Biology subjects

Adegbaju, M. S.

Publications and source records attributed to Adegbaju, M. S..

4 recordsLinked to original sources

bioRxiv2026

The E2F1 regulon orchestrates a proliferative emergency and vascular programming in fetal endothelial progenitors exposed to GDM: a sex-stratified systems medicine approach

Maternal Gestational Diabetes Mellitus (GDM) and obesity are major drivers of the Developmental Origins of Health and Disease (DOHaD), predisposing offspring to premature cardiovascular disease. However, the specific molecular pathways that program this sex-specific vascular risk remain poorly defined due to the cellular complexity of the placenta. We sought to identify the primary regulatory engines of fetal vascular programming in a sex-stratified neonatal cohort. We analyzed purified neonatal Endothelial Colony Forming Cells (ECFCs)--the fundamental progenitors of the fetal vasculature--from pregnancies complicated by GDM and pre-pregnancy obesity. Using a sex-stratified regulatory inference framework, we decoupled the priming effects of obesity from the acute transcriptomic insult of GDM. Our findings reveal a profound functional asymmetry in fetal vascular adaptation. While male progenitors maintain metabolic resilience through AKT3-mediated buffering, the female fetal-placental interface undergoes a systemic proliferative emergency. This maladaptive state is driven by a massive unshackling of the E2F1-regulon (NES = 16.86), triggered by a maternal-fetal surge in CDK/MAPK signaling. This female-specific program prioritizes unscheduled cell-cycle progression at the metabolic expense of angiogenic maturation and innate immune surveillance. GDM imposes a sex-specific epigenetic scar on female fetal endothelial progenitors, characterized by a quantity-over-quality trade-off in vascular development. This identification of the E2F1-pathway as a driver of fetal vascular exhaustion provides a mechanistic basis for the increased cardiovascular vulnerability in female offspring and identifies the cell cycle as a potential therapeutic target for mitigating the long-term sequelae of GDM.

genomics↗

bioRxiv2026

Comparative pangenomics of Trypanosoma brucei reveal host specialization is driven by targeted or segmental genome streamlining in human and equine-restricted lineages

How the eukaryotic parasite Trypanosoma brucei remodels its genome during host specialization remains a fundamental question in evolutionary biology. In contrast to the uniform, systemic gene loss seen in resident bacterial genomes, the structural variations driving niche restriction in extracellular pathogens are poorly defined. Here, we establish a high-resolution comparative structural pangenomic map of the T. brucei complex. By analyzing the human-restricted specialist DAL972 and the equine-restricted specialist Trypanosoma equiperdum IVM-t1 against the conserved TREU927 backbone, we determine how host-vector constraints dictate eukaryotic genome architecture. Our analyses reveal that host specialization is governed by a coordinated spatial blueprint that segregates structural variation into two distinct evolutionary pathways: targeted perimeter streamlining and systemic core erosion. The human specialist DAL972 preserves its core metabolic toolkit under intense purifying selection, restricting genomic variation to the compartmentalized trimming of its sub-telomeric variant surface glycoprotein (VSG) archives. Conversely, the equine specialist IVM-t1, which has completely abandoned cyclical tsetse fly transmission, displays multi-focal core erosion across internal domains. We demonstrate that vector abandonment forces a shift to strict asexual clonal population dynamics. This transition eases purifying selection, allowing obsolete, insect-stage flagellar and cytoskeletal structures to decay through neutral genetic drift. At the chromosomal perimeters, this structural allocation unmasks an unannotated sub-telomeric reservoir of 86 profile-validated retrotransposon hot spot (RHS) and catalytic DDE transposase domains organized into 23 discrete loci. Operating under adaptive positive selection in the human specialist, these silent, repetitive elements function as physical recombination anchors that stabilize strand exchange. This mechanism drives rapid antigenic diversification while insulating the core genome from dangerous macro-rearrangements. Importantly, we bridge this macro-scale chromosomal architecture to micro-scale proteomic execution through tertiary modeling of these unannotated specialized loci. This structural translation unmasks a biophysical mechanism of structural sequestration, where lineage-specific mutations and specificity-determining positions are deeply buried within hydrophobic protein cores to shield functional divergence from host immune surveillance. By pairing these rigid, hidden core packing networks with hyper-variable surface tiles and dynamic boundary hinges, the parasite deploys tiered molecular mimicry to selectively manipulate host cellular networks. Together, these findings redefine our understanding of structural and non-coding architecture as mechanical drivers of parasitic adaptability, uncovering a direct pipeline from pangenomic spatial variations to stable, structure-based allosteric drug targets.

genomics↗

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↗