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  • 1
    Publication Date: 2012-07-27
    Description: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappaB signalling in Group 4, suggest future avenues for rational, targeted therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683624/" 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/PMC3683624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Northcott, Paul A -- Shih, David J H -- Peacock, John -- Garzia, Livia -- Morrissy, A Sorana -- Zichner, Thomas -- Stutz, Adrian M -- Korshunov, Andrey -- Reimand, Juri -- Schumacher, Steven E -- Beroukhim, Rameen -- Ellison, David W -- Marshall, Christian R -- Lionel, Anath C -- Mack, Stephen -- Dubuc, Adrian -- Yao, Yuan -- Ramaswamy, Vijay -- Luu, Betty -- Rolider, Adi -- Cavalli, Florence M G -- Wang, Xin -- Remke, Marc -- Wu, Xiaochong -- Chiu, Readman Y B -- Chu, Andy -- Chuah, Eric -- Corbett, Richard D -- Hoad, Gemma R -- Jackman, Shaun D -- Li, Yisu -- Lo, Allan -- Mungall, Karen L -- Nip, Ka Ming -- Qian, Jenny Q -- Raymond, Anthony G J -- Thiessen, Nina T -- Varhol, Richard J -- Birol, Inanc -- Moore, Richard A -- Mungall, Andrew J -- Holt, Robert -- Kawauchi, Daisuke -- Roussel, Martine F -- Kool, Marcel -- Jones, David T W -- Witt, Hendrick -- Fernandez-L, Africa -- Kenney, Anna M -- Wechsler-Reya, Robert J -- Dirks, Peter -- Aviv, Tzvi -- Grajkowska, Wieslawa A -- Perek-Polnik, Marta -- Haberler, Christine C -- Delattre, Olivier -- Reynaud, Stephanie S -- Doz, Francois F -- Pernet-Fattet, Sarah S -- Cho, Byung-Kyu -- Kim, Seung-Ki -- Wang, Kyu-Chang -- Scheurlen, Wolfram -- Eberhart, Charles G -- Fevre-Montange, Michelle -- Jouvet, Anne -- Pollack, Ian F -- Fan, Xing -- Muraszko, Karin M -- Gillespie, G Yancey -- Di Rocco, Concezio -- Massimi, Luca -- Michiels, Erna M C -- Kloosterhof, Nanne K -- French, Pim J -- Kros, Johan M -- Olson, James M -- Ellenbogen, Richard G -- Zitterbart, Karel -- Kren, Leos -- Thompson, Reid C -- Cooper, Michael K -- Lach, Boleslaw -- McLendon, Roger E -- Bigner, Darell D -- Fontebasso, Adam -- Albrecht, Steffen -- Jabado, Nada -- Lindsey, Janet C -- Bailey, Simon -- Gupta, Nalin -- Weiss, William A -- Bognar, Laszlo -- Klekner, Almos -- Van Meter, Timothy E -- Kumabe, Toshihiro -- Tominaga, Teiji -- Elbabaa, Samer K -- Leonard, Jeffrey R -- Rubin, Joshua B -- Liau, Linda M -- Van Meir, Erwin G -- Fouladi, Maryam -- Nakamura, Hideo -- Cinalli, Giuseppe -- Garami, Miklos -- Hauser, Peter -- Saad, Ali G -- Iolascon, Achille -- Jung, Shin -- Carlotti, Carlos G -- Vibhakar, Rajeev -- Ra, Young Shin -- Robinson, Shenandoah -- Zollo, Massimo -- Faria, Claudia C -- Chan, Jennifer A -- Levy, Michael L -- Sorensen, Poul H B -- Meyerson, Matthew -- Pomeroy, Scott L -- Cho, Yoon-Jae -- Bader, Gary D -- Tabori, Uri -- Hawkins, Cynthia E -- Bouffet, Eric -- Scherer, Stephen W -- Rutka, James T -- Malkin, David -- Clifford, Steven C -- Jones, Steven J M -- Korbel, Jan O -- Pfister, Stefan M -- Marra, Marco A -- Taylor, Michael D -- AT1-112286/Canadian Institutes of Health Research/Canada -- CA116804/CA/NCI NIH HHS/ -- CA138292/CA/NCI NIH HHS/ -- CA159859/CA/NCI NIH HHS/ -- CA86335/CA/NCI NIH HHS/ -- K08 NS059790/NS/NINDS NIH HHS/ -- P20 CA151129/CA/NCI NIH HHS/ -- P30 CA138292/CA/NCI NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P41 GM103504/GM/NIGMS NIH HHS/ -- R01 CA086335/CA/NCI NIH HHS/ -- R01 CA109467/CA/NCI NIH HHS/ -- R01 CA114567/CA/NCI NIH HHS/ -- R01 CA116804/CA/NCI NIH HHS/ -- R01 CA148621/CA/NCI NIH HHS/ -- R01 CA155360/CA/NCI NIH HHS/ -- R01 CA159859/CA/NCI NIH HHS/ -- R01 CA163737/CA/NCI NIH HHS/ -- R01 NS061070/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Aug 2;488(7409):49-56. doi: 10.1038/nature11327.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22832581" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/genetics ; Cerebellar Neoplasms/*classification/*genetics/metabolism ; Child ; DNA Copy Number Variations/genetics ; Gene Duplication/genetics ; Genes, myc/genetics ; Genome, Human/*genetics ; Genomic Structural Variation/*genetics ; Genomics ; Hedgehog Proteins/metabolism ; Humans ; Medulloblastoma/*classification/*genetics/metabolism ; NF-kappa B/metabolism ; Nerve Tissue Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; Proteins/genetics ; RNA, Long Noncoding ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Translocation, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-01-14
