ALBERT

Description: The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores (comb jellies) have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes, and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well recognized in ctenophores, many bilaterian neuron-specific genes and genes of 'classical' neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337882/" 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/PMC4337882/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moroz, Leonid L -- Kocot, Kevin M -- Citarella, Mathew R -- Dosung, Sohn -- Norekian, Tigran P -- Povolotskaya, Inna S -- Grigorenko, Anastasia P -- Dailey, Christopher -- Berezikov, Eugene -- Buckley, Katherine M -- Ptitsyn, Andrey -- Reshetov, Denis -- Mukherjee, Krishanu -- Moroz, Tatiana P -- Bobkova, Yelena -- Yu, Fahong -- Kapitonov, Vladimir V -- Jurka, Jerzy -- Bobkov, Yuri V -- Swore, Joshua J -- Girardo, David O -- Fodor, Alexander -- Gusev, Fedor -- Sanford, Rachel -- Bruders, Rebecca -- Kittler, Ellen -- Mills, Claudia E -- Rast, Jonathan P -- Derelle, Romain -- Solovyev, Victor V -- Kondrashov, Fyodor A -- Swalla, Billie J -- Sweedler, Jonathan V -- Rogaev, Evgeny I -- Halanych, Kenneth M -- Kohn, Andrea B -- 1R01GM097502/GM/NIGMS NIH HHS/ -- 1S10RR027052/RR/NCRR NIH HHS/ -- 55007424/Howard Hughes Medical Institute/ -- 5R21DA030118/DA/NIDA NIH HHS/ -- P30 DA018310/DA/NIDA NIH HHS/ -- R01 AG029360/AG/NIA NIH HHS/ -- R01 GM097502/GM/NIGMS NIH HHS/ -- R01 MH097062/MH/NIMH NIH HHS/ -- R01MH097062/MH/NIMH NIH HHS/ -- R21 DA030118/DA/NIDA NIH HHS/ -- R21 RR025699/RR/NCRR NIH HHS/ -- R21RR025699/RR/NCRR NIH HHS/ -- S10 RR027052/RR/NCRR NIH HHS/ -- England -- Nature. 2014 Jun 5;510(7503):109-14. doi: 10.1038/nature13400. Epub 2014 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Whitney Laboratory for Marine Bioscience, University of Florida, 9505 Ocean Shore Blvd, St Augustine, Florida 32080, USA [2] Department of Neuroscience & McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA [3] Friday Harbor Laboratories, University of Washington, Friday Harbor, Washington 98250, USA. ; Department of Biological Sciences, Auburn University, 101 Rouse Life Sciences, Auburn, Alabama 36849, USA. ; The Whitney Laboratory for Marine Bioscience, University of Florida, 9505 Ocean Shore Blvd, St Augustine, Florida 32080, USA. ; 1] The Whitney Laboratory for Marine Bioscience, University of Florida, 9505 Ocean Shore Blvd, St Augustine, Florida 32080, USA [2] Friday Harbor Laboratories, University of Washington, Friday Harbor, Washington 98250, USA. ; 1] Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain. ; 1] Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 303 Belmont Street, Worcester, Massachusetts 01604, USA [2] Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), Gubkina 3, Moscow 119991, Russia. ; Department of Chemistry and the Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, USA. ; European Research Institute for the Biology of Ageing, University of Groningen Medical Center, Antonius Deusinglaan 1, Building 3226, Room 03.34, 9713 AV Groningen, The Netherlands. ; Department of Medical Biophysics and Department of Immunology, University of Toronto, Sunnybrook Research Institute 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. ; Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), Gubkina 3, Moscow 119991, Russia. ; Department of Neuroscience & McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA. ; Genetic Information Research Institute, 1925 Landings Dr., Mountain View, California 94043, USA. ; Program in Molecular Medicine, University of Massachusetts Medical School, 222 Maple Avenue, Shrewsbury, Massachusetts 01545, USA. ; Friday Harbor Laboratories, University of Washington, Friday Harbor, Washington 98250, USA. ; Department of Computer Science, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK. ; 1] Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain [3] Institucio Catalana de Recerca i Estudis Avancats (ICREA), Pg. Lluis Companys 23, 08010 Barcelona, Spain. ; 1] Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 303 Belmont Street, Worcester, Massachusetts 01604, USA [2] Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), Gubkina 3, Moscow 119991, Russia [3] Center for Brain Neurobiology and Neurogenetics and Institute of Cytology and Genetics, RAS, Lavrentyev Avenue, 10, Novosibirsk 630090, Russia [4] Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskiye Gory, 119991 Moscow, Russia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847885" target="_blank"〉PubMed〈/a〉

