Institution
University of Tokyo
Education•Tokyo, Japan•
About: University of Tokyo is a education organization based out in Tokyo, Japan. It is known for research contribution in the topics: Population & Gene. The organization has 134564 authors who have published 337567 publications receiving 10178620 citations. The organization is also known as: Todai & Universitas Tociensis.
Topics: Population, Gene, Catalysis, Magnetic field, Magnetization
Papers published on a yearly basis
Papers
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TL;DR: The results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity, and demonstrate that phosphorylated ubiquit in is a parkin activator.
Abstract: Ubiquitin, known for its role in post-translational modification of other proteins, undergoes post-translational modification itself; after a decrease in mitochondrial membrane potential, the kinase enzyme PINK1 phosphorylates ubiquitin at Ser 65, and the phosphorylated ubiquitin then interacts with ubiquitin ligase (E3) enzyme parkin, which is also phosphorylated by PINK1, and this process is sufficient for full activation of parkin enzymatic activity. The small protein ubiquitin, familiar for its role in post-translational modification of other proteins by binding to them and regulating their activity or stability, is shown here to be the substrate of the kinase PINK1, which together with the ubiquitin ligase parkin is a causal gene for hereditary recessive Parkinsonism. Noriyuki Matsuda and colleagues show that following a decrease in mitochondrial membrane potential, PINK1 phosphorylates ubiquitin at serine residue 65; the phosphorylated ubiquitin then interacts with parkin, which is also phosphorylated by PINK1. This interaction allows full activation of parkin enzymatic activity, which involves tagging mitochondrial substrates with ubiquitin. PINK1 (PTEN induced putative kinase 1) and PARKIN (also known as PARK2) have been identified as the causal genes responsible for hereditary recessive early-onset Parkinsonism1,2. PINK1 is a Ser/Thr kinase that specifically accumulates on depolarized mitochondria, whereas parkin is an E3 ubiquitin ligase that catalyses ubiquitin transfer to mitochondrial substrates3,4,5. PINK1 acts as an upstream factor for parkin6,7 and is essential both for the activation of latent E3 parkin activity8 and for recruiting parkin onto depolarized mitochondria8,9,10,11,12. Recently, mechanistic insights into mitochondrial quality control mediated by PINK1 and parkin have been revealed3,4,5, and PINK1-dependent phosphorylation of parkin has been reported13,14,15. However, the requirement of PINK1 for parkin activation was not bypassed by phosphomimetic parkin mutation15, and how PINK1 accelerates the E3 activity of parkin on damaged mitochondria is still obscure. Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential. Unexpectedly, phosphomimetic ubiquitin bypassed PINK1-dependent activation of a phosphomimetic parkin mutant in cells. Furthermore, phosphomimetic ubiquitin accelerates discharge of the thioester conjugate formed by UBCH7 (also known as UBE2L3) and ubiquitin (UBCH7∼ubiquitin) in the presence of parkin in vitro, indicating that it acts allosterically. The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator.
1,128 citations
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Hungarian Academy of Sciences1, Budapest University of Technology and Economics2, University of Stuttgart3, Fraunhofer Institute for Manufacturing Engineering and Automation4, National Institute of Advanced Industrial Science and Technology5, Pennsylvania State University6, Technische Universität München7, Fraunhofer Society8, RWTH Aachen University9, University of Tokyo10
TL;DR: There are significant roots in general and in particular to the CIRP community – which point towards CPPS, and expectations towards research in and implementation of CPS and CPPS are outlined.
Abstract: One of the most significant advances in the development of computer science, information and communication technologies is represented by the cyber-physical systems (CPS). They are systems of collaborating computational entities which are in intensive connection with the surrounding physical world and its on-going processes, providing and using, at the same time, data-accessing and data-processing services available on the Internet. Cyber-physical production systems (CPPS), relying on the latest, and the foreseeable further developments of computer science, information and communication technologies on one hand, and of manufacturing science and technology, on the other, may lead to the 4th industrial revolution, frequently noted as Industrie 4.0. The paper underlines that there are significant roots in general – and in particular to the CIRP community – which point towards CPPS. Expectations towards research in and implementation of CPS and CPPS are outlined and some case studies are introduced. Related new R&D challenges are highlighted.
