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  • Wiley-Blackwell  (119)
  • Nature Publishing Group (NPG)  (11)
  • 1
    Publication Date: 2008-05-16
    Description: Changes in past atmospheric carbon dioxide concentrations can be determined by measuring the composition of air trapped in ice cores from Antarctica. So far, the Antarctic Vostok and EPICA Dome C ice cores have provided a composite record of atmospheric carbon dioxide levels over the past 650,000 years. Here we present results of the lowest 200 m of the Dome C ice core, extending the record of atmospheric carbon dioxide concentration by two complete glacial cycles to 800,000 yr before present. From previously published data and the present work, we find that atmospheric carbon dioxide is strongly correlated with Antarctic temperature throughout eight glacial cycles but with significantly lower concentrations between 650,000 and 750,000 yr before present. Carbon dioxide levels are below 180 parts per million by volume (p.p.m.v.) for a period of 3,000 yr during Marine Isotope Stage 16, possibly reflecting more pronounced oceanic carbon storage. We report the lowest carbon dioxide concentration measured in an ice core, which extends the pre-industrial range of carbon dioxide concentrations during the late Quaternary by about 10 p.p.m.v. to 172-300 p.p.m.v.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luthi, Dieter -- Le Floch, Martine -- Bereiter, Bernhard -- Blunier, Thomas -- Barnola, Jean-Marc -- Siegenthaler, Urs -- Raynaud, Dominique -- Jouzel, Jean -- Fischer, Hubertus -- Kawamura, Kenji -- Stocker, Thomas F -- England -- Nature. 2008 May 15;453(7193):379-82. doi: 10.1038/nature06949.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Climate and Environmental Physics, Physics Institute, University of Bern, Sidlerstrasse 5, CH-3012 Bern, Switzerland. luethi@climate.unibe.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480821" target="_blank"〉PubMed〈/a〉
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  • 2
    Publication Date: 2008-04-11
    Description: Terrestrial vegetation, especially tropical rain forest, releases vast quantities of volatile organic compounds (VOCs) to the atmosphere, which are removed by oxidation reactions and deposition of reaction products. The oxidation is mainly initiated by hydroxyl radicals (OH), primarily formed through the photodissociation of ozone. Previously it was thought that, in unpolluted air, biogenic VOCs deplete OH and reduce the atmospheric oxidation capacity. Conversely, in polluted air VOC oxidation leads to noxious oxidant build-up by the catalytic action of nitrogen oxides (NO(x) = NO + NO2). Here we report aircraft measurements of atmospheric trace gases performed over the pristine Amazon forest. Our data reveal unexpectedly high OH concentrations. We propose that natural VOC oxidation, notably of isoprene, recycles OH efficiently in low-NO(x) air through reactions of organic peroxy radicals. Computations with an atmospheric chemistry model and the results of laboratory experiments suggest that an OH recycling efficiency of 40-80 per cent in isoprene oxidation may be able to explain the high OH levels we observed in the field. Although further laboratory studies are necessary to explore the chemical mechanism responsible for OH recycling in more detail, our results demonstrate that the biosphere maintains a remarkable balance with the atmospheric environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lelieveld, J -- Butler, T M -- Crowley, J N -- Dillon, T J -- Fischer, H -- Ganzeveld, L -- Harder, H -- Lawrence, M G -- Martinez, M -- Taraborrelli, D -- Williams, J -- England -- Nature. 2008 Apr 10;452(7188):737-40. doi: 10.1038/nature06870.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Chemistry, 27 Becherweg, 55128 Mainz, Germany. lelieveld@mpch-mainz.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401407" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atlantic Ocean ; Atmosphere/*chemistry ; Butadienes/metabolism ; French Guiana ; Guyana ; Hemiterpenes/metabolism ; Hydroxyl Radical/metabolism ; Nitric Oxide/metabolism ; Oxidation-Reduction ; Ozone/analysis ; Pentanes/metabolism ; Suriname ; Trees/*metabolism ; *Tropical Climate
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  • 3
    Publication Date: 2008-04-19
