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Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity

Angewandte Chemie 2016年第1期129卷

作者： Yusuke Kimura Toru Komatsu Kouichi Yanagi Kenjiro Hanaoka Tasuku Ueno Takuya Terai Hirotatsu Kojima Takayoshi Okabe Tetsuo Nagano Yasuteru Urano Graduate School of Pharmaceutical Sciences The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan Precursory Research for Embryonic Science and Technology PRESTO Japan Science and Technology Agency JST 4-1-8 Honcho Kawaguchi Saitama 332-0012 Japan Graduate School of Pharmaceutical Sciences The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan Discovery Initiative (DDI) The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan Graduate School of Medicine The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan Core Research for Evolutional Science and Technology CREST Investigator Japan Agency for Medical Research and Development AMED 1-7-1 Otemachi Chiyoda-ku Tokyo 100-0004 Japan

We have established a coupled assay system targeting protein l ‐isoaspartyl methyltransferase (PIMT), a key enzyme in the metabolism of isoaspartyl peptides and proteins. The system utilizes a fluorogenic peptide probe containing an isoaspartyl residue at the P1′ position of the caspase‐3 recognition sequence. Following PIMT‐catalyzed methyl transfer reaction, the methylated probe is specifically cleaved by caspase‐3 to give fluorescence activation. High‐throughput screening of our chemical library with this assay system identified PIMT inhibitors that may be useful as leads in the design of chemical probes for controlling PIMT activity.

关键词： Aktivitätsbasierte Sonden Enzyme Fluoreszenzsonden Inhibitoren Methyltransferasen

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Abstracts from the Food Allergy and Anaphylaxis Meeting 2016 Abstracts

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CLINICAL AND TRANSLATIONAL ALLERGY 2017年第SUPPL 1期7卷 10-10页

作者： [Anonymous] Department of Pediatrics Children’s Hospital Roubaix France Division of Pulmonology and Allergology Department of Pediatrics Faculty of Medicine and Children’s Hospital Lille France Allergy Vigilance Network Vandoeuvre les Nancy France Université Lille 2 CHU Lille EA 2694 - Santé Publique: épidémiologie et qualité des soins Lille France Biostatistics Unit Maison Régionale de la Recherche Clinique CHRU Lille Lille France Department of Allergology Emile Durkheim Hospital Epinal France Centre d’Epidémiologie sur les Causes Médicales de Décès INSERM CHU de Bicêtre Le Kremlin-Bicêtre France The Allergy Vigilance Network University Hospital Nancy Nancy France Pediatric Pulmonology and Allergy Department Hôpital Jeanne de Flandre CHU Lille Lille France Charité - Universitätsmedizin Berlin Berlin Germany Institute for Social Medicine Epidemiology and Health Economics Charité - Universitätsmedizin Berlin Berlin Germany Institute of Social Medicine Epidemiology and Health Economics Charité Universitätsmedizin Berlin Berlin Germany Department of Dermatology and Allergology Comprehensive Allergy Center Charité Charité – Universitätsmedizin Berlin Berlin Germany Department of Dermatology and Allergy Allergie-Centrum-Charité Charité-Universiätsmedizin Berlin Berlin Germany Department of Dermatology and Allergology Comprehensive Allergy Center Charité Charité Universitätsmedizin Berlin Berlin Germany University Hospital Basel Basel Switzerland Allergy Unit Department of Dermatology University Hospital Basel Switzerland Universitätsklinikum Salzburg Salzburg Austria Department of Dermatology and Allergy Centre Odense Research Center for Anaphylaxis (ORCA) Odense University Hospital Odense Denmark Odense University Hospital Odense Denmark Serviço de ImunoalergologiaCentro Hospitalar de São João E.P.E. Porto Portugal GRIAC Research Institute University of Groningen University Medical Center Groningen Groningen The Netherlands Serviço de Imunoalergologia Centr

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Microsupercapacitors: Lithographically Integrated Microsupercapacitors for Compact, High Performance, and Designable Energy Circuits (Adv. Energy Mater. 18/2015)

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Advanced Energy Materials 2015年第18期5卷

作者： Karolina U. Laszczyk Kazufumi Kobashi Shunsuke Sakurai Atsuko Sekiguchi Don N. Futaba Takeo Yamada Kenji Hata National Institute of Advanced Industrial Science and Technology (AIST) Central 5 1‐1‐1 Higashi Tsukuba Ibaraki 305‐8565 Japan Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) Kawaguchi 332‐0012 Japan

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New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases

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World Journal of Biological Chemistry 2014年第4期5卷 409-428页

作者： Naoki Adachi Tadahiro Numakawa Misty Richards Shingo Nakajima Hiroshi Kunugi Department of Mental Disorder Research National Institute of Neuroscience National Center of Neurology and Psychiatry Tokyo 187-8502 Japan Core Research for Evolutional Science and Technology Program Japan Science and Technology Agency Saitama 332-0012 Japan Albany Medical College Albany NY 12208 United States

Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.

