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  • 1
    Publication Date: 2009-08-14
    Description: TRAF6 is a ubiquitin ligase that is essential for the activation of NF-kappaB and MAP kinases in several signalling pathways, including those emanating from the interleukin 1 and Toll-like receptors. TRAF6 functions together with a ubiquitin-conjugating enzyme complex consisting of UBC13 (also known as UBE2N) and UEV1A (UBE2V1) to catalyse Lys 63-linked polyubiquitination, which activates the TAK1 (also known as MAP3K7) kinase complex. TAK1 in turn phosphorylates and activates IkappaB kinase (IKK), leading to the activation of NF-kappaB. Although several proteins are known to be polyubiquitinated in the IL1R and Toll-like receptor pathways, it is not clear whether ubiquitination of any of these proteins is important for TAK1 or IKK activation. By reconstituting TAK1 activation in vitro using purified proteins, here we show that free Lys 63 polyubiquitin chains, which are not conjugated to any target protein, directly activate TAK1 by binding to the ubiquitin receptor TAB2 (also known as MAP3K7IP2). This binding leads to autophosphorylation and activation of TAK1. Furthermore, we found that unanchored polyubiquitin chains synthesized by TRAF6 and UBCH5C (also known as UBE2D3) activate the IKK complex. Disassembly of the polyubiquitin chains by deubiquitination enzymes prevented TAK1 and IKK activation. These results indicate that unanchored polyubiquitin chains directly activate TAK1 and IKK, suggesting a new mechanism of protein kinase regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747300/" 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/PMC2747300/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xia, Zong-Ping -- Sun, Lijun -- Chen, Xiang -- Pineda, Gabriel -- Jiang, Xiaomo -- Adhikari, Anirban -- Zeng, Wenwen -- Chen, Zhijian J -- R01 AI060919/AI/NIAID NIH HHS/ -- R01 AI060919-05/AI/NIAID NIH HHS/ -- R01 GM063692/GM/NIGMS NIH HHS/ -- R01 GM063692-08/GM/NIGMS NIH HHS/ -- R01-AI09919/AI/NIAID NIH HHS/ -- R01-GM63692/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Sep 3;461(7260):114-9. doi: 10.1038/nature08247. Epub 2009 Aug 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19675569" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Cell Line ; DEAD-box RNA Helicases/metabolism ; Enzyme Activation/drug effects ; HeLa Cells ; Humans ; I-kappa B Kinase/*metabolism ; Interleukin-1beta/pharmacology ; Lysine/metabolism ; MAP Kinase Kinase Kinases/*metabolism ; Phosphorylation ; Polyubiquitin/biosynthesis/*metabolism ; TNF Receptor-Associated Factor 6/metabolism ; Tumor Suppressor Proteins/metabolism ; Ubiquitin-Conjugating Enzymes ; Ubiquitination
    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: 2015-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Yi-Gang -- Shi, Wei-Feng -- Liu, Di -- Qian, Jun -- Liang, Long -- Bo, Xiao-Chen -- Liu, Jun -- Ren, Hong-Guang -- Fan, Hang -- Ni, Ming -- Sun, Yang -- Jin, Yuan -- Teng, Yue -- Li, Zhen -- Kargbo, David -- Dafae, Foday -- Kanu, Alex -- Chen, Cheng-Chao -- Lan, Zhi-Heng -- Jiang, Hui -- Luo, Yang -- Lu, Hui-Jun -- Zhang, Xiao-Guang -- Yang, Fan -- Hu, Yi -- Cao, Yu-Xi -- Deng, Yong-Qiang -- Su, Hao-Xiang -- Sun, Yu -- Liu, Wen-Sen -- Wang, Zhuang -- Wang, Cheng-Yu -- Bu, Zhao-Yang -- Guo, Zhen-Dong -- Zhang, Liu-Bo -- Nie, Wei-Min -- Bai, Chang-Qing -- Sun, Chun-Hua -- An, Xiao-Ping -- Xu, Pei-Song -- Zhang, Xiang-Li-Lan -- Huang, Yong -- Mi, Zhi-Qiang -- Yu, Dong -- Yao, Hong-Wu -- Feng, Yong -- Xia, Zhi-Ping -- Zheng, Xue-Xing -- Yang, Song-Tao -- Lu, Bing -- Jiang, Jia-Fu -- Kargbo, Brima -- He, Fu-Chu -- Gao, George F -- Cao, Wu-Chun -- China Mobile Laboratory Testing Team in Sierra Leone -- England -- Nature. 2015 Oct 22;526(7574):595. doi: 10.1038/nature15255. Epub 2015 Aug 26.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26308898" target="_blank"〉PubMed〈/a〉
    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: 2015-05-15
    Description: A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 x 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 x 10(-3) to 1.41 x 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Yi-Gang -- Shi, Wei-Feng -- Liu, Di -- Qian, Jun -- Liang, Long -- Bo, Xiao-Chen -- Liu, Jun -- Ren, Hong-Guang -- Fan, Hang -- Ni, Ming -- Sun, Yang -- Jin, Yuan -- Teng, Yue -- Li, Zhen -- Kargbo, David -- Dafae, Foday -- Kanu, Alex -- Chen, Cheng-Chao -- Lan, Zhi-Heng -- Jiang, Hui -- Luo, Yang -- Lu, Hui-Jun -- Zhang, Xiao-Guang -- Yang, Fan -- Hu, Yi -- Cao, Yu-Xi -- Deng, Yong-Qiang -- Su, Hao-Xiang -- Sun, Yu -- Liu, Wen-Sen -- Wang, Zhuang -- Wang, Cheng-Yu -- Bu, Zhao-Yang -- Guo, Zhen-Dong -- Zhang, Liu-Bo -- Nie, Wei-Min -- Bai, Chang-Qing -- Sun, Chun-Hua -- An, Xiao-Ping -- Xu, Pei-Song -- Zhang, Xiang-Li-Lan -- Huang, Yong -- Mi, Zhi-Qiang -- Yu, Dong -- Yao, Hong-Wu -- Feng, Yong -- Xia, Zhi-Ping -- Zheng, Xue-Xing -- Yang, Song-Tao -- Lu, Bing -- Jiang, Jia-Fu -- Kargbo, Brima -- He, Fu-Chu -- Gao, George F -- Cao, Wu-Chun -- China Mobile Laboratory Testing Team in Sierra Leone -- England -- Nature. 2015 Aug 6;524(7563):93-6. doi: 10.1038/nature14490. Epub 2015 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China. ; Institute of Pathogen Biology, Taishan Medical College, Taian 271000, China. ; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. ; Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China. ; Beijing Key Laboratory of New Molecular Diagnostics Technology, Beijing 100850, China. ; Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. ; Sierra Leone Ministry of Health and Sanitation, Freetown, Sierra Leone. ; Sierra Leone-China Friendship Hospital, Freetown, Sierra Leone. ; BGI-Shenzhen, Shenzhen 518083, China. ; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK. ; Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China. ; Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing 100021, China. ; The No. 302 Hospital, Beijing 100039, China. ; The No. 307 Hospital, Beijing 100071, China. ; Department of international cooperation, National Health and Family Planning Commission, Beijing 100044, China. ; State Key Laboratory of Proteomics, Beijing 102206, China. ; 1] Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China [2] Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China [3] Chinese Center for Disease Control and Prevention, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25970247" target="_blank"〉PubMed〈/a〉
    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: 2002-12-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2016-07-22
    Description: WASH has a critical role in NK cell cytotoxicity through Lck-mediated phosphorylation Cell Death and Disease 7, e2301 (July 2016). doi:10.1038/cddis.2016.212 Authors: L Huang, P Zhu, P Xia & Z Fan
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 6
    Publication Date: 2015-05-13
    Description: Spreading of a water based ferrofluid core, cladded by a diamagnetic fluid, in three-stream micromixer channels was studied. This spreading, induced by an external magnetic field, is known as magnetofluidic spreading (MFS). MFS is useful for various novel applications where control of fluid-fluid interface is desired, such as micromixers or micro-chemical reactors. However, fundamental aspects of MFS are still unclear, and a model without correction factors is lacking. Hence, in this work, both experimental and numerical analyses were undertaken to study MFS. We show that MFS increased for higher applied magnetic fields, slower flow speed of both fluids, smaller flow rate of ferrofluid relative to cladding, and higher initial magnetic particle concentration. Spreading, mainly due to connective diffusion, was observed mostly near the channel walls. Our multi-physics model, which combines magnetic and fluidic analyses, showed, for the first time, excellent agreement between theory and experiment. These results can be useful for lab-on-a-chip devices.
    Print ISSN: 1070-6631
    Electronic ISSN: 1089-7666
    Topics: Physics
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  • 7
    Publication Date: 2016-06-02
    Description: The Pearl River is the largest river in southern China; it has eight outlets flowing into the South China Sea, four of which (Humen, Jiaomen, Hongqili and Hengmen) empty via Lingdingyang Bay. Tides, discharge strength and the presence of islands control sediments within these four outlets. Sediments are deposited, and form three shoals and two channels. The shoreline and its seabed topography have changed dramatically with increasing human impact. In order to understand the geomorphological evolution of Lingdingyang Bay and its hydrodynamics, we integrated data obtained from two marine environment investigations conducted by the Guangzhou Marine Geological Survey (GMGS) in 2003 and in 2012, together with remote sensing multi-temporal images and historical materials, and analysed them using a geographical information system (GIS). The results obtained show that the outlets are becoming narrower; the surface water area of Lingdingyang Bay is diminishing. Meanwhile, the sediment flux is reducing and becoming finer grained because the currents are being blocked by shoals and islands. Some parts of the bay are becoming deeper (27–37 m in the Chuanbi Channel). Correspondingly, the hydrodynamics in the bay are becoming weaker and sediments easier to deposit. Water exchange between the inner and outer sea is decreasing under the influence of unrestricted anthropogenic activities. Lingdingyang Bay should be managed and protected continuously based on a scientific framework: otherwise, it will become narrower and, perhaps, even evolving eventually into a river, which may result in serious futures disasters through flooding and tides.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
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  • 8
    Publication Date: 2003-05-15
    Print ISSN: 0021-8979
    Electronic ISSN: 1089-7550
    Topics: Physics
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  • 9
    Publication Date: 2005-02-15
    Print ISSN: 1945-0877
    Electronic ISSN: 1937-9145
    Topics: Biology , Medicine
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  • 10
    Publication Date: 2019-11-01
    Print ISSN: 2169-9097
    Electronic ISSN: 2169-9100
    Topics: Geosciences , Physics
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