Search

Virus assembly, budding, or surface proteins play important roles such as viral attachment to cells, fusion, and entry into cells. The present study aimed to identify potential antigenic proteins and epitopes that could be used to develop a vaccine or diagnostic assay against the Monkeypox virus (MPXV) which may cause a potential epidemic. To do this, 39 MPXV proteins (including assembly, budding, and surface proteins) were analyzed using an in silico approach. Of these 39 proteins, the F5L virus protein was found to be the best vaccine candidate due to its signal peptide properties, negative GRAVY value, low transmembrane helix content, moderate aliphatic index, large molecular weight, long-estimated half-life, beta wrap motifs, and being stable, soluble, and containing non-allergic features. Moreover, the F5L protein exhibited alpha-helical secondary structures, making it a potential "structural antigen" recognized by antibodies. The other viral protein candidates were A9 and A43, but A9 lacked beta wrap motifs, while A43 had a positive GRAVY value and was insoluble. These two proteins were not as suitable candidates as the F5L protein. The KRVNISLTCL epitope from the F5L protein demonstrated the highest antigen score (2.4684) for MHC-I, while the GRFGYVPYVGYKCI epitope from the A9 protein exhibited the highest antigenicity (1.754) for MHC-II. Both epitopes met the criteria for high antigenicity, non-toxicity, solubility, non-allergenicity, and the presence of cleavage sites. Molecular docking and dynamics (MD) simulations further validated their potential, revealing stable and energetically favorable interactions with MHC molecules. The immunogenicity assessment showed that GRFGYVPYVGYKCI could strongly induce immune responses through both IFN-γ and IL-4 pathways, suggesting its capacity to provoke a balanced Th1 and Th2 response. In contrast, KRVNISLTCL exhibited limited immunostimulatory potential. Overall, these findings lay the groundwork for future vaccine development, indicating that F5L, particularly the GRFGYVPYVGYKCI epitope, may serve as an effective candidate for peptide-based vaccine design against MPXV., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The human gut microbiota is an extensive population of microorganisms, and it shows significant variations between periods of optimal health and periods of illness. Vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae (CRKP) are both pathogenic agents (BPAs) that can colonize in the gut after dysbiosis of microbiotal composition following antibiotic treatment. Methods: This study aimed to investigate the impact of antibiotics on the microbiotal composition of the gut. For this purpose, the first pass meconiums of 20 patients and the first rectal swabs containing BPAs of the same patients after antibiotic treatment were studied using next-generation sequencing-based 16S rRNA gene analysis. The V1-V9 region of 16S rRNA was sequenced with Oxford Nanopore. Results: Twenty-five phyla were detected in the meconiums, and 12 of them were absent after antibiotic treatment. The four most prevalent phyla in meconiums were Bacillota, Pseudomonadota, Bacteroidota, and Actinomycetota. Only the relative abundance of Pseudomonadota was increased, while a significant decrease was observed in the other three phyla ( p < 0.05). A significant decrease was observed in alpha-diversity in rectal swabs containing BPAs versus meconiums ( p = 0.00408), whereas an increased variance was observed in beta-diversity in all samples ( p < 0.05). As a result of a LEfSe analysis, Pseudomonadota was found to have a higher relative abundance in rectal swabs, and Bacillota was significantly higher in the meconiums of the twins. Conclusions: Our study strongly verified the relationship between the administration of antibiotics, dysbiosis, and colonization of BPAs in the infants' gut microbiota. Further research would be beneficial and needed, comprising the natural development process of the infants' gut microbiota.

MYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN), prompting a deeper investigation into potential novel oncogenic mechanisms. Analysing comprehensive genomics profiles of 236 "IDH-mutant 1p/19q non-co-deleted" lower-grade gliomas from The Cancer Genome Atlas, we identified somatic genomic alterations within the PMN. In tumours without PMN-alterations but with MYC-overexpression, genes correlated with MYC-overexpression were identified. Our analyses yielded that 86/236 of astrocytomas exhibited no PMN-alterations, a subset of 21/86 displaying relative MYC overexpression. Within this subset, we discovered 42 genes inversely correlated with relative MYC expression, all on 19q. Further analysis pinpointed a minimal common region at 19q13.43, encompassing 15 genes. The inverse correlations of these 15 genes with relative MYC overexpression were re-confirmed using independent scRNAseq data. Further, the micro-deleted astrocytoma subset displayed significantly higher genomic instability compared to WT cases, but lower instability compared to PMN-hit cases. This newly identified 19q micro-deletion represents a potential novel mechanism underlying MYC dysregulation in astrocytomas. Given the prominence of 19q loss in IDH-mutant gliomas, our findings bear significant implications for understanding gliomagenesis., (© 2024. The Author(s).)