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: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.', 'To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.', 'Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.', 'Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.', 'Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.
Answer: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.
Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways?

Context: To determine if central sympathetic blockade by dexmedetomidine, a selective alpha(2) adrenergic receptor agonist, prevents cardiac dysfunction associated with intracranial hypertension (ICH) in a rat model.', 'Following intracisternal administration of dexmedetomidine (1 microg.microL(-1), 10 microL volume) or the stereoisomer levomedetomidine (1 microg.microL(-l), 10 microL volume) in halothane-anesthetized rats, a subdural balloon catheter was inflated for 60 sec to produce ICH. Intracranial pressure, hemodynamic, left ventricular (LV) pressures and electrocardiographic (ECG) changes were recorded. Plasma and myocardial catecholamines and malondialdehyde (MDA) levels were measured.', 'After levomedetomidine administration, subdural balloon inflation precipitated an increase in mean arterial pressure (149 +/- 33% of baseline), heart rate (122 +/- 19% of baseline), LV systolic pressure (LVP), LV end-diastolic pressure (LVEDP), LV developed pressure (LVDP), LV dP/dtmax and rate pressure product (RPP) (132 +/- 19%, 260 +/- 142%, 119 +/- 15%, 126 +/- 24% and 146 +/- 33% of baseline value, respectively). ICH decelerated LVP fall (tau), as tau increased from 7.75 +/- 1.1 to 14.37 +/- 4.5 msec. Moreover, plasma norepinephrine levels were elevated (169 +/- 50% of baseline) and there was the appearance of cardiac dysrhythmias and other ECG abnormalities. This response was transient and cardiac function deteriorated in a temporal manner. Intracisternal dexmedetomidine prevented the rise in plasma norepinephrine, blocked the ECG abnormalities, and preserved cardiac function. Moreover, dexmedetomidine attenuated the rise in MDA levels.
Answer: The results demonstrate that dexmedetomidine attenuates cardiac dysfunction associated with ICH. Our results provide evidence for the role of central sympathetic hyperactivity in the development of cardiac dysfunction associated with ICH.

Does central dexmedetomidine attenuate cardiac dysfunction in a rodent model of intracranial hypertension?