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Tumor Necrosis Factor-Alpha Is Produced By Dying Retinal Neurons And Is Required For Müller Glia Proliferation During Zebrafish Retinal Regeneration, Craig M. Nelson, Kristin M. Ackerman, Patrick O'Hayer, Travis J. Bailey, Ryne A. Gorsuch, David R. Hyde

Biology

Intense light exposure causes photoreceptor apoptosis in dark-adapted adult albino zebrafish (Danio rerio). Subsequently, Müller glia increase expression of the Achaete-scute complex-like 1a (Ascl1a) and Signal transducer and activator of transcription 3 (Stat3) transcription factors and re-enter the cell cycle to yield undifferentiated neuronal progenitors that continue to proliferate, migrate to the outer nuclear layer, and differentiate into photoreceptors. A proteomic analysis of light-damaged retinal homogenates, which induced Müller glia proliferation when injected into an undamaged eye, revealed increased expression of tumor necrosis factor α (TNFα) signaling proteins relative to undamaged retinal homogenates. TNFα expression initially increased in apoptotic photoreceptors …

De Novo Orfs In Drosophila Are Important To Organismal Fitness And Evolved Rapidly From Previously Non-Coding Sequences, Josephine A. Reinhardt, Betty M. Wanjiru, Alicia T. Brant, Perot Saelao, David J. Begun, Corbin D. Jones

Biology

How non-coding DNA gives rise to new protein-coding genes (de novo genes) is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution …

Not All Dogs Go To Heaven: Judaism’S Lessons In Beastly Morality, Mark Goldfeder

Scholarly Works

This Essay examines the moral status of animals and the definition of humanity under traditional Jewish law, as contained in Biblical texts and commentaries by ancient and historical Jewish scholars. Examining whether animals are capable of moral behavior, it provides examples from various Judaic sources to support the idea that animals are capable of making conscious, moral choices. This Essay goes on to investigate the effect that morality has on the rights and rewards given to animals under Jewish law, and whether, as conscious moral actors, animals have souls. Turning more broadly to the definition of humanity, this Essay discusses …

Cattle-Related Injuries And Farm Management Practices On Kentucky Beef Cattle Farms, Steven R. Browning, Susan C. Westneat, Wayne T. Sanderson, Deborah B. Reed

Epidemiology and Environmental Health Faculty Publications

While working on farms with livestock increases the risk of injury among farm workers in comparison to other commodity farms, few studies have examined the role offarm management practices in association with the risk of cattle-related injury. We examined the farm management practices of Kentucky beef cattle farms in association with self-reported rates of cattle-related injuries among workers. We conducted a mail survey of a random sample of 2,500 members of the Kentucky Cattlemen's Association. Results from 1,149 farm operators who were currently raising beef cattle and provided complete survey response are reported. During the busy season, the principal operator …

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …

Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson

Dartmouth Scholarship

Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …

Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, And Management, Deborah E Meyers, Haseeb Ilias Basha, Mary Kay Koenig

The Texas Heart Institute Journal

Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory …

Candida Albicans Induces Arginine Biosynthetic Genes In Response To Host-Derived Reactive Oxygen Species, Claudia Jimenez-Lopez, John R. Collette, Kimberly M. Brothers, Kelly M. Shepardson, Robert A. Kramer

Dartmouth Scholarship

The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is …

System Analysis Of Spatial Frequency Domain Imaging For Quantitative Mapping Of Surgically Resected Breast Tissues, Ashley M. Laughney, Venkataramanan Krishnaswamy, Tyler B. Rice, David J. Cuccia

Dartmouth Scholarship

No abstract provided.

