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  • 11
    Publikationsdatum: 2012-03-31
    Beschreibung: The circadian clock acts at the genomic level to coordinate internal behavioural and physiological rhythms via the CLOCK-BMAL1 transcriptional heterodimer. Although the nuclear receptors REV-ERB-alpha and REV-ERB-beta have been proposed to form an accessory feedback loop that contributes to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential, we determined the genome-wide cis-acting targets (cistromes) of both REV-ERB isoforms in murine liver, which revealed shared recognition at over 50% of their total DNA binding sites and extensive overlap with the master circadian regulator BMAL1. Although REV-ERB-alpha has been shown to regulate Bmal1 expression directly, our cistromic analysis reveals a more profound connection between BMAL1 and the REV-ERB-alpha and REV-ERB-beta genomic regulatory circuits than was previously suspected. Genes within the intersection of the BMAL1, REV-ERB-alpha and REV-ERB-beta cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erb-alpha and Rev-erb-beta function by creating double-knockout mice profoundly disrupted circadian expression of core circadian clock and lipid homeostatic gene networks. As a result, double-knockout mice show markedly altered circadian wheel-running behaviour and deregulated lipid metabolism. These data now unite REV-ERB-alpha and REV-ERB-beta with PER, CRY and other components of the principal feedback loop that drives circadian expression and indicate a more integral mechanism for the coordination of circadian rhythm and metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367514/" 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/PMC3367514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Han -- Zhao, Xuan -- Hatori, Megumi -- Yu, Ruth T -- Barish, Grant D -- Lam, Michael T -- Chong, Ling-Wa -- DiTacchio, Luciano -- Atkins, Annette R -- Glass, Christopher K -- Liddle, Christopher -- Auwerx, Johan -- Downes, Michael -- Panda, Satchidananda -- Evans, Ronald M -- DK057978/DK/NIDDK NIH HHS/ -- DK062434/DK/NIDDK NIH HHS/ -- DK090962/DK/NIDDK NIH HHS/ -- DK091618/DK/NIDDK NIH HHS/ -- HL105278/HL/NHLBI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01 DK091618/DK/NIDDK NIH HHS/ -- R01 HL105278/HL/NHLBI NIH HHS/ -- R01 HL105278-21/HL/NHLBI NIH HHS/ -- R24 DK090962/DK/NIDDK NIH HHS/ -- R24 DK090962-02/DK/NIDDK NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- R37 DK057978-34/DK/NIDDK NIH HHS/ -- T32 HL007770/HL/NHLBI NIH HHS/ -- T32 HL007770-15/HL/NHLBI NIH HHS/ -- T32-HL007770/HL/NHLBI NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19 DK062434-10/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 29;485(7396):123-7. doi: 10.1038/nature11048.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460952" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Biological Clocks/drug effects/genetics ; Circadian Rhythm/genetics/*physiology ; Cryptochromes/deficiency/genetics/metabolism ; *Energy Metabolism/genetics ; Feedback, Physiological ; Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Homeostasis/genetics ; *Lipid Metabolism/genetics ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Motor Activity/genetics/physiology ; Nuclear Receptor Subfamily 1, Group D, Member 1/deficiency/genetics/*metabolism ; Period Circadian Proteins/deficiency/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolism ; Repressor Proteins/deficiency/genetics/*metabolism ; Transcriptome/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Publikationsdatum: 2013-07-05
    Beschreibung: Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (alpha2,3-linked sialic acid) and human-type (alpha2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1beta, MCP-1, IL-6, IL-8 and IFN-alpha were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Jianfang -- Wang, Dayan -- Gao, Rongbao -- Zhao, Baihui -- Song, Jingdong -- Qi, Xian -- Zhang, Yanjun -- Shi, Yonglin -- Yang, Lei -- Zhu, Wenfei -- Bai, Tian -- Qin, Kun -- Lan, Yu -- Zou, Shumei -- Guo, Junfeng -- Dong, Jie -- Dong, Libo -- Zhang, Ye -- Wei, Hejiang -- Li, Xiaodan -- Lu, Jian -- Liu, Liqi -- Zhao, Xiang -- Li, Xiyan -- Huang, Weijuan -- Wen, Leying -- Bo, Hong -- Xin, Li -- Chen, Yongkun -- Xu, Cuilin -- Pei, Yuquan -- Yang, Yue -- Zhang, Xiaodong -- Wang, Shiwen -- Feng, Zijian -- Han, Jun -- Yang, Weizhong -- Gao, George F -- Wu, Guizhen -- Li, Dexin -- Wang, Yu -- Shu, Yuelong -- England -- Nature. 2013 Jul 25;499(7459):500-3. doi: 10.1038/nature12379. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823727" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antibodies, Viral/immunology ; Birds/virology ; Bronchi/cytology/metabolism/virology ; Cell Line ; Chemokines/blood ; China ; Cross Reactions/immunology ; Epithelial Cells/virology ; Host Specificity ; Humans ; In Vitro Techniques ; Influenza A Virus, H5N1 Subtype/immunology/physiology ; Influenza A virus/immunology/pathogenicity/*physiology ; Influenza Vaccines/immunology ; Influenza in Birds/transmission/*virology ; Influenza, Human/blood/immunology/virology ; Lung/virology ; N-Acetylneuraminic Acid/analogs & derivatives/chemistry/metabolism ; Organ Specificity ; Pulmonary Alveoli/cytology/metabolism/virology ; Receptors, Virus/chemistry/*metabolism ; Trachea/virology ; Virus Replication ; Zoonoses/transmission/virology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    Publikationsdatum: 2014-03-29
