Denervation does not induce muscle atrophy through oxidative stress

Denervation leads to the activation of the catabolic pathways, such as the ubiquitin-proteasome and autophagy, resulting in skeletal muscle atrophy and weakness. Furthermore, denervation induces oxidative stress in skeletal muscle, which is thought to contribute to the induction of skeletal muscle atrophy. Several muscle diseases are characterized by denervation, but the molecular pathways contributing to muscle atrophy have been only partially described. Our study delineates the kinetics of activation of oxidative stress response in skeletal muscle following denervation. Despite the denervation-dependent induction of oxidative stress in skeletal muscle, treatments with anti-oxidant drugs do not prevent the reduction of muscle mass. Our results indicate that, although oxidative stress may contribute to the activation of the response to denervation, it is not responsible by itself of oxidative damage or neurogenic muscle atrophy

Peroxynitrite activates the NLRP3 inflammasome cascade in SOD1(G93A) mouse model of amyotrophic lateral sclerosis

Neuroinflammation, characterized by the appearance of reactive microglial and astroglial cells, is one of the several pathogenic mechanisms of amyotrophic lateral sclerosis (ALS), a fast-progressing and fatal neurodegenerative disease. Cerebrospinal fluid and spinal cord of ALS patients and SOD1 mutant mice show high concentrations of IL-1β. This interleukin, expressed as an inactive precursor, undergoes a proteolytic maturation by caspase1, whose activation, in turn, depends on inflammasomes. Whether and how inflammasome is activated in ALS models is still to be clarified. The mechanism of inflammasome activation was studied in murine microglial cells overexpressing hSOD1(G93A) and verified in the spinal cord of hSOD1(G93A) mice. Murine microglial hSOD1(G93A) cells express all the inflammasome components and LPS activates caspase1 leading to an increase in the secretion of IL-1β. By activating NF-κB, LPS increases ROS and NO levels that spontaneously react to form peroxynitrite, thus leading to protein nitration. Reduction in peroxynitrite levels results in a decrease in caspase1 activity. Protein nitration and caspase1 activity are concomitantly increased in the spinal cord of pre-symptomatic SOD1(G93A) mice. Oxidative/nitrosative stress induces peroxynitrite formation that may be a key trigger of caspase1/inflammasome activation. Peroxynitrite formation may play a critical role in inflammasome activation and might be exploited as potential therapeutic target for ALS

Symbolic Consumption and Alternative Signals of Status

My dissertation is composed of three papers on symbolic consumption–how consumers use products, brands, and time to express who they are and signal status. The first paper (Brand Tourists: How Non–Core Users Enhance the Brand Image by Eliciting Pride) demonstrates the positive impact of non-core users of a prestige brand perceived as “brand tourists” into the brand community. The second paper (The Red Sneakers Effect: Inferring Status and Competence from Signals of Nonconformity) investigates the conditions under which nonconforming behaviors, such as wearing red sneakers in a professional setting, can act as a particular form of conspicuous consumption and lead to positive inferences of status and competence in the eyes of others. The third paper (Conspicuous Consumption of Time: When Busyness and Lack of Leisure Time Become a Status Symbol) further extends this line of investigation on alternative signals of status by uncovering the role of long hours of work and lack of leisure time as a status symbol. I conclude with a discussion of current working papers and future research agenda on symbolic consumption and branding

Consumer Minimalism

We define consumer minimalism as a value comprised of three dimensions: number of possessions, sparse aesthetic, and mindfully curated consumption. We develop the 12-item Minimalist Consumer Scale to measure the construct and situate the scale within the nomological network of related constructs

Role of misfolding in rare enzymatic deficits and use of pharmacological chaperones as therapeutic approach

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