    Description: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (〈5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (〈12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morrissy, A Sorana -- Garzia, Livia -- Shih, David J H -- Zuyderduyn, Scott -- Huang, Xi -- Skowron, Patryk -- Remke, Marc -- Cavalli, Florence M G -- Ramaswamy, Vijay -- Lindsay, Patricia E -- Jelveh, Salomeh -- Donovan, Laura K -- Wang, Xin -- Luu, Betty -- Zayne, Kory -- Li, Yisu -- Mayoh, Chelsea -- Thiessen, Nina -- Mercier, Eloi -- Mungall, Karen L -- Ma, Yusanne -- Tse, Kane -- Zeng, Thomas -- Shumansky, Karey -- Roth, Andrew J L -- Shah, Sohrab -- Farooq, Hamza -- Kijima, Noriyuki -- Holgado, Borja L -- Lee, John J Y -- Matan-Lithwick, Stuart -- Liu, Jessica -- Mack, Stephen C -- Manno, Alex -- Michealraj, K A -- Nor, Carolina -- Peacock, John -- Qin, Lei -- Reimand, Juri -- Rolider, Adi -- Thompson, Yuan Y -- Wu, Xiaochong -- Pugh, Trevor -- Ally, Adrian -- Bilenky, Mikhail -- Butterfield, Yaron S N -- Carlsen, Rebecca -- Cheng, Young -- Chuah, Eric -- Corbett, Richard D -- Dhalla, Noreen -- He, An -- Lee, Darlene -- Li, Haiyan I -- Long, William -- Mayo, Michael -- Plettner, Patrick -- Qian, Jenny Q -- Schein, Jacqueline E -- Tam, Angela -- Wong, Tina -- Birol, Inanc -- Zhao, Yongjun -- Faria, Claudia C -- Pimentel, Jose -- Nunes, Sofia -- Shalaby, Tarek -- Grotzer, Michael -- Pollack, Ian F -- Hamilton, Ronald L -- Li, Xiao-Nan -- Bendel, Anne E -- Fults, Daniel W -- Walter, Andrew W -- Kumabe, Toshihiro -- Tominaga, Teiji -- Collins, V Peter -- Cho, Yoon-Jae -- Hoffman, Caitlin -- Lyden, David -- Wisoff, Jeffrey H -- Garvin, James H Jr -- Stearns, Duncan S -- Massimi, Luca -- Schuller, Ulrich -- Sterba, Jaroslav -- Zitterbart, Karel -- Puget, Stephanie -- Ayrault, Olivier -- Dunn, Sandra E -- Tirapelli, Daniela P C -- Carlotti, Carlos G -- Wheeler, Helen -- Hallahan, Andrew R -- Ingram, Wendy -- MacDonald, Tobey J -- Olson, Jeffrey J -- Van Meir, Erwin G -- Lee, Ji-Yeoun -- Wang, Kyu-Chang -- Kim, Seung-Ki -- Cho, Byung-Kyu -- Pietsch, Torsten -- Fleischhack, Gudrun -- Tippelt, Stephan -- Ra, Young Shin -- Bailey, Simon -- Lindsey, Janet C -- Clifford, Steven C -- Eberhart, Charles G -- Cooper, Michael K -- Packer, Roger J -- Massimino, Maura -- Garre, Maria Luisa -- Bartels, Ute -- Tabori, Uri -- Hawkins, Cynthia E -- Dirks, Peter -- Bouffet, Eric -- Rutka, James T -- Wechsler-Reya, Robert J -- Weiss, William A -- Collier, Lara S -- Dupuy, Adam J -- Korshunov, Andrey -- Jones, David T W -- Kool, Marcel -- Northcott, Paul A -- Pfister, Stefan M -- Largaespada, David A -- Mungall, Andrew J -- Moore, Richard A -- Jabado, Nada -- Bader, Gary D -- Jones, Steven J M -- Malkin, David -- Marra, Marco A -- Taylor, Michael D -- R01 CA163722/CA/NCI NIH HHS/ -- R01 NS096236/NS/NINDS NIH HHS/ -- R01CA148699/CA/NCI NIH HHS/ -- R01CA159859/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Jan 21;529(7586):351-7. doi: 10.1038/nature16478. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. ; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada. ; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Dusseldorf, M5S 3E1, Germany. ; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada. ; Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9, Canada. ; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada. ; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; Center for Stem Cell &Regenerative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. ; Clinical Genomics Research Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario 44195, Canada. ; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. ; School of Computing Science, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. ; Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal. ; Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal. ; Unidade de Neuro-Oncologia Pediatrica, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisbon 1099-023, Portugal. ; Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich 8032, Switzerland. ; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA. ; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. ; Brain Tumor Program, Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. ; Pediatric Hematology-Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota 55404, USA. ; Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah 84132, USA. ; A I duPont Hospital for