Proteomic and transcriptomic changes in hibernating grizzly bears reveal metabolic and signaling pathways that protect against muscle atrophy

Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment

On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes

The sensitivity of a search for sources of TeV neutrinos can be improved by grouping potential sources together into generic classes in a procedure that is known as source stacking. In this paper, we define catalogs of Active Galactic Nuclei (AGN) and use them to perform a source stacking analysis. The grouping of AGN into classes is done in two steps: first, AGN classes are defined, then, sources to be stacked are selected assuming that a potential neutrino flux is linearly correlated with the photon luminosity in a certain energy band (radio, IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino production in AGN, this correlation is motivated by hadronic AGN models, as briefly reviewed in this paper. The source stacking search for neutrinos from generic AGN classes is illustrated using the data collected by the AMANDA-II high energy neutrino detector during the year 2000. No significant excess for any of the suggested groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic

Systemic effects of a high saturated fat diet in grizzly bears (Ursus arctos horribilis)

Food sources for North America's brown bear (Ursus arctos horribilis Ord, 1815) population have changed as habitats have fragmented, altering available resources and putting bears in contact with unnatural foods. Bears have evolved mechanisms to tolerate obesity, and do not develop adverse health consequences despite storing massive amounts of body fat. Captive adult grizzly bears were used to determine the effects of dietary fat on health. Group 1 was fed a diet high in polyunsaturated fatty acids (PUFA) wherein 9.5% of available calories came from saturated fatty acids (SFA). Group 2 was fed a diet wherein 28.8% of calories came from SFA. Plasma fatty acids, serum lipid profiles, insulin, inflammatory markers, systolic and diastolic blood pressure, and cardiac function parameters were measured. Serum lipids, SFA, and insulin did not differ between the two groups, although omega-3 fatty acids differed. Bears eating the SFA diet had significantly higher circulating adiponectin, interleukin 7 and 15, and tumor necrosis factor-alpha. Mild, asymptomatic systolic and diastolic dysfunction were detected by strain echocardiography in the SFA group. The SFA diet group exhibited higher diastolic arterial pressures. Even though mild metabolic derangements were observed, grizzly bears were remarkably resistant to metabolic effects of diets high in SFA.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Detecting wildlife orthologues for tumor necrosis factor (TNF) and interleukin-6 (IL-6)

Detection and quantification of cytokines is important to better understand disease processes in populations. This study assessed the feasibility of quantifying wildlife orthologues for tumor necrosis factor (TNF) and interleukin-6 (IL-6) using two bioassays combined with an in vitro model for immune stimulation. For all species, heparinized blood (1 ml) was exposed to lipopolysaccharide (LPS; 10 pg to 50 micro g) for 6 hr (37 degrees C) after which plasma was collected. Neutralizing antibodies were used to demonstrate that grizzly bear (Ursus arctos) TNF can be quantified with a WEHI-164 bioassay, and expression of TNF in the LPS stimulated model is dose-dependent. A B9 bioassay demonstrated LPS-dose-dependent production of IL-6 for grizzly bears, although neutralizing antibodies were not available to confirm that IL-6 was responsible for these results. The B9 assay may have detected IL-6 orthologues for bighorn sheep (Ovis canadensis canadensis), elk (Cervus elaphus) and bison (Bison bison). These assays combined with the LPS stimulated blood model could provide a rapid means for assessing immunological effects of pathogens and toxicants