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  • 1
    Publication Date: 2008-02-16
    Description: Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. We investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to the sedative effects of alcohol. In a randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with an NK1R antagonist (LY686017; n = 25) or placebo (n = 25). LY686017 suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses to affective stimuli likewise suggested beneficial LY686017 effects. Thus, as assessed by these surrogate markers of efficacy, NK1R antagonism warrants further investigation as a treatment in alcoholism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉George, David T -- Gilman, Jodi -- Hersh, Jacqueline -- Thorsell, Annika -- Herion, David -- Geyer, Christopher -- Peng, Xiaomei -- Kielbasa, William -- Rawlings, Robert -- Brandt, John E -- Gehlert, Donald R -- Tauscher, Johannes T -- Hunt, Stephen P -- Hommer, Daniel -- Heilig, Markus -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2008 Mar 14;319(5869):1536-9. doi: 10.1126/science.1153813. Epub 2008 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276852" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; *Alcohol Drinking/drug therapy ; Alcoholism/*drug therapy ; Animals ; Behavior, Addictive/drug therapy ; Brain/drug effects/physiology ; Emotions/drug effects ; Ethanol/administration & dosage/pharmacology ; Female ; Humans ; Hydrocortisone/blood ; Magnetic Resonance Imaging ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; *Neurokinin-1 Receptor Antagonists ; Pyridines/administration & dosage/pharmacology/*therapeutic use ; Receptors, Neurokinin-1/deficiency/genetics/*physiology ; Triazoles/administration & dosage/pharmacology/*therapeutic use
    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
    Publication Date: 2015-02-14
    Description: Plastic debris in the marine environment is widely documented, but the quantity of plastic entering the ocean from waste generated on land is unknown. By linking worldwide data on solid waste, population density, and economic status, we estimated the mass of land-based plastic waste entering the ocean. We calculate that 275 million metric tons (MT) of plastic waste was generated in 192 coastal countries in 2010, with 4.8 to 12.7 million MT entering the ocean. Population size and the quality of waste management systems largely determine which countries contribute the greatest mass of uncaptured waste available to become plastic marine debris. Without waste management infrastructure improvements, the cumulative quantity of plastic waste available to enter the ocean from land is predicted to increase by an order of magnitude by 2025.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jambeck, Jenna R -- Geyer, Roland -- Wilcox, Chris -- Siegler, Theodore R -- Perryman, Miriam -- Andrady, Anthony -- Narayan, Ramani -- Law, Kara Lavender -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):768-71. doi: 10.1126/science.1260352.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Engineering, University of Georgia, 412 Driftmier Engineering Center, Athens, GA 30602, USA. jjambeck@uga.edu. ; Bren School of Environmental Science and Management, University of California, Santa Barbara, CA 93106, USA. ; Oceans and Atmosphere Flagship, Commonwealth Scientific and Industrial Research Organization, Castray Esplanade, Hobart, Tasmania 7000, Australia. ; DSM Environmental Services, Windsor, VT 05089, USA. ; College of Engineering, University of Georgia, 412 Driftmier Engineering Center, Athens, GA 30602, USA. ; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA. ; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA. ; Sea Education Association, Woods Hole, MA 02543, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678662" target="_blank"〉PubMed〈/a〉
    Keywords: Environmental Pollution/*statistics & numerical data ; Oceans and Seas ; *Plastics ; Seawater ; Waste Management/*statistics & numerical data ; *Waste Products ; *Water Pollutants, Chemical
    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
    Publication Date: 2016-04-30
    Description: Systems in thermodynamic equilibrium are not only characterized by time-independent macroscopic properties, but also satisfy the principle of detailed balance in the transitions between microscopic configurations. Living systems function out of equilibrium and are characterized by directed fluxes through chemical states, which violate detailed balance at the molecular scale. Here we introduce a method to probe for broken detailed balance and demonstrate how such nonequilibrium dynamics are manifest at the mesosopic scale. The periodic beating of an isolated flagellum from Chlamydomonas reinhardtii exhibits probability flux in the phase space of shapes. With a model, we show how the breaking of detailed balance can also be quantified in stationary, nonequilibrium stochastic systems in the absence of periodic motion. We further demonstrate such broken detailed balance in the nonperiodic fluctuations of primary cilia of epithelial cells. Our analysis provides a general tool to identify nonequilibrium dynamics in cells and tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Battle, Christopher -- Broedersz, Chase P -- Fakhri, Nikta -- Geyer, Veikko F -- Howard, Jonathon -- Schmidt, Christoph F -- MacKintosh, Fred C -- P50GM068763/GM/NIGMS NIH HHS/ -- R13GM085967/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):604-7. doi: 10.1126/science.aac8167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drittes Physikalisches Institut, Georg-August-Universitat, 37077 Gottingen, Germany. The Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106, USA. ; The Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106, USA. Arnold-Sommerfeld-Center for Theoretical Physics and Center for NanoScience, Ludwig-Maximilians-Universitat Munchen, Theresienstrasse 37, D-80333 Munchen, Germany. Lewis-Sigler Institute for Integrative Genomics and Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, USA. ; Drittes Physikalisches Institut, Georg-August-Universitat, 37077 Gottingen, Germany. The Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106, USA. Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. ; Drittes Physikalisches Institut, Georg-August-Universitat, 37077 Gottingen, Germany. The Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106, USA. fcmack@gmail.com christoph.schmidt@phys.uni-goettingen.de. ; The Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106, USA. Department of Physics and Astronomy, Vrije Universiteit, Amsterdam, Netherlands. fcmack@gmail.com christoph.schmidt@phys.uni-goettingen.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126047" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chlamydomonas reinhardtii/*physiology ; Cilia/physiology ; Dogs ; Epithelial Cells/physiology ; Flagella/*physiology ; Madin Darby Canine Kidney Cells ; Microscopy/methods ; Models, Biological ; *Motion ; Thermodynamics
    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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