Early Hemodynamic And Biochemical Changes In Overloaded Swine Ventricleearly Hemodynamic And Biochemical Changes In Overloaded Swine Ventricle, Sandro Gelsomino, Fabiana Lucà, Chiara Nediani, Sandra Zecchi Orlandini, Daniele Bani, Antonio S Rubino, Attilio Renzulli, Roberto Lorusso, Andrea Consolo, Antonino Lo Cascio, Jos Maessen, Gian Franco Gensini

The Texas Heart Institute Journal

The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload. In 54 study-group pigs, weighing 40±5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr). All indices of left ventricular function declined significantly, with a …

The Pathobiology Of Acute Coronary Syndromes: Clinical Implications And Central Role Of The Mitochondria, L Maximilian Buja

The Texas Heart Institute Journal

Ongoing investigation has provided new insights into the pathobiology of myocardial ischemic injury. These include an improved understanding of the roles of the major modes of cell injury and death, including oncosis, apoptosis, and unregulated autophagy, as well as the central role of the mitochondria in the progression of myocardial ischemic injury, reperfusion injury, and myocardial conditioning. This understanding is providing insights for developing new pathophysiologic, pharmacologic, and cell-based therapies, alone or in combination with percutaneous coronary interventions, for better preservation of myocardium and reduction of morbidity and mortality rates from ischemic heart disease.

Induction Of Early Biomarkers In A Thrombus-Induced Sheep Model Of Ischemic Heart Failure, Aluganti N Chandrakala, Pawel Kwiatkowski, Chittoor B Sai-Sudhakar, Benjamin Sun, Angela Phillips, Sampath Parthasarathy

The Texas Heart Institute Journal

The levels of brain natriuretic peptide (BNP) and monocyte chemoattractant protein-1 (MCP-1) are known to be increased in the sera of subjects with heart failure. Existing models do not account for the biomass of thrombus that occurs in patients undergoing myocardial infarction. In this study, we compared the expressions of sheep-derived genes for BNP, MCP-1, and atrial natriuretic peptide in a new large-animal model of thrombus-induced heart failure. Thrombus of autologous platelets was injected directly into the left circumflex coronary arteries of sheep. Cardiac ischemic injury was evaluated by troponin I levels, and heart failure progression was monitored with the …

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

Immune Response To Snake Envenoming And Treatment With Antivenom; Complement Activation, Cytokine Production And Mast Cell Degranulation, Shelley Stone, Geoffrey K. Isbister, Seyed Shahmy, Fahim Mohamed, Chandana Abeysinghe, Harendra Karunathilake, Ariaranee Ariaratnam, Tamara E. Jacoby-Alner, Claire L. Cotterell, Simon G A Brown

Research outputs 2013

Background:Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.Methodology/Principal Findings:Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and …

A Necrotic Stimulus Is Required To Maximize Matrix-Mediated Myogenesis In Mice, Drew Kuraitis, Maria Grazia Berardinelli, Erik J. Suuronen, Antonio Musaro

Research outputs 2013

Biomaterials that are similar to skeletal muscle extracellular matrix have been shown to augment regeneration in ischemic muscle. In this study, treatment with a collagen-based matrix stimulated molecular myogenesis in an mdx murine model of necrosis. Matrix-treated animals ran ≥ 40% further, demonstrating functional regeneration, and expressed increased levels of myogenic transcripts. By contrast, matrix treatment was unable to induce transcriptional or functional changes in an MLC/SOD1G93A atrophic mouse model. In vitro, satellite cells were cultured under standard conditions, on matrix, in the presence of myocyte debris (to simulate a necrotic-like environment) or with both matrix and necrotic stimuli. Exposure …

Cd2ap Links Cortactin And Capping Protein At The Cell Periphery To Facilitate Formation Of Lamellipodia, Jianping Zhao, Serawit Bruck, Saso Cemerski, Lei Zhang, Boyd Butler, Adish Dani, John A. Cooper, Andrey S. Shaw

Open Access Publications

Understanding the physiology of complex relationships between components of signaling pathways and the actin cytoskeleton is an important challenge. CD2AP is a membrane scaffold protein implicated in a variety of physiological and disease processes. The physiological function of CD2AP is unclear, but its biochemical interactions suggest that it has a role in dynamic actin assembly. Here, we report that CD2AP functions to facilitate the recruitment of actin capping protein (CP) to the Src kinase substrate, cortactin, at the cell periphery, and that this is necessary for formation of the short branched filaments that characterize lamellipodium formation and are required for …

Chronic Ethanol Feeding Alters Mirna Expression Dynamics During Liver Regeneration., Rachael P Dippold, Rajanikanth Vadigepalli, Gregory E. Gonye, Biswanath Patra, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Adaptation to chronic ethanol (EtOH) treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease.