关键词： Brain-derived neurotrophic factor Transcription Transport Secretion Neurodegenerative disorders Psychiatric disorders

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Formation and control of line defects caused by tectonics of water droplet arrays during self-organized honeycomb-patterned polymer film formation (vol 10, pg 2741, 2014)

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SOFT MATTER 2014年第33期10卷 6357-6357页

作者： Yamazaki, Hidekazu Ito, Koju Yabu, Hiroshi Shimomura, Masatsugu [a ] Production Engineering & Development Center Research & Development Management Headquarters Fujifilm Corporation 210 Nakanuma Minamiashigara-shi Japan E-mail: hidekazu.yamazaki@fujifilm.co Fax: +81 465 73 7960 Tel: +81 465 73 7330 [b ] Institute of Multidisciplinary Research for Advanced Materials (IMRAM) 2-1-1 Katahira Aoba-ku Sendai Japan [c ] WPI-Advanced Institute for Materials Research Tohoku University 2-1-1 Katahira Aoba-ku Sendai Japan [d ] Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) 4-1-8 Kawaguchi Japan

This study describes the formation of macro-scale defects of the honeycomb-patterned polymer film and we discovered two types of new line defects which differ from the defects reported in the past studies. We examined... 详细信息

关键词： Molecular Structure Particle Size Polymers/chemical synthesis Polymers/chemistry Surface Properties Water/chemistry

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Real-time monitoring of voltage shift based on enzymatically released pyrophosphate using phenylboronic acid-immobilized gate field-effect transistor

Real-time monitoring of voltage shift based on enzymatically...

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作者： Nishida, Hirokazu Takahashi, Kiyofumi Tabuse, Yuki Kambara, Hideki Sakata, Toshiya Central Research Laboratory Hitachi Ltd Kokubunji Tokyo 185-8601 Japan Consolidated Research Institute for Advanced Science and Medical Care Waseda University Shinjuku Tokyo 162-0041 Japan Department of Materials Engineering Graduate School of Engineering University of Tokyo Bunkyo Tokyo 113-0033 Japan Core Research for Evolutional Science and Technology Chiyoda Tokyo 101-0062 Japan

Pyrophosphate (PPi) is ubiquitous in living cells and is often produced by enzymatic reactions, e.g., DNA synthesis by DNA polymerase. We have developed a novel detection system for the voltage shift associated with the change in PPi concentration resulting from an enzymatic reaction using a phenylboronic acid (PBA)-coated gate field-effect transistor (FET), since PBA coating is effective for detecting ion accumulation associated with PPi production from enzymatic reactions. To detect enzymatic reactions more efficiently, we employed the enzyme-electrode conjugation method using specific peptide sequences, which are spontaneously tethered to a gold substrate. The combination of the enzyme-electrode conjugation method with the charge detection using the PBA-coated FET enables the effective detection of enzymatic reactions. © 2014 The Japan Society of Applied Physics.

关键词： Electrodes

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Regioselective Synthesis and Characterization of Multinuclear Convex‐Bound Ruthenium‐[n]Cycloparaphenylene (n=5 and 6) Complexes

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Angewandte Chemie 2015年第1期128卷

作者： Eiichi Kayahara Vijay Kumar Patel Audrey Mercier E. Peter Kündig Shigeru Yamago Institute for Chemical Research Kyoto University Kyoto 611 0011 (Japan) Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) Tokyo (Japan) Department of Organic Chemistry University of Geneva 30 Quai Ernest Ansermet 1211 Geneva 4 (Switzerland)

Mono‐ and multinuclear complexes of ruthenium and [ n ]cycloparaphenylene (CPP, n =5 and 6) were synthesized in excellent yields through ligand exchange of the cationic complex [(Cp)Ru(CH 3 CN) 3 ](PF 6 ) with CPP. In the multinuclear complexes, ruthenium selectively coordinated to alternate paraphenylene units to give bis‐ and tris‐coordinated Ru complexes for [5] and [6]CPPs, respectively. Single‐crystal X‐ray analysis revealed the Ru was coordinated with η 6 ‐hapticity on the convex surface of CPP.

关键词： Arenliganden Cycloparaphenylene Regioselektivität Röntgenbeugung Ruthenium

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The Biological Actions and Mechanisms of Brain-Derived Neurotrophic Factor in Healthy and Disordered Brains

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Neuroscience & Medicine 2014年第4期5卷 183-195页

作者： Toshiyuki Mizui Yuichiro Tanima Hiroko Komatsu Haruko Kumanogoh Masami Kojima Bio-Interface Research Group Health Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Ikeda Japan Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) Kawaguchi Japan Global Discovery Research Neuroscience and General Medicine Product Creation Unit Eisai Product Creation Systems Eisai Co. Ltd. Tsukuba Japan

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are mediated via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor and the low-affinity p75 neurotrophin receptor (p75NTR). Recent findings regarding the actions and mechanisms of BDNF are reviewed here. Activity-dependent synaptic plasticity, as exemplified by long-term potentiation (LTP) and long-term depression (LTD), underlies the cellular mechanism of learning and memory. An accumulating body of evidence shows that BDNF modulates synaptic plasticity. This function requires extracellular neurotrophin release, synaptic activity-dependent local protein synthesis. In addition, a precursor of BDNF, proBDNF, is emerging as a new ligand with biological activities that are distinct from those of BDNF. The proteolytic cleavage of proBDNF is also proposed as a mechanism that determines the direction of BDNF actions. This review discusses the post-translational processing of proBDNF, the modulatory roles of the human BDNF polymorphism Val66Met, recent reports of the novel mechanisms of BDNF expression, and clinical reports showing the roles of BDNF in the blood. Taken together, these data provide new insights into the biological roles of BDNF and its related molecules in the central nervous system.

关键词： Component Brain-Derived Neurotrophic Factor (BDNF) Tropomyosin-Related Kinase B (TrkB) Synaptic Plasticity Polymorphism Proteolytic Cleavage

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Two-Dimensional pH Mapping of a Histamine-Stimulated Gastric Mucosa by Using an Ion Image Sensor in the Guinea Pig

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Journal of Health science 2014年第3期2卷 157-163页

作者： Yasuko Fukushi Takashi Sakurai Hidenori Taki Kazuaki Sawada Susumu Terakawa Medical Photonics Research Center Hamamatsu University School of Medicine Hamamatsu 431-3192 Japan Electronics-Inspired Interdisciplinary Research Institute Toyohashi University of Technology Toyohashi 441-8580 Japan Japan Science and Technology Agency Core Research for Evolutional Science and Technology Tokyo 102-0076 Japan Department of Electrical and Electronic Information Engineering Toyohashi University of Technology Toyohashi 441-8580 Japan

In order to examine the hydronium ion （proton）-releasing functions in cells, [pH]out （extracellular pH） was measured using an ion image sensor composed of a 2D （two-dimensional） array of potential sensitive pixels. Using gastric tissues prepared from the stomach, pH distribution was observed during the histamine stimulation. The 2D distribution of [pH]out in the gastric tissues showed clear differences between the mucosal sides and the serous side. Even before the histamine stimulation, the mucosal side of the gastric mucosa showed a slightly lower pH than that of serous side. In the mucosal side, [pH]out decreased after the onset of the stimulation. The ion image sensor was capable of visualizing [pH]out in the gastric tissues. The present chemical-sensing technique realized a label-free microscopic assessment of the 2D distributions of biologically interesting substances, and consequently, [pH] out imaging via chemical microscopy has a future potential in medical fields for endoscopic analysis of gastric ulcers.

关键词： Proton ion image sensor extracellular pH gastric acid secretion.

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On-chip square wave voltammetric pulse generator for redox measurement employing array structure

On-chip square wave voltammetric pulse generator for redox m...

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IEEE Biomedical Circuits and Systems (BIOCAS)

作者： Byounghyun Lim Sou Takahashi Masato Futagawa Fumihiro Dasai Makoto Ishida Kazuaki Sawada Department of Electrical and Electronic Information Engineering Toyohashi University of Technology Toyohashi Japan Department of Electrical and Electronic Engineering Shizuoka University Hamamatsu Japan Core Research for Evolutional Science and Technology Japan Science and Technology Agency Chiyoda Tokyo Japan Electronics-Inspired Interdisciplinary Research Institute (EIIRIS) Toyohashi University of Technology Toyohashi Japan

A square wave voltammetric pulse generator circuit has been developed with CMOS technology and it was integrated with a redox array sensor. The pulse generator circuit consists of a presetter, two counters, a selector, a D flip-flop, an R-2R ladder DAC, and a voltage shifter. We can control the frequency, the square wave amplitude, and the step increment of square wave voltammetry. We confirmed that the square wave pulse and the 64 peak currents are obtained using the pulse generator circuit and 8 × 8 array working electrodes with potassium ferricyanide solution. Each read-out signal of array electrodes is read in sequence using the shift resistor.

关键词： Arrays Radiation detectors Pulse generation Microelectrodes Current measurement Clocks

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