Children, Wilmington, Delaware 19803, USA. ; Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan. ; Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. ; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. ; Departments of Neurosurgery, Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. ; Departments of Pediatrics, Cell &Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA. ; Department of Neurosurgery, NYU Langone Medical Center, New York, New York 10016, USA. ; Department of Pediatrics, Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University, New York, New York 10032, USA. ; Department of Pediatrics-Hematology and Oncology, Rainbow Babies &Children's Hospital and Department of Pediatrics-Hematology and Oncology, Case Western Reserve, Cleveland, Ohio 44106, USA. ; Pediatric Neurosurgery, Catholic University Medical School, Rome 00198, Italy. ; Center for Neuropathology, Ludwig-Maximilians-Universitat, Munich 81377, Germany. ; Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno 625 00, Czech Republic. ; AP-HP, Department of Neurosurgery, Necker-Enfants Malades Hospital, Universite Rene Descartes, Paris 75743, France. ; Signaling in Development and Brain Tumors, CNRS UMR 3347 / INSERM U1021, Institut Curie, Paris Cedex 5 91405, France. ; Division of Hematology/Oncology, British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada. ; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, Universidade de Sao Paulo, Brazil, Rebeirao Preto, Sao Paulo 14049-900, Brazil. ; Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales 2065, Australia. ; Queensland Children's Medical Research Institute, Children's Health Queensland, Brisbane, Queensland 4029, Australia. ; Division of Oncology, Children's Health Queensland, Brisbane, Queensland 4029, Australia. ; UQ Child Health Research Centre, The University of Queensland, Brisbane 4029, Australia. ; Pediatric Neuro-Oncology Program, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30307, USA. ; Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. ; Department of Hematology &Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. ; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea. ; Institute for Neuropathology, University of Bonn D-53105, Germany. ; Children's University Hospital of Essen D-45147, Germany. ; Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul 05505, South Korea. ; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, UK. ; Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Neurology, Vanderbilt Medical Center, Nashville, Tennessee 37232-8550, USA. ; Department of Neurology, Children's National Medical Center, Washington DC 20010-2970, USA. ; Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy. ; U.O. Neurochirurgia, Istituto Giannina Gaslini, Genova 16147, Italy. ; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Division of Pathology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA. ; Departments of Pediatrics, Neurology and Neurosurgery, University of California San Francisco, San Francisco, California 94158, USA. ; School of Pharmacology, University of Wisconsin, Madison, Wisconsin 53715, USA. ; Molecular &Cellular Biology Program, University of Iowa, Iowa City, Iowa 52242, USA. ; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany. ; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Division of Hematology/Oncology, McGill University, Montreal, Quebec H2W 1S6., Canada. ; McLaughlin Centre and Department of Molecular Genetics, Banting and Best Department of Medical Research and Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Department of Molecular Biology &Biochemistry, Simon Fraser University, Burnaby, British Columbia M5G 1L7, Canada. ; Department of Pediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760213" 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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  • 3
    Publication Date: 2014-11-02
