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  • 1
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    Alternative standardization approaches to improving streamflow reconstructions with ring-width indices of riparian trees (2015)
    Sage
    In: Holocene
    Details
    Publication Date: 2015-06-06
    Description: Old, multi-aged populations of riparian trees provide an opportunity to improve reconstructions of streamflow. Here, ring widths of 394 plains cottonwood ( Populus deltoides , ssp. monilifera ) trees in the North Unit of Theodore Roosevelt National Park, North Dakota, are used to reconstruct streamflow along the Little Missouri River (LMR), North Dakota, US. Different versions of the cottonwood chronology are developed by (1) age-curve standardization (ACS), using age-stratified samples and a single estimated curve of ring width against estimated ring age, and (2) time-curve standardization (TCS), using a subset of longer ring-width series individually detrended with cubic smoothing splines of width against year. The cottonwood chronologies are combined with the first principal component of four upland conifer chronologies developed by conventional methods to investigate the possible value of riparian tree-ring chronologies for streamflow reconstruction of the LMR. Regression modeling indicates that the statistical signal for flow is stronger in the riparian cottonwood than in the upland chronologies. The flow signal from cottonwood complements rather than repeats the signal from upland conifers and is especially strong in young trees (e.g. 5–35 years). Reconstructions using a combination of cottonwoods and upland conifers are found to explain more than 50% of the variance of LMR flow over a 1935–1990 calibration period and to yield reconstruction of flow to 1658. The low-frequency component of reconstructed flow is sensitive to the choice of standardization method for the cottonwood. In contrast to the TCS version, the ACS reconstruction features persistent low flows in the 19th century. Results demonstrate the value to streamflow reconstruction of riparian cottonwood and suggest that more studies are needed to exploit the low-frequency streamflow signal in densely sampled age-stratified stands of riparian trees.
    Print ISSN: 0959-6836
    Electronic ISSN: 1477-0911
    Topics: Geography , Geosciences
    Published by Sage
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  • 2
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    Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-04-03
    Description: We report the development of a pseudorabies virus that can be used for retrograde tracing from selected neurons. This virus encodes a green fluorescent protein marker and replicates only in neurons that express the Cre recombinase and in neurons in synaptic contact with the originally infected cells. The virus was injected into the arcuate nucleus of mice that express Cre only in those neurons that express neuropeptide Y or the leptin receptor. Sectioning of the brains revealed that these neurons receive inputs from neurons in other regions of the hypothalamus, as well as the amygdala, cortex, and other brain regions. These data suggest that higher cortical centers modulate leptin signaling in the hypothalamus. This method of neural tracing may prove useful in studies of other complex neural circuits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeFalco, J -- Tomishima, M -- Liu, H -- Zhao, C -- Cai, X -- Marth, J D -- Enquist, L -- Friedman, J M -- DK48247/DK/NIDDK NIH HHS/ -- R01133506/PHS HHS/ -- R01DK41096/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 30;291(5513):2608-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11283374" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways ; Animals ; Arcuate Nucleus of Hypothalamus/cytology/*physiology/virology ; Brain/cytology/*physiology/virology ; Brain Mapping ; Carrier Proteins/genetics/metabolism ; Chromosomes, Artificial, Bacterial ; *Eating ; Gene Expression ; Green Fluorescent Proteins ; Herpesvirus 1, Suid/*genetics/physiology ; Hypothalamus/cytology/*physiology/virology ; Integrases/genetics/metabolism ; Luminescent Proteins/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/*metabolism/virology ; Neuropeptide Y/genetics/metabolism ; *Receptors, Cell Surface ; Receptors, Leptin ; Recombinant Fusion Proteins/metabolism ; Recombination, Genetic ; *Viral Proteins ; Virus Replication ; tau Proteins/genetics/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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    UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-08-01
    Description: The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101536/" 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/PMC4101536/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andrews, Zane B -- Liu, Zhong-Wu -- Walllingford, Nicholas -- Erion, Derek M -- Borok, Erzsebet -- Friedman, Jeffery M -- Tschop, Matthias H -- Shanabrough, Marya -- Cline, Gary -- Shulman, Gerald I -- Coppola, Anna -- Gao, Xiao-Bing -- Horvath, Tamas L -- Diano, Sabrina -- R01 AG022880/AG/NIA NIH HHS/ -- R01 DK040936/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Aug 14;454(7206):846-51. doi: 10.1038/nature07181. Epub 2008 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Comparative Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, Howard Hughes Medical Institute, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18668043" target="_blank"〉PubMed〈/a〉
