Lancet
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Inherited, iatrogenic, and metabolic corneal disease could be potentially treated by supplying a functional gene or changing the expression levels of specific genes. Viral-based gene therapy is efficient, but restricted by evoking immune responses and inflammation. This study aimed to transfect mouse cornea with a non-viral based (oscillating magnetofection) method. ⋯ Welsh Clinical Academic Training Scheme.
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Background GRIN2A encodes the GluN2A subunit of the NMDA receptor (NMDAR), an ionotropic glutamate receptor that has important roles in synaptogenesis and synaptic plasticity. Some individuals with early onset epilepsies and intellectual disability carry heterozygous missense mutations in this gene, including a de-novo mutation in the receptor pore region (GluN2A(N615K)). We hypothesised that this mutation underlies the carrier's brain disorder and sought to explore its functional consequences. ⋯ Wellcome Trust via an Edinburgh Clinical Academic Training PhD Fellowship.
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Uniquely, alloantigen is recognised by two pathways: as intact antigen on the surface of donor antigen-presenting cells (direct) and as self-restricted processed allopeptide (indirect). The indirect pathway is believed to be longlasting, and is generally considered to be a single entity. Here we address how indirect responses against different alloantigens differ in their strength and longevity, and how this knowledge could be used to direct immunoregulatory therapy with antigen-specific regulatory T cells (Tregs). ⋯ Wellcome Trust Clinical Research Training Fellowship.
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Hyperphosphataemia is a risk factor for accelerated cardiovascular disease in chronic kidney disease. The mechanism is poorly understood; it is unclear whether phosphate has direct effects or effects mediated via calcification or FGF23. We investigated direct effects of phosphate on endothelial function using myography to study rat and human blood vessels. In addition we assessed the effects of phosphate loading on endothelial function in a clinical study. ⋯ British Heart Foundation, Darlinda's Charity for Renal Research.