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Isolation and characterization ofβ-transducin repeat-containing protein ligands screened using a high-throughput screening system

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Oncology Research 2023年第5期31卷 645-654页

作者： XINTONG LIU EMIKO SANADA JIANG LI XIAOMENG LI HIROYUKI OSADA NOBUMOTO watanabe Chemical Resource Development Research Unit RIKEN CSRSWakoSaitama351-0198Japan Department of RIKEN Molecular and Chemical Somatology Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyokuTokyo113-8510Japan Bioprobe Application Research Unit RIKEN CSRSWakoSaitama351-0198Japan Chemical Biology Research Group RIKEN CSRSWakoSaitama351-0198Japan Guangdong Engineering Research Center of Oral Restoration and Reconstruction Affiliated Stomatology Hospital of Guangzhou Medical UniversityGuangzhou510180China KingMed School of Laboratory Medicine Guangzhou Medical UniversityGuangzhou510182China Department of Pharmaceutical Sciences University of ShizuokaSuruga-kuShizuoka422-8526Japan

β-transducin repeat-containing protein(β-TrCP)is an F-box protein subunit of the E3 Skp1-Cullin-F box(SCF)type ubiquitin-ligase complex,and provides the substrate specificity for the *** find potent ligands ofβ-TrCP useful for the proteolysis targeting chimera(PROTAC)system usingβ-TrCP in the future,we developed a high-throughput screening system for small moleculeβ-TrCP *** screened the chemical library utilizing the system and obtained several hit *** effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were *** compounds NPD5943,NPL62020-01,and NPL42040-01 inhibited the TNFα-induced degradation of IκBαand its phosphorylated ***,they inhibited the activation of the transcription activity of NF-κB,indicating the effective inhibition ofβ-TrCP by the hit compounds in ***,we performed an in silico analysis of the hit compounds to determine the important moieties of the hit *** groups of NPL62020-01 and NPL42040-01 and hydroxyl groups of NPD5943 created hydrogen bonds withβ-TrCP similar to those created by intrinsic target phosphopeptides ofβ-*** findings enhance our knowledge of useful small molecule ligands ofβ-TrCP and the importance of residues that can be ligands ofβ-TrCP.

关键词： Ubiquitin F-box protein Chemical biology

Handedness found in a wild group of moor monkeys Macaca maurus in the Karaenta Nature Reserve, South Sulawesi,Indonesia

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Current Zoology 2010年第2期56卷 209-212页

作者： Kunio watanabe Primate Research Institute Kyoto University

Hand preference of wild moor monkeys Macaca mounts was investigated in food reaching situations at the KaraentaNature Reserve, South Sulawesi, Indonesia. The frequency picking up sweet-corn grains to take into the mouth by either hand ofmonkeys was counted directly at the feeding ground where sweet-corn grains were scattered for monkeys. Among the 20 monkeysexamined, 8 were right-handed, 8 were left-handed, and 4 were ambilateral. The results indicated the prevailed hand preferenceon individual level but not either trends of left- or right-hand preference on population level. The trend toward a higher proportionof left-handed monkeys found in Japanese and rhesus monkeys was not found. Some other characteristics found in moormonkeys are discussed in comparison with those previous findings in Japanese and Tibetan macaques in order to evaluate variationswithin the genus

关键词：自然保护区野生猕猴沼泽印尼流行趋势玉米粒猴子偏好

The Theaflavin Monomers Inhibit the Cancer Cells Growth in Vitro

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 508-512页

作者： Naoharu watanabe Department of Applied Biological Chemistry 836 Ohya Shizuoka 422-8529 Shizuoka University Japan

The inhibition effects of tea theaflavins complex (TFs), theaflavin-3-3’-digallate (TFDG), theaflavin-3’-gallate (TF2B), and an unidentified compound (UC) on the growth of human liver cancer BEL-7402 cells, gastric cancer MKN-28 cells and acute promyelocytic leukemia LH-60 cells were investigated. TFs was obtained through the catalysis of catechins with immobilized polyphenols oxidase. TFDG, TF2B and UC were isolated from TFs with high speed countercurrent chromatography (HSCCC). The results showed that TF2B significantly inhibited the growth of all three kinds of cancer cells, TFs, TFDG and UC had some effect on BEL-7402 and MKN-28, but little activity on LH-60. The inhibition effects of TF2B, TFDG, and UC on BEL-7402 and MKN-28 were stronger than TFs. The relationship coefficients between monomer concentration and its inhibition rate against MKN-28 and BEL-7402 were 0.87 and 0.98 for TF2B, 0.96 and 0.98 for UC, respectively. The IC50 values of TFs, TF2B, and TFDG were 0.18, 0.11, and 0.16 mM on BEL-7402 cells, and 1.11, 0.22, and 0.25 mM on MKN-28 cells respectively.