    Description: Past atmospheric methane concentrations show strong fluctuations in parallel to rapid glacial climate changes in the Northern Hemisphere superimposed on a glacial-interglacial doubling of methane concentrations. The processes driving the observed fluctuations remain uncertain but can be constrained using methane isotopic information from ice cores. Here we present an ice core record of carbon isotopic ratios in methane over the entire last glacial-interglacial transition. Our data show that the carbon in atmospheric methane was isotopically much heavier in cold climate periods. With the help of a box model constrained by the present data and previously published results, we are able to estimate the magnitude of past individual methane emission sources and the atmospheric lifetime of methane. We find that methane emissions due to biomass burning were about 45 Tg methane per year, and that these remained roughly constant throughout the glacial termination. The atmospheric lifetime of methane is reduced during cold climate periods. We also show that boreal wetlands are an important source of methane during warm events, but their methane emissions are essentially shut down during cold climate conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Hubertus -- Behrens, Melanie -- Bock, Michael -- Richter, Ulrike -- Schmitt, Jochen -- Loulergue, Laetitia -- Chappellaz, Jerome -- Spahni, Renato -- Blunier, Thomas -- Leuenberger, Markus -- Stocker, Thomas F -- England -- Nature. 2008 Apr 17;452(7189):864-7. doi: 10.1038/nature06825.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Alfred Wegener Institute for Polar and Marine Research, Columbusstrasse, 27568 Bremerhaven, Germany. hubertus.fischer@awi.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421351" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; *Biomass ; Carbon/analysis ; Carbon Isotopes ; Cold Climate ; Fires/*statistics & numerical data ; Greenland ; History, Ancient ; Hydrogen/analysis ; *Ice Cover ; Methane/*analysis/*chemistry/metabolism ; Monte Carlo Method ; *Temperature ; Trees/*metabolism ; Wetlands
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  • 4
    Publication Date: 2009-09-26
    Description: Reconstructions of atmospheric CO(2) concentrations based on Antarctic ice cores reveal significant changes during the Holocene epoch, but the processes responsible for these changes in CO(2) concentrations have not been unambiguously identified. Distinct characteristics in the carbon isotope signatures of the major carbon reservoirs (ocean, biosphere, sediments and atmosphere) constrain variations in the CO(2) fluxes between those reservoirs. Here we present a highly resolved atmospheric delta(13)C record for the past 11,000 years from measurements on atmospheric CO(2) trapped in an Antarctic ice core. From mass-balance inverse model calculations performed with a simplified carbon cycle model, we show that the decrease in atmospheric CO(2) of about 5 parts per million by volume (p.p.m.v.). The increase in delta(13)C of about 0.25 per thousand during the early Holocene is most probably the result of a combination of carbon uptake of about 290 gigatonnes of carbon by the land biosphere and carbon release from the ocean in response to carbonate compensation of the terrestrial uptake during the termination of the last ice age. The 20 p.p.m.v. increase of atmospheric CO(2) and the small decrease in delta(13)C of about 0.05 per thousand during the later Holocene can mostly be explained by contributions from carbonate compensation of earlier land-biosphere uptake and coral reef formation, with only a minor contribution from a small decrease of the land-biosphere carbon inventory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elsig, Joachim -- Schmitt, Jochen -- Leuenberger, Daiana -- Schneider, Robert -- Eyer, Marc -- Leuenberger, Markus -- Joos, Fortunat -- Fischer, Hubertus -- Stocker, Thomas F -- England -- Nature. 2009 Sep 24;461(7263):507-10. doi: 10.1038/nature08393.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Climate and Environmental Physics, Physics Institute, University of Bern, Sidlerstrasse 5, CH-3012 Bern, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779448" target="_blank"〉PubMed〈/a〉
    Keywords: Air/analysis ; Animals ; Antarctic Regions ; Anthozoa/growth & development/metabolism ; Atmosphere/chemistry ; Carbon/*analysis/*metabolism ; Carbon Dioxide/analysis/*metabolism ; Carbon Isotopes ; Climate ; Ecosystem ; History, Ancient ; Ice Cover/*chemistry ; Time Factors
