Daf-2 Signaling Modifies Mutant SOD1 Toxicity in C. elegans

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS

Financial analysis of renewable energy investments in Italy in 2013

The present paper analyses the financial aspects of investing in different renewable energy technologies: photovoltaic, wind and hydro. To perform the financial analysis on the afore-mentioned plants for different types of investors, three different sizes of system have been considered: 5 kW for domestic uses, 20 kW for small business activities and 1 MW for companies involved in producing and selling energy. A description of present incentives in renewable energy production in Italy in 2013 has been reported. For each case study a comparison of different cost solution has been proposed. To evaluate the financial convenience of the investments specific economical indices have been used and compared

Opposing actions of the synapse-associated protein of 97-kDa molecular weight (SAP97) and Disrupted in Schizophrenia 1 (DISC1) on Wnt/β-catenin signaling

It has been suggested that synapse-associated protein of 97kDa molecular weight (SAP97) is a susceptibility factor for childhood and adult neuropsychiatric disorders. SAP97 is a scaffolding protein that shares direct and indirect binding partners with the DISC1 gene product, a gene with strong association with neuropsychiatric disorders. Here we investigated the possibility that these two proteins converge upon a common molecular pathway. Since DISC1 modifies Wnt/β-catenin signaling via changes in GSK3β phosphorylation, we asked if SAP97 impacts Wnt/β-catenin signaling and GSK3β phosphorylation. We find that SAP97 acts as inhibitor of Wnt signaling activity and can suppress the stimulatory effects of DISC1 on β-catenin transcriptional activity. Reductions in SAP97 abundance also decrease GSK3β phosphorylation. In addition, we find that over expression of DISC1 leads to an increase in the abundance of SAP97, by inhibiting its proteasomal degradation. Our findings suggest that SAP97 and DISC1 contribute to maintaining Wnt/β-catenin signaling activity within a homeostatic range by regulating GSK3β phosphorylation

Mechanisms and aging related diseases

Le vieillissement est une perte progressive et inéluctable des capacités fonctionnelles de l’organisme. Des caractéristiques socio-économiques, des facteurs génétiques et le genre influent sur ce processus et en déterminent la complexité. Les mécanismes moléculaires et cellulaires, qui fondent la physiologie du vieillissement et de la longévité, commencent à être mieux élucidés. Souvent ambivalents, ils sont aussi impliqués dans la survenue de nombreuses pathologies liées à l’âge. Certains d’entre-eux (les principaux) sont décrits dans cet article (restriction calorique, séquences télomériques, klotho, Apolipoprotéine E, voie de signalisation mTOR, axe IGF-1/PI3 kinase/insuline, sirtuines, autophagie, radicaux libres, etc.). Une meilleure compréhension de ces mécanismes suscite beaucoup d’espoirs en termes de prévention et de perspectives thérapeutiques. Néanmoins, des dérives éthiques possibles sont redoutées. Le vieillissement est, ainsi, un enjeu sociétal et de santé publique aussi bien dans les pays développés que dans les pays en développement. Le problème de sa prise en charge se posera avec acuité devant l’augmentation de l’espérance de vie et du nombre de personnes âgées dans le monde.Aging is known as a process leading to a progressive and relentless decline of functional capacities. Social, economic, gender and genetic factors are key modulators of its complexity. A better understanding of cellular and molecular mechanisms that underlie aging and life span physiology is slowly but surely occurring. Here, we give a comprehensive synthesis of the main biological mechanisms controlling aging and aging related diseases (caloric restriction, telomeric sequences, Klotho, Apolipoproteine E, mTOR pathway, IGF-1/PI3 kinase/insulin axis, sirtuins, autophagy, free radicals...). Promising hopes in terms of aging prevention and therapeutic perspectives are made in the near future. Nevertheless, general public fear ethical excesses. At all events, aging is becoming a social and public health stake in developed and developing countries. The elderly care management will be a huge issue regarding the enhancement of life span and the growing number of seniors worldwide