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  • 1
    Publication Date: 2012-11-07
    Description: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491803/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491803/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jostins, Luke -- Ripke, Stephan -- Weersma, Rinse K -- Duerr, Richard H -- McGovern, Dermot P -- Hui, Ken Y -- Lee, James C -- Schumm, L Philip -- Sharma, Yashoda -- Anderson, Carl A -- Essers, Jonah -- Mitrovic, Mitja -- Ning, Kaida -- Cleynen, Isabelle -- Theatre, Emilie -- Spain, Sarah L -- Raychaudhuri, Soumya -- Goyette, Philippe -- Wei, Zhi -- Abraham, Clara -- Achkar, Jean-Paul -- Ahmad, Tariq -- Amininejad, Leila -- Ananthakrishnan, Ashwin N -- Andersen, Vibeke -- Andrews, Jane M -- Baidoo, Leonard -- Balschun, Tobias -- Bampton, Peter A -- Bitton, Alain -- Boucher, Gabrielle -- Brand, Stephan -- Buning, Carsten -- Cohain, Ariella -- Cichon, Sven -- D'Amato, Mauro -- De Jong, Dirk -- Devaney, Kathy L -- Dubinsky, Marla -- Edwards, Cathryn -- Ellinghaus, David -- Ferguson, Lynnette R -- Franchimont, Denis -- Fransen, Karin -- Gearry, Richard -- Georges, Michel -- Gieger, Christian -- Glas, Jurgen -- Haritunians, Talin -- Hart, Ailsa -- Hawkey, Chris -- Hedl, Matija -- Hu, Xinli -- Karlsen, Tom H -- Kupcinskas, Limas -- Kugathasan, Subra -- Latiano, Anna -- Laukens, Debby -- Lawrance, Ian C -- Lees, Charlie W -- Louis, Edouard -- Mahy, Gillian -- Mansfield, John -- Morgan, Angharad R -- Mowat, Craig -- Newman, William -- Palmieri, Orazio -- Ponsioen, Cyriel Y -- Potocnik, Uros -- Prescott, Natalie J -- Regueiro, Miguel -- Rotter, Jerome I -- Russell, Richard K -- Sanderson, Jeremy D -- Sans, Miquel -- Satsangi, Jack -- Schreiber, Stefan -- Simms, Lisa A -- Sventoraityte, Jurgita -- Targan, Stephan R -- Taylor, Kent D -- Tremelling, Mark -- Verspaget, Hein W -- De Vos, Martine -- Wijmenga, Cisca -- Wilson, David C -- Winkelmann, Juliane -- Xavier, Ramnik J -- Zeissig, Sebastian -- Zhang, Bin -- Zhang, Clarence K -- Zhao, Hongyu -- International IBD Genetics Consortium (IIBDGC) -- Silverberg, Mark S -- Annese, Vito -- Hakonarson, Hakon -- Brant, Steven R -- Radford-Smith, Graham -- Mathew, Christopher G -- Rioux, John D -- Schadt, Eric E -- Daly, Mark J -- Franke, Andre -- Parkes, Miles -- Vermeire, Severine -- Barrett, Jeffrey C -- Cho, Judy H -- 068545/Z/02/Wellcome Trust/United Kingdom -- 083948/Z/07/Z/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 089120/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- AI062773/AI/NIAID NIH HHS/ -- CA141743/CA/NCI NIH HHS/ -- CZB/4/540/Chief Scientist Office/United Kingdom -- DK043351/DK/NIDDK NIH HHS/ -- DK062413/DK/NIDDK NIH HHS/ -- DK062420/DK/NIDDK NIH HHS/ -- DK062422/DK/NIDDK NIH HHS/ -- DK062423/DK/NIDDK NIH HHS/ -- DK062429/DK/NIDDK NIH HHS/ -- DK062429-S1/DK/NIDDK NIH HHS/ -- DK062431/DK/NIDDK NIH HHS/ -- DK062432/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK076984/DK/NIDDK NIH HHS/ -- DK084554/DK/NIDDK NIH HHS/ -- DK83756/DK/NIDDK NIH HHS/ -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/British Heart Foundation/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0800675/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G1002033/Medical Research Council/United Kingdom -- K23 DK097142/DK/NIDDK NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- P01 DK046763/DK/NIDDK NIH HHS/ -- P01DK046763/DK/NIDDK NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- R01 CA141743/CA/NCI NIH HHS/ -- R01 DK055731/DK/NIDDK NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 DK062420/DK/NIDDK NIH HHS/ -- U01 DK062422/DK/NIDDK NIH HHS/ -- U01 DK062429/DK/NIDDK NIH HHS/ -- U01 DK062431/DK/NIDDK NIH HHS/ -- U01 DK062432/DK/NIDDK NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1 TR000124-01/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128233" target="_blank"〉PubMed〈/a〉
    Keywords: Colitis, Ulcerative/genetics/immunology/microbiology/physiopathology ; Crohn Disease/genetics/immunology/microbiology/physiopathology ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; *Genome-Wide Association Study ; Haplotypes/genetics ; *Host-Pathogen Interactions/genetics/immunology ; Humans ; Inflammatory Bowel Diseases/*genetics/immunology/*microbiology/physiopathology ; Mycobacterium/*immunology/pathogenicity ; Mycobacterium Infections/genetics/microbiology ; Mycobacterium tuberculosis/immunology/pathogenicity ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-04-30