    Description: Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor beta (NGFbeta), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFbeta or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFbeta was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFbeta-TRKA signaling in pathogen-specific host immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255479/" 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/PMC4255479/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hepburn, Lucy -- Prajsnar, Tomasz K -- Klapholz, Catherine -- Moreno, Pablo -- Loynes, Catherine A -- Ogryzko, Nikolay V -- Brown, Karen -- Schiebler, Mark -- Hegyi, Krisztina -- Antrobus, Robin -- Hammond, Katherine L -- Connolly, John -- Ochoa, Bernardo -- Bryant, Clare -- Otto, Michael -- Surewaard, Bas -- Seneviratne, Suranjith L -- Grogono, Dorothy M -- Cachat, Julien -- Ny, Tor -- Kaser, Arthur -- Torok, M Estee -- Peacock, Sharon J -- Holden, Matthew -- Blundell, Tom -- Wang, Lihui -- Ligoxygakis, Petros -- Minichiello, Liliana -- Woods, C Geoff -- Foster, Simon J -- Renshaw, Stephen A -- Floto, R Andres -- 084953/Wellcome Trust/United Kingdom -- 089981/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- G0700091/Medical Research Council/United Kingdom -- G0701932/Medical Research Council/United Kingdom -- NC/K500392/1/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom -- Department of Health/United Kingdom -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):641-6. doi: 10.1126/science.1258705.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research, University of Cambridge, UK. Department of Medicine, University of Cambridge, UK. ; Krebs Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. Bateson Centre, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. ; Cambridge Institute for Medical Research, University of Cambridge, UK. ; Bateson Centre, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. Department of Infection and Immunity, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. ; Bateson Centre, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. ; Cambridge Institute for Medical Research, University of Cambridge, UK. Department of Medicine, University of Cambridge, UK. Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK. ; Krebs Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. ; Department of Biochemistry, University of Cambridge, UK. ; Department of Veterinary Medicine, University of Cambridge, UK. ; Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, USA. ; Department of Medical Microbiology, University Medical Centre, Utrecht, Netherlands. ; Department of Clinical Immunology, Royal Free Hospital London, UK. ; Department of Medicine, University of Cambridge, UK. Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK. ; Department of Pathology and Immunology, Geneva University, Switzerland. ; Department of Medical Biochemistry and Biophysics, Umea University, Sweden. ; Department of Medicine, University of Cambridge, UK. ; Department of Medicine, University of Cambridge, UK. Wellcome Trust Sanger Institute, Hinxton, UK. ; Wellcome Trust Sanger Institute, Hinxton, UK. School of Medicine, University of St. Andrews, UK. ; Biochemistry Department, Oxford University, UK. ; Pharmacology Department, Oxford University, UK. ; Cambridge Institute for Medical Research, University of Cambridge, UK. Department of Medical Genetics, University of Cambridge, UK. ; Krebs Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. Bateson Centre, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. Department of Infection and Immunity, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. arf27@cam.ac.uk s.a.renshaw@sheffield.ac.uk. ; Cambridge Institute for Medical Research, University of Cambridge, UK. Department of Medicine, University of Cambridge, UK. Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK. arf27@cam.ac.uk s.a.renshaw@sheffield.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila melanogaster/genetics/immunology ; Evolution, Molecular ; Gene Knockdown Techniques ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Macrophages/immunology ; Nerve Growth Factor/genetics/*immunology ; Phagocytosis/genetics/immunology ; Receptor, trkA/genetics/*immunology ; Staphylococcal Infections/genetics/*immunology ; Staphylococcus aureus/*immunology ; Zebrafish/genetics/immunology
    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: 2014-02-21
