Lancet
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Metabolically unhealthy obesity is associated with adipose tissue inflammation and increased risk of type 2 diabetes. Dysfunctional adipose tissue remodelling has been implicated in development of metabolically unhealthy obesity, but the pathogenesis remains poorly characterised. We hypothesised that in health, tissue inhibitor of metalloproteinases 3 (TIMP3) modulates adipose tissue remodelling by regulating extracellular matrix turnover and shedding of the adipogenic regulator DLK1, but that in adipose tissue inflammation it might drive development of metabolically unhealthy obesity. ⋯ British Heart Foundation, Diabetes Research and Wellness Foundation Open Funding 2011.
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The myeloproliferative neoplasms are a group of haematological malignancies characterised by pathological activation of the JAK/STAT (Janus kinase and signal transducer and activator of transcription) intracellular signalling pathway. 50-95% of patients have an acquired mutation (JAK2V617F) causing constitutive activation of JAK2. Our aim was to find new treatments for myeloproliferative neoplasms by identifying compounds that suppress JAK/STAT pathway activation. ⋯ Cancer Research UK, Yorkshire Cancer Research, UK Medical Research Council, Wellcome Trust, EU Framework Cancer Pathways.
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Skin microbiota are likely to be important in the development of conditions such as psoriatic arthritis. Profiling the bacterial community in the psosriatic plaques will contribute to our understanding of the role of the skin microbiome in these conditions. The aim of this work was to determine the optimum study design for work on the skin microbiome with use of the MiSeq platform. The objectives were to compare data generated from two platforms for two primer pairs in a low density mock bacterial community. ⋯ NIHR Manchester Musculoskeletal Biomedical Research Unit.
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Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population.
Selected populations of murine natural killer (NK) cells possess memory features to haptens, cytokines, and viruses. Liver-specific adhesion molecules CXCR6 and CD49a have been identified as surface markers in mice. In people, expansion of long-lived terminally differentiated NKG2C+ populations occur in the blood after viral infection. We aimed to compare intrahepatic and blood NK cell receptor expression to determine the existence of CD49a+ and CXCR6+ NK cells in human liver and define the maturation status of NKG2C+ NK cells at this site. ⋯ MRC Clinical Research Fellowship.
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Only half of patients with locally invasive rectal carcinoma respond to short-course preoperative radiotherapy. A predictive test enabling better patient selection could avoid unneccessary radiation exposure to poor responders. Macrophages within the tumour immune microenvironment with tumoricidal M1 and tumour-protective M2 phenotypes could be modulating this response. This study investigated the possible predictive value of M1 and M2 subpopulations in identifying patients' likely response to short-course preoperative radiotherapy. ⋯ None.