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  • 1
    Publication Date: 2015-12-04
    Description: In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681099/" 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/PMC4681099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forslund, Kristoffer -- Hildebrand, Falk -- Nielsen, Trine -- Falony, Gwen -- Le Chatelier, Emmanuelle -- Sunagawa, Shinichi -- Prifti, Edi -- Vieira-Silva, Sara -- Gudmundsdottir, Valborg -- Krogh Pedersen, Helle -- Arumugam, Manimozhiyan -- Kristiansen, Karsten -- Voigt, Anita Yvonne -- Vestergaard, Henrik -- Hercog, Rajna -- Igor Costea, Paul -- Kultima, Jens Roat -- Li, Junhua -- Jorgensen, Torben -- Levenez, Florence -- Dore, Joel -- MetaHIT consortium -- Nielsen, H Bjorn -- Brunak, Soren -- Raes, Jeroen -- Hansen, Torben -- Wang, Jun -- Ehrlich, S Dusko -- Bork, Peer -- Pedersen, Oluf -- England -- Nature. 2015 Dec 10;528(7581):262-6. doi: 10.1038/nature15766. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany. ; VIB Center for the Biology of Disease, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; Department of Bioscience Engineering, Vrije Universiteit Brussel, 1040 Brussels, Belgium. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. ; MICALIS, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Metagenopolis, Institut National de la Recherche Agronomique, 78352 Jouy en Josas, France. ; Institute of Cardiometabolism and Nutrition, 75013 Paris, France. ; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. ; Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany. ; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany. ; Bejing Genomics Institute (BGI)-Shenzhen, 518083 Shenzhen, China. ; Research Centre for Prevention and Health, Capital Region of Denmark, 2600 Glostrup, Denmark. ; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2600 Copenhagen, Denmark. ; Faculty of Medicine, University of Aalborg, 9100 Aalborg, Denmark. ; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ; Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark. ; Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, 80205 Jeddah, Saudi Arabia. ; Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. ; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong. ; Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, King's College London, London SE1 9RT , UK. ; Max Delbruck Centre for Molecular Medicine, 13125 Berlin, Germany. ; Department of Bioinformatics, University of Wuerzburg, 97074 Wurzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633628" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; Diabetes Mellitus, Type 2/drug therapy/*microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics/*physiology ; Humans ; Hypoglycemic Agents/pharmacology/therapeutic use ; Male ; Metagenome/drug effects/physiology ; Metformin/*pharmacology/therapeutic use ; RNA, Ribosomal, 16S/genetics
    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: 2014-02-14
    Description: Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 (14)C years before present (bp) (13,000 to 12,600 calendar years bp). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology. However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans. An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum. Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 +/- 35 (14)C years bp (approximately 12,707-12,556 calendar years bp) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4x and show that the gene flow from the Siberian Upper Palaeolithic Mal'ta population into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years bp. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rasmussen, Morten -- Anzick, Sarah L -- Waters, Michael R -- Skoglund, Pontus -- DeGiorgio, Michael -- Stafford, Thomas W Jr -- Rasmussen, Simon -- Moltke, Ida -- Albrechtsen, Anders -- Doyle, Shane M -- Poznik, G David -- Gudmundsdottir, Valborg -- Yadav, Rachita -- Malaspinas, Anna-Sapfo -- White, Samuel Stockton 5th -- Allentoft, Morten E -- Cornejo, Omar E -- Tambets, Kristiina -- Eriksson, Anders -- Heintzman, Peter D -- Karmin, Monika -- Korneliussen, Thorfinn Sand -- Meltzer, David J -- Pierre, Tracey L -- Stenderup, Jesper -- Saag, Lauri -- Warmuth, Vera M -- Lopes, Margarida C -- Malhi, Ripan S -- Brunak, Soren -- Sicheritz-Ponten, Thomas -- Barnes, Ian -- Collins, Matthew -- Orlando, Ludovic -- Balloux, Francois -- Manica, Andrea -- Gupta, Ramneek -- Metspalu, Mait -- Bustamante, Carlos D -- Jakobsson, Mattias -- Nielsen, Rasmus -- Willerslev, Eske -- BB/H005854/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/H008802/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- P25032/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2014 Feb 13;506(7487):225-9. doi: 10.1038/nature13025.