Cigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects.
Results
We found no evidence of an association between any of the 14 XRCC1 polymorphisms and bladder cancer risk. However, we found carriage of the variant Arg280His allele to be marginally associated with increased bladder cancer risk compared to the wild-type genotype (adjusted odds ratio [95% confidence interval], 1.50 [0.98–2.28], p = 0.06). The association was stronger for current smokers such that individuals carrying the variant 280His allele had a two to three-fold increased risk of bladder cancer compared to those carrying the wildtype genotype (p = 0.09). However, the evidence for gene-environment interaction was not statistically significant (p = 0.45).
Conclusion
We provide no evidence of an association between polymorphisms in XRCC1 and bladder cancer risk, although our study had only limited power to detect the association for low frequency variants, such as Arg280His. 相似文献
Plant Cell, Tissue and Organ Culture (PCTOC) - Jasminanthes tuyetanhiae is one of the precious herbs and good for human health, discovered in the Da-Bia Mountain (Phu Yen province, Vietnam). The... 相似文献
In the tryptophan synthase bienzyme complex, indole produced by substrate cleavage at the alpha-site is channeled to the beta-site via a 25 A long tunnel. Within the beta-site, indole and l-Ser react with pyridoxal 5'-phosphate in a two-stage reaction to give l-Trp. In stage I, l-Ser forms an external aldimine, E(Aex1), which converts to the alpha-aminoacrylate aldimine, E(A-A). Formation of E(A-A) at the beta-site activates the alpha-site >30-fold. In stage II, indole reacts with E(A-A) to give l-Trp. The binding of alpha-site ligands (ASLs) exerts strong allosteric effects on the reaction of substrates at the beta-site: the distribution of intermediates formed in stage I is shifted in favor of E(A-A), and the binding of ASLs triggers a conformational change in the beta-site to a state with an increased affinity for l-Ser. Here, we compare the behavior of new ASLs as allosteric effectors of stage I with the behavior of the natural product, d-glyceraldehyde 3-phosphate. Rapid kinetics and kinetic isotope effects show these ASLs bind with affinities ranging from micro- to millimolar, and the rate-determining step for conversion of E(Aex1) to E(A-A) is increased by 8-10-fold. To derive a structure-based mechanism for stage I, X-ray structures of both the E(Aex1) and E(A-A) states complexed with the different ASLs were determined and compared with structures of the ASL complexes with the internal aldimine [Ngo, H., Harris, R., Kimmich, N., Casino, P., Niks, D., Blumenstein, L., Barends, T. R., Kulik, V., Weyand, M., Schlichting, I., and Dunn, M. F. (2007) Biochemistry 46, 7713-7727]. 相似文献
Fbh1 (F-box DNA helicase 1) orthologues are conserved from Schizosaccharomyces pombe to chickens and humans. Here, we report the disruption of the FBH1 gene in DT40 cells. Although the yeast fbh1 mutant shows an increase in sensitivity to DNA damaging agents, FBH1(-)(/)(-) DT40 clones show no prominent sensitivity, suggesting that the loss of FBH1 might be compensated by other genes. However, FBH1(-)(/)(-) cells exhibit increases in both sister chromatid exchange and the formation of radial structures between homologous chromosomes without showing a defect in homologous recombination. This phenotype is reminiscent of BLM(-)(/)(-) cells and suggests that Fbh1 may be involved in preventing extensive strand exchange during homologous recombination. In addition, disruption of RAD54, a major homologous recombination factor in FBH1(-)(/)(-) cells, results in a marked increase in chromosome-type breaks (breaks on both sister chromatids at the same place) following replication fork arrest. Further, FBH1BLM cells showed additive increases in both sister chromatid exchange and the formation of radial chromosomes. These data suggest that Fbh1 acts in parallel with Bloom helicase to control recombination-mediated double-strand-break repair at replication blocks and to reduce the frequency of crossover. 相似文献
A new species of Magnolia sect. Gwillimia DC., Magnoliaceae from Vietnam is described and illustrated. Magnolia tiepii is recognized from southern Vietnam, where it occurs in Khanh Vinh slope, Khanh Vinh District, Khanh Hoa Province. It is distinguished from the closely related M. henryi by having narrowly cuneate leaf blade, short petiole, stipular scar at the base of the leaf blade, short peduncle and ellipsoid fruit. 相似文献
Optimal conditions of hyper thermal (HT) acid hydrolysis of the Saccharina japonica was determined to a seaweed slurry content of 12% (w/v) and 144 mM H2SO4 at 160 °C for 10 min. Enzymatic saccharification was carried out at 50 °C and 150 rpm for 48 h using the three enzymes at concentrations of 16 U/mL. Celluclast 1.5 L showed the lowest half-velocity constant (Km) of 0.168 g/L, indicating a higher affinity for S. japonica hydrolysate. Pretreatment yielded a maximum monosaccharide concentration of 36.2 g/L and 45.7% conversion from total fermentable monosaccharides of 79.2 g/L with 120 g dry weight/L S. japonica slurry. High cell densities of Clostridium acetobutylicum and Clostridium tyrobutyricum were obtained using the retarding agents KH2PO4 (50 mM) and NaHCO3 (200 mM). Adaptive evolution facilitated the efficient use of mixed monosaccharides. Therefore, adaptive evolution and retarding agents can enhance the overall butanol and butyric acid yields from S. japonica.
