Digital Commons Network^™

Derivation Of Multivariate Syndromic Outcome Metrics For Consistent Testing Across Multiple Models Of Cervical Spinal Cord Injury In Rats, Adam R. Ferguson, Karen-Amanda Irvine, John C. Gensel, Jessica L. Nielson, Amity Lin, Johnathan Ly, Mark R. Segal, Rajiv R. Ratan, Jacqueline C. Bresnahan, Michael S. Beattie

Physiology Faculty Publications

Spinal cord injury (SCI) and other neurological disorders involve complex biological and functional changes. Well-characterized preclinical models provide a powerful tool for understanding mechanisms of disease; however managing information produced by experimental models represents a significant challenge for translating findings across research projects and presents a substantial hurdle for translation of novel therapies to humans. In the present work we demonstrate a novel 'syndromic' information-processing approach for capitalizing on heterogeneous data from diverse preclinical models of SCI to discover translational outcomes for therapeutic testing. We first built a large, detailed repository of preclinical outcome data from 10 years of basic …

Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin

Dartmouth Scholarship

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report …

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …

Experimental And Natural Warming Elevates Mercury Concentrations In Estuarine Fish, Jennifer A. Dijkstra, Kate L. Buckman, Darren Ward, David W. Evans, Michele Dionne, Celia Y. Chen

Dartmouth Scholarship

Marine food webs are the most important link between the global contaminant, methylmercury (MeHg), and human exposure through consumption of seafood. Warming temperatures may increase human exposure to MeHg, a potent neurotoxin, by increasing MeHg production as well as bioaccumulation and trophic transfer through marine food webs. Studies of the effects of temperature on MeHg bioaccumulation are rare and no study has specifically related temperature to MeHg fate by linking laboratory experiments with natural field manipulations in coastal ecosystems. We performed laboratory and field experiments on MeHg accumulation under varying temperature regimes using the killifish, Fundulus heteroclitus. Temperature treatments …

Melanopsin, Photosensitive Ganglion Cells, And Seasonal Affective Disorder., Kathryn A Roecklein, Patricia M Wong, Megan A Miller, Shannon D Donofry, Marissa L Kamarck, George C Brainard

Department of Neurology Faculty Papers

In two recent reports, melanopsin gene variations were associated with seasonal affective disorder (SAD), and in changes in the timing of sleep and activity in healthy individuals. New studies have deepened our understanding of the retinohypothalamic tract, which translates environmental light received by the retina into neural signals sent to a set of nonvisual nuclei in the brain that are responsible for functions other than sight including circadian, neuroendocrine and neurobehavioral regulation. Because this pathway mediates seasonal changes in physiology, behavior, and mood, individual variations in the pathway may explain why approximately 1-2% of the North American population develops mood …

Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel

Open Access Publications

Primate evolution has been accompanied by complex reorganizations in brain anatomy and function. Little is known, however, about the relationship between anatomical and functional changes induced through primate evolution. Using functional magnetic resonance imaging, we assessed spatial and temporal correspondences of cortical networks in humans and monkeys. We provided evidence for topologically and functionally correspondent networks in sensory-motor and attention regions. More specifically, we revealed a possible monkey equivalent of the human ventral attention network. For other human networks, such as the language and the default-mode networks, we detected topological correspondent networks in the monkey, but with different functional signatures. …

The Disruption Of Celf6, A Gene Identified By Translational Profiling Of Serotonergic Neurons, Results In Autism-Related Behaviors, Joseph D. Dougherty, Susan E. Maloney, David F. Wozniak, Michael A. Rieger, Lisa Sonnenblick, Giovanni Coppola, Nathaniel G. Mahieu, Juliet Zhang, Jinlu Cai, Gary J. Patti, Brett S. Abrahams, Daniel H. Geschwind, Nathaniel Heintz

