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    Publication Date: 2008-05-10
    Description: We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803040/" 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/PMC2803040/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Wesley C -- Hillier, LaDeana W -- Marshall Graves, Jennifer A -- Birney, Ewan -- Ponting, Chris P -- Grutzner, Frank -- Belov, Katherine -- Miller, Webb -- Clarke, Laura -- Chinwalla, Asif T -- Yang, Shiaw-Pyng -- Heger, Andreas -- Locke, Devin P -- Miethke, Pat -- Waters, Paul D -- Veyrunes, Frederic -- Fulton, Lucinda -- Fulton, Bob -- Graves, Tina -- Wallis, John -- Puente, Xose S -- Lopez-Otin, Carlos -- Ordonez, Gonzalo R -- Eichler, Evan E -- Chen, Lin -- Cheng, Ze -- Deakin, Janine E -- Alsop, Amber -- Thompson, Katherine -- Kirby, Patrick -- Papenfuss, Anthony T -- Wakefield, Matthew J -- Olender, Tsviya -- Lancet, Doron -- Huttley, Gavin A -- Smit, Arian F A -- Pask, Andrew -- Temple-Smith, Peter -- Batzer, Mark A -- Walker, Jerilyn A -- Konkel, Miriam K -- Harris, Robert S -- Whittington, Camilla M -- Wong, Emily S W -- Gemmell, Neil J -- Buschiazzo, Emmanuel -- Vargas Jentzsch, Iris M -- Merkel, Angelika -- Schmitz, Juergen -- Zemann, Anja -- Churakov, Gennady -- Kriegs, Jan Ole -- Brosius, Juergen -- Murchison, Elizabeth P -- Sachidanandam, Ravi -- Smith, Carly -- Hannon, Gregory J -- Tsend-Ayush, Enkhjargal -- McMillan, Daniel -- Attenborough, Rosalind -- Rens, Willem -- Ferguson-Smith, Malcolm -- Lefevre, Christophe M -- Sharp, Julie A -- Nicholas, Kevin R -- Ray, David A -- Kube, Michael -- Reinhardt, Richard -- Pringle, Thomas H -- Taylor, James -- Jones, Russell C -- Nixon, Brett -- Dacheux, Jean-Louis -- Niwa, Hitoshi -- Sekita, Yoko -- Huang, Xiaoqiu -- Stark, Alexander -- Kheradpour, Pouya -- Kellis, Manolis -- Flicek, Paul -- Chen, Yuan -- Webber, Caleb -- Hardison, Ross -- Nelson, Joanne -- Hallsworth-Pepin, Kym -- Delehaunty, Kim -- Markovic, Chris -- Minx, Pat -- Feng, Yucheng -- Kremitzki, Colin -- Mitreva, Makedonka -- Glasscock, Jarret -- Wylie, Todd -- Wohldmann, Patricia -- Thiru, Prathapan -- Nhan, Michael N -- Pohl, Craig S -- Smith, Scott M -- Hou, Shunfeng -- Nefedov, Mikhail -- de Jong, Pieter J -- Renfree, Marilyn B -- Mardis, Elaine R -- Wilson, Richard K -- 062023/Wellcome Trust/United Kingdom -- HG002238/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-37/CA/NCI NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG004037-02/HG/NHGRI NIH HHS/ -- R01HG02385/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2008 May 8;453(7192):175-83. doi: 10.1038/nature06936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. wwarren@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Dentition ; *Evolution, Molecular ; Female ; Genome/*genetics ; Genomic Imprinting/genetics ; Humans ; Immunity/genetics ; Male ; Mammals/genetics ; MicroRNAs/genetics ; Milk Proteins/genetics ; Phylogeny ; Platypus/*genetics/immunology/physiology ; Receptors, Odorant/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Reptiles/genetics ; Sequence Analysis, DNA ; Spermatozoa/metabolism ; Venoms/genetics ; Zona Pellucida/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2009-06-19
    Description: Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725363/" 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/PMC2725363/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Koning-Ward, Tania F -- Gilson, Paul R -- Boddey, Justin A -- Rug, Melanie -- Smith, Brian J -- Papenfuss, Anthony T -- Sanders, Paul R -- Lundie, Rachel J -- Maier, Alexander G -- Cowman, Alan F -- Crabb, Brendan S -- R01 AI044008-11/AI/NIAID NIH HHS/ -- R01 AI44008/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 18;459(7249):945-9. doi: 10.1038/nature08104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter & Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Malaria, Falciparum/*parasitology ; Models, Biological ; Multiprotein Complexes/*chemistry/*metabolism ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-09-15
