ALBERT

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〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patch, Ann-Marie -- Christie, Elizabeth L -- Etemadmoghadam, Dariush -- Garsed, Dale W -- George, Joshy -- Fereday, Sian -- Nones, Katia -- Cowin, Prue -- Alsop, Kathryn -- Bailey, Peter J -- Kassahn, Karin S -- Newell, Felicity -- Quinn, Michael C J -- Kazakoff, Stephen -- Quek, Kelly -- Wilhelm-Benartzi, Charlotte -- Curry, Ed -- Leong, Huei San -- Australian Ovarian Cancer Study Group -- Hamilton, Anne -- Mileshkin, Linda -- Au-Yeung, George -- Kennedy, Catherine -- Hung, Jillian -- Chiew, Yoke-Eng -- Harnett, Paul -- Friedlander, Michael -- Quinn, Michael -- Pyman, Jan -- Cordner, Stephen -- O'Brien, Patricia -- Leditschke, Jodie -- Young, Greg -- Strachan, Kate -- Waring, Paul -- Azar, Walid -- Mitchell, Chris -- Traficante, Nadia -- Hendley, Joy -- Thorne, Heather -- Shackleton, Mark -- Miller, David K -- Arnau, Gisela Mir -- Tothill, Richard W -- Holloway, Timothy P -- Semple, Timothy -- Harliwong, Ivon -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Idrisoglu, Senel -- Bruxner, Timothy J C -- Christ, Angelika N -- Poudel, Barsha -- Holmes, Oliver -- Anderson, Matthew -- Leonard, Conrad -- Lonie, Andrew -- Hall, Nathan -- Wood, Scott -- Taylor, Darrin F -- Xu, Qinying -- Fink, J Lynn -- Waddell, Nick -- Drapkin, Ronny -- Stronach, Euan -- Gabra, Hani -- Brown, Robert -- Jewell, Andrea -- Nagaraj, Shivashankar H -- Markham, Emma -- Wilson, Peter J -- Ellul, Jason -- McNally, Orla -- Doyle, Maria A -- Vedururu, Ravikiran -- Stewart, Collin -- Lengyel, Ernst -- Pearson, John V -- Waddell, Nicola -- deFazio, Anna -- Grimmond, Sean M -- Bowtell, David D L -- England -- Nature. 2015 Nov 19;527(7578):398. doi: 10.1038/nature15716. Epub 2015 Oct 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26503049" target="_blank"〉PubMed〈/a〉

Description: Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patch, Ann-Marie -- Christie, Elizabeth L -- Etemadmoghadam, Dariush -- Garsed, Dale W -- George, Joshy -- Fereday, Sian -- Nones, Katia -- Cowin, Prue -- Alsop, Kathryn -- Bailey, Peter J -- Kassahn, Karin S -- Newell, Felicity -- Quinn, Michael C J -- Kazakoff, Stephen -- Quek, Kelly -- Wilhelm-Benartzi, Charlotte -- Curry, Ed -- Leong, Huei San -- Australian Ovarian Cancer Study Group -- Hamilton, Anne -- Mileshkin, Linda -- Au-Yeung, George -- Kennedy, Catherine -- Hung, Jillian -- Chiew, Yoke-Eng -- Harnett, Paul -- Friedlander, Michael -- Quinn, Michael -- Pyman, Jan -- Cordner, Stephen -- O'Brien, Patricia -- Leditschke, Jodie -- Young, Greg -- Strachan, Kate -- Waring, Paul -- Azar, Walid -- Mitchell, Chris -- Traficante, Nadia -- Hendley, Joy -- Thorne, Heather -- Shackleton, Mark -- Miller, David K -- Arnau, Gisela Mir -- Tothill, Richard W -- Holloway, Timothy P -- Semple, Timothy -- Harliwong, Ivon -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Idrisoglu, Senel -- Bruxner, Timothy J C -- Christ, Angelika N -- Poudel, Barsha -- Holmes, Oliver -- Anderson, Matthew -- Leonard, Conrad -- Lonie, Andrew -- Hall, Nathan -- Wood, Scott -- Taylor, Darrin F -- Xu, Qinying -- Fink, J Lynn -- Waddell, Nick -- Drapkin, Ronny -- Stronach, Euan -- Gabra, Hani -- Brown, Robert -- Jewell, Andrea -- Nagaraj, Shivashankar H -- Markham, Emma -- Wilson, Peter J -- Ellul, Jason -- McNally, Orla -- Doyle, Maria A -- Vedururu, Ravikiran -- Stewart, Collin -- Lengyel, Ernst -- Pearson, John V -- Waddell, Nicola -- deFazio, Anna -- Grimmond, Sean M -- Bowtell, David D L -- 13086/Cancer Research UK/United Kingdom -- England -- Nature. 2015 May 28;521(7553):489-94. doi: 10.1038/nature14410.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia [2] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. ; 1] Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia [3] Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. ; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06030, USA. ; 1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia [2] WolfsonWohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. ; 1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia [2] Technology Advancement Unit, Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia 5000, Australia. ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia. ; Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. ; 1] Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Department of Medicine, University of Melbourne, Parkville, Victoria 3052, Australia [3] The Royal Women's Hospital, Parkville, Victoria 3052, Australia. ; 1] Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. ; Centre for Cancer Research, University of Sydney at Westmead Millennium Institute, and Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales 2145, Australia. ; Crown Princess Mary Cancer Centre and University of Sydney at Westmead Hospital, Westmead, Sydney, New South Wales 2145, Australia. ; Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2031, Australia. ; The Royal Women's Hospital, Parkville, Victoria 3052, Australia. ; Victorian Institute of Forensic Medicine, Southbank, Victoria 3006, Australia. ; Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia. ; Victorian Life Sciences Computation Initiative, Carlton, Victoria 3053, Australia. ; La Trobe Institute for Molecular Science, Bundoora, Victoria 3083, Australia. ; Dana-Farber Cancer Institute, Boston, Massachusetts 02115-5450, USA. ; University of Chicago, Chicago, Illinois 60637, USA. ; The University of Western Australia, Crawley, Western Australia 6009, Australia. ; 1] Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia [3] Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia [4] Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK [5] Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26017449" target="_blank"〉PubMed〈/a〉

