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  • 1
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    G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-01-21
    Description: The regulated release of anorexigenic alpha-melanocyte stimulating hormone (alpha-MSH) and orexigenic Agouti-related protein (AgRP) from discrete hypothalamic arcuate neurons onto common target sites in the central nervous system has a fundamental role in the regulation of energy homeostasis. Both peptides bind with high affinity to the melanocortin-4 receptor (MC4R); existing data show that alpha-MSH is an agonist that couples the receptor to the Galphas signalling pathway, while AgRP binds competitively to block alpha-MSH binding and blocks the constitutive activity mediated by the ligand-mimetic amino-terminal domain of the receptor. Here we show that, in mice, regulation of firing activity of neurons from the paraventricular nucleus of the hypothalamus (PVN) by alpha-MSH and AgRP can be mediated independently of Galphas signalling by ligand-induced coupling of MC4R to closure of inwardly rectifying potassium channel, Kir7.1. Furthermore, AgRP is a biased agonist that hyperpolarizes neurons by binding to MC4R and opening Kir7.1, independently of its inhibition of alpha-MSH binding. Consequently, Kir7.1 signalling appears to be central to melanocortin-mediated regulation of energy homeostasis within the PVN. Coupling of MC4R to Kir7.1 may explain unusual aspects of the control of energy homeostasis by melanocortin signalling, including the gene dosage effect of MC4R and the sustained effects of AgRP on food intake.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383680/" 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/PMC4383680/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghamari-Langroudi, Masoud -- Digby, Gregory J -- Sebag, Julien A -- Millhauser, Glenn L -- Palomino, Rafael -- Matthews, Robert -- Gillyard, Taneisha -- Panaro, Brandon L -- Tough, Iain R -- Cox, Helen M -- Denton, Jerod S -- Cone, Roger D -- 5R01 DK082884-03/DK/NIDDK NIH HHS/ -- DK020593/DK/NIDDK NIH HHS/ -- F31 DK102343/DK/NIDDK NIH HHS/ -- P30 DK020593/DK/NIDDK NIH HHS/ -- R01 DK064265/DK/NIDDK NIH HHS/ -- R01 DK070332/DK/NIDDK NIH HHS/ -- R01DK064265/DK/NIDDK NIH HHS/ -- R01DK070332/DK/NIDDK NIH HHS/ -- R25 GM059994/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):94-8. doi: 10.1038/nature14051. Epub 2015 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. ; Department of Chemistry &Biochemistry, University of California, Santa Cruz, California 95064, USA. ; 1] Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA [2] Department of Pharmacology, Meharry Medical College, Nashville, Tennessee 37208, USA. ; King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London SE1 1UL, UK. ; 1] Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA [2] Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25600267" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Agouti-Related Protein/metabolism ; Animals ; Eating/genetics ; Energy Metabolism ; Female ; *GTP-Binding Protein alpha Subunits, Gs ; HEK293 Cells ; Homeostasis/genetics ; Humans ; Ligands ; Male ; Melanocortins/metabolism ; Mice ; Neurons/*metabolism ; Paraventricular Hypothalamic Nucleus/*cytology ; Potassium Channels, Inwardly Rectifying/*metabolism ; Receptor, Melanocortin, Type 4/genetics/*metabolism ; Signal Transduction/genetics ; alpha-MSH/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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  • 2
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    Careers in science. More women in science (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-08-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Handelsman, Jo -- Cantor, Nancy -- Carnes, Molly -- Denton, Denice -- Fine, Eve -- Grosz, Barbara -- Hinshaw, Virginia -- Marrett, Cora -- Rosser, Sue -- Shalala, Donna -- Sheridan, Jennifer -- New York, N.Y. -- Science. 2005 Aug 19;309(5738):1190-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, University of Wisconsin - Madison, 1630 Linden Dr., Madison, WI 53706, USA. joh@ plantpath.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16109868" target="_blank"〉PubMed〈/a〉
    Keywords: Career Choice ; *Career Mobility ; Education, Graduate ; *Faculty ; Family ; Female ; Humans ; Personnel Selection ; Prejudice ; *Science ; Universities ; *Women
