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  • 1
    Publication Date: 2014-01-28
    Description: Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Brana-Arintero site in Leon, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Brana individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269527/" 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/PMC4269527/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olalde, Inigo -- Allentoft, Morten E -- Sanchez-Quinto, Federico -- Santpere, Gabriel -- Chiang, Charleston W K -- DeGiorgio, Michael -- Prado-Martinez, Javier -- Rodriguez, Juan Antonio -- Rasmussen, Simon -- Quilez, Javier -- Ramirez, Oscar -- Marigorta, Urko M -- Fernandez-Callejo, Marcos -- Prada, Maria Encina -- Encinas, Julio Manuel Vidal -- Nielsen, Rasmus -- Netea, Mihai G -- Novembre, John -- Sturm, Richard A -- Sabeti, Pardis -- Marques-Bonet, Tomas -- Navarro, Arcadi -- Willerslev, Eske -- Lalueza-Fox, Carles -- F32 GM106656/GM/NIGMS NIH HHS/ -- F32GM106656/GM/NIGMS NIH HHS/ -- R01 HG007089/HG/NHGRI NIH HHS/ -- R01-HG007089/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):225-8. doi: 10.1038/nature12960. Epub 2014 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2]. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark [2]. ; Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA. ; 1] Department of Integrative Biology, University of California, Berkeley, California 94720, USA [2] Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA. ; Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark. ; I.E.S.O. 'Los Salados', Junta de Castilla y Leon, E-49600 Benavente, Spain. ; Junta de Castilla y Leon, Servicio de Cultura de Leon, E-24071 Leon, Spain. ; Center for Theoretical Evolutionary Genomics, University of California, Berkeley, California 94720, USA. ; Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, 6500 Nijmegen, The Netherlands. ; Department of Human Genetics, University of Chicago, Illinois 60637, USA. ; Institute for Molecular Bioscience, Melanogenix Group, The University of Queensland, Brisbane, Queensland 4072, Australia. ; 1] Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain. ; 1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain [3] Centre de Regulacio Genomica (CRG), Barcelona 08003, Catalonia, Spain [4] National Institute for Bioinformatics (INB), Barcelona 08003, Catalonia, Spain. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463515" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; *Alleles ; Biological Evolution ; Caves ; European Continental Ancestry Group/*genetics ; Eye Color/genetics ; *Fossils ; Genome, Human/genetics ; Genomics ; History, Ancient ; Humans ; Immunity/*genetics ; Lactose Intolerance/genetics ; Male ; Pigmentation/*genetics ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; Skeleton ; Skin Pigmentation/genetics ; Spain/ethnology
    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: 2014-08-01
    Description: Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4(-/-) MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410707/" 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/PMC4410707/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santos, Margarida A -- Faryabi, Robert B -- Ergen, Aysegul V -- Day, Amanda M -- Malhowski, Amy -- Canela, Andres -- Onozawa, Masahiro -- Lee, Ji-Eun -- Callen, Elsa -- Gutierrez-Martinez, Paula -- Chen, Hua-Tang -- Wong, Nancy -- Finkel, Nadia -- Deshpande, Aniruddha -- Sharrow, Susan -- Rossi, Derrick J -- Ito, Keisuke -- Ge, Kai -- Aplan, Peter D -- Armstrong, Scott A -- Nussenzweig, Andre -- CA140575/CA/NCI NIH HHS/ -- CA66996/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R00 CA139009/CA/NCI NIH HHS/ -- R01 DK098263/DK/NIDDK NIH HHS/ -- R01 DK100689/DK/NIDDK NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):107-11. doi: 10.1038/nature13483. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2]. ; The Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Human Oncology and Pathogenesis Program and Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Departments of Cell Biology and Medicine, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ataxia Telangiectasia Mutated Proteins/metabolism ; BRCA1 Protein/genetics/metabolism ; Cell Transformation, Neoplastic ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA Repair ; Female ; Gene Expression Regulation, Neoplastic ; Genes, BRCA1 ; Hematopoietic Stem Cells/cytology/metabolism/pathology ; Histone-Lysine N-Methyltransferase/deficiency/genetics/metabolism ; Leukemia, Myeloid, Acute/*enzymology/*pathology ; Male ; Mice ; *Myelopoiesis ; Oncogene Proteins, Fusion/genetics/metabolism ; Reactive Oxygen Species/metabolism
    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: 2014-01-25
