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101.
Role of the Cytosolic Heat Shock Protein 70 Ssa5 in the Ciliate Protozoan Tetrahymena thermophila 下载免费PDF全文
Yasuhiro Fukuda Takahiko Akematsu Rizwan Attiq Chika Tada Yutaka Nakai Ronald E. Pearlman 《The Journal of eukaryotic microbiology》2015,62(4):481-493
Heat shock protein 70 (Hsp70) is a member of a family of conserved chaperone proteins whose function is well investigated in many model organisms. Here we focus on an Hsp70 called Ssa5 in the ciliate protozoan Tetrahymena thermophila, and reveal that its translation is heat inducible as for general Hsps. Moreover, the protein is abundantly expressed in the cytoplasm during sexual reproduction (conjugation) as well as in response to heat‐stress. Knocking out of SSA5 (ΔSSA5) does not affect the survival of the cell under heat‐stress, likely due to other Hsp70 paralogs compensating for the defect. During conjugation, ΔSSA5 leads to a fertilization defect in which the two pronuclei are in close proximity but never fuse. The unfertilized pronuclei differentiate, resulting in a heterokaryon with developed haploid germline and somatic nuclei. In addition, degeneration of the parental somatic nucleus is not affected. These results suggest a specific involvement of Ssa5 in pronuclear fusion and fertilization. 相似文献
102.
Nishizawa R Nishiyama T Hisaichi K Minamoto C Murota M Takaoka Y Nakai H Tada H Sagawa K Shibayama S Fukushima D Maeda K Mitsuya H 《Bioorganic & medicinal chemistry》2011,19(13):4028-4042
Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. 相似文献
103.
Yoshida M Mori A Morimoto S Kotani E Oka M Notoya K Makino H Ono M Shirasaki M Tada N Fujita H Ban J Ikeda Y Kawamoto T Goto M Kimura H Baba A Yasuma T 《Bioorganic & medicinal chemistry》2011,19(6):1881-1894
The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. 相似文献
104.
105.
Tada Mikiro; Shiroishi Masahide; Hasegawa Kiyozo; Suzuki Tetsuya; Iwai Kazuo 《Plant & cell physiology》1982,23(4):607-614
The effect of light on the production of ergosterol and phytoeneand on the composition of carotenoids in Rhodotorula minutawas studied to determine which part of the pathway of carotenoidsynthesis regulated by light. The ergosterol content in the cells was in the range of 3.43.6mg/g dry cells regardless of the presence or absence of illuminationand the light intensity. The phytoene production in the cellswas markedly stimulated by light and was dependent on the lightintensity according to the amount of carotenoid pigments produced.In addition, the ratio of phytoene to carotenoid was in therange of 0.360.44, regardless of the presence or absenceof illumination and the light intensity. The fact that the ratio of carotenoid fractionated on the basisof the functional group involved in each carotenoid to the totalamount of carotenoid was almost constant regardless of the lightintensity suggested that the composition of the carotenoidssynthesized in the cells is not affected by light. It was deduced from these results that light induced the productionof enzyme(s) required for phytoene biosynthesis in Rhodotorulaminuta. (Received November 7, 1981; Accepted March 19, 1982) 相似文献
106.
Takuya Fujimoto Mamoru Tobisu Noriko Konishi Masaki Kawamura Norio Tada Terufumi Takagi Keiji Kubo 《Bioorganic & medicinal chemistry》2009,17(23):7993-8002
We have recently discovered imidazo[1,5-c]imidazol-3-one derivative 1 as a potent, selective, and orally bioavailable factor Xa (FXa) inhibitor. In this study, we have synthesized metabolites of 1 and evaluated their biological activities. As a result, we identified the active metabolites S-5 and 6 with a potent FXa inhibitory activity comparable to 1 and a favorable pharmacokinetic profile in monkeys. 相似文献
107.
108.