    Keywords: Agouti-Related Protein/genetics/*metabolism ; Animals ; Carnitine O-Palmitoyltransferase/metabolism ; Fatty Acids/metabolism ; Feeding Behavior/drug effects ; Gene Expression Regulation/drug effects ; Ghrelin/*metabolism/pharmacology ; Hypothalamus/drug effects/metabolism ; Ion Channels/genetics/*metabolism ; Membrane Potential, Mitochondrial/drug effects/physiology ; Mice ; Mitochondria/drug effects/physiology ; Mitochondrial Proteins/genetics/*metabolism ; Neurons/drug effects/*metabolism ; Neuropeptide Y/genetics/*metabolism ; Phosphorylation/drug effects ; Reactive Oxygen Species/*metabolism ; Synapses/drug effects/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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  • 4
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    Obesity: Causes and control of excess body fat (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-05-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedman, Jeffrey M -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 May 21;459(7245):340-2. doi: 10.1038/459340a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458707" target="_blank"〉PubMed〈/a〉
    Keywords: Adiposity/genetics/physiology ; Amyloid/therapeutic use ; Asian Continental Ancestry Group ; Body Mass Index ; Body Weight/genetics/physiology ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Energy Metabolism ; Feedback, Physiological ; Feeding Behavior/*physiology ; Humans ; Islet Amyloid Polypeptide ; Leptin/genetics/metabolism/therapeutic use ; Neural Pathways/physiology ; Obesity/epidemiology/genetics/*physiopathology/therapy ; Receptors, Leptin/genetics/metabolism ; United States/epidemiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-06-26
    Description: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kohlstaedt, L A -- Wang, J -- Friedman, J M -- Rice, P A -- Steitz, T A -- GM 39546/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jun 26;256(5065):1783-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1377403" target="_blank"〉PubMed〈/a〉
    Keywords: Azepines/pharmacology ; Binding Sites ; Crystallography ; DNA Polymerase I/chemistry ; Escherichia coli/genetics ; HIV-1/*enzymology ; Models, Molecular ; Molecular Structure ; Nevirapine ; Protein Conformation ; Pyridines/pharmacology ; RNA-Directed DNA Polymerase/*chemistry
    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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  • 6
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    Human chromosome 7: DNA sequence and biology (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-04-12
    Description: DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" 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/PMC2882961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scherer, Stephen W -- Cheung, Joseph -- MacDonald, Jeffrey R -- Osborne, Lucy R -- Nakabayashi, Kazuhiko -- Herbrick, Jo-Anne -- Carson, Andrew R -- Parker-Katiraee, Layla -- Skaug, Jennifer -- Khaja, Razi -- Zhang, Junjun -- Hudek, Alexander K -- Li, Martin -- Haddad, May -- Duggan, Gavin E -- Fernandez, Bridget A -- Kanematsu, Emiko -- Gentles, Simone -- Christopoulos, Constantine C -- Choufani, Sanaa -- Kwasnicka, Dorota -- Zheng, Xiangqun H -- Lai, Zhongwu -- Nusskern, Deborah -- Zhang, Qing -- Gu, Zhiping -- Lu, Fu -- Zeesman, Susan -- Nowaczyk, Malgorzata J -- Teshima, Ikuko -- Chitayat, David -- Shuman, Cheryl -- Weksberg, Rosanna -- Zackai, Elaine H -- Grebe, Theresa A -- Cox, Sarah R -- Kirkpatrick, Susan J -- Rahman, Nazneen -- Friedman, Jan M -- Heng, Henry H Q -- Pelicci, Pier Giuseppe -- Lo-Coco, Francesco -- Belloni, Elena -- Shaffer, Lisa G -- Pober, Barbara -- Morton, Cynthia C -- Gusella, James F -- Bruns, Gail A P -- Korf, Bruce R -- Quade, Bradley J -- Ligon, Azra H -- Ferguson, Heather -- Higgins, Anne W -- Leach, Natalia T -- Herrick, Steven R -- Lemyre, Emmanuelle -- Farra, Chantal G -- Kim, Hyung-Goo -- Summers, Anne M -- Gripp, Karen W -- Roberts, Wendy -- Szatmari, Peter -- Winsor, Elizabeth J T -- Grzeschik, Karl-Heinz -- Teebi, Ahmed -- Minassian, Berge A -- Kere, Juha -- Armengol, Lluis -- Pujana, Miguel Angel -- Estivill, Xavier -- Wilson, Michael D -- Koop, Ben F -- Tosi, Sabrina -- Moore, Gudrun E -- Boright, Andrew P -- Zlotorynski, Eitan -- Kerem, Batsheva -- Kroisel, Peter M -- Petek, Erwin -- Oscier, David G -- Mould, Sarah J -- Dohner, Hartmut -- Dohner, Konstanze -- Rommens, Johanna M -- Vincent, John B -- Venter, J Craig -- Li, Peter W -- Mural, Richard J -- Adams, Mark D -- Tsui, Lap-Chee -- 38103/Canadian Institutes of Health Research/Canada -- P01 GM061354/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8. steve@genet.sickkids.on.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690205" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics ; Chromosome Aberrations ; Chromosome Fragile Sites ; Chromosome Fragility ; Chromosome Mapping ; Chromosomes, Human, Pair 7/*genetics ; Computational Biology ; Congenital Abnormalities/genetics ; CpG Islands ; DNA, Complementary ; Databases, Genetic ; Euchromatin/genetics ; Expressed Sequence Tags ; Gene Duplication ; Genes, Overlapping ; Genetic Diseases, Inborn/genetics ; Genomic Imprinting ; Humans ; In Situ Hybridization, Fluorescence ; Limb Deformities, Congenital/genetics ; Mice ; Molecular Sequence Data ; Mutation ; Neoplasms/genetics ; Pseudogenes ; RNA/genetics ; Retroelements ; *Sequence Analysis, DNA ; Williams Syndrome/genetics
    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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  • 7
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    A war on obesity, not the obese (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-02-08
    Description: In their efforts to lose weight, obese individuals may be fighting a powerful set of evolutionary forces honed in an environment drastically different from that of today.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedman, Jeffrey M -- R01-DK41096/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2003 Feb 7;299(5608):856-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, The Rockefeller University, 1230 New York Avenue, New York, NY 10021. USA. friedj@mail.rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12574619" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism ; Body Mass Index ; Body Weight ; Diet ; Energy Intake ; Energy Metabolism ; Feeding Behavior ; Female ; Genes ; Homeostasis ; Humans ; Hunger ; Incidence ; Leptin/metabolism/therapeutic use ; Life Style ; Male ; *Obesity/epidemiology/genetics/physiopathology/prevention & control ; Public Health ; Selection, Genetic ; United States/epidemiology ; Weight Loss
    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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  • 8
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    Rapid rewiring of arcuate nucleus feeding circuits by leptin (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-04-06
    Description: The fat-derived hormone leptin regulates energy balance in part by modulating the activity of neuropeptide Y and proopiomelanocortin neurons in the hypothalamic arcuate nucleus. To study the intrinsic activity of these neurons and their responses to leptin, we generated mice that express distinct green fluorescent proteins in these two neuronal types. Leptin-deficient (ob/ob) mice differed from wild-type mice in the numbers of excitatory and inhibitory synapses and postsynaptic currents onto neuropeptide Y and proopiomelanocortin neurons. When leptin was delivered systemically to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake. These data suggest that leptin-mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's behavioral effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinto, Shirly -- Roseberry, Aaron G -- Liu, Hongyan -- Diano, Sabrina -- Shanabrough, Marya -- Cai, Xiaoli -- Friedman, Jeffrey M -- Horvath, Tamas L -- DK060711/DK/NIDDK NIH HHS/ -- F32DK61176/DK/NIDDK NIH HHS/ -- F32NS046921/NS/NINDS NIH HHS/ -- R01 DK041096/DK/NIDDK NIH HHS/ -- R01 DK061619/DK/NIDDK NIH HHS/ -- RR014451/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2004 Apr 2;304(5667):110-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15064421" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arcuate Nucleus of Hypothalamus/cytology/*physiology ; Body Weight/drug effects ; Eating ; Evoked Potentials ; Excitatory Postsynaptic Potentials ; *Feeding Behavior/drug effects ; Ghrelin ; Glutamic Acid/analysis ; Green Fluorescent Proteins ; In Vitro Techniques ; Leptin/genetics/pharmacology/*physiology ; Luminescent Proteins/analysis ; Mice ; Mice, Obese ; Mice, Transgenic ; Neuronal Plasticity/*physiology ; Neurons/drug effects/*physiology ; Neuropeptide Y/genetics/physiology ; Patch-Clamp Techniques ; Peptide Hormones/pharmacology ; Pro-Opiomelanocortin/genetics/physiology ; Recombinant Fusion Proteins/analysis ; Synapses/chemistry/ultrastructure ; Tetrodotoxin/pharmacology ; Transgenes ; gamma-Aminobutyric Acid/analysis
    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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  • 9
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    Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-07-13