A comparative study of wheat–wheatgrass substituted cultivars and lines resistant to leaf rust developed by the Agricultural Research Institute for Southeast Regions (Multi 6R, Belyanka, Favorit, Voevoda, Lebedushka) and Samara Agricultural Research Institute (Tulaikovskaya 5, Tulaikovskaya 10, Tulaikovskaya 100, Tulaikovskaya Zolotistaya) breeding was conducted. A complex analysis using molecular cytogenetic (C-differential banding, fluorescent (FISH) and genomic (GISH) in situ hybridization), molecular (PLUG markers), and biochemical (electrophoretic analysis of gliadins) markers demonstrated that they have a substitition of wheat chromosome 6D by the chromosomes 6Agi and 6Agi2 belonging to the J(=E) Agropyron intermedium (Host) Beauv (=Thinopyrum intermedium (Host) Barkworth & D.R. Dewey) subgenome. In spite of the fact that the chromosomes 6Agi and 6Agi2 differ in the C-banding pattern and demonstrated minor differences in the blocks of gliadin components, they had the identical pattern of pSc119.2 and pAs1 probe distribution and conjugated between themselves with insignificant disturbance. Thus, it was demonstrated that 6Agi and 6Agi2 are homologous chromosomes; however, the question about allelism of their leaf rust resistance genes between themselves requires special studies. Nevertheless, using STS and SCAR markers and taking into account the type of reaction to Puccinia triticina, their non-allelism to the Lr9, Lr19, Lr24, Lr29, Lr38, and Lr47 genes was established. It was revealed that the 6Agi and 6Agi2 chromosomes have a different level of transmission in hybrid F2 populations depending on the hybrid combination gene background. 相似文献
The taxonomic status of Rhinolophus macrotis sensu lato (s.l.) in Vietnam and adjacent territories remains problematic. To address this issue, we performed an integrated study of morphological, acoustic, and genetic characters of R. macrotis s.l. specimens and compared these with sympatric species within the philippinensis group (R. marshalli, R. paradoxolophus, and R. rex). Our results reveal that in addition to a cryptic species of R. macrotis previously found in Jiangxi and Jingmen, China, R. macrotis s.l. in continental Asia includes three further species, namely R. cf. siamensis, R. cf. macrotis, and R. cf. macrotis “Phia Oac.” These four taxa are distinguished from genuine R. macrotis in Nepal and R. siamensis in Thailand by their morphological and/or genetic features. Further taxonomic evaluation of the subspecies of R. macrotis s.l. is needed to determine their affinities with recently recognized cryptic species and to possibly describe new taxa. Our results also show that interspecific divergences in mitochondrial DNA sequences (Cytb and COI genes) among taxa within the philippinensis group (particularly between R. cf. siamensis/R. cf. macrotis and R. rex/R. paradoxolophus) are significantly lower than those of other morphological groups in the genus. These phylogenetic patterns might be explained by recent allopatric speciation or ancient introgression events among ancestors of the taxa during the Pleistocene. However, further investigations including genetic analyses of nuclear genes are needed to test the latter hypothesis. 相似文献