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  • 1
    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
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  • 2
    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
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  • 3
    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
    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
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  • 5
    Publication Date: 2019-07-18
    Description: The storm-time inner magnetospheric electric field morphology and dynamics are assessed by comparing numerical modeling results of the plasmasphere and ring current with many in situ and remote sensing data sets. Two magnetic storms are analyzed, April 22,2001 and October 21-23,2001, which are the events selected for the Geospace Environment Modeling (GEM) Inner Magnetosphere/Storms (IM/S) Assessment Challenge (IMSAC). The IMSAC seeks to quantify the accuracy of inner magnetospheric models as well as synthesize our understanding of this region. For each storm, the ring current-atmosphere interaction model (RAM) and the dynamic global core plasma model (DGCPM) were run together with various settings for the large-scale convection electric field and the nightside ionospheric conductance. DGCPM plasmaspheric parameters were compared with IMAGE-EUV plasmapause extractions and LANL-MPA plume locations and velocities. RAM parameters were compared with Dst*, LANL-MPA fluxes and moments, IMAGE-MENA images, and IMAGE-HENA images. Both qualitative and quantitative comparisons were made to determine the electric field morphology that allows the model results to best fit the plasma data at various times during these events. The simulations with self-consistent electric fields were, in general, better than those with prescribed field choices. This indicates that the time-dependent modulation of the inner magnetospheric electric fields by the nightside ionosphere is quite significant for accurate determination of these fields (and their effects). It was determined that a shielded Volland-Stern field description driven by the 3-hour Kp index yields accurate results much of the time, but can be quite inconsistent. The modified Mcllwain field description clearly lagged in overall accuracy compared to the other fields, but matched some data sets (like Dst*) quite well. The rankings between the simulations varied depending on the storm and the individual data sets, indicating that each field description did well for some place, time, and energy range during the events, as well as doing less well in other places, times, and energies. Several unresolved issues regarding the storm-time inner magnetospheric electric field are discussed.
    Keywords: Geophysics
    Format: text
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  • 6
    Publication Date: 2019-07-13
    Description: The sample return capsule of the Stardust spacecraft will be recovered in northern Utah on January 15, 2006, and under nominal conditions it will be delivered to the new Stardust Curation Laboratory at the Johnson Space Center two days later. Within the first week we plan to begin the harvesting of aerogel cells, and the comet nucleus samples they contain for detailed analysis. By the time of the LPSC meeting we will have been analyzing selected removed grains for more than one month. This presentation will present the first results from the mineralogical and petrological analyses that will have been performed.
    Keywords: Geophysics
    Type: Ipsc; Mar 11, 2006 - Mar 17, 2006; Houston, TX; United States
    Format: application/pdf
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  • 7
    Publication Date: 2019-07-13
    Description: Latitudinal variations in the nighttime plasma temperatures of the equatorial topside ionosphere during northern winter at solar maximum have been examined by using values modelled by SUPIM (Sheffield University Plasmasphere Ionosphere Model) and observations made by the DMSP F10 satellite at 21.00 LT near 800 km altitude. The modelled values confirm that the crests observed near 15 deg latitude in the winter hemisphere are due to adiabatic heating and the troughs observed near the magnetic equator are due to adiabatic cooling as plasma is transported along the magnetic field lines from the summer hemisphere to the winter hemisphere. The modelled values also confirm that the interhemispheric plasma transport needed to produce the required adiabatic heating/cooling can be induced by F-region neutral winds. It is shown that the longitudinal variations in the observed troughs and crests arise mainly from the longitudinal variations in the magnetic meridional wind. At longitudes where the magnetic declination angle is positive the eastward geographic zonal wind combines with the northward (summer hemisphere to winter hemisphere) geographic meridional wind to enhance the northward magnetic meridional wind. This leads to deeper troughs and enhanced crests. At longitudes where the magnetic declination angle is negative the eastward geographic zonal wind opposes the northward geographic meridional wind and the trough depth and crest values are reduced. The characteristic features of the troughs and crests depend, in a complicated manner, on the field-aligned flow of plasma, thermal conduction, and inter-gas heat transfer. At the latitudes of the troughs/crests, the low/high plasma temperatures lead to increased/decreased plasma concentrations.
    Keywords: Geophysics
    Type: Annales Geophysicae; 18; 1435-1446
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