METHODS: In this study, we investigated the effect of chronic EtOH intake on hepatic microRNA (miRNA) expression in male Sprague-Dawley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using miRNA microarrays. miRNA expression during adaptation to EtOH was investigated using RT-qPCR. Nuclear factor kappa B (NFκB) binding at target miRNA promoters was investigated with chromatin immunoprecipitation.

RESULTS: Unsupervised clustering of …

Inhibitory Effect Of Il-17 On Neural Stem Cell Proliferation And Neural Cell Differentiation., Zichen Li, Ke Li, Lin Zhu, Quancheng Kan, Yaping Yan, Priyanka Kumar, Hui Xu, Abdolmohamad Rostami, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system.

METHODS: We first detected IL-17 receptor expression in NSCs with immunostaining and real time PCR. We then cultured NSCs with IL-17 and determined NSC proliferation by neurosphere formation …

Probiotic Pediococcus Acidilactici Modulates Both Localised Intestinal- And Peripheral-Immunity In Tilapia (Oreochromis Niloticus)., B. T. Standen, M. D. Rawling, S. J. Davies, M. Castex, A. Foey, G. Gioacchini, O. Carnevali, D. L. Merrifield

School of Biological and Marine Sciences

The application of probiotics in aquaculture has received concerted research efforts but the localised intestinal immunological response of fish to probiotic bacteria is poorly understood. Therefore, a study was conducted to evaluate the probiotic effect of Pediococcus acidilactici on Nile tilapia (Oreochromis niloticus) with specific emphasis on intestinal health and probiotic levels as well as system level responses such as growth performance, feed utilization and haemato-immunological parameters under non-challenged conditions. Fish (9.19 ± 0.04 g) were fed either a control diet or a P. acidilactici supplemented diet (at 2.81 × 10(6) CFU g(-)(1)) for six weeks. At the end of …

A Fimh Inhibitor Prevents Acute Bladder Infection And Treats Chronic Cystitis Caused By Multidrug-Resistant Uropathogenic Escherichia Coli St131., Makrina Totsika, Maria Kostakioti, Thomas J. Hannan, Mathew Upton, Scott A. Beatson, James W. Janetka, Scott J. Hultgren, Mark A. Schembri

School of Biomedical Sciences

BACKGROUND: Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent. METHODS: Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958. RESULTS: We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration …

Loss Of Sox10 Function Contributes To The Phenotype Of Human Merlin-Null Schwannoma Cells., Robin D.S. Doddrell, Xin Peng Dun, Aditya Shivane, M. Laura Feltri, Lawrence Wrabetz, Michael Wegner, Elisabeth Sock, C. Oliver Hanemann, David B. Parkinson

Peninsula Medical School

Loss of the Merlin tumour suppressor causes abnormal de-differentiation and proliferation of Schwann cells and formation of schwannoma tumours in patients with neurofibromatosis type 2. Within the mature peripheral nerve the normal development, differentiation and maintenance of myelinating and non-myelinating Schwann cells is regulated by a network of transcription factors that include SOX10, OCT6 (now known as POU3F1), NFATC4 and KROX20 (also known as Egr2). We have examined for the first time how their regulation of Schwann cell development is disrupted in primary human schwannoma cells. We find that induction of both KROX20 and OCT6 is impaired, whereas enforced expression …

Tolerance Of Sponge Assemblages To Temperature Anomalies: Resilience And Proliferation Of Sponges Following The 1997-8 El-Niño Southern Oscillation., Francisco Kelmo, James J. Bell, Martin J. Attrill