Description: An optimal search theory, the so-called Levy-flight foraging hypothesis, predicts that predators should adopt search strategies known as Levy flights where prey is sparse and distributed unpredictably, but that Brownian movement is sufficiently efficient for locating abundant prey. Empirical studies have generated controversy because the accuracy of statistical methods that have been used to identify Levy behaviour has recently been questioned. Consequently, whether foragers exhibit Levy flights in the wild remains unclear. Crucially, moreover, it has not been tested whether observed movement patterns across natural landscapes having different expected resource distributions conform to the theory's central predictions. Here we use maximum-likelihood methods to test for Levy patterns in relation to environmental gradients in the largest animal movement data set assembled for this purpose. Strong support was found for Levy search patterns across 14 species of open-ocean predatory fish (sharks, tuna, billfish and ocean sunfish), with some individuals switching between Levy and Brownian movement as they traversed different habitat types. We tested the spatial occurrence of these two principal patterns and found Levy behaviour to be associated with less productive waters (sparser prey) and Brownian movements to be associated with productive shelf or convergence-front habitats (abundant prey). These results are consistent with the Levy-flight foraging hypothesis, supporting the contention that organism search strategies naturally evolved in such a way that they exploit optimal Levy patterns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Humphries, Nicolas E -- Queiroz, Nuno -- Dyer, Jennifer R M -- Pade, Nicolas G -- Musyl, Michael K -- Schaefer, Kurt M -- Fuller, Daniel W -- Brunnschweiler, Juerg M -- Doyle, Thomas K -- Houghton, Jonathan D R -- Hays, Graeme C -- Jones, Catherine S -- Noble, Leslie R -- Wearmouth, Victoria J -- Southall, Emily J -- Sims, David W -- England -- Nature. 2010 Jun 24;465(7301):1066-9. doi: 10.1038/nature09116. Epub 2010 Jun 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marine Biological Association of the United Kingdom, The Laboratory, Citadel Hill, Plymouth PL1 2PB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20531470" target="_blank"〉PubMed〈/a〉

Description: The bacteria that colonize humans and our built environments have the potential to influence our health. Microbial communities associated with seven families and their homes over 6 weeks were assessed, including three families that moved their home. Microbial communities differed substantially among homes, and the home microbiome was largely sourced from humans. The microbiota in each home were identifiable by family. Network analysis identified humans as the primary bacterial vector, and a Bayesian method significantly matched individuals to their dwellings. Draft genomes of potential human pathogens observed on a kitchen counter could be matched to the hands of occupants. After a house move, the microbial community in the new house rapidly converged on the microbial community of the occupants' former house, suggesting rapid colonization by the family's microbiota.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337996/" 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/PMC4337996/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lax, Simon -- Smith, Daniel P -- Hampton-Marcell, Jarrad -- Owens, Sarah M -- Handley, Kim M -- Scott, Nicole M -- Gibbons, Sean M -- Larsen, Peter -- Shogan, Benjamin D -- Weiss, Sophie -- Metcalf, Jessica L -- Ursell, Luke K -- Vazquez-Baeza, Yoshiki -- Van Treuren, Will -- Hasan, Nur A -- Gibson, Molly K -- Colwell, Rita -- Dantas, Gautam -- Knight, Rob -- Gilbert, Jack A -- DP2 DK098089/DK/NIDDK NIH HHS/ -- DP2-DK-098089/DK/NIDDK NIH HHS/ -- P01 DK078669/DK/NIDDK NIH HHS/ -- R01 HG004872/HG/NHGRI NIH HHS/ -- T32 GM008759/GM/NIGMS NIH HHS/ -- U01 HG004866/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1048-52. doi: 10.1126/science.1254529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, University of Chicago, 1101 E 57th Street, Chicago, IL 60637, USA. Institute for Genomic and Systems Biology, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. ; Department of Ecology and Evolution, University of Chicago, 1101 E 57th Street, Chicago, IL 60637, USA. Institute for Genomic and Systems Biology, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. ; Institute for Genomic and Systems Biology, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Computation Institute, University of Chicago, Chicago, IL 60637, USA. ; Institute for Genomic and Systems Biology, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637, USA. ; Department of Bioscience, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA. ; Department of Surgery, University of Chicago Medicine, 5841 South Maryland Avenue, Chicago, IL 60637, USA. ; Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80304, USA. Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO 80304, USA. ; Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80304, USA. ; Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80304, USA. Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80304, USA. ; Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80304, USA. Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80304, USA. Department of Computer Science, University of Colorado at Boulder, Boulder, CO 80304, USA. ; CosmosID, 387 Technology Drive, Suite 3119, College Park, MD 20742, USA. Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, University of Maryland College Park, College Park, MD 20742, USA. ; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA. ; Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80304, USA. Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80304, USA. Howard Hughes Medical Institute, Boulder, CO 80309, USA. ; Department of Ecology and Evolution, University of Chicago, 1101 E 57th Street, Chicago, IL 60637, USA. Institute for Genomic and Systems Biology, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA. Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637, USA. gilbertjack@anl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170151" target="_blank"〉PubMed〈/a〉

Description: Climate change-induced increases in summer water temperature have been associated with elevated mortality of adult sockeye salmon (Oncorhynchus nerka) during river migration. We show that cardiorespiratory physiology varies at the population level among Fraser River sockeye salmon and relates to historical environmental conditions encountered while migrating. Fish from populations with more challenging migratory environments have greater aerobic scope, larger hearts, and better coronary supply. Furthermore, thermal optima for aerobic, cardiac, and heart rate scopes are consistent with the historic river temperature ranges for each population. This study suggests that physiological adaptation occurs at a very local scale, with population-specific thermal limits being set by physiological limitations in aerobic performance, possibly due to cardiac collapse at high temperatures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eliason, Erika J -- Clark, Timothy D -- Hague, Merran J -- Hanson, Linda M -- Gallagher, Zoe S -- Jeffries, Ken M -- Gale, Marika K -- Patterson, David A -- Hinch, Scott G -- Farrell, Anthony P -- New York, N.Y. -- Science. 2011 Apr 1;332(6025):109-12. doi: 10.1126/science.1199158.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, BC, Canada, V6T 1Z4. eliason@zoology.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21454790" target="_blank"〉PubMed〈/a〉

Description: Evolutionary relationships among the eight major lineages of Mollusca have remained unresolved despite their diversity and importance. Previous investigations of molluscan phylogeny, based primarily on nuclear ribosomal gene sequences or morphological data, have been unsuccessful at elucidating these relationships. Recently, phylogenomic studies using dozens to hundreds of genes have greatly improved our understanding of deep animal relationships. However, limited genomic resources spanning molluscan diversity has prevented use of a phylogenomic approach. Here we use transcriptome and genome data from all major lineages (except Monoplacophora) and recover a well-supported topology for Mollusca. Our results strongly support the Aculifera hypothesis placing Polyplacophora (chitons) in a clade with a monophyletic Aplacophora (worm-like molluscs). Additionally, within Conchifera, a sister-taxon relationship between Gastropoda and Bivalvia is supported. This grouping has received little consideration and contains most (〉95%) molluscan species. Thus we propose the node-based name Pleistomollusca. In light of these results, we examined the evolution of morphological characters and found support for advanced cephalization and shells as possibly having multiple origins within Mollusca.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024475/" 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/PMC4024475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kocot, Kevin M -- Cannon, Johanna T -- Todt, Christiane -- Citarella, Mathew R -- Kohn, Andrea B -- Meyer, Achim -- Santos, Scott R -- Schander, Christoffer -- Moroz, Leonid L -- Lieb, Bernhard -- Halanych, Kenneth M -- 1R01GM097502/GM/NIGMS NIH HHS/ -- 1R01NS06076/NS/NINDS NIH HHS/ -- R01 GM097502/GM/NIGMS NIH HHS/ -- R01 NS039103/NS/NINDS NIH HHS/ -- R21 DA030118/DA/NIDA NIH HHS/ -- R21 RR025699/RR/NCRR NIH HHS/ -- R21DA030118/DA/NIDA NIH HHS/ -- England -- Nature. 