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  • 1
    Publication Date: 2018-06-14
    Description: Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4 , Pipistrellus pipistrellus coronavirus HKU5 , and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io , from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV. IMPORTANCE Previous studies suggested that MERS-CoV originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses in eight bat species. We provide evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus, HKU4. Our study expands the host ranges of MERS-related CoV and represents an important step toward establishing bats as the natural reservoir of MERS-CoV. These findings may lead to improved epidemiological surveillance of MERS-CoV and the prevention and control of the spread of MERS-CoV to humans.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 2
  • 3
    Publication Date: 2011-02-04
    Description: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" 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/PMC3753179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Zhihu -- Wu, Chang-Jiun -- Chu, Gerald C -- Xiao, Yonghong -- Ho, Dennis -- Zhang, Jingfang -- Perry, Samuel R -- Labrot, Emma S -- Wu, Xiaoqiu -- Lis, Rosina -- Hoshida, Yujin -- Hiller, David -- Hu, Baoli -- Jiang, Shan -- Zheng, Hongwu -- Stegh, Alexander H -- Scott, Kenneth L -- Signoretti, Sabina -- Bardeesy, Nabeel -- Wang, Y Alan -- Hill, David E -- Golub, Todd R -- Stampfer, Meir J -- Wong, Wing H -- Loda, Massimo -- Mucci, Lorelei -- Chin, Lynda -- DePinho, Ronald A -- P50 CA090381/CA/NCI NIH HHS/ -- P50 CA090381-08/CA/NCI NIH HHS/ -- P50 CA90381/CA/NCI NIH HHS/ -- R01 5R01CA136578/CA/NCI NIH HHS/ -- R01 CA131945/CA/NCI NIH HHS/ -- R01CA131945/CA/NCI NIH HHS/ -- R01CA141298/CA/NCI NIH HHS/ -- U01-CA84313/CA/NCI NIH HHS/ -- England -- Nature. 2011 Feb 10;470(7333):269-73. doi: 10.1038/nature09677. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; *Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor/physiology ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/*pathology ; Osteopontin/genetics/metabolism ; PTEN Phosphohydrolase/deficiency/genetics ; Penetrance ; Prognosis ; Prostate/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/diagnosis/genetics/*pathology ; Smad4 Protein/deficiency/genetics/*metabolism ; Transforming Growth Factor beta
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-09-19
    Description: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P 〈 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185210/" 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/PMC4185210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, John R B -- Day, Felix -- Elks, Cathy E -- Sulem, Patrick -- Thompson, Deborah J -- Ferreira, Teresa -- He, Chunyan -- Chasman, Daniel I -- Esko, Tonu -- Thorleifsson, Gudmar -- Albrecht, Eva -- Ang, Wei Q -- Corre, Tanguy -- Cousminer, Diana L -- Feenstra, Bjarke -- Franceschini, Nora -- Ganna, Andrea -- Johnson, Andrew D -- Kjellqvist, Sanela -- Lunetta, Kathryn L -- McMahon, George -- Nolte, Ilja M -- Paternoster, Lavinia -- Porcu, Eleonora -- Smith, Albert V -- Stolk, Lisette -- Teumer, Alexander -- Tsernikova, Natalia -- Tikkanen, Emmi -- Ulivi, Sheila -- Wagner, Erin K -- Amin, Najaf -- Bierut, Laura J -- Byrne, Enda M -- Hottenga, Jouke-Jan -- Koller, Daniel L -- Mangino, Massimo -- Pers, Tune H -- Yerges-Armstrong, Laura M -- Hua Zhao, Jing -- Andrulis, Irene L -- Anton-Culver, Hoda -- Atsma, Femke -- Bandinelli, Stefania -- Beckmann, Matthias W -- Benitez, Javier -- Blomqvist, Carl -- Bojesen, Stig E -- Bolla, Manjeet K -- Bonanni, Bernardo -- Brauch, Hiltrud -- Brenner, Hermann -- Buring, Julie E -- Chang-Claude, Jenny -- Chanock, Stephen -- Chen, Jinhui -- Chenevix-Trench, Georgia -- Collee, J Margriet -- Couch, Fergus J -- Couper, David -- Coviello, Andrea D -- Cox, Angela -- Czene, Kamila -- D'adamo, Adamo Pio -- Davey Smith, George -- De Vivo, Immaculata -- Demerath, Ellen W -- Dennis, Joe -- Devilee, Peter -- Dieffenbach, Aida K -- Dunning, Alison M -- Eiriksdottir, Gudny -- Eriksson, Johan G -- Fasching, Peter A -- Ferrucci, Luigi -- Flesch-Janys, Dieter -- Flyger, Henrik -- Foroud, Tatiana -- Franke, Lude -- Garcia, Melissa E -- Garcia-Closas, Montserrat -- Geller, Frank -- de Geus, Eco E J -- Giles, Graham G -- Gudbjartsson, Daniel F -- Gudnason, Vilmundur -- Guenel, Pascal -- Guo, Suiqun -- Hall, Per -- Hamann, Ute -- Haring, Robin -- Hartman, Catharina A -- Heath, Andrew C -- Hofman, Albert -- Hooning, Maartje J -- Hopper, John L -- Hu, Frank B -- Hunter, David J -- Karasik, David -- Kiel, Douglas P -- Knight, Julia A -- Kosma, Veli-Matti -- Kutalik, Zoltan -- Lai, Sandra -- Lambrechts, Diether -- Lindblom, Annika -- Magi, Reedik -- Magnusson, Patrik K -- Mannermaa, Arto -- Martin, Nicholas G -- Masson, Gisli -- McArdle, Patrick F -- McArdle, Wendy L -- Melbye, Mads -- Michailidou, Kyriaki -- Mihailov, Evelin -- Milani, Lili -- Milne, Roger L -- Nevanlinna, Heli -- Neven, Patrick -- Nohr, Ellen A -- Oldehinkel, Albertine J -- Oostra, Ben A -- Palotie, Aarno -- Peacock, Munro -- Pedersen, Nancy L -- Peterlongo, Paolo -- Peto, Julian -- Pharoah, Paul D P -- Postma, Dirkje S -- Pouta, Anneli -- Pylkas, Katri -- Radice, Paolo -- Ring, Susan -- Rivadeneira, Fernando -- Robino, Antonietta -- Rose, Lynda M -- Rudolph, Anja -- Salomaa, Veikko -- Sanna, Serena -- Schlessinger, David -- Schmidt, Marjanka K -- Southey, Mellissa C -- Sovio, Ulla -- Stampfer, Meir J -- Stockl, Doris -- Storniolo, Anna M -- Timpson, Nicholas J -- Tyrer, Jonathan -- Visser, Jenny A -- Vollenweider, Peter -- Volzke, Henry -- Waeber, Gerard -- Waldenberger, Melanie -- Wallaschofski, Henri -- Wang, Qin -- Willemsen, Gonneke -- Winqvist, Robert -- Wolffenbuttel, Bruce H R -- Wright, Margaret J -- Australian Ovarian Cancer Study -- GENICA Network -- kConFab -- LifeLines Cohort Study -- InterAct Consortium -- Early Growth Genetics (EGG) Consortium -- Boomsma, Dorret I -- Econs, Michael J -- Khaw, Kay-Tee -- Loos, Ruth J F -- McCarthy, Mark I -- Montgomery, Grant W -- Rice, John P -- Streeten, Elizabeth A -- Thorsteinsdottir, Unnur -- van Duijn, Cornelia M -- Alizadeh, Behrooz Z -- Bergmann, Sven -- Boerwinkle, Eric -- Boyd, Heather A -- Crisponi, Laura -- Gasparini, Paolo -- Gieger, Christian -- Harris, Tamara B -- Ingelsson, Erik -- Jarvelin, Marjo-Riitta -- Kraft, Peter -- Lawlor, Debbie -- Metspalu, Andres -- Pennell, Craig E -- Ridker, Paul M -- Snieder, Harold -- Sorensen, Thorkild I A -- Spector, Tim D -- Strachan, David P -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Widen, Elisabeth -- Zygmunt, Marek -- Murray, Anna -- Easton, Douglas F -- Stefansson, Kari -- Murabito, Joanne M -- Ong, Ken K -- 098381/Wellcome Trust/United Kingdom -- 10118/Cancer Research UK/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106179472/Medical Research Council/United Kingdom -- MC_UU_12013/1/Medical Research Council/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- MC_UU_12015/1/Medical Research Council/United Kingdom -- MC_UU_12015/2/Medical Research Council/United Kingdom -- MR/J012165/1/Medical Research Council/United Kingdom -- P50 CA116201/CA/NCI NIH HHS/ -- R01 AG041517/AG/NIA NIH HHS/ -- UL1 TR001108/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):92-7. doi: 10.1038/nature13545. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [4] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. [5]. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2]. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2]. ; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Department of Epidemiology, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana 46202, USA. [2] Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, USA. ; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. [2] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [3] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [4] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; deCODE Genetics, Reykjavik IS-101, Iceland. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; School of Women's and Infants' Health, The University of Western Australia, WA-6009, Australia. ; 1] Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland. [2] Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. ; Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark. ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7400, USA. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden. ; NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. ; Science for Life Laboratory, Karolinska Institutet, Stockholm, Box 1031, 17121 Solna, Sweden. ; 1] NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. [2] Boston University School of Public Health, Department of Biostatistics, Boston, Massachusetts 02118, USA. ; 1] MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. [2] School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; 1] Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy. [2] University of Sassari, Department of Biomedical Sciences, 07100 Sassari, Italy. ; 1] Icelandic Heart Association, IS-201 Kopavogur, Iceland. [2] University of Iceland, IS-101 Reykjavik, Iceland. ; 1] Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. [2] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. [2] Department of Biotechnology, University of Tartu, 51010 Tartu, Estonia. ; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. [2] Hjelt Institute, University of Helsinki, FI-00014, Finland. ; Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy. ; Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands. ; Department of Psychiatry, Washington University, St Louis, Missouri 63110, USA. ; 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland 4072, Australia. [2] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, USA. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [3] Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Center for Biological Sequence Analysis, Department of Systems Biology, Technical 142 University of Denmark, DK-2800 Lyngby, Denmark. ; Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; 1] Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Epidemiology, University of California Irvine, Irvine, California 92697-7550, USA. ; Sanquin Research, 6525 GA Nijmegen, The Netherlands. ; 1] Tuscany Regional Health Agency, Florence, Italy, I.O.T. and Department of Medical and Surgical Critical Care, University of Florence, 50134 Florence, Italy. [2] Geriatric Unit, Azienda Sanitaria di Firenze, 50122 Florence, Italy. ; University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, D-91054 Erlangen, Germany. ; 1] Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain. [2] Centro de Investigacion en Red de Enfermedades Raras (CIBERER), E-46010 Valencia, Spain. ; Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00100 Helsinki, Finland. ; 1] Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark. [2] Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark. ; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), 20139 Milan, Italy. ; 1] DrMargarete Fischer-Bosch-Institute of Clinical Pharmacology, D-70376 Stuttgart, Germany. [2] University of Tubingen, D-72074 Tubingen, Germany. ; 1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. [2] German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany. ; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. ; 1] Departments of Anatomy and Neurological Surgery, Indiana University school of Medicine, Indianapolis, Indiana 46202, USA. [2] Stark Neuroscience Research Center, Indiana University school of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006 Australia. ; Department of Clinical Genetics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands. ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7420, USA. ; Boston University School of Medicine, Department of Medicine, Sections of Preventive Medicine and Endocrinology, Boston, Massachusetts 02118, USA. ; Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK. ; 1] Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy. [2] Department of Clinical Medical Sciences, Surgical and Health, University of Trieste, 34149 Trieste, Italy. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Department of Human Genetics &Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge CB1 8RN, UK. ; Icelandic Heart Association, IS-201 Kopavogur, Iceland. ; 1] National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. [2] Department of General Practice and Primary health Care, University of Helsinki, FI-00014 Helsinki, Finland. [3] Helsinki University Central Hospital, Unit of General Practice, FI-00029 HUS Helsinki, Finland. [4] Folkhalsan Research Centre, FI-00290 Helsinki, Finland. ; Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 20892, USA. ; Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, D-20246 Hamburg, Germany. ; Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark. ; Department of Genetics, University of Groningen, University Medical Centre Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; National Insitute on Aging, National Institutes of Health, Baltimore, Maryland 20892, USA. ; 1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. [2] Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London SW3 6JB, UK. ; 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. [2] EMGO + Institute for Health and Care Research, VU University Medical Centre, Van der Boechorststraat 7, 1081 Bt, Amsterdam, The Netherlands. ; 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2] Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; 1] Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, F-94807 Villejuif, France. [2] University Paris-Sud, UMRS 1018, F-94807 Villejuif, France. ; Department of Obstetrics and Gynecology, Southern Medical University, 510515 Guangzhou, China. ; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; Washington University, Department of Psychiatry, St Louis, Missouri 63110, USA. ; Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands. ; Department of Medical Oncology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. ; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [3] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts 02131, USA. ; 1] Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts 02131, USA. [2] Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. ; 1] School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. [2] Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, P.O. Box 100, FI-70029 Kuopio, Finland. ; Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy. ; 1] Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium. [2] Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. ; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. ; Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. ; School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. ; 1] Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark. [2] Department of Medicine, Stanford School of Medicine, Stanford, California 94305-5101, USA. ; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, P.O. Box 100, FI-00029 HUS Helsinki, Finland. ; KULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, 3000 Leuven, Belgium. ; Research Unit of Obstetrics &Gynecology, Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark. ; Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. ; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. [2] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Psychiatric &Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy. ; Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. ; University Groningen, University Medical Center Groningen, Department Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, P.O. Box 30.001, NL-9700 RB Groningen, The Netherlands. ; 1] National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. [2] Department of Obstetrics and Gynecology, Oulu University Hospital, P.O. Box 10, FI-90029 OYS Oulu, Finland. ; Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital/NordLab Oulu, P.O. Box 3000, FI-90014 Oulu, Finland. ; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy. ; 1] Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. [2] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. [3] Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. ; National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224-6825, USA. ; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Postbus 90203, 1006 BE Amsterdam, The Netherlands. ; Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [2] Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge CB2 0SW, UK. ; 1] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-8576 Neuherberg, Germany. [2] Department of Obstetrics and Gynaecology, Campus Grosshadern, Ludwig-Maximilians-University, D-81377 Munich, Germany. ; Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. ; Department of Internal Medicine, Lausanne University Hospital, CH-1015 Lausanne, Switzerland. ; 1] Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-8576 Neuherberg, Germany. ; 1] Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Department of Endocrinology, University of Groningen, University Medical Centre Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; Queensland Insitute of Medical Research, Brisbane, Queensland 4029, Australia. ; 1] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, USA. [2] Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0QQ, UK. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, Box 1003, New York, New York 10029, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LE, UK. [3] Oxford Centre for Diabetes, Endocrinology, &Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. ; 1] Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Geriatric Research and Education Clinical Center (GRECC) - Veterans Administration Medical Center, Baltimore, Maryland 21201, USA. ; 1] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. [2] Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands. [3] Centre of Medical Systems Biology, PO Box 9600, 2300 RC Leiden, the Netherlands. ; Human Genetics Center and Divof Epidemiology, University of Houston, P.O. Box 20186, Texas 77025 USA. ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Box 256, 751 05 Uppsala, Sweden. ; 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [2] Institute of Health Sciences, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland. [3] Biocenter Oulu, University of Oulu, P.O. Box 5000, Aapistie 5A, FI-90014 Oulu, Finland. [4] Department of Children and Young People and Families, National Institute for Health and Welfare, Aapistie 1, Box 310, FI-90101 Oulu, Finland. [5] Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220 Oulu, 90029 OYS, Finland. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Denmark. [2] Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, DK-2000 Frederiksberg, Denmark. ; Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. ; Department of Obstetrics and Gynecology, University Medicine Greifswald, D-17475 Greifswald, Germany. ; University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2] Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. [3]. ; 1] NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. [2] Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine, Boston, Massachusetts 02118, USA. [3]. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK. [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231870" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Age Factors ; *Alleles ; Body Mass Index ; Breast Neoplasms/genetics ; Cardiovascular Diseases/genetics ; Child ; Diabetes Mellitus, Type 2/genetics ; Europe/ethnology ; Female ; Genetic Loci/*genetics ; Genome-Wide Association Study ; Genomic Imprinting/genetics ; Humans ; Hypothalamo-Hypophyseal System/physiology ; Intercellular Signaling Peptides and Proteins/genetics ; Male ; Membrane Proteins/genetics ; Menarche/*genetics ; Obesity/genetics ; Ovary/physiology ; *Parents ; Polymorphism, Single Nucleotide/genetics ; Potassium Channels, Tandem Pore Domain/genetics ; Proteins/genetics ; Quantitative Trait Loci/genetics ; Receptors, GABA-B/metabolism ; Receptors, Retinoic Acid/metabolism ; Ribonucleoproteins/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2018-11-08
    Description: Type 2 diabetes and risk of colorectal cancer in two large U.S. prospective cohorts Type 2 diabetes and risk of colorectal cancer in two large U.S. prospective cohorts, Published online: 07 November 2018; doi:10.1038/s41416-018-0314-4 Type 2 diabetes and risk of colorectal cancer in two large U.S. prospective cohorts
    Print ISSN: 0007-0920
    Electronic ISSN: 1532-1827
    Topics: Medicine
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  • 6
    Publication Date: 2012-08-17
    Description: Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712624/" 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/PMC3712624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Florian L -- Colla, Simona -- Aquilanti, Elisa -- Manzo, Veronica E -- Genovese, Giannicola -- Lee, Jaclyn -- Eisenson, Daniel -- Narurkar, Rujuta -- Deng, Pingna -- Nezi, Luigi -- Lee, Michelle A -- Hu, Baoli -- Hu, Jian -- Sahin, Ergun -- Ong, Derrick -- Fletcher-Sananikone, Eliot -- Ho, Dennis -- Kwong, Lawrence -- Brennan, Cameron -- Wang, Y Alan -- Chin, Lynda -- DePinho, Ronald A -- 3 P01 CA095616-08S1/CA/NCI NIH HHS/ -- 57006984/Howard Hughes Medical Institute/ -- P01 CA095616/CA/NCI NIH HHS/ -- P01CA95616/CA/NCI NIH HHS/ -- T32-CA009361/CA/NCI NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):337-42. doi: 10.1038/nature11331.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895339" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers, Tumor/deficiency/genetics ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Chromosomes, Human, Pair 1/genetics ; DNA-Binding Proteins/deficiency/genetics ; Enzyme Inhibitors ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genes, Essential/*genetics ; Genes, Tumor Suppressor ; Glioblastoma/*drug therapy/*genetics/pathology ; Homozygote ; Humans ; Hydroxamic Acids/pharmacology/therapeutic use ; Mice ; Molecular Targeted Therapy/*methods ; Neoplasm Transplantation ; Phosphonoacetic Acid/analogs & derivatives/pharmacology/therapeutic use ; Phosphopyruvate Hydratase/antagonists & inhibitors/deficiency/genetics/metabolism ; RNA, Small Interfering/genetics ; Sequence Deletion/*genetics ; Tumor Suppressor Proteins/deficiency/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-10-19
    Description: Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer. This association could be explained by the hypothesis that the same factors and pathways important for wound healing also promote tumorigenesis. A sensor of tissue damage should induce these factors to promote tissue repair and regulate their action to prevent development of cancer. Interleukin 22 (IL-22), a cytokine of the IL-10 superfamily, has an important role in colonic epithelial cell repair, and its levels are increased in the blood and intestine of inflammatory bowel disease patients. This cytokine can be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP, also known as IL22RA2); however, the significance of endogenous IL-22BP in vivo and the pathways that regulate this receptor are unknown. Here we describe that IL-22BP has a crucial role in controlling tumorigenesis and epithelial cell proliferation in the colon. IL-22BP is highly expressed by dendritic cells in the colon in steady-state conditions. Sensing of intestinal tissue damage via the NLRP3 or NLRP6 inflammasomes led to an IL-18-dependent downregulation of IL-22BP, thereby increasing the ratio of IL-22/IL-22BP. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumour development if uncontrolled during the recovery phase. Thus, the IL-22-IL-22BP axis critically regulates intestinal tissue repair and tumorigenesis in the colon.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493690/" 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/PMC3493690/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huber, Samuel -- Gagliani, Nicola -- Zenewicz, Lauren A -- Huber, Francis J -- Bosurgi, Lidia -- Hu, Bo -- Hedl, Matija -- Zhang, Wei -- O'Connor, William Jr -- Murphy, Andrew J -- Valenzuela, David M -- Yancopoulos, George D -- Booth, Carmen J -- Cho, Judy H -- Ouyang, Wenjun -- Abraham, Clara -- Flavell, Richard A -- DK-P30-34989/DK/NIDDK NIH HHS/ -- P30 DK034989/DK/NIDDK NIH HHS/ -- R01 DK077905/DK/NIDDK NIH HHS/ -- R01DK077905/DK/NIDDK NIH HHS/ -- U19 AI082713/AI/NIAID NIH HHS/ -- U19-AI082713/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Nov 8;491(7423):259-63. doi: 10.1038/nature11535. Epub 2012 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23075849" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Transformation, Neoplastic ; Colitis/complications/metabolism/pathology ; Colon/metabolism/pathology ; Colonic Neoplasms/complications/metabolism/pathology ; Disease Models, Animal ; Down-Regulation ; Epithelial Cells/metabolism/pathology ; Genes, APC ; Inflammasomes/*metabolism ; Interleukin-18/metabolism ; Interleukins/deficiency/genetics/metabolism ; Intestines/*metabolism/*pathology ; Mice ; Mice, Knockout ; Receptors, Interleukin/deficiency/genetics/*metabolism ; Time Factors ; Weight Loss
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-11-01
    Description: The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ge, Xing-Yi -- Li, Jia-Lu -- Yang, Xing-Lou -- Chmura, Aleksei A -- Zhu, Guangjian -- Epstein, Jonathan H -- Mazet, Jonna K -- Hu, Ben -- Zhang, Wei -- Peng, Cheng -- Zhang, Yu-Ji -- Luo, Chu-Ming -- Tan, Bing -- Wang, Ning -- Zhu, Yan -- Crameri, Gary -- Zhang, Shu-Yi -- Wang, Lin-Fa -- Daszak, Peter -- Shi, Zheng-Li -- R01AI079231/AI/NIAID NIH HHS/ -- R01TW005869/TW/FIC NIH HHS/ -- R56TW009502/TW/FIC NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):535-8. doi: 10.1038/nature12711. Epub 2013 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Emerging Infectious Diseases, State Key Laboratory of Virology, Wuhan Institute of Virology of the Chinese Academy of Sciences, Wuhan 430071, China [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24172901" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cercopithecus aethiops ; China ; Chiroptera/*virology ; Disease Reservoirs/virology ; Feces/virology ; Fluorescent Antibody Technique ; Genome, Viral/genetics ; Host Specificity ; Humans ; Molecular Sequence Data ; Pandemics/prevention & control/veterinary ; Peptidyl-Dipeptidase A/genetics/*metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Virus/genetics/metabolism ; SARS Virus/genetics/*isolation & purification/*metabolism/ultrastructure ; Severe Acute Respiratory Syndrome/prevention & ; control/transmission/veterinary/virology ; Species Specificity ; Spike Glycoprotein, Coronavirus/chemistry/metabolism ; Vero Cells ; Virion/isolation & purification/ultrastructure ; Virus Internalization ; Viverridae/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-03-29
    Description: Cancer cells induce a set of adaptive response pathways to survive in the face of stressors due to inadequate vascularization. One such adaptive pathway is the unfolded protein (UPR) or endoplasmic reticulum (ER) stress response mediated in part by the ER-localized transmembrane sensor IRE1 (ref. 2) and its substrate XBP1 (ref. 3). Previous studies report UPR activation in various human tumours, but the role of XBP1 in cancer progression in mammary epithelial cells is largely unknown. Triple-negative breast cancer (TNBC)--a form of breast cancer in which tumour cells do not express the genes for oestrogen receptor, progesterone receptor and HER2 (also called ERBB2 or NEU)--is a highly aggressive malignancy with limited treatment options. Here we report that XBP1 is activated in TNBC and has a pivotal role in the tumorigenicity and progression of this human breast cancer subtype. In breast cancer cell line models, depletion of XBP1 inhibited tumour growth and tumour relapse and reduced the CD44(high)CD24(low) population. Hypoxia-inducing factor 1alpha (HIF1alpha) is known to be hyperactivated in TNBCs. Genome-wide mapping of the XBP1 transcriptional regulatory network revealed that XBP1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1alpha that regulates the expression of HIF1alpha targets via the recruitment of RNA polymerase II. Analysis of independent cohorts of patients with TNBC revealed a specific XBP1 gene expression signature that was highly correlated with HIF1alpha and hypoxia-driven signatures and that strongly associated with poor prognosis. Our findings reveal a key function for the XBP1 branch of the UPR in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105133/" 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/PMC4105133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Xi -- Iliopoulos, Dimitrios -- Zhang, Qing -- Tang, Qianzi -- Greenblatt, Matthew B -- Hatziapostolou, Maria -- Lim, Elgene -- Tam, Wai Leong -- Ni, Min -- Chen, Yiwen -- Mai, Junhua -- Shen, Haifa -- Hu, Dorothy Z -- Adoro, Stanley -- Hu, Bella -- Song, Minkyung -- Tan, Chen -- Landis, Melissa D -- Ferrari, Mauro -- Shin, Sandra J -- Brown, Myles -- Chang, Jenny C -- Liu, X Shirley -- Glimcher, Laurie H -- AI32412/AI/NIAID NIH HHS/ -- CA112663/CA/NCI NIH HHS/ -- K99 CA175290/CA/NCI NIH HHS/ -- K99CA175290/CA/NCI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- R00 CA160351/CA/NCI NIH HHS/ -- R01 AI032412/AI/NIAID NIH HHS/ -- R01 CA112663/CA/NCI NIH HHS/ -- R01 HG004069/HG/NHGRI NIH HHS/ -- R01HG004069/HG/NHGRI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Apr 3;508(7494):103-7. doi: 10.1038/nature13119. Epub 2014 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Sandra and Edward Meyer Cancer Center of Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. ; 1] Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [3]. ; 1] Lineberger Comprehensive Cancer Center, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2]. ; 1] Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China [2] Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Ya'an, Sichuan 625014, China [3]. ; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; 1] Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02215, USA. ; Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA. ; 1] Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA [2] Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. ; Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. ; Houston Methodist Cancer Center, Houston, Texas 77030, USA. ; 1] Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. ; 1] Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Houston Methodist Cancer Center, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670641" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD24/metabolism ; Antigens, CD44/metabolism ; Cell Hypoxia/genetics ; Cell Line, Tumor ; Cell Proliferation ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Gene Silencing ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Mice ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; RNA Polymerase II/metabolism ; Transcription Factors/deficiency/genetics/*metabolism ; Transcription, Genetic ; Triple Negative Breast Neoplasms/blood supply/genetics/*metabolism/*pathology ; Unfolded Protein Response
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-07-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Florian -- Colla, Simona -- Aquilanti, Elisa -- Manzo, Veronica E -- Genovese, Giannicola -- Lee, Jaclyn -- Eisenson, Daniel -- Narurkar, Rujuta -- Deng, Pingna -- Nezi, Luigi -- Lee, Michelle -- Hu, Baoli -- Hu, Jian -- Sahin, Ergun -- Ong, Derrick -- Fletcher-Sananikone, Eliot -- Ho, Dennis -- Kwong, Lawrence -- Brennan, Cameron -- Wang, Y Alan -- Chin, Lynda -- DePinho, Ronald A -- England -- Nature. 2015 Sep 10;525(7568):278. doi: 10.1038/nature14609. Epub 2015 Jul 8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26153864" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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