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  • 1
    Publication Date: 2011-12-06
    Description: Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335296/" 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/PMC3335296/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gieger, Christian -- Radhakrishnan, Aparna -- Cvejic, Ana -- Tang, Weihong -- Porcu, Eleonora -- Pistis, Giorgio -- Serbanovic-Canic, Jovana -- Elling, Ulrich -- Goodall, Alison H -- Labrune, Yann -- Lopez, Lorna M -- Magi, Reedik -- Meacham, Stuart -- Okada, Yukinori -- Pirastu, Nicola -- Sorice, Rossella -- Teumer, Alexander -- Voss, Katrin -- Zhang, Weihua -- Ramirez-Solis, Ramiro -- Bis, Joshua C -- Ellinghaus, David -- Gogele, Martin -- Hottenga, Jouke-Jan -- Langenberg, Claudia -- Kovacs, Peter -- O'Reilly, Paul F -- Shin, So-Youn -- Esko, Tonu -- Hartiala, Jaana -- Kanoni, Stavroula -- Murgia, Federico -- Parsa, Afshin -- Stephens, Jonathan -- van der Harst, Pim -- Ellen van der Schoot, C -- Allayee, Hooman -- Attwood, Antony -- Balkau, Beverley -- Bastardot, Francois -- Basu, Saonli -- Baumeister, Sebastian E -- Biino, Ginevra -- Bomba, Lorenzo -- Bonnefond, Amelie -- Cambien, Francois -- Chambers, John C -- Cucca, Francesco -- D'Adamo, Pio -- Davies, Gail -- de Boer, Rudolf A -- de Geus, Eco J C -- Doring, Angela -- Elliott, Paul -- Erdmann, Jeanette -- Evans, David M -- Falchi, Mario -- Feng, Wei -- Folsom, Aaron R -- Frazer, Ian H -- Gibson, Quince D -- Glazer, Nicole L -- Hammond, Chris -- Hartikainen, Anna-Liisa -- Heckbert, Susan R -- Hengstenberg, Christian -- Hersch, Micha -- Illig, Thomas -- Loos, Ruth J F -- Jolley, Jennifer -- Khaw, Kay Tee -- Kuhnel, Brigitte -- Kyrtsonis, Marie-Christine -- Lagou, Vasiliki -- Lloyd-Jones, Heather -- Lumley, Thomas -- Mangino, Massimo -- Maschio, Andrea -- Mateo Leach, Irene -- McKnight, Barbara -- Memari, Yasin -- Mitchell, Braxton D -- Montgomery, Grant W -- Nakamura, Yusuke -- Nauck, Matthias -- Navis, Gerjan -- Nothlings, Ute -- Nolte, Ilja M -- Porteous, David J -- Pouta, Anneli -- Pramstaller, Peter P -- Pullat, Janne -- Ring, Susan M -- Rotter, Jerome I -- Ruggiero, Daniela -- Ruokonen, Aimo -- Sala, Cinzia -- Samani, Nilesh J -- Sambrook, Jennifer -- Schlessinger, David -- Schreiber, Stefan -- Schunkert, Heribert -- Scott, James -- Smith, Nicholas L -- Snieder, Harold -- Starr, John M -- Stumvoll, Michael -- Takahashi, Atsushi -- Tang, W H Wilson -- Taylor, Kent -- Tenesa, Albert -- Lay Thein, Swee -- Tonjes, Anke -- Uda, Manuela -- Ulivi, Sheila -- van Veldhuisen, Dirk J -- Visscher, Peter M -- Volker, Uwe -- Wichmann, H-Erich -- Wiggins, Kerri L -- Willemsen, Gonneke -- Yang, Tsun-Po -- Hua Zhao, Jing -- Zitting, Paavo -- Bradley, John R -- Dedoussis, George V -- Gasparini, Paolo -- Hazen, Stanley L -- Metspalu, Andres -- Pirastu, Mario -- Shuldiner, Alan R -- Joost van Pelt, L -- Zwaginga, Jaap-Jan -- Boomsma, Dorret I -- Deary, Ian J -- Franke, Andre -- Froguel, Philippe -- Ganesh, Santhi K -- Jarvelin, Marjo-Riitta -- Martin, Nicholas G -- Meisinger, Christa -- Psaty, Bruce M -- Spector, Timothy D -- Wareham, Nicholas J -- Akkerman, Jan-Willem N -- Ciullo, Marina -- Deloukas, Panos -- Greinacher, Andreas -- Jupe, Steve -- Kamatani, Naoyuki -- Khadake, Jyoti -- Kooner, Jaspal S -- Penninger, Josef -- Prokopenko, Inga -- Stemple, Derek -- Toniolo, Daniela -- Wernisch, Lorenz -- Sanna, Serena -- Hicks, Andrew A -- Rendon, Augusto -- Ferreira, Manuel A -- Ouwehand, Willem H -- Soranzo, Nicole -- 092731/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- CZB/4/505/Chief Scientist Office/United Kingdom -- ETM/55/Chief Scientist Office/United Kingdom -- G0000111/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701120/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- K12 RR023250/RR/NCRR NIH HHS/ -- K12 RR023250-05/RR/NCRR NIH HHS/ -- M01 RR016500/RR/NCRR NIH HHS/ -- M01 RR016500-08/RR/NCRR NIH HHS/ -- MC_U105260799/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- N01 HC055015/HC/NHLBI NIH HHS/ -- N01 HC055016/HC/NHLBI NIH HHS/ -- N01 HC055018/HC/NHLBI NIH HHS/ -- N01 HC055019/HC/NHLBI NIH HHS/ -- N01 HC055020/HC/NHLBI NIH HHS/ -- N01 HC055021/HC/NHLBI NIH HHS/ -- N01 HC055022/HC/NHLBI NIH HHS/ -- N01 HC085079/HC/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL076491-09/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- P01 HL098055-03/HL/NHLBI NIH HHS/ -- P30 DK072488/DK/NIDDK NIH HHS/ -- P30 DK072488-08/DK/NIDDK NIH HHS/ -- P41 HG003751/HG/NHGRI NIH HHS/ -- R01 AG018728/AG/NIA NIH HHS/ -- R01 AG018728-05S1/AG/NIA NIH HHS/ -- R01 GM053275/GM/NIGMS NIH HHS/ -- R01 GM053275-14/GM/NIGMS NIH HHS/ -- R01 HD042157/HD/NICHD NIH HHS/ -- R01 HD042157-01A1/HD/NICHD NIH HHS/ -- R01 HL059367/HL/NHLBI NIH HHS/ -- R01 HL059367-11/HL/NHLBI NIH HHS/ -- R01 HL068986/HL/NHLBI NIH HHS/ -- R01 HL068986-06/HL/NHLBI NIH HHS/ -- R01 HL073410/HL/NHLBI NIH HHS/ -- R01 HL073410-08/HL/NHLBI NIH HHS/ -- R01 HL085251/HL/NHLBI NIH HHS/ -- R01 HL085251-04/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL086694-05/HL/NHLBI NIH HHS/ -- R01 HL087641/HL/NHLBI NIH HHS/ -- R01 HL087641-03/HL/NHLBI NIH HHS/ -- R01 HL087679-03/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 HL088119-04/HL/NHLBI NIH HHS/ -- R01 HL103866/HL/NHLBI NIH HHS/ -- R01 HL103866-03/HL/NHLBI NIH HHS/ -- R01 HL105756/HL/NHLBI NIH HHS/ -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RL1 MH083268/MH/NIMH NIH HHS/ -- RL1 MH083268-05/MH/NIMH NIH HHS/ -- U01 GM074518/GM/NIGMS NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 HL084756-03/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- U54 RR020278-06/RR/NCRR NIH HHS/ -- UL1 RR025005/RR/NCRR NIH HHS/ -- UL1 RR025005-05/RR/NCRR NIH HHS/ -- WT077037/Z/05/Z/Wellcome Trust/United Kingdom -- WT077047/Z/05/Z/Wellcome Trust/United Kingdom -- WT082597/Z/07/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Nov 30;480(7376):201-8. doi: 10.1038/nature10659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstadter Landstr 1, 85764 Neuherberg, Germany. christian.gieger@helmholtz-muenchen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22139419" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Platelets/*cytology/metabolism ; Cell Size ; Drosophila Proteins/genetics ; Drosophila melanogaster/genetics ; Europe ; Gene Expression Profiling ; Gene Silencing ; Genome, Human/genetics ; Genome-Wide Association Study ; Hematopoiesis/*genetics ; Humans ; Megakaryocytes/*cytology/metabolism ; Platelet Count ; Protein Interaction Maps ; Transcription, Genetic/genetics ; Zebrafish/genetics ; Zebrafish Proteins/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: 2012-12-12
    Description: Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P 〈 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623669/" 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/PMC3623669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van der Harst, Pim -- Zhang, Weihua -- Mateo Leach, Irene -- Rendon, Augusto -- Verweij, Niek -- Sehmi, Joban -- Paul, Dirk S -- Elling, Ulrich -- Allayee, Hooman -- Li, Xinzhong -- Radhakrishnan, Aparna -- Tan, Sian-Tsung -- Voss, Katrin -- Weichenberger, Christian X -- Albers, Cornelis A -- Al-Hussani, Abtehale -- Asselbergs, Folkert W -- Ciullo, Marina -- Danjou, Fabrice -- Dina, Christian -- Esko, Tonu -- Evans, David M -- Franke, Lude -- Gogele, Martin -- Hartiala, Jaana -- Hersch, Micha -- Holm, Hilma -- Hottenga, Jouke-Jan -- Kanoni, Stavroula -- Kleber, Marcus E -- Lagou, Vasiliki -- Langenberg, Claudia -- Lopez, Lorna M -- Lyytikainen, Leo-Pekka -- Melander, Olle -- Murgia, Federico -- Nolte, Ilja M -- O'Reilly, Paul F -- Padmanabhan, Sandosh -- Parsa, Afshin -- Pirastu, Nicola -- Porcu, Eleonora -- Portas, Laura -- Prokopenko, Inga -- Ried, Janina S -- Shin, So-Youn -- Tang, Clara S -- Teumer, Alexander -- Traglia, Michela -- Ulivi, Sheila -- Westra, Harm-Jan -- Yang, Jian -- Zhao, Jing Hua -- Anni, Franco -- Abdellaoui, Abdel -- Attwood, Antony -- Balkau, Beverley -- Bandinelli, Stefania -- Bastardot, Francois -- Benyamin, Beben -- Boehm, Bernhard O -- Cookson, William O -- Das, Debashish -- de Bakker, Paul I W -- de Boer, Rudolf A -- de Geus, Eco J C -- de Moor, Marleen H -- Dimitriou, Maria -- Domingues, Francisco S -- Doring, Angela -- Engstrom, Gunnar -- Eyjolfsson, Gudmundur Ingi -- Ferrucci, Luigi -- Fischer, Krista -- Galanello, Renzo -- Garner, Stephen F -- Genser, Bernd -- Gibson, Quince D -- Girotto, Giorgia -- Gudbjartsson, Daniel Fannar -- Harris, Sarah E -- Hartikainen, Anna-Liisa -- Hastie, Claire E -- Hedblad, Bo -- Illig, Thomas -- Jolley, Jennifer -- Kahonen, Mika -- Kema, Ido P -- Kemp, John P -- Liang, Liming -- Lloyd-Jones, Heather -- Loos, Ruth J F -- Meacham, Stuart -- Medland, Sarah E -- Meisinger, Christa -- Memari, Yasin -- Mihailov, Evelin -- Miller, Kathy -- Moffatt, Miriam F -- Nauck, Matthias -- Novatchkova, Maria -- Nutile, Teresa -- Olafsson, Isleifur -- Onundarson, Pall T -- Parracciani, Debora -- Penninx, Brenda W -- Perseu, Lucia -- Piga, Antonio -- Pistis, Giorgio -- Pouta, Anneli -- Puc, Ursula -- Raitakari, Olli -- Ring, Susan M -- Robino, Antonietta -- Ruggiero, Daniela -- Ruokonen, Aimo -- Saint-Pierre, Aude -- Sala, Cinzia -- Salumets, Andres -- Sambrook, Jennifer -- Schepers, Hein -- Schmidt, Carsten Oliver -- Sillje, Herman H W -- Sladek, Rob -- Smit, Johannes H -- Starr, John M -- Stephens, Jonathan -- Sulem, Patrick -- Tanaka, Toshiko -- Thorsteinsdottir, Unnur -- Tragante, Vinicius -- van Gilst, Wiek H -- van Pelt, L Joost -- van Veldhuisen, Dirk J -- Volker, Uwe -- Whitfield, John B -- Willemsen, Gonneke -- Winkelmann, Bernhard R -- Wirnsberger, Gerald -- Algra, Ale -- Cucca, Francesco -- d'Adamo, Adamo Pio -- Danesh, John -- Deary, Ian J -- Dominiczak, Anna F -- Elliott, Paul -- Fortina, Paolo -- Froguel, Philippe -- Gasparini, Paolo -- Greinacher, Andreas -- Hazen, Stanley L -- Jarvelin, Marjo-Riitta -- Khaw, Kay Tee -- Lehtimaki, Terho -- Maerz, Winfried -- Martin, Nicholas G -- Metspalu, Andres -- Mitchell, Braxton D -- Montgomery, Grant W -- Moore, Carmel -- Navis, Gerjan -- Pirastu, Mario -- Pramstaller, Peter P -- Ramirez-Solis, Ramiro -- Schadt, Eric -- Scott, James -- Shuldiner, Alan R -- Smith, George Davey -- Smith, J Gustav -- Snieder, Harold -- Sorice, Rossella -- Spector, Tim D -- Stefansson, Kari -- Stumvoll, Michael -- Tang, W H Wilson -- Toniolo, Daniela -- Tonjes, Anke -- Visscher, Peter M -- Vollenweider, Peter -- Wareham, Nicholas J -- Wolffenbuttel, Bruce H R -- Boomsma, Dorret I -- Beckmann, Jacques S -- Dedoussis, George V -- Deloukas, Panos -- Ferreira, Manuel A -- Sanna, Serena -- Uda, Manuela -- Hicks, Andrew A -- Penninger, Josef Martin -- Gieger, Christian -- Kooner, Jaspal S -- Ouwehand, Willem H -- Soranzo, Nicole -- Chambers, John C -- 092731/Wellcome Trust/United Kingdom -- 097117/Wellcome Trust/United Kingdom -- 14136/Cancer Research UK/United Kingdom -- CZB/4/505/Chief Scientist Office/United Kingdom -- ETM/55/Chief Scientist Office/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G1002084/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- HHSN268201100005C/HL/NHLBI NIH HHS/ -- HHSN268201100006C/HL/NHLBI NIH HHS/ -- HHSN268201100007C/HL/NHLBI NIH HHS/ -- HHSN268201100008C/HL/NHLBI NIH HHS/ -- HHSN268201100009C/HL/NHLBI NIH HHS/ -- HHSN268201100010C/HL/NHLBI NIH HHS/ -- HHSN268201100011C/HL/NHLBI NIH HHS/ -- HHSN268201100012C/HL/NHLBI NIH HHS/ -- HHSN271201100005C/DA/NIDA NIH HHS/ -- K12 RR023250/RR/NCRR NIH HHS/ -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- N01AG12109/AG/NIA NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- P20 HL113452/HL/NHLBI NIH HHS/ -- P30 DK072488/DK/NIDDK NIH HHS/ -- R01 AG018728/AG/NIA NIH HHS/ -- R01 CA165001/CA/NCI NIH HHS/ -- R01 GM053275/GM/NIGMS NIH HHS/ -- R01 HD042157/HD/NICHD NIH HHS/ -- R01 