    Description: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174313/" 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/PMC4174313/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mack, S C -- Witt, H -- Piro, R M -- Gu, L -- Zuyderduyn, S -- Stutz, A M -- Wang, X -- Gallo, M -- Garzia, L -- Zayne, K -- Zhang, X -- Ramaswamy, V -- Jager, N -- Jones, D T W -- Sill, M -- Pugh, T J -- Ryzhova, M -- Wani, K M -- Shih, D J H -- Head, R -- Remke, M -- Bailey, S D -- Zichner, T -- Faria, C C -- Barszczyk, M -- Stark, S -- Seker-Cin, H -- Hutter, S -- Johann, P -- Bender, S -- Hovestadt, V -- Tzaridis, T -- Dubuc, A M -- Northcott, P A -- Peacock, J -- Bertrand, K C -- Agnihotri, S -- Cavalli, F M G -- Clarke, I -- Nethery-Brokx, K -- Creasy, C L -- Verma, S K -- Koster, J -- Wu, X -- Yao, Y -- Milde, T -- Sin-Chan, P -- Zuccaro, J -- Lau, L -- Pereira, S -- Castelo-Branco, P -- Hirst, M -- Marra, M A -- Roberts, S S -- Fults, D -- Massimi, L -- Cho, Y J -- Van Meter, T -- Grajkowska, W -- Lach, B -- Kulozik, A E -- von Deimling, A -- Witt, O -- Scherer, S W -- Fan, X -- Muraszko, K M -- Kool, M -- Pomeroy, S L -- Gupta, N -- Phillips, J -- Huang, A -- Tabori, U -- Hawkins, C -- Malkin, D -- Kongkham, P N -- Weiss, W A -- Jabado, N -- Rutka, J T -- Bouffet, E -- Korbel, J O -- Lupien, M -- Aldape, K D -- Bader, G D -- Eils, R -- Lichter, P -- Dirks, P B -- Pfister, S M -- Korshunov, A -- Taylor, M D -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA097257/CA/NCI NIH HHS/ -- R01 CA121941/CA/NCI NIH HHS/ -- R01 CA148621/CA/NCI NIH HHS/ -- R01 CA163737/CA/NCI NIH HHS/ -- R01CA148699/CA/NCI NIH HHS/ -- R01CA159859/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Feb 27;506(7489):445-50. doi: 10.1038/nature13108. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4]. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [3] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [4]. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Molecular Genetics, Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Toronto, Ontario M4N 1X8, Canada. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Genome Biology, European Molecular Biology, Laboratory Meyerhofstr. 1, Heidelberg 69117, Germany. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada. ; Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Neurology, Harvard Medical School, Children's Hospital Boston, MIT, Boston, Massachusetts 02115, USA. ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] Ontario Cancer Institute, Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario M5G 1L7, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 1L7, Canada. ; Cancer Epigenetics Discovery Performance Unit, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania 19426, USA. ; Department of Oncogenomics, Academic Medical Center, Amsterdam 1105, The Netherlands. ; 1] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [3] CCU Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; 1] Centre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, Vancouver, V6T 1Z4 British Columbia, Canada [2] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada. ; Department of Pediatrics and National Capital Consortium, Uniformed Services University, Bethesda, Maryland 20814, USA. ; Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. ; Pediatric Neurosurgery, Catholic University Medical School, Gemelli Hospital, Rome 00168, Italy. ; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Pediatrics, Virginia Commonwealth, Richmond, Virginia 23298-0646, USA. ; Department of Pathology, University of Warsaw, Children's Memorial Health Institute University of Warsaw, Warsaw 04-730, Poland. ; Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton General Hospital, Hamilton, Ontario L8S 4K1, Canada. ; 1] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Department of Neuropathology Ruprecht-Karls-University Heidelberg, Institute of Pathology, Heidelberg 69120, Germany. ; 1] University of Michigan Cell and Developmental Biology, Ann Arbor, Michigan 48109-2200, USA [2] Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Neurosurgery, University of California San Francisco, San Francisco, California 94143-0112, USA. ; Departments of Neurology, Pediatrics, and Neurosurgery, University of California, San Francisco, The Helen Diller Family Cancer Research Building, San Francisco, California 94158, USA. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Department of Neuro-oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Departments of Pediatrics and Human Genetics, McGill University and the McGill University Health Center Research Institute, Montreal, Quebec H3Z 2Z3, Canada. ; Department of Neuro-oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Genome Biology, European Molecular Biology, Laboratory Meyerhofstr. 