81 research outputs found

    The UBA-UIM Domains of the USP25 Regulate the Enzyme Ubiquitination State and Modulate Substrate Recognition

    Get PDF
    USP25m is the muscle isoform of the deubiquitinating (DUB) enzyme USP25. Similarly to most DUBs, data on USP25 regulation and substrate recognition is scarce. In silico analysis predicted three ubiquitin binding domains (UBDs) at the N-terminus: one ubiquitin-associated domain (UBA) and two ubiquitin-interacting motifs (UIMs), whereas no clear structural homology at the extended C-terminal region outside the catalytic domains were detected. In order to asses the contribution of the UBDs and the C-terminus to the regulation of USP25m catalytic activity, ubiquitination state and substrate interaction, serial and combinatorial deletions were generated. Our results showed that USP25m catalytic activity did not strictly depend on the UBDs, but required a coiled-coil stretch between amino acids 679 to 769. USP25 oligomerized but this interaction did not require either the UBDs or the C-terminus. Besides, USP25 was monoubiquitinated and able to autodeubiquitinate in a possible loop of autoregulation. UBDs favored the monoubiquitination of USP25m at the preferential site lysine 99 (K99). This residue had been previously shown to be a target for SUMO and this modification inhibited USP25 activity. We showed that mutation of K99 clearly diminished USP25-dependent rescue of the specific substrate MyBPC1 from proteasome degradation, thereby supporting a new mechanistic model, in which USP25m is regulated through alternative conjugation of ubiquitin (activating) or SUMO (inhibiting) to the same lysine residue (K99), which may promote the interaction with distinct intramolecular regulatory domains

    Observation of a new boson at a mass of 125 GeV with the CMS experiment at the LHC

    Get PDF

    Treatment of the ageing hand with dermal fillers

    No full text
    Following the trend in facial cosmetic procedures, patients are now increasingly requesting hand rejuvenation treatments. Intrinsic ageing of the hands is characterized by loss of dermal elasticity and atrophy of the subcutaneous tissue. Thus, veins, tendons and bony structures become apparent. Among the available procedures, intrinsic ageing of the hands is best improved by restoring the volume of soft tissue. Volume restoration can be achieved with a number of long-lasting dermal fillers with varying degrees of improvement and treatment longevity. The dermal fillers used in hand rejuvenation include autologous fat, collagen, hyaluronic acid, calcium hydroxylapatite and poly-L-lactic acid. Here, we describe our preferred injection method for hand rejuvenation using calcium hydroxylapatite and a single-bolus injection

    Determinants of inter-individual cholesterol levels variations in an unbiased young male sample

    Full text link
    Question under study: Affected by individual life style, total cholesterol serum level is a major morbidity and mortality risk factor for atherosclerotic cardiovascular disease (CVD). We present total cholesterol values and possible etiological factors of young Swiss conscripts. Particularly, we focus on the varying impact of such a component depending on different levels of individual cholesterol. Methods: Male conscripts (n=19’272) of the 2005 census of the conscripts have been examined, reflecting ca. 59% of a total Swiss male citizen birth cohort. Quantile regression allows us to analyze the reagibility of arbitrary quantiles with respect to variables of interest. Results: Eleven percent of all conscripts show an increased total cholesterol level. A major association of high individual cholesterol level is with French mother tongue. The largest socio-economic subsample – agricultural and construction sectors – show significantly higher individual cholesterol levels than employees in the industry sector and students, respectively. Conclusions: We were able to find and exclude various as yet unstudied factors influencing individual total cholesterol levels. Such a screening programme offers a unique opportunity to target persons at high-risk for CVD morbidity and mortality already early in life

    Expertenbericht Advanced Practice Nursing APN

    No full text
    corecore