HL059367/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL087641/HL/NHLBI NIH HHS/ -- R01 HL087679/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 HL103866/HL/NHLBI NIH HHS/ -- R01 HL103931/HL/NHLBI NIH HHS/ -- R01 LM010098/LM/NLM NIH HHS/ -- R01 MH081802/MH/NIMH NIH HHS/ -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RL1 MH083268/MH/NIMH NIH HHS/ -- U01 GM074518/GM/NIGMS NIH HHS/ -- U01 HG004402/HG/NHGRI NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U24 MH068457/MH/NIMH NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1 RR025005/RR/NCRR NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- England -- Nature. 2012 Dec 20;492(7429):369-75. doi: 10.1038/nature11677. Epub 2012 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. p.van.der.harst@umcg.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222517" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle/genetics ; Cytokines/metabolism ; Drosophila melanogaster/genetics ; Erythrocytes/cytology/*metabolism ; Female ; Gene Expression Regulation/genetics ; *Genetic Loci ; *Genome-Wide Association Study ; Hematopoiesis/genetics ; Hemoglobins/genetics ; Humans ; Male ; Mice ; Organ Specificity ; *Phenotype ; Polymorphism, Single Nucleotide/genetics ; RNA Interference ; Signal Transduction/genetics
    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: 2014-05-03
    Description: Regulation of cell volume is critical for many cellular and organismal functions, yet the molecular identity of a key player, the volume-regulated anion channel VRAC, has remained unknown. A genome-wide small interfering RNA screen in mammalian cells identified LRRC8A as a VRAC component. LRRC8A formed heteromers with other LRRC8 multispan membrane proteins. Genomic disruption of LRRC8A ablated VRAC currents. Cells with disruption of all five LRRC8 genes required LRRC8A cotransfection with other LRRC8 isoforms to reconstitute VRAC currents. The isoform combination determined VRAC inactivation kinetics. Taurine flux and regulatory volume decrease also depended on LRRC8 proteins. Our work shows that VRAC defines a class of anion channels, suggests that VRAC is identical to the volume-sensitive organic osmolyte/anion channel VSOAC, and explains the heterogeneity of native VRAC currents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Voss, Felizia K -- Ullrich, Florian -- Munch, Jonas -- Lazarow, Katina -- Lutter, Darius -- Mah, Nancy -- Andrade-Navarro, Miguel A -- von Kries, Jens P -- Stauber, Tobias -- Jentsch, Thomas J -- New York, N.Y. -- Science. 2014 May 9;344(6184):634-8. doi: 10.1126/science.1252826. Epub 2014 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz-Institut fur Molekulare Pharmakologie (FMP), Berlin.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24790029" target="_blank"〉PubMed〈/a〉
    Keywords: Agammaglobulinemia/genetics ; *Cell Size ; Chloride Channels/*metabolism ; Gene Knockout Techniques ; Genome-Wide Association Study ; HCT116 Cells ; HEK293 Cells ; Humans ; Membrane Proteins/genetics/*metabolism ; Mutation ; Protein Multimerization ; RNA Interference ; RNA, Small Interfering/genetics ; Taurine/metabolism ; Transfection
    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: 2014-09-27
    Description: Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254742/" 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/PMC4254742/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lu -- Kostadima, Myrto -- Martens, Joost H A -- Canu, Giovanni -- Garcia, Sara P -- Turro, Ernest -- Downes, Kate -- Macaulay, Iain C -- Bielczyk-Maczynska, Ewa -- Coe, Sophia -- Farrow, Samantha -- Poudel, Pawan -- Burden, Frances -- Jansen, Sjoert B G -- Astle, William J -- Attwood, Antony -- Bariana, Tadbir -- de Bono, Bernard -- Breschi, Alessandra -- Chambers, John C -- BRIDGE Consortium -- Choudry, Fizzah A -- Clarke, Laura -- Coupland, Paul -- van der Ent, Martijn -- Erber, Wendy N -- Jansen, Joop H -- Favier, Remi -- Fenech, Matthew E -- Foad, Nicola -- Freson, Kathleen -- van Geet, Chris -- Gomez, Keith -- Guigo, Roderic -- Hampshire, Daniel -- Kelly, Anne M -- Kerstens, Hindrik H D -- Kooner, Jaspal S -- Laffan, Michael -- Lentaigne, Claire -- Labalette, Charlotte -- Martin, Tiphaine -- Meacham, Stuart -- Mumford, Andrew -- Nurnberg, Sylvia -- Palumbo, Emilio -- van der Reijden, Bert A -- Richardson, David -- Sammut, Stephen J -- Slodkowicz, Greg -- Tamuri, Asif U -- Vasquez, Louella -- Voss, Katrin -- Watt, Stephen -- Westbury, Sarah -- Flicek, Paul -- Loos, Remco -- Goldman, Nick -- Bertone, Paul -- Read, Randy J -- Richardson, Sylvia -- Cvejic, Ana -- Soranzo, Nicole -- Ouwehand, Willem H -- Stunnenberg, Hendrik G -- Frontini, Mattia -- Rendon, Augusto -- 082961/Wellcome Trust/United Kingdom -- 082961/Z/07/Z/Wellcome Trust/United Kingdom -- 084183/Z/07/Z/Wellcome Trust/United Kingdom -- 095908/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- C45041/A14953/Cancer Research UK/United Kingdom -- FS/12/27/29405/British Heart Foundation/United Kingdom -- MC_UP_0801/1/Medical Research Council/United Kingdom -- MR/J011711/1/Medical Research Council/United Kingdom -- MR/K006584/1/Medical Research Council/United Kingdom -- MR/K023489/1/Medical Research Council/United Kingdom -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RG/09/12/28096/British Heart Foundation/United Kingdom -- RP-PG-0310-1002/British Heart Foundation/United Kingdom -- RP-PG-0310-1002/Department of Health/United Kingdom -- WT091310/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1251033. doi: 10.1126/science.1251033.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. ; Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, Netherlands. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. ; Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK. ; Department of Haematology, University College London Cancer Institute, London WC1E 6DD, UK. The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London NW3 2QG, UK. ; CHIME Institute, University College London, Archway Campus, London NW1 2DA, UK. Auckland Bioengineering Institute, University of Auckland, Auckland 1010, New Zealand. ; Centre for Genomic Regulation and University Pompeu Fabra, 08002 Barcelona, Spain. ; Imperial College Healthcare NHS Trust, DuCane Road, London W12 0HS, UK. Ealing Hospital NHS Trust, Southall, Middlesex UB1 3HW, UK. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia. ; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. ; Assistance Publique-Hopitaux de Paris, INSERM U1009, 94805 Villejuif, France. ; Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK. ; Center for Molecular and Vascular Biology, University of Leuven, 3000 Leuven, Belgium. ; The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London NW3 2QG, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge B2 0QQ, UK. ; Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London W12 0HS, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. Department of Twin Research & Genetic Epidemiology, Genetics and Molecular Medicine Division, St Thomas' Hospital, King's College, London SE1 7EH, UK. ; School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK. ; Department of Oncology, Addenbrooke's Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge CB2 0RE, UK. Cancer Research UK, Cambridge Institute, Cambridge Biomedical Campus, Cambridge CB2 0RE, UK. ; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. ; School of Clinical Sciences, University of Bristol, Bristol BS2 8DZ, UK. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, 69117 Heidelberg, Germany. Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK. ; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK. ; Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. ar506@cam.ac.uk mf471@cam.ac.uk. ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK. Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK. ar506@cam.ac.uk mf471@cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25258084" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Cell Lineage/*genetics ; Genetic Variation ; Hematopoiesis/*genetics ; Hematopoietic Stem Cells/*cytology/metabolism ; Humans ; NFI Transcription Factors/genetics/metabolism ; RNA-Binding Proteins/metabolism ; Thrombopoiesis/genetics ; Transcriptome
