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.

Stromal fibroblasts of the mesenchyme regulate critical signaling gradients along the crypt–villus axis in the intestine and provide a niche that supports intestinal stem cells. In this study, we reported that PDGFRA-expressing fibroblasts secrete ligands that promote a fetal-like state in the intestinal mucosa during early WNT-mediated tumorigenesis. Data from a mouse model of WNT-driven oncogenesis and single-cell RNA sequencing of mesenchymal cell populations revealed a dynamic reprogramming of PDGFRA+ fibroblasts that facilitates WNT-mediated tissue transformation. Functional assays of potential mediators of cell-to-cell communication between these fibroblasts and the oncogenic epithelium revealed that TGFβ signaling is notably induced in PDGFRA+ fibroblasts in the presence of oncogenic epithelium, and TGFβ was essential to sustain the fetal-like growth of organoids ex vivo. Reduction of CDX2 in β-catenin mutant intestinal epithelium elevated the fetal-like transcriptome and accelerated WNT-dependent oncogenic transformation in vivo. These results demonstrate that PDGFRA+ fibroblasts are activated during WNT-driven oncogenesis to promote a fetal-like state in the epithelium that precedes and facilitates tumor formation. Significance: TGFβ signaling activated in PDGFRA+ fibroblasts in response to the initial transformation of WNT-hyperactive epithelial cells mediates expression of pro-regeneration ligands that reciprocally induce a fetal-like state in the epithelium, facilitating tumorigenesis.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Modification of Epiregulin levels in mesenchyme or enteroids does not impact growth or viability of either control or β-cateninGOF enteroids

Increased expression of both pro-regenerative and Wnt signaling antagonists occur in Pdgfra-lo cells exposed to oncogenic epithelium