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Mori T Hidaka M Lin YC Yoshizawa I Okabe T Egashira S Kojima H Nagano T Koketsu M Takamiya M Uchida T 《Biochemical and biophysical research communications》2011,406(3):5355-443
Pin1, a peptidyl prolyl cis/trans isomerase (PPIase), is a potential target molecule for cancer, infectious disease, and Alzheimer’s disease. We established a high-throughput screening method for Pin1 inhibitors, which employs a real-time fluorescence detector. This screening method identified 66 compounds that inhibit Pin1 out of 9756 compounds from structurally diverse chemical libraries. Further evaluations of surface plasmon resonance methods and a cell proliferation assay were performed. We discovered a cell-active inhibitor, TME-001 (2-(3-chloro-4-fluoro-phenyl)-isothiazol-3-one). Surprisingly, kinetic analyses revealed that TME-001 is the first compound that exhibits dual inhibition of Pin1 (IC50 = 6.1 μM) and cyclophilin, another type of PPIase, (IC50 = 13.7 μM). This compound does not inhibit FKBP. This finding suggests the existence of similarities of structure and reaction mechanism between Pin1 and cyclophilin, and may lead to a more complete understanding of the active sites of PPIases. 相似文献
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Aline Satie Takamiya Douglas Roberto Monteiro Valentim Adelino Ricardo Barão Ana Carolina Pero Marco Antonio Compagnoni Debora Barros Barbosa 《Gerodontology》2011,28(2):91-96
Gerodontology 2010; doi: 10.1111/j.1741‐2358.2010.00369.x Complete denture hygiene and nocturnal wearing habits among patients attending the Prosthodontic Department in a Dental University in Brazil Objective: The aim of this study was to evaluate the overnight wearing and cleaning habits of complete denture wearers. Background: Successful complete denture treatment can be achieved when the patients are motivated and aware of appropriate denture wear and hygiene. Materials and methods: A sample of 224 complete denture wearers (162 women) aged 37–89 years was studied. Inclusion criteria comprised edentulous subjects who had received their new complete dentures between 2000 and 2005 in the Dental Clinic of the Araçatuba and Araraquara Dental School, São Paulo State University. Ethical approval was sought and granted. Subjects were interviewed using questions related to overnight denture wearing and denture cleaning habits. Possible statistical relationships among some of items were analysed by the chi‐square test at 5% significance level. Results: Of the patients, 55.8% removed their dentures during the overnight period and 88% did this every day. Among them, 66.4% removed both dentures. Most of the patients used brushing with toothpaste (105 patients – 46.87%) as a cleaning method. More than a half of the subjects (63.4%) showed biofilm and calculus on their dentures. Conclusion: The patients need instructions and motivation concerning denture hygienic and denture removal overnight. 相似文献
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Shinji Masuda Rei Ikeda Tatsuru Masuda Haruki Hashimoto Tohru Tsuchiya Hiroko Kojima Jiro Nomata Yuichi Fujita Mamoru Mimuro Hiroyuki Ohta Ken‐ichiro Takamiya 《The Plant journal : for cell and molecular biology》2009,58(6):952-960
In angiosperms, chlorophyll biosynthesis is light dependent. A key factor in this process is protochlorophyllide oxidoreductase (POR), which requires light to catalyze the reduction of protochlorophyllide to chlorophyllide. It is believed that this protein originated from an ancient cyanobacterial enzyme that was introduced into proto‐plant cells during the primary symbiosis. Here we report that PORs from the cyanobacteria Gloeobacter violaceus PCC7421 and Synechocystis sp. PCC6803 function in plastids. First, we found that the G. violaceus POR shows a higher affinity to its substrate protochlorophyllide than the Synechocystis POR but a similar affinity to plant PORs. Secondly, the reduced size of prolamellar bodies caused by a knockdown mutation of one of the POR genes, PORA, in Arabidopsis could be complemented by heterologous expression of the cyanobacterial PORs. Photoactive protochlorophyllide in the etioplasts of the complementing lines, however, was retained at a low level as in the parent PORA knockdown mutant, indicating that the observed formation of prolamellar bodies was irrelevant to the assembly of photoactive protochlorophyllide. This work reveals a new view on the formation of prolamellar bodies and provides new clues about the function of POR in the etioplast–chloroplast transition. 相似文献
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Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory 总被引:32,自引:0,他引:32
Lee HK Takamiya K Han JS Man H Kim CH Rumbaugh G Yu S Ding L He C Petralia RS Wenthold RJ Gallagher M Huganir RL 《Cell》2003,112(5):631-643
Plasticity of the nervous system is dependent on mechanisms that regulate the strength of synaptic transmission. Excitatory synapses in the brain undergo long-term potentiation (LTP) and long-term depression (LTD), cellular models of learning and memory. Protein phosphorylation is required for the induction of many forms of synaptic plasticity, including LTP and LTD. However, the critical kinase substrates that mediate plasticity have not been identified. We previously reported that phosphorylation of the GluR1 subunit of AMPA receptors, which mediate rapid excitatory transmission in the brain, is modulated during LTP and LTD. To test if GluR1 phosphorylation is necessary for plasticity and learning and memory, we generated mice with knockin mutations in the GluR1 phosphorylation sites. The phosphomutant mice show deficits in LTD and LTP and have memory defects in spatial learning tasks. These results demonstrate that phosphorylation of GluR1 is critical for LTD and LTP expression and the retention of memories. 相似文献
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Effects of various factors, such as uncouplers, inhibitors andinhibitory treatments of chloroplasts, on light-dependent (KL)and -independent (KD) parameters estimated from the light intensity-activityrelationship, were studied. In the Hill-reaction with ferricyanide or methyl viologen aselectron acceptor, a reagent or treatment affecting electrontransport on one side of system II, which included the rate-limitingstep for the entire electron transport, affected only KD. Incontrast, a change in the rate of electron transfer on the otherside of system II affected only KL. We inferred that KD representsthe rate of the dark rate-limiting step at infinite light intensity.On the other hand, KL is concerned to the quantum yield of theprimary reaction, as well as to the rate constant of the reactionon the side of system II opposite to that of the rate-limitingstep at infinite light intensity. Effects of inhibitors and treatments on the reaction parameterschanged markedly depending on the pH of the reaction medium.However, the contrasting effects of inhibitors affecting theopposite sides of system II were consistently observed in definedlevels of pH. This was also the case in the photoreduction ofmethyl viologen with the ascorbate-DPIP couple as electron donor.
1 Present address: Department of Biology, Faculty of Science,Toho University, Narashino, Chiba, Japan. (Received May 2, 1972; ) 相似文献