    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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  • 5
    Publication Date: 2015-12-18
    Description: The Gorkha earthquake (magnitude 7.8) on 25 April 2015 and later aftershocks struck South Asia, killing ~9000 people and damaging a large region. Supported by a large campaign of responsive satellite data acquisitions over the earthquake disaster zone, our team undertook a satellite image survey of the earthquakes' induced geohazards in Nepal and China and an assessment of the geomorphic, tectonic, and lithologic controls on quake-induced landslides. Timely analysis and communication aided response and recovery and informed decision-makers. We mapped 4312 coseismic and postseismic landslides. We also surveyed 491 glacier lakes for earthquake damage but found only nine landslide-impacted lakes and no visible satellite evidence of outbursts. Landslide densities correlate with slope, peak ground acceleration, surface downdrop, and specific metamorphic lithologies and large plutonic intrusions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kargel, J S -- Leonard, G J -- Shugar, D H -- Haritashya, U K -- Bevington, A -- Fielding, E J -- Fujita, K -- Geertsema, M -- Miles, E S -- Steiner, J -- Anderson, E -- Bajracharya, S -- Bawden, G W -- Breashears, D F -- Byers, A -- Collins, B -- Dhital, M R -- Donnellan, A -- Evans, T L -- Geai, M L -- Glasscoe, M T -- Green, D -- Gurung, D R -- Heijenk, R -- Hilborn, A -- Hudnut, K -- Huyck, C -- Immerzeel, W W -- Liming, Jiang -- Jibson, R -- Kaab, A -- Khanal, N R -- Kirschbaum, D -- Kraaijenbrink, P D A -- Lamsal, D -- Shiyin, Liu -- Mingyang, Lv -- McKinney, D -- Nahirnick, N K -- Zhuotong, Nan -- Ojha, S -- Olsenholler, J -- Painter, T H -- Pleasants, M -- Pratima, K C -- Yuan, Q I -- Raup, B H -- Regmi, D -- Rounce, D R -- Sakai, A -- Donghui, Shangguan -- Shea, J M -- Shrestha, A B -- Shukla, A -- Stumm, D -- van der Kooij, M -- Voss, K -- Xin, Wang -- Weihs, B -- Wolfe, D -- Lizong, Wu -- Xiaojun, Yao -- Yoder, M R -- Young, N -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):aac8353. doi: 10.1126/science.aac8353. Epub 2015 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Hydrology and Water Resources, University of Arizona, Tucson, AZ, USA. kargel@hwr.arizona.edu dshugar@uw.edu uharitashya1@udayton.edu. ; Department of Hydrology and Water Resources, University of Arizona, Tucson, AZ, USA. ; School of Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA. kargel@hwr.arizona.edu dshugar@uw.edu uharitashya1@udayton.edu. ; Department of Geology, University of Dayton, Dayton, OH, USA. kargel@hwr.arizona.edu dshugar@uw.edu uharitashya1@udayton.edu. ; Ministry of Forests, Lands and Natural Resource Operations, Prince George, BC, Canada. ; Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, USA. ; Graduate School of Environmental Studies, Nagoya University, Nagoya, Japan. ; Scott Polar Research Institute, University of Cambridge, Cambridge, UK. ; Institute of Environmental Engineering, Federal Institute of Technology-ETH, Zurich, Switzerland. ; NASA Marshall Space Flight Center, Huntsville, AL, USA. ; International Centre for Integrated Mountain Development, Kathmandu, Nepal. ; NASA Headquarters, Washington, DC, USA. ; GlacierWorks, Marblehead, MA, USA. ; The Mountain Institute, Elkins, WV, USA. ; U.S. Geological Survey, Menlo Park, CA, USA. ; Central Department of Geology, Tribhuvan University, Kirtipur, Kathmandu, Nepal. ; Department of Geography, University of