    Description: Bromodomain and extra terminal protein (BET) inhibitors are first-in-class targeted therapies that deliver a new therapeutic opportunity by directly targeting bromodomain proteins that bind acetylated chromatin marks. Early clinical trials have shown promise, especially in acute myeloid leukaemia, and therefore the evaluation of resistance mechanisms is crucial to optimize the clinical efficacy of these drugs. Here we use primary mouse haematopoietic stem and progenitor cells immortalized with the fusion protein MLL-AF9 to generate several single-cell clones that demonstrate resistance, in vitro and in vivo, to the prototypical BET inhibitor, I-BET. Resistance to I-BET confers cross-resistance to chemically distinct BET inhibitors such as JQ1, as well as resistance to genetic knockdown of BET proteins. Resistance is not mediated through increased drug efflux or metabolism, but is shown to emerge from leukaemia stem cells both ex vivo and in vivo. Chromatin-bound BRD4 is globally reduced in resistant cells, whereas the expression of key target genes such as Myc remains unaltered, highlighting the existence of alternative mechanisms to regulate transcription. We demonstrate that resistance to BET inhibitors, in human and mouse leukaemia cells, is in part a consequence of increased Wnt/beta-catenin signalling, and negative regulation of this pathway results in restoration of sensitivity to I-BET in vitro and in vivo. Together, these findings provide new insights into the biology of acute myeloid leukaemia, highlight potential therapeutic limitations of BET inhibitors, and identify strategies that may enhance the clinical utility of these unique targeted therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fong, Chun Yew -- Gilan, Omer -- Lam, Enid Y N -- Rubin, Alan F -- Ftouni, Sarah -- Tyler, Dean -- Stanley, Kym -- Sinha, Devbarna -- Yeh, Paul -- Morison, Jessica -- Giotopoulos, George -- Lugo, Dave -- Jeffrey, Philip -- Lee, Stanley Chun-Wei -- Carpenter, Christopher -- Gregory, Richard -- Ramsay, Robert G -- Lane, Steven W -- Abdel-Wahab, Omar -- Kouzarides, Tony -- Johnstone, Ricky W -- Dawson, Sarah-Jane -- Huntly, Brian J P -- Prinjha, Rab K -- Papenfuss, Anthony T -- Dawson, Mark A -- England -- Nature. 2015 Sep 24;525(7570):538-42. doi: 10.1038/nature14888. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, East Melbourne, Victoria 3002, Australia. ; Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. ; Bioinformatics Division, The Walter &Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. ; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia. ; Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust-MRC Stem Cell Institute, Cambridge CB2 0XY, UK. ; Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK. ; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA. ; QIMR Berghofer Medical Research Institute, University of Queensland, Brisbane, Queensland 4029, Australia. ; Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367796" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Azepines/pharmacology ; Benzodiazepines/*pharmacology ; Cell Line, Tumor ; Cells, Cultured ; Chromatin/metabolism ; Clone Cells/drug effects/metabolism/pathology ; Drug Resistance, Neoplasm/*drug effects/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, myc/genetics ; Hematopoietic Stem Cells/cytology/drug effects/metabolism ; Humans ; Leukemia, Myeloid, Acute/*drug therapy/genetics/*metabolism/pathology ; Mice ; Molecular Targeted Therapy ; Neoplastic Stem Cells/*drug effects/metabolism/*pathology ; Nuclear Proteins/*antagonists & inhibitors/metabolism ; Transcription Factors/*antagonists & inhibitors/metabolism ; Transcription, Genetic/drug effects ; Triazoles/pharmacology ; Wnt Signaling Pathway/drug effects ; beta Catenin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2010-01-02