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2]. ; 1] Anzick Family, 31 Old Clyde Park Road, Livingston, Montana 59047, USA [2]. ; Center for the Study of the First Americans, Departments of Anthropology and Geography, Texas A&M University, 4352 TAMU, College Station, Texas 77843-4352, USA. ; Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 752 36 Uppsala, Sweden. ; 1] Department of Integrative Biology, University of California, Berkeley, 4134 Valley Life Sciences Building, Berkeley, California 94720, USA [2] Earth Sciences Department, Natural History Museum, Cromwell Road, London SW7 5BD, UK (I.B.); Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA (M.D.). ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] AMS 14C Dating Centre, Department of Physics & Astronomy, University of Aarhus, Ny Munkegade 120, DK-8000 Aarhus C, Denmark. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, Kgs. Lyngby DK-2800, Denmark. ; 1] The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark [2] Department of Human Genetics, University of Chicago, 920 E. 58th Street, CLSC 4th floor, Chicago, Illinois 60637, USA. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark. ; Education Department, Montana State University, Box 5103, Bozeman, Montana 59717, USA. ; Program in Biomedical Informatics and Department of Statistics, Stanford University, Stanford, California 94305, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark. ; Anthropology Department, PhD Program, University of Montana, 4100 Mullan Road, no. 217, Missoula, Montana 59808, USA. ; School of Biological Sciences, Washington State University, PO Box 644236, Eastlick Hall 395, Pullman, Washington 99164, USA. ; Department of Evolutionary Biology, Estonian Biocentre and University of Tartu, Riia 23b, 51010 Tartu, Estonia. ; 1] Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK [2] Integrative Systems Biology Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia. ; School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK. ; Department of Anthropology, Southern Methodist University, Dallas, Texas 75275, USA. ; 1] Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK [2] Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK. ; Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK. ; Department of Anthropology and Institute for Genomic Biology, University of Illinois Urbana-Champaign, 209F Davenport Hall, 607 Matthews Avenue, Urbana, Illinois 61801, USA. ; 1] School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK [2] Earth Sciences Department, Natural History Museum, Cromwell Road, London SW7 5BD, UK (I.B.); Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA (M.D.). ; BioArCh, Departments of Biology, Archaeology and Chemistry, University of York, Wentworth Way, York YO10 5DD, UK. ; MRC Centre for Outbreak, Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, Imperial College Faculty of Medicine, London W2 1PG, UK. ; Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. ; 1] Department of Genetics, School of Medicine, Stanford University, Littlefield Center, Stanford, California 94305, USA [2] Center for Evolutionary and Human Genomics, Stanford University, Littlefield Center, Stanford, California 94305, USA. ; 1] Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 752 36 Uppsala, Sweden [2] Science for Life Laboratory, Uppsala University, Norbyvagen 18D, 752 36 Uppsala, Sweden. ; Department of Integrative Biology, University of California, Berkeley, 4134 Valley Life Sciences Building, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522598" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeology ; Asia/ethnology ; Bone and Bones ; Burial ; Chromosomes, Human, Y/genetics ; DNA, Mitochondrial/genetics ; Emigration and Immigration/history ; Europe/ethnology ; Gene Flow/genetics ; Genome, Human/*genetics ; Haplotypes/genetics ; History, Ancient ; Humans ; Indians, North American/*genetics ; Infant ; Male ; Models, Genetic ; Molecular Sequence Data ; Montana ; *Phylogeny ; Population Dynamics ; Radiometric Dating
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-08-24
    Description: Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end, 4137 proteins covering most predicted extracellular proteins were measured in the serum of 5457 Icelanders over 65 years of age. Pairwise correlation between proteins as they varied across individuals revealed 27 different network modules of serum proteins, many of which were associated with cardiovascular and metabolic disease states, as well as overall survival. The protein modules were controlled by cis- and trans-acting genetic variants, which in many cases were also associated with complex disease. This revealed co-regulated groups of circulating proteins that incorporated regulatory control between tissues and demonstrated close relationships to past, current, and future disease states.
    Keywords: Engineering, Genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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