LA TRANSIZIONE ENERGETICA NELLA MACROREGIONE ALPINA: DEFINIZIONE DELLA SITUAZIONE DI PARTENZA

Nowadays energy transition is a recurring topic, which describes the process of an energy system moving from fossil-based sources towards renewables. The transition can unfold at different levels, from the single initiative of a local com-munity to a complex cross-border agreement. The latter type is well represented by EUSALP, the European macro-regional strategy for the Alpine region. One of its aims is to transform its territory into a model region for energy efficiency and renewable energy. To support a well-informed decision making process, this study provides the first insight about the status quo of energy balances in EUSALP, at local as well as aggregated level. Moreover, it offers an overview on the various energy targets defined by the territorial units that constitute the EUSALP region. Data has been retrieved via a bottom-up quality-oriented process consisting of (i) a survey targeted at responsible person in local energy departments; and (ii) data control and harmonization. We found that the EUSALP region is actually a model region only in clean power production, whereas starting point as well as energy targets of territories are highly heterogeneous. We al-so identified the need of more harmonized data collection methodologies. We conclude that this bottom-up process can support and legitimate policy makers in cross-border cooperation activities under a smart macro-regional energy strategy, which pursues an increment in energy savings, renewable energy production and a broad engagement of relevant stakeholders. DOI: http://dx.medra.org/10.19254/LaborEst.16.1

LA TRANSIZIONE ENERGETICA NELLA MACROREGIONE ALPINA: DEFINIZIONE DELLA SITUAZIONE DI PARTENZA

Nowadays energy transition is a recurring topic, which describes the process of an energy system moving from fossil-based sources towards renewables. The transition can unfold at different levels, from the single initiative of a local com-munity to a complex cross-border agreement. The latter type is well represented by EUSALP, the European macro-regional strategy for the Alpine region. One of its aims is to transform its territory into a model region for energy efficiency and renewable energy. To support a well-informed decision making process, this study provides the first insight about the status quo of energy balances in EUSALP, at local as well as aggregated level. Moreover, it offers an overview on the various energy targets defined by the territorial units that constitute the EUSALP region. Data has been retrieved via a bottom-up quality-oriented process consisting of (i) a survey targeted at responsible person in local energy departments; and (ii) data control and harmonization. We found that the EUSALP region is actually a model region only in clean power production, whereas starting point as well as energy targets of territories are highly heterogeneous. We al-so identified the need of more harmonized data collection methodologies. We conclude that this bottom-up process can support and legitimate policy makers in cross-border cooperation activities under a smart macro-regional energy strategy, which pursues an increment in energy savings, renewable energy production and a broad engagement of relevant stakeholders

Huntingtin-mediated axonal transport requires arginine methylation by PRMT6

The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated HTT and find that it is dimethylated at a highly conserved arginine residue (R118) by the protein arginine methyltransferase 6 (PRMT6). Without R118 methylation, HTT associates less with vesicles, anterograde trafficking is diminished, and neuronal death ensues—very similar to what occurs in HD. Inhibiting PRMT6 in HD cells and neurons exacerbates mutant HTT (mHTT) toxicity and impairs axonal trafficking, whereas overexpressing PRMT6 restores axonal transport and neuronal viability, except in the presence of a methylation-defective variant of mHTT. In HD flies, overexpressing PRMT6 rescues axonal defects and eclosion. Arginine methylation thus regulates HTT-mediated vesicular transport along the axon, and increasing HTT methylation could be of therapeutic interest for HD.Telethon-Italy and Autonomous Province of Trento (TCP12013 to M.P.); Association Française contre les Myopathies (AFM-22221 to M.P. and M.B.); PRIN-MUR (2017F2A2C5 to M.P.); National Institutes of Health (1R21NS111768-01 to M.P. and U.B.P.); PROGRAM RARE DISEASES CNCCS-Scarl-Pomezia (M.P.); FONDAZIONE AIRC-Italy (24423 to M.P.); Alzheimer Trento Onlus with the legato Baldrachi (M.B.); the Agence Nationale de la Recherche (ANR-15-JPWG-0003-05 JPND CIRCPROT and ANR-18-CE16-0009-01 AXYON to F.S.) and the Spanish Ministry of Science, Innovation and Universities (RTI2018-096322-B-I00 MCIU/AEI/FEDER-UE to J.J.L.

Polyglutamine-Expanded Androgen Receptor Alteration of Skeletal Muscle Homeostasis and Myonuclear Aggregation Are Affected by Sex, Age and Muscle Metabolism

Polyglutamine (polyQ) expansions in the androgen receptor (AR) gene cause spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease characterized by lower motor neuron (MN) loss and skeletal muscle atrophy, with an unknown mechanism. We generated new mouse models of SBMA for constitutive and inducible expression of mutant AR and performed biochemical, histological and functional analyses of phenotype. We show that polyQ-expanded AR causes motor dysfunction, premature death, IIb-to-IIa/IIx fiber-type change, glycolytic-to-oxidative fiber-type switching, upregulation of atrogenes and autophagy genes and mitochondrial dysfunction in skeletal muscle, together with signs of muscle denervation at late stage of disease. PolyQ expansions in the AR resulted in nuclear enrichment. Within the nucleus, mutant AR formed 2% sodium dodecyl sulfate (SDS)-resistant aggregates and inclusion bodies in myofibers, but not spinal cord and brainstem, in a process exacerbated by age and sex. Finally, we found that two-week induction of expression of polyQ-expanded AR in adult mice was sufficient to cause premature death, body weight loss and muscle atrophy, but not aggregation, metabolic alterations, motor coordination and fiber-type switch, indicating that expression of the disease protein in the adulthood is sufficient to recapitulate several, but not all SBMA manifestations in mice. These results imply that chronic expression of polyQ-expanded AR, i.e. during development and prepuberty, is key to induce the full SBMA muscle pathology observed in patients. Our data support a model whereby chronic expression of polyQ-expanded AR triggers muscle atrophy through toxic (neomorphic) gain of function mechanisms distinct from normal (hypermorphic) gain of function mechanisms

