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The mutational landscape of normal human endometrial epithelium 期刊论文
NATURE, 2020, 580 (7805) : 640-+
作者:  Rogelj, Joeri;  Forster, Piers M.;  Kriegler, Elmar;  Smith, Christopher J.;  Seferian, Roland
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03

All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium(1,2). Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry '  driver'  mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues-perhaps shaped by differences in their structure and physiology-and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life.


Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.


  
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes 期刊论文
NATURE, 2020, 578 (7793) : 102-+
作者:  Clark, Timothy D.;  Raby, Graham D.;  Roche, Dominique G.;  Binning, Sandra A.;  Speers-Roesch, Ben;  Jutfelt, Fredrik;  Sundin, Josefin
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

The discovery of drivers of cancer has traditionally focused on protein-coding genes(1-4). Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium(5) of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers(6,7), raise doubts about others and identify novel candidates, including point mutations in the 5'  region of TP53, in the 3'  untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.


  
Experimental strategies to assess the biological ramifications of multiple drivers of global ocean change-A review 期刊论文
GLOBAL CHANGE BIOLOGY, 2018, 24 (6) : 2239-2261
作者:  Boyd, Philip W.;  Collins, Sinead;  Dupont, Sam;  Fabricius, Katharina;  Gattuso, Jean-Pierre;  Havenhand, Jonathan;  Hutchins, David A.;  Riebesell, Ulf;  Rintoul, Max S.;  Vichi, Marcello;  Biswas, Haimanti;  Ciotti, Aurea;  Gao, Kunshan;  Gehlen, Marion;  Hurd, Catriona L.;  Kurihara, Haruko;  McGraw, Christina M.;  Navarro, Jorge M.;  Nilsson, Goeran E.;  Passow, Uta;  Poertner, Hans-Otto
收藏  |  浏览/下载:30/0  |  提交时间:2019/04/09
design  experiments  multiple drivers  ocean  stressors  
Temporal scale dependent interactions between multiple environmental disturbances in microcosm ecosystems 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (12)
作者:  Garnier, Aurelie;  Pennekamp, Frank;  Lemoine, Melissa;  Petchey, Owen L.
收藏  |  浏览/下载:13/0  |  提交时间:2019/04/09
environmental changes  microbial aquatic system  multiple drivers  predictability  resilience  resistance  return time  temporal scales  
Catching sea cucumber fever in coastal communities: Conceptualizing the impacts of shocks versus trends on social-ecological systems 期刊论文
GLOBAL ENVIRONMENTAL CHANGE-HUMAN AND POLICY DIMENSIONS, 2017, 45
作者:  Kaplan-Hallam, Maery;  Bennett, Nathan J.;  Satterfield, Terre
收藏  |  浏览/下载:25/0  |  提交时间:2019/04/09
Social-ecological systems  Social drivers  Multiple stressors  Vulnerability and adaptive capacity  Coastal communities  Small-scale fisheries  
Assessing long-term effects of multiple, potentially confounded drivers in ecosystems from species traits 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (6)
作者:  Floury, Mathieu;  Usseglio-Polatera, Philippe;  Delattre, Cecile;  Souchon, Yves
收藏  |  浏览/下载:17/0  |  提交时间:2019/04/09
climate change  confounding effect  invertebrates  large rivers  long-term trends  multiple drivers  species traits  water quality  
Radiochemically-Supported Microbial Communities: A Potential Mechanism for Biocolloid Production of Importance to Actinide Transport 科技报告
来源:US Department of Energy (DOE). 出版年: 2014
作者:  Moser, Duane P;  Hamilton-Brehm, Scott D;  Fisher, Jenny C;  Bruckner, James C;  Kruger, Brittany;  Sackett, Joshua;  Russell, Charles E;  Onstott, Tullis C;  Czerwinski, Ken
收藏  |  浏览/下载:42/0  |  提交时间:2019/04/05
Due to the legacy of Cold War nuclear weapons testing  the Nevada National Security Site (NNSS  formerly known as the Nevada Test Site (NTS)) contains millions of Curies of radioactive contamination. Presented here is a summary of the results of the first comprehensive study of subsurface microbial communities of radioactive and nonradioactive aquifers at this site. To achieve the objectives of this project  cooperative actions between the Desert Research Institute (DRI)  the Nevada Field Office of the National Nuclear Security Administration (NNSA)  the Underground Test Area Activity (UGTA)  and contractors such as Navarro-Interra (NI)  were required. Ultimately  fluids from 17 boreholes and two water-filled tunnels were sampled (sometimes on multiple occasions and from multiple depths) from the NNSS  the adjacent Nevada Test and Training Range (NTTR)  and a reference hole in the Amargosa Valley near Death Valley. The sites sampled ranged from highly-radioactive nuclear device test cavities to uncontaminated perched and regional aquifers. Specific areas sampled included recharge  intermediate  and discharge zones of a 100  000-km2 internally-draining province  known as the Death Valley Regional Flow System (DVRFS)  which encompasses the entirety of the NNSS/NTTR and surrounding areas. Specific geological features sampled included: West Pahute and Ranier Mesas (recharge zone)  Yucca and Frenchman Flats (transitional zone)  and the Western edge of the Amargosa Valley near Death Valley (discharge zone). The original overarching question underlying the proposal supporting this work was stated as: Can radiochemically-produced substrates support indigenous microbial communities and subsequently stimulate biocolloid formation that can affect radionuclides in NNSS subsurface nuclear test/detonation sites? Radioactive and non-radioactive groundwater samples were thus characterized for physical parameters  aqueous geochemistry  and microbial communities using both DNA- and cultivation-based tools in an effort to understand the drivers of microbial community structure (including radioactivity) and microbial interactions with select radionuclides and other factors across the range of habitats surveyed.