ALBERT

Description: We present the first results of an all-sky search for continuous gravitational waves from unknown spinning neutron stars in binary systems using LIGO and Virgo data. Using a specially developed analysis program, the TwoSpect algorithm, the search was carried out on data from the sixth LIGO science run and the second and third Virgo science runs. The search covers a range of frequencies from 20 Hz to 520 Hz, a range of orbital periods from 2 to 2,254 h and a frequency- and period-dependent range of frequency modulation depths from 0.277 to 100 mHz. This corresponds to a range of projected semimajor axes of the orbit from 0.6 10(exp 3) ls to 6,500 ls assuming the orbit of the binary is circular. While no plausible candidate gravitational wave events survive the pipeline, upper limits are set on the analyzed data. The most sensitive 95% confidence upper limit obtained on gravitational wave strain is 2.3 10(exp 24) at 217 Hz, assuming the source waves are circularly polarized. Although this search has been optimized for circular binary orbits, the upper limits obtained remain valid for orbital eccentricities as large as 0.9. In addition, upper limits are placed on continuous gravitational wave emission from the low-mass x-ray binary Scorpius X-1 between 20 Hz and 57.25 Hz.

Description: Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201514/" 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/PMC4201514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Northcott, Paul A -- Lee, Catherine -- Zichner, Thomas -- Stutz, Adrian M -- Erkek, Serap -- Kawauchi, Daisuke -- Shih, David J H -- Hovestadt, Volker -- Zapatka, Marc -- Sturm, Dominik -- Jones, David T W -- Kool, Marcel -- Remke, Marc -- Cavalli, Florence M G -- Zuyderduyn, Scott -- Bader, Gary D -- VandenBerg, Scott -- Esparza, Lourdes Adriana -- Ryzhova, Marina -- Wang, Wei -- Wittmann, Andrea -- Stark, Sebastian -- Sieber, Laura -- Seker-Cin, Huriye -- Linke, Linda -- Kratochwil, Fabian -- Jager, Natalie -- Buchhalter, Ivo -- Imbusch, Charles D -- Zipprich, Gideon -- Raeder, Benjamin -- Schmidt, Sabine -- Diessl, Nicolle -- Wolf, Stephan -- Wiemann, Stefan -- Brors, Benedikt -- Lawerenz, Chris -- Eils, Jurgen -- Warnatz, Hans-Jorg -- Risch, Thomas -- Yaspo, Marie-Laure -- Weber, Ursula D -- Bartholomae, Cynthia C -- von Kalle, Christof -- Turanyi, Eszter -- Hauser, Peter -- Sanden, Emma -- Darabi, Anna -- Siesjo, Peter -- Sterba, Jaroslav -- Zitterbart, Karel -- Sumerauer, David -- van Sluis, Peter -- Versteeg, Rogier -- Volckmann, Richard -- Koster, Jan -- Schuhmann, Martin U -- Ebinger, Martin -- Grimes, H Leighton -- Robinson, Giles W -- Gajjar, Amar -- Mynarek, Martin -- von Hoff, Katja -- Rutkowski, Stefan -- Pietsch, Torsten -- Scheurlen, Wolfram -- Felsberg, Jorg -- Reifenberger, Guido -- Kulozik, Andreas E -- von Deimling, Andreas -- Witt, Olaf -- Eils, Roland -- Gilbertson, Richard J -- Korshunov, Andrey -- Taylor, Michael D -- Lichter, Peter -- Korbel, Jan O -- Wechsler-Reya, Robert J -- Pfister, Stefan M -- 5P30CA030199/CA/NCI NIH HHS/ -- P01 CA096832/CA/NCI NIH HHS/ -- P30 CA030199/CA/NCI NIH HHS/ -- P41GM103504/GM/NIGMS NIH HHS/ -- R01 CA159859/CA/NCI NIH HHS/ -- England -- Nature. 2014 Jul 24;511(7510):428-34. doi: 10.1038/nature13379. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2]. ; 1] Biomedical Sciences Graduate Program, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0685, USA [2] Tumor Initiation and Maintenance Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA [3]. ; 1] European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany [2]. ; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany. ; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. ; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada. ; Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Tumor Initiation and Maintenance Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Neuropathology, NN Burdenko Neurosurgical Institute, 4th Tverskaya-Yamskaya 16, Moscow 125047, Russia. ; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; Data Management Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin 14195, Germany. ; Division of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg 69120, Germany. ; 1] Division of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg 69120, Germany [2] Heidelberg Center for Personalised Oncology (DKFZ-HIPO), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; 1st Department of Pathology and Experimental Cancer Research, Semmelweis University SE, II.sz. Gyermekklinika, Budapest 1094, Hungary. ; 2nd Department of Pediatrics, Semmelweis University, SE, II.sz. Gyermekklinika, Budapest 1094, Hungary. ; 1] Glioma Immunotherapy Group, Division