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Abstract The substantial photosubstitution of 5-fluoro-1,3-dimethyluracil with substituted benzenes is first achieved by the addition of trifluoroacetic acid to the reaction mixture. The presence of protons is essential for the formation of 5-aryl-1,3-dimethyluracils. 相似文献
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Eita Uenishi Tadao Shibasaki Harumi Takahashi Chihiro Seki Hitomi Hamaguchi Takao Yasuda Masao Tatebe Yutaka Oiso Tadaomi Takenawa Susumu Seino 《The Journal of biological chemistry》2013,288(36):25851-25864
Actin dynamics in pancreatic β-cells is involved in insulin secretion. However, the molecular mechanisms of the regulation of actin dynamics by intracellular signals in pancreatic β-cells and its role in phasic insulin secretion are largely unknown. In this study, we elucidate the regulation of actin dynamics by neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin in pancreatic β-cells and demonstrate its role in glucose-induced insulin secretion (GIIS). N-WASP, which promotes actin polymerization through activation of the actin nucleation factor Arp2/3 complex, was found to be activated by glucose stimulation in insulin-secreting clonal pancreatic β-cells (MIN6-K8 β-cells). Introduction of a dominant-negative mutant of N-WASP, which lacks G-actin and Arp2/3 complex-binding region VCA, into MIN6-K8 β-cells or knockdown of N-WASP suppressed GIIS, especially the second phase. We also found that cofilin, which severs F-actin in its dephosphorylated (active) form, is converted to the phosphorylated (inactive) form by glucose stimulation in MIN6-K8 β-cells, thereby promoting F-actin remodeling. In addition, the dominant-negative mutant of cofilin, which inhibits activation of endogenous cofilin, or knockdown of cofilin reduced the second phase of GIIS. However, the first phase of GIIS occurs in the G-actin predominant state, in which cofilin activity predominates over N-WASP activity. Thus, actin dynamics regulated by the balance of N-WASP and cofilin activities determines the biphasic response of GIIS. 相似文献
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Takahiro Seki Lijie Gong Aislinn J. Williams Norio Sakai Sokol V. Todi Henry L. Paulson 《The Journal of biological chemistry》2013,288(24):17145-17155
The functional diversity of deubiquitinating enzymes (DUBs) is not well understood. The MJD family of DUBs consists of four cysteine proteases that share a catalytic “Josephin” domain. The family is named after the DUB ATXN3, which causes the neurodegenerative disease Machado-Joseph disease. The two closely related Josephin domain-containing (JosD) proteins 1 and 2 consist of little more than the Josephin domain. To gain insight into the properties of Josephin domains, we investigated JosD1 and JosD2. JosD1 and JosD2 were found to differ fundamentally in many respects. In vitro, only JosD2 can cleave ubiquitin chains. In contrast, JosD1 cleaves ubiquitin chains only after it is monoubiquitinated, a form of posttranslational-dependent regulation shared with ATXN3. A significant fraction of JosD1 is monoubiquitinated in diverse mouse tissues. In cell-based studies, JosD2 localizes to the cytoplasm whereas JosD1 preferentially localizes to the plasma membrane, particularly when ubiquitinated. The membrane occupancy by JosD1 suggests that it could participate in membrane-dependent events such as cell motility and endocytosis. Indeed, time-lapse imaging revealed that JosD1 enhances membrane dynamics and cell motility. JosD1 also influences endocytosis in cultured cells by increasing the uptake of endocytic markers of macropinocytosis while decreasing those for clathrin- and caveolae-mediated endocytosis. Our results establish that two closely related DUBs differ markedly in activity and function and that JosD1, a membrane-associated DUB whose activity is regulated by ubiquitination, helps regulate membrane dynamics, cell motility, and endocytosis. 相似文献
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Maki Seki Osamu Tsuruta Ryo Tatsumi Aki Soejima 《Bioorganic & medicinal chemistry letters》2013,23(14):4230-4234
A novel series of pyrrolidine derivatives as Na+ channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na+ channels. Structure–activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na+ channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. 相似文献
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Akira Sakurai Yukiharu Sato Keun Hyung Park Nobutaka Takahashi Naohiko Yanagishima Isao Banno 《Bioscience, biotechnology, and biochemistry》2013,77(6):1451-1453
The pullulanase gene (pul) of Klebsiella aerogenes was transferred in vivo to Escherichia coli by using RP4:: Mu cts. The pul gene was expressed in E. coli, although the level of pullulanase activity in E. coli was lower than that in K. aerogenes, and the Pul+ transconjugants were relatively unstable in an unselective medium. Production of pullulanase, which is used to make maltose from starch, was induced in E. coli by pullulan, waxy maize amylopectin, soluble starch and maltose. When the transconjugant cells of E. coli were grown with pullulan or maltose, most pullulanase was produced intracellularly, whereas K. aerogenes produced pullulanase extracellularly. Retransfer of the pulk gene from E. coli to K. aerogenes by conjugation resulted in an increase of the production of extracellular pullulanase. 相似文献
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Akira Sakurai Saburo Tamura Naohiko Yanagishima Chikashi Shimoda Michio Hagiya Narao Takao 《Bioscience, biotechnology, and biochemistry》2013,77(1):231-232
5-Fluorotryptophan (5FT), indolmycin (IM), 4-fluorotryptophan and 7-azatryptophan were found on screening to be tryptophan antagonists among various chemically synthesized and naturally occurring tryptophan analogues for the isolation of l-tryptophan (l-Trp) producing mutants of Bacillus subtilis K.From among 5FT resistant mutants, potent l-Trp producers were obtained using an improved isolation medium. Growth of the isolated 5FT-resistant l-Trp producer, AJ 11709, was inhibited by IM. From among 5FT and IM resistant mutants, the best strain, AJ 11979, which produced 9.0 g/liter of l-Trp from 13% glucose on 120hr cultivation, was selected. 相似文献
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Kazuaki Kyogoku Katsuo Hatayama Sadakazu Yokomori Teruya Seki Ichiro Tanaka 《Bioscience, biotechnology, and biochemistry》2013,77(11):2291-2292
Nicotine has been found an effective photosensitizer for DDT. At DDT: nicotine (1:5), DDT along with its formed degradation products DDD, DDE and DBP disappeared within 18 and 60 days under UV and sunlight respectively. Because of persistence, nicotine proved a superior photosensitizer to N,N′-diethylaniline. In DDT emulsifiable concentrates it led to high alkalinity but no DDT degradation up to 60 days at 20~25°C. 0.1 and 0.5% DDT emulsions from these formulations showed no adverse effect on Daucus carrota, Vicia faba, Brassica oleracea var. botrytis, and Dahlia sp., but showed mild to severe phytotoxicity against Pisum sativum and Cicer arietinum; caused by high concentration of nicotine. On Clerodendrum sp. in sunlight, these formulations showed over 20% faster DDT loss between 3~15 days of application. DDT-nicotine mixtures showed no synergism against Tribolium castaneum Herbst. 相似文献