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  • 5
    Publication Date: 2009-06-23
    Description: In fasted mammals, circulating pancreatic glucagon stimulates hepatic gluconeogenesis in part through the CREB regulated transcription coactivator 2 (CRTC2, also referred to as TORC2). Hepatic glucose production is increased in obesity, reflecting chronic increases in endoplasmic reticulum (ER) stress that promote insulin resistance. Whether ER stress also modulates the gluconeogenic program directly, however, is unclear. Here we show that CRTC2 functions as a dual sensor for ER stress and fasting signals. Acute increases in ER stress triggered the dephosphorylation and nuclear entry of CRTC2, which in turn promoted the expression of ER quality control genes through an association with activating transcription factor 6 alpha (ATF6alpha, also known as ATF6)--an integral branch of the unfolded protein response. In addition to mediating CRTC2 recruitment to ER stress inducible promoters, ATF6alpha also reduced hepatic glucose output by disrupting the CREB-CRTC2 interaction and thereby inhibiting CRTC2 occupancy over gluconeogenic genes. Conversely, hepatic glucose output was upregulated when hepatic ATF6alpha protein amounts were reduced, either by RNA interference (RNAi)-mediated knockdown or as a result of persistent stress in obesity. Because ATF6alpha overexpression in the livers of obese mice reversed CRTC2 effects on the gluconeogenic program and lowered hepatic glucose output, our results demonstrate how cross-talk between ER stress and fasting pathways at the level of a transcriptional coactivator contributes to glucose homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730924/" 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/PMC2730924/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yiguo -- Vera, Liliana -- Fischer, Wolfgang H -- Montminy, Marc -- R01 DK064142/DK/NIDDK NIH HHS/ -- R01 DK064142-06/DK/NIDDK NIH HHS/ -- R01 DK083834/DK/NIDDK NIH HHS/ -- R01 DK083834-25/DK/NIDDK NIH HHS/ -- R37 DK083834/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Jul 23;460(7254):534-7. doi: 10.1038/nature08111. Epub 2009 Jun 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 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/19543265" target="_blank"〉PubMed〈/a〉
    Keywords: Activating Transcription Factor 6 ; Animals ; Cell Nucleus/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Endoplasmic Reticulum/*metabolism ; Fasting/*physiology ; Gene Expression Regulation ; Gluconeogenesis/*physiology ; Liver/*metabolism ; Male ; Membrane Proteins/metabolism ; Mice ; Obesity/physiopathology ; Protein Transport ; Stress, Physiological/*physiology ; Trans-Activators/*metabolism ; Transcription Factors/*metabolism
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  • 6
    Publication Date: 2014-12-17
    Description: Nitrous oxide (N2O) is an important greenhouse gas and ozone-depleting substance that has anthropogenic as well as natural marine and terrestrial sources. The tropospheric N2O concentrations have varied substantially in the past in concert with changing climate on glacial-interglacial and millennial timescales. It is not well understood, however, how N2O emissions from marine and terrestrial sources change in response to varying environmental conditions. The distinct isotopic compositions of marine and terrestrial N2O sources can help disentangle the relative changes in marine and terrestrial N2O emissions during past climate variations. Here we present N2O concentration and isotopic data for the last deglaciation, from 16,000 to 10,000 years before present, retrieved from air bubbles trapped in polar ice at Taylor Glacier, Antarctica. With the help of our data and a box model of the N2O cycle, we find a 30 per cent increase in total N2O emissions from the late glacial to the interglacial, with terrestrial and marine emissions contributing equally to the overall increase and generally evolving in parallel over the last deglaciation, even though there is no a priori connection between the drivers of the two sources. However, we find that terrestrial emissions dominated on centennial timescales, consistent with a state-of-the-art dynamic global vegetation and land surface process model that suggests that during the last deglaciation emission changes were strongly influenced by temperature and precipitation patterns over land surfaces. The results improve our understanding of the drivers of natural N2O emissions and are consistent with the idea that natural N2O emissions will probably increase in response to anthropogenic warming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schilt, Adrian -- Brook, Edward J -- Bauska, Thomas K -- Baggenstos, Daniel -- Fischer, Hubertus -- Joos, Fortunat -- Petrenko, Vasilii V -- Schaefer, Hinrich -- Schmitt, Jochen -- Severinghaus, Jeffrey P -- Spahni, Renato -- Stocker, Thomas F -- England -- Nature. 2014 Dec 11;516(7530):234-7. doi: 10.1038/nature13971.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, Oregon 97331, USA [2] Climate and Environmental Physics, Physics Institute, and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; College of Earth, Ocean, and Atmospheric Sciences, Oregon State University, Corvallis, Oregon 97331, USA. ; Scripps Institution of Oceanography, University of California, San Diego, California 92037, USA. ; Climate and Environmental Physics, Physics Institute, and Oeschger Centre for Climate Change Research, University of Bern, 3012 Bern, Switzerland. ; Department of Earth and Environmental Sciences, University of Rochester, Rochester, New York 14627, USA. ; National Institute of Water and Atmospheric Research, Wellington 6021, New Zealand.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503236" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Aquatic Organisms/*metabolism ; Atmosphere/*chemistry ; Global Warming ; History, Ancient ; *Ice Cover ; Nitrogen Isotopes/analysis ; Nitrous Oxide/analysis/history/*metabolism ; Oxygen Isotopes/analysis ; Rain ; Temperature ; Time Factors
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  • 7
    Publication Date: 2015-01-28
    Description: Comets are composed of dust and frozen gases. The ices are mixed with the refractory material either as an icy conglomerate, or as an aggregate of pre-solar grains (grains that existed prior to the formation of the Solar System), mantled by an ice layer. The presence of water-ice grains in periodic comets is now well established. Modelling of infrared spectra obtained about ten kilometres from the nucleus of comet Hartley 2 suggests that larger dust particles are being physically decoupled from fine-grained water-ice particles that may be aggregates, which supports the icy-conglomerate model. It is known that comets build up crusts of dust that are subsequently shed as they approach perihelion. Micrometre-sized interplanetary dust particles collected in the Earth's stratosphere and certain micrometeorites are assumed to be of cometary origin. Here we report that grains collected from the Jupiter-family comet 67P/Churyumov-Gerasimenko come from a dusty crust that quenches the material outflow activity at the comet surface. The larger grains (exceeding 50 micrometres across) are fluffy (with porosity over 50 per cent), and many shattered when collected on the target plate, suggesting that they are agglomerates of entities in the size range of interplanetary dust particles. Their surfaces are generally rich in sodium, which explains the high sodium abundance in cometary meteoroids. The particles collected to date therefore probably represent parent material of interplanetary dust particles. This argues against comet dust being composed of a silicate core mantled by organic refractory material and then by a mixture of water-dominated ices. At its previous recurrence (orbital period 6.5 years), the comet's dust production doubled when it was between 2.7 and 2.5 astronomical units from the Sun, indicating that this was when the nucleus shed its mantle. Once the mantle is shed, unprocessed material starts to supply the developing coma, radically changing its dust component, which then also contains icy grains, as detected during encounters with other comets closer to the Sun.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schulz, Rita -- Hilchenbach, Martin -- Langevin, Yves -- Kissel, Jochen -- Silen, Johan -- Briois, Christelle -- Engrand, Cecile -- Hornung, Klaus -- Baklouti, Donia -- Bardyn, Anais -- Cottin, Herve -- Fischer, Henning -- Fray, Nicolas -- Godard, Marie -- Lehto, Harry -- Le Roy, Lena -- Merouane, Sihane -- Orthous-Daunay, Francois-Regis -- Paquette, John -- Ryno, Jouni -- Siljestrom, Sandra -- Stenzel, Oliver -- Thirkell, Laurent -- Varmuza, Kurt -- Zaprudin, Boris -- England -- Nature. 