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Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also with proteins of the sarcoplasmic reticulum and costameres. Here, we report experiments aiming to better understand the contribution of obscurin to skeletal muscle fibers, starting with a detailed characterization of the diaphragm muscle function, which we previously reported to be the most affected muscle in obscurin (Obscn) KO mice. Twitch and tetanus tension were not significantly different in the diaphragm of WT and Obscn KO mice, while the time to peak (TTP) and half relaxation time (HRT) were prolonged. Differences in force-frequency and force-velocity relationships and an enhanced fatigability are observed in an Obscn KO diaphragm with respect to WT controls. Voltage clamp experiments show that a sarcoplasmic reticulum's Ca2+ release and SERCA reuptake rates were decreased in muscle fibers from Obscn KO mice, suggesting that an impairment in intracellular Ca2+ dynamics could explain the observed differences in the TTP and HRT in the diaphragm. In partial contrast with previous observations, Obscn KO mice show a normal exercise tolerance, but fiber damage, the altered sarcomere ultrastructure and M-band disarray are still observed after intense exercise.

Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enigmatic. While obscurin is highly expressed in striated muscles, Obsl1 is found ubiquitously. Accordingly, obscurin mutations have been linked to myopathies, whereas mutations in Obsl1 result in 3M-growth syndrome. To further study unique and redundant functions of these closely related proteins, we generated and characterized Obsl1 knockouts. Global Obsl1 knockouts are embryonically lethal. In contrast, skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization. To gain unbiased insights into changes to the muscle proteome, we analyzed tibialis anterior and soleus muscles by mass spectrometry, uncovering additional changes to the muscle metabolism. Our analyses suggest that all obscurin protein family members play functions for muscle membrane systems.

This article deals with national communities in Naples and their churches during the early modern period. Florentine, Lombard, and Genoese merchants had all received special privileges that exempted them from taxes on their trading and from local jurisdiction. These three nationes had different forms of government and the foundations and following stories of their churches differed dramatically. In fact, each of them fostered its own identity in several ways, hiring artists or employing iconographies from the motherland, allowing the coexistence of a 'pantheon' of patron saints or decorating their churches with techniques that were more common abroad. The Genoese nation is probably the most difficult to outline, as often its members decided to spread their patronage into the most important Neapolitan churches rather than gather in San Giorgio dei Genovesi. [ABSTRACT FROM AUTHOR]

The decarbonization of the electricity grid is one of the actions that can help reduce fossil fuel emissions, and thus their impact on global warming in the future. This decarbonization will be achieved mainly through the integration and widespread diffusion of renewable power sources. This is also going to be supported by the shift from the paradigm of production–transmission–distribution, where electricity production oversees large-size power plants, to renewable-based distributed/diffused production, where electricity is generated very close or even by the same (group of) user(s) (or prosumers in the latter case). The number of mid-/small-size installations based on renewable energy technologies will therefore increase substantially, and the related renewable generation will be dominant against that from large-size power plants. Unfortunately, this will very likely reduce the reliability of the grid, unless appropriate countermeasures are taken/implemented, hopefully at the same time that the paradigm shift is being achieved. To this aim, it is important to identify the anomalies and main fault causes that might possibly affect some of the central renewable (wind, PV, hydrogen) and ancillary technologies that will be used to establish future renewable-based power systems. Accordingly, this paper presents a literature survey, also extending the focus to related datasets that can be used for deeper investigation. It is highlighted that the gaps mainly refer to a lack of a common taxonomy that prevents the establishment of structured knowledge in the scope of renewable-based power systems, a lack of contributions to anomalies/faults specific to wind turbines, and a lack of datasets related to electrolyzers, fuel cells, DC/x conversion, and monitoring and communication systems. Further, in the case of monitoring and communication systems, the scientific literature is both very dated, therefore not considering possible new aspects that would be currently worthy of investigation, and not oriented toward the particular domain addressed, thus considering peculiar aspects that are left out. [ABSTRACT FROM AUTHOR]

This paper was conceived to investigate some central issues related to the upheaval of current energy scenarios in Sicily. New power connection lines that are about to be built in the Mediterranean area, planned with a view to a constantly increasing renewable generation, encourage the carrying out of analyses on how the Sicilian electric power system will be able to make itself ready to support large power injections, especially due to new renewables plants that will be established in the region soon. This study, carried out in close collaboration with the Italian TSO Terna S.p.A and the University of Palermo, defines what the impacts of new renewable power plants will be on the Sicilian power transmission grid under intact and non-intact grid conditions. This study consists of steady-state simulations carried out using WinCreso® software version 7.62.1-3 in two energy scenarios estimated for the years 2024 and 2027, based on real connection requests by producers to Terna, and allows one to go beyond the studies conducted so far on a 2030 basis through the precise identification of network nodes or lines in difficulty. Finally, as well as presenting an interesting case study due to Sicily's strategic position in the Mediterranean Sea, this article proposes a methodological approach that can easily be adopted in other contexts and by other TSOs to analyze similar situations. [ABSTRACT FROM AUTHOR]

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population. [ABSTRACT FROM AUTHOR]

This work focuses on the modeling of a zero-emissions, high-speed catamaran ferry employing a full-electric propulsion system. It addresses the global emphasis on full-electric vessels to align with IMO regulations regarding ship emissions and energy efficiency improvement. Using the AVL Cruise-M software, this research verified the implementation of an onboard fuel cell power-generating system integrated with a propulsion plant, aiming to assess its dynamic performance under load variations. The catamaran was 30 m long and 10 m wide with a cruise speed of 20 knots. The power system consisted of a proton-exchange membrane fuel cell (PEM) system, with a nominal power of 1600 kWe, a battery pack with a capacity of 2 kWh, two 777 kW electric motors, and their relative balance of the plant (BoP) subsystems. The simulation results show that the battery effectively supported the PEM during the maneuvering phase, enhancing its overall performance and energy economy. [ABSTRACT FROM AUTHOR]