We describe a structural and functional study of the G protein-coupled apelin receptor, which binds two endogenous peptide ligands, apelin and Elabela/Toddler (ELA), to regulate cardiovascular development and function. Characterisation of naturally occurring apelin receptor variants from the UK Genomics England 100,000 Genomes Project, and AlphaFold2 modelling, identifies T89 as important in the ELA binding site, and R168 as forming extensive interactions with the C-termini of both peptides. Base editing to introduce an R/H168 variant into human stem cell-derived cardiomyocytes demonstrates that this residue is critical for receptor binding and function.
View Article and Find Full Text PDFBackground: Two scientific and clinical challenges for treating cannabis use disorder (CUD) are developing efficacious treatments with high likelihood of uptake and scalability, and testing the clinical mechanisms by which treatments work. Because young adults experience more CUD than other age groups, a need exists to test the efficacy and hypothesized causal pathways of novel treatments for CUD. Text-delivered treatments have the potential to reach young adults by increasing access and perceived privacy.
View Article and Find Full Text PDFBackground/objectives: The projected increase from 58 million older adults in 2022 to 82 million by 2050 in the United States highlights the urgency of preparing nursing students to care for this aging population. However, studies reveal negative attitudes among nursing students toward older adults. A three-phased educational intervention that included an artificial intelligence (AI)-driven virtual simulation was implemented to address this.
View Article and Find Full Text PDFComputed tomography coronary angiography (CTCA) is under-utilised in detecting coronary artery disease (CAD) in obese patients due to concerns about non-evaluable testing. We hypothesise that these concerns are predominantly related to smaller and branch coronary vessels, and CTCA remains adequate for proximal segment stenosis interpretation, which has significant clinical implications. This retrospective cohort study, on consecutive patients referred for CTCA for suspected CAD, grouped patients by body mass index.
View Article and Find Full Text PDFEfficient delivery of sensitive nucleic acid payloads, including mRNA, in remains challenging, especially with traditional, labor-intensive transgenesis methods. We addressed these challenges using polymeric nanogels (NGs) as an advanced platform for mRNA delivery in . These polymeric delivery vehicles can be engineered to suit desired applications owing to their chemical versatility, resulting from the ability to conjugate multiple functional groups onto the same backbone.
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