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  • 1
    Publication Date: 2014-08-15
    Description: Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hassaine, Gherici -- Deluz, Cedric -- Grasso, Luigino -- Wyss, Romain -- Tol, Menno B -- Hovius, Ruud -- Graff, Alexandra -- Stahlberg, Henning -- Tomizaki, Takashi -- Desmyter, Aline -- Moreau, Christophe -- Li, Xiao-Dan -- Poitevin, Frederic -- Vogel, Horst -- Nury, Hugues -- England -- Nature. 2014 Aug 21;512(7514):276-81. doi: 10.1038/nature13552. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] [3] Theranyx, 163 Avenue de Luminy, 13288 Marseille, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2]. ; Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland. ; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, CH-4058 Basel, Switzerland. ; Swiss Light Source, Paul Scherrer Institute, CH-5234 Villigen, Switzerland. ; Architecture et Fonction des Macromolecules Biologiques, CNRS UMR 7257 and Universite Aix-Marseille, F-13288 Marseille, France. ; 1] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [2] CNRS, IBS, F-38000 Grenoble, France [3] CEA, DSV, IBS, F-38000 Grenoble, France. ; Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Unite de Dynamique Structurale des Macromolecules, Institut Pasteur, CNRS UMR3528, F-75015 Paris, France. ; 1] Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland [2] Universite Grenoble Alpes, IBS, F-38000 Grenoble, France [3] CNRS, IBS, F-38000 Grenoble, France [4] CEA, DSV, IBS, F-38000 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119048" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Agents/metabolism ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Receptors, Serotonin, 5-HT3/*chemistry/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: 2013-08-14
    Description: The Kangdian iron oxide copper-gold (IOCG) metallogenic province contains a number of economically important Fe-Cu deposits in South China and northern Vietnam. Due to the lack of precise mineralization ages, the metallogenesis of this province has long been a matter of debate. In this study, molybdenite Re-Os, pyrite Re-Os, and Rb-Sr isotope methods are used to date the Yinachang and E’touchang Fe-Cu deposits in the central part of this province. Fine-grained (〈0.1 mm) molybdenite occurs as veinlets along bandings or fractures of magnetite ores and hydrothermal veins in the Yinachang deposit. Molybdenite separates from magnetite ores have highly reproducible Re-Os model ages of 1654 ± 7 Ma, whereas those from hydrothermal veins have a much younger Re-Os model age of 1451 ± 6 Ma. Euhedral pyrite grains occur locally along foliations of hematite ores and their proximal alteration assemblages in the E’touchang deposit. Pyrite separates have an Re-Os isochron age of 1487 ± 110 Ma and a single-grain Rb-Sr isochron age of 1453 ± 28 Ma, both of which are compatible with the molybdenite Re-Os age of hydrothermal veins from the Yinachang deposit. The molybdenite age of magnetite ores is in good agreement with zircon U-Pb ages of dolerite intrusions in the region, and is considered to represent the timing of a major ore formation event at ~1655 Ma. The younger Re-Os and Rb-Sr ages likely record a secondary hydrothermal overprint event at ~1450 Ma, which has not been recognized before. The mineralization potential and implications of this event need to be investigated in future studies. Our new isotopic data set hence demonstrates that the Kangdian IOCG deposits were likely formed at ~1655 Ma, synchronous with the late Paleoproterozoic intracontinental rifting event of the western Yangtze block.
    Print ISSN: 0361-0128
    Topics: Geosciences
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  • 3
    Publication Date: 2014-05-21
    Description: Atmospheric particle pollution is a serious environmental issue in China, especially the northern regions. Ambient air loadings (ng m−3), pollution sources and apportionment, and transport pathways of trace (Cd, Co, Cu, Ni, Pb, V, and Zn) and major (Al, Ca, Fe, and Mg) metals associated with inhalable particulate matters (PM10 aerosols) were characterized in urban, rural village, and rural field areas of seven cities (from inland in the west to the coast in the east: Wuwei, Yinchuan, Taiyuan, Beijing, Dezhou, Yantai, and Dalian) across northern China by taking one 72 h sample each site within a month for a whole year (April 2010 to March 2011). Ambient PM10 pollution in northern China is especially significant in the cold season (October–March) due to the combustion of coal for heating and dust storms in the winter and spring. Owing to variations in emission intensity and meteorological conditions, there is a trend of decrease in PM10 levels in cities from west to east. Both air PM10 and the associated metal loadings for urban and rural areas were comparable, showing that the current pattern of regional pollution in China differs from the decreasing urban–rural-background transect that is usual in other parts of the world. The average metal levels are Zn (276 ng m−3) ≫ Pb (93.7) ≫ Cu (54.9) ≫ Ni (9.37) 〉 V (8.34) ≫ Cd (2.84) 〉 Co (1.76). Judging from concentrations (mg kg−1), enrichment factors (EFs), a multivariate statistical analysis (principal component analysis, PCA), and a receptor model (absolute principal component scores-multiple linear regression analysis, APCS-MLR), the airborne trace metals (Zn, Pb, Cu, and Cd) in northern China were mainly anthropogenic, and mostly attributable to coal combustion and vehicle emissions with additional industrial sources. However, the Co was mostly of crustal origin, and the V and Ni were mainly from soil/dust in the western region and mostly from the petrochemical industry/oil combustion in the east. The accumulation of typical "urban metals" (Pb, Zn, Cd, and Cu) showed a trend of increase from west to east, indicating their higher anthropogenic contribution in eastern cities. The winter northwestern monsoon and westerly jet stream were the dominant forces in the long-range transport of airborne PM metals in northern China, with potentially global implications.
    Electronic ISSN: 1680-7375
    Topics: Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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