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  • 1
    Publication Date: 2011-07-06
    Description: The biogenesis and maintenance of the endoplasmic reticulum (ER) requires membrane fusion. ER homotypic fusion is driven by the large GTPase atlastin. Domain analysis of atlastin shows that a conserved region of the C-terminal cytoplasmic tail is absolutely required for fusion activity. Atlastin in adjacent membranes must associate to bring the ER membranes into molecular contact. Drosophila atlastin dimerizes in the presence of GTPγS but is monomeric with GDP or without nucleotide. Oligomerization requires the juxtamembrane middle domain three-helix bundle, as does efficient GTPase activity. A soluble version of the N-terminal cytoplasmic domain that contains the GTPase domain and the middle domain three-helix bundle serves as a potent, concentration-dependent inhibitor of membrane fusion both in vitro and in vivo. However, atlastin domains lacking the middle domain are without effect. GTP-dependent dimerization of atlastin generates an enzymatically active protein that drives membrane fusion after nucleotide hydrolysis and conformational reorganization.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2011-09-28
    Description: The mechanisms governing atlastin-mediated membrane fusion are unknown. Here we demonstrate that a three-helix bundle (3HB) within the middle domain is required for oligomerization. Mutation of core hydrophobic residues within these helices inactivates atlastin function by preventing membrane tethering and the subsequent fusion. GTP binding induces a conformational change that reorients the GTPase domain relative to the 3HB to permit self-association, but the ability to hydrolyze GTP is required for full fusion, indicating that nucleotide binding and hydrolysis play distinct roles. Oligomerization of atlastin stimulates its ability to hydrolyze GTP, and the energy released drives lipid bilayer merger. Mutations that prevent atlastin self-association also abolish oligomerization-dependent stimulation of GTPase activity. Furthermore, increasing the distance of atlastin complex formation from the membrane inhibits fusion, suggesting that this distance is crucial for atlastin to promote fusion.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2009-07-28
    Description: Establishment and maintenance of proper architecture is essential for endoplasmic reticulum (ER) function. Homotypic membrane fusion is required for ER biogenesis and maintenance, and has been shown to depend on GTP hydrolysis. Here we demonstrate that Drosophila Atlastin--the fly homologue of the mammalian GTPase atlastin 1 involved in hereditary spastic paraplegia--localizes on ER membranes and that its loss causes ER fragmentation. Drosophila Atlastin embedded in distinct membranes has the ability to form trans-oligomeric complexes and its overexpression induces enlargement of ER profiles, consistent with excessive fusion of ER membranes. In vitro experiments confirm that Atlastin autonomously drives membrane fusion in a GTP-dependent fashion. In contrast, GTPase-deficient Atlastin is inactive, unable to form trans-oligomeric complexes owing to failure to self-associate, and incapable of promoting fusion in vitro. These results demonstrate that Atlastin mediates membrane tethering and fusion and strongly suggest that it is the GTPase activity that is required for ER homotypic fusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orso, Genny -- Pendin, Diana -- Liu, Song -- Tosetto, Jessica -- Moss, Tyler J -- Faust, Joseph E -- Micaroni, Massimo -- Egorova, Anastasia -- Martinuzzi, Andrea -- McNew, James A -- Daga, Andrea -- GM71832/GM/NIGMS NIH HHS/ -- GTF08001/Telethon/Italy -- R01 GM071832/GM/NIGMS NIH HHS/ -- TCR08004/Telethon/Italy -- England -- Nature. 2009 Aug 20;460(7258):978-83. doi: 10.1038/nature08280. Epub 2009 Jul 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eugenio Medea Scientific Institute, Conegliano 31015, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19633650" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila Proteins/deficiency/genetics/*metabolism ; Drosophila melanogaster/*cytology/*enzymology/genetics ; *Dynamins ; Endoplasmic Reticulum/*metabolism/pathology ; GTP Phosphohydrolases/deficiency/genetics/*metabolism ; HeLa Cells ; Humans ; *Membrane Fusion ; Protein Transport ; Proteolipids/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1995-04-28
    Description: The Son of sevenless (Sos) protein functions as a guanine nucleotide transfer factor for Ras and interacts with the receptor tyrosine kinase Sevenless through the protein Drk, a homolog of mammalian Grb2. In vivo structure-function analysis revealed that the amino terminus of Sos was essential for its function in flies. A molecule lacking the amino terminus was a potent dominant negative. In contrast, a Sos fragment lacking the Drk binding sites was functional and its activity was dependent on the presence of the Sevenless receptor. Furthermore, membrane localization of Sos was independent of Drk. A possible role for Drk as an activator of Sos is discussed and a Drk-independent interaction between Sos and Sevenless is proposed that is likely mediated by the pleckstrin homology domain within the amino terminus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlovich, C A -- Bonfini, L -- McCollam, L -- Rogge, R D -- Daga, A -- Czech, M P -- Banerjee, U -- GM-07104/GM/NIGMS NIH HHS/ -- GM-08375/GM/NIGMS NIH HHS/ -- R01EY08152-06/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1995 Apr 28;268(5210):576-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Molecular Biology Institute, University of California, Los Angeles 90024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7725106" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Membrane/metabolism ; Drosophila ; *Drosophila Proteins ; Eye Proteins/*metabolism ; Guanine Nucleotide Exchange Factors ; Insect Hormones/physiology ; Membrane Glycoproteins/*metabolism ; Membrane Proteins/chemistry/*metabolism ; Photoreceptor Cells, Invertebrate/cytology/metabolism ; Proteins/*metabolism ; Receptor Protein-Tyrosine Kinases/*metabolism ; Signal Transduction ; Son of Sevenless Proteins ; ras Guanine Nucleotide Exchange Factors