2011 Sep 4;477(7365):452-6. doi: 10.1038/nature10382.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Auburn University, 101 Rouse Life Sciences, Auburn, Alabama 36849, USA. kmkocot@auburn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21892190" 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: Tumours with mutant BRAF are dependent on the RAF-MEK-ERK signalling pathway for their growth. We found that ATP-competitive RAF inhibitors inhibit ERK signalling in cells with mutant BRAF, but unexpectedly enhance signalling in cells with wild-type BRAF. Here we demonstrate the mechanistic basis for these findings. We used chemical genetic methods to show that drug-mediated transactivation of RAF dimers is responsible for paradoxical activation of the enzyme by inhibitors. Induction of ERK signalling requires direct binding of the drug to the ATP-binding site of one kinase of the dimer and is dependent on RAS activity. Drug binding to one member of RAF homodimers (CRAF-CRAF) or heterodimers (CRAF-BRAF) inhibits one protomer, but results in transactivation of the drug-free protomer. In BRAF(V600E) tumours, RAS is not activated, thus transactivation is minimal and ERK signalling is inhibited in cells exposed to RAF inhibitors. These results indicate that RAF inhibitors will be effective in tumours in which BRAF is mutated. Furthermore, because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation. These predictions have been borne out in a recent clinical trial of the RAF inhibitor PLX4032 (refs 4, 5). The model indicates that promotion of RAF dimerization by elevation of wild-type RAF expression or RAS activity could lead to drug resistance in mutant BRAF tumours. In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178447/" 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/PMC3178447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poulikakos, Poulikos I -- Zhang, Chao -- Bollag, Gideon -- Shokat, Kevan M -- Rosen, Neal -- 1P01CA129243-02/CA/NCI NIH HHS/ -- 2R01EB001987/EB/NIBIB NIH HHS/ -- P01 CA129243-010002/CA/NCI NIH HHS/ -- R01 EB001987/EB/NIBIB NIH HHS/ -- U01 CA091178/CA/NCI NIH HHS/ -- U01 CA091178-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):427-30. doi: 10.1038/nature08902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20179705" target="_blank"〉PubMed〈/a〉

Description: The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night. During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and although rhythmic control of insulin release is recognized to be dysregulated in humans with diabetes, it is not known how the circadian clock may affect this process. Here we show that pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism and insulin signalling is delayed in circadian mutant mice, and both Clock and Bmal1 (also called Arntl) mutants show impaired glucose tolerance, reduced insulin secretion and defects in size and proliferation of pancreatic islets that worsen with age. Clock disruption leads to transcriptome-wide alterations in the expression of islet genes involved in growth, survival and synaptic vesicle assembly. Notably, conditional ablation of the pancreatic clock causes diabetes mellitus due to defective beta-cell function at the very latest stage of stimulus-secretion coupling. These results demonstrate a role for the beta-cell clock in coordinating insulin secretion with the sleep-wake cycle, and reveal that ablation of the pancreatic clock can trigger the onset of diabetes mellitus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920067/" 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/PMC2920067/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marcheva, Biliana -- Ramsey, Kathryn Moynihan -- Buhr, Ethan D -- Kobayashi, Yumiko -- Su, Hong -- Ko, Caroline H -- Ivanova, Ganka -- Omura, Chiaki -- Mo, Shelley -- Vitaterna, Martha H -- Lopez, James P -- Philipson, Louis H -- Bradfield, Christopher A -- Crosby, Seth D -- JeBailey, Lellean -- Wang, Xiaozhong -- Takahashi, Joseph S -- Bass, Joseph -- P01 AG011412/AG/NIA NIH HHS/ -- P01 AG011412-080011/AG/NIA NIH HHS/ -- R01 HL097817/HL/NHLBI NIH HHS/ -- R01 HL097817-01/HL/NHLBI NIH HHS/ -- R37 ES005703/ES/NIEHS NIH HHS/ -- R37-ES-005703/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 29;466(7306):627-31. doi: 10.1038/nature09253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20562852" target="_blank"〉PubMed〈/a〉

