32 research outputs found

    Physical inactivity induced dysregulation of skeletal muscle and adipose tissue metabolism

    Get PDF
    Includes bibliographical references.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Vita."May 2005"Dissertations, Academic -- University of Missouri--Columbia -- physiology (Medicine).Thesis (Ph. D.) University of Missouri-Columbia 2005.There has been a precipitous decline in the daily physical activity in humans that has been accompanied by an epidemic rise in the incidence of obesity and type II diabetes. This rapid decline in physical activity in humans was simulated using a rate model where male rats that were physically active on voluntary running wheels for 21 days had their running wheels locked for 5-53 hours. During this time frame (between 5 and 53 hours of reduced physical activity), there is decreased insulin sensitivity in the epitrochlearis muscle, an increase in the mass of the epididymal and omental fat depots, and an increase in the size of epididymal adipocytes. In the epitrochlearis muscle, there was a decrease in multiple descriptive indices of insulin receptor activation that was associated with the decreased insulin sensitivity. In epididymal fat, there was an increase in triacylglycerol synthesis above that of animals that did not have access to running wheels; this was paralleled by an increase in the enzyme activity of mitochondrial glycerol-3-phosphate acyltransferase (GPAT), a key regulatory point in the triacylglycerol synthesis pathway. An increase in mitochondrial GPAT protein is at least partly responsible for the increased enzyme activity. These studies provide a seminal foundation of mechanistic insights on how reduced physical activity elicits physiological changes that are commonly associated with common modern chronic diseases

    Sal-Site: Integrating new and existing ambystomatid salamander research and informational resources

    Get PDF
    Salamanders of the genus Ambystoma are a unique model organism system because they enable natural history and biomedical research in the laboratory or field. We developed Sal-Site to integrate new and existing ambystomatid salamander research resources in support of this model system. Sal-Site hosts six important resources: 1) Salamander Genome Project: an information-based web-site describing progress in genome resource development, 2) Ambystoma EST Database: a database of manually edited and analyzed contigs assembled from ESTs that were collected from A. tigrinum tigrinum and A. mexicanum, 3) Ambystoma Gene Collection: a database containing full-length protein-coding sequences, 4) Ambystoma Map and Marker Collection: an image and database resource that shows the location of mapped markers on linkage groups, provides information about markers, and provides integrating links to Ambystoma EST Database and Ambystoma Gene Collection databases, 5) Ambystoma Genetic Stock Center: a website and collection of databases that describe an NSF funded salamander rearing facility that generates and distributes biological materials to researchers and educators throughout the world, and 6) Ambystoma Research Coordination Network: a web-site detailing current research projects and activities involving an international group of researchers. Sal-Site is accessible at

    From Biomedicine to Natural History Research: EST Resources for Ambystomatid Aalamanders

    Get PDF
    BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories. RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human - Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species. CONCLUSIONS: Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research

    Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader–Willi syndrome

    Get PDF
    RNA transcripts encoding the 2C-subtype of serotonin (5HT2C) receptor undergo up to five adenosine-to-inosine editing events to encode twenty-four protein isoforms. To examine the effects of altered 5HT2C editing in vivo, we generated mutant mice solely expressing the fully-edited (VGV) isoform of the receptor. Mutant animals present phenotypic characteristics of Prader-Willi Syndrome (PWS) including a failure to thrive, decreased somatic growth, neonatal muscular hypotonia, and reduced food consumption followed by post-weaning hyperphagia. Though previous studies have identified alterations in both 5HT2C receptor expression and 5HT2C-mediated behaviors in both PWS patients and mouse models of this disorder, to our knowledge the 5HT2C gene is the first locus outside the PWS imprinted region in which mutations can phenocopy numerous aspects of this syndrome. These results not only strengthen the link between the molecular etiology of PWS and altered 5HT2C expression, but also demonstrate the importance of normal patterns of 5HT2C RNA editing in vivo

    Will ocean acidification affect marine microbes?

    Get PDF
    Author Posting. Β© The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 5 (2011): 1-7, doi:10.1038/ismej.2010.79.The pH of the surface ocean is changing as a result of increases in atmospheric carbon dioxide (CO2) and there are concerns about potential impacts of lower pH and associated alterations in seawater carbonate chemistry on the biogeochemical processes in the ocean. However, it is important to place these changes within the context of pH in the present day ocean, which is not constant; it varies systematically with season, depth and along productivity gradients. Yet this natural variability in pH has rarely been considered in assessments of the effect of ocean acidification on marine microbes. Surface pH can change as a consequence of microbial utilisation and production of carbon dioxide, and to a lesser extent other microbiallymediated processes such as nitrification. Useful comparisons can be made with microbes in other aquatic environments that readily accommodate very large and rapid pH change. For example, in many freshwater lakes, pH changes that are orders of magnitude greater than those projected for the 22nd century oceans can occur over periods of hours. Marine and freshwater assemblages have always experienced variable pH conditions. Therefore, an appropriate null hypothesis may be, until evidence is obtained to the contrary, that major biogeochemical processes in the oceans other than calcification will not be fundamentally different under future higher CO2 / lower pH conditions.Funding from the Gordon and Betty Moore Foundation, and logistical support from the Plymouth Marine Laboratory and the Center for Microbial Oceanography: Research and Education (National Science Foundation grant EF-0424599) are gratefully acknowledged