    Description: The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982769/" 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/PMC2982769/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murchison, Elizabeth P -- Tovar, Cesar -- Hsu, Arthur -- Bender, Hannah S -- Kheradpour, Pouya -- Rebbeck, Clare A -- Obendorf, David -- Conlan, Carly -- Bahlo, Melanie -- Blizzard, Catherine A -- Pyecroft, Stephen -- Kreiss, Alexandre -- Kellis, Manolis -- Stark, Alexander -- Harkins, Timothy T -- Marshall Graves, Jennifer A -- Woods, Gregory M -- Hannon, Gregory J -- Papenfuss, Anthony T -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-38/CA/NCI NIH HHS/ -- R01 GM062534/GM/NIGMS NIH HHS/ -- R01 GM062534-10/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 1;327(5961):84-7. doi: 10.1126/science.1180616.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. elizabeth.murchison@sanger.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers, Tumor/analysis ; Bites and Stings/veterinary ; Cell Differentiation ; Facial Neoplasms/diagnosis/genetics/pathology/*veterinary ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Genome, Mitochondrial ; Genotype ; *Marsupialia/genetics ; Membrane Proteins/genetics/metabolism ; MicroRNAs/genetics ; Microsatellite Repeats ; Myelin Basic Protein/genetics ; Nerve Sheath Neoplasms/diagnosis/genetics/pathology/*veterinary ; *Schwann Cells/physiology ; Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Publication Date: 2016-06-17
    Description: New tools and algorithms for geological remote sensing are developed and verified at test sites throughout the world in preparation of the German hyperspectral satellite Mission (EnMAP), which is an Environmental Mapping and Analysis Program. The Aggeneys Cu-Pb-Zn deposit, situated in the arid north western part of South Africa, represents a unique field laboratory for testing these new tools. Here spaceborne hyperspectral data covering the Swartberg, Big Syncline and Gamsberg area were collected by the Hyperion sensor. New synergies between multispectral and hyperspectral spaceborne data can be demonstrated, such as the Iron Feature Depth index (IFD), which has recently been proposed for mine waste mapping in the North West Province of South Africa and for gossan detection at Haib River in South Namibia. The work presented here explores the potential of the IFD for gossan mapping and characterization at Gamsberg and Big Syncline, from EO-1 ALI and Landsat-8 OLI data together with mineral maps from expert systems such as the United States Geological Survey (USGS) Material Identification and Characterization Algorithm (MICA), and first results from EnMAPs EnGeoMAP algorithm. Field spectroscopic measurements and field sampling were carried out to validate and calibrate the results from the expert systems and the IFD. This ground truthing is a necessary complementary step to link the results from the expert systems and the IFD to in-situ field spectroscopy. Future mineral exploration initiatives may benefit from the techniques described here, because they can significantly narrow the expensive, exploration activities such as hyperspectral airborne data, field activities and drilling, by identifying the most promising mineral anomalies in an area from the spaceborne data.
    Print ISSN: 1012-0750
    Topics: Geosciences
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  • 9
    Publication Date: 2014-04-11
    Description: Motivation: Methods for detecting somatic genome rearrangements in tumours using next-generation sequencing are vital in cancer genomics. Available algorithms use one or more sources of evidence, such as read depth, paired-end reads or split reads to predict structural variants. However, the problem remains challenging due to the significant computational burden and high false-positive or false-negative rates. Results: In this article, we present Socrates (SOft Clip re-alignment To idEntify Structural variants), a highly efficient and effective method for detecting genomic rearrangements in tumours that uses only split-read data. Socrates has single-nucleotide resolution, identifies micro-homologies and untemplated sequence at break points, has high sensitivity and high specificity and takes advantage of parallelism for efficient use of resources. We demonstrate using simulated and real data that Socrates performs well compared with a number of existing structural variant detection tools. Availability and implementation: Socrates is released as open source and available from http://bioinf.wehi.edu.au/socrates . Contact: papenfuss@wehi.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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    Publication Date: 2011-08-03
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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