Translational Research Platform for Veterinary Biologicals (India)

Japanese encephalitis virus (JEV) remains a major health threat across Asia, yet the contribution of genotype-specific variation in the multifunctional NS5 protein to viral fitness is not fully resolved. This study evaluated how sequence differences among JEV genotypes G1-G5 shape NS5 stability and, in turn, replication potential. A unified in-silico workflow combined physicochemical profiling, residue-level substitution mapping, and atomistic molecular dynamics to compare structural stability and conformational behavior across genotypes, with a focus on substitutions predicted to modulate enzymatic performance. Analyses revealed that G5 NS5 maintains a balanced electrostatic environment and persistent hydrogen-bonding networks, yielding greater structural stability than other genotypes. In contrast, G4 NS5 presented a charge imbalance and reduced stability. Simulations consistently supported the robustness of G5 dynamics, with specific substitutions, including Y65, M59, E182, and T191, contributing to improved packing, favorable local interactions, and putative gains in catalytic efficiency. These molecular attributes align with heightened replication capacity and provide a mechanistic rationale for the recent prominence of G5 strains relative to G1-G4. Comprising together, our results demonstrate that genotype-linked substitutions in NS5 directly influence protein stability, replication efficiency, and adaptive potential. Translationally, prioritizing G5-informed NS5 features may guide the design of small-molecule inhibitors and vaccine antigens with broader protective value.

Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using invivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM progression. In parallel, we quantified circulating metabolites, revealing kynurenic acid as a differentially abundant molecule that impaired the interaction between cancer cells and the brain vasculature in exvivo functional assays. Together, these results illuminate the potential role of gut microbiota in modulating breast-BrM via the gut-to-brain axis.

The phrase ἀπὸ καταβολῆς κόσμου (apo katabolēs kosmou, “from the foundation of the world”) in Revelation 13:8 has sparked considerabledebate among scholars due to its grammatical flexibility and theological depth. This article is an attemptto determine whether it modifies “the book of life”(implying the names were written from the foundation of the world) or “the Lamb who was slain”(implying the Lamb was foreordained to be slain from the foundation of the world

Understanding the nature of linkage disequilibrium (LD) between molecular markers reflects the degree of non-random association between their alleles, which is essential for genome-wide association studies. The main objective of this study was to assess the chromosome-wise linkage disequilibrium and haplotype block structure in indigenous cattle breeds of Tamil Nadu, India. A total of 79 animals belonging to five indigenous cattle breeds were considered as single indigenous cattle population and three samples per breed were sequenced using Illumina NovaSeqTM 6000 and Illumina HiSeq 2500. The LD parameter (r2) was estimated for a total of 62,095,778 pair- wise SNPs for all autosomes. The chromosome-wise number of SNP pairs, mean r2±standard deviation and median r2 values were 2,141,234, 0.484±0.246 and 0.493, respectively. Chromosome-wise mean r2 of different distance bins were calculated and it showed the maximum r2 value of 0.839 at 31-70 kb distance for Chromosome 11 and minimum r2 value of zero for Chromosome 7, 11, 15, 20 and 29, respectively at a distance 71-100 kb. This study also revealed a total of 413, 277 haplotype blocks which covered 2.34% of the autosomal genome. There was a total of 1,589,118 SNPs distributed within the haplotype blocks, covering a total length of 53.62 mb. The results of the study suggest the need for breed-specific reference populations for indigenous cattle breeds, which have a greater density of molecular markers of economic significance and thereby to identify breed-specific haplotypes in future.