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141.
Urbahns K Yura T Mogi M Tajimi M Fujishima H Masuda T Yoshida N Moriwaki T Lowinger TB Meier H Chan F Madge D Gupta JB 《Bioorganic & medicinal chemistry letters》2011,21(11):3354-3357
We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration. 相似文献
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Reexamination of the dnaP18 mutant strain of Escherichia coli revealed that the mutation responsible for the arrest of DNA replication and cell growth at high temperatures resides in the dnaG gene rather than in the dnaP locus as previously thought; this mutation has been designated dnaG2903. 相似文献
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Indirect selection for plasmid mutants: isolation of ColVBtrp mutants defective in self-maintenance in Escherichia coli. 总被引:2,自引:4,他引:2 下载免费PDF全文
An efficient method for isolation of a large number of plasmid mutants is described. It is based on the fact that N-methyl-N'-nitro-N-nitrosoguanidine induces a number of closely linked mutations within a short segment of the bacterial chromosome. Thus, selection for reversions of an auxotrophic marker located on the ColVBtrp plasmid yielded a large fraction (more than 50 percent) of mutants defective in some plasmid functions, including its own maintenance in the host bacteria. The results of preliminary characterization of strains carrying these mutated plasmids are presented. 相似文献
148.
Sato M Harada K Yura Y Azuma M Kawamata H Iga H Tsujimoto H Yoshida H Adachi M 《Apoptosis : an international journal on programmed cell death》1997,2(3):313-318
A patient with histopathological recurrent oral cancer with well-differentiated squamous cell carcinoma, was treated with differentiation- and apoptosis-inducing agent, vesnarinone, per os at a dose of 180 mg/day for 56 days and then at a dose of 60 mg/day for 93 days. The vesnarinone administration caused complete remission of the tumour. It has been found by immunohistochemical staining and PCR-SSCP analysis that the recurrent tumour has wild type p53 gene and relative high level of LeY expression as well as DNA fragmentation in the cancer cells, as assessed by nick-end labelling. These findings suggest that the cure of oral squamous cell carcinoma observed in this case might be associated with induction of differentiation and apoptosis of cancer cells by vesnarinone. 相似文献
149.
Genetic transformation is widely utilized in molecular biology as a tool for gene cloning in Escherichia coli and for gene mapping in Bacillus subtilis. Several strains of eubacteria can naturally take up exogenous DNA and integrate the DNA into their own genomes. Molecular details of natural transformation, however, remained to be elucidated. The complete genome of a cyanobacterium, Synechocystis sp. PCC6803, has been sequenced. This bacterium has been used to examine functions of a particular gene. The genome is considered to carry information on natural transformable characteristics of Synechocystis. The first step in genetic transformation is the uptake of exogenous DNA. Proteins with non-specific DNA binding features are required, because specificity in the exogenous DNA has not been demonstrated. Such proteins have modules interacting with the phosphate backbone of DNA, including helix-turn-helix modules. Using a consensus pattern of the phosphate-binding helix-turn-helix module, we searched through the genome data of Synechocystis for genes or open reading frame (ORF) products with the pattern in primary structures. We found that an ORF, slr0197, has the pattern in duplicate at the C-terminal region. We also found that the ORF product has a hydrophobic segment at the N-terminal region, which is followed by two internal repeats of the endonuclease domain. Based on these observations, we propose a model for the initial stage of genetic transformation. This is apparently the first report on molecular mechanisms of natural transformation. 相似文献
150.
Takayuki Noda Soichi Iwai Masakazu Hamada Yusei Fujita Yoshiaki Yura 《Apoptosis : an international journal on programmed cell death》2009,14(3):287-297
The protein kinase C (PKC) inhibitor safingol increased rounding and detachment of human oral squamous cell carcinoma (SCC)
cells in monolayer cultures. When dissociated cells were incubated in the presence of safingol, cell adhesion was prevented
and cell viability was lost gradually, while most cells survived in the absence of safingol even if their attachment was blocked
by coating the culture plates with polyhydroxyethyl methacrylate. Flow cytometric analysis and agarose gel electrophoresis
of cellular DNA revealed an increase in the proportion of sub-G1 cells and DNA fragmentation, indicating that safingol induced apoptosis of dissociated cells. During the induction of apoptosis
in cell suspensions by safingol, there was an increase of the pro-apoptotic BH-3 only protein Bim and decrease of pro-survival
Bcl-2 family proteins Bcl-xL and mitochondrial pro-apoptogenic factor endonuclease G translocated to the nucleus. The level
of phosphorylated focal adhesion kinase (FAK) required for cell survival also rapidly decreased, followed by a decrease in
the protein level. The introduction of siRNA against PKCα into SAS cells resulted in an increase of Bim, a decrease of Bcl-xL,
the translocation of endonuclease G, and a decrease in the phosphorylation of FAK. These results suggest that Bim, Bcl-xL,
FAK and endonuclease G are involved in safingol-induced apoptosis of detached oral SCC cells. Safingol can be used to induce
apoptosis with cell detachment, anoikis, of oral SCC cells. 相似文献