2015 Feb 12;518(7538):216-8. doi: 10.1038/nature14159. Epub 2015 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Space Agency, Scientific Support Office, Keplerlaan 1, Postbus 299, 2200 AG Noordwijk, The Netherlands. ; Max-Planck-Institut fur Sonnensystemforschung, Justus-von-Liebig-Weg 3, 37077 Gottingen, Germany. ; Institut d'Astrophysique Spatiale, CNRS/Universite Paris Sud, Batiment 121, 91405 Orsay, France. ; Finnish Meteorological Institute, Observation services, Erik Palmenin aukio 1, FI-00560 Helsinki, Finland. ; Laboratoire de Physique et Chimie de l'Environnement et de l'Espace (LPC2E), CNRS/Universite d'Orleans, 45071 Orleans, France. ; Centre de Sciences Nucleaires et de Sciences de la Matiere, CNRS/IN2P3-Universite Paris Sud-UMR8609, Batiment 104, 91405 Orsay campus, France. ; Universitat der Bundeswehr, LRT-7, Werner Heisenberg Weg 39, 85577 Neubiberg, Germany. ; 1] Laboratoire de Physique et Chimie de l'Environnement et de l'Espace (LPC2E), CNRS/Universite d'Orleans, 45071 Orleans, France [2] Laboratoire Interuniversitaire des Systemes Atmospheriques (LISA), UMR CNRS 7583, Universite Paris Est Creteil et Universite Paris Diderot, Institut Pierre Simon Laplace, 94000 Creteil, France. ; Laboratoire Interuniversitaire des Systemes Atmospheriques (LISA), UMR CNRS 7583, Universite Paris Est Creteil et Universite Paris Diderot, Institut Pierre Simon Laplace, 94000 Creteil, France. ; University of Turku, Department of Physics and Astronomy, Tuorla Observatory Vaisalantie 20, 21500 Piikkio, Finland. ; Center for Space and Habitability (CSH), University of Bern, Sidlerstrasse 5, 3012 Bern, Switzerland. ; Universite Grenoble Alpes/CNRS, Institut de Planetologie et d'Astrophysique de Grenoble, 414 Rue de la Piscine, Domaine Universitaire, 38000 Grenoble, France. ; Department of Chemistry, Materials and Surfaces, SP Technical Research Institute of Sweden, Box 857, 50115 Boras, Sweden. ; Institut fur Statistik und Wahrscheinlichkeitstheorie, Technische Universitat Wien, Wiedner Hauptstrasse 7, 1040 Wien, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25624103" target="_blank"〉PubMed〈/a〉
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  • 8
    Publication Date: 2014-07-25
    Description: Magnetic devices are a leading contender for the implementation of memory and logic technologies that are non-volatile, that can scale to high density and high speed, and that do not wear out. However, widespread application of magnetic memory and logic devices will require the development of efficient mechanisms for reorienting their magnetization using the least possible current and power. There has been considerable recent progress in this effort; in particular, it has been discovered that spin-orbit interactions in heavy-metal/ferromagnet bilayers can produce strong current-driven torques on the magnetic layer, via the spin Hall effect in the heavy metal or the Rashba-Edelstein effect in the ferromagnet. In the search for materials to provide even more efficient spin-orbit-induced torques, some proposals have suggested topological insulators, which possess a surface state in which the effects of spin-orbit coupling are maximal in the sense that an electron's spin orientation is fixed relative to its propagation direction. Here we report experiments showing that charge current flowing in-plane in a thin film of the topological insulator bismuth selenide (Bi2Se3) at room temperature can indeed exert a strong spin-transfer torque on an adjacent ferromagnetic permalloy (Ni81Fe19) thin film, with a direction consistent with that expected from the topological surface state. We find that the strength of the torque per unit charge current density in Bi2Se3 is greater than for any source of spin-transfer torque measured so far, even for non-ideal topological insulator films in which the surface states coexist with bulk conduction. Our data suggest that topological insulators could enable very efficient electrical manipulation of magnetic materials at room temperature, for memory and logic applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellnik, A R -- Lee, J S -- Richardella, A -- Grab, J L -- Mintun, P J -- Fischer, M H -- Vaezi, A -- Manchon, A -- Kim, E-A -- Samarth, N -- Ralph, D C -- England -- Nature. 