    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: 2007-06-30
    Description: Circadian and other natural clock-like endogenous rhythms may have evolved to anticipate regular temporal changes in the environment. We report that a mutation in the circadian clock gene timeless in Drosophila melanogaster has arisen and spread by natural selection relatively recently in Europe. We found that, when introduced into different genetic backgrounds, natural and artificial alleles of the timeless gene affect the incidence of diapause in response to changes in light and temperature. The natural mutant allele alters an important life history trait that may enhance the fly's adaptation to seasonal conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tauber, Eran -- Zordan, Mauro -- Sandrelli, Federica -- Pegoraro, Mirko -- Osterwalder, Nicolo -- Breda, Carlo -- Daga, Andrea -- Selmin, Alessandro -- Monger, Karen -- Benna, Clara -- Rosato, Ezio -- Kyriacou, Charalambos P -- Costa, Rodolfo -- New York, N.Y. -- Science. 2007 Jun 29;316(5833):1895-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17600215" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Base Sequence ; Circadian Rhythm/genetics ; Drosophila Proteins/*genetics/physiology ; Drosophila melanogaster/*genetics/*physiology ; Europe ; Evolution, Molecular ; Female ; Geography ; Haplotypes ; Molecular Sequence Data ; Mutation ; *Photoperiod ; Phylogeny ; Polymorphism, Genetic ; Protein Isoforms/genetics/physiology ; Reproduction ; *Seasons ; *Selection, Genetic ; Temperature ; Transformation, Genetic
    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
    Publication Date: 2016-12-25
    Description: The crater lake and associated hydrothermal features of Copahue volcano have been studied intensively over the last 20 years (1995–2015). The geochemical and isotopic compositions of the waters provide insights into the processes occurring in the volcanic–hydrothermal system, the crater lake and the thermal springs. Variations in the temperature and chemical composition of the waters reveal fundamental changes in the system that precede and accompany the magmatic and phreatic eruptive events at Copahue. A conceptual model of the summit system was developed involving the intrusion of slivers of magma in the hot acidic hydrothermal cell, the saturation of waters with secondary minerals leading to reduced permeability, the blocking of fluid pathways by liquid sulphur during heating events and the transport of gas from the magma through the ductile–brittle transition into the hydrothermal system. Geophysical data were integrated with the chemical data to provide new insights into the behaviour of the deep magmatic system that feeds the volcano edifice. Multidisciplinary studies were used to identify precursory signals of eruptive activity to give an early warning of pending volcanic hazards. Several geochemical ratios in river water were identified as potential indicators of upcoming volcanic activity, which could be used in co-operation with the community and local authorities to deal with these volcanic hazards.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
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  • 7
    ISSN: 1432-1041
    Keywords: hyperlipoproteinaemia ; fenofibrate ; single daily dose ; plasma lipids ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The safety and efficacy of a single daily dose of fenofibrate (200 mg) have been evaluated in 12 Type IIB hyperlipidaemic patients in a three-month study. At the same time the pharmacokinetics was studied to check whether this new dosage schedule would give a therapeutic plasma levels of fenofibrate. At the single daily dose of 200 mg, fenofibrate was highly effective, very well tolerated, and it reached therapeutic plasma levels without accumulation. It appears that fenofibrate can usefully be employed at this dosage in hyperlipidaemia, especially since patient compliance is better when only one daily dose need be taken.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Photochemistry and Photobiology B: Biology 2 (1988), S. 515-521 
    ISSN: 1011-1344
    Keywords: Photoaddition ; UV-A. ; angelicin ; unsaturated lipids
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 90 (2001), S. 1509-1515 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Pb(Zr, Ti)O3 (PZT) thin films with (100) preferred orientation were prepared using metalorganic chemical vapor deposition on LaNiO3 (LNO) buffered platinized Si with thickness varying from 25–100 nm. The dependence of electrical properties of PZT films on thickness was studied using several techniques, including polarization–electric field (P–E), temperature variable current–voltage (I–V), and capacitance–voltage (C–V) measurements. Because of the formation of Schottky barriers at ferroelectric/electrode interfaces, built-in electric fields are present. A progressive increment in carrier concentration and interfacial built-in electric field versus reducing PZT film thickness was observed, which is believed to be a dominant factor controlling the measured dielectric/ferroelectric properties. The higher built-in electric field in thinner PZT films would pin the dipoles at the interfacial region and retard the response of dipoles to the external electric field. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 79 (2001), S. 3782-3784 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Dense, high-index, and reproducible scandium oxide (Sc2O3) thin films with high mechanical strength were grown on glass substrates by metalorganic chemical-vapor deposition. The influence of deposition temperature on the microstructure evolution and optical properties of Sc2O3 thin films was investigated by x-ray diffraction, scanning electron microscopy, atomic-force microscopy, transmission electron microscopy, and spectrophotometry. A close relationship between microstructure and optical properties was found for Sc2O3 thin films prepared at different deposition temperatures. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
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