Antimicrobial resistance (AMR) is a global crisis for human public health which threatens the effective prevention and control of ever-increasing infectious diseases. The advent of pandrug-resistant bacteria makes most, if not all, available antibiotics invalid. Meanwhile, the pipeline of novel antibiotics development stagnates, which prompts scientists and pharmacists to develop unconventional antimicrobials. Bacteriophage-derived endolysins are cell wall hydrolases which could hydrolyze the peptidoglycan layer from within and outside of bacterial pathogens. With high specificity, rapid action, high efficiency, and low risk of resistance development, endolysins are believed to be among the best alternative therapeutic agents to treat multidrug resistant (MDR) bacteria. As of now, endolysins have been applied to diverse aspects. In this review, we comprehensively introduce the structures and activities of endolysins and summarize the latest application progress of recombinant endolysins in the fields of medical treatment, pathogen diagnosis, food safety, and agriculture.
Exiguobacterium spp. are alkaliphilic, halotolerant, non-spore-forming Gram-positive bacilli, hitherto uncharacterized from human infections. Six isolates of Exiguobacterium aurantiacum were obtained from patients with bacteraemia, three of whom had myeloma. All isolates formed orange-yellow pigmented colonies on blood agar, were catalase- and DNase-positive, and grew on nutrient agar at pH 10 and in the presence of NaCl 6% w/v. The six isolates were susceptible to all antimicrobial agents tested and were uniform in their fatty acid and mass spectrum profiles.
As one of the post-translational modifications, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) often occurs on serine (Ser) and threonine (Thr) residues of specific substrate cellular proteins via the addition of O-GlcNAc group by O-GlcNAc transferase (OGT). Maintenance of normal intracellular levels of O-GlcNAcylation is controlled by OGT and glycoside hydrolase O-GlcNAcase (OGA). Unbalanced O-GlcNAcylation levels have been involved in many diseases, including diabetes, cancer, and neurodegenerative disease. Recent research data reveal that O-GlcNAcylation at histones or non-histone proteins may provide recognition platforms for subsequent protein recruitment and further initiate intracellular biological processes. Here, we review the current understanding of the ‘O-GlcNAc code’ mediated intracellular biological functions of downstream proteins.
Objective: The objective of this study was to assess the attitude and hesitancy towards vaccine against COVID-19 in a Pakistani Population. Materials and Methods: A mix-method, prospective study was conducted and adults (aged ≥18 years) residing in Pakistan were invited to participate..The questionnaire was prepared, hosted in Google Forms and circulated through electronic platforms and was also available to be done in in-person. Data was compiled from 15 th September to 30 th November 2020. Results: The response rate was 80%. A total of 1003 participants were included in the final analysis. Of them, 75% completed survey questionnaire online, while remaining 25% responded in-person. The mean age of the participants was 29.62±10.47 years. The majority of participants were females; 60.9% (n=611). 57.02% (n=572) of the participants were employed at the time of survey. Overall, 70.68% (n=709) of the participants had previous experience of vaccines such as the flu vaccine Only 4.9% (n=49) participants thought that they will be seriously ill from COVID-19 within six months and 39% (n=392) participants were confident that they will get COVID-19. A total of 71.29% of the participants reported they would consider getting vaccinated once available. There was statistical association between gender and getting vaccinated (P<0.001). Conclusion: This study demonstrated that majority of the participants showed positive attitude towards considering COVID-19 vaccine. However awareness with informed knowledge of efficacy, possible adverse effects and cost would be of added great value to increase the real response of Pakistani population towards COVID-19 vaccination.
Transcriptional activation of p21 (cyclin-dependent kinase inhibitor 1A) due to DNA damage often alters the distribution of histone variant H2A.Z at the p21 gene. However, whether the human INO80 complex regulates changes in H2A.Z at the p21 promoter is unclear. We show here that activation of p21 expression by doxorubicin (Doxo) in U2OS cells is required for removal of H2A.Z by INO80 at the p53-binding site proximal region (-2.2 kb) of the p21 promoter. A purified INO80 complex, but not the INO80E653Q mutant-complex, which lost DNA-sliding activity, is mainly responsible for removing H2A.Z from reconstituted nucleosomes in vitro. This activity was enhanced with MOF-mediated histone acetylation, suggesting that INO80 more readily removes H2A.Z from loosened nucleosomes. Also, co-occupancy of INO80 and H2A.Z -2.2 kb upstream of the p21 transcriptional start site (TSS) was observed. H2A.Z at this region was removed in a short time after Doxo treatment and activated p21 expression. However, p21 induction was inhibited by INO80 knockdown by delaying H2A.Z removal, indicating the need for INO80. Moreover, shMOF-mediated histone acetylation reduced recruitment of INO80 -2.2 kb upstream of p21 TSS and inhibited the removal of H2A.Z in Doxo-treated cells. These data provide new insights into the transcriptional regulation of p21 by the INO80 complex.
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