revealed that all four subunits of polymerase delta, a high-fidelity DNA replication, and repair polymerase are downregulated at the mRNA level in the context of miR-155 overexpression. FOXO3a, a transcription factor and known target of miR-155, has one or more putative binding site(s) in the promoter of all four polymerase delta subunits. Finally, suppression of FOXO3a by miR-155 or by siRNA knockdown is sufficient to repress the expression of the catalytic subunit of polymerase delta, POLD1, at the protein level, indicating that FOXO3a contributes to the regulation of polymerase delta levels.


Output: Does miR-155 Overexpression promote Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-Prone DSB Repair?