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991.
Richard H. Weisbart Grace Chan Emil Heinze Rachel Mory Robert N. Nishimura Keith Colburn 《The Journal of biological chemistry》2010,285(45):34299-34303
Synovial fibroblasts destroy articular cartilage and bone in rheumatoid arthritis, but the mechanism of fibroblast transformation remains elusive. Because gain-of-function mutations of BRAF can transform fibroblasts, we examined BRAF in rheumatoid synovial fibroblasts. The strong gain-of-function mutation, V600R, of BRAF found in melanomas and other cancers was identified in first passage synovial fibroblasts from two of nine rheumatoid arthritis patients and confirmed by restriction site mapping. BRAF-specific siRNA inhibited proliferation of synovial fibroblasts with V600R mutations. A BRAF aberrant splice variant with an intact kinase domain and partial loss of the N-terminal autoinhibitory domain was identified in fibroblasts from an additional patient, and fibroblast proliferation was inhibited by BRAF-specific siRNA. Our finding is the first to establish mechanisms for fibroblast transformation responsible for destruction of articular cartilage and bone in rheumatoid arthritis and establishes a new target for therapeutic intervention. 相似文献
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Much of the recent neuropsychological literature on false beliefs (delusions) has tended to focus on individual or single beliefs, with few studies actually investigating the relationship or co-occurrence between different types of co-existing beliefs. Quine and Ullian proposed the hypothesis that our beliefs form an interconnected web in which the beliefs that make up that system must somehow “cohere” with one another and avoid cognitive dissonance. As such beliefs are unlikely to be encapsulated (i.e., exist in isolation from other beliefs). The aim of this preliminary study was to empirically evaluate the probability of belief co-occurrence as one indicator of coherence in a large sample of subjects involving three different thematic sets of beliefs (delusion-like, paranormal & religious, and societal/cultural). Results showed that the degree of belief co-endorsement between beliefs within thematic groupings was greater than random occurrence, lending support to Quine and Ullian’s coherentist account. Some associations, however, were relatively weak, providing for well-established examples of cognitive dissonance. 相似文献
993.
Rachel O. Coats Andrew D. Wilson Winona Snapp-Childs Aaron J. Fath Geoffrey P. Bingham 《PloS one》2014,9(1)
We recently found that older adults show reduced learning rates when learning a new pattern of coordinated rhythmic movement. The purpose of this study was to extend that finding by examining the performance of all ages across the lifespan from the 20 s through to the 80 s to determine how learning rates change with age. We tested whether adults could learn to produce a novel coordinated rhythmic movement (90° relative phase) in a visually guided unimanual task. We determined learning rates to quantify changes in learning with age and to determine at what ages the changes occur. We found, as before, that learning rates of participants in their 70 s and 80 s were half those of participants in their 20 s. We also found a gradual slow decline in learning rate with age until approximately age 50, when there was a sudden drop to a reduced learning rate for the 60 though 80 year olds. We discuss possible causes for the “50 s cliff” in perceptuo-motor learning rates and suggest that age related deficits in perception of complex motions may be the key to understanding this result. 相似文献
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Juliana R. Bernardi Charles F. Ferreira Gabrielle Senter Rachel Krolow Bianca W. de Aguiar André K. Portella Márcia Kauer-Sant'Anna Flávio Kapczinski Carla Dalmaz Marcelo Z. Goldani Patrícia P. Silveira 《PloS one》2013,8(4)
Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32°C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animal''s body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood. 相似文献
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