Victoria, Victoria, BC, Canada. ; CVA Engineering, Suresnes, France. ; Earthquake Science Center, U.S. Geological Survey, Pasadena, CA, USA. ; ImageCat, Long Beach, CA, USA. ; Faculty of Geosciences, Utrecht University, Utrecht, Netherlands. ; State Key Laboratory of Geodesy and Earth's Dynamics, Institute of Geodesy and Geophysics, Chinese Academy of Sciences, Wuhan, Hubei Province, China. ; U.S. Geological Survey, Golden, CO, USA. ; Department of Geosciences, University of Oslo, Blindern, Oslo, Norway. ; Hydrological Sciences Laboratory, NASA Goddard Space Flight Center, Greenbelt, MD, USA. ; Cold and Arid Regions of Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, China. ; School of Earth Sciences and Engineering, Nanjing University, Nanjing, China. ; Department of Civil, Architectural and Environmental Engineering, University of Texas at Austin, Austin, TX, USA. ; School of Geography Science, Nanjing Normal University, Nanjing, China. ; Department of Geography, Texas A&M University, College Station, TX, USA. ; Department of Geology, University of Dayton, Dayton, OH, USA. ; Arizona Remote Sensing Center, School of Natural Resources and the Environment, University of Arizona, Tucson, AZ, USA. ; National Snow and Ice Data Center, University of Colorado, Boulder, CO, USA. ; Himalayan Research Center, Kathmandu, Nepal. ; Environmental and Water Resources Engineering, University of Texas at Austin, Austin, TX, USA. ; Wadia Institute of Himalayan Geology, Dehradun, India. ; MacDonald Dettwiler and Associates-GSI, Ottawa, Ontario, Canada. ; Department of Geography, University of California, Santa Barbara, Santa Barbara, CA, USA. ; College of Architecture and Urban Planning, Hunan University of Science and Technology, Xiangtan, China. ; Geography Department, Kansas State University, Manhattan, KS, USA. ; Global Land Ice Measurements from Space (GLIMS) Steward, Alaska Region, Anchorage, AK, USA. ; College of Geographical Science and Environment, Northwest Normal University, China. ; Department of Physics, University of California, Davis, Davis, CA, USA. ; Antarctic Climate and Ecosystems Cooperative Research Centre, University of Tasmania, Hobart, TAS, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26676355" target="_blank"〉PubMed〈/a〉
    Keywords: Disasters/*prevention & control ; Earthquakes/*mortality ; Environmental Monitoring/*methods ; Floods ; Humans ; Lakes ; Landslides/*mortality ; Nepal ; Safety Management/*methods ; Satellite Imagery
    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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  • 6
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    Unknown
    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Medizin - Bibliothek - Information; VOL: 9; DOC21 /20090929/
    Publication Date: 2009-09-30
    Description: The Library of the Medical Faculty is an autonomous part of the library system specific to the medical department of the Ruhr-University Bochum. Its collection concentrates on theoretical medicine, while the clinical field is covered by the central university library and several libraries located at the different hospitals that jointly form the university clinic (Bochumer Modell). All libraries closely cooperate to provide a wide range of electronic journals and books. Recently the Library of the Medical Faculty also built up an extensive collection of textbooks.
    Description: Die Bibliothek der Medizinischen Fakultät der Ruhr-Universität ist für die Literaturversorgung der ungefähr 200 Wissenschaftlichen Mitarbeiter und Professoren des Hauses zuständig und stellt Zeitschriften für den vorklinischen Bereich zur Verfügung. Der klinische Bereich wird durch die Universitätsbibliothek der Ruhr-Universität und die Klinikbibliotheken in den Lehrkrankenhäusern abgedeckt. Aktuelle Lehrbücher gehören seit 1995 zum Bestand. Seitdem nutzen Studenten die Bibliothek mit den 56 Arbeitsplätzen gern als ruhigen Studienort.
