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  • 1
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    The fine-scale genetic structure of the British population (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-03-20
    Description: Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide single nucleotide polymorphism (SNP) data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom. This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography. The regional genetic differentiation and differing patterns of shared ancestry with 6,209 individuals from across Europe carry clear signals of historical demographic events. We estimate the genetic contribution to southeastern England from Anglo-Saxon migrations to be under half, and identify the regions not carrying genetic material from these migrations. We suggest significant pre-Roman but post-Mesolithic movement into southeastern England from continental Europe, and show that in non-Saxon parts of the United Kingdom, there exist genetically differentiated subgroups rather than a general 'Celtic' population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632200/" 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/PMC4632200/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Stephen -- Winney, Bruce -- Hellenthal, Garrett -- Davison, Dan -- Boumertit, Abdelhamid -- Day, Tammy -- Hutnik, Katarzyna -- Royrvik, Ellen C -- Cunliffe, Barry -- Wellcome Trust Case Control Consortium 2 -- International Multiple Sclerosis Genetics Consortium -- Lawson, Daniel J -- Falush, Daniel -- Freeman, Colin -- Pirinen, Matti -- Myers, Simon -- Robinson, Mark -- Donnelly, Peter -- Bodmer, Walter -- 072974/Wellcome Trust/United Kingdom -- 072974/Z/03/Z/Wellcome Trust/United Kingdom -- 075491/Wellcome Trust/United Kingdom -- 075491/Z/04/A/Wellcome Trust/United Kingdom -- 075491/Z/04/B/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084818/Wellcome Trust/United Kingdom -- 084818/Z/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 085475DONNELLY/Wellcome Trust/United Kingdom -- 088262/Wellcome Trust/United Kingdom -- 088262/Z/09/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 095552/Z/11/Z/Wellcome Trust/United Kingdom -- 098386/Wellcome Trust/United Kingdom -- 098386/Z/12/Z/Wellcome Trust/United Kingdom -- 098387/Wellcome Trust/United Kingdom -- 098387/Z/12/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Mar 19;519(7543):309-14. doi: 10.1038/nature14230.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia [2] University of Melbourne, Department of Mathematics and Statistics, Parkville, Victoria 3010, Australia [3] University of Oxford, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. ; University of Oxford, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. ; University College London Genetics Institute, Darwin Building, Gower Street, London WC1E 6BT, UK. ; Counsyl, 180 Kimball Way, South San Francisco, California 94080, USA. ; University of Oxford, Institute of Archaeology, 36 Beaumont Street, Oxford OX1 2PG, UK. ; University of Bristol, Department of Mathematics, University Walk, Bristol BS8 1TW, UK. ; College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK. ; The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK. ; University of Helsinki, P.O. Box 20, Helsinki, FI-00014, Finland. ; University of Oxford, Department of Statistics, 1 South Parks Road, Oxford OX1 3TG, UK. ; University of Oxford, University Museum of Natural History, Parks Road, Oxford OX1 3PW, UK. ; 1] The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK [2] University of Oxford, Department of Statistics, 1 South Parks Road, Oxford OX1 3TG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25788095" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; European Continental Ancestry Group/genetics ; *Genetics, Population ; Great Britain/ethnology ; Haplotypes/*genetics ; Humans ; Polymorphism, Single Nucleotide/*genetics ; Principal Component Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-07-24
    Description: Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, specifically PI(3)Kgamma. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754787/" 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/PMC4754787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Pulin -- Lahvic, Jamie L -- Binder, Vera -- Pugach, Emily K -- Riley, Elizabeth B -- Tamplin, Owen J -- Panigrahy, Dipak -- Bowman, Teresa V -- Barrett, Francesca G -- Heffner, Garrett C -- McKinney-Freeman, Shannon -- Schlaeger, Thorsten M -- Daley, George Q -- Zeldin, Darryl C -- Zon, Leonard I -- 1R01HL097794-04/HL/NHLBI NIH HHS/ -- 5P30 DK49216/DK/NIDDK NIH HHS/ -- 5R01DK53298/DK/NIDDK NIH HHS/ -- 5U01 HL10001-05/HL/NHLBI NIH HHS/ -- P015P01HL32262-32/HL/NHLBI NIH HHS/ -- P30-HD18655/HD/NICHD NIH HHS/ -- P50-NS40828/NS/NINDS NIH HHS/ -- R01 CA148633/CA/NCI NIH HHS/ -- R01 HL04880/HL/NHLBI NIH HHS/ -- R0CA148633-01A5/PHS HHS/ -- R24 DK092760/DK/NIDDK NIH HHS/ -- Z01 ES025034/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Jul 23;523(7561):468-71. doi: 10.1038/nature14569.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Stem Cell Program and Division of Haematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachuestts 02115, USA [2] Chemical Biology Program, Harvard University, Cambridge, Massachusetts 02138, USA. ; Stem Cell Program and Division of Haematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachuestts 02115, USA. ; 1] Stem Cell Program and Division of Haematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachuestts 02115, USA [2] Department of Hematology and Oncology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, 80337 Munich, Germany. ; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Haematology, St Jude Children's Research Hospital, Memphis, Tennessee 38105-3678, USA. ; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26201599" target="_blank"〉PubMed〈/a〉
    Keywords: 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/metabolism ; Animals ; Cell Line ; Cell Movement ; Core Binding Factor Alpha 2 Subunit/metabolism ; Female ; Gene Expression Regulation ; *Hematopoiesis ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney/cytology ; Male ; Mice ; Phosphatidylinositol 3-Kinases ; Transcription Factor AP-1/metabolism ; Transcription, Genetic ; Zebrafish/*embryology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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