    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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    Gender differences and performance in science (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Carol B -- Ride, Sally M -- Fouke, Janie -- Whitney, Telle -- Denton, Denice D -- Cantor, Nancy -- Nelson, Donna J -- Plummer, Jim -- Busch-Vishniac, Ilene -- Meyers, Carolyn -- Rosser, Sue V -- Schiebinger, Londa -- Roberts, Eric -- Burgess, David -- Beeson, Craig -- Metz, Susan Staffin -- Sanders, Lucinda -- Watford, Bevlee A -- Ivey, Elizabeth S -- Frank Fox, Mary -- Wettack, Sheldon -- Klawe, Maria -- Wulf, William A -- Girgus, Joan -- Leboy, Phoebe S -- Babco, Eleanor L -- Shanahan, Betty -- Didion, Catherine -- Chubin, Daryl E -- Frize, Monique -- Ganter, Susan L -- Nalley, E Ann -- Franz, Judy -- Abruna, Hector D -- Strober, Myra H -- Zimmer Daniels, Jane -- Carter, Emily A -- Rhodes, Jean H -- Schrijver, Iris -- Zakian, Virginia A -- Simons, Barbara -- Martin, Ursula -- Boaler, Jo -- Jolluck, Katherine Rose -- Mankekar, Purnima -- Gray, Robert M -- Conkey, Margaret W -- Stansky, Peter -- Xie, Aihua -- Martin, Pino -- Katehi, Linda P B -- Miller, Jo Anne -- Tess Thornton, Amelia -- Lapaugh, Andrea -- Rhode, Deborah L -- Gelpi, Barbara C -- Harrold, Mary Jean -- Spencer, Cherrill M -- Schlatter Ellis, Carla -- Lord, Susan -- Quinn, Helen -- Murnane, Margaret -- Jones, Patricia P -- Hellman, Frances -- Wight, Gail -- O'hara, Ruth -- Pickering, Mary -- Sheppard, Sheri -- Leith, David -- Paytan, Adina -- Sommer, Matthew H -- Shafer, Audrey -- Grusky, David -- Yennello, Sherry -- Madan, Ashima -- Johnson, Denise L -- Yanagisako, Sylvia -- Chou-Green, Jennifer M -- Robinson, Sandra -- New York, N.Y. -- Science. 2005 Feb 18;307(5712):1043.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15718449" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Female ; Humans ; Male ; *Science ; *Sex Characteristics ; Social Change
    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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    Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-11-03
    Description: Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder common in North Africa that segregates with microsatellite markers at chromosome 13q12. Here, it is shown that a mutation in the gene encoding the 35-kilodalton dystrophin-associated glycoprotein, gamma-sarcoglycan, is likely to be the primary genetic defect in this disorder. The human gamma-sarcoglycan gene was mapped to chromosome 13q12, and deletions that alter its reading frame were identified in three families and one of four sporadic cases of SCARMD. These mutations not only affect gamma-sarcoglycan but also disrupt the integrity of the entire sarcoglycan complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noguchi, S -- McNally, E M -- Ben Othmane, K -- Hagiwara, Y -- Mizuno, Y -- Yoshida, M -- Yamamoto, H -- Bonnemann, C G -- Gussoni, E -- Denton, P H -- Kyriakides, T -- Middleton, L -- Hentati, F -- Ben Hamida, M -- Nonaka, I -- Vance, J M -- Kunkel, L M -- Ozawa, E -- NS23740/NS/NINDS NIH HHS/ -- P01-NS26630/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1995 Nov 3;270(5237):819-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Neuroscience, National Center for Neurology and Psychiatry, Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481775" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Chromosome Mapping ; *Chromosomes, Human, Pair 13 ; *Cytoskeletal Proteins ; DNA, Complementary/genetics ; Dystrophin/chemistry/genetics/metabolism ; Humans ; Linkage Disequilibrium ; Membrane Glycoproteins/chemistry/*genetics/metabolism ; Molecular Sequence Data ; Molecular Weight ; Muscle, Skeletal/chemistry/metabolism ; Muscular Dystrophies/*genetics ; Mutation ; Phenotype ; Rabbits ; Sarcoglycans ; Sequence Deletion
    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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  • 5
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    Late Wisconsin and early holocene glacial history, inner Ross Embayment, Antarctica (1991)
    In:  CASI
    Details
    Publication Date: 2013-08-31