1, Heidelberg 69117, Germany. ; 1] Ontario Cancer Institute, Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario M5G 1L7, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 1L7, Canada [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [3] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] University of Michigan Cell and Developmental Biology, Ann Arbor, Michigan 48109-2200, USA [3] CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553142" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Neoplasms/drug therapy/genetics ; CpG Islands/*genetics ; DNA Methylation/drug effects ; Embryonic Stem Cells/metabolism ; Ependymoma/drug therapy/*genetics ; Epigenesis, Genetic/*genetics ; Epigenomics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing/drug effects ; Histones/drug effects/metabolism ; Humans ; Infant ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mutation/genetics ; Phenotype ; Polycomb Repressive Complex 2/metabolism ; Prognosis ; Rhombencephalon/pathology ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-04-02
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001322/" 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/PMC4001322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cartwright, Edward J P -- Koser, Claudio U -- Peacock, Sharon J -- G1000803/Medical Research Council/United Kingdom -- England -- Nature. 2011 Mar 31;471(7340):578. doi: 10.1038/471578d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21455159" target="_blank"〉PubMed〈/a〉
    Keywords: Communicable Diseases/epidemiology/microbiology/virology ; Drug Resistance, Microbial ; Genome, Bacterial/*genetics ; Genome, Viral/*genetics ; *Genomics ; Human Genome Project ; Humans ; Molecular Epidemiology/methods/*trends ; *Public Health
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2018-05-15
    Description: Author Correction: Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis Author Correction: Analysis of mutations in 〈i〉pncA〈/i〉 reveals non-overlapping patterns among various lineages of 〈i〉Mycobacterium tuberculosis〈/i〉, Published online: 15 May 2018; doi:10.1038/s41598-018-25809-7 Author Correction: Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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  • 7
    Publication Date: 2015-03-20
    Description: Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brienen, R J W -- Phillips, O L -- Feldpausch, T R -- Gloor, E -- Baker, T R -- Lloyd, J -- Lopez-Gonzalez, G -- Monteagudo-Mendoza, A -- Malhi, Y -- Lewis, S L -- Vasquez Martinez, R -- Alexiades, M -- Alvarez Davila, E -- Alvarez-Loayza, P -- Andrade, A -- Aragao, L E O C -- Araujo-Murakami, A -- Arets, E J M M -- Arroyo, L -- Aymard C, G A -- Banki, O S -- Baraloto, C -- Barroso, J -- Bonal, D -- Boot, R G A -- Camargo, J L C -- Castilho, C V -- Chama, V -- Chao, K J -- Chave, J -- Comiskey, J A -- Cornejo Valverde, F -- da Costa, L -- de Oliveira, E A -- Di Fiore, A -- Erwin, T L -- Fauset, S -- Forsthofer, M -- Galbraith, D R -- Grahame, E S -- Groot, N -- Herault, B -- Higuchi, N -- Honorio Coronado, E N -- Keeling, H -- Killeen, T J -- Laurance, W F -- Laurance, S -- Licona, J -- Magnussen, W E -- Marimon, B S -- Marimon-Junior, B H -- Mendoza, C -- Neill, D A -- Nogueira, E M -- Nunez, P -- Pallqui Camacho, N C -- Parada, A -- Pardo-Molina, G -- Peacock, J -- Pena-Claros, M -- Pickavance, G C -- Pitman, N C A -- Poorter, L -- Prieto, A -- Quesada, C A -- Ramirez, F -- Ramirez-Angulo, H -- Restrepo, Z -- Roopsind, A -- Rudas, A -- Salomao, R P -- Schwarz, M -- Silva, N -- Silva-Espejo, J E -- Silveira, M -- Stropp, J -- Talbot, J -- ter Steege, H -- Teran-Aguilar, J -- Terborgh, J -- Thomas-Caesar, R -- Toledo, M -- Torello-Raventos, M -- Umetsu, R K -- van der Heijden, G M F -- van der Hout, P -- Guimaraes Vieira, I C -- Vieira, S A -- Vilanova, E -- Vos, V A -- Zagt, R J -- England -- Nature. 2015 Mar 19;519(7543):344-8. doi: 10.1038/nature14283.