146 research outputs found

    Development of a method for fabricating metallic matrix composite shapes by a continuous mechanical process

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    Attempts made to develop processes capable of producing metal composites in structural shapes and sizes suitable for space applications are described. The processes must be continuous and promise to lower fabrication costs. Special attention was given to the aluminum boride (Al/b) composite system. Results show that despite adequate temperature control, the consolidation characteristics did not improve as expected. Inadequate binder removal was identified as the cause responsible. An Al/c (aluminum-graphite) composite was also examined

    Established non-union of an operatively managed trans-scaphoid perilunate fracture dislocation progressing to spontaneous union

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    Perilunate dislocations and fracture dislocations represent uncommon and unusual injuries that are often missed at initial presentation and diagnosed late in up to 25% of cases. Prompt open reduction, carpal stabilisation and ligamentous repair is required to reduce the risk of complications. We report a case of an established scaphoid non-union in an operatively managed perilunate fracture dislocation that spontaneously united almost 2 years after the initial injury, just before a planned revision scaphoid fixation with bone grafting. This case highlights the importance of initial clinical assessment together with appropriate radiographs and follow-up of these injuries post-operatively, especially when complications such as non-union arise

    PKCε Stimulated Arginine Methylation of RIP140 for Its Nuclear-Cytoplasmic Export in Adipocyte Differentiation

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    Receptor interacting protein 140 (RIP140) is a versatile transcriptional co-repressor that plays roles in diverse metabolic processes including fat accumulation in adipocytes. Previously we identified three methylated arginine residues in RIP140, which rendered its export to the cytoplasm; but it was unclear what triggered RIP140 arginine methylation.In this study, we determined the activated PKCepsilon as the specific trigger for RIP140 arginine methylation and its subsequent export. We identified two PKCepsilon-phosphorylated residues of RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the nuclear gene-repressive activity of RIP140 was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation was effectively rescued by the phosphorylation-deficient mutant RIP140 that resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140 that was exported to the cytoplasm.This study uncovers a novel means, via a cascade of protein modifications, to inactivate, or suppress, the nuclear action of an important transcription coregulator RIP140, and delineates the first specific phosphorylation-arginine methylation cascade that could alter protein subcellular distribution and biological activity

    Phospholipase D signaling: orchestration by PIP2 and small GTPases

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    Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP2 by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP2 and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions

    Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes

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    Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes

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