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  • 1
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    Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-06-26
    Description: Outer hair cells (OHCs) of the mammalian cochlea actively change their cell length in response to changes in membrane potential. This electromotility, thought to be the basis of cochlear amplification, is mediated by a voltage-sensitive motor molecule recently identified as the membrane protein prestin. Here, we show that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well as the characteristic nonlinear charge movement ("gating currents") driving the underlying structural rearrangements of the protein. The results support a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule and thus trigger the conformational changes required for motility of OHCs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oliver, D -- He, D Z -- Klocker, N -- Ludwig, J -- Schulte, U -- Waldegger, S -- Ruppersberg, J P -- Dallos, P -- Fakler, B -- DC00089/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 22;292(5525):2340-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology II, University of Tubingen, 72074 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423665" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Anion Transport Proteins ; Anions/pharmacology ; Bicarbonates/*metabolism/pharmacology ; CHO Cells ; Cations/pharmacology ; Cell Membrane/metabolism ; Chlorides/*metabolism/pharmacology ; Cricetinae ; Electric Conductivity ; Electrophysiology ; Hair Cells, Auditory, Outer/*physiology ; Models, Biological ; Mutation ; Patch-Clamp Techniques ; Protein Conformation ; Proteins/chemistry/genetics/*metabolism ; Rats
    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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  • 2
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    Neighborhood effects on the long-term well-being of low-income adults (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-09-22
    Description: Nearly 9 million Americans live in extreme-poverty neighborhoods, places that also tend to be racially segregated and dangerous. Yet, the effects on the well-being of residents of moving out of such communities into less distressed areas remain uncertain. Using data from Moving to Opportunity, a unique randomized housing mobility experiment, we found that moving from a high-poverty to lower-poverty neighborhood leads to long-term (10- to 15-year) improvements in adult physical and mental health and subjective well-being, despite not affecting economic self-sufficiency. A 1-standard deviation decline in neighborhood poverty (13 percentage points) increases subjective well-being by an amount equal to the gap in subjective well-being between people whose annual incomes differ by $13,000--a large amount given that the average control group income is $20,000. Subjective well-being is more strongly affected by changes in neighborhood economic disadvantage than racial segregation, which is important because racial segregation has been declining since 1970, but income segregation has been increasing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491569/" 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/PMC3491569/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ludwig, Jens -- Duncan, Greg J -- Gennetian, Lisa A -- Katz, Lawrence F -- Kessler, Ronald C -- Kling, Jeffrey R -- Sanbonmatsu, Lisa -- P01 AG005842/AG/NIA NIH HHS/ -- P01-AG005842-22S1/AG/NIA NIH HHS/ -- P20-AG012180/AG/NIA NIH HHS/ -- P30 AG012810/AG/NIA NIH HHS/ -- R01 AG031259/AG/NIA NIH HHS/ -- R01 HD040404/HD/NICHD NIH HHS/ -- R01 HD040444/HD/NICHD NIH HHS/ -- R01 MH077026/MH/NIMH NIH HHS/ -- R01-HD040404/HD/NICHD NIH HHS/ -- R01-HD040444/HD/NICHD NIH HHS/ -- R01-MH077026/MH/NIMH NIH HHS/ -- R24 HD051152/HD/NICHD NIH HHS/ -- R24-HD051152-04/HD/NICHD NIH HHS/ -- R49-CE000906/CE/NCIPC CDC HHS/ -- R56 AG031259/AG/NIA NIH HHS/ -- R56-AG031259/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 21;337(6101):1505-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harris School of Public Policy, University of Chicago, 1155 East 60th Street, Chicago, IL 60637, USA. jludwig@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22997331" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Happiness ; *Housing ; Humans ; Income ; *Mental Health ; *Personal Satisfaction ; *Poverty ; *Quality of Life ; *Residence Characteristics ; Social Conditions ; United States ; United States Government Agencies
    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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    LMBR1L regulates lymphopoiesis through Wnt/{beta}-catenin signaling (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Precise control of Wnt signaling is necessary for immune system development. In this study, we detected severely impaired development of all lymphoid lineages in mice, resulting from an 〈i〉N〈/i〉-ethyl-〈i〉N〈/i〉-nitrosourea–induced mutation in the limb region 1–like gene (〈i〉Lmbr1l〈/i〉), which encodes a membrane-spanning protein with no previously described function in immunity. The interaction of LMBR1L with glycoprotein 78 (GP78) and ubiquitin-associated domain–containing protein 2 (UBAC2) attenuated Wnt signaling in lymphocytes by preventing the maturation of FZD6 and LRP6 through ubiquitination within the endoplasmic reticulum and by stabilizing "destruction complex" proteins. LMBR1L-deficient T cells exhibited hallmarks of Wnt/β-catenin activation and underwent apoptotic cell death in response to proliferative stimuli. LMBR1L has an essential function during lymphopoiesis and lymphoid activation, acting as a negative regulator of the Wnt/β-catenin pathway.〈/p〉
    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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  • 4
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    Interrupted carbonyl-olefin metathesis via oxygen atom transfer (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-09-28
    Description: Some of the simplest and most powerful carbon-carbon bond forming strategies take advantage of readily accessible ubiquitous motifs: carbonyls and olefins. Here we report a fundamentally distinct mode of reactivity between carbonyls and olefins that differs from established acid-catalyzed carbonyl-ene, Prins, and carbonyl-olefin metathesis reaction paths. A range of epsilon, zeta-unsaturated ketones undergo Brønsted acid–catalyzed intramolecular cyclization to provide tetrahydrofluorene products via the formation of two new carbon-carbon bonds. Theoretical calculations and accompanying mechanistic studies suggest that this carbocyclization reaction proceeds through the intermediacy of a transient oxetane formed by oxygen atom transfer. The complex polycyclic frameworks in this product class appear as common substructures in organic materials, bioactive natural products, and recently developed pharmaceuticals.
    Keywords: Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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