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Geography, University of Leeds, Leeds LS2 9JT, UK. ; 1] School of Geography, University of Leeds, Leeds LS2 9JT, UK. [2] Geography, College of Life and Environmental Sciences, University of Exeter, Rennes Drive, Exeter EX4 4RJ, UK. ; 1] Department of Life Sciences, Imperial College London, Silwood Park Campus, Buckhurst Road, Ascot, Berkshire SL5 7PY, UK. [2] School of Marine and Tropical Biology, James Cook University, Cairns, 4870 Queenland, Australia. ; Jardin Botanico de Missouri, Prolongacion Bolognesi Mz.e, Lote 6, Oxapampa, Pasco, Peru. ; Environmental Change Institute, School of Geography and the Environment, University of Oxford, Oxford OX1 3QK, UK. ; 1] School of Geography, University of Leeds, Leeds LS2 9JT, UK. [2] Department of Geography, University College London, Pearson Building, Gower Street, London WC1E 6BT, UK. ; School of Anthropology and Conservation, Marlowe Building, University of Kent, Canterbury CT1 3EH, UK. ; Servicios Ecosistemicos y Cambio Climatico, Jardin Botanico de Medellin, Calle 73 no. 51 D-14, C.P. 050010, Medellin, Colombia. ; Center for Tropical Conservation, Duke University, Box 90381, Durham, North Carolina 27708, USA. ; Biological Dynamics of Forest Fragment Project (INPA &STRI), C.P. 478, Manaus AM 69011-970, Brazil. ; 1] Geography, College of Life and Environmental Sciences, University of Exeter, Rennes Drive, Exeter EX4 4RJ, UK. [2] National Institute for Space Research (INPE), Av. Dos Astronautas, 1758, Sao Jose dos Campos, Sao Paulo 12227-010, Brazil. ; Museo de Historia Natural Noel Kempff Mercado, Universidad Autonoma Gabriel Rene Moreno, Casilla 2489, Av. Irala 565, Santa Cruz, Bolivia. ; Alterra, Wageningen University and Research Centre, PO Box 47, 6700 AA Wageningen, The Netherlands. ; UNELLEZ-Guanare, Programa de Ciencias del Agro y el Mar, Herbario Universitario (PORT), Mesa de Cavacas, Estado Portuguesa, 3350 Venezuela. ; Biodiversiteit en Ecosysteem Dynamica, University of Amsterdam, Postbus 94248, 1090 GE Amsterdam, The Netherlands. ; 1] Institut National de la Recherche Agronomique, UMR EcoFoG, Campus Agronomique, 97310 Kourou, French Guiana. [2] International Center for Tropical Botany, Department of Biological Sciences, Florida International University, Miami, Florida 33199, USA. ; Universidade Federal do Acre, Campus de Cruzeiro do Sul, Rio Branco, Brazil. ; INRA, UMR 1137 ''Ecologie et Ecophysiologie Forestiere'' 54280 Champenoux, France. ; Embrapa Roraima, Caixa Postal 133, Boa Vista, RR, CEP 69301-970, Brazil. ; Universidad Nacional San Antonio Abad del Cusco, Av. de la Cultura N degrees 733, Cusco, Peru. ; 1] School of Geography, University of Leeds, Leeds LS2 9JT, UK. [2] International Master Program of Agriculture, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung 40227, Taiwan. ; Universite Paul Sabatier CNRS, UMR 5174 Evolution et Diversite Biologique, Batiment 4R1, 31062 Toulouse, France. ; Northeast Region Inventory and Monitoring Program, National Park Service, 120 Chatham Lane, Fredericksburg, Virginia 22405, USA. ; Andes to Amazon Biodiversity Program, Puerto Maldonado, Madre de Dios, Peru. ; Universidade Federal do Para, Centro de Geociencias, Belem, CEP 66017-970 Para, Brazil. ; Universidade do Estado de Mato Grosso, Campus de Nova Xavantina, Caixa Postal 08, CEP 78.690-000, Nova Xavantina MT, Brazil. ; Department of Anthropology, University of Texas at Austin, SAC Room 5.150, 2201 Speedway Stop C3200, Austin, Texas 78712, USA. ; Department of Entomology, Smithsonian Institution, PO Box 37012, MRC 187, Washington DC 20013-7012, USA. ; Cirad, UMR Ecologie des Forets de Guyane, Campus Agronomique, 97310 Kourou, French Guiana. ; 1] School of Geography, University of Leeds, Leeds LS2 9JT, UK. [2] Instituto de Investigaciones de la Amazonia Peruana, Av. A. Jose Quinones km 2.5, Iquitos, Peru. ; World Wildlife Fund, 1250 24th Street NW, Washington DC 20037, USA. ; Centre for Tropical Environmental and Sustainability Science (TESS) and School of Marine and Environmental Sciences, James Cook University, Cairns, Queensland 4878, Australia. ; Instituto Boliviano de Investigacion Forestal, C.P. 6201, Santa Cruz de la Sierra, Bolivia. ; National Institute for Research in Amazonia (INPA), C.P. 478, Manaus, Amazonas, CEP 69011-970, Brazil. ; 1] FOMABO, Manejo Forestal en las Tierras Tropicales de Bolivia, Sacta, Bolivia. [2] Escuela de Ciencias Forestales (ESFOR), Universidad Mayor de San Simon (UMSS), Sacta, Bolivia. ; Universidad Estatal Amazonica, Facultad de Ingenieria Ambiental, Paso lateral km 2 1/2 via Napo, Puyo, Pastaza, Ecuador. ; National Institute for Research in Amazonia (INPA), C.P. 2223, 69080-971, Manaus, Amazonas, Brazil. ; Universidad Autonoma del Beni, Campus Universitario, Av. Ejercito Nacional, Riberalta, Beni, Bolivia. ; 1] Instituto Boliviano de Investigacion Forestal, C.P. 6201, Santa Cruz de la Sierra, Bolivia. [2] Forest Ecology and Forest Management Group, Wageningen University, PO Box 47, 6700 AA Wageningen, The Netherlands. ; 