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Integrative approaches to understanding human adaptation and acclimatization to high altitude
No full textHigh altitude and the hypobaric hypoxia associated with it impose significant physiological stressors on the human body. The human response to hypoxia varies between and within populations of differing genetic ancestries. This variation provides a natural experiment where potential mechanisms of hypoxia response can be investigated, especially for groups that have adapted to high altitude. This dissertation investigates the human response to hypoxia and high altitude by studying distinct populations through various biological approaches. The first chapter combines genetics, proteomics, and metabolomics data from Andean highlanders into a multi-omics analysis to predict phenotypes related to high-altitude adaptation, such as basic physiological traits, hematological traits, metabolism, and ventilation. The analysis identifies key contributors from each of the different -omics to various phenotypes. The second chapter characterizes the hypoxic ventilatory response in Tibetan women residing at high altitude and identifies an association between menopausal status and ventilation. The study further identifies genetic associations with ventilatory traits and genes under positive selection that may play a role in control of breathing. The third chapter is the results of a randomized, double-blinded, placebo-controlled study testing the effect of the probiotic SLAB51 on sea-level residents acclimatizing to high altitude. The study shows individuals that ingest the probiotic have a higher oxygen saturation and less symptoms of Acute Mountain Sickness at high altitude than those that receive a placebo. Taken together, this dissertation provides novel insights into how humans adapt and acclimatize to high altitude
Doctor of Philosophy
No full textdissertationHumans have lived at high altitude for hundreds of generations despite unavoidable challenges imposed by hypobaric hypoxia. The lower barometric pressure at high altitude reduces the number of oxygen molecules available in each breath of air, yet oxygen-dependent physiological processes must be maintained for survival. Cellular and system responses to hypoxic stress can result in altitude illness and may prove fatal in a small proportion of maladapted individuals. Native high-altitude populations, however, exhibit a unique suite of heritable traits that afford tolerance to hypoxia. Compared to lowland visitors and Andean highlanders, Tibetans exhibit lower hemoglobin (Hb) levels at high altitude, which tend to be similar to those expected under sea-level conditions. Such differences suggest this population has unique adaptations to their native environment. It has been hypothesized that genes specifically involved in the hypoxia inducible factor (HIF) pathway could underlie adaptive changes in high-altitude populations. Genome-wide analyses provide the first lines of evidence in support of genetic adaptation to high altitude. Three regions of the genome that contain genes associated with the human response to hypoxia show evidence of selection and are associated with decreased Hb levels, and two of these are also associated with metabolite levels. These phenotypic associations provide corroborative evidence for adaptive roles of genomic regions targeted by strong positive selection in Tibetans. iv While many of the same selection candidate genes are reported by studies of different Tibetan populations, some signals of selection and association are unique to particular groups. The genetic makeup of Tibetan groups located throughout the plateau is therefore important to consider in studies of high-altitude adaptation. Taken together, the data presented in this dissertation demonstrate that multiple genes are involved in Tibetan adaptation to high altitude. Some of these genes have been linked to hematological and metabolic phenotypes characterized thus far, providing further support for roles in physiological adaptation to this extreme environment. Studies aimed to identify associations between specific genetic variants, mechanisms, and phenotypes will help bridge the gap between genetic variation and organismal responses to hypoxia, and will have important implications for understanding human health and disease
Review: Body Knowledge Performance, Intermediality, and American Entertainment at the Turn of the Twentieth Century, by Mary Simonson
No full textIn this book, Mary Simonson examines the American entertainment in the early 1900's, a time of great transformation in which boundaries were challenged and redefined. Her main tool in this examination is "intermediality," a notion which is traditionally found in discussions relevant to media. Simonson argues that intermediality allows one to cast a new look into the past which brings to light things that might have been overlooked. She assists the reader in exploring the interconnectedness between various disciplines, and ultimately enriches the current discourse on performance and musicological values and methodologies. The author highlights that intermediality has often been used to describe new media and postmodernism and in this book she sets out to prove how intermediality lends itself to examining early twentieth-century performances. Simonson's viewpoint offers the reader a bird's eye view on the performers' work in America at the turn of the twentieth century
Innate Immune Phenotypes During Acute High-Altitude Exposure.