    Description: Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhernakova, Alexandra -- Kurilshikov, Alexander -- Bonder, Marc Jan -- Tigchelaar, Ettje F -- Schirmer, Melanie -- Vatanen, Tommi -- Mujagic, Zlatan -- Vila, Arnau Vich -- Falony, Gwen -- Vieira-Silva, Sara -- Wang, Jun -- Imhann, Floris -- Brandsma, Eelke -- Jankipersadsing, Soesma A -- Joossens, Marie -- Cenit, Maria Carmen -- Deelen, Patrick -- Swertz, Morris A -- LifeLines cohort study -- Weersma, Rinse K -- Feskens, Edith J M -- Netea, Mihai G -- Gevers, Dirk -- Jonkers, Daisy -- Franke, Lude -- Aulchenko, Yurii S -- Huttenhower, Curtis -- Raes, Jeroen -- Hofker, Marten H -- Xavier, Ramnik J -- Wijmenga, Cisca -- Fu, Jingyuan -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):565-9. doi: 10.1126/science.aad3369. Epub 2016 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl. ; Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. Novosibirsk State University, Novosibirsk, Russia. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Computer Science, Aalto University School of Science, Espoo, Finland. ; Top Institute Food and Nutrition, Wageningen, Netherlands. Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands. ; University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, Netherlands. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. ; University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands. ; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Microbial Ecology, Nutrition and Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain. Department of Pediatrics, Dr. Peset University Hospital, Valencia, Spain. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, Netherlands. ; Top Institute Food and Nutrition, Wageningen, Netherlands. Division of Human Nutrition, Wageningen University, Wageningen, Netherlands. ; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. ; Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands. ; Novosibirsk State University, Novosibirsk, Russia. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. PolyOmica, Groningen, Netherlands. Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl. ; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126040" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*classification/genetics/isolation & purification ; Chromogranin A/analysis/metabolism ; Diet ; Enteroendocrine Cells/metabolism ; Feces/chemistry/microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Genetic Markers ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; Netherlands ; Phylogeny ; RNA, Ribosomal, 16S/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2021-09-23
    Description: In kidney transplantation, microthrombi and fibrin deposition may lead to local perfusion disorders and subsequently poor initial graft function. Microthrombi are often regarded as donor-derived. However, the incidence, time of development, and potential difference between living donor kidneys (LDK) and deceased donor kidneys(DDK), remains unclear. Two open-needle biopsies, taken at preimplantation and after reperfusion, were obtained from 17 LDK and 28 DDK transplanted between 2005 and 2008. Paraffin-embedded sections were immunohistochemically stained with anti-fibrinogen antibody. Fibrin deposition intensity in peritubular capillaries(PTC) and glomeruli was categorized as negative, weak, moderate or strong and the number of microthrombi/mm2 was quantified. Reperfusion biopsies showed more fibrin deposition (20% to 100% moderate/strong, p 
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 4
    Publication Date: 2021-10-22
    Description: Purpose In a search for potentially modifiable factors to improve long-term outcome among kidney transplant recipients (KTR), we hypothesized that boron exposure is associated with improved long-term outcome in KTR. Methods We determined 24 h urinary boron excretion using inductively coupled plasma mass spectrometry as a measure of boron exposure in 693 stable KTR (57% male, mean age 53y), enrolled in the TransplantLines Food and Nutrition Biobank and Cohort Study. Dietary intake was assessed using validated food-frequency questionnaires. Results Linear regression analyses showed that dietary intake of fruit, wine and nuts were key determinants of boron excretion. In addition, boron excretion was negatively correlated with homocysteine and inflammatory parameters. In total, 73 (32%), 47 (20%) and 30 (13%) KTR died among the lowest, middle and highest tertiles of 24 h urinary boron excretion, respectively (Plog-rank 
    Print ISSN: 1436-6207
    Electronic ISSN: 1436-6215
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Published by Springer
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