School of Biological and Marine Sciences

Coral reefs across the world are under threat from a range of stressors, and while there has been considerable focus on the impacts of these stressors on corals, far less is known about their effect on other reef organisms. The 1997-8 El-Niño Southern Oscillation (ENSO) had notable and severe impacts on coral reefs worldwide, but not all reef organisms were negatively impacted by this large-scale event. Here we describe how the sponge fauna at Bahia, Brazil was influenced by the 1997-8 ENSO event. Sponge assemblages from three contrasting reef habitats (reef tops, walls and shallow banks) at four sites were …

Critical Comparison Of Intravenous Injection Of Tio2 Nanoparticles With Waterborne And Dietary Exposures Concludes Minimal Environmentally-Relevant Toxicity In Juvenile Rainbow Trout Oncorhynchus Mykiss., D Boyle, Ga Al-Bairuty, Tb Henry, Rd Handy

School of Biological and Marine Sciences

A critical comparison of studies that have investigated tissue accumulation and toxicity of TiO2-NPs in fish is necessary to resolve inconsistencies. The present study used identical TiO2-NPs, toxicological endpoints, and fish (juvenile rainbow trout Oncorhynchus mykiss) as previous studies that investigated waterborne and dietary toxicity of TiO2-NPs, and conducted a critical comparison of results after intravenous caudal-vein injection of 50 μg of TiO2-NPs and bulk TiO2. Injected TiO2-NPs accumulated only in kidney (94% of measured Ti) and to a lesser extent in spleen; and injected bulk TiO2 was found only in kidney. No toxicity of TiO2 was observed in kidney, …

Relative Sensitivity Of Two Marine Bivalves For Detection Of Genotoxic And Cytotoxic Effects: A Field Assessment In The Tamar Estuary, South West England., Lorna J. Dallas, Victoria V. Cheung, Andrew S. Fisher, Awadhesh N. Jha

School of Geography, Earth and Environmental Sciences

The input of anthropogenic contaminants to the aquatic environment is a major concern for scientists, regulators and the public. This is especially relevant in areas such as the Tamar valley in SW England, which has a legacy of contamination from industrial activity in the nineteenth and twentieth centuries. Following on from previous laboratory validation studies, this study aimed to assess the relationship between genotoxic and cytotoxic responses and heavy metal concentrations in two bivalve species sampled from locations along the Tamar estuary. Adult cockles, Cerastoderma edule, and blue mussels, Mytilus edulis, were sampled from five locations in the Tamar and …

Effect Of Muscle Length On Cross-Bridge Kinetics In Intact Cardiac Trabeculae At Body Temperature, Nima Milani-Nejad, Ying Xu, Jonathan P. Davis, Kenneth S. Campbell, Paul M. L. Janssen

Physiology Faculty Publications

Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank–Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (k_tr; which depends …

Global Profiling Of Alternative Splicing Events And Gene Expression Regulated By Hnrnph/F, Erming Wang, Vahid Aslanzadeh, Filomena Papa, Haiyan Zhu, Pierre De La Grange, Franca Cambi

Neurology Faculty Publications

In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events …

Vegf And Angiopoietin-1 Exert Opposing Effects On Cell Junctions By Regulating The Rho Gef Syx, Siu P. Ngok, Rory Geyer, Miaoliang Liu, Antonis Kourtidis, Sudesh Agrawal, Chuanshen Wu, Himabindu Reddy Seerapu, Laura J. Lewis-Tuffin, Karen L. Moodie, Deborah Huveldt, Ruth Marx, Jay M. Baraban, Peter Storz, Arie Horowitz, Panos Z. Anastasiadis

Dartmouth Scholarship

Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was …

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …

Degeneration Of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits Following Mid-Cervical Spinal Contusion In Mice., Charles Nicaise, Rajarshi Putatunda, Tamara J Hala, Kathleen A Regan, David M Frank, Jean-Pierre Brion, Karelle Leroy, Roland Pochet, Megan C Wright, Angelo C Lepore

Department of Neuroscience Faculty Papers

A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have …