    Description: Dust deposition in the Southern Ocean constitutes a critical modulator of past global climate variability, but how it has varied temporally and geographically is underdetermined. Here, we present data sets of glacial-interglacial dust-supply cycles from the largest Southern Ocean sector, the polar South Pacific, indicating three times higher dust deposition during glacial periods than during interglacials for the past million years. Although the most likely dust source for the South Pacific is Australia and New Zealand, the glacial-interglacial pattern and timing of lithogenic sediment deposition is similar to dust records from Antarctica and the South Atlantic dominated by Patagonian sources. These similarities imply large-scale common climate forcings, such as latitudinal shifts of the southern westerlies and regionally enhanced glaciogenic dust mobilization in New Zealand and Patagonia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lamy, F -- Gersonde, R -- Winckler, G -- Esper, O -- Jaeschke, A -- Kuhn, G -- Ullermann, J -- Martinez-Garcia, A -- Lambert, F -- Kilian, R -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):403-7. doi: 10.1126/science.1245424.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Alfred-Wegener-Institut (AWI) Helmholtz-Zentrum fur Polar- und Meeresforschung, Bremerhaven, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458637" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change ; *Dust ; *Geologic Sediments ; *Ice Cover ; New Zealand ; Pacific Ocean ; *Seawater
    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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  • 4
    Publication Date: 2014-12-20
    Description: During the last interglacial period, global temperatures were ~2 degrees C warmer than at present and sea level was 6 to 8 meters higher. Southern Ocean sediments reveal a spike in authigenic uranium 127,000 years ago, within the last interglacial, reflecting decreased oxygenation of deep water by Antarctic Bottom Water (AABW). Unlike ice age reductions in AABW, the interglacial stagnation event appears decoupled from open ocean conditions and may have resulted from coastal freshening due to mass loss from the Antarctic ice sheet. AABW reduction coincided with increased North Atlantic Deep Water (NADW) formation, and the subsequent reinvigoration in AABW coincided with reduced NADW formation. Thus, alternation of deep water formation between the Antarctic and the North Atlantic, believed to characterize ice ages, apparently also occurs in warm climates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayes, Christopher T -- Martinez-Garcia, Alfredo -- Hasenfratz, Adam P -- Jaccard, Samuel L -- Hodell, David A -- Sigman, Daniel M -- Haug, Gerald H -- Anderson, Robert F -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1514-7. doi: 10.1126/science.1256620.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA. Lamont-Doherty Earth Observatory of Columbia University, Palisades, NY 10964, USA. cthayes@mit.edu. ; Geological Institute, ETH Zurich, 8092 Zurich, Switzerland. ; Institute of Geological Sciences and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; Department of Earth Sciences, University of Cambridge, Cambridge CB2 3EQ, UK. ; Department of Geosciences, Princeton University, Princeton, NJ 08544, USA. ; Lamont-Doherty Earth Observatory of Columbia University, Palisades, NY 10964, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525246" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Climate Change ; *Ice Cover ; Oxygen/analysis ; Salinity ; *Seawater
    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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  • 5
    Publication Date: 2014-05-09
    Description: Throughout life, new neurons are continuously added to the dentate gyrus. As this continuous addition remodels hippocampal circuits, computational models predict that neurogenesis leads to degradation or forgetting of established memories. Consistent with this, increasing neurogenesis after the formation of a memory was sufficient to induce forgetting in adult mice. By contrast, during infancy, when hippocampal neurogenesis levels are high and freshly generated memories tend to be rapidly forgotten (infantile amnesia), decreasing neurogenesis after memory formation mitigated forgetting. In precocial species, including guinea pigs and degus, most granule cells are generated prenatally. Consistent with reduced levels of postnatal hippocampal neurogenesis, infant guinea pigs and degus did not exhibit forgetting. However, increasing neurogenesis after memory formation induced infantile amnesia in these species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akers, Katherine G -- Martinez-Canabal, Alonso -- Restivo, Leonardo -- Yiu, Adelaide P -- De Cristofaro, Antonietta -- Hsiang, Hwa-Lin Liz -- Wheeler, Anne L -- Guskjolen, Axel -- Niibori, Yosuke -- Shoji, Hirotaka -- Ohira, Koji -- Richards, Blake A -- Miyakawa, Tsuyoshi -- Josselyn, Sheena A -- Frankland, Paul W -- MOP74650/Canadian Institutes of Health Research/Canada -- MOP86762/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 May 9;344(6184):598-602. doi: 10.1126/science.1248903.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812394" target="_blank"〉PubMed〈/a〉
    Keywords: Amnesia/*pathology/*physiopathology ; Animals ; Dentate Gyrus/cytology ; Female ; Guinea Pigs ; Hippocampus/*cytology ; Male ; *Memory ; Mice ; Mice, Inbred C57BL ; *Neurogenesis ; Neurons/cytology
    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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