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.

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.
Does severe hypoxia exert parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells?

Context: Cysteine, a sulfur-containing amino acid, plays an important role in a variety of cellular functions such as protein biosynthesis, methylation, and polyamine and glutathione syntheses. In trypanosomatids, glutathione is conjugated with spermidine to form the specific antioxidant thiol trypanothione (T[SH]2) that plays a central role in maintaining intracellular redox homeostasis and providing defence against oxidative stress.', 'We cloned and characterised genes coding for a cystathionine β-synthase (CβS) and cysteine synthase (CS), key enzymes of the transsulfuration and assimilatory pathways, respectively, from the hemoflagellate protozoan parasite Trypanosoma rangeli.', 'Our results show that T. rangeli CβS (TrCβS), similar to its homologs in T. cruzi, contains the catalytic domain essential for enzymatic activity. Unlike the enzymes in bacteria, plants, and other parasites, T. rangeli CS lacks two of the four lysine residues (Lys26 and Lys184) required for activity. Enzymatic studies using T. rangeli extracts confirmed the absence of CS activity but confirmed the expression of an active CβS. Moreover, CβS biochemical assays revealed that the T. rangeli CβS enzyme also has serine sulfhydrylase activity.
Answer: These findings demonstrate that the RTS pathway is active in T. rangeli, suggesting that this may be the only pathway for cysteine biosynthesis in this parasite. In this sense, the RTS pathway appears to have an important functional role during the insect stage of the life cycle of this protozoan parasite.
Is transsulfuration an active pathway for cysteine biosynthesis in Trypanosoma rangeli?

Context: To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits.', 'Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30 mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h).', 'Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis.
Answer: COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin. Treatment with the COX-2 inhibitor DFU is associated with improvement of mucosal damage, which may have therapeutic implications.

Is selective COX-2 inhibition associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis?