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  • 1
    Publication Date: 2012-01-13
    Description: Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-gamma co-activator-1 alpha (PGC1-alpha). Here we show in mouse that PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522098/" 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/PMC3522098/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bostrom, Pontus -- Wu, Jun -- Jedrychowski, Mark P -- Korde, Anisha -- Ye, Li -- Lo, James C -- Rasbach, Kyle A -- Bostrom, Elisabeth Almer -- Choi, Jang Hyun -- Long, Jonathan Z -- Kajimura, Shingo -- Zingaretti, Maria Cristina -- Vind, Birgitte F -- Tu, Hua -- Cinti, Saverio -- Hojlund, Kurt -- Gygi, Steven P -- Spiegelman, Bruce M -- DK31405/DK/NIDDK NIH HHS/ -- DK54477/DK/NIDDK NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R01 DK054477/DK/NIDDK NIH HHS/ -- R01 DK061562/DK/NIDDK NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- England -- Nature. 2012 Jan 11;481(7382):463-8. doi: 10.1038/nature10777.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237023" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/drug effects/metabolism ; Adipose Tissue, Brown/*cytology/drug effects/metabolism ; Adipose Tissue, White/*cytology/drug effects/metabolism ; Animals ; Cell Respiration/drug effects ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Energy Metabolism/drug effects/genetics/physiology ; Exercise/physiology ; Gene Expression Regulation/drug effects/genetics ; Hormones/metabolism/secretion ; Humans ; Insulin Resistance/physiology ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Ion Channels/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Mitochondrial Proteins/metabolism ; Models, Animal ; Muscle Cells/metabolism ; Obesity/blood/chemically induced/prevention & control ; Physical Conditioning, Animal/physiology ; Plasma/chemistry ; Subcutaneous Fat/cytology/drug effects/metabolism ; *Thermogenesis/drug effects/genetics ; Trans-Activators/deficiency/genetics/*metabolism/secretion ; Transcription Factors
    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: 2014-12-19
    Description: Carbon-carbon (C-C) bonds form the backbone of many important molecules, including polymers, dyes and pharmaceutical agents. The development of new methods to create these essential connections in a rapid and practical fashion has been the focus of numerous organic chemists. This endeavour relies heavily on the ability to form C-C bonds in the presence of sensitive functional groups and congested structural environments. Here we report a chemical transformation that allows the facile construction of highly substituted and uniquely functionalized C-C bonds. Using a simple iron catalyst, an inexpensive silane and a benign solvent under ambient atmosphere, heteroatom-substituted olefins are easily reacted with electron-deficient olefins to create molecular architectures that were previously difficult or impossible to access. More than 60 examples are presented with a wide array of substrates, demonstrating the chemoselectivity and mildness of this simple reaction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271735/" 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/PMC4271735/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo, Julian C -- Gui, Jinghan -- Yabe, Yuki -- Pan, Chung-Mao -- Baran, Phil S -- GM-097444/GM/NIGMS NIH HHS/ -- R01 GM097444/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Dec 18;516(7531):343-8. doi: 10.1038/nature14006.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519131" target="_blank"〉PubMed〈/a〉
    Keywords: Alkenes/*chemistry ; Carbon/*chemistry ; Chemistry Techniques, Synthetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2007-04-14
    Description: Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin (LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators of key enzymes that control lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein receptor-deficient mice, which lack the ability to control lipid levels in the blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin beta receptor decoy protein attenuated the dyslipidemia. These results suggest that the immune system directly influences lipid metabolism and that LT modulating agents may represent a novel therapeutic route for the treatment of dyslipidemia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo, James C -- Wang, Yugang -- Tumanov, Alexei V -- Bamji, Michelle -- Yao, Zemin -- Reardon, Catherine A -- Getz, Godfrey S -- Fu, Yang-Xin -- 5 T32 GM07281/GM/NIGMS NIH HHS/ -- AI062026/AI/NIAID NIH HHS/ -- CA097296/CA/NCI NIH HHS/ -- DK58891/DK/NIDDK NIH HHS/ -- HL 85516/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):285-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431181" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dyslipidemias/drug therapy/etiology/metabolism ; Female ; Homeostasis ; Humans ; Hypercholesterolemia/etiology ; *Lipid Metabolism ; Lipids/blood ; Liver/*metabolism ; Lymphotoxin beta Receptor/*metabolism/therapeutic use ; Lymphotoxin-alpha/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; T-Lymphocytes/metabolism ; Tumor Necrosis Factor Ligand Superfamily Member ; 14/genetics/*metabolism/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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  • 4
    Publication Date: 2015-05-23
    Description: The synthesis and functionalization of amines are fundamentally important in a vast range of chemical contexts. We present an amine synthesis that repurposes two simple feedstock building blocks: olefins and nitro(hetero)arenes. Using readily available reactants in an operationally simple procedure, the protocol smoothly yields secondary amines in a formal olefin hydroamination. Because of the presumed radical nature of the process, hindered amines can easily be accessed in a highly chemoselective transformation. A screen of more than 100 substrate combinations showcases tolerance of numerous unprotected functional groups such as alcohols, amines, and even boronic acids. This process is orthogonal to other aryl amine syntheses, such as the Buchwald-Hartwig, Ullmann, and classical amine-carbonyl reductive aminations, as it tolerates aryl halides and carbonyl compounds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gui, Jinghan -- Pan, Chung-Mao -- Jin, Ying -- Qin, Tian -- Lo, Julian C -- Lee, Bryan J -- Spergel, Steven H -- Mertzman, Michael E -- Pitts, William J -- La Cruz, Thomas E -- Schmidt, Michael A -- Darvatkar, Nitin -- Natarajan, Swaminathan R -- Baran, Phil S -- GM-097444/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):886-91. doi: 10.1126/science.aab0245. Epub 2015 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA. ; Discovery Chemistry, Bristol-Myers Squibb, Princeton, NJ 08543, USA. ; Chemical Development, Bristol-Myers Squibb, New Brunswick, NJ 08903, USA. ; Kemxtree LLC, 1370 Hamilton Street, Somerset, NJ 08873, USA. ; Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA. pbaran@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999503" target="_blank"〉PubMed〈/a〉
    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: 2017-02-23
    Description: A new exceptionally preserved marginal marine biota is reported from the Late Ordovician Big Hill Formation of Stonington Peninsula in Michigan's Upper Peninsula. The new Lagerstätte hosts a moderately diverse fauna of medusae, linguloid brachiopods, non-mineralized arthropods and orthocone nautiloids, alongside dasycladalean green algae. The biota is similar to those of Lagerstätten from the Late Ordovician of Canada, revealing an extensive distribution of a distinctive marginal marine palaeocommunity in Laurentia at this time. The Big Hill biota extends the geographical range of exceptionally preserved Late Ordovician faunas in Laurentia and indicates that further examples remain to be discovered.
    Print ISSN: 0016-7649
    Topics: Geosciences
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  • 6
    Publication Date: 2017-01-07
    Description: A new exceptionally preserved marginal marine biota is reported from the Late Ordovician Big Hill Formation of Stonington Peninsula in Michigan's Upper Peninsula. The new Lagerstätte hosts a moderately diverse fauna of medusae, linguloid brachiopods, non-mineralized arthropods and orthocone nautiloids, alongside dasycladalean green algae. The biota is similar to those of Lagerstätten from the Late Ordovician of Canada, revealing an extensive distribution of a distinctive marginal marine palaeocommunity in Laurentia at this time. The Big Hill biota extends the geographical range of exceptionally preserved Late Ordovician faunas in Laurentia and indicates that further examples remain to be discovered.
    Print ISSN: 0016-7649
    Topics: Geosciences
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  • 7
  • 8
    Publication Date: 2016-05-12
    Description: The sleep–wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep–wake-dependent regulation of cognition in 16 men and 18 women in...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
  • 10
    Publication Date: 2011-04-27
    Description: The cysteine-rich secretory proteins (CRISPs) are a group of four proteins in the mouse that are expressed abundantly in the male reproductive tract, and to a lesser extent in other tissues. Analysis of reptile CRISPs and mouse CRISP2 has shown that CRISPs can regulate cellular homeostasis via ion channels. With the exception of the ability of CRISP2 to regulate ryanodine receptors, the in vivo targets of mammalian CRISPs function are unknown. In this study, we have characterized the ion channel regulatory activity of epididymal CRISP4 using electrophysiology, cell assays, and mouse models. Through patch-clamping of testicular sperm, the CRISP4 CRISP domain was shown to inhibit the transient receptor potential (TRP) ion channel TRPM8. These data were confirmed using a stably transfected CHO cell line. TRPM8 is a major cold receptor in the body, but is found in other tissues, including the testis and on the tail and head of mouse and human sperm. Functional assays using sperm from wild-type mice showed that TRPM8 activation significantly reduced the number of sperm undergoing the progesterone-induced acrosome reaction following capacitation, and that this response was reversed by the coaddition of CRISP4. In accordance, sperm from Crisp4 null mice had a compromised ability to undergo to the progesterone-induced acrosome reaction. Collectively, these data identify CRISP4 as an endogenous regulator of TRPM8 with a role in normal sperm function.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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