of Neurosurgery, Lund University, Paradisgatan 2, Lund 221 00, Sweden [2] Department of Clinical Sciences, Lund University, Paradisgatan 2, Lund 221 00, Sweden. ; Department of Pediatric Oncology, Masaryk University and University Hospital, Brno, Cernopolni 9 Brno 613 00, Czech Republic. ; Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, Prague 150 06, Czech Republic. ; Department of Oncogenomics, AMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105, AZ Netherlands. ; Department of Neurosurgery, Tubingen University Hospital, Hoppe-Seyler Strasse 3, Tubingen 72076, Germany. ; Division of Immunobiology, Program in Cancer Pathology of the Divisions of Experimental Hematology and Pathology, Program in Hematologic Malignancies of the Cancer and Blood Disease Insitute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 452229, USA. ; 1] Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA [2] Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA. ; Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA. ; Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. ; Department of Neuropathology, University of Bonn, Sigmund-Freud-Str. 25, Bonn 53105, Germany. ; Cnopf'sche Kinderklinik, Nurnberg Children's Hospital, St-Johannis-Muhlgasse 19, Nurnberg 90419, Germany. ; Department of Neuropathology, Heinrich-Heine-University Dusseldorf, Moorenstrasse 5, Dusseldorf 40225, Germany. ; Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany. ; Department of Neuropathology, University of Heidelberg, Im Neuenheimer Feld 220, Heidelberg 69120, Germany. ; 1] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] Heidelberg Center for Personalised Oncology (DKFZ-HIPO), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; 1] The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada [2] Division of Neurosurgery, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. ; 1] Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] Heidelberg Center for Personalised Oncology (DKFZ-HIPO), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. ; 1] European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany [2] EMBL, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Saffron Walden CB10 1SD, UK. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043047" target="_blank"〉PubMed〈/a〉

Description: 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〉

Description: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174313/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174313/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mack, S C -- Witt, H -- Piro, R M -- Gu, L -- Zuyderduyn, S -- Stutz, A M -- Wang, X -- Gallo, M -- Garzia, L -- Zayne, K -- Zhang, X -- Ramaswamy, V -- Jager, N -- Jones, D T W -- Sill, M -- Pugh, T J -- Ryzhova, M -- Wani, K M -- Shih, D J H -- Head, R -- Remke, M -- Bailey, S D -- Zichner, T -- Faria, C C -- Barszczyk, M -- Stark, S -- Seker-Cin, H -- Hutter, S -- Johann, P -- Bender, S -- Hovestadt, V -- Tzaridis, T -- Dubuc, A M -- Northcott, P A -- Peacock, J -- Bertrand, K C -- Agnihotri, S -- Cavalli, F M G -- Clarke, I -- Nethery-Brokx, K -- Creasy, C L -- Verma, S K -- Koster, J -- Wu, X -- Yao, Y -- Milde, T -- Sin-Chan, P -- Zuccaro, J -- Lau, L -- Pereira, S -- Castelo-Branco, P -- Hirst, M -- Marra, M A -- Roberts, S S -- Fults, D -- Massimi, L -- Cho, Y J -- Van Meter, T -- Grajkowska, W -- Lach, B -- Kulozik, A E -- von Deimling, A -- Witt, O -- Scherer, S W -- Fan, X -- Muraszko, K M -- Kool, M -- Pomeroy, S L -- Gupta, N -- Phillips, J -- Huang, A -- Tabori, U -- Hawkins, C -- Malkin, D -- Kongkham, P N -- Weiss, W A -- Jabado, N -- Rutka, J T -- Bouffet, E -- Korbel, J O -- Lupien, M -- Aldape, K D -- Bader, G D -- Eils, R -- Lichter, P -- Dirks, P B -- Pfister, S M -- Korshunov, A -- Taylor, M D -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA097257/CA/NCI NIH HHS/ -- R01 CA121941/CA/NCI NIH HHS/ -- R01 CA148621/CA/NCI NIH HHS/ -- R01 CA163737/CA/NCI NIH HHS/ -- R01CA148699/CA/NCI NIH HHS/ -- R01CA159859/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Feb 27;506(7489):445-50. doi: 10.1038/nature13108. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4]. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [3] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [4]. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Molecular Genetics, Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Toronto, Ontario M4N 1X8, Canada. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Genome Biology, European Molecular Biology, Laboratory Meyerhofstr. 1, Heidelberg 69117, Germany. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada. ; Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Neurology, Harvard Medical School, Children's Hospital Boston, MIT, Boston, Massachusetts 02115, USA. ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; 1] Ontario Cancer Institute, Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario M5G 1L7, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 1L7, Canada. ; Cancer Epigenetics Discovery Performance Unit, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania 19426, USA. ; Department of Oncogenomics, Academic Medical Center, Amsterdam 1105, The Netherlands. ; 1] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [3] CCU Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; 1] Centre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, Vancouver, V6T 1Z4 British Columbia, Canada [2] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada. ; Department of Pediatrics and National Capital Consortium, Uniformed Services University, Bethesda, Maryland 20814, USA. ; Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. ; Pediatric Neurosurgery, Catholic University Medical School, Gemelli Hospital, Rome 00168, Italy. ; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Pediatrics, Virginia Commonwealth, Richmond, Virginia 23298-0646, USA. ; Department of Pathology, University of Warsaw, Children's Memorial Health Institute University of Warsaw, Warsaw 04-730, Poland. ; Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton General Hospital, Hamilton, Ontario L8S 4K1, Canada. ; 1] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Department of Neuropathology Ruprecht-Karls-University Heidelberg, Institute of Pathology, Heidelberg 69120, Germany. ; 1] University of Michigan Cell and Developmental Biology, Ann Arbor, Michigan 48109-2200, USA [2] Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Neurosurgery, University of California San Francisco, San Francisco, California 94143-0112, USA. ; Departments of Neurology, Pediatrics, and Neurosurgery, University of California, San Francisco, The Helen Diller Family Cancer Research Building, San Francisco, California 94158, USA. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Department of Neuro-oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Departments of Pediatrics and Human Genetics, McGill University and the McGill University Health Center Research Institute, Montreal, Quebec H3Z 2Z3, Canada. ; Department of Neuro-oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Genome Biology, European Molecular Biology, Laboratory Meyerhofstr. 1, Heidelberg 69117, Germany. ; 1] Ontario Cancer Institute, Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario M5G 1L7, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 1L7, Canada [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada. ; 1] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [3] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. ; 1] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] University of Michigan Cell and Developmental Biology, Ann Arbor, Michigan 48109-2200, USA [3] CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553142" target="_blank"〉PubMed〈/a〉

Description: The Curiosity rover investigated the mineralogy of the Sheepbed mudstone member of the Yellowknife Bay formation in Gale crater. Data from the Chemistry and Mineralogy (CheMin) X-ray diffractometer (XRD) helped identify phyllosilicates in the two drilled samples, John Klein and Cumberland. These patterns showed peaks at low angles, consistent with (001) peaks in 2:1 swelling phyllosilicates [1]. Evolved gas analyses (EGA) by the Sample Analysis at Mars (SAM) instrument of these samples confirmed the presence of phyllosilicates through the release of H2O at high temperatures, consistent with dehydroxylation of octahedral OH in phyllosilicates [2]. CheMin data for the phyllosilicates at John Klein and Cumberland show that they are structurally similar in that their (02l) peaks are near 22.5 deg 2theta, suggesting both samples contain trioctahedral 2:1 phyllosilicates [1]. However, the positions of the (001) peaks differ: the phyllosilicate at John Klein has its (001) peak at 10 Angstroms, whereas the phyllosilicate at Cumberland has an (001) peak at 14 Angstroms. Such differences in (001) dspacings can be ascribed to the type of cation in the interlayer site [3]. For example, large monovalent cations (e.g., K(+)) have low hydration energies and readily lose their H2O of hydration, whereas small divalent cations (e.g., Mg(2+)) have high energies of hydration and retain H2O in the phyllosilicate interlayers [3,4]. The goal of this study is to determine whether differences in the interlayer cation composition can explain the CheMin data from John Klein and Cumberland and to use this knowledge to better understand phyllosilicate formation mechanisms.

