Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes.
Author information: Babon JA1, DeNicola ME1, Blodgett DM1, Crèvecoeur I2, Buttrick TS3, Maehr R4, Bottino R5,6, Naji A7, Kaddis J8, Elyaman W3, James EA9, Haliyur R10, Brissova M10, Overbergh L2, Mathieu C2, Delong T11, Haskins K11, Pugliese A12, Campbell-Thompson M13, Mathews C13, Atkinson MA13, Powers AC10,14,15, Harlan DM1, Kent SC1.
1Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
3Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
4Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
5Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania, USA.
6Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
7Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
8Department of Information Sciences, Beckman Research Institute, City of Hope, Duarte, California, USA.
9Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
10Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
11Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
12Diabetes Research Institute, University of Miami, Miami, Florida, USA.
13Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.
14Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
15Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Journal: Nature Medicine
Date of e-pub: October 2016
Abstract: A major therapeutic goal for type 1 diabetes (T1D) is to induce autoantigen-specific tolerance of T cells. This could suppress autoimmunity in those at risk for the development of T1D, as well as in those with established disease who receive islet replacement or regeneration therapy. Because functional studies of human autoreactive T cell responses have been limited largely to peripheral blood-derived T cells, it is unclear how representative the peripheral T cell repertoire is of T cells infiltrating the islets. Our knowledge of the insulitic T cell repertoire is derived from histological and immunohistochemical analyses of insulitis, the identification of autoreactive CD8+ T cells in situ, in islets of human leukocyte antigen (HLA)-A2+ donors and isolation and identification of DQ8 and DQ2-DQ8 heterodimer-restricted, proinsulin-reactive CD4+ T cells grown from islets of a single donor with T1D. Here we present an analysis of 50 of a total of 236 CD4+ and CD8+ T cell lines grown from individual handpicked islets or clones directly sorted from handpicked, dispersed islets from nine donors with T1D. Seventeen of these T cell lines and clones reacted to a broad range of studied native islet antigens and to post-translationally modified peptides. These studies demonstrate the existence of a variety of islet-infiltrating, islet-autoantigen reactive T cells in individuals with T1D, and these data have implications for the design of successful immunotherapies.
Current Limitations and Recommendations to Improve Testing for the Environmental Assessment of Endocrine Active Substances.
Author information: Coady KK1, Biever RC2, Denslow ND3, Gross M4, Guiney PD5, Holbech H6, Karouna-Renier NK7, Katsiadaki I8, Krueger H9, Levine SL10, Maack G11, Williams M12, Wolf JC13, Ankley GT14.
1The Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI, 48674. firstname.lastname@example.org.
2Smithers Viscient Laboratories, 790 Main Street Wareham, Wareham, MA, 02571.
3Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, 32611.
4wca, Brunel House, Volunteer Way, Faringdon, SN7 7YR, UK.
5Molecular & Environmental Toxicology Center, University of Wisconsin, 1010B McArdle Bldg., 1400 University Avenue, Madison, WI, 53706.
6Department of Biology, University of Southern Denmark, Campusvej 55, Odense, 5230, Odense M., Denmark.
7USGS Patuxent Wildlife Research Center, BARC-East, Building 308, 10300 Baltimore Avenue, Beltsville, MD, 20705.
8Centre for Environment Fisheries and Aquaculture science (Cefas), Barrack Road, Weymouth, Dorset, DT4 8UB, UK.
9Wildlife International, a Division of EAG, 8598 Commerce Drive, Easton, MD, 21601.
10Global Regulatory Sciences, Monsanto Company, 800 N. Lindbergh Blvd, St Louis, MO, 63017.
11German Environment Agency (UBA), Wörlitzer Platz 1, D-06844, Dessau-Roßlau, Germany.
12CSIRO Land and Water, Waite Campus, Urrbrae SA, SA, 5064, Australia.
13Experimental Pathology Laboratories, Inc., 45600 Terminal Drive, Sterling, VA, 20166.
14US Environmental Protection Agency, 6201 Congdon Blvd, Duluth, MN, 55804.
Journal: Integrated Environmental Assessment and Management
Date of e-pub: October 2016
Abstract: In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or the environment. Current test systems include in silico, in vitro and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life-stages, 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern, and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive in regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to, and guidance for existing test methods, and reduce uncertainty. For example, in vitro high throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assay(s) for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen and thyroid signaling.
Author information: Bourque S1, Jeandroz S2, Grandperret V2, Lehotai N2, Aimé S2, Soltis DE3, Miles NW4, Melkonian M5, Deyholos MK6, Leebens-Mack JH7, Chase MW8, Rothfels CJ9, Stevenson DW10, Graham SW11, Wang X12, Wu S12, Pires JC13, Edger PP14, Yan Z15, Xie Y15, Carpenter EJ16, Wong GK17, Wendehenne D2, Nicolas-Francès V2.
1Agroécologie, AgroSup Dijon, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Université Bourgogne Franche-Comté, 21000 Dijon, France. Electronic address: email@example.com.
2Agroécologie, AgroSup Dijon, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Université Bourgogne Franche-Comté, 21000 Dijon, France.
3Department of Biology, Florida Museum of Natural History, Gainesville, FL 32611, USA; Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
4Department of Biological Sciences, University of North Texas, 1155 Union Circle, Denton, TX 76201, USA.
5Botanical Institute, Cologne Biocenter, University of Cologne, 50674 Cologne, Germany.
6Department of Biology, University of British Columbia, Kelowna, BC V1V 1V7, Canada.
7Department of Plant Biology, University of Georgia, Athens, GA 30602, USA.
8Jodrell Laboratory, Royal Botanic Gardens Kew, Richmond, Surrey, UK; Plant Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, 6009, Western Australia.
9University Herbarium and Department of Integrative Biology, University of California Berkeley, Berkeley, CA 94720, USA.
10New York Botanical Garden, 2900 Southern Boulevard, Bronx, NY 10458, USA.
11Department of Botany, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
12Chinese Academy of Sciences (CAS) Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, CAS, 1-104 Beichen West Road, Chaoyang District, Beijing 100101, China.
13Division of Biological Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
14Department of Horticulture, Michigan State University, East Lansing, MI 48823, USA.
15Beijing Genomics Institute (BGI)-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
16Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
17Beijing Genomics Institute (BGI)-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada; Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Journal: Trends in Plant Science
Date of e-pub: October 2016
Abstract: In eukaryotes, protein deacetylation is carried out by two well-conserved histone deacetylase (HDAC) families: RPD3/HDA1 and SIR2. Intriguingly, model plants such as Arabidopsis express an additional plant-specific HDAC family, termed type-2 HDACs (HD2s). Transcriptomic analyses from more than 1300 green plants generated by the 1000 plants (1KP) consortium showed that HD2s appeared early in green plant evolution, the first members being detected in several streptophyte green alga. The HD2 family has expanded via several rounds of successive duplication; members are expressed in all major green plant clades. Interestingly, angiosperm species express new HD2 genes devoid of a zinc-finger domain, one of the main structural features of HD2s. These variants may have been associated with the origin and/or the biology of the ovule/seed.
Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola.
Author information: Azarian T1, Ali A1,2, Johnson JA1,3, Jubair M1,2, Cella E1,4,5, Ciccozzi M5,6, Nolan DJ1,3, Farmerie W7, Rashid MH1, Sinha-Ray S1, Alam MT1,2, Morris JG1,8, Salemi M1,3.
1Emerging Pathogens Institute, University of Florida, Gainesville, USA.
2Department of Environmental and Global Health, College of Public Health and Health Profession, University of Florida, Gainesville, Florida, USA.
3Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, USA.
4Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
5Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
6University Hospital Campus Bio-Medico, Italy.
7Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, Florida, USA.
8Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
Journal: Science Reports
Date of e-pub: October 2016
Abstract: Vibrio cholerae is ubiquitous in aquatic environments, with environmental toxigenic V. cholerae O1 strains serving as a source for recurrent cholera epidemics and pandemic disease. However, a number of questions remain about long-term survival and evolution of V. cholerae strains within these aquatic environmental reservoirs. Through monitoring of the Haitian aquatic environment following the 2010 cholera epidemic, we isolated two novel non-toxigenic (ctxA/B-negative) Vibrio cholerae O1. These two isolates underwent whole-genome sequencing and were investigated through comparative genomics and Bayesian coalescent analysis. These isolates cluster in the evolutionary tree with strains responsible for clinical cholera, possessing genomic components of 6th and 7th pandemic lineages, and diverge from “modern” cholera strains around 1548 C.E. [95% HPD: 1532-1555]. Vibrio Pathogenicity Island (VPI)-1 was present; however, SXT/R391-family ICE and VPI-2 were absent. Rugose phenotype conversion and vibriophage resistance evidenced adaption for persistence in aquatic environments. The identification of V. cholerae O1 strains in the Haitian environment, which predate the first reported cholera pandemic in 1817, broadens our understanding of the history of pandemics. It also raises the possibility that these and similar environmental strains could acquire virulence genes from the 2010 Haitian epidemic clone, including the cholera toxin producing CTXϕ.
Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity.
Author information: Bonifacio E1,2, Mathieu C3, Nepom GT4, Ziegler AG5,6, Anhalt H7, Haller MJ8, Harrison LC9,10, Hebrok M11, Kushner JA12, Norris JM13, Peakman M14,15, Powers AC16,17, Todd JA18, Atkinson MA19.
1DFG Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Fetscherstrasse 105, 01307, Dresden, Germany. firstname.lastname@example.org.
2Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Technische Universität Dresden, Dresden, Germany. email@example.com.
3Clinical and Experimental Endocrinology, University Hospital of Leuven, Leuven, Belgium.
4Benaroya Research Institute at Virginia Mason, The University of Washington School of Medicine, Seattle, WA, USA.
5Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany.
6Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
7T1D Exchange, Boston, MA, USA.
8Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
9Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
10Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia.
11University of California, San Francisco Diabetes Center, San Francisco, CA, USA.
12McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College Medical Center, Houston, TX, USA.
13Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
14Department of Immunobiology, King’s College London Faculty of Life Sciences & Medicine, London, UK.
15National Institute of Health Research Biomedical Research Centre at Guy’s and St Thomas’ Hospitals and King’s College London, London, UK.
16Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University School of Medicine, Nashville, TN, USA.
17VA Tennessee Valley Healthcare System, Nashville, TN, USA.
18JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
19Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
Date of e-pub: October 2016
Abstract: The asymptomatic phase of type 1 diabetes is recognised by the presence of beta cell autoantibodies in the absence of hyperglycaemia. We propose that an accurate description of this stage is provided by the name ‘Autoimmune Beta Cell Disorder’ (ABCD). Specifically, we suggest that this nomenclature and diagnosis will, in a proactive manner, shift the paradigm towards type 1 diabetes being first and foremost an immune-mediated disease and only later a metabolic disease, presaging more active therapeutic intervention in the asymptomatic stage of disease, before end-stage beta cell failure. Furthermore, we argue that accepting ABCD as a diagnosis will be critical in order to accelerate pharmaceutical, academic and public activities leading to clinical trials that could reverse beta cell autoimmunity and halt progression to symptomatic insulin-requiring type 1 diabetes. We recognize that there are both opportunities and challenges in the implementation of the ABCD concept but hope that the notion of ‘asymptomatic autoimmune disease’ as a disorder will be widely discussed and eventually accepted.
Effects of four commercial fungal formulations on mortality and sporulation in house flies (Musca domestica) and stable flies (Stomoxys calcitrans).
Author information: Weeks EN1, Machtinger ET2, Gezan SA3, Kaufman PE4, Geden CJ5.
1Department of Entomology and Nematology, University of Florida, Gainesville, FL, U.S.A.. firstname.lastname@example.org.
2Invasive Insect Biocontrol and Behaviour Laboratory, U.S. Department of Agriculture-Agricultural Research Service (USDA-ARS), Beltsville, MD, U.S.A.
3School of Forest Resources and Conservation, University of Florida, Gainesville, FL, U.S.A.
4Department of Entomology and Nematology, University of Florida, Gainesville, FL, U.S.A.
5Center for Medical, Agricultural and Veterinary Entomology, USDA-ARS, Gainesville, FL, U.S.A.
Journal: Medical and Veterinary Entomology
Date of e-pub: October 2016
Abstract: The house fly Musca domestica L. (Diptera: Muscidae) and stable fly Stomoxys calcitrans (L.) (Diptera: Muscidae) are major pests of livestock. Biological control is an important tool in an integrated control framework. Increased mortality in filth flies has been documented with entomopathogenic fungi, several strains of which are commercially available. Three strains of Beauveria bassiana (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitaceae) and one strain of Metarhizium brunneum (Petch) (Hypocreales: Clavicipitaceae) were tested in commercial formulations for pathogenicity against house flies and stable flies. There was a significant increase in mortality of house flies with three of the formulations, BotaniGard® ES, Mycotrol® O, and Met52® EC, during days 4-9 in comparison with balEnce™ and the control. In stable flies, mortality rates were highest with Met52® EC, followed by Mycotrol® O, BotaniGard® ES and, finally, balEnce™. There was a significant fungal effect on sporulation in both house flies and stable flies. Product formulation, species differences and fungal strains may be responsible for some of the differences observed. Future testing in field situations is necessary. These commercial biopesticides may represent important tools in integrated fly management programmes.
NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine