Lancet
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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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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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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.
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DNA damage transactivates tumour protein p53 (TP53)-regulated surveillance, crucial in suppressing tumorigenesis. TP53 mediates this process directly by transcriptionally modulating gene and microRNA (miRNA) expression and indirectly by regulating miRNA biogenesis. However, the role of TP53 in regulating miRNA-AGO2 loading and global changes in AGO2 binding to its gene targets in response to DNA damage are unknown. These processes might be novel mechanisms by which TP53 regulates miRNAs in response to DNA damage. ⋯ UK Medical Research Council, Action Against Cancer.
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CD4 T cells with features of both T-helper-type 1 (Th1) and 17 (Th17) cells have been implicated in several autoimmune diseases suggesting that plasticity among CD4 T-cell lineages is potentially pathogenic. However, the factors that regulate T-cell lineage stability are largely unknown. Retinoic acid (RA) is synthesised at sites of inflammation. We hypothesised that retinoic acid, a profound epigenetic modifier, could regulate T-cell lineage stability. ⋯ Wellcome Trust.