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  • 1
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    Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-14
    Description: Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saitoh, Tatsuya -- Fujita, Naonobu -- Jang, Myoung Ho -- Uematsu, Satoshi -- Yang, Bo-Gie -- Satoh, Takashi -- Omori, Hiroko -- Noda, Takeshi -- Yamamoto, Naoki -- Komatsu, Masaaki -- Tanaka, Keiji -- Kawai, Taro -- Tsujimura, Tohru -- Takeuchi, Osamu -- Yoshimori, Tamotsu -- Akira, Shizuo -- AI070167/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Nov 13;456(7219):264-8. doi: 10.1038/nature07383. Epub 2008 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18849965" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/analogs & derivatives/pharmacology ; Animals ; Autophagy/*genetics ; Carrier Proteins/*genetics ; Chimera ; Colitis/chemically induced/immunology ; Dextran Sulfate/pharmacology ; Female ; Gene Expression Regulation/*drug effects ; Interleukin-1beta/*biosynthesis/metabolism ; Lipopolysaccharides/*pharmacology ; Macrophages/*drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Mutation
    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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  • 2
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    Discovery of Atg5/Atg7-independent alternative macroautophagy (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-02
    Description: Macroautophagy is a process that leads to the bulk degradation of subcellular constituents by producing autophagosomes/autolysosomes. It is believed that Atg5 (ref. 4) and Atg7 (ref. 5) are essential genes for mammalian macroautophagy. Here we show, however, that mouse cells lacking Atg5 or Atg7 can still form autophagosomes/autolysosomes and perform autophagy-mediated protein degradation when subjected to certain stressors. Although lipidation of the microtubule-associated protein light chain 3 (LC3, also known as Map1lc3a) to form LC3-II is generally considered to be a good indicator of macroautophagy, it did not occur during the Atg5/Atg7-independent alternative process of macroautophagy. We also found that this alternative process of macroautophagy was regulated by several autophagic proteins, including Unc-51-like kinase 1 (Ulk1) and beclin 1. Unlike conventional macroautophagy, autophagosomes seemed to be generated in a Rab9-dependent manner by the fusion of isolation membranes with vesicles derived from the trans-Golgi and late endosomes. In vivo, Atg5-independent alternative macroautophagy was detected in several embryonic tissues. It also had a function in clearing mitochondria during erythroid maturation. These results indicate that mammalian macroautophagy can occur through at least two different pathways: an Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishida, Yuya -- Arakawa, Satoko -- Fujitani, Kenji -- Yamaguchi, Hirofumi -- Mizuta, Takeshi -- Kanaseki, Toku -- Komatsu, Masaaki -- Otsu, Kinya -- Tsujimoto, Yoshihide -- Shimizu, Shigeomi -- England -- Nature. 2009 Oct 1;461(7264):654-8. doi: 10.1038/nature08455.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19794493" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins/metabolism ; Autophagy/drug effects/*physiology ; Etoposide/pharmacology ; Fibroblasts/cytology/drug effects/metabolism ; Food Deprivation ; Mice ; Mice, Knockout ; Microtubule-Associated Proteins/*deficiency/genetics/metabolism ; Phagosomes/drug effects/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; rab GTP-Binding Proteins/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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  • 3
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    Autophagy regulates lipid metabolism (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-03
    Description: The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676208/" 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/PMC2676208/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, Rajat -- Kaushik, Susmita -- Wang, Yongjun -- Xiang, Youqing -- Novak, Inna -- Komatsu, Masaaki -- Tanaka, Keiji -- Cuervo, Ana Maria -- Czaja, Mark J -- K01 DK087776/DK/NIDDK NIH HHS/ -- P01 AG031782/AG/NIA NIH HHS/ -- P01 AG031782-01A1/AG/NIA NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 AG021904/AG/NIA NIH HHS/ -- R01 AG021904-07/AG/NIA NIH HHS/ -- R01 DK061498/DK/NIDDK NIH HHS/ -- R01 DK061498-05/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1131-5. doi: 10.1038/nature07976. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339967" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/drug effects/*physiology ; Cell Line ; Cholesterol/metabolism ; Dietary Fats/pharmacology ; Fatty Acids/*metabolism ; Food Deprivation ; Hepatocytes/cytology/drug effects/metabolism ; *Lipid Metabolism/drug effects ; Lipolysis/drug effects ; Liver/cytology/drug effects/metabolism ; Lysosomes/metabolism ; Mice ; Microtubule-Associated Proteins/deficiency/genetics ; Oxidation-Reduction ; Phagosomes/metabolism ; Rats ; Triglycerides/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
    Electronic Resource
    Electronic Resource
    Spontaneous alloying of copper atoms into gold clusters at reduced temperatures (1993)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 73 (1993), S. 1100-1103 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The alloying behavior of copper atoms into gold clusters at temperatures lower than 300 K was examined using a 200 kV transmission electron microscope equipped with a double source evaporator in the specimen chamber. Isolated gold clusters of about 4 nm in mean diameter were prepared on a supporting film and were cooled down to 245, 215, 165, or 125 K. Copper atoms were then deposited onto the same film. Upon the deposition of copper, the gold clusters quickly changed into completely or partially alloyed clusters, depending upon the substrate temperature. The copper diffusivity estimated from such spontaneous alloying was many orders of magnitude faster than that in bulk gold. A possible mechanism behind the spontaneous alloying is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.353272
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  • 5
    Electronic Resource
    Electronic Resource
