Lancet
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Cutaneous squamous cell carcinoma is the most common malignancy in renal transplant recipients and a major cause of morbidity and mortality. Various measures have been proposed to identify recipients at increased risk of developing this cancer to allow targeted intervention. CD57 expression might represent a marker of T-cell exhaustion; we hypothesised that expression could predict development of squamous cell carcinoma in renal transplant recipients, and undertook a prospective cohort study to assess its predictive value. ⋯ Wellcome Trust, Oxford University Hospitals Research Services Committee.
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Epilepsy is characterised by disturbed neuronal activity in the brain rendering it more susceptible to seizures. An understanding of the molecular mechanisms by which the balance between excitability and inhibition in neuronal networks is controlled will help to devise better treatment options. Hyperpolarising synaptic inhibition through GABAA (γ aminobutyric acid type A) and glycine receptors depends on the presence of the neuronal cation-chloride-cotransporter protein, KCC2. Several transcriptional and post-transcriptional mechanisms have been shown to regulate KCC2 and thereby affect the polarity and efficacy of inhibitory synaptic transmission. However, it is unknown whether regulation of KCC2 enables the transporter to attain different levels of activity, thus allowing a neuron to modulate the strength of inhibitory synaptic transmission to its changing requirements. We therefore investigated whether phosphorylation can allow KCC2 to achieve distinct levels of intracellular chloride ion concentrations in neurons. ⋯ Royal Society.
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Patients with loss-of-function mutation in neurokinin B (NKB) and its receptor show hypogonadotropic hypogonadism characterised by failure to progress through puberty, indicating the involvement of this newly described hypothalamic peptide in human reproduction. However the role of NKB in regulating ovarian function in adult women is unknown. We tested the hypothesis that a NKB antagonist would decrease gonadotropin secretion and inhibit folliculogenesis in healthy women. ⋯ Wellcome Trust through the Scottish Translational and Therapeutics Initiative.
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Signalling though the melanocortin 4 receptor (MC4R), which is widely expressed in the hypothalamus, mediates food intake and macronutrient preference in rodents. Studies in patients with MC4R deficiency can provide insights into the role of this pathway in man. We investigated the role of melanocortin signalling in fat and sucrose preference in human beings by studying patients with loss of function mutations in MC4R. ⋯ Wellcome Trust, NIHR Cambridge Biomedical Research Centre, Bernard Wolfe Health Neuroscience Fund, NeuroFAST consortium, which is funded by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 245009.
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MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of mRNAs and are aberrantly expressed in cancer with important roles in tumorigenesis. A broad analysis of the combined effects of altered activities of miRNAs in pancreatic ductal adenocarcinoma (PDAC) has not been done, and how miRNAs might affect tumour progression or patient outcomes is unclear. ⋯ Peel Medical Research Trust, Alliance Family Foundation, Action Against Cancer, National Institute for Health Research, Association for International Cancer Research, Jason Boas Fellowship, Imperial Biomedical Research Centre, Rosetrees Trust, Joseph Ettedgui Charitable Foundation.