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  • 1
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    Genomic instability in mice lacking histone H2AX (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" 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/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
    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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  • 2
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    Impaired nociception and pain sensation in mice lacking the capsaicin receptor (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-04-15
    Description: The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (〉43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caterina, M J -- Leffler, A -- Malmberg, A B -- Martin, W J -- Trafton, J -- Petersen-Zeitz, K R -- Koltzenburg, M -- Basbaum, A I -- Julius, D -- NS07265/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 14;288(5464):306-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143-0450, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10764638" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Temperature/drug effects ; Calcium/metabolism ; Capsaicin/metabolism/*pharmacology ; Cells, Cultured ; Diterpenes/pharmacology ; Ganglia, Spinal/cytology ; Gene Targeting ; Hot Temperature ; Hydrogen-Ion Concentration ; Inflammation/physiopathology ; Mice ; Mice, Knockout ; Nerve Fibers/physiology ; Neurons/physiology ; Neurons, Afferent/*physiology ; Nociceptors/*physiology ; Pain/*physiopathology ; Pain Threshold ; Receptors, Drug/*physiology ; Spinal Cord/cytology/physiology ; TRPV Cation Channels
    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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  • 3
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    Bone marrow as a potential source of hepatic oval cells (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-05-15
    Description: Bone marrow stem cells develop into hematopoietic and mesenchymal lineages but have not been known to participate in production of hepatocytes, biliary cells, or oval cells during liver regeneration. Cross-sex or cross-strain bone marrow and whole liver transplantation were used to trace the origin of the repopulating liver cells. Transplanted rats were treated with 2-acetylaminofluorene, to block hepatocyte proliferation, and then hepatic injury, to induce oval cell proliferation. Markers for Y chromosome, dipeptidyl peptidase IV enzyme, and L21-6 antigen were used to identify liver cells of bone marrow origin. From these cells, a proportion of the regenerated hepatic cells were shown to be donor-derived. Thus, a stem cell associated with the bone marrow has epithelial cell lineage capability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, B E -- Bowen, W C -- Patrene, K D -- Mars, W M -- Sullivan, A K -- Murase, N -- Boggs, S S -- Greenberger, J S -- Goff, J P -- New York, N.Y. -- Science. 1999 May 14;284(5417):1168-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. bryon+@pitt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10325227" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Acetylaminofluorene/pharmacology ; Animals ; Bone Marrow Cells/*cytology ; Bone Marrow Transplantation ; Carbon Tetrachloride/pharmacology ; Cell Differentiation ; Cell Division ; DNA-Binding Proteins/genetics ; Dipeptidyl Peptidase 4/metabolism ; Epithelial Cells/cytology ; Female ; Hematopoietic Stem Cells/cytology ; In Situ Hybridization ; Liver/*cytology/drug effects/physiology ; *Liver Regeneration ; Liver Transplantation ; Male ; *Nuclear Proteins ; Polymerase Chain Reaction ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Sex-Determining Region Y Protein ; Stem Cells/*cytology ; *Transcription Factors ; Y Chromosome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-07-18
    Description: Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning. A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation. However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the V(m) of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the V(m) correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the V(m) of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poulet, James F A -- Petersen, Carl C H -- England -- Nature. 2008 Aug 14;454(7206):881-5. doi: 10.1038/nature07150. Epub 2008 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18633351" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electroencephalography ; Exploratory Behavior/*physiology ; Male ; Membrane Potentials/*physiology ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Somatosensory Cortex/*physiology ; Wakefulness/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-05-14
    Description: Regeneration requires initiation of programs tailored to the identity of missing parts. Head-versus-tail regeneration in planarians presents a paradigm for study of this phenomenon. After injury, Wnt signaling promotes tail regeneration. We report that wounding elicits expression of the Wnt inhibitor notum preferentially at anterior-facing wounds. This expression asymmetry occurs at essentially any wound, even if the anterior pole is intact. Inhibition of notum with RNA interference (RNAi) causes regeneration of an anterior-facing tail instead of a head, and double-RNAi experiments indicate that notum inhibits Wnt signaling to promote head regeneration. notum expression is itself controlled by Wnt signaling, suggesting that regulation of feedback inhibition controls the binary head-tail regeneration outcome. We conclude that local detection of wound orientation with respect to tissue axes results in distinct signaling environments that initiate appropriate regeneration responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320723/" 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/PMC3320723/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, Christian P -- Reddien, Peter W -- R01 GM080639/GM/NIGMS NIH HHS/ -- R01 GM080639-04/GM/NIGMS NIH HHS/ -- R01GM080639/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 May 13;332(6031):852-5. doi: 10.1126/science.1202143.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21566195" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Feedback, Physiological ; Gene Expression Regulation ; Genes, Helminth ; Head ; Helminth Proteins/genetics/*metabolism ; Hydrolases/genetics/*metabolism ; Molecular Sequence Data ; Planarians/cytology/genetics/*physiology ; RNA Interference ; *Regeneration ; *Signal Transduction ; Tail ; Wnt Proteins/genetics/*metabolism ; Wnt1 Protein/genetics/metabolism ; beta Catenin/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Wild pollinators enhance fruit set of crops regardless of honey bee abundance (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-03-02
    Description: The diversity and abundance of wild insect pollinators have declined in many agricultural landscapes. Whether such declines reduce crop yields, or are mitigated by managed pollinators such as honey bees, is unclear. We found universally positive associations of fruit set with flower visitation by wild insects in 41 crop systems worldwide. In contrast, fruit set increased significantly with flower visitation by honey bees in only 14% of the systems surveyed. Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation. Visitation by wild insects and honey bees promoted fruit set independently, so pollination by managed honey bees supplemented, rather than substituted for, pollination by wild insects. Our results suggest that new practices for integrated management of both honey bees and diverse wild insect assemblages will enhance global crop yields.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garibaldi, Lucas A -- Steffan-Dewenter, Ingolf -- Winfree, Rachael -- Aizen, Marcelo A -- Bommarco, Riccardo -- Cunningham, Saul A -- Kremen, Claire -- Carvalheiro, Luisa G -- Harder, Lawrence D -- Afik, Ohad -- Bartomeus, Ignasi -- Benjamin, Faye -- Boreux, Virginie -- Cariveau, Daniel -- Chacoff, Natacha P -- Dudenhoffer, Jan H -- Freitas, Breno M -- Ghazoul, Jaboury -- Greenleaf, Sarah -- Hipolito, Juliana -- Holzschuh, Andrea -- Howlett, Brad -- Isaacs, Rufus -- Javorek, Steven K -- Kennedy, Christina M -- Krewenka, Kristin M -- Krishnan, Smitha -- Mandelik, Yael -- Mayfield, Margaret M -- Motzke, Iris -- Munyuli, Theodore -- Nault, Brian A -- Otieno, Mark -- Petersen, Jessica -- Pisanty, Gideon -- Potts, Simon G -- Rader, Romina -- Ricketts, Taylor H -- Rundlof, Maj -- Seymour, Colleen L -- Schuepp, Christof -- Szentgyorgyi, Hajnalka -- Taki, Hisatomo -- Tscharntke, Teja -- Vergara, Carlos H -- Viana, Blandina F -- Wanger, Thomas C -- Westphal, Catrin -- Williams, Neal -- Klein, Alexandra M -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1608-11. doi: 10.1126/science.1230200. Epub 2013 Feb 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sede Andina, Universidad Nacional de Rio Negro (UNRN) and Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), San Carlos de Bariloche, Rio Negro, Argentina. lgaribaldi@unrn.edu.ar〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449997" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bees/physiology ; Crops, Agricultural/*growth & development ; Flowers/physiology ; Fruit/*growth & development ; Insects/*physiology ; *Pollination
    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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  • 7
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    Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-05-01
    Description: The functional and anatomical rearrangements of cortical sensory maps accompanying changes in experience are not well understood. We examined in vivo and in vitro how the sensory map and underlying synaptic connectivity of the developing rat barrel cortex are altered when the sensory input to the cortex is partially deprived. In the nondeprived cortex, both the sensory responses and synaptic connectivity between columns were strengthened through an increase in the synaptic connection probability between L2/3 pyramids in adjacent columns. This was accompanied by a selective growth of L2/3pyramid axonal arbors between spared columns. In contrast, deprived and nondeprived cortical columns became weakly connected in their L2/3 pyramid connections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, Carl C H -- Brecht, Michael -- Hahn, Thomas T G -- Sakmann, Bert -- New York, N.Y. -- Science. 2004 Apr 30;304(5671):739-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Physiology, Max-Planck-Institute for Medical Research, Jahnstrasse 29, Heidelberg D-69120, Germany. carl.petersen@epfl.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15118164" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Brain Mapping ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Image Processing, Computer-Assisted ; In Vitro Techniques ; Nerve Net/physiology ; *Neuronal Plasticity ; Patch-Clamp Techniques ; Pyramidal Cells/*physiology/ultrastructure ; Rats ; Rats, Wistar ; Somatosensory Cortex/cytology/growth & development/*physiology ; Synapses/*physiology ; Synaptic Transmission ; Vibrissae/*physiology
    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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  • 8
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    Hydrogen is an energy source for hydrothermal vent symbioses (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-08-13
    Description: The discovery of deep-sea hydrothermal vents in 1977 revolutionized our understanding of the energy sources that fuel primary productivity on Earth. Hydrothermal vent ecosystems are dominated by animals that live in symbiosis with chemosynthetic bacteria. So far, only two energy sources have been shown to power chemosynthetic symbioses: reduced sulphur compounds and methane. Using metagenome sequencing, single-gene fluorescence in situ hybridization, immunohistochemistry, shipboard incubations and in situ mass spectrometry, we show here that the symbionts of the hydrothermal vent mussel Bathymodiolus from the Mid-Atlantic Ridge use hydrogen to power primary production. In addition, we show that the symbionts of Bathymodiolus mussels from Pacific vents have hupL, the key gene for hydrogen oxidation. Furthermore, the symbionts of other vent animals such as the tubeworm Riftia pachyptila and the shrimp Rimicaris exoculata also have hupL. We propose that the ability to use hydrogen as an energy source is widespread in hydrothermal vent symbioses, particularly at sites where hydrogen is abundant.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, Jillian M -- Zielinski, Frank U -- Pape, Thomas -- Seifert, Richard -- Moraru, Cristina -- Amann, Rudolf -- Hourdez, Stephane -- Girguis, Peter R -- Wankel, Scott D -- Barbe, Valerie -- Pelletier, Eric -- Fink, Dennis -- Borowski, Christian -- Bach, Wolfgang -- Dubilier, Nicole -- England -- Nature. 2011 Aug 10;476(7359):176-80. doi: 10.1038/nature10325.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Marine Microbiology, Celsiusstrasse 1, 28359 Bremen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atlantic Ocean ; Bivalvia/drug effects/metabolism/*microbiology ; Dose-Response Relationship, Drug ; *Ecosystem ; *Energy Metabolism ; Geologic Sediments/chemistry ; Gills/drug effects/metabolism/microbiology ; Hot Springs/*chemistry/microbiology ; Hydrogen/analysis/*metabolism/pharmacology ; Hydrogenase/genetics/metabolism ; Molecular Sequence Data ; Oxidation-Reduction ; Partial Pressure ; Seawater/chemistry/microbiology ; Sulfides/metabolism ; Sulfur/metabolism ; Symbiosis/drug effects/genetics/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-10-30