    Description: Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver. Leptin was found to specifically repress RNA levels and enzymatic activity of hepatic stearoyl-CoA desaturase-1 (SCD-1), which catalyzes the biosynthesis of monounsaturated fatty acids. Mice lacking SCD-1 were lean and hypermetabolic. ob/ob mice with mutations in SCD-1 were significantly less obese than ob/ob controls and had markedly increased energy expenditure. ob/ob mice with mutations in SCD-1 had histologically normal livers with significantly reduced triglyceride storage and VLDL (very low density lipoprotein) production. These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Paul -- Miyazaki, Makoto -- Socci, Nicholas D -- Hagge-Greenberg, Aaron -- Liedtke, Wolfgang -- Soukas, Alexander A -- Sharma, Ratnendra -- Hudgins, Lisa C -- Ntambi, James M -- Friedman, Jeffrey M -- GM07739/GM/NIGMS NIH HHS/ -- R01-DK41096/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 12;297(5579):240-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics, Center for Studies in Physics and Biology, Rogosin Institute, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12114623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Weight ; Crosses, Genetic ; Down-Regulation ; Eating ; Energy Metabolism ; Female ; Gene Expression ; Gene Expression Profiling ; Leptin/genetics/*physiology ; Lipid Metabolism ; Lipids/analysis ; Lipoproteins, VLDL/metabolism ; Liver/*enzymology/metabolism/ultrastructure ; Male ; Mice ; Mice, Obese ; Microsomes, Liver/enzymology ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oxygen Consumption ; RNA, Messenger/genetics/metabolism ; Stearoyl-CoA Desaturase/genetics/*metabolism ; Vacuoles/chemistry/ultrastructure ; *Weight Loss
    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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  • 10
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    Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-12-14
    Description: Ventral tegmental area (VTA) dopamine neurons in the brain's reward circuit have a crucial role in mediating stress responses, including determining susceptibility versus resilience to social-stress-induced behavioural abnormalities. VTA dopamine neurons show two in vivo patterns of firing: low frequency tonic firing and high frequency phasic firing. Phasic firing of the neurons, which is well known to encode reward signals, is upregulated by repeated social-defeat stress, a highly validated mouse model of depression. Surprisingly, this pathophysiological effect is seen in susceptible mice only, with no apparent change in firing rate in resilient individuals. However, direct evidence--in real time--linking dopamine neuron phasic firing in promoting the susceptible (depression-like) phenotype is lacking. Here we took advantage of the temporal precision and cell-type and projection-pathway specificity of optogenetics to show that enhanced phasic firing of these neurons mediates susceptibility to social-defeat stress in freely behaving mice. We show that optogenetic induction of phasic, but not tonic, firing in VTA dopamine neurons of mice undergoing a subthreshold social-defeat paradigm rapidly induced a susceptible phenotype as measured by social avoidance and decreased sucrose preference. Optogenetic phasic stimulation of these neurons also quickly induced a susceptible phenotype in previously resilient mice that had been subjected to repeated social-defeat stress. Furthermore, we show differences in projection-pathway specificity in promoting stress susceptibility: phasic activation of VTA neurons projecting to the nucleus accumbens (NAc), but not to the medial prefrontal cortex (mPFC), induced susceptibility to social-defeat stress. Conversely, optogenetic inhibition of the VTA-NAc projection induced resilience, whereas inhibition of the VTA-mPFC projection promoted susceptibility. Overall, these studies reveal novel firing-pattern- and neural-circuit-specific mechanisms of depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554860/" 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/PMC3554860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaudhury, Dipesh -- Walsh, Jessica J -- Friedman, Allyson K -- Juarez, Barbara -- Ku, Stacy M -- Koo, Ja Wook -- Ferguson, Deveroux -- Tsai, Hsing-Chen -- Pomeranz, Lisa -- Christoffel, Daniel J -- Nectow, Alexander R -- Ekstrand, Mats -- Domingos, Ana -- Mazei-Robison, Michelle S -- Mouzon, Ezekiell -- Lobo, Mary Kay -- Neve, Rachael L -- Friedman, Jeffrey M -- Russo, Scott J -- Deisseroth, Karl -- Nestler, Eric J -- Han, Ming-Hu -- F31 MH095425/MH/NIMH NIH HHS/ -- F32 MH096464/MH/NIMH NIH HHS/ -- K99 MH094405/MH/NIMH NIH HHS/ -- R01 MH092306/MH/NIMH NIH HHS/ -- R25 GM064118/GM/NIGMS NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- T32 MH087004/MH/NIMH NIH HHS/ -- T32 MH096678/MH/NIMH NIH HHS/ -- England -- Nature. 2013 Jan 24;493(7433):532-6. doi: 10.1038/nature11713. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Systems Therapeutics, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Depression/etiology/*physiopathology ; Dopaminergic Neurons/*metabolism ; Food Preferences ; Male ; Mesencephalon/*cytology ; Mice ; Neural Pathways ; Nucleus Accumbens/physiology ; Optogenetics ; Phenotype ; Prefrontal Cortex/physiology ; *Social Behavior ; Stress, Psychological/complications/*physiopathology ; Sucrose/administration & dosage ; Time Factors ; Ventral Tegmental Area/physiology
    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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