Description: The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to identify drug-like molecules that bind to a site on the GDP-bound form of Ral. The compounds RBC6, RBC8 and RBC10 inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and (1)H-(15)N transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. Our results show the utility of structure-based discovery for the development of therapeutics for Ral-dependent cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351747/" 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/PMC4351747/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, Chao -- Liu, Degang -- Li, Liwei -- Wempe, Michael F -- Guin, Sunny -- Khanna, May -- Meier, Jeremy -- Hoffman, Brenton -- Owens, Charles -- Wysoczynski, Christina L -- Nitz, Matthew D -- Knabe, William E -- Ahmed, Mansoor -- Brautigan, David L -- Paschal, Bryce M -- Schwartz, Martin A -- Jones, David N M -- Ross, David -- Meroueh, Samy O -- Theodorescu, Dan -- CA075115/CA/NCI NIH HHS/ -- CA091846/CA/NCI NIH HHS/ -- CA104106/CA/NCI NIH HHS/ -- GM47214/GM/NIGMS NIH HHS/ -- P01 CA104106/CA/NCI NIH HHS/ -- P30 CA044579/CA/NCI NIH HHS/ -- P30 CA046934/CA/NCI NIH HHS/ -- P50 CA091846/CA/NCI NIH HHS/ -- R01 CA075115/CA/NCI NIH HHS/ -- R01 CA143971/CA/NCI NIH HHS/ -- T32 GM007635/GM/NIGMS NIH HHS/ -- UL1 TR001082/TR/NCATS NIH HHS/ -- UL1TR001082/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):443-7. doi: 10.1038/nature13713. Epub 2014 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, University of Colorado, Aurora, Colorado 80045, USA. ; Department of Biochemistry, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Pharmaceutical Sciences, University of Colorado, Aurora, Colorado 80045, USA. ; Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Pharmacology, University of Colorado, Aurora, Colorado 80045, USA. ; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Department of Cardiology, Yale University, New Haven, Connecticut 06511, USA [2] Department of Cell Biology, Yale University, New Haven, Connecticut 06511, USA. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Department of Biochemistry, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [2] Department of Chemistry and Chemical Biology, Indiana University - Purdue University, Indianapolis, Indiana 46202, USA. ; 1] Department of Surgery, University of Colorado, Aurora, Colorado 80045, USA [2] Department of Pharmacology, University of Colorado, Aurora, Colorado 80045, USA [3] University of Colorado Comprehensive Cancer Center, Aurora, Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25219851" target="_blank"〉PubMed〈/a〉

Description: The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105188/" 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/PMC4105188/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Jeremy A -- Ding, Song-Lin -- Sunkin, Susan M -- Smith, Kimberly A -- Ng, Lydia -- Szafer, Aaron -- Ebbert, Amanda -- Riley, Zackery L -- Royall, Joshua J -- Aiona, Kaylynn -- Arnold, James M -- Bennet, Crissa -- Bertagnolli, Darren -- Brouner, Krissy -- Butler, Stephanie -- Caldejon, Shiella -- Carey, Anita -- Cuhaciyan, Christine -- Dalley, Rachel A -- Dee, Nick -- Dolbeare, Tim A -- Facer, Benjamin A C -- Feng, David -- Fliss, Tim P -- Gee, Garrett -- Goldy, Jeff -- Gourley, Lindsey -- Gregor, Benjamin W -- Gu, Guangyu -- Howard, Robert E -- Jochim, Jayson M -- Kuan, Chihchau L -- Lau, Christopher -- Lee, Chang-Kyu -- Lee, Felix -- Lemon, Tracy A -- Lesnar, Phil -- McMurray, Bergen -- Mastan, Naveed -- Mosqueda, Nerick -- Naluai-Cecchini, Theresa -- Ngo, Nhan-Kiet -- Nyhus, Julie -- Oldre, Aaron -- Olson, Eric -- Parente, Jody -- Parker, Patrick D -- Parry, Sheana E -- Stevens, Allison -- Pletikos, Mihovil -- Reding, Melissa -- Roll, Kate -- Sandman, David -- Sarreal, Melaine -- Shapouri, Sheila -- Shapovalova, Nadiya V -- Shen, Elaine H -- Sjoquist, Nathan -- Slaughterbeck, Clifford R -- Smith, Michael -- Sodt, Andy J -- Williams, Derric -- Zollei, Lilla -- Fischl, Bruce -- Gerstein, Mark B -- Geschwind, Daniel H -- Glass, Ian A -- Hawrylycz, Michael J -- Hevner, Robert F -- Huang, Hao -- Jones, Allan R -- Knowles, James A -- Levitt, Pat -- Phillips, John W -- Sestan, Nenad -- Wohnoutka, Paul -- Dang, Chinh -- Bernard, Amy -- Hohmann, John G -- Lein, Ed S -- 5R24HD0008836/HD/NICHD NIH HHS/ -- R00 HD061485/HD/NICHD NIH HHS/ -- R01 MH092535/MH/NIMH NIH HHS/ -- R24 HD000836/HD/NICHD NIH HHS/ -- RC2 MH089921/MH/NIMH NIH HHS/ -- RC2MH089921/MH/NIMH NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):199-206. doi: 10.1038/nature13185. Epub 2014 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Allen Institute for Brain Science, Seattle, Washington 98103, USA [2]. ; Allen Institute for Brain Science, Seattle, Washington 98103, USA. ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, 1959 North East Pacific Street, Box 356320, Seattle, Washington 98195, USA. ; 1] Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Computer Science and AI Lab, MIT, Cambridge, Massachusetts 02139, USA. ; Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA. ; Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. ; 1] Program in Computational Biology and Bioinformatics, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA [2] Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA. ; Program in Neurogenetics, Department of Neurology and Semel Institute David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA. ; 1] Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA [2] Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98105, USA. ; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas 75390, USA. ; Zilkha Neurogenetic Institute, and Department of Psychiatry, University of Southern California, Los Angeles, California 90033, USA. ; 1] Department of Pediatrics, Children's Hospital, Los Angeles, California 90027, USA [2] Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695229" target="_blank"〉PubMed〈/a〉

Description: A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of 〉100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating approximately 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944098/" 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/PMC3944098/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Yukinori -- Wu, Di -- Trynka, Gosia -- Raj, Towfique -- Terao, Chikashi -- Ikari, Katsunori -- Kochi, Yuta -- Ohmura, Koichiro -- Suzuki, Akari -- Yoshida, Shinji -- Graham, Robert R -- Manoharan, Arun -- Ortmann, Ward -- Bhangale, Tushar -- Denny, Joshua C -- Carroll, Robert J -- Eyler, Anne E -- Greenberg, Jeffrey D -- Kremer, Joel M -- Pappas, Dimitrios A -- Jiang, Lei -- Yin, Jian -- Ye, Lingying -- Su, Ding-Feng -- Yang, Jian -- Xie, Gang -- Keystone, Ed -- Westra, Harm-Jan -- Esko, Tonu -- Metspalu, Andres -- Zhou, Xuezhong -- Gupta, Namrata -- Mirel, Daniel -- Stahl, Eli A -- Diogo, Dorothee -- Cui, Jing -- Liao, Katherine -- Guo, Michael H -- Myouzen, Keiko -- Kawaguchi, Takahisa -- Coenen, Marieke J H -- van Riel, Piet L C M -- van de Laar, Mart A F J -- Guchelaar, Henk-Jan -- Huizinga, Tom W J -- Dieude, Philippe -- Mariette, Xavier -- Bridges, S Louis Jr -- Zhernakova, Alexandra -- Toes, Rene E M -- Tak, Paul P -- Miceli-Richard, Corinne -- Bang, So-Young -- Lee, Hye-Soon -- Martin, Javier -- Gonzalez-Gay, Miguel A -- Rodriguez-Rodriguez, Luis -- Rantapaa-Dahlqvist, Solbritt -- Arlestig, Lisbeth -- Choi, Hyon K -- Kamatani, Yoichiro -- Galan, Pilar -- Lathrop, Mark -- RACI consortium -- GARNET consortium -- Eyre, Steve -- Bowes, John -- Barton, Anne -- de Vries, Niek -- Moreland, Larry W -- Criswell, Lindsey A -- Karlson, Elizabeth W -- Taniguchi, Atsuo -- Yamada, Ryo -- Kubo, Michiaki -- Liu, Jun S -- Bae, Sang-Cheol -- Worthington, Jane -- Padyukov, Leonid -- Klareskog, Lars -- Gregersen, Peter K -- Raychaudhuri, Soumya -- Stranger, Barbara E -- De Jager, Philip L -- Franke, Lude -- Visscher, Peter M -- Brown, Matthew A -- Yamanaka, Hisashi -- Mimori, Tsuneyo -- Takahashi, Atsushi -- Xu, Huji -- Behrens, Timothy W -- Siminovitch, Katherine A -- Momohara, Shigeki -- Matsuda, Fumihiko -- Yamamoto, Kazuhiko -- Plenge, Robert M -- 20385/Arthritis Research UK/United Kingdom -- 79321/Canadian Institutes of Health Research/Canada -- K08-KAR055688A/PHS HHS/ -- K24 AR052403/AR/NIAMS NIH HHS/ -- P60 AR047785/AR/NIAMS NIH HHS/ -- R01 AR056768/AR/NIAMS NIH HHS/ -- R01 AR057108/AR/NIAMS NIH HHS/ -- R01 AR059648/AR/NIAMS NIH HHS/ -- R01 AR063759/AR/NIAMS NIH HHS/ -- R01-AR056291/AR/NIAMS NIH HHS/ -- R01-AR056768/AR/NIAMS NIH HHS/ -- R01-AR057108/AR/NIAMS NIH HHS/ -- R01-AR059648/AR/NIAMS NIH HHS/ -- R01-AR065944/AR/NIAMS NIH HHS/ -- R01AR063759-01A1/AR/NIAMS NIH HHS/ -- R21 AR056042/AR/NIAMS NIH HHS/ -- T15 LM007450/LM/NLM NIH HHS/ -- U01 GM092691/GM/NIGMS NIH HHS/ -- U01-GM092691/GM/NIGMS NIH HHS/ -- U19 HL065962/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Feb 20;506(7488):376-81. doi: 10.1038/nature12873. Epub 2013 Dec 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. ; 1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Department of Statistics, Harvard University, Cambridge, Massachusetts 02138, USA. [5] Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria 3800, Australia. ; 1] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [3] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; 1] Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. [2] Department of Rheumatology and Clinical immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan. ; Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan. ; Department of Rheumatology and Clinical immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. ; Immunology Biomarkers Group, Genentech, South San Francisco, California 94080, USA. ; 1] Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. [2] Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; New York University Hospital for Joint Diseases, New York, New York 10003, USA. ; Department of Medicine, Albany Medical Center and The Center for Rheumatology, Albany, New York 12206, USA. ; Division of Rheumatology, Department of Medicine, New York, Presbyterian Hospital, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. ; Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. ; Department of Pharmacology, Second Military Medical University, Shanghai 200433, China. ; 1] University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4072, Australia. [2] Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia. ; 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Toronto General Research Institute, Toronto, Ontario M5G 2M9, Canada. [3] Department of Medicine, University of Toronto, Toronto, Ontario M5S 2J7, Canada. ; Department of Medicine, Mount Sinai Hospital and University of Toronto, Toronto M5S 2J7, Canada. ; Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands. ; 1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [2] Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia. [3] Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA. ; Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia. ; School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044, China. ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. ; The Department of Psychiatry at Mount Sinai School of Medicine, New York, New York 10029, USA. ; 1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [3] Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA. ; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. ; Department of Human Genetics, Radboud University Medical Centre, Nijmegen 6500 HB, the Netherlands. ; Department of Rheumatology, Radboud University Medical Centre, Nijmegen 6500 HB, the Netherlands. ; Department of Rheumatology and Clinical Immunology, Arthritis Center Twente, University Twente & Medisch Spectrum Twente, Enschede 7500 AE, the Netherlands. ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands. ; Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands. ; 1] Service de Rhumatologie et INSERM U699 Hopital Bichat Claude Bernard, Assistance Publique des Hopitaux de Paris, Paris 75018, France. [2] Universite Paris 7-Diderot, Paris 75013, France. ; Institut National de la Sante et de la Recherche Medicale (INSERM) U1012, Universite Paris-Sud, Rhumatologie, Hopitaux Universitaires Paris-Sud, Assistance Publique-Hopitaux de Paris (AP-HP), Le Kremlin Bicetre 94275, France. ; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. ; 1] Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands. [2] Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands. ; 1] AMC/University of Amsterdam, Amsterdam 1105 AZ, the Netherlands. [2] GlaxoSmithKline, Stevenage SG1 2NY, UK. [3] University of Cambridge, Cambridge CB2 1TN, UK. ; Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea. ; Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada 18100, Spain. ; Department of Rheumatology, Hospital Marques de Valdecilla, IFIMAV, Santander 39008, Spain. ; Hospital Clinico San Carlos, Madrid 28040, Spain. ; 1] Department of Public Health and Clinical Medicine, Umea University, Umea SE-901 87, Sweden. [2] Department of Rheumatology, Umea University, Umea SE-901 87, Sweden. ; 1] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02115, Massachusetts, USA. [2] Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [3] Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts 02118, USA. ; Centre d'Etude du Polymorphisme Humain (CEPH), Paris 75010, France. ; Universite Paris 13 Sorbonne Paris Cite, UREN (Nutritional Epidemiology Research Unit), Inserm (U557), Inra (U1125), Cnam, Bobigny 93017, France. ; McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 0G1 Canada. ; 1] Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK. [2] National Institute for Health Research, Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK. ; Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK. ; Department of Clinical Immunology and Rheumatology & Department of Genome Analysis, Academic Medical Center/University of Amsterdam, Amsterdam 1105 AZ, the Netherlands. ; Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. ; Rosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, California 94117, USA. ; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Unit of Statistical Genetics, Center for Genomic Medicine Graduate School of Medicine Kyoto University, Kyoto 606-8507, Japan. ; Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan. ; Department of Statistics, Harvard University, Cambridge, Massachusetts 02138, USA. ; Rheumatology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm SE-171 76, Sweden. ; The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA. ; 1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] NIHR Manchester Musculoskeletal Biomedical, Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK. ; 1] Section of Genetic Medicine, University of Chicago, Chicago, Illinois 60637, USA. [2] Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA. ; University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4072, Australia. ; Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan. ; 1] Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. [2] Core Research for Evolutional Science and Technology (CREST) program, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan. [3] Institut National de la Sante et de la Recherche Medicale (INSERM) Unite U852, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. ; 1] Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan. [2] Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390342" target="_blank"〉PubMed〈/a〉

