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Alamri, S.

Publications and source records attributed to Alamri, S..

4 recordsLinked to original sources

LDL Signals Through Scarf1 to Drive a Pro-Fibrotic Secretory Response in Endothelial Cells

BACKGROUNDEndothelial cells lining the vasculature form a polarised secretory organ that releases proteins apically into the circulation and basally into the subendothelial matrix. While this secretion plays many critical roles in homeostasis, the potential roles for endothelial secretion in vascular disease remain under-studied. METHODSWe treated polarised monolayers of primary human endothelial cells with native and oxidised LDL and identified the proteins secreted from the apical and basal endothelial surfaces by tandem mass tag mass spectrometry. RESULTSTreatment with either native or oxidised LDL led to increased secretion of a cohort of 21 mostly pro-fibrotic proteins. We focussed on fibronectin, which was secreted apically or basally, depending on the direction of LDL treatment. LDL-stimulated fibronectin secretion did not require well-characterised endothelial LDL receptors but was instead mediated by the poorly characterised scavenger receptor Scarf1 and the cholesterol-sensitive SNARE proteins syntaxin 4 and 6. This LDL-stimulated secretion did not involve increased fibronectin expression but instead appeared to result from a decrease in fibronectin turnover and a re-routing of intracellular sorting. CONCLUSIONSThis novel endothelial secretory pathway links circulating LDL to the release of pro-fibrotic proteins from the endothelium, supporting a role for endothelial cell secretion in the progression of lipid-induced fibrotic disease.

cell biology↗

Amplicon and metagenomic analysis of MERS-CoV and the microbiome in patients with severe Middle East respiratory syndrome (MERS)

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a zoonotic infection that emerged in the Middle East in 2012. Symptoms range from mild to severe and include both respiratory and gastrointestinal illnesses. The virus is mainly present in camel populations with occasional spill overs into humans. The severity of infection in humans is influenced by numerous factors and similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underlying health complications can play a major role. Currently, MERS-CoV and SARS-CoV-2 are co-incident in the Middle East and a rapid way is required of sequencing MERS-CoV to derive genotype information for molecular epidemiology. Additionally, complicating factors in MERS-CoV infections are co-infections that require clinical management. The ability to rapidly characterise these infections would be advantageous. To rapidly sequence MERS-CoV, we developed an amplicon-based approach coupled to Oxford Nanopore long read length sequencing. The advantage of this approach is that insertions and deletions can be identified - which are the major drivers of genotype change in coronaviruses. This and a metagenomic approach were evaluated on clinical samples from patients with MERS. The data illustrated that whole genome or near whole genome information on MERS-CoV could be rapidly obtained. This approach provided data on both consensus genomes and the presence of minor variants including deletion mutants. Whereas, the metagenomic analysis provided information of the background microbiome.

molecular biology↗

PAX2 Induces Tubular-Like Structures in Normal and Ovarian Cancer Cells

In adult tissues, PAX2 protein is expressed in normal oviductal epithelial cells but not in normal ovarian surface epithelial cells. Studies have reported that PAX2 is expressed in a subset of serous ovarian carcinoma cases but the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of this study was to understand the biological consequences of Pax2 expression in normal and cancerous mouse epithelial (MOSE) cells. We found that Pax2 overexpression in both normal and cancerous ovarian epithelial cells induced the formation of vascular channels both in vitro and in vivo. The results indicate a possible contribution of PAX2 to ovarian cancer progression by increasing the vascular channels to supply nutrients to the tumor cells.

cancer biology↗

Comparative Genomic Evidence For Self-Domestication In Homo sapiens

This study identifies and analyzes statistically significant overlaps between selective sweep screens in anatomically modern humans and several domesticated species. The results obtained suggest that (paleo-) genomic data can be exploited to complement the fossil record and support the idea of self-domestication in Homo sapiens, a process that likely intensified as our species populated its niche. Our analysis lends support to attempts to capture the \"domestication syndrome\" in terms of alterations to certain signaling pathways and cell lineages, such as the neural crest.

genomics↗