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  • 1
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    Black mamba venom peptides target acid-sensing ion channels to abolish pain (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-10-05
    Description: Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels. In the field of pain, they led to important advances in basic research and even to clinical applications. Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway, including in humans. A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain. Here we show that a new class of three-finger peptides from another snake, the black mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diochot, Sylvie -- Baron, Anne -- Salinas, Miguel -- Douguet, Dominique -- Scarzello, Sabine -- Dabert-Gay, Anne-Sophie -- Debayle, Delphine -- Friend, Valerie -- Alloui, Abdelkrim -- Lazdunski, Michel -- Lingueglia, Eric -- England -- Nature. 2012 Oct 25;490(7421):552-5. doi: 10.1038/nature11494. Epub 2012 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, UMR 7275, 06560 Valbonne, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23034652" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Sensing Ion Channel Blockers/chemistry/*pharmacology/therapeutic use ; Acid Sensing Ion Channels/classification/genetics/*metabolism ; Analgesics/adverse effects/chemistry/*pharmacology/therapeutic use ; Animals ; Drug Tolerance ; Elapid Venoms/administration & dosage/chemistry/*pharmacology/therapeutic use ; Injections, Spinal ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Morphine/adverse effects/pharmacology ; Naloxone/pharmacology ; Nociceptors/chemistry/metabolism ; Oocytes/drug effects/metabolism ; Pain/*drug therapy/metabolism ; Peptides/administration & dosage/chemistry/*pharmacology/*therapeutic use ; Protein Subunits/antagonists & inhibitors/metabolism ; Rats ; Respiratory Insufficiency/chemically induced ; Xenopus laevis
    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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  • 2
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    Evolution of a novel phenolic pathway for pollen development (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-09-26
    Description: Metabolic plasticity, which largely relies on the creation of new genes, is an essential feature of plant adaptation and speciation and has led to the evolution of large gene families. A typical example is provided by the diversification of the cytochrome P450 enzymes in plants. We describe here a retroposition, neofunctionalization, and duplication sequence that, via selective and local amino acid replacement, led to the evolution of a novel phenolic pathway in Brassicaceae. This pathway involves a cascade of six successive hydroxylations by two partially redundant cytochromes P450, leading to the formation of N1,N5-di(hydroxyferuloyl)-N10-sinapoylspermidine, a major pollen constituent and so-far-overlooked player in phenylpropanoid metabolism. This example shows how positive Darwinian selection can favor structured clusters of nonsynonymous substitutions that are needed for the transition of enzymes to new functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuno, Michiyo -- Compagnon, Vincent -- Schoch, Guillaume A -- Schmitt, Martine -- Debayle, Delphine -- Bassard, Jean-Etienne -- Pollet, Brigitte -- Hehn, Alain -- Heintz, Dimitri -- Ullmann, Pascaline -- Lapierre, Catherine -- Bernier, Francois -- Ehlting, Jurgen -- Werck-Reichhart, Daniele -- New York, N.Y. -- Science. 2009 Sep 25;325(5948):1688-92. doi: 10.1126/science.1174095.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Biologie Moleculaire des Plantes, CNRS-UPR2357, Universite de Strasbourg, 28 Rue Goethe, 67083 Strasbourg Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779199" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/metabolism ; Base Sequence ; Brassica napus/genetics/growth & development/metabolism ; Brassicaceae/genetics/growth & development/*metabolism ; Cytochrome P-450 Enzyme System/chemistry/genetics/*metabolism ; *Evolution, Molecular ; Gene Duplication ; Hydroxylation ; Metabolic Networks and Pathways ; Methylation ; Models, Molecular ; Molecular Sequence Data ; Plant Proteins/chemistry/genetics/metabolism ; Pollen/*growth & development/metabolism ; RNA Interference ; Retroelements ; Selection, Genetic ; Spermidine/*analogs & derivatives/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Laser plasma interaction on rugby hohlraum on the Omega Laser Facility: Comparisons between cylinder, rugby, and elliptical hohlraums (2016)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2016-02-12
    Description: Gas-filled rugby-shaped hohlraums have demonstrated high performances compared to a classical similar diameter cylinder hohlraum with a nearly 40% increase of x-ray drive, 10% higher measured peak drive temperature, and an increase in neutron production. Experimental comparisons have been done between rugby, cylinder, and elliptical hohlraums. The impact of these geometry differences on the laser plasma instabilities is examined. Using comparisons with hydrodynamic simulations carried out with the code FCI2 and postprocessed by Piranah, we have been able to reproduce the stimulated Raman and Brillouin scattering spectrum of the different beams. Using a methodology based on a statistical analysis for the gain calculations, we show that the behavior of the laser plasma instabilities in rugby hohlraums can be reproduced. The efficiency of laser smoothing techniques to mitigate these instabilities are discussed, and we show that while rugby hohlraums exhibit more laser plasma instabilities than cylinder hohlraum, the latter can be mitigated in the case of an elliptical hohlraum.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
    Published by American Institute of Physics (AIP)
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