Description: The accumulation of species-specific enemies around adults is hypothesized to maintain plant diversity by limiting the recruitment of conspecific seedlings relative to heterospecific seedlings. Although previous studies in forested ecosystems have documented patterns consistent with the process of negative feedback, these studies are unable to address which classes of enemies (for example, pathogens, invertebrates, mammals) exhibit species-specific effects strong enough to generate negative feedback, and whether negative feedback at the level of the individual tree is sufficient to influence community-wide forest composition. Here we use fully reciprocal shade-house and field experiments to test whether the performance of conspecific tree seedlings (relative to heterospecific seedlings) is reduced when grown in the presence of enemies associated with adult trees. Both experiments provide strong evidence for negative plant-soil feedback mediated by soil biota. In contrast, above-ground enemies (mammals, foliar herbivores and foliar pathogens) contributed little to negative feedback observed in the field. In both experiments, we found that tree species that showed stronger negative feedback were less common as adults in the forest community, indicating that susceptibility to soil biota may determine species relative abundance in these tropical forests. Finally, our simulation models confirm that the strength of local negative feedback that we measured is sufficient to produce the observed community-wide patterns in tree-species relative abundance. Our findings indicate that plant-soil feedback is an important mechanism that can maintain species diversity and explain patterns of tree-species relative abundance in tropical forests.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mangan, Scott A -- Schnitzer, Stefan A -- Herre, Edward A -- Mack, Keenan M L -- Valencia, Mariana C -- Sanchez, Evelyn I -- Bever, James D -- R01 GM092660/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):752-5. doi: 10.1038/nature09273.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Wisconsin-Milwaukee, Wisconsin 53201, USA. smangan37@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20581819" target="_blank"〉PubMed〈/a〉

Description: Ever since the conversion of the 11-cis retinal chromophore to its all-trans form in rhodopsin was identified as the primary photochemical event in vision, experimentalists and theoreticians have tried to unravel the molecular details of this process. The high quantum yield of 0.65 (ref. 2), the production of the primary ground-state rhodopsin photoproduct within a mere 200 fs (refs 3-7), and the storage of considerable energy in the first stable bathorhodopsin intermediate all suggest an unusually fast and efficient photoactivated one-way reaction. Rhodopsin's unique reactivity is generally attributed to a conical intersection between the potential energy surfaces of the ground and excited electronic states enabling the efficient and ultrafast conversion of photon energy into chemical energy. But obtaining direct experimental evidence for the involvement of a conical intersection is challenging: the energy gap between the electronic states of the reacting molecule changes significantly over an ultrashort timescale, which calls for observational methods that combine high temporal resolution with a broad spectral observation window. Here we show that ultrafast optical spectroscopy with sub-20-fs time resolution and spectral coverage from the visible to the near-infrared allows us to follow the dynamics leading to the conical intersection in rhodopsin isomerization. We track coherent wave-packet motion from the photoexcited Franck-Condon region to the photoproduct by monitoring the loss of reactant emission and the subsequent appearance of photoproduct absorption, and find excellent agreement between the experimental observations and molecular dynamics calculations that involve a true electronic state crossing. Taken together, these findings constitute the most compelling evidence to date for the existence and importance of conical intersections in visual photochemistry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polli, Dario -- Altoe, Piero -- Weingart, Oliver -- Spillane, Katelyn M -- Manzoni, Cristian -- Brida, Daniele -- Tomasello, Gaia -- Orlandi, Giorgio -- Kukura, Philipp -- Mathies, Richard A -- Garavelli, Marco -- Cerullo, Giulio -- England -- Nature. 2010 Sep 23;467(7314):440-3. doi: 10.1038/nature09346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IFN-CNR, Dipartimento di Fisica, Politecnico di Milano, Piazza L. da Vinci 32, 20133 Milano, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20864998" target="_blank"〉PubMed〈/a〉