    Keywords: Ruhr-Universität Bochum ; Library of the Medical Faculty ; Ruhr-Universität Bochum ; Bibliothek der Medizinischen Fakultät ; Bochumer Modell ; ddc: 610
    Language: German
    Type: article
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 28 (1968), S. 376-377 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 58 (1982), S. 9-16 
    ISSN: 1432-0533
    Keywords: Brain tumour ; Nuclear morphometry ; Nuclear densitometry ; Automated image analysis ; Grading
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tumours of the neuroglia, 172 in all (50 glioblastomas, 65 fibrillar and gemistocytic astrocytomas, 26 pilocytic astrocytomas and 31 oligodendrogliomas), were studied by automated microscopic picture analysis. Thirteen morphometric and densitometric parameters of the tumour cell nuclei as well as two mitotic parameters were determined on 4 μm thick Feulgen slide preparations. The correlation of the results with subjectively established grade of malignancy was examined. A close correlation was found between almost all morphometric-densitometric nuclear parameters and the morphologically established behaviour of the tumours under study. Based on these results both the method of automated microscopic picture analysis and the selected parameters have been assessed as efficient for the evaluation of the behaviour of glial tumours. The results are readily reproducible and can be obtained without requiring much time. An other advantage of this method is the use of histological preparations, which allows a comparison of the overall structure of the tumour as well as a pinpointed examination of those regions that are representative of the tumour. Subjective grading of glial tumours has been greatly objective by automation.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0533
    Keywords: Gliomas ; Automated image analysis ; Karyometry ; Automated classification ; Discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A karyometric analysis of 346 Feulgenstained biopsy preparations (4 μm) of gliomas (glioblastomas; fibrillar, protoplasmic and gemistocytic astrocytomas; pilocytic astrocytomas; oligodendrogliomas) using the automated microscope picture analysis (AMPA) was carried out in continuation of a previous paper (Martin and Voss 1982). Fifteen morphometrical, densitometrical and mitotic preparation features were evaluated: Parameters of the spatial density of nuclei — KRNZ, AREA; Parameters of nuclear size — KOFL, KFRL, P 250; Parameters of nuclear shape — FOFK, FOFR, P 150; Parameters of chromatin density — EXTU, EXTS, EXSR, EXTM, EXMR; Mitotic parameters — MITZ, VHMK. On the basis of these and some additional data (TIM 1, AGE, SEX, LOC) an automatic classifier has been elaborated which differentiates in an optimum manner the four tumour classes under study from one another. This classifier was elaborated on 172 slide preparations that had, on four occasions, been consistently classified and graded by three pathologists (“classified” sample). Subsequently, the classifier was used for the automatic classification of the whole material (346 slide preparations). From among the classified sample (n=172) the computer classified 159 tumours (92.4%) correctly and rejected 13 (7.6%); no tumour was classified wrongly. From among the whole material 295 tumours (85.3%) were classified correctly, 26 (7.5%) were rejected and 25 (7.2%) were classified wrongly. The following were the most important parameters for the discrimination and hence the automatic classification of the tumour classes: FOFK (form factor), FOFR (relative variation of form factors), KRNZ (number of nuclei), KFRL (relative variation of nuclear areas) and EXTS (mean extinction sum of tumour cell nuclei). Consequently, karyometrical data permit a reliable classification of glioblastomas and other gliomas. With the help of AMPA the necessary karyometrical data can be obtained in an easily objectifyable and reproducible manner requiring just about 10 min for each slide preparation.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0533
    Keywords: Glioma ; Nuclear morphometry ; Nuclear densitometry ; Automated image analysis ; Automated grading
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A system of automated microscopic picture analysis was used in an examination of 272 gliomas (70 glioblastomas, 91 astrocytomas, 56 pilocytic astrocytomas or spongioblastomas, and 55 oligodendrogliomas). The specimens were prepared as Feulgen sections, 4μm in thickness. Thirteen morphometricdensitometric parameters of tumor cell nuclei were tested together with two mitotic parameters. Objective and reproducible data on numerical nuclear density (KRNZ, AREA), nuclear size (KOFL, KFRL, P250), nuclear shape (FOFK, FOFR, P150), optical density (EXTU, EXTS, EXSR, EXTM, EXMR), and mitotic activity (MITZ, VHMK) of the gliomas were obtained from the morphometric-densitometric parameters. All gliomas but glioblastomas were subdivided by four tumor grades. The morphometric-densitometric and mitotic data recorded were statistically checked, depending on tumor grade (Student'st-test, Wilcoxon's test, α=0.05). Numerical nuclear density, deformation of nuclei, and mitotic activity were found to grow with significance along with increasing tumor grade up to glioblastoma. The relative standard deviation (SD) of nuclear size (KFRL), relative SD of shape factors (FOFR), and relative SD of extinction sums (EXSR) are high-accuracy parameters for the pathologist to describe variability of sizes, polymorphism, and polychromasia of nuclei. These parameters show a significant increase of values in parallel with rising tumor grades, with maximum values being recordable from cases of glioblastomas. In cases of astrocytomas, optical values of nuclei decrease along with rising tumor grade. The data thus obtained were used as reference values for objective, reproducibel automatic glioma grading. The classifier method, described in an earlier publication, proved to be more effective than the regression method.
    Type of Medium: Electronic Resource
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