2014 Jul 24;511(7510):449-51. doi: 10.1038/nature13534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cornell University, Ithaca, New York 14853, USA. ; Department of Physics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Cornell University, Ithaca, New York 14853, USA [2] Weizmann Institute of Science, Rehovot 76100, Israel. ; King Abdullah University of Science and Technology, Physical Sciences and Engineering Division, Thuwal 23955-6900, Saudi Arabia. ; 1] Cornell University, Ithaca, New York 14853, USA [2] Kavli Institute at Cornell, Ithaca, New York 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25056062" target="_blank"〉PubMed〈/a〉
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2011-10-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Edmond Henri -- England -- Nature. 2011 Oct 12;478(7368):S5. doi: 10.1038/478S5a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21993825" target="_blank"〉PubMed〈/a〉
    Keywords: *Biochemistry/history ; Disease ; History, 20th Century ; History, 21st Century ; Life ; *Nobel Prize ; Phosphorylation
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  • 10
    Publication Date: 2012-04-13
    Description: In the fasted state, increases in circulating glucagon promote hepatic glucose production through induction of the gluconeogenic program. Triggering of the cyclic AMP pathway increases gluconeogenic gene expression via the de-phosphorylation of the CREB co-activator CRTC2 (ref. 1). Glucagon promotes CRTC2 dephosphorylation in part through the protein kinase A (PKA)-mediated inhibition of the CRTC2 kinase SIK2. A number of Ser/Thr phosphatases seem to be capable of dephosphorylating CRTC2 (refs 2, 3), but the mechanisms by which hormonal cues regulate these enzymes remain unclear. Here we show in mice that glucagon stimulates CRTC2 dephosphorylation in hepatocytes by mobilizing intracellular calcium stores and activating the calcium/calmodulin-dependent Ser/Thr-phosphatase calcineurin (also known as PP3CA). Glucagon increased cytosolic calcium concentration through the PKA-mediated phosphorylation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs), which associate with CRTC2. After their activation, InsP(3)Rs enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2. During feeding, increases in insulin signalling reduced CRTC2 activity via the AKT-mediated inactivation of InsP(3)Rs. InsP(3)R activity was increased in diabetes, leading to upregulation of the gluconeogenic program. As hepatic downregulation of InsP(3)Rs and calcineurin improved circulating glucose levels in insulin resistance, these results demonstrate how interactions between cAMP and calcium pathways at the level of the InsP(3)R modulate hepatic glucose production under fasting conditions and in diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343222/" 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/PMC3343222/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yiguo -- Li, Gang -- Goode, Jason -- Paz, Jose C -- Ouyang, Kunfu -- Screaton, Robert -- Fischer, Wolfgang H -- Chen, Ju -- Tabas, Ira -- Montminy, Marc -- HL087123/HL/NHLBI NIH HHS/ -- P01 HL087123/HL/NHLBI NIH HHS/ -- P01 HL087123-05/HL/NHLBI NIH HHS/ -- R01 DK049777/DK/NIDDK NIH HHS/ -- R01 DK049777-19/DK/NIDDK NIH HHS/ -- R01 DK091618/DK/NIDDK NIH HHS/ -- R01 DK091618-02/DK/NIDDK NIH HHS/ -- R01-DK049777/DK/NIDDK NIH HHS/ -- R01-DK083834/DK/NIDDK NIH HHS/ -- R01-DK091618/DK/NIDDK NIH HHS/ -- R37 DK083834/DK/NIDDK NIH HHS/ -- R37 DK083834-29/DK/NIDDK NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Apr 8;485(7396):128-32. doi: 10.1038/nature10988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 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/22495310" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/*metabolism ; Calcineurin/metabolism ; Calcium/metabolism ; Calcium Signaling ; Cells, Cultured ; Cyclic AMP/metabolism ; Diabetes Mellitus/blood/genetics/*metabolism ; Fasting/blood/*metabolism ; Gene Expression Regulation/drug effects ; Glucagon/pharmacology ; *Gluconeogenesis/genetics ; HEK293 Cells ; Hepatocytes/metabolism ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Insulin Resistance ; Liver/cytology/*metabolism ; Mice ; Phosphorylation/drug effects ; Trans-Activators/metabolism ; 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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