    Description: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" 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/PMC3530898/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biankin, Andrew V -- Waddell, Nicola -- Kassahn, Karin S -- Gingras, Marie-Claude -- Muthuswamy, Lakshmi B -- Johns, Amber L -- Miller, David K -- Wilson, Peter J -- Patch, Ann-Marie -- Wu, Jianmin -- Chang, David K -- Cowley, Mark J -- Gardiner, Brooke B -- Song, Sarah -- Harliwong, Ivon -- Idrisoglu, Senel -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Wani, Shivangi -- Gongora, Milena -- Pajic, Marina -- Scarlett, Christopher J -- Gill, Anthony J -- Pinho, Andreia V -- Rooman, Ilse -- Anderson, Matthew -- Holmes, Oliver -- Leonard, Conrad -- Taylor, Darrin -- Wood, Scott -- Xu, Qinying -- Nones, Katia -- Fink, J Lynn -- Christ, Angelika -- Bruxner, Tim -- Cloonan, Nicole -- Kolle, Gabriel -- Newell, Felicity -- Pinese, Mark -- Mead, R Scott -- Humphris, Jeremy L -- Kaplan, Warren -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chou, Angela -- Chin, Venessa T -- Chantrill, Lorraine A -- Mawson, Amanda -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Daly, Roger J -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Australian Pancreatic Cancer Genome Initiative -- Kakkar, Nipun -- Zhao, Fengmei -- Wu, Yuan Qing -- Wang, Min -- Muzny, Donna M -- Fisher, William E -- Brunicardi, F Charles -- Hodges, Sally E -- Reid, Jeffrey G -- Drummond, Jennifer -- Chang, Kyle -- Han, Yi -- Lewis, Lora R -- Dinh, Huyen -- Buhay, Christian J -- Beck, Timothy -- Timms, Lee -- Sam, Michelle -- Begley, Kimberly -- Brown, Andrew -- Pai, Deepa -- Panchal, Ami -- Buchner, Nicholas -- De Borja, Richard -- Denroche, Robert E -- Yung, Christina K -- Serra, Stefano -- Onetto, Nicole -- Mukhopadhyay, Debabrata -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Gallinger, Steven -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Schulick, Richard D -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Capelli, Paola -- Corbo, Vincenzo -- Scardoni, Maria -- Tortora, Giampaolo -- Tempero, Margaret A -- Mann, Karen M -- Jenkins, Nancy A -- Perez-Mancera, Pedro A -- Adams, David J -- Largaespada, David A -- Wessels, Lodewyk F A -- Rust, Alistair G -- Stein, Lincoln D -- Tuveson, David A -- Copeland, Neal G -- Musgrove, Elizabeth A -- Scarpa, Aldo -- Eshleman, James R -- Hudson, Thomas J -- Sutherland, Robert L -- Wheeler, David A -- Pearson, John V -- McPherson, John D -- Gibbs, Richard A -- Grimmond, Sean M -- 13031/Cancer Research UK/United Kingdom -- 2P50CA101955/CA/NCI NIH HHS/ -- P01CA134292/CA/NCI NIH HHS/ -- P50 CA101955/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50CA062924/CA/NCI NIH HHS/ -- R01 CA097075/CA/NCI NIH HHS/ -- R01 CA97075/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):399-405. doi: 10.1038/nature11547. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103869" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*metabolism ; Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genome/*genetics ; Humans ; Kaplan-Meier Estimate ; Mice ; Mutation ; Pancreatic Neoplasms/*genetics/*pathology ; Proteins/genetics ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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    Severe malaria is associated with parasite binding to endothelial protein C receptor (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-06-07
    Description: Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was unknown. Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRalpha1) of DC8 and group A PfEMP1 subfamilies, and that CIDRalpha1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the development of new malaria interventions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870021/" 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/PMC3870021/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turner, Louise -- Lavstsen, Thomas -- Berger, Sanne S -- Wang, Christian W -- Petersen, Jens E V -- Avril, Marion -- Brazier, Andrew J -- Freeth, Jim -- Jespersen, Jakob S -- Nielsen, Morten A -- Magistrado, Pamela -- Lusingu, John -- Smith, Joseph D -- Higgins, Matthew K -- Theander, Thor G -- G0901062/Medical Research Council/United Kingdom -- R01 AI047953/AI/NIAID NIH HHS/ -- R01 AI47953/AI/NIAID NIH HHS/ -- U19 AI089688/AI/NIAID NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Jun 27;498(7455):502-5. doi: 10.1038/nature12216. Epub 2013 Jun 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, University of Copenhagen and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. lturner@sund.ku.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23739325" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*metabolism ; Blood Coagulation ; Brain/blood supply ; CHO Cells ; Cell Adhesion ; Cell Line ; Cricetinae ; Endothelial Cells/metabolism ; Erythrocyte Membrane/metabolism ; Humans ; Inflammation/complications/parasitology/pathology ; Malaria, Falciparum/complications/*parasitology/*pathology ; Microcirculation ; Plasmodium falciparum/chemistry/*metabolism/pathogenicity ; Protozoan Proteins/chemistry/metabolism ; Receptors, Cell Surface/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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