Description: When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per angstrom. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vampa, G -- Hammond, T J -- Thire, N -- Schmidt, B E -- Legare, F -- McDonald, C R -- Brabec, T -- Corkum, P B -- England -- Nature. 2015 Jun 25;522(7557):462-4. doi: 10.1038/nature14517.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. ; INRS-EMT, 1650 boulevard Lionel-Boulet, CP 1020, Varennes, Quebec J3X 1S2, Canada. ; 1] Department of Physics, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada [2] National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26108855" target="_blank"〉PubMed〈/a〉

Description: The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Lan -- Oliver, Eduardo -- Maratou, Klio -- Atanur, Santosh S -- Dubois, Olivier D -- Cotroneo, Emanuele -- Chen, Chien-Nien -- Wang, Lei -- Arce, Cristina -- Chabosseau, Pauline L -- Ponsa-Cobas, Joan -- Frid, Maria G -- Moyon, Benjamin -- Webster, Zoe -- Aldashev, Almaz -- Ferrer, Jorge -- Rutter, Guy A -- Stenmark, Kurt R -- Aitman, Timothy J -- Wilkins, Martin R -- 098424/Wellcome Trust/United Kingdom -- 101033/Wellcome Trust/United Kingdom -- MR/J0003042/1/Medical Research Council/United Kingdom -- P01 HL014985/HL/NHLBI NIH HHS/ -- PG/04/035/16912/British Heart Foundation/United Kingdom -- PG/10/59/28478/British Heart Foundation/United Kingdom -- PG/12/61/29818/British Heart Foundation/United Kingdom -- PG/2000137/British Heart Foundation/United Kingdom -- PG/95170/British Heart Foundation/United Kingdom -- PG/98018/British Heart Foundation/United Kingdom -- RG/10/16/28575/British Heart Foundation/United Kingdom -- WT098424AIA/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Aug 20;524(7565):356-60. doi: 10.1038/nature14620. Epub 2015 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. ; Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK. ; Section of Epigenomics and Disease, Department of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK. ; Department of Pediatrics and Medicine, Division of Critical Care Medicine and Cardiovascular Pulmonary Research Laboratories, University of Colorado Denver, Denver, Colorado 80045, USA. ; Transgenics and Embryonic Stem Cell Laboratory, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK. ; Institute of Molecular Biology and Medicine, 3 Togolok Moldo Street, Bishkek 720040, Kyrgyzstan. ; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26258299" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marks, Tobin J -- Hersam, Mark C -- England -- Nature. 2015 Apr 30;520(7549):631-2. doi: 10.1038/520631a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, the Department of Chemistry and the Materials Research Center, Northwestern University, Evanston, Illinois 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25925475" target="_blank"〉PubMed〈/a〉

Description: Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual's cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals' phased genome, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499021/" 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/PMC4499021/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schultz, Matthew D -- He, Yupeng -- Whitaker, John W -- Hariharan, Manoj -- Mukamel, Eran A -- Leung, Danny -- Rajagopal, Nisha -- Nery, Joseph R -- Urich, Mark A -- Chen, Huaming -- Lin, Shin -- Lin, Yiing -- Jung, Inkyung -- Schmitt, Anthony D -- Selvaraj, Siddarth -- Ren, Bing -- Sejnowski, Terrence J -- Wang, Wei -- Ecker, Joseph R -- F32 HL110473/HL/NHLBI NIH HHS/ -- F32HL110473/HL/NHLBI NIH HHS/ -- K99 HL119617/HL/NHLBI NIH HHS/ -- K99 NS080911/NS/NINDS NIH HHS/ -- K99HL119617/HL/NHLBI NIH HHS/ -- R00 NS080911/NS/NINDS NIH HHS/ -- R00NS080911/NS/NINDS NIH HHS/ -- R01 ES024984/ES/NIEHS NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jul 9;523(7559):212-6. doi: 10.1038/nature14465. Epub 2015 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Bioinformatics Program, University of California, San Diego, La Jolla, California 92093, USA [2] Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA. ; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; 1] Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Department of Cognitive Science, University of California, San Diego, La Jolla, California 92037, USA. ; Ludwig Institute for Cancer Research, La Jolla, California 92093, USA. ; Department of Genetics, Stanford University, 300 Pasteur Drive, M-344 Stanford, California 94305, USA. ; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, Missouri 63110, USA. ; Bioinformatics Program, University of California, San Diego, La Jolla, California 92093, USA. ; 1] Ludwig Institute for Cancer Research, La Jolla, California 92093, USA [2] University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, La Jolla, California 92093, USA. ; 1] Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Division of Biological Sciences, University of California at San Diego, La Jolla, California 92037, USA [3] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. ; 1] Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA [2] Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; 1] Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26030523" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cahill, Thomas J -- Stables, Rod -- England -- Nature. 2015 Sep 17;525(7569):321. doi: 10.1038/525321b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oxford University Hospitals NHS Trust, Oxford, UK. ; Liverpool Heart and Chest Hospital, Liverpool, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26381974" target="_blank"〉PubMed〈/a〉

Description: Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adhikari, Avishek -- Lerner, Talia N -- Finkelstein, Joel -- Pak, Sally -- Jennings, Joshua H -- Davidson, Thomas J -- Ferenczi, Emily -- Gunaydin, Lisa A -- Mirzabekov, Julie J -- Ye, Li -- Kim, Sung-Yon -- Lei, Anna -- Deisseroth, Karl -- 1F32MH105053-01/MH/NIMH NIH HHS/ -- K99 MH106649/MH/NIMH NIH HHS/ -- K99MH106649/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Nov 12;527(7577):179-85. doi: 10.1038/nature15698. Epub 2015 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA. ; CNC Program, Stanford University, Stanford, California 94304, USA. ; Neurosciences Program, Stanford University, Stanford, California 94305, USA. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA. ; Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26536109" target="_blank"〉PubMed〈/a〉

Description: The origin of the eukaryotic cell remains one of the most contentious puzzles in modern biology. Recent studies have provided support for the emergence of the eukaryotic host cell from within the archaeal domain of life, but the identity and nature of the putative archaeal ancestor remain a subject of debate. Here we describe the discovery of 'Lokiarchaeota', a novel candidate archaeal phylum, which forms a monophyletic group with eukaryotes in phylogenomic analyses, and whose genomes encode an expanded repertoire of eukaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities. Our results provide strong support for hypotheses in which the eukaryotic host evolved from a bona fide archaeon, and demonstrate that many components that underpin eukaryote-specific features were already present in that ancestor. This provided the host with a rich genomic 'starter-kit' to support the increase in the cellular and genomic complexity that is characteristic of eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444528/" 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/PMC4444528/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spang, Anja -- Saw, Jimmy H -- Jorgensen, Steffen L -- Zaremba-Niedzwiedzka, Katarzyna -- Martijn, Joran -- Lind, Anders E -- van Eijk, Roel -- Schleper, Christa -- Guy, Lionel -- Ettema, Thijs J G -- 310039/European Research Council/International -- England -- Nature. 2015 May 14;521(7551):173-9. doi: 10.1038/nature14447. Epub 2015 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden. ; Department of Biology, Centre for Geobiology, University of Bergen, N-5020 Bergen, Norway. ; 1] Department of Biology, Centre for Geobiology, University of Bergen, N-5020 Bergen, Norway [2] Division of Archaea Biology and Ecogenomics, Department of Ecogenomics and Systems Biology, University of Vienna, A-1090 Vienna, Austria. ; 1] Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden [2] Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25945739" target="_blank"〉PubMed〈/a〉