Significance: NER removes helix-destabilizing bulky adducts including UV lesions and crosslinks generated by formaldehyde. NER protects skin cells from carcinogenesis. XP patients deficient in NER develop progressive neurological dysfunction. We discovered that collaboration between TOP1 and the BER pathway can substitute for the lack of NER. This previously unappreciated repair pathway is initiated by TOP1-dependent sensing topological alterations near UV lesions and subsequent SSB formation followed by BER. Considering that the SSB formation by TOP1 is the rate-limiting step, and TOP1 expression is very low in the skin and neuronal tissues, our finding may help understand the molecular mechanisms and genetic determinants underlying the neurological dysfunction of XP patients, although TOP1-relevant endogenous lesions are currently unknown.
30 August 2023 in Transboundary and Emerging Diseases
Foot-and-mouth disease (FMD) in cloven-hoofed animals is considered an economically devastating disease in endemic countries like Bangladesh, where the livestock sector contributes to a greater portion of the nation’s economy. The causative agent of the disease, foot-and-mouth disease virus (FMDV), equipped with higher mutational frequency challenges the efficacy of the existing vaccine and control measures. This study, including 32 districts and 71 outbreaks to reveal epidemiological patterns and mutational trends of FMDV over the past 10 years (2012–2021), reported a 54.7% prevalence of FMD, with the majority of outbreaks occurring during the rainy season. Different risk factors such as age, gender, farming system, and vaccination status demonstrated a significant association with FMD cases which was confirmed by the χ2 test ( ). VP1 sequence analyses reported the predominance of serotype O (85%) over serotype A (11%) and serotype Asia 1 (4%). Bangladesh has foreseen the emergence of several novel FMDV strains during this decade. Novel sublineages, Ind-2001BD1 (Ind-2001e) and Ind-2001BD2, were reported under serotype O, the G-IX lineage of serotype Asia 1 emerged in 2018, and most recently in 2021, a new genotype named MYMBD21 under the lineage SA-2018 was detected for the first time in Bangladesh. Until now, Ind-2001e (Ind-2001BD1) sublineage under serotype O became the predominant sublineage in Bangladesh. From the mutational trend analysis, highly variable sites were observed at positions 138 and 140 within the G-H loop for serotype O. For serotype A and Asia 1, 45th and 44th residues within the B-C loop showed the highest amino acid variations, respectively. A changing mutational pattern among the 2019–2021 FMDV O and A isolates was also observed. The findings of the study would be crucial to understand the FMD situation and designing necessary preventive steps according to the progressive control pathway for FMD control in Bangladesh.
Frequent vaccine failure leading to recurrent outbreaks of Foot-and-Mouth Disease (FMD) in livestock populations necessitates the development of a customizable vaccine platform comprising potential antigenic determinants of circulating lineages of FMD viruses. Artificially designed, chimaeric protein-based recombinant vaccines are novel approaches to combat the phylogenetically diverse FMD Virus (FMDV) strains. Among seven recognized serotypes, only serotypes O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages of FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant proteins, procuring immunogenicity against circulating diverse genotypes of FMDV serotypes O and A. Two chimaeric proteins, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guinea pigs with a considerable antigen load of B1 and B3 followed by serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimaeric proteins strongly indicate their credibility as novel vaccine candidates for existing serotypes O and A of FMDV in Bangladesh and surrounding territories.
COVID-19 vaccination strategies, including heterologous prime–boost regimens and additional booster doses, aim to optimize immune responses. However, seroepidemiological studies on immune responses to different COVID-19 vaccine types and schedules remain limited. This study investigated antibody levels following homologous and heterologous prime-and-boost COVID-19 vaccination in Bangladesh. In a cohort of 606 participants who received first/second/booster doses of vaccines (AstraZeneca, Moderna, Pfizer-BioNTech, and Sinopharm), anti-spike IgG and anti-nucleocapsid IgG levels were measured. Antibody titer variations with respect to age, gender, intervals between doses, and prior infection status were analyzed. mRNA vaccines elicited the highest antibody levels after homologous and heterologous boosting. The AstraZeneca booster resulted in a sharp titer decline rate of ~0.04 units per day. Second or booster vaccine doses significantly increased antibody levels, especially in males (p < 0.05). Older age correlated with higher titers, likely reflecting previous infection, which was further confirmed by the elevation of anti-nucleocapsid IgG levels. About 95.5% of non-Sinopharm recipients were anti-nucleocapsid IgG positive, suggesting prior exposure exceeding self-reported infections (12.5%). mRNA and heterologous COVID-19 boosting enhances humoral immunity over homologous prime–boost vector/inactivated vaccination. However, waning immunity merits further investigation across vaccine platforms.
Although the Bay of Bengal (BoB) is the world’s largest bay, possessing distinct physiochemical properties, it has garnered little research focus concerning its microbial diversity and ecological importance. Here, we present amplicon (16S and 18S) profiling and shotgun metagenomics data regarding microbial communities from BoB’s eastern coast, viz., Saint Martin and Cox’s Bazar, Bangladesh. From the 16S sequencing data, Proteobacteria appeared to be the dominant phylum in both locations, with Alteromonas , Methylophaga , Anaerospora , Marivita , and Vibrio dominating in Cox’s Bazar and Pseudoalteromonas , Nautella , Marinomonas , Vibrio , and Alteromonas dominating the Saint Martin site. From the 18S sequencing data, Ochrophyta, Chlorophyta, and Protalveolata appeared among the most abundant eukaryotic divisions in both locations, with significantly higher abundance of Choanoflagellida, Florideophycidae, and Dinoflagellata in Cox’s Bazar. Functional annotations revealed that the microbial communities in these samples harbor genes for biofilm formation, quorum sensing, xenobiotics degradation, antimicrobial resistance, and a variety of other processes. Together, these results provide the first molecular insight into the functional and phylogenetic diversity of microbes along the BoB coast of Bangladesh and lay the foundation for further in-depth assessment of microbial community dynamics and functional potential in the context of global change in this region.
Monkeypox (Mpox) disease, caused by the Monkeypox virus (Mpox virus), emerged as a significant global health threat during the 2022 outbreak, prompting the World Health Organisation (WHO) to declare it a Public Health Emergency of International Concern (PHEIC). Rapid evolution through genomic modifications enhanced its outbreak potential. Zoonotic transmission occurs through close contact with infected rodents or primates; human-to-human transmission occurs via close contact or homosexual intercourse. The virus disseminates via the lymphatic system, causing symptoms ranging from mild skin lesions to severe multi-system complications or even death. Diagnosis incorporates clinical symptoms as well as advanced molecular and immunological methods. Currently, no specific antiviral medications or vaccines are available for Mpox, necessitating reliance on conventional therapeutic supports and treatments developed for smallpox. Raising awareness, promoting protective practices, implementing surveillance, enabling rapid diagnosis, ensuring timely treatment, and promoting mass vaccination are crucial to curb Mpox transmission. This narrative review provides a comprehensive overview of the current knowledge on epidemiology, evolution, transmission, pathogenesis, clinical signs, diagnosis, treatment, vaccination, and prevention strategies for Mpox.