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111.
Clustered damage in DNA includes two or more closely spaced oxidized bases, strand breaks or abasic sites that are induced
by high- or low-linear-energy-transfer (LET) radiation, and these have been found to be repair-resistant and potentially mutagenic.
In the present study we found that abasic clustered damages are also induced in primary human fibroblast cells by low-LET
X-rays even at very low doses. In response to the induction of the abasic sites, primary fibroblasts irradiated by low doses
of X-rays in the range 10–100 cGy showed dose-dependent up-regulation of the DNA repair enzyme, ApeI. We found that the abasic
clusters in primary fibroblasts were more lethal to cells when hApeI enzyme expression was down-regulated by transfecting
primary fibroblasts with hApeI siRNA as determined by clonogenic survival assay. Endonuclease activity of hApeI was found
to be directly proportional to hApeI gene-silencing efficiency. The DNA repair profile showed that processing of abasic clusters
was delayed in hApeI-siRNA-silenced fibroblasts, which challenges the survival of the cells even at very low doses of X-rays.
Thus, the present study is the first to attempt to understand the induction of cluster DNA damage at very low doses of low-LET
radiation in primary human fibroblasts and their processing by DNA repair enzyme ApeI and their relation with the survival
of the cells. 相似文献
112.
Tina R. Clark Amanda M. Lackey Betsy Kleba Lonnie O. Driskell Erika I. Lutter Craig Martens David O. Wood Ted Hackstadt 《Journal of bacteriology》2011,193(18):4993-4995
Transformation frequencies of a mariner-based transposon system in Rickettsia rickettsii were determined using a plaque assay system for enumeration and isolation of mutants. Sequence analysis of insertion sites in both R. rickettsii and R. prowazekii indicated that insertions were random. Transposon mutagenesis provides a useful tool for rickettsial research. 相似文献
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Ting L. Luo Michael E. Vanek Carlos Gonzalez-Cabezas Carl F. Marrs Betsy Foxman Alexander H. Rickard 《Journal of applied microbiology》2022,132(2):855-871
Numerous in vitro biofilm model systems are available to study oral biofilms. Over the past several decades, increased understanding of oral biology and advances in technology have facilitated more accurate simulation of intraoral conditions and have allowed for the increased generalizability of in vitro oral biofilm studies. The integration of contemporary systems with confocal microscopy and 16S rRNA community profiling has enhanced the capabilities of in vitro biofilm model systems to quantify biofilm architecture and analyse microbial community composition. In this review, we describe several model systems relevant to modern in vitro oral biofilm studies: the constant depth film fermenter, Sorbarod perfusion system, drip–flow reactor, modified Robbins device, flowcells and microfluidic systems. We highlight how combining these systems with confocal microscopy and community composition analysis tools aids exploration of oral biofilm development under different conditions and in response to antimicrobial/anti-biofilm agents. The review closes with a discussion of future directions for the field of in vitro oral biofilm imaging and analysis. 相似文献
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RP Madan C Carpenter T Fiedler S Kalyoussef TC McAndrew S Viswanathan M Kim MJ Keller DN Fredricks BC Herold 《PloS one》2012,7(7):e40415
Background
Genital secretions collected from adult women exhibit in vitro activity against herpes simplex virus (HSV) and Escherichia coli (E. coli), but prior studies have not investigated this endogenous antimicrobial activity or its mediators in adolescent females.Methodology/Principal Findings
Anti-HSV and anti-E.coli activity were quantified from cervicovaginal lavage (CVL) specimens collected from 20 sexually active adolescent females (15–18 years). Soluble immune mediators that may influence this activity were measured in CVL, and concentrations of Lactobacillus jensenii and crispatus were quantified by PCR from vaginal swabs. Results for adolescents were compared to those obtained from 54 healthy, premenopausal adult women. Relative to specimens collected from adults, CVL collected from adolescent subjects had significantly reduced activity against E. coli and diminished concentrations of protein, IgG, and IgA but significantly increased anti-HSV activity and concentrations of interleukin (IL)-1α, IL-6 and IL-1 receptor antagonist. Vaginal swabs collected from adolescent subjects had comparable concentrations of L. crispatus but significantly reduced concentrations of L. jensenii, relative to adult swabs.Conclusions/Significance
Biomarkers of genital mucosal innate immunity may differ substantially between sexually active adolescents and adult women. These findings warrant further study and may have significant implications for prevention of sexually transmitted infections in adolescent females. 相似文献120.
Mao P Gallagher P Nedungadi S Manczak M Shirendeb UP Kohama SG Ferguson B Park BS Reddy PH 《Biochimica et biophysica acta》2012,1822(2):111-119
The purpose of this study was to determine the relationship between mitochondrial DNA (mtDNA) deletions, mtDNA content and aging in rhesus monkeys. Using 2 sets of specific primers, we amplified an 8 kb mtDNA fragment covering a common 5.7 kb deletion and the entire 16.5 kb mitochondrial genome in the brain and buffy-coats of young and aged monkeys. We studied a total of 66 DNA samples: 39 were prepared from a buffy-coat and 27 were prepared from occipital cortex tissues. The mtDNA data were assessed using a permutation test to identify differences in mtDNA, in the different monkey groups. Using real-time RT-PCR strategy, we also assessed both mtDNA and nuclear DNA levels for young, aged and male and female monkeys. We found a 5.7 kb mtDNA deletion in 81.8% (54 of 66) of the total tested samples. In the young group of buffy-coat DNA, we found 5.7 kb deletions in 7 of 17 (41%), and in the aged group, we found 5.7 kb deletions in 12 of 22 (54%), suggesting that the prevalence of mtDNA deletions is related to age. We found decreased mRNA levels of mtDNA in aged monkeys relative to young monkeys. The increases in mtDNA deletions and mtDNA levels in aged rhesus monkeys suggest that damaged DNA accumulates as rhesus monkeys age and these altered mtDNA changes may have physiological relevance to compensate decreased mitochondrial function. 相似文献