Metabolism and cancer:Old and new players

[No abstract available

Targeting the epigenetic modifications of synovial cells

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial tissues of joints. Like in other autoimmune-related disorders, both the etiology as well as the pathogenesis of RA has not yet been completely unravelled. It is generally accepted, though, that autoimmune disorders develop through a combination of the individual genetic susceptibility, environmental factors, and dysregulated immune responses. Genetic predisposition has been described in RA, in particular as “shared epitope”, a distinct sequence of amino acids within the antigen presenting peptide groove of the major histocompatibility complex (MHC). Imbalanced immunity is reflected by the production of autoantibodies and the accumulation of reactive helper T cells within the rheumatoid synovium. In addition, environmental factors have been postulated as disease modulating agents, including smoking, nutrition and infectious agents. So far, these factors have been studied almost exclusively as separate agents. However, the way genes are transcribed can be affected by environment, nutrition, and ageing – without changes in the nucleotide sequence of the underlying DNA. These patterns of alterations in the gene expression profiles are called epigenetics. The term epigenetics is used to refer to molecular processes that regulate gene expression patterns, however without changing the DNA nucleotide sequence. These epigenetic changes comprise the postsynthetical methylation of DNA and posttranscriptional modifications of histones, including methylation, phosphorylation, ubiquitination, sumoylation, biotinlyation and, most importantly, deacetylation and acetylation. With respect to the complex pathogenesis of rheumatic diseases, the epigenome is an emerging concept that integrates different etiologies and, thus, offers the opportunity for novel therapeutic strategies. Based on the fact that current therapies have not resulted in an ACR 70 above 60% and have never been targeting the activated synovial fibroblast, novel therapeutic strategies should target the epigenetic pathways of synovial activation in RA

Effect of Friction Stir Processing on the Kinetics of Superplastic Deformation in an Al-Mg-Zr Alloy

The effect of friction stir processing on the superplastic behavior of extruded Al-4Mg-1Zr was examined at 350 °C to 600 °C and at initial strain rates of 1×10−3 to 1 s−1. A combination of a fine grain size of 1.5 μm and high-angle grain boundaries in the friction stir-processed (FSP) alloy led to considerably enhanced superplastic ductility, much-reduced flow stress, and a shift to a higher optimum strain rate and lower optimum temperature. The as-extruded alloy exhibited the highest superplastic ductility of 1015 pct at 580 °C and an initial strain rate of 1×10−2s−1, whereas a maximum elongation of 1280 pct was obtained at 525 °C and an initial strain rate of 1×10−1s−1 for the FSP alloy. The FSP alloy exhibited enhanced superplastic deformation kinetics compared to that predicted by the constitutive relationship for superplasticity in fine-grained aluminum alloys. A possible origin for enhanced superplastic deformation kinetics in the FSP condition is proposed