    Beschreibung: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" 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/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    Publikationsdatum: 2014-08-12
    Beschreibung: Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration and high rates of mortality. Through chemical screening and optimization, we identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 messenger RNA with high selectivity. Administration of these compounds to Delta7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naryshkin, Nikolai A -- Weetall, Marla -- Dakka, Amal -- Narasimhan, Jana -- Zhao, Xin -- Feng, Zhihua -- Ling, Karen K Y -- Karp, Gary M -- Qi, Hongyan -- Woll, Matthew G -- Chen, Guangming -- Zhang, Nanjing -- Gabbeta, Vijayalakshmi -- Vazirani, Priya -- Bhattacharyya, Anuradha -- Furia, Bansri -- Risher, Nicole -- Sheedy, Josephine -- Kong, Ronald -- Ma, Jiyuan -- Turpoff, Anthony -- Lee, Chang-Sun -- Zhang, Xiaoyan -- Moon, Young-Choon -- Trifillis, Panayiota -- Welch, Ellen M -- Colacino, Joseph M -- Babiak, John -- Almstead, Neil G -- Peltz, Stuart W -- Eng, Loren A -- Chen, Karen S -- Mull, Jesse L -- Lynes, Maureen S -- Rubin, Lee L -- Fontoura, Paulo -- Santarelli, Luca -- Haehnke, Daniel -- McCarthy, Kathleen D -- Schmucki, Roland -- Ebeling, Martin -- Sivaramakrishnan, Manaswini -- Ko, Chien-Ping -- Paushkin, Sergey V -- Ratni, Hasane -- Gerlach, Irene -- Ghosh, Anirvan -- Metzger, Friedrich -- New York, N.Y. -- Science. 2014 Aug 8;345(6197):688-93. doi: 10.1126/science.1250127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. ; Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA. ; PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. friedrich.metzger@roche.com speltz@ptcbio.com. ; SMA Foundation, 888 Seventh Avenue, Suite 400, New York, NY 10019, USA. ; Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. ; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. ; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. friedrich.metzger@roche.com speltz@ptcbio.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25104390" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Administration, Oral ; Alternative Splicing/*drug effects ; Animals ; Cells, Cultured ; Coumarins/*administration & dosage/chemistry ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Isocoumarins/*administration & dosage/chemistry ; Longevity/*drug effects ; Mice ; Muscular Atrophy, Spinal/*drug therapy/genetics/metabolism ; Pyrimidinones/*administration & dosage/chemistry ; RNA, Messenger/genetics ; Sequence Deletion ; Small Molecule Libraries/*administration & dosage/chemistry ; Survival of Motor Neuron 2 Protein/*genetics/metabolism
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Publikationsdatum: 2007-04-28
    Beschreibung: The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engelman, Jeffrey A -- Zejnullahu, Kreshnik -- Mitsudomi, Tetsuya -- Song, Youngchul -- Hyland, Courtney -- Park, Joon Oh -- Lindeman, Neal -- Gale, Christopher-Michael -- Zhao, Xiaojun -- Christensen, James -- Kosaka, Takayuki -- Holmes, Alison J -- Rogers, Andrew M -- Cappuzzo, Federico -- Mok, Tony -- Lee, Charles -- Johnson, Bruce E -- Cantley, Lewis C -- Janne, Pasi A -- 1K12CA87723-01/CA/NCI NIH HHS/ -- GM41890/GM/NIGMS NIH HHS/ -- K08CA120060-01/CA/NCI NIH HHS/ -- P01 CA089021/CA/NCI NIH HHS/ -- P20CA90578-02/CA/NCI NIH HHS/ -- R01 GM041890/GM/NIGMS NIH HHS/ -- R01-CA111560/CA/NCI NIH HHS/ -- R01CA114465-01/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 18;316(5827):1039-43. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463250" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; CHO Cells ; Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cricetinae ; Cricetulus ; Drug Resistance, Neoplasm ; Enzyme Inhibitors ; *Gene Amplification ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-met ; Quinazolines/*pharmacology/therapeutic use ; Receptor, ErbB-3/*metabolism ; Receptors, Growth Factor/*genetics/metabolism ; *Signal Transduction ; Sulfones/pharmacology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    Publikationsdatum: 2009-09-19
    Beschreibung: Nearly all of the large-bodied predators (〉2.5 tons) on northern continents during the Late Cretaceous were tyrannosaurid dinosaurs. We show that their most conspicuous functional specializations--a proportionately large skull, incisiform premaxillary teeth, expanded jaw-closing musculature, diminutive forelimbs, and hindlimbs with cursorial proportions--were present in a new, small-bodied, basal tyrannosauroid from Lower Cretaceous rocks in northeastern China. These specializations, which were later scaled up in Late Cretaceous tyrannosaurids with body masses approaching 100 times greater, drove the most dominant radiation of macropredators of the Mesozoic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sereno, Paul C -- Tan, Lin -- Brusatte, Stephen L -- Kriegstein, Henry J -- Zhao, Xijin -- Cloward, Karen -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):418-22. doi: 10.1126/science.1177428. Epub 2009 Sep 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA. dinosaur@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762599" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Biological Evolution ; Body Size ; Bone and Bones/*anatomy & histology ; Cerebrum/anatomy & histology ; China ; *Dinosaurs/anatomy & histology/classification ; Forelimb/anatomy & histology ; *Fossils ; Hindlimb/anatomy & histology ; Phylogeny ; Skeleton ; Skull/anatomy & histology ; Tooth/anatomy & histology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    Publikationsdatum: 2016-03-31
    Beschreibung: Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia), has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone artefacts and remains of other extinct endemic fauna, were dated to between about 95 and 12 thousand calendar years (kyr) ago. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago. Here we report new stratigraphic and chronological evidence from Liang Bua that does not support the ages inferred previously for the H. floresiensis holotype (LB1), ~18 thousand calibrated radiocarbon years before present (kyr cal. BP), or the time of last appearance of this species (about 17 or 13-11 kyr cal. BP). Instead, the skeletal remains of H. floresiensis and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago--potentially encountering modern humans on Flores or other hominins dispersing through southeast Asia, such as Denisovans--is an open question.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sutikna, Thomas -- Tocheri, Matthew W -- Morwood, Michael J -- Saptomo, E Wahyu -- Jatmiko -- Awe, Rokus Due -- Wasisto, Sri -- Westaway, Kira E -- Aubert, Maxime -- Li, Bo -- Zhao, Jian-xin -- Storey, Michael -- Alloway, Brent V -- Morley, Mike W -- Meijer, Hanneke J M -- van den Bergh, Gerrit D -- Grun, Rainer -- Dosseto, Anthony -- Brumm, Adam -- Jungers, William L -- Roberts, Richard G -- England -- Nature. 2016 Apr 21;532(7599):366-9. doi: 10.1038/nature17179. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Archaeological Science, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; Pusat Penelitian Arkeologi Nasional, Jakarta 12510, Indonesia. ; Department of Anthropology, Lakehead University, Thunder Bay, Ontario P7B 5E1, Canada. ; Human Origins Program, Department of Anthropology, National Museum of Natural History, Smithsonian Institution, Washington DC 20013, USA. ; Traps MQ Luminescence Dating Facility, Department of Environmental Sciences, Macquarie University, Sydney, New South Wales 2109, Australia. ; Research Centre for Human Evolution, Place, Evolution and Rock Art Heritage Unit, Griffith University, Gold Coast, Queensland 4222, Australia. ; School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; School of Earth Sciences, University of Queensland, Brisbane, Queensland 4072, Australia. ; QUADLAB, Section of Earth and Planetary System Science, Natural History Museum of Denmark, 1350 Copenhagen, Denmark. ; School of Geography, Environment and Earth Sciences, Victoria University of Wellington, Wellington 6012, New Zealand. ; Department of Natural History, University Museum of Bergen, University of Bergen, 5007 Bergen, Norway. ; Research Centre for Human Evolution, Environmental Futures Research Institute, Griffith University, Brisbane, Queensland 4111, Australia. ; Research School of Earth Sciences, Australian National University, Canberra, Australian Capital Territory 0200, Australia. ; GeoQuEST Research Centre, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; Department of Anatomical Sciences, Stony Brook University Medical Center, Stony Brook, New York 11794, USA. ; Association Vahatra, BP 3972, Antananarivo 101, Madagascar.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027286" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aluminum Silicates ; Animals ; *Archaeology ; Australia ; Calibration ; Caves ; *Fossils ; Geologic Sediments/analysis ; Glass ; *Hominidae ; Humans ; Indonesia ; Potassium Compounds ; Quartz ; *Radiometric Dating ; Time Factors ; Uncertainty
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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