169 research outputs found

    Environmental Stewardship on the URI Campus

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    This poster campaign and report was an effort to get environmental stewardship to be more of a part of the student government at URI. It was used to raise awareness and link people\u27s actions to theory so that future work could be built off this and assessed for its effectiveness

    A Computational Model of Reactive Oxygen Species and Redox Balance in Cardiac Mitochondria

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    AbstractElevated levels of reactive oxygen species (ROS) play a critical role in cardiac myocyte signaling in both healthy and diseased cells. Mitochondria represent the predominant cellular source of ROS, specifically the activity of complexes I and III. The model presented here explores the modulation of electron transport chain ROS production for state 3 and state 4 respiration and the role of substrates and respiratory inhibitors. Model simulations show that ROS production from complex III increases exponentially with membrane potential (ΔΨm) when in state 4. Complex I ROS release in the model can occur in the presence of NADH and succinate (reverse electron flow), leading to a highly reduced ubiquinone pool, displaying the highest ROS production flux in state 4. In the presence of ample ROS scavenging, total ROS production is moderate in state 3 and increases substantially under state 4 conditions. The ROS production model was extended by combining it with a minimal model of ROS scavenging. When the mitochondrial redox status was oxidized by increasing the proton permeability of the inner mitochondrial membrane, simulations with the combined model show that ROS levels initially decline as production drops off with decreasing ΔΨm and then increase as scavenging capacity is exhausted. Hence, this mechanistic model of ROS production demonstrates how ROS levels are controlled by mitochondrial redox balance

    Star Unfolding Convex Polyhedra via Quasigeodesic Loops

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    We extend the notion of star unfolding to be based on a quasigeodesic loop Q rather than on a point. This gives a new general method to unfold the surface of any convex polyhedron P to a simple (non-overlapping), planar polygon: cut along one shortest path from each vertex of P to Q, and cut all but one segment of Q.Comment: 10 pages, 7 figures. v2 improves the description of cut locus, and adds references. v3 improves two figures and their captions. New version v4 offers a completely different proof of non-overlap in the quasigeodesic loop case, and contains several other substantive improvements. This version is 23 pages long, with 15 figure

    Fatty acid binding protein deletion suppresses inflammatory pain through endocannabinoid/N-acylethanolamine-dependent mechanisms

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    Background Fatty acid binding proteins (FABPs) serve as intracellular carriers that deliver endocannabinoids and N-acylethanolamines to their catabolic enzymes. Inhibition of FABPs reduces endocannabinoid transport and catabolism in cells and FABP inhibitors produce antinociceptive and anti-inflammatory effects in mice. Potential analgesic effects in mice lacking FABPs, however, have not been tested. Findings Mice lacking FABP5 and FABP7, which exhibit highest affinities for endocannabinoids, possessed elevated levels of the endocannabinoid anandamide and the related N-acylethanolamines palmitoylethanolamide and oleoylethanolamide. There were no compensatory changes in the expression of other FABPs or in endocannabinoid-related proteins in the brains of FABP5/7 knockout mice. These mice exhibited reduced nociception in the carrageenan, formalin, and acetic acid tests of inflammatory and visceral pain. The antinociceptive effects in FABP5/7 knockout mice were reversed by pretreatment with cannabinoid receptor 1, peroxisome proliferator-activated receptor alpha, and transient receptor potential vanilloid 1 receptor antagonists in a modality specific manner. Lastly, the knockout mice did not possess motor impairments. Conclusions This study demonstrates that mice lacking FABPs possess elevated levels of N-acylethanolamines, consistent with the idea that FABPs regulate the endocannabinoid and N-acylethanolamine tone in vivo. The antinociceptive effects observed in the knockout mice support a role for FABPs in regulating nociception and suggest that these proteins should serve as targets for the development of future analgesics

    Spectral decomposition of internal gravity wave sea surface height in global models

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    Two global ocean models ranging in horizontal resolution from 1/12° to 1/48° are used to study the space and time scales of sea surface height (SSH) signals associated with internal gravity waves (IGWs). Frequency‐horizontal wavenumber SSH spectral densities are computed over seven regions of the world ocean from two simulations of the HYbrid Coordinate Ocean Model (HYCOM) and three simulations of the Massachusetts Institute of Technology general circulation model (MITgcm). High wavenumber, high‐frequency SSH variance follows the predicted IGW linear dispersion curves. The realism of high‐frequency motions (>0.87  cpd) in the models is tested through comparison of the frequency spectral density of dynamic height variance computed from the highest‐resolution runs of each model (1/25° HYCOM and 1/48° MITgcm) with dynamic height variance frequency spectral density computed from nine in situ profiling instruments. These high‐frequency motions are of particular interest because of their contributions to the small‐scale SSH variability that will be observed on a global scale in the upcoming Surface Water and Ocean Topography (SWOT) satellite altimetry mission. The variance at supertidal frequencies can be comparable to the tidal and low‐frequency variance for high wavenumbers (length scales smaller than ∼50 km), especially in the higher‐resolution simulations. In the highest‐resolution simulations, the high‐frequency variance can be greater than the low‐frequency variance at these scales.Key PointsTwo high‐resolution ocean models compare well against data in frequency spectral density of dynamic heightSea surface height frequency‐horizontal wavenumber spectral densities show high variance along internal gravity wave dispersion curvesTwo high‐resolution ocean models give different estimates of variance in high‐frequency, high wavenumber phenomenaPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/1/jgrc22465-sup-0002-2017JC013009-fs01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/2/jgrc22465-sup-0003-2017JC013009-fs02.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/3/jgrc22465_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/4/jgrc22465.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/5/jgrc22465-sup-0007-2017JC013009-fs06.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/6/jgrc22465-sup-0009-2017JC013009-fs08.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/7/jgrc22465-sup-0004-2017JC013009-fs03.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/8/jgrc22465-sup-0005-2017JC013009-fs04.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/9/jgrc22465-sup-0006-2017JC013009-fs05.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/10/jgrc22465-sup-0001-2017JC013009-s01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139946/11/jgrc22465-sup-0008-2017JC013009-fs07.pd

    SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

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    SUMMARY A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression

    The effectiveness and experience of self-management following acute coronary syndrome : a review of the literature

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    Evidence of the effectiveness of self-management interventions among people with acute coronary syndrome remains inconclusive. Findings from the patients' experiences in relation to self-management following acute coronary syndrome provided important insights into what problems patients might have encountered during self-managing recovery and what support they might need, which can be used to inform the development of self-management interventions. Theoretical or conceptual frameworks have been minimally employed in these studies and should be incorporated in future development and evaluation of self-management interventions as a way of ensuring clarity and consistency related to how interventions are conceptualised, operationalised and empirically studied. Further research is needed to evaluate self-management interventions among people following acute coronary syndrome for sustained effect and within different health care contexts

    PFKFB3-Mediated Glycolysis Rescues Myopathic Outcomes in the Ischemic Limb

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    Compromised muscle mitochondrial metabolism is a hallmark of peripheral arterial disease, especially in patients with the most severe clinical manifestation — critical limb ischemia (CLI). We asked whether inflexibility in metabolism is critical for the development of myopathy in ischemic limb muscles. Using Polg mtDNA mutator (D257A) mice, we reveal remarkable protection from hind limb ischemia (HLI) due to a unique and beneficial adaptive enhancement of glycolytic metabolism and elevated ischemic muscle PFKFB3. Similar to the relationship between mitochondria from CLI and claudicating patient muscles, BALB/c muscle mitochondria are uniquely dysfunctional after HLI onset as compared with the C57BL/6 (BL6) parental strain. AAV-mediated overexpression of PFKFB3 in BALB/c limb muscles improved muscle contractile function and limb blood flow following HLI. Enrichment analysis of RNA sequencing data on muscle from CLI patients revealed a unique deficit in the glucose metabolism Reactome. Muscles from these patients express lower PFKFB3 protein, and their muscle progenitor cells possess decreased glycolytic flux capacity in vitro. Here, we show supplementary glycolytic flux as sufficient to protect against ischemic myopathy in instances where reduced blood flow–related mitochondrial function is compromised preclinically. Additionally, our data reveal reduced glycolytic flux as a common characteristic of the failing CLI patient limb skeletal muscle
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