Project description:Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1β and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.
Project description:Acute high-altitude pulmonary edema (HAPE) is a pathology involving multifactorial triggers that are associated with ascents to altitudes over 2,500 meters above sea level (m). Here, we report two pediatric cases of reentry HAPE, from the city of Huaraz, Peru, located at 3,052?m. The characteristics of both cases were similar, wherein acclimatization to sea level and a subsequent return to the city of origin occurred, and we speculate that it was caused by activation of predisposing factors to HAPE. The diagnosis and management associated with pulmonary hypertension became a determining factor for therapy.
Project description:This study evaluates genetic and phenotypic variation in the high altitude Colla population living in the Argentinean Andes above 3500 m. They were compared to the Wichà population living in the nearby lowlands of the Gran Chaco region. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to hypobaric hypoxia. We have genotyped 25 individuals from both populations for 730,525 SNPs. DNA from 25 saliva samples from Collas living >3500 m and 25 saliva samples from Wichà living <500 m from the Province of Salta in Argentina was genotyped
Project description:High altitudes (>8,000 ft or 2,500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past ~25 years in Andeans, Tibetans, and, less often, Ethiopians show varied but distinct O2 transport traits from those of acclimatized newcomers, providing indirect evidence for genetic adaptation to high altitude. Short-term (acclimatization, developmental) and long-term (genetic) responses to high altitude exhibit a temporal gradient such that, although all influence O2 content, the latter also improve O2 delivery and metabolism. Much has been learned concerning the underlying physiological processes, but additional studies are needed on the regulation of blood flow and O2 utilization. Direct evidence of genetic adaptation comes from single-nucleotide polymorphism (SNP)-based genome scans and whole genome sequencing studies that have identified gene regions acted upon by natural selection. Efforts have begun to understand the connections between the two with Andean studies on the genetic factors raising uterine blood flow, fetal growth, and susceptibility to Chronic Mountain Sickness and Tibetan studies on genes serving to lower hemoglobin and pulmonary arterial pressure. Critical for future studies will be the selection of phenotypes with demonstrable effects on reproductive success, the calculation of actual fitness costs, and greater inclusion of women among the subjects being studied. The well-characterized nature of the O2 transport system, the presence of multiple long-resident populations, and relevance for understanding hypoxic disorders in all persons underscore the importance of understanding how evolutionary adaptation to high altitude has occurred.NEW & NOTEWORTHY Variation in O2 transport characteristics among Andean, Tibetan, and, when available, Ethiopian high-altitude residents supports the existence of genetic adaptations that improve the distribution of blood flow to vital organs and the efficiency of O2 utilization. Genome scans and whole genome sequencing studies implicate a broad range of gene regions. Future studies are needed using phenotypes of clear relevance for reproductive success for determining the mechanisms by which naturally selected genes are acting.
Project description:BackgroundOur study was designed to determine the incidence and risk factors of severe acute high-altitude illness (AHAI) in healthy adults first entering the northern Tibetan Plateau of over 5,000 m.MethodsIn our prospective observational study, we enrolled 500 people who were scheduled for fast ascension to the northern Tibetan Plateau. The primary outcome variable was severe AHAI, defined as the presence of serious symptoms that could not be ameliorated by general treatment and required evacuation to lower altitudes. According to the inclusion and exclusion criteria, a cohort of 383 healthy people was included in the statistical analysis. We calculated the incidence of severe AHAI, identified the risk factors, and the differences in the most severe symptoms experienced.ResultsSixty-eight people were diagnosed with severe AHAI, and the incidence was 17.8%. Compared to individuals without severe AHAI, those with severe AHAI were more likely to be over the age of 40 years, of Han Chinese nationality, and living at an altitude of <1,500 m. They were less likely to belong to the Yi nationality, had a lower altitude of permanent residence, and exhibited decreased levels of lymphocyte count and hemoglobin concentration. Multivariable logistic regression showed that the mean altitude of permanent residence [per kilometer, adjusted odds ratio (AOR) = 0.464; 95% confidence interval (CI), 0.304-0.708; p < 0.001] and lymphocyte count (AOR = 0.606; 95% CI, 0.378-0.970; p = 0.037) were the independent risk factors. Headache and dyspnea ranked in the top two of the most severe symptoms for people with severe AHAI.ConclusionLiving at lower altitudes and having a decreased lymphocyte level were the risk factors of severe AHAI in healthy adults first entering the plateau of over 5,000 m.
Project description:This study evaluates genetic and phenotypic variation in the high altitude Colla population living in the Argentinean Andes above 3500 m. They were compared to the Wichí population living in the nearby lowlands of the Gran Chaco region. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to hypobaric hypoxia. We have genotyped 25 individuals from both populations for 730,525 SNPs.
Project description:BackgroundSpecies living at high altitude are subject to strong selective pressures due to inhospitable environments (e.g., hypoxia, low temperature, high solar radiation, and lack of biological production), making these species valuable models for comparative analyses of local adaptation. Studies that have examined high-altitude adaptation have identified a vast array of rapidly evolving genes that characterize the dramatic phenotypic changes in high-altitude animals. However, how high-altitude environment shapes gene expression programs remains largely unknown.FindingsWe generated a total of 910 Gb of high-quality RNA-seq data for 180 samples derived from 6 tissues of 5 agriculturally important high-altitude vertebrates (Tibetan chicken, Tibetan pig, Tibetan sheep, Tibetan goat, and yak) and their cross-fertile relatives living in geographically neighboring low-altitude regions. Of these, ∼75% reads could be aligned to their respective reference genomes, and on average ∼60% of annotated protein coding genes in each organism showed FPKM expression values greater than 0.5. We observed a general concordance in topological relationships between the nucleotide alignments and gene expression-based trees. Tissue and species accounted for markedly more variance than altitude based on either the expression or the alternative splicing patterns. Cross-species clustering analyses showed a tissue-dominated pattern of gene expression and a species-dominated pattern for alternative splicing. We also identified numerous differentially expressed genes that could potentially be involved in phenotypic divergence shaped by high-altitude adaptation.ConclusionsThese data serve as a valuable resource for examining the convergence and divergence of gene expression changes between species as they adapt or acclimatize to high-altitude environments.