    Description: Lateral drift sheets of outlet glaciers that pass through the Transantarctic Mountains constrain past changes of the huge Ross ice drainage system of the Antarctic Ice Sheet. Drift stratigraphy suggests correlation of Reedy III (Reedy Glacier), Beardmore, Britannia (Hatherton/Darwin Glaciers), Ross Sea (McMurdo Sound), and younger (Terra Nova Bay) drifts; radiocarbon dates place the outer limits of Ross Sea drift in late Wisconsin time at 24,000 to 13,000 yr B.P. Outlet glacier profiles from these drifts constrain late Wisconsin ice sheet surface elevations. Within these constraint, two extreme late Wisconsin reconstructions are given of the Ross ice drainage system. Both show little elevation change of the polar plateau coincident with extensive ice shelf grounding along the inner Ross Embayment. However, in the central Ross Embayment, one reconstruction shows floating shelf ice, where as the other shows a grounded ice sheet. Massive late Wisconsin/Holocene recession of grounded ice from the western Ross Embayment, which was underway at 13,040 yr B.P. and completed by 6600 to 6020 yr B.P., was accompanied by little change in plateau ice levels inland of the Transantarctic Mountains.
    Keywords: GEOPHYSICS
    Type: NASA. Goddard Space Flight Center, West Antarctic Ice Sheet Initiative. Volume 2: Discipline Reviews; p 55-86
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  • 6
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    Low-frequency fluctuations in the magnetosheath near the magnetopause (1995)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: There are four low-frequency modes which may propagate in a high-beta nearly bi-Maxwellian plasma. These are the magnetosonic, Alfven, ion acoustic, and mirror modes. This manuscript defines a procedure based on linear Vlasov theory for the unique identification of these modes by use of transport ratios, dimensionless ratios of the fluctuating field and plasma quantities. A single parameter, the mode deviation is calculated using the plasma and magnetic field data gathered by the Active Magnetospheric Particle Tracer Explorers/Ion Release Module (AMPTE/IRM) spacecraft to identify the modes observed in the terrestial magnetosheath near the magnetopause. As well as determining the mode which best describes the observed fluctuations, it gives us a measure of whether or not the resulting identification is unique. Using 17 time periods temporally close to a magnetopause crossing, and confining our study to the frequency range from 0.01 to 0.04 Hz, we find that the only clearly identified mode in this frequency range is the mirror mode. Most commonly, the quasi-perpendicular mirror mode (with wave vector k roughly perpendicular to the background magnetic field B(sub zero) is observed. In two events the quasi-parallel mirror mode k parallel B(sub zero) was identified.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 100; A4; p. 5665-5679
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  • 7
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    An MHD simulation study of the poloidal mode field line resonance in the Earth's dipole magnetosphere (1995)
    In:  Other Sources
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    Publication Date: 2019-07-13
    Description: The poloidal mode field line resonance in the Earth's dipole magnetic field is investigated using cold plasma ideal MHD simulations in dipole geometry. In order to excite the poloidal mode resonance, we use either an initial or a continuous velocity perturbation to drive the system. The perturbation is localized at magnetic shell L = 7 with plasma flow in the radial direction (electric field component in the azimuthal direction). It is found that with the initial perturbation alone, no polodial mode resonance can be obtained and the initially localized perturbation spreads out across all magnetic L shells. With the continuous perturbation, oscillating near the poloidal resonance frequency, a global-scale poloidal cavity mode can be obtained. For the first time, a localized guided poloidal mode resonance is obtained when a radial component of electric field is added to the initial perturbation such that the curl of the electric field is everywhere perpendicular to the background dipole magnetic field. During the localized poloidal resonance, plasma vortices parallel/antiparallel to the background dipole magnetic field B(sub 0). This circular flow, elongated radially, results in twisting of magnetic field flux tubes, which, in turn, leads to the slowdown of the circular plasma flow and reversal of the plasma vortices. The energy associated with the localized poloidal resonance is conserved as it shifts back and forth between the oscillating plasma vortices and the alternately twisted magnetic flux tubes. In the simulations the eigenfunctions associated with the localized poloidal resonance are grid-scale singular functions. This result indicates that ideal MHD is inadequate to describe the underlying problem and nonideal MHD effects are needed for mode broadening.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 100; A1; p. 63-77