    A Phylometagenomic Exploration of Oceanic Alphaproteobacteria Reveals Mitochondrial Relatives Unrelated to the SAR11 Clade

    Get PDF
    BACKGROUND: According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from an ancestral Alphaproteobacterium. Phylogenetic studies indicate that the mitochondrial ancestor is most closely related to the Rickettsiales. Recently, it was suggested that Candidatus Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the oceans, is a sister taxon to the mitochondrial-Rickettsiales clade. The availability of ocean metagenome data substantially increases the sampling of Alphaproteobacteria inhabiting the oxygen-containing waters of the oceans that likely resemble the originating environment of mitochondria. METHODOLOGY/PRINCIPAL FINDINGS: We present a phylogenetic study of the origin of mitochondria that incorporates metagenome data from the Global Ocean Sampling (GOS) expedition. We identify mitochondrially related sequences in the GOS dataset that represent a rare group of Alphaproteobacteria, designated OMAC (Oceanic Mitochondria Affiliated Clade) as the closest free-living relatives to mitochondria in the oceans. In addition, our analyses reject the hypothesis that the mitochondrial system for aerobic respiration is affiliated with that of the SAR11 clade. CONCLUSIONS/SIGNIFICANCE: Our results allude to the existence of an alphaproteobacterial clade in the oxygen-rich surface waters of the oceans that represents the closest free-living relative to mitochondria identified thus far. In addition, our findings underscore the importance of expanding the taxonomic diversity in phylogenetic analyses beyond that represented by cultivated bacteria to study the origin of mitochondria

    Genome-wide association mapping identifies a new arsenate reductase enzyme critical for limiting arsenic accumulation in plants

    Get PDF
    Inorganic arsenic is a carcinogen, and its ingestion through foods such as rice presents a significant risk to human health. Plants chemically reduce arsenate to arsenite. Using genome-wide association (GWA) mapping of loci controlling natural variation in arsenic accumulation in Arabidopsis thaliana allowed us to identify the arsenate reductase required for this reduction, which we named High Arsenic Content 1 (HAC1). Complementation verified the identity of HAC1, and expression in Escherichia coli lacking a functional arsenate reductase confirmed the arsenate reductase activity of HAC1. The HAC1 protein accumulates in the epidermis, the outer cell layer of the root, and also in the pericycle cells surrounding the central vascular tissue. Plants lacking HAC1 lose their ability to efflux arsenite from roots, leading to both increased transport of arsenic into the central vascular tissue and on into the shoot. HAC1 therefore functions to reduce arsenate to arsenite in the outer cell layer of the root, facilitating efflux of arsenic as arsenite back into the soil to limit both its accumulation in the root and transport to the shoot. Arsenate reduction by HAC1 in the pericycle may play a role in limiting arsenic loading into the xylem. Loss of HAC1-encoded arsenic reduction leads to a significant increase in arsenic accumulation in shoots, causing an increased sensitivity to arsenate toxicity. We also confirmed the previous observation that the ACR2 arsenate reductase in A. thaliana plays no detectable role in arsenic metabolism. Furthermore, ACR2 does not interact epistatically with HAC1, since arsenic metabolism in the acr2 hac1 double mutant is disrupted in an identical manner to that described for the hac1 single mutant. Our identification of HAC1 and its associated natural variation provides an important new resource for the development of low arsenic-containing food such as rice

    Confusion and dependence in uses of history

    Get PDF
    Many people argue that history makes a special difference to the subjects of biology and psychology, and that history does not make this special difference to other parts of the world. This paper will show that historical properties make no more or less of a difference to biology or psychology than to chemistry, physics, or other sciences. Although historical properties indeed make a certain kind of difference to biology and psychology, this paper will show that historical properties make the same kind of difference to geology, sociology, astronomy, and other sciences. Similarly, many people argue that nonhistorical properties make a special difference to the nonbiological and the nonpsychological world. This paper will show that nonhistorical properties make the same difference to all things in the world when it comes to their causal behavior and that historical properties make the same difference to all things in the world when it comes to their distributions. Although history is special, it is special in the same way to all parts of the worl
    corecore