Open Access Publications

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, …

Wolbachia Association With The Tsetse Fly, Glossina Fuscipes Fuscipes, Reveals High Levels Of Genetic Diversity And Complex Evolutionary Dynamics, Rebecca E. Symula, Uzma Alam, Corey L. Brelsfoard, Yineng Wu, Richard Echodu, Loyce M. Okedi, Serap Aksoy, Adalgisa Caccone

Entomology Faculty Publications

BACKGROUND: Wolbachia pipientis, a diverse group of α-proteobacteria, can alter arthropod host reproduction and confer a reproductive advantage to Wolbachia-infected females (cytoplasmic incompatibility (CI)). This advantage can alter host population genetics because Wolbachia-infected females produce more offspring with their own mitochondrial DNA (mtDNA) haplotypes than uninfected females. Thus, these host haplotypes become common or fixed (selective sweep). Although simulations suggest that for a CI-mediated sweep to occur, there must be a transient phase with repeated initial infections of multiple individual hosts by different Wolbachia strains, this has not been observed empirically. Wolbachia has been found in the tsetse fly, Glossina …

Caveolin-1 Deficiency Induces Spontaneous Endothelial-To-Mesenchymal Transition In Murine Pulmonary Endothelial Cells In Vitro., Zhaodong Li, Peter J. Wermuth, Bryan S. Benn, Michael P. Lisanti, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

It was previously demonstrated that transforming growth factor β (TGF-β) induces endothelial-to-mesenchymal transition (EndoMT) in murine lung endothelial cells (ECs) in vitro. Owing to the important role of caveolin-1 (CAV1) in TGF-β receptor internalization and TGF-β signaling, the participation of CAV1 in the induction of EndoMT in murine lung ECs was investigated. Pulmonary ECs were isolated from wild-type and Cav1 knockout mice using immunomagnetic methods with sequential anti-CD31 and anti-CD102 antibody selection followed by in vitro culture and treatment with TGF-β1. EndoMT was assessed by semiquantitative RT-PCR for Acta2, Col1a1, Snai1, and Snai2; by immunofluorescence for α-smooth muscle actin; and …

Molecular Diversity Of Bacteroidales In Fecal And Environmental Samples And Swine-Associated Subpopulations, Regina Lamendella, Kent C. Li, Daniel B. Oerther, Jorge W. Santo Domingo

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Several swine-specific microbial source tracking methods are based on PCR assays targeting Bacteroidales 16S rRNA gene sequences. The limited application of these assays can be explained by the poor understanding of their molecular diversity in fecal sources and environmental waters. In order to address this, we studied the diversity of 9,340 partial (>600bp in length) Bacteroidales 16S rRNA gene sequences from 13 fecal sources and nine feces-contaminated watersheds. The compositions of major Bacteroidales populations were analyzed to determine which host and environmental sequences were contributing to each group. This information allowed us to identify populations which were both exclusive …

Genome-Wide Analysis Reveals Selection For Important Traits In Domestic Horse Breeds, Jessica L. Petersen, James R. Mickelson, Aaron K. Rendahl, Stephanie J. Valberg, Lisa S. Andersson, Jeanette Axelsson, Ernie Bailey, Danika Bannasch, Matthew M. Binns, Alexandre S. Borges, Pieter Brama, Artur Da Câmara Machado, Stefano Capomaccio, Katia Cappelli, E. Gus Cothran, Ottmar Distl, Laura Fox-Clipsham, Kathryn T. Graves, Gérard Guérin, Bianca Haase, Telhisa Hasegawa, Karin Hemmann, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, Hannes Lohi, Maria Susana Lopes, Beatrice A. Mcgivney, Sofia Mikko, Nicholas Orr, M. Cecilia T. Penedo, Richard J. Piercy, Marja Raekallio, Stefan Rieder, Knut H Røed, June Swinburne, Teruaki Tozaki, Mark Vaudin, Claire M. Wade, Molly E. Mccue

Veterinary Science Faculty Publications

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST)-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with …

Dual-Tracer Background Subtraction Approach For Fluorescent Molecular Tomography, Kenneth M. Tichauer, Robert W. Holt, Fadi El-Ghussein, Scott C. Davis, Kimberly S. Samkoe, Jason R. Gunn, Frederic Leblond, Brian W. Pogue

