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Mosley Gravgaard posted an update 2 days, 12 hours ago
The molecular mechanism underlying the development of vancomycin-intermediate Staphylococcus aureus (VISA) remains unclear. The abuses of antibacterial compounds lead to a change in the bacterial susceptibility patterns. Therefore, we examined the effect of Chlorhexidine (CHX) on in vitro development of VISA and reported CHX-selected VISA mutant Tm1 with phenotypic features similar to the clinical VISA isolates. WalKR, VraTSR, and GraSR are the most common regulatory systems involved in VISA evaluation. The expression of these systems, as well as walKR-regulated autolysins and VraTSR-regulated cell wall stimulon, were compared, by RT-qPCR, between the mutant and parental strains. The results revealed the downregulation of walKR, vraTSR, atlA, sle1, lytM, and pbpB genes in Tm1. The complete sequences of walKR and vraTSR genes was compared using the Sanger sequencing method. We detected Walk.R55C, WalR.A38T, and VraS·N340-D347del novel mutations in Tm1. These mutations were classified as deleterious mutations and predicted to affect protein function using the SIFT prediction algorithm. Novel mutations in Tm1 confirm the genetic diversity of VISA isolates. We suggest that WalKR and VraTSR may be involved in sense and response to CHX. Kynurenic acid In this regard, CHX may have a role in cell wall degradation of S. aureus and the emergence of VISA due to mutations in the CA domain of the Walk and VraS and the REC domain of WalR. Therefore, CHX should be used with caution.Transposable elements (TEs) regularly capture fragments of genes. When the host silences these TEs, siRNAs homologous to the captured regions may also target the genes. This epigenetic crosstalk establishes an intragenomic conflict silencing the TEs has the cost of silencing the genes. If genes are important, however, natural selection may maintain function by moderating the silencing response, which may also advantage the TEs. In this study, we examined this model by focusing on Helitrons, Pack-MULEs, and Sirevirus LTR retrotransposons in the maize genome. We documented 1263 TEs containing exon fragments from 1629 donor genes. Consistent with epigenetic conflict, donor genes mapped more siRNAs and were more methylated than genes with no evidence of capture. However, these patterns differed between syntelog versus translocated donor genes. Syntelogs appeared to maintain function, as measured by gene expression, consistent with moderation of silencing for functionally important genes. Epigenetic marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH methylation. Translocated genes, in contrast, bore the signature of silencing. They were highly methylated and less expressed, but also overrepresented among donor genes and located away from chromosomal arms, which suggests a link between capture and gene movement. Splitting genes into potential functional categories based on evolutionary constraint supported the synteny-based findings. TE families captured genes in different ways, but the evidence for their advantage was generally less obvious; nevertheless, TEs with captured fragments were older, mapped fewer siRNAs, and were slightly less methylated than TEs without captured fragments. Collectively, our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.Cytogenetic abnormalities are a recognized factor in the pathogenesis of multiple myeloma (MM). While chromosomal translocations involving the IGH gene have been investigated and reported, the implications of deletions or amplifications in the IGH gene have been less frequently examined. We conducted a retrospective analysis of 260 patients with MM from Northern Israel. Fluorescent in situ hybridization (FISH) analysis of separated CD-138 positive cells was done on bone marrow samples collected between 2016 and 2018. We used IGH break apart probes to identify IGH abnormalities and performed statistical analysis of clinical and prognostic features, comparing the different cytogenetic groups. Deletions in the variable region of the IGH (IGHv) were found in 17.3 % (n = 45) of patients and correlated with significantly worse progression free survival (PFS) after two years of follow up (p = 0.008), as well as with a worse response to 1st line treatment (p = 0.037). The median PFS was 7.1 and 17.7 months in patients with and without IGHv deletion, respectively. PFS differences remained significant (p = 0.017) in subgroup analysis of patients with high-risk cytogenetics (n = 108, 19 with IGHv deletion). Overall survival was not significantly different in the two groups. Constant region (IGHc) amplifications, were less frequently found (6.15 %, n = 16), yet significantly correlated with worse PFS after two years of follow up (p = 0.023). This difference remained valid in the high-risk subgroup (p = 0.001). In Conclusion, we identified that deletion of the IGH variable region and amplification in the IGH constant region, are both associated with poor prognosis and inferior outcome in MM.Clove (Eugenia caryophyllata Thunb.) essential oil (CEO) has been extensively utilized and well-recognized due to its wide medicinal activities. In our study, the gas chromatography-mass spectrometry (GC-MS) technology was applied in characterizing the CEO chemical composition. Altogether 58 volatile components were discovered from bud CEO. To further clarify the antioxidant and anti-aging activities of CEO in vivo, the nematode C. elegans was used as an animal model. The results suggested that, chronic CEO treatment significantly extended the lifespan and promoted the production and health. As expected, CEO possessed antioxidant activities against the reactive oxygen species (ROS) through inducing the expression of SOD-3 or GST-4. Meanwhile, it was found that CEO treatment induced the DAF-16/FOXO nuclear translocation from the cytoplasm. Finally, the results indicated that CEO caused the apoptosis of germ cells in acep-1 and daf-16 dependent manner. Overall, our research suggests that CEO possesses antioxidant and anti-aging activities, and that DAF-16 may be essential for its biological functions.