关键词： theaflavin monomer separation cancer cells inhibition

Early development of peer dominance relationships in a captive group of Japanese macaques Macaca fuscata

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Current Zoology 2010年第2期56卷 190-197页

作者： RIZALDI Kunio watanabe Primate Research Institute Kyoto University Department of Biology Faculty of Sciences Andalas University

We studied early development of peer dominance relationships in a captive group of Japanese macaques Macacafuscata fuscata at the Primate Research Institute of Kyoto University. This study aims to give detailed descriptions on characteristicpatterns of maternal rank acquisition from infant to juvenile. Focal subjects were 22 young monkeys belonging to three cohortsborn in 2002, 2003 and 2005. Data were collected with a total 2130 sessions of 30-minute continuous recording of focal subjectscombined with all occurrence-sampling methods. The onset of aggressive behavior varied per cohort and was delayed in cohortswith fewer close-aged associates. More than 60% of dyadic combinations in agonistic interactions between peers were unidirectionalthroughout the study period. Although some bidirectional interactions could have involved unstable relationships betweenparticular individuals, most of the bidirectional interactions included a few continuous series of alternating one-sided interactions.A linear order could be found among peers from the first appearance of aggressive behavior, and nearly 90% of those dyads wereconcordant with that of their mother's rank order. Young males were responsible for most of the dominance relations that wouldnot be predicted based on their mother's rank. These results suggest that infant monkeys may recognize their own social statusrelative to their opponent's before onset of aggressive behavior and adjust themselves into the matrilineal rank system

关键词：早期发展猕猴圈养日本优势攻击行为重点学科动物研究所

Ultrasound-guided rectus sheath block for anterior cutaneous nerve entrapment syndrome after laparoscopic surgery:A case report

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World Journal of Clinical Cases 2022年第7期10卷 2357-2362页

作者： Ryuji Sawada Kunitaro watanabe Joho Tokumine Alan Kawarai Lefor Tadao Ando Tomoko Yorozu Department of Pain Clinic NTT Medical Center TokyoHigashigotanda 141-8625TokyoJapan Department of Anesthesiology Hino Municipal HospitalTamadaira 191-0062TokyoJapan Department of Anesthesiology Kyorin University School of MedicineMitaka 181-8611TokyoJapan Department of Surgery Jichi Medical UniversityShimotsuke 329-0498TochigiJapan

BACKGROUND Anterior cutaneous nerve entrapment syndrome is defined as abdominal pain due to entrapped intercostal *** is the first report of a patient successfully treated for anterior cutaneous nerve entrapment syndrome after laparoscopic surgery with an ultrasound-guided rectus sheath *** rectus sheath block physically lysed adhesions and relieved pain from anterior cutaneous nerve entrapment *** SUMMARY The patient is a 44-year-old man who presented with severe left upper abdominal pain at an operative scar one month after laparoscopic ulcer *** and treatment were performed using an ultrasound-guided rectus sheath block with 0.1%lidocaine 20 *** pain was relieved after the *** diagnosis was anterior cutaneous nerve entrapment *** sheath block may be effective for patients with anterior cutaneous nerve entrapment *** Ultrasound-guided rectus sheath block is a promising treatment modality for patients with postoperative anterior cutaneous nerve entrapment syndrome due to adhesions.

关键词： Anterior cutaneous nerve entrapment syndrome Rectus sheath block Hydrodissection Laparoscopic surgery Case report

Comparative assessment of primary and secondary infection risks in a norovirus outbreak using a household model simulation

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Journal of Environmental Sciences 2016年第12期28卷 13-20页

作者： Fuminari Miura Toru watanabe Kozo watanabe Kazuhiko Takemoto Kensuke Fukushi Department of Urban Engineering Graduate School of Engineering the University of Tokyo Department of Food Life and Environmental Sciences Faculty of Agriculture Yamagata University Department of Civil and Environmental Engineering Ehime University Institute for the Advanced Study of Sustainability the United Nations University Todai Institutes for Advanced Study(TODIAS) Integrated Research System for Sustainability Science(IR3S) The University of Tokyo

Diarrheal diseases can be transmitted via both primary infection due to exposures to contaminated materials from the environment and secondary infection due to person- to-person contacts. Usually, the importance of secondary infection is empirically assessed by fitting mathematical models to the epidemic curves. However, these empirical models may not be applicable to other epidemic cases because they are developed only for the target epidemics and they don＇t consider the detail routes of infection. In our previous study, we developed a theoretical model taking into account the various routes of infection that commonly occur in households （e.g., shaking hands, food handling, and changing diapers）. This model was made flexible and applicable to any epidemics by means of adjusting model parameters. In this study, we proposed a new index ＂Vulnerability indicator to secondary infection （VISI）＂, which expressed a ratio of secondary infection to primary infection risks and calculated this index in a simulated norouirus （NOV） epidemic that involved I0,000 households. The results demonstrated that households composed of more than three members including infant（s） had much higher levels of VlSl （5-45） than two-member-households with VlSI （0.1-4）. These results concluded that the infants were likely to be a hub of secondary infections in highly dense families and therefore careful handling of diapers was deemed indispensible in such families to effectively control the secondary infections.

关键词： Norovirus Quantitative microbial riskassessment Secondary infection

Decomposition of Glycerine by Water Plasmas at Atmospheric Pressure

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Plasma Science and Technology 2013年第4期15卷 357-361页

作者： Takayuki watanabe NARENGERILE Department of Environmental Chemistry and Engineering Tokyo Institute of Technology 4259 NagatsutaYokohama 226-8502 Japan

High concentration of aqueous glycerine was decomposed using a direct current （DC） plasma torch at atmospheric pressure. The torch can generate the plasma with water as the plasma-supporting gas in the absence of any additionM gas supply system and cooling devices. The results indicated that 5 mol% glycerine was completely decomposed by water plasmas at arc powers of 0.55~1.05 kW. The major products in the effluent gas were H2 （68.9%~71.1%）, CO2 （18.9%~23.0%）, and CO （0.2%~0.6%）. However, trace levels of formic acid （HCOOH） and formaldehyde （HCHO） were observed in the liquid effluent. The results indicated that the water plasma waste treatment process is capable of being an alternative green technology for organic waste decomposition.

关键词： thermal plasma water plasma glycerine decomposition

Evaluation of Important Factors Affecting Quench Distortion of Carburized Hypoid Gear with Shaft by Using Computer Simulation Methods

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材料热处理学报 2004年第5期25卷 480-485页

作者： Tsuyoshi Sugimoto Youichi watanabe Nissan Motor Co. Ltd. 6-1 Daikoku-cho Tsurumi Yokohama JapanNissan Motor Co. Ltd. 6-1 Daikoku-cho Tsurumi Yokohama Japan

To minimize quenching distortion and dispersion, carburizing and quenching process conditions must be optimized; this includes the parts racking design used for quenching. We investigated some factors affecting carburized quenching distortion with an experiment using a hypoid gear having a shaft and with numerical simulation methods. The experimental results and those obtained from simulation were generally in agreement. Focusing on the surface temperature distribution in the gear, we studied quenching distortion characteristics in terms of changes in tooth profile and helix deviation. In our experiments, distortions occur during quenching in 373 K oil after austenitized temperature treatments conducted with various attitudes. We calculated the distortions by simulating the carburized oil-quenching process for the hypoid gear. Our results show large differences between the cooling rates of the tooth toe, middle section, and heel edges, and these greatly influence the change in tooth profile and helix deviation. We found that reducing the differences in temperatures on the gear surfaces during quenching is most important for minimizing the quench distortion of the hypoid gear.

关键词：淬火变形螺旋偏差外形偏差冷却曲线传热系数准双曲面齿轮

Relapse of prostate cancer from the viewpoint of total gland volume kinetics theory

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Asian Journal of Andrology 2015年第6期17卷 904-907页

作者： Hiroki watanabe Director Watanabe Memorial Choumei ResearchLaboratory Shiga Japan Honorary Professor KyotoPrefectural University of Medicine and Meiji Universityof Integrated Medicine Kyoto Japan.

In many cases of prostate cancer, changes of prostate volume were measured very frequently after castration by means of transrectal ultrasound. For short-term observations, a factor called as ＂reduction time （tau [τ]）,＂ which means the time required for the volume of ＂effective portion＂（volume responded to castration） to be reduced to one-tenth of its original value, correlated very well with patients＇ prognosis. For long-term observations for relapse, changes of prostate volume could be divided clearly into two types, namely, ＂metastatic progressive type＂ with metastasis without volume increase and ＂local progressive type＂ with remarkable volume increase without metastasis. ＂τ＂ in the ＂local progressive type＂ was far shorter than that in the ＂metastatic progressive type.＂ Much longer survival was obtained when the patient belonged to the ＂local progressive type＂ than to the ＂metastatic progressive type.＂ Thus, ＂τ＂ was the most important and the most reliable factor to predict the prognosis. Based upon these observations, a schematic analysis of prostate cancer relapse was shown.

关键词： Relapse prostate theory