1,123 citations
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23 Apr 2012TL;DR: The brat rapid annotation tool (BRAT) is introduced, an intuitive web-based tool for text annotation supported by Natural Language Processing (NLP) technology and an evaluation of annotation assisted by semantic class disambiguation on a multicategory entity mention annotation task, showing a 15% decrease in total annotation time.
Abstract: We introduce the brat rapid annotation tool (BRAT), an intuitive web-based tool for text annotation supported by Natural Language Processing (NLP) technology. BRAT has been developed for rich structured annotation for a variety of NLP tasks and aims to support manual curation efforts and increase annotator productivity using NLP techniques. We discuss several case studies of real-world annotation projects using pre-release versions of BRAT and present an evaluation of annotation assisted by semantic class disambiguation on a multicategory entity mention annotation task, showing a 15% decrease in total annotation time. BRAT is available under an open-source license from: http://brat.nlplab.org
1,121 citations
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TL;DR: In this paper, the authors identify the reconnection region as the site of particle acceleration, suggesting that the basic physics of the magnetic reconnection process may be common to both types of flares.
Abstract: SOLAR flares are thought to be the result of magnetic reconnection — the merging of antiparallel magnetic fields and the consequent release of magnetic energy. Flares are classified into two types1: compact and two-ribbon. The two-ribbon flares, which appear as slowly-developing, long-lived large loops, are understood theoretically2–6 as arising from an eruption of a solar prominence that pulls magnetic field lines upward into the corona. As the field lines form an inverted Y-shaped structure and relax, the reconnection of the field lines takes place. This view has been supported by recent observations7–10. A different mechanism seemed to be required, however, to produce the short-lived, impulsive compact flares. Here we report observations made with the Yohkoh11 Hard X-ray Telescope12 and Soft X-ray Telescope13, which show a compact flare with a geometry similar to that of a two-ribbon flare. We identify the reconnection region as the site of particle acceleration, suggesting that the basic physics of the reconnection process (which remains uncertain) may be common to both types of flare.
1,121 citations
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TL;DR: The relation between two different interpretations of the Hall conductance as topological invariants is clarified and it is found that vortices are given by the edge states when they are degenerate with the bulk states.
Abstract: We consider the integer quantum Hall effect on a square lattice in a uniform rational magnetic field. The relation between two different interpretations of the Hall conductance as topological invariants is clarified. One is the Thouless--Kohmoto--Nightingale--den Nijs (TKNN) integer in the infinite system and the other is a winding number of the edge state. In the TKNN form of the Hall conductance, a phase of the Bloch wave function defines U(1) vortices on the magnetic Brillouin zone and the total vorticity gives ${\mathrm{\ensuremath{\sigma}}}_{\mathit{x}\mathit{y}}$. We find that these vortices are given by the edge states when they are degenerate with the bulk states.
1,118 citations
Authors
Showing all 135252 results
Name | H-index | Papers | Citations |
---|---|---|---|
Ronald C. Kessler | 274 | 1332 | 328983 |
Donald P. Schneider | 242 | 1622 | 263641 |
George M. Whitesides | 240 | 1739 | 269833 |
Jing Wang | 184 | 4046 | 202769 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Yusuke Nakamura | 179 | 2076 | 160313 |
Dennis J. Selkoe | 177 | 607 | 145825 |
David L. Kaplan | 177 | 1944 | 146082 |
D. M. Strom | 176 | 3167 | 194314 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Krzysztof Matyjaszewski | 169 | 1431 | 128585 |
Yang Yang | 164 | 2704 | 144071 |
Qiang Zhang | 161 | 1137 | 100950 |
Kenji Kangawa | 153 | 1117 | 110059 |
Takashi Taniguchi | 152 | 2141 | 110658 |