The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.
It has been demonstrated that deuterium oxide enhances the SOS response of Escherichia coli cells induced by chemical genotoxicants and mutagens. This demonstrates that the heavy nonradioactive hydrogen isotope deuterium can be considered to be a comutagen.
Although the pericentromeric regions of chromosomes that are enriched in tandemly repeated satellite DNA represent a significant part of eukaryotic genomes, they remain understudied, which is mainly due to interdisciplinary knowledge gaps. Recent studies suggest their important role in genome regulation, karyotype stability, and evolution. Thus, the idea of satellite DNA as a junk part of the genome has been refuted. The integration of data regarding molecular composition, chromosome behaviour, and the details of the in situ organization of pericentromeric regions is of great interest. The objective of this work was a cytogenetic analysis of the interactions between pericentromeric regions from non-homologous chromosomes in mouse spermatocytes using immuno-FISH. We analysed two events: the associations between centromeric regions of the X chromosome and autosomes and the associations between the centromeric regions of the autosomal bivalents that form chromocenters. We concluded that the X chromosome forms temporary synaptic associations with different autosomes in early meiotic prophase I, which can normally be found until the pachytene–diplotene, without signs of pachytene arrest. These associations are formed between the satellite-DNA-rich centromeric regions of the X chromosome and different autosomes but do not involve the satellite-DNA-poor centromeric region of the Y chromosome. We suggest the hypothetical model of X chromosome competitive replacement from such associations during synaptic correction. We showed that the centromeric region of the X chromosome in association remains free of γH2Ax-dependent chromatin inactivation, while the Y chromosome is completely inactivated. This finding highlights the predominant role of associations between satellite DNA-rich regions of different chromosomes, including the X chromosome. We suppose that X-autosomal transient associations are a manifestation of an additional synaptic disorder checkpoint. These associations are normally corrected before the late diplotene stage. We revealed that the intense spreading conditions that were applied to the spermatocyte I nuclei did not lead to the destruction of stretched chromatin fibers of elongated chromocenters enriched in satellite DNA. The tight associations that we revealed between the pericentromeric regions of different autosomal bivalents and the X chromosome may represent the basis for a mechanism for maintaining the repeats stability in the autosomes and in the X chromosome. The consequences of our findings are discussed.
The lux biosensor of E. coli MG1655 (pDinI::lux) was constructed and a comparative study of the SOS response of three biosensors E. coli MG1655 (pRecA::lux), E. coli MG1655 (pColD::lux), and E. coli MG1655 (pDinI::lux) under the action of genotoxic agents was performed. The listed biosensors were named, respectively, PRecA, PColD, and PDinI. The response amplitude (RA) was chosen as an indicator of the SOS response level of lux biosensors. It was shown that RA of the PDinI biosensor was more expressed than RA of the PRecA biosensor under the action of hydrogen peroxide, alkylating agents such as NMU, MMS, and streptozotocin, antibacterial agent such as dioxidine, and cytostatics such as mitomycin C and cisplatin. Antimetabolite 5-fluorouracil showed activity only with PDinI. Furacilin and 4-NQO, whose metabolites form adducts with DNA, were more active on PColD than on PRecA and PDinI. DNA gyrase inhibitors such as nalidixic acid and ciprofloxacin were less active on PDinI than on PColD and PRecA. Overall, among 13 tested substances, 8 more actively induced SOS response in the PDinI biosensor than in PColD and PRecA. At the same time, 5-fluororacil induced SOS response only with the PDinI biosensor. It was concluded that the PDinI biosensor can be successfully used for the primary detection of potential genotoxicants by their ability to induce SOS response in E. coli cells.
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