Oxidative stress-induced changes in the transcriptomic profile of extracellular vesicles.

Extracellular vesicles (EVs) have been proposed to play dual roles in cellular homeostasis, functioning both to remove unwanted intracellular molecules, and to enable communication between cells as a means of modulating cellular responses in different physiological and pathological scenarios. EVs contain a broad range of cargoes, including multiple biotypes of RNA, which can vary depending on the cell status, and may function as signalling molecules. In this study, we carried out comparative transcriptomic analysis of EVs and cells, demonstrating that the RNA profile of EVs is distinct from cells and shows dose-dependent changes in response to oxidative stress.

Comparative and integrated analysis of plasma extracellular vesicle isolation methods in healthy volunteers and patients following myocardial infarction.

Plasma extracellular vesicle (EV) number and composition are altered following myocardial infarction (MI), but to properly understand the significance of these changes it is essential to appreciate how the different isolation methods affect EV characteristics, proteome and sphingolipidome. Here, we compared plasma EV isolated from platelet-poor plasma from four healthy donors and six MI patients at presentation and 1-month post-MI using ultracentrifugation (UC), polyethylene glycol precipitation, acoustic trapping, size-exclusion chromatography (SEC) and immunoaffinity capture. The isolated EV were evaluated by Nanoparticle Tracking Analysis (NTA), Western blot, transmission electron microscopy (TEM), an EV-protein array, untargeted proteomics (LC-MS/MS) and targeted sphingolipidomics (LC-MS/MS).

P-TEFb goes viral.

Positive transcription elongation factor b (P-TEFb), which comprises cyclin-dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P-TEFb is required for productive elongation of transcription of protein-coding genes by RNA polymerase II (pol II). In addition, P-TEFb-mediated phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle.

Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics.

Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT).