ABSTRACT: Acclimatization to high altitude over 21 days, and upon re-ascent 7 and 21 days post-descent. See Subudhi et al. (2014) PLOS ONE 9(3):e92191, PMCID PMC3962396 for experiment details.
Project description:Acclimatization to high altitude over 21 days, and upon re-ascent 7 and 21 days post-descent. See Subudhi et al. (2014) PLoS One 9(3):e92191, PMCID PMC3962396, PMID 24658407 for experiment details.
Project description:Acclimatization to high altitude over 21 days, and upon re-ascent 7 and 21 days post-descent. See Subudhi et al. (2014) PLoS One 9(3):e92191, PMCID PMC3962396, PMID 24658407 for experiment details.
Project description:Altitude acclimatization is the physiological process to restore oxygen delivery to the tissues and promote the oxygen application under high altitude hypoxia. High altitude illness could happen in individuals who did not get acclimatization. Unraveling the molecular underpinnings of altitude acclimatization would help people to understand the beneficial response of body to high altitude hypoxia and disturbed biological process in un-acclimatized individuals. Here, we measured physiological adjustments and circulating microRNAs (cmiRNAs) profiles of individuals exposed to high altitude to explore the altitude acclimatization in humans.
Project description:Understanding molecular mechanism associated with high altitude exposure during acclimatization/adaptation/maladaptation. Data reveals specific components of the complex molecular circuitry underlying high altitude pulmonary edema.
Project description:Cord blood stem cells were expanded and differentiated to NK cells. Samples taken at different days after induction of differentiation were analyzed and compared to undifferentiated expanded stem cells. The most highly upregulated genes were further analyzed. Results based on the analyses have been published in Lehmann et al., Stem Cells Develop 21, 2926-38 (2012), Lehmann et al., PloS One 9, e87131 (2014) and Post et al., submitted (2017).
Project description:Understanding molecular mechanism associated with high altitude exposure during acclimatization/adaptation/maladaptation. Data reveals specific components of the complex molecular circuitry underlying high altitude pulmonary edema. Individualized outcome prediction were constructed through expression profiling of 39400 genes in sea level sojourners who were acclimatized to high altitude and grouped as controls (n=14), high altitude natives (n=14) and individuals who developed high altitude pulmonary edema within 48-72 hours after air induction to high altitude (n=17).
Project description:In humans and other species, Longlong-term hypoxia (LTH) during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF), and other problems in humans and rodents. In contrast, sheep appear to undergo relatively successful acclimatization, not demonstrating any of the above-mentioned problems except at extremely high altitude. To identify the signal transduction genetic pathways and those critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA) from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified, mRNA from 38 genes upregulated (> 2 fFold; (P < 0.05) and 9 genes downregulated (> 2-f Fold; (P < 0.05). The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF) binding protein 3, IGF type 2 receptor, transforming growth factor (TGF) Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. The majority of genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3M-bM-^@M-^Y un -translated region (UTR). Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region, with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L). We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may help it to play a role in the acclimatizatione successfully response to high-altitude associated LTH. In these series of experiments we examined changes in gene expression in sheep carotids. Pregnant sheep and non-pregnant adult sheep were exposed to 110 days of hypoxia at 3801 meters of altitude. Carotid arteries from fetuses from non-pregnant adult from sea-level controls and those from high-altitude were compared by Agilent ovine custom array
Project description:In humans and other species, Longlong-term hypoxia (LTH) during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF), and other problems in humans and rodents. In contrast, sheep appear to undergo relatively successful acclimatization, not demonstrating any of the above-mentioned problems except at extremely high altitude. To identify the signal transduction genetic pathways and those critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA) from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified, mRNA from 38 genes upregulated (> 2 fFold; (P < 0.05) and 9 genes downregulated (> 2-f Fold; (P < 0.05). The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF) binding protein 3, IGF type 2 receptor, transforming growth factor (TGF) Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. The majority of genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3’ un -translated region (UTR). Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region, with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L). We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may help it to play a role in the acclimatizatione successfully response to high-altitude associated LTH.
Project description:Investigation of how gene expression and epigenetics contribute to conservation of birth weight at high altitudes by examining mRNA and DNA methylation differences between placentas of indigenous Andeans and placentas of European descent residing at high and low altitude
Project description:To explore the exceptional mechanisms of gene expression and DNA methylation that are induced by low altitude environments in Tibetan pigs, we performed a comparative transcriptomic analysis of skeletal muscle in indigenous Tibetan pigs that reside in high altitude regions (~4,000 m) and their counterparts that migrated to the geographically neighboring low-altitude regions (~500 m) for nearly ten generations. We identified protein coding genes that related to hypoxia response (EGLN3 and FLT1), oxygen transport and energy metabolism (TFB2M), and two long non-coding RNAs (TCONS_00039686 and TCONS_00084992) that associated with the regulation of transcription and various nucleolus and organelle lumen, were differentially expressed between Tibetan pigs and their counterparts in low-altitude regions, thus might be the potential candidate regulators in skeletal muscle of low-altitude acclimation in Tibetan pigs. We also found genes embedded in differentially methylated regions between Tibetan pigs and their counterparts in low-altitude regions were mainly involved in ‘Starch and sucrose metabolism’, ‘glucuronosyltransferase activity’ processes, hypoxia and energy metabolism. We envision that this study will serve as a valuable resource for mammal acclimatization research and agricultural food industry.