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  • 8
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    Electromagnetic ion cyclotron waves in the plasma depletion layer (1993)
    In:  Other Sources
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    Publication Date: 2019-08-27
    Description: Results of a study of the theoretical properties of electromagnetic ion cyclotron (EMIC) waves which occur in the plasma depletion layer are presented. The analysis assumes a homogeneous plasma with the characteristics which were measured by the AMPTE/CCE satellite at 1450-1501 UT on October 5, 1984. Waves were observed in the Pc 1 frequency range below the hydrogen gyrofrequency, and these waves are identified as EMIC waves. The higher-frequency instability is driven by the temperature anisotropy of the H(+) ions, while the lower-frequency instability is driven by the temperature anisotropy of the He(2+) ions. It is argued that the higher-frequency waves will have k roughly parallel to B(0) and will be left-hand polarized, while the lower frequency wave band will have k oblique to B(0) and will be linearly polarized, in agreement with observations.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 98; A8; p. 13,477-13,490.
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  • 9
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    Low-frequency magnetic fluctuation spectra in the magnetosheath and plasma depletion layer (1994)
    In:  Other Sources
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    Publication Date: 2019-08-28
    Description: Recent observations have delineated several different kinds of enhanced magnetic fluctuation spectra below the proton cyclotron frequency in the terrestrial magnetosheath. A model is presented that represents the variation of plasma parameters across the plasma depletion layer and into the magnetosheath proper. Using this model, we find that many of the properties of the observed spectra follow directly from the predictions of linear Vlasov instability theory. The observed progression of spectral features is a natural progression from mirror mode to merged (in frequency range) proton and He(2+) cyclotron modes to bifurcated (in frequency range) cyclotron modes as plasma convects earthward in the magnetosheath. The necessary change in dispersion surface topology from separated proton and He(2+) cyclotron surfaces at low beta to merged surfaces at high beta is described.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 99; A4; p. 5893-5901
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  • 10
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    The proton cyclotron instability and the anisotropy/B inverse correlation (1994)
    In:  Other Sources
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    Publication Date: 2019-08-28
    Description: Spacecraft observations in the strongly compressed subsolar magnetosheath show an inverse correlation between the proton temperature anistrophy (T(sub perpendicular to p)/T(sub parallel to p) greater than 1 where perpendicular to and parallel to denote directions perpendicular and parallel to the background magnetic field) and the parallel proton beta (beta(sub parallel to p). This manuscript uses one-dimensional hybrid simulations of the proton cyclotron anisotropy instability in homogeneous electron-proton plasmas to study this correlation which may represent a limited closure relation for fluid theories of anisotropic space plasmas. The emphasis is on driven simulation which increase the temperature anisotropy by periodically reducing the magnetic-field-aligned velocities of the protons. The late-time states from ensembles of both initial value and driven simulations yield very similar expressions for the proton anisotropy/beta(sub parallel to P) inverse correlation, and provide a basis for explaining differences between sheath observations from different spacecraft. The driven simulations also yield expressions for the maximum instability growth rate and the fluctuating field energy as functions of beta (sub parallel to p) and a parameter characterizing the anisotropy driver.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 99; A4; p. 5903-5914
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