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.

[EX Q]: Context: The endosteum of the bone marrow provides a specialized hypoxic niche that may serve to preserve the integrity, pluripotency, longevity and stemness of resident mesenchymal stem cells (MSCs). To explore the molecular genetic consequences of such a niche we subjected human (h) MSCs to a pO2 of 4 mmHg and analyzed global gene expression and alternative splicing (AS) by genome-exon microarray and RT-qPCR, and phenotype by western blot and immunostaining.', 'Out of 446 genes differentially regulated by >2.5-fold, down-regulated genes outnumbered up-regulated genes by 243:203. Exon analyses revealed 60 hypoxia-regulated AS events with splice indices (SI) >1.0 from 53 genes and a correlation between high SI and degree of transcript regulation. Parallel analyses of a publicly available AS study on human umbilical vein endothelial cells (HUVECs) showed that there was a strong cell-specific component with only 11 genes commonly regulated in hMSCs and HUVECs and 17 common differentially spliced genes. Only 3 genes were differentially responsive to hypoxia at the gene (>2.0) and AS levels in both cell types. Functional assignments revealed unique profiles of gene expression with complex regulation of differentiation, extracellular matrix, intermediate filament and metabolic marker genes. Antioxidant genes, striated muscle genes and insulin/IGF-1 signaling intermediates were down-regulated. There was a coordinate induction of 9 out of 12 acidic keratins that along with other epithelial and cell adhesion markers implies a partial mesenchymal to epithelial transition.
Answer: We conclude that severe hypoxia confers a quiescent phenotype in hMSCs that is reflected by both the transcriptome profile and gene-specific changes of splicosome actions. The results reveal that severe hypoxia imposes markedly different patterns of gene regulation of MSCs compared with more moderate hypoxia. This is the first study to report hypoxia-regulation of AS in stem/progenitor cells and the first molecular genetic characterization of MSC in a hypoxia-induced quiescent immobile state.
[EX A]: Does severe hypoxia exert parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells?

[EX Q]: Context: The BXD2 mouse strain spontaneously develops glomerulonephritis and erosive arthritis. The goal of this study was to identify the antigenic target proteins and epitopes and to unravel the mechanisms by which the related conditions arise in BXD2 mice.', 'Individual hybridomas isolated from the spleen of a 10-month-old BXD2 mouse were injected intraperitoneally into nonautoimmune mice for evaluation of pathogenicity of each autoantibody. Autoantigens were immunoprecipitated with the pathogenic autoantibody L3A4. Autoantigens were identified using enzyme-linked immunosorbent assay, Western blotting, 2-dimensional gel electrophoresis, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and tandem MS. Antigenic epitopes were determined using a high-throughput epitope mapping method.', 'The production of autoantibodies in BXD2 mice occurred in an orderly progression, with peak levels of autoantibodies to nitrotyrosine (NT)-modified enolase, Ro, alpha-actin, and heat-shock proteins (HSPs) preceding peak levels of antihistone, anti-DNA, and rheumatoid factor. Two monoclonal autoantibodies, L3A4 and T56G10, were identified that could induce immune complexes, renal disease, and/or arthritis. Both L3A4 and T56G10 were polyreactive, and each reacted with separate sets of autoantigens. The antigenic targets of L3A4 consisted of NT-modified enolase, ATP5b, alpha-actin, and Hsp70 family proteins including Hspa5 and Hsp74. The antigenic epitopes of NT-modified enolase and Hspa5 exhibited sequence homology and cross-reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism.
Answer: The polyreactivity of autoantibodies that target a novel class of autoantigens may enable these autoantibodies to induce erosive arthritis or glomerulonephritis either by direct pathogenic mechanisms or indirectly via Fc or immune complex deposition.
[EX A]: Does production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice cause glomerulonephritis and arthritis?

[EX Q]: Context: The surgical treatment method in which the peritoneal cavity is opened anteriorly and deliberately left open, hence often called "open abdomen" has become the standard of care in damage-control procedures as well as in the management of intra-abdominal hypertension and in severe intra-abdominal sepsis. Whereas open abdomen has been closed in two stages traditionally, a modern trend is to close the fascial layers within the initial hospitalization to avoid complications like enterocutaneous fistula and hernia formation. The aim of this study was to determine crucial factors influencing the possibility of fascial closure after open abdomen.', 'Between 2003 and 2013, 355 adult patients were treated with open abdomen in our institution. Their data were collected and retrospectively analyzed. They were divided into two groups depending on fascial closure or not (fascial closure, n\xa0=\xa0137 (39%) vs. non-fascial closure, n\xa0=\xa0218 (61%)).', 'The patients who reached fascial closure had a significantly higher rate of initially performed open abdomen (97 patients (71%) vs. 118 (54%), p\xa0=\xa00.002) and the periods of time until a second and a third look operation were significantly shorter (2.7\xa0±\xa02.5 vs. 4.2\xa0±\xa06.6 days, p\xa0=\xa00.021 and 5.6\xa0±\xa03.7 vs. 8.5\xa0±\xa08.6 days, p\xa0=\xa00.006). Furthermore, the presence of peritonitis (64 patients (47%) vs. 83 patients (38%), p\xa0=\xa00.023) and large bowel resection (74 patients (54%) vs. 90 patients (41%), p\xa0=\xa00.022) were significantly higher in this group. Rates of in-hospital mortality (97 patients (44%) vs. 38 patients (28%), p\xa0=\xa00.002) and the presence of pancreatitis (19 patients (9%) vs. 3 patients (2%), p\xa0=\xa00.013) were significantly higher in the non-fascial closure group.
Answer: The probability to reach fascial closure after open abdomen seems to increase when open abdomen is performed initially and when early second and third look operations are performed. The presence of pancreatitis seems to be the only negative prognostic marker concerning fascial closure.
[EX A]:
Are fascial closure after open abdomen : initial indication and early revisions decisive factors -- a retrospective cohort study?