Dartmouth Scholarship

Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction …

Gleevec, An Abl Family Inhibitor, Produces A Profound Change In Cell Shape And Migration, Zaozao Chen, Elizabeth Lessey, Matthew E. Berginski, Li Cao, Jonathan Li, Xavier Trepat, Michelle Itano, Shawn M. Gomez, Maryna Kapustina, Cai Huang, Keith Burridge, George Truskey, Ken Jacobson

Markey Cancer Center Faculty Publications

The issue of how contractility and adhesion are related to cell shape and migration pattern remains largely unresolved. In this paper we report that Gleevec (Imatinib), an Abl family kinase inhibitor, produces a profound change in the shape and migration of rat bladder tumor cells (NBTII) plated on collagen-coated substrates. Cells treated with Gleevec adopt a highly spread D-shape and migrate more rapidly with greater persistence. Accompanying this more spread state is an increase in integrin-mediated adhesion coupled with increases in the size and number of discrete adhesions. In addition, both total internal reflection fluorescence microscopy (TIRFM) and interference reflection …

Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber

College of Science & Mathematics Departmental Research

BACKGROUND: Chronic alcohol use causes widespread changes in the cellular biology of the amygdala's central nucleus (CeA), a GABAergic center that integrates autonomic physiology with the emotional aspects of motivation and learning. While alcohol-induced neurochemical changes play a role in dependence and drinking behavior, little is known about the CeA's dynamic changes during withdrawal, a period of emotional and physiologic disturbance.

METHODS: We used a qRT-PCR platform to measure 139 transcripts in 92 rat CeA samples from control (N = 33), chronically alcohol exposed (N = 26), and withdrawn rats (t = 4, 8, 18, 32, and 48 hours; N …

Evaluation Of Copper Concentration In Subclinical Cases Of White Muscle Disease And Its Relationship With Cardiac Troponin I, F. Ataollahi, M. Mohri, H.A. Seifi, Belinda Pingguan-Murphy, Wan Abu Bakar Wan Abas, Noor Azuan Abu Osman

Research Publications (2011 to 2015)

The present study aims to evaluate the serum level of copper (Cu) in lambs suffering from subclinical forms of white muscle disease (WMD) and its relationship with cardiac troponin I (cTn-I) as a novel biomarker of cardiovascular disorders. Ten milliliters of jugular blood were taken from 200 lambs less than one year old to measure serum concentrations of Cu, selenium (Se), and cTn-I. The subjects were divided into 2 groups, namely, the deficient group which included 36 lambs, and the control group which included 164 lambs according to the reference serum Se concentration (50 ng/mL). Serum Se levels in the …

Therapies For Neovascular Age-Related Macular Degeneration: Current Approaches And Pharmacologic Agents In Development., Mostafa Hanout, Daniel Ferraz, Mehreen Ansari, Natasha Maqsood, Saleema Kherani, Yasir J. Sepah, Nithya Rajagopalan, Mohamed Ibrahim, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is …

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 …

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 …

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 …

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.

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 …

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 …

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 …

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 …

Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini

Dartmouth Scholarship

We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …

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 …

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 …

The P2y(12) Antagonists, 2mesamp And Cangrelor, Inhibit Platelet Activation Through P2y(12)/G(I)-Dependent Mechanism, Binggang Xiang, Guoying Zhang, Hongmei Ren, Manjula Sunkara, Andrew J. Morris, T. Kent Gartner, Susan S. Smyth, Zhenyu Li

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism.

METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to …

Reactive Oxygen Species Production And Brugia Pahangi Survivorship In Aedes Polynesiensis With Artificial Wolbachia Infection Types, Elizabeth S. Andrews, Philip R. Crain, Yuqing Fu, Daniel K. Howe, Stephen L. Dobson

Entomology Faculty Publications

Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF) throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB") experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive …