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  • 1
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    Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-26
    Description: T cell-mediated destruction of insulin-producing beta cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in beta cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in beta cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in beta cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delong, Thomas -- Wiles, Timothy A -- Baker, Rocky L -- Bradley, Brenda -- Barbour, Gene -- Reisdorph, Richard -- Armstrong, Michael -- Powell, Roger L -- Reisdorph, Nichole -- Kumar, Nitesh -- Elso, Colleen M -- DeNicola, Megan -- Bottino, Rita -- Powers, Alvin C -- Harlan, David M -- Kent, Sally C -- Mannering, Stuart I -- Haskins, Kathryn -- 1K01DK094941/DK/NIDDK NIH HHS/ -- 1R01DK081166/DK/NIDDK NIH HHS/ -- 5U01DK89572/DK/NIDDK NIH HHS/ -- DK104211/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):711-4. doi: 10.1126/science.aad2791.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. thomas.delong@ucdenver.edu katie.haskins@ucdenver.edu. ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. ; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. ; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA. ; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA. ; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. VA Tennessee Valley Healthcare System, Nashville, TN, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912858" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; C-Peptide/chemistry/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Clone Cells ; Diabetes Mellitus, Experimental/*immunology/pathology ; Diabetes Mellitus, Type 1/*immunology/pathology ; Epitopes/*immunology ; Immune Tolerance ; Insulin-Secreting Cells/*immunology/pathology ; Mice ; Mice, Inbred NOD ; Molecular Sequence Data ; Peptides/chemistry/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    PaCTS 1.0: A Crowdsourced Reporting Standard for Paleoclimate Data (2019)
    Wiley
    Details
    Publication Date: 2019
    Description: Abstract The progress of science is tied to the standardization of measurements, instruments, and data. This is especially true in the Big Data age, where analyzing large data volumes critically hinges on the data being standardized. Accordingly, the lack of community‐sanctioned data standards in paleoclimatology has largely precluded the benefits of Big Data advances in the field. Building upon recent efforts to standardize the format and terminology of paleoclimate data, this article describes the Paleoclimate Community reporTing Standard (PaCTS), a crowdsourced reporting standard for such data. PaCTS captures which information should be included when reporting paleoclimate data, with the goal of maximizing the reuse value of paleoclimate datasets, particularly for synthesis work and comparison to climate model simulations. Initiated by the LinkedEarth project, the process to elicit a reporting standard involved an international workshop in 2016, various forms of digital community engagement over the next few years, and grassroots working groups. Participants in this process identified important properties across paleoclimate archives, in addition to the reporting of uncertainties and chronologies; they also identified archive‐specific properties and distinguished reporting standards for new vs. legacy datasets. This work shows that at least 135 respondents overwhelmingly support a drastic increase in the amount of metadata accompanying paleoclimate datasets. Since such goals are at odds with present practices, we discuss a transparent path towards implementing or revising these recommendations in the near future, using both bottom‐up and top‐down approaches.
    Print ISSN: 0883-8305
    Electronic ISSN: 2572-4525
    Topics: Geosciences
    Published by Wiley on behalf of American Geophysical Union (AGU).
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