Tada Y Kusaka K Betsuyaku S Shinogi T Sakamoto M Ohura Y Hata S Mori T Tosa Y Mayama S 《Plant & cell physiology》2005,46(11):1787-1798
The host-selective toxin victorin is produced by Cochliobolus victoriae, the causal agent of victoria blight of oats. Victorin has been shown to bind to the P protein of the glycine decarboxylase complex (GDC) in mitochondria, and induce defense-related responses such as phytoalexin synthesis, extracellular alkalization and programmed cell death. However, evidence demonstrating that the GDC plays a critical role in the onset of cell death is still lacking, and the role of defense-like responses in the pathogenicity has yet to be elucidated. Here, cytofluorimetric analyses, using the fluorescein (VicFluor) or bovine serum albumin-fluorescein derivative of victorin (VicBSA), demonstrated that victorin-induced cell death occurs before these conjugates traverse the plasma membrane. As with native victorin, VicBSA clearly elicits apoptosis-like cell death, production of phytoalexin, extracellular alkalization, and generation of nitric oxide and reactive oxygen intermediates. These results suggest that the initial recognition of victorin takes place on the cell surface, not in mitochondria, and leads to the activation of a battery of victorin-induced responses. Pharmacological studies showed that extracellular alkalization is the essential regulator for both victorin- and VicBSA-induced cellular responses. We propose a model where victorin may kill the host cell by activating an HR-like response, independent of the binding to the GDC, through ion fluxes across the plasma membrane. 相似文献
109.
Several strategies for mapping ventricular outflow tract tachycardia have been reported as useful indices for differentiating between those originating from the right and the left side. Recently, tissue tracking imaging (TTI) has been demonstrated as a novel non-invasive modality for identifying the origin of outflow tract tachycardias. Tissue tracking imaging is an ultrasonographic technique that measures the myocardial motion amplitude towards the transducer in each region during systole, identifying regional myocardial displacement on the basis of myocardial velocities using color Doppler myocardial imaging principles. In this technique, the origin of the arrhythmia could be recognized as the site where the earliest color-coded signal (ECCS) appeared on the myocardium at the onset of the systole. In preliminary studies this modality was found to be useful in differentiating outflow tract ventricular tachycardias. ECCS was always found below or at the level of the pulmonary valve in all arrhythmias which could be ablated from the right ventricular outflow tract, while in those where the ECCS was above and close to the pulmonary valve it could be ablated from the left sinus of valsalva. These results indicate that TTI can provide detailed and accurate information on the arrhythmia origin of outflow tract tachycardia and may be useful for differentiating between an outflow tract tachycardia originating from the LV epicardium remote from the LSV and that from the LSV. Newer advances in echocardiographic technologies like high resolution, high frame rate real time three dimensional echocardiography with speckle tracking may further improve the precise localization of arrhythmias in the future. 相似文献
110.
Yasunaga M Tada S Torikai-Nishikawa S Nakano Y Okada M Jakt LM Nishikawa S Chiba T Era T Nishikawa S 《Nature biotechnology》2005,23(12):1542-1550
Preparation of specific lineages at high purities from embryonic stem (ES) cells requires both selective culture conditions and markers to guide and monitor the differentiation. In this study, we distinguished definitive and visceral endoderm by using a mouse ES cell line that bears the gfp and human IL2R alpha (also known as CD25) marker genes in the goosecoid (Gsc) and Sox17 loci, respectively. This cell line allowed us to monitor the generation of Gsc+ Sox17+ definitive endoderm and Gsc- Sox17+ visceral endoderm and to define culture conditions that differentially induce definitive and visceral endoderm. By comparing the gene expression profiles of definitive and visceral endoderm, we identified seven surface molecules that are expressed differentially in the two populations. One of the seven markers, Cxcr4, to which a monoclonal antibody is available allowed us to monitor and purify the Gsc+ population from genetically unmanipulated ES cells under the condition that selects definitive endoderm. 相似文献