Neuronal network maturation differently affects secretory vesicles and mitochondria transport in axons

Abstract Studying intracellular dynamics in neurons is crucial to better understand how brain circuits communicate and adapt to environmental changes. In neurons, axonal secretory vesicles underlie various functions from growth during development to plasticity in the mature brain. Similarly, transport of mitochondria, the power plant of the cell, regulates both axonal development and synaptic homeostasis. However, because of their submicrometric size and rapid velocities, studying the kinetics of these organelles in projecting axons in vivo is technically challenging. In parallel, primary neuronal cultures are adapted to study axonal transport but they lack the physiological organization of neuronal networks, which in turn may bias observations. We previously developed a microfluidic platform to reconstruct a physiologically-relevant and functional corticostriatal network in vitro that is compatible with high-resolution videorecording of axonal trafficking. Here, using this system we report progressive changes in axonal transport kinetics of both dense core vesicles and mitochondria that correlate with network development and maturation. Interestingly, axonal flow of both types of organelles change in opposite directions, with rates increasing for vesicles and decreasing for mitochondria. Overall, our observations highlight the need for a better spatiotemporal control for the study of intracellular dynamics in order to avoid misinterpretations and improve reproducibility

EUSALP, a model region for smart energy transition: Setting the baseline

Nowadays energy transition is a recurring topic, which describes the process of an energy system moving from fossil-based sources towards renewables. The transition can unfold at different levels, from the single initiative of a local community to a complex cross-border agreement. The latter type is well represented by EUSALP, the European macro-regional strategy for the Alpine region. One of its aims is to transform its territory into a model region for energy efficiency and renewable energy. To support a well-informed decision making process, this study provides the first insight about the status quo of energy balances in EUSALP, at local as well as aggregated level. Moreover, it offers an overview on the various energy targets defined by the territorial units that constitute the EUSALP region. Data has been retrieved via a bottom-up quality-oriented process consisting of (i) a survey targeted at responsible person in local energy departments; and (ii) data control and harmonization. We found that the EUSALP region is actually a model region only in clean power production, whereas starting point as well as energy targets of territories are highly heterogeneous. We also identified the need of more harmonized data collection methodologies. We conclude that this bottom-up process can support and legitimate policy makers in cross-border cooperation activities under a smart macro-regional energy strategy, which pursues an increment in energy savings, renewable energy production and a broad engagement of relevant stakeholders

High prevalence of autoimmune diseases in women with endometriosis. a case-control study

The immune system seems to be involved in the pathogenesis of endometriosis. Peritoneal chronic inflammation is present and natural killer cells and macrophages abnormalities have been reported in women with the disease. Moreover, a higher production of serum autoantibodies has been found, which could be related to various factors; some still need to be clarified. The correlation between endometriosis and autoimmune diseases is still unclear with few and conflicting available data. The aim of this study was to evaluate the prevalence of autoimmune diseases, as conditions with a possible common pathogenetic factor, in women affected by endometriosis, in order to address future research on its pathogenesis. This retrospective case-control study includes one hundred and forty-eight women with endometriosis and 150 controls. All women were aged between 18 and 45. Informed consent was obtained from all participants of the study. Considered autoimmune diseases include systemic lupus erythematosus (SLE), celiac disease (CD), inflammatory bowel disease (IBD), and autoimmune thyroiditis. Statistical comparison of patients and control group was performed by means of chi-square test or Fisher’s exact test as appropriate. Statistical comparison of parametric variable (age) among the groups was performed by t-test for unpaired data. Age was expressed as mean. A value of.05 or less was considered as significant. In the case group, five patients were affected by IBD, while the disease was not observed in the control group (p =.07). SLE was found in eight patients in the case group, while only one was found in the control group (p =.01). Fifteen women in the case group were affected by CD, while the disease was present only in one woman in the control group (p<.0001). A significant correlation was also found between endometriosis and autoimmune thyroiditis: 80 patients with endometriosis had thyroid diseases versus 14 patients in the control group (p<.0001). Our study reports an association between endometriosis and autoimmune disorders, showing a higher prevalence of autoimmune diseases in women affected by endometriosis. These results support a possible autoimmune pathogenesis of endometriosis

Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what's the best choice?

Combined oral contraceptives (COC) and progestogens are widely used for the treatment of endometriosis. The objective of the study is to compare the efficacy of dienogest 2 mg vs continuous oral levonorgestrel/EE (levonorgestrel 0.1 mg/ethinyl estradiol 0.02 mg) on ovarian endometriomas, deep infiltrating endometriosis (DIE), chronic pelvic pain (CPP), dyspareunia, analgesic use, quality of life (QoL), compliance and side effects

Increasing brain palmitoylation rescues behavior and neuropathology in Huntington disease mice

International audienceRestoring huntingtin-mediated intracellular trafficking rescues Huntington disease mice