Biology subjects

Ismael, A.

Publications and source records attributed to Ismael, A..

3 recordsLinked to original sources

bioRxiv2024

Cytokine and Chemokine Receptor Profiles in Adipose Tissue Vasculature Unravel Endothelial Cell Responses in HIV

Chronic systemic inflammation contributes to a substantially elevated risk of myocardial infarction in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis that contribute to cardiovascular disease. Our objective was to study the effects of plasma from PLWH on endothelial cell (EC) function, with the hypothesis that cytokines and chemokines are major drivers of EC activation. We first broadly phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in adipose tissue in the subcutaneous adipose tissue of 59 PLWH using single cell transcriptomic analysis. We used CellChat to predict cell-cell interactions between ECs and other cells in the adipose tissue and Spearman correlation to measure the association between ECs and plasma cytokines. Finally, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk sequencing to study the direct effects ex-vivo. We observed that arterial and capillary ECs expressed higher interferon and tumor necrosis factor (TNF) receptors. Venous ECs had more interleukin (IL)-1R1 and ACKR1 receptors, and VSMCs had high significant IL-6R expression. CellChat predicted ligand-receptor interactions between adipose tissue immune cells as senders and capillary ECs as recipients in TNF-TNFRSF1A/B interactions. Chemokines expressed largely by capillary ECs were predicted to bind ACKR1 receptors on venous ECs. Beyond the adipose tissue, the proportion of venous ECs and VSMCs were positively plasma IL-6. In ex-vivo experiments, HAECs cultured with plasma-conditioned media from PLWH expressed transcripts that enriched for the TNF- and reactive oxidative phosphorylation pathways. In conclusion, ECs demonstrate heterogeneity in cytokine and chemokine receptor expression. Further research is needed to fully elucidate the role of cytokines and chemokines in EC dysfunction and to develop effective therapeutic strategies.

cell biology↗

bioRxiv2021

Comparative Genome Analysis Reveals Human Pathogenic Potential of ESBL-Escherichia coli Isolated from Swine Microbiomes

BackgroundExtended-spectrum {beta}-lactamase-producing E. coli (ESBL-Ec) harbouring virulence genes in the microbiome of food animals could likely threaten human health but is poorly understood in Cameroon and South Africa. Here, we assessed the resistome, virulome and mobilome of ESBL-Ec isolated from swine microbiomes in these countries, using whole genome sequencing (WGS). Materials/methodsEleven clonally-related phenotypic ESBL-Ec isolates were subjected to WGS. The isolates were de novo assembled using the CLC Genomics Workbench and SPAdes while RAST and PROKKA were used for annotation of the assembled contigs. Prediction of antibiotic resistance genes, virulence factors and plasmids was performed using ResFinder, VirulenceFinder and PlasmidFinder, respectively. ResultsDiverse STs were detected with sequence types ST2144 and ST88 predominating and blaCTX-M-15 (55%) as principal ESBL genes. Although the isolates belonged mainly to commensal phylogroups A/B1 (45/28.3%) and C (18.18%), all harboured at least three extraintestinal pathogenic E. coli (ExPEC) VFs with one isolate harbouring up to 18 ExPEC VFs. ConclusionThe resistance and pathogenic potential of ESBL-Ec colonizing the gut microbiota of swine in both countries demonstrate the urgent need to implement effective strategies to contain the dissemination of virulent ESBL-Ec through the food chain in Cameroon and South Africa.

genomics↗

bioRxiv2020

Ase1 domains dynamically slow anaphase spindle elongation and recruit Bim1 to the midzone

How cells regulate microtubule crosslinking activity to control the rate and duration of spindle elongation during anaphase is poorly understood. In this study, we test the hypothesis that PRC1/Ase1 proteins use distinct microtubule-binding domains to control spindle elongation rate. Using budding-yeast Ase1, we identify unique contributions for the spectrin and carboxy-terminal domains during different phases of spindle elongation. We show that the spectrin domain uses conserved, basic residues to promote the recruitment of Ase1 to the midzone before anaphase onset and slow spindle elongation during early anaphase. In contrast, a partial Ase1 carboxy-terminal truncation fails to form a stable midzone in late anaphase, produces faster elongation rates after early anaphase, and exhibits frequent spindle collapses. We find that the carboxy-terminal domain interacts with the plus-end tracking protein EB1/Bim1 and recruits Bim1 to the midzone to maintain midzone length. Overall, our results suggest that the Ase1 domains provide cells with a modular system to tune midzone activity and control elongation rates.

cell biology↗