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Nicholls-Grzemski FA Belling GB Priestly BG Calder IC Burcham PC 《Journal of biochemical and molecular toxicology》2000,14(6):335-345
Pretreatment with peroxisome proliferators protects mice against various hepatotoxicants. Since our previous work suggested that the hepatoprotection may involve an increased ability to cope with oxidative stress, the present work directly addressed this possibility. Several observations indicated a heightened defense against oxidative stress accompanies the hepatoprotection produced by clofibrate. Firstly, the carbonyl content of hepatic proteins from clofibrate-pretreated mice was 40% lower than those from vehicle-treated controls. Secondly, liver homogenates from clofibrate-pretreated mice produced less thiobarbituric acid reactive substances upon incubation under aerobic conditions or exposure to ferrous sulfate. This effect was not due to lower levels of peroxidation-prone polyunsaturated fatty acids in clofibrate-treated livers. Thirdly, in vitro experiments indicated that the antioxidant factor in liver homogenates from clofibrate-pretreated mice was not glutathione. Rather, since it was inactivated by proteases and heat treatment, we concluded that a protein is involved. Collectively, our results suggest that a resistance to lipid peroxidation develops in mouse liver during exposure to clofibrate. The identity of the putative antioxidant protein and its contribution to the protection against liver toxicity observed in this and other laboratories awaits future investigation. 相似文献
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Marie GB Hansen Mette Christoffersen Line R Thuesen Morten R Petersen Anders M Bojesen 《Acta veterinaria Scandinavica》2010,52(1):3
Background
Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum are able to infect horses. However, the extend to which Danish horses are infected and seroconvert due to these two bacteria is unknown. The aim of the present study was to evaluate the seroprevalence of B. burgdorferi sensu lato and A. phagocytophilum in Danish horses.Methods
A total of 390 blood samples collected from all major regions of Denmark and with a geographical distribution corresponding to the density of the Danish horse population were analyzed. All samples were examined for the presence of antibodies against B. burgdorferi sensu lato and A. phagocytophilum by the use of the SNAP®4DX ® ELISA test.Results
Overall, 29.0% of the horses were seropositive for B. burgdorferi sensu lato whereas 22.3% were seropositive for A. phagocytophilum.Conclusions
Antibodies against B burgdorferi sensu lato and A. phagocytophilum are commonly found among Danish horses thus showing that Danish horses are frequently infected by these organisms.4.
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Estimates of DNA and protein sequence divergence: an examination of some assumptions 总被引:5,自引:3,他引:2
Some of the assumptions underlying estimates of DNA and protein sequence
divergence are examined. A solution for the variance of these estimates
that allows for different mutation rates and different population sizes in
each species and for an arbitrary structure in the initial population is
obtained. It is shown that these conditions do not strongly affect
estimates of divergence. In general, they cause the variance of divergence
to be smaller than a binomial variance. Thus, the binomial variance that is
usually assumed for these estimates is safely conservative. It is shown
that variability in the mutation rate among sites can have an effect as
large as or larger than variability in the mutation rate among bases.
Variability in the mutation rate among bases and among sites causes the
number of substitutions between two sequences to be underestimated. Protein
and DNA sequences from several species are collected to estimate the
variability in mutation rates among sites. When many homologous sequences
are known, standard methods to estimate this variability can be used. The
estimates of this variability show that this factor is important when
considering the spectrum of spontaneous mutations and is strongly reflected
in the divergence of sequences. Smaller variability is found for the third
position of codons than for the first and second codon positions. This may
be because of less selective constraints on this position or because the
third position has been saturated with mutations for the sequences
examined.
相似文献
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Xue Lin Jan Stenvang Mads Heilskov Rasmussen Shida Zhu Niels Frank Jensen Line S Tarpgaard Guangxia Yang Kirstine Belling Claus Lindbjerg Andersen Jian Li Lars Bolund Nils Brünner 《BMC genomics》2015,16(1)
Background
Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown.Results
We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38 or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of ‘DNA methylation entropy’ to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples.Conclusion
Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1552-y) contains supplementary material, which is available to authorized users. 相似文献10.