No full textVargas, Abel, Veronica Penuelas, Karapet G Mkrtchyan, Kathy Pham, Shyleen Frost, Esteban A Moya, James J Yu, Tatum S Simonson, and Erica C Heinrich. Innate immune phenotypes during acute high-altitude exposure. High Alt Med Biol. 00:00-00, 2025. Introduction: High altitude is a physiologically stressful environment due to limited oxygen availability. Decades of study reveal the complex plasticity in many physiological systems that manifests at high altitude to maintain oxygen delivery. However, there are gaps in our knowledge regarding how high-altitude exposure influences immune function. Since tissue and cellular hypoxia occur during injury and infection, we hypothesized that sustained hypoxemia during high-altitude travel may impact inflammatory and immune phenotypes due to crosstalk between hypoxia and inflammatory response pathways. Methods: We recruited 17 healthy participants and examined their immune phenotypes at sea level and during 3 days at 3,800 m elevation. Specific attention was paid to neutrophil phenotypes because changes in these cells have not been reported at high altitude. Results: We found several impacts of high altitude on immune cell populations, including shifts in monocytes from classical to intermediate (p = 0.004 after 1 night at high altitude [HA1], and p \u3c 0.001 after 2 nights at high altitude [HA2]) and nonclassical subsets (p = 0.013 on HA2), and increases in total B cells (p = 0.001 on HA2, p = 0.004 [HA3]). An effect of altitude was found for neutrophil CD15 expression (p \u3c 0.001), with a trend toward increased expression over time at high altitude. Higher Acute Mountain Sickness (AMS) scores on the second day at high altitude were associated with more pronounced shifts to nonclassical monocyte populations (R2 = 0.79, p = 0.001). These data indicate that acute high-altitude travel results in a pro-inflammatory immune response, which may contribute to AMS. This response appears to blunt with acclimatization, although elevation in B cells remain by HA3
Ancestry of the Iban is predominantly Southeast Asian: Genetic evidence from autosomal, mitochondrial, and Y chromosomes
No full textExtent: 8p.Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that southto-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry.
Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-tosouth migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y(NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data.Tatum S. Simonson, Jinchuan Xing, Robert Barrett, Edward Jerah, Peter Loa, Yuhua Zhang, W. Scott Watkins, David J. Witherspoon, Chad D. Huff, Scott Woodward, Bryan Mowry, Lynn B.Jord
A whole universe: pluridimensionality and inter-artistic links within the inocents of Hermann Brochn
No full textilustraciones, graficasLa presente investigación busca analizar los nexos interartísticos presentes en la novela Los inocentes, escrita por el autor austríaco Hermann Broch y publicada en 1950. Dichos nexos se presentan especialmente entre literatura, música y pintura y con ellos se pretende definir una nueva propuesta poética. (Texto tomado de la fuente)This research seeks to analyse the inter-artistic links present in the novel The Innocents, written by Austrian author Hermann Broch and published in 1950. These links are particularly present between literature, music and painting and the author uses them to define a new poetic proposal.MaestríaMagíster en Estudios Literario
Review of Body Knowledge Performance, Intermediality, and American Entertainment at the Turn of the Twentieth Century
No full textIn this book, Mary Simonson examines the American entertainment in the early 1900's, a time of great transformation in which boundaries were challenged and redefined. Her main tool in this examination is "intermediality," a notion which is traditionally found in discussions relevant to media. Simonson argues that intermediality allows one to cast a new look into the past which brings to light things that might have been overlooked. She assists the reader in exploring the interconnectedness between various disciplines, and ultimately enriches the current discourse on performance and musicological values and methodologies. The author highlights that intermediality has often been used to describe new media and postmodernism and in this book she sets out to prove how intermediality lends itself to examining early twentieth-century performances. Simonson's viewpoint offers the reader a bird's eye view on the performers' work in America at the turn of the twentieth century
Review of Body Knowledge Performance, Intermediality, and American Entertainment at the Turn of the Twentieth Century
No full textIn this book, Mary Simonson examines the American entertainment in the early 1900's, a time of great transformation in which boundaries were challenged and redefined. Her main tool in this examination is "intermediality," a notion which is traditionally found in discussions relevant to media. Simonson argues that intermediality allows one to cast a new look into the past which brings to light things that might have been overlooked. She assists the reader in exploring the interconnectedness between various disciplines, and ultimately enriches the current discourse on performance and musicological values and methodologies. The author highlights that intermediality has often been used to describe new media and postmodernism and in this book she sets out to prove how intermediality lends itself to examining early twentieth-century performances. Simonson's viewpoint offers the reader a bird's eye view on the performers' work in America at the turn of the twentieth century
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