1] Center for Tropical Conservation, Duke University, Box 90381, Durham, North Carolina 27708, USA. [2] The Field Museum, 1400 South Lake Shore Drive, Chicago, Illinois 60605-2496, USA. ; Forest Ecology and Forest Management Group, Wageningen University, PO Box 47, 6700 AA Wageningen, The Netherlands. ; Universidad Nacional de la Amazonia Peruana, Iquitos, Loreto, Peru. ; Instituto de Investigaciones para el Desarrollo Forestal (INDEFOR), Universidad de Los Andes, Facultad de Ciencias Forestales y Ambientales, Conjunto Forestal, C.P. 5101, Merida, Venezuela. ; Iwokrama International Centre for Rainforest Conservation and Development, 77 High Street Kingston, Georgetown, Guyana. ; Museu Paraense Emilio Goeldi, Av. Magalhaes Barata, 376 - Sao Braz, CEP 66040-170, Belem PA, Brazil. ; UFRA, Av. Presidente Tancredo Neves 2501, CEP 66.077-901, Belem, Para, Brazil. ; Museu Universitario, Universidade Federal do Acre, Rio Branco AC 69910-900, Brazil. ; European Commission - DG Joint Research Centre, Institute for Environment and Sustainability, Via Enrico Fermi 274, 21010 Ispra, Italy. ; 1] Naturalis Biodiversity Center, PO Box, 2300 RA, Leiden, The Netherlands. [2] Ecology and Biodiversity Group, Utrecht University, PO Box 80084, 3508 TB Utrecht, The Netherlands. ; Museo de Historia Natural Alcide D'Orbigny, Av. Potosi no 1458, Cochabamba, Bolivia. ; 1] School of Earth and Environmental Science, James Cook University, Cairns, Queensland 4870, Australia. [2] Centre for Tropical Environmental and Sustainability Science (TESS) and School of Marine and Tropical Biology, James Cook University, Cairns, Queensland 4878, Australia. ; 1] Northumbria University, School of Geography, Ellison Place, Newcastle upon Tyne, Newcastle NE1 8ST, UK. [2] University of Wisconsin, Milwaukee, Wisconsin 53202, USA. [3] Smithsonian Tropical Research Institute, Apartado Postal 0843-03092, Panama, Republic of Panama. ; Van der Hout Forestry Consulting, Jan Trooststraat 6, 3078 HP Rotterdam, The Netherlands. ; Universidade Estadual de Campinas, NEPAM, Rua dos Flamboyants, 155- Cidade Universitaria Zeferino Vaz, Campinas, CEP 13083-867, Sao Paulo, Brazil. ; 1] Universidad Autonoma del Beni, Campus Universitario, Av. Ejercito Nacional, Riberalta, Beni, Bolivia. [2] Centro de Investigacion y Promocion del Campesinado, regional Norte Amazonico, C/ Nicanor Gonzalo Salvatierra N degrees 362, Casilla 16, Riberalta, Bolivia. ; Tropenbos International, PO Box 232, 6700 AE Wageningen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25788097" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Biomass ; Brazil ; Carbon/analysis/metabolism ; Carbon Dioxide/*analysis/metabolism ; *Carbon Sequestration ; Plant Stems/metabolism ; *Rainforest ; Trees/growth & development/metabolism ; Tropical Climate ; Wood/analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-09-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alberts, Bruce -- Beachy, Roger -- Baulcombe, David -- Blobel, Gunter -- Datta, Swapan -- Fedoroff, Nina -- Kennedy, Donald -- Khush, Gurdev S -- Peacock, Jim -- Rees, Martin -- Sharp, Phillip -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1320. doi: 10.1126/science.1245017.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24052276" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Carotenoids/chemistry/genetics/metabolism ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; *Oryza ; Philippines ; *Plants, Genetically Modified ; Seeds/chemistry/genetics ; Violence/*prevention & control ; Vitamin A/metabolism ; Vitamin A Deficiency/*prevention & control
    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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  • 9
    Keywords: CANCER ; CELLS ; DISTINCT ; CENTRAL-NERVOUS-SYSTEM ; METHYLATION ; ADULT ; BRAIN-TUMORS ; TELOMERASE ACTIVITY ; RISK STRATIFICATION ; SELF-RENEWAL
    Abstract: Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in 〈5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes.
    Type of Publication: Journal article published
    PubMed ID: 24174164
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  • 10
    Abstract: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (〈5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (〈12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
    Type of Publication: Journal article published
    PubMed ID: 26760213
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