Biology subjects

Thomas, B. N.

Publications and source records attributed to Thomas, B. N..

3 recordsLinked to original sources

bioRxiv2022

Molecular evolution and inheritance pattern of Sox gene family among Bovidae

Sox gene is an evolutionarily conserved family of transcription factors that play important roles in cellular differentiation and numerous complex developmental processes. In vertebrates, Sox proteins are required for cell fate decision, morphogenesis, and control self-renewal in embryonic and adult stem cells. Sox gene family has been well studied in multiple species including humans but scanty or no study in Bovidae. In this study, we conducted a detailed evolutionary analysis of this gene family in Bovidae, including their physicochemical properties, biological functions, and patterns of inheritance. We performed a genome-wide cataloguing to explore the Sox gene family using multiple bioinformatics tools. Our analysis revealed conserved motifs that are crucial to the ability of Sox genes to interact with the regulatory regions of target genes and orchestrate multiple developmental and physiological processes. Importantly, we report a unique motif being EFDQYL/ELDQYL found in SoxE and SoxF groups. Further analysis revealed that this motif sequence accounts for the binding and transactivation potential of Sox proteins. Protein-protein interaction showed significant interaction among Sox genes and related genes implicated in embryonic development and the regulation of cell differentiation. We conclude that Sox gene family uniquely evolved among Bovidae with a few exhibiting important motifs that drives several developmental and physiological processes.

evolutionary biology↗

bioRxiv2022

Deciphering inhibitory mechanism of coronavirus replication through host miRNAs-RNA-dependent RNA polymerase (RdRp) interactome

Despite what we know so far, Covid-19, caused by SARS-CoV-2 virus, remains a pandemic that still require urgent healthcare intervention. The frequent mutations of the SARS-CoV-2 virus has rendered disease control with vaccines and antiviral drugs quite difficult and challenging, with newer variants surfacing constantly. There is therefore the need for newer, effective and efficacious drugs against coronaviruses. Considering the role of RNA dependent, RNA polymerase (RdRp) as an important enzyme necessary for the virus life cycle and its conservation among coronaviruses, we investigated potential host miRNAs that can be employed as broad-range antiviral drugs averse to coronaviruses, with particular emphasis on BCoV, MERS-CoV, SARS-CoV and SARS-CoV-2. miRNAs are small molecules capable of binding mRNA and regulate expression at transcriptional or translational levels. Our hypothesis is that host miRNAs have the potential of blocking coronavirus replication through miRNA-RdRp mRNA interaction. To investigate this, we downloaded the open reading frame (ORF 1ab) nucleotide sequences and used them to interrogate miRNA databases for miRNAs that can bind them. We employed various bioinformatics tools to predict and identify the most effective host miRNAs. In all, we found 27 miRNAs that target RdRp mRNA of multiple coronaviruses, of which three - hsa-miR-1283, hsa-miR-579-3p, and hsa-miR-664b-3p target BCoV, SARS-CoV and SARS-CoV-2. Additionally, hsa-miR-374a-5p has three bovine miRNAs homologs viz bta-miR-374a, bta-miR-374b, and bta-miR-374c. Inhibiting the expression of RdRp enzyme via non-coding RNA is novel and of great therapeutic importance in the control of coronavirus replication, and could serve as a broad-spectrum antiviral, with hsa-miR-1283, hsa-miR-579-3p, and hsa-miR-664b-3p highly promising.

genomics↗

bioRxiv2021

Transcriptome profiling reveals CD73 and age-driven changes in neutrophil responses against Streptococcus pneumoniae

Neutrophils are required for host resistance against Streptococcus pneumoniae but their function declines with age. We previously found that CD73, an enzyme required for antimicrobial activity, is down-regulated in neutrophils from aged mice. This study explored transcriptional changes in neutrophils induced by S. pneumoniae to identify pathways controlled by CD73 and dysregulated with age. Ultrapure bone marrow-derived neutrophils isolated from wild type (WT) young, old, and CD73KO young mice were mock-challenged or infected with S. pneumoniae ex vivo. RNA sequencing was performed to identify differentially expressed genes (DEGs). We found that infection triggered distinct global transcriptional changes across hosts, that were strongest in CD73KO neutrophils. Surprisingly, there were more down-regulated than up-regulated genes in all groups upon infection. Down-regulated DEGs indicated a dampening of immune responses in old and CD73KO hosts. Further analysis revealed that CD73KO neutrophils expressed higher numbers of long non-coding RNAs (lncRNAs) compared to WT controls. Predicted network analysis indicated that CD73KO specific lncRNAs control several signaling pathways. We found that genes in the JNK-MAPK-pathway were up-regulated upon infection in CD73KO and WT old but not in young mice. This corresponded to functional differences, as phosphorylation of the downstream AP-1 transcription factor component c-Jun was significantly higher in infected CD73KO and old mice neutrophils. Importantly, inhibiting JNK/AP-1 rescued the ability of these neutrophils to kill S. pneumoniae. Altogether, our findings revealed that neutrophils modify their gene expression to better adapt to bacterial infection and that this capacity declines with age and is regulated by CD73.

immunology↗