Description: Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050669/" 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/PMC4050669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Matthew -- Mohankumar, Kumarasamypet M -- Punchihewa, Chandanamali -- Weinlich, Ricardo -- Dalton, James D -- Li, Yongjin -- Lee, Ryan -- Tatevossian, Ruth G -- Phoenix, Timothy N -- Thiruvenkatam, Radhika -- White, Elsie -- Tang, Bo -- Orisme, Wilda -- Gupta, Kirti -- Rusch, Michael -- Chen, Xiang -- Li, Yuxin -- Nagahawhatte, Panduka -- Hedlund, Erin -- Finkelstein, David -- Wu, Gang -- Shurtleff, Sheila -- Easton, John -- Boggs, Kristy -- Yergeau, Donald -- Vadodaria, Bhavin -- Mulder, Heather L -- Becksfort, Jared -- Gupta, Pankaj -- Huether, Robert -- Ma, Jing -- Song, Guangchun -- Gajjar, Amar -- Merchant, Thomas -- Boop, Frederick -- Smith, Amy A -- Ding, Li -- Lu, Charles -- Ochoa, Kerri -- Zhao, David -- Fulton, Robert S -- Fulton, Lucinda L -- Mardis, Elaine R -- Wilson, Richard K -- Downing, James R -- Green, Douglas R -- Zhang, Jinghui -- Ellison, David W -- Gilbertson, Richard J -- P01 CA096832/CA/NCI NIH HHS/ -- P01CA96832/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01CA129541/CA/NCI NIH HHS/ -- England -- Nature. 2014 Feb 27;506(7489):451-5. doi: 10.1038/nature13109. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [3]. ; 1] Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2]. ; 1] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2]. ; 1] Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2]. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2] Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA. ; Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; MD Anderson Cancer Center Orlando, Pediatric Hematology/Oncology, 92 West Miller MP 318, Orlando, Florida 32806, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA [3] Department of Genetics, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA [3] Department of Genetics, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA [4] Siteman Cancer Center, Washington University School of Medicine in St Louis, St Louis, Missouri 63108, USA. ; Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA [2] Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553141" target="_blank"〉PubMed〈/a〉

Description: Remote sensing observations meet some limitations when used to study the bulk atmospheric composition of the giant planets of our solar system. A remarkable example of the superiority of in situ probe measurements is illustratedby the exploration of Jupiter, where key measurements such as the determination of the noble gases abundances and the precise measurement of the helium mixing ratio have only been made available through in situ measurements by the Galileo probe. This paper describes the main scienti-c goals to be addressed by the future in situ exploration of Saturn placing the Galileo probe exploration of Jupiter in a broader context and before the future probe exploration of the more remote ice giants. In situ exploration of Saturn's atmosphere addresses two broad themes that are discussedthroughout this paper : rst, the formation history of our solar system and second, the processes at play in planetary atmospheres. In this context, we detail the reasons why measurements of Saturn's bulk elemental and isotopiccomposition would place important constraints on the volatile reservoirs in the protosolar nebula. We also show that the in situ measurement of CO (or any other disequilibrium species that is depleted by reaction with water) in Saturn's upper troposphere may help constraining its bulk OH ratio. We compare predictions of Jupiter and Saturn's bulk compositions from different formation scenarios, and highlight the key measurements required to distinguish competing theories to shed light on giant planet formation as a common process in planetary systems with potential applications to mostextrasolar systems. In situ measurements of Saturn's stratospheric and tropospheric dynamics, chemistry and cloud-forming processes will provide access to phenomena unreachable to remote sensing studies. Dierent mission architectures are envisaged, which would benet from strong international collaborations, all based on an entry probe that would descend through Saturn's stratosphere and troposphere under parachute down to a minimum of 10 bars of atmospheric pressure. We rally discuss the science payload required on a Saturn probe to match the measurement requirements.