    Alloying behavior of gold atoms into nm-sized copper clusters (1992)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 61 (1992), S. 2173-2174 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Alloying behavior of gold atoms into copper clusters has been studied using a 200 kV transmission electron microscope (TEM) equipped with a double source evaporator in the specimen chamber. Isolated copper clusters of approximately 4 nm in diameter were first prepared on a supporting film of amorphous carbon, and then gold atoms were deposited onto the same film kept at room temperature. Upon the deposition of gold, the copper clusters quickly changed into homogeneously mixed Cu-Au alloy clusters. The gold diffusivities in the clusters estimated from the experimental results are at least 19 orders of magnitude faster than those in the bulk copper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.108285
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  • 6
    Electronic Resource
    Electronic Resource
    Metamorphism and granite genesis in the Hidaka Metamorphic Belt, Hokkaido, Japan (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of metamorphic geology 9 (1991), S. 0 
    Details
    ISSN: 1525-1314
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: The Main Zone of the Hidaka Metamorphic Belt is an uplifted crustal section of island-arc type. The crust was formed during early Tertiary time, as a result of collision between two arc–trench systems of Cretaceous age. The crustal metamorphic sequence is divided into four metamorphic zones (I–IV), in which zone IV is in the granulite facies.A detailed study of the evolution of the Hidaka Belt, based on a revised P–T–t analysis of the metamorphic rocks, notably a newly found staurolite-bearing granulite, confirms a prograde isobaric heating path, after a supposed event of tectonic thickening of accretionary sedimentary and oceanic crustal rocks. During the peak metamorphic event (c. 53 Ma), the regional geothermal gradient attained 33–40° C km−1, and the highest P–T condition obtained from the lowest part of the granulite unit is 830° C, 7 kbar. In this part, XH2O of Gt–Opx–Cd gneiss is about 0.15 and that of Gt–Cd–Bt gneiss is 0.4. The P–T–XH2O condition of the granulite unit is well within a field where fluid-present partial melting of pelitic and greywacke metamorphic rocks takes place. This is in harmony with the restitic nature of the Gt–Opx–Cd gneiss in the lowest part of the granulite unit.The possibility that partial melting took place in the Main Zone is significant for the genesis of the peraluminous (S-type) granitic rocks within it. The S-type granitic rocks in this zone are Opx–Gt–Bt tonalite in the granulite zone, Gt–Cd–Bt tonalite in the amphibolite zone, and Cd–Bt–Mus tonalite in the Bt–Mus gneiss zone. The mineralogical and chemical nature of these strongly peraluminous tonalitic rocks permit them to be regarded as having been derived from S-type granitic magma generated by crustal anatexis of pelitic metamorphic rocks in deeper crust.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1525-1314.1991.tb00508.x
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  • 7
    Electronic Resource
    Electronic Resource
    High-strength silicon nitride ceramics obtained by grain-boundary crystallization (1991)
    Springer
    Journal of materials science 26 (1991), S. 5513-5516 
    Details
    ISSN: 1573-4803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A monolithic type of toughened silicon nitride ceramics has been developed from Si3N4-Y2O3 systems. However, because of the existence of a second phase, the fracture strength decreases at elevated temperatures. To improve the high-temperature strength of silicon nitride, some additional components were investigated. It was found that the addition of hafnia to the Si3N4-Y2O3-AIN system gave a greater high-temperature strength based on the promotion of grain-boundary phase crystallization: namely, 126 kg mm−2 in 3-point bend strength at 1300 °C for the hot-pressed specimen, and 90 kg mm−2 at 1300 °C for the pressureless sintered specimen. The role of the hafnia in crystallization is not yet clear, and is being characterized by electron microscopy and microanalysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553652
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  • 8
    Electronic Resource
    Electronic Resource
    Corrosion of silicon nitride ceramics under hydrothermal conditions (1991)
    Springer
    Journal of materials science 26 (1991), S. 1749-1754 
    Details
    ISSN: 1573-4803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Corrosion behaviour of Si3N4 ceramics containing Y2O3, Al2O3 and AIN as sintering aids was investigated under hydrothermal conditions at 200–300
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543597
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  • 9
    Electronic Resource
    Electronic Resource
    High-strength silicon nitride ceramics obtained by grain-boundary crystallization (1991)
    Springer
    Journal of materials science 26 (1991), S. 5513-5516 
    Details
    ISSN: 1573-4803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A monolithic type of toughened silicon nitride ceramics has been developed from Si3N4-Y2O3 systems. However, because of the existence of a second phase, the fracture strength decreases at elevated temperatures. To improve the high-temperature strength of silicon nitride, some additional components were investigated. It was found that the addition of hafnia to the Si3N4-Y2O3-AIN system gave a greater high-temperature strength based on the promotion of grain-boundary phase crystallization: namely, 126 kg mm−2 in 3-point bend strength at 1300 °C for the hot-pressed specimen, and 90 kg mm−2 at 1300 °C for the pressureless sintered specimen. The role of the hafnia in crystallization is not yet clear, and is being characterized by electron microscopy and microanalysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02403951
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  • 10
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    Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds (2006)
    National Academy of Sciences
    Details
    Publication Date: 2006-02-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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