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Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP, PSEN1, PSEN2, MAPT, GRN, and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1, 11 MAPT, 9 PSEN2, and 4 APP. Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.

DNA methylation is a critical epigenetic mechanism involved in numerous physiological processes. Alterations in DNA methylation patterns are associated with various brain disorders, including dementias such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Investigating these alterations is essential for understanding the pathogenesis and progression of these disorders. Among the various methods for detecting DNA methylation, DNA sequencing is one of the most widely employed. Specifically, two main sequencing approaches are commonly used for DNA methylation analysis: bisulfite sequencing and single-molecule long-read sequencing. In this review, we compared the performances of CpG methylation detection obtained using two popular sequencing platforms, Illumina for bisulfite sequencing and Oxford Nanopore (ON) for long-read sequencing. Our comparison considers several factors, including accuracy, efficiency, genomic regions, costs, wet-lab protocols, and bioinformatics pipelines. We provide insights into the strengths and limitations of both methods with a particular focus on their application in research on AD and FTD.

One of the challenges of our age is climate change and the ways in which it affects the Earth’s global ecosystem. To face the problems linked to such an issue, the international community has defined actions aimed at the reduction in greenhouse gas emissions in several sectors, including the aviation industry, which has been requested to mitigate its environmental impact. Conventional aircraft propulsion systems depend on fossil fuels, significantly contributing to global carbon emissions. For this reason, innovative propulsion technologies are needed to reduce aviation’s impact on the environment. Electric propulsion has emerged as a promising solution among the several innovative technologies introduced to face climate change challenges. It offers, in fact, a pathway to more sustainable air travel by eliminating direct greenhouse gas emissions, enhancing energy efficiency. Unfortunately, integrating electric motors into aircraft is currently a big challenge, primarily due to thermal management-related issues. Efficient heat dissipation is crucial to maintain optimal performance, reliability, and safety of the electric motor, but aeronautic applications are highly demanding in terms of power, so ad hoc Thermal Management Systems (TMSs) must be developed. The present paper explores the design and optimization of a TMS tailored for a megawatt electric motor in aviation, suitable for regional aircraft (~80 pax). The proposed system relies on coolant oil injected through a hollow shaft and radial tubes to directly reach hot spots and ensure effective heat distribution inside the permanent magnet cavity. The goal of this paper is to demonstrate how advanced TMS strategies can enhance operational efficiency and extend the lifespan of electric motors for aeronautic applications. The effectiveness of the radial tube configuration is assessed by means of advanced Computational Fluid Dynamics (CFD) analysis with the aim of verifying that the proposed design is able to maintain system thermal stability and prevent its overheating.

Octocorals have proven to be a prolific source of bioactive natural products, exhibiting a wide spectrum of pharmacological activities. Among octocorals, Pennatulaceans, commonly known as sea pens, are among the most dominant soft coral species living in benthic communities. Nonetheless, reports on bioactivity and chemical investigations of this genus are scarce. This prompted us to shed light on the pharmacological potential of the extracts of the sea pen Pennatula phosphorea, Linneus 1758, and gain an overview of its metabolome. Crude octocoral extracts, obtained with a modified Kupchan extraction protocol, were assessed for their bioactivity potential, revealing the hexanic extract to exert anti-inflammatory effects and interesting protective properties in an in vitro model of sarcopenia and in auditory HEI-OC1 cisplatin-treated cells, while the chloroformic extract was active in reducing A375 melanoma cell viability in a concentration-dependent manner. An untargeted metabolomic analysis unveiled that P. phosphorea collects a wide array of glycerophospholipids and phosphosphingolipids belonging to the ceramide phosphoinositol class, which were exclusive or more abundant in the hexanic extract. Their proven anti-inflammatory and cytoprotective effects could demonstrate the activity shown by the P. phosphorea hexanic extract. In addition, a group of prostaglandins, eluted mainly in the chloroformic extract, were putatively annotated. Since prostanoids from marine origin have been demonstrated to exert cytotoxic and anti-proliferative properties against various cancer cell lines, the presence of PGs in the P. phosphorea chloroform extract could justify its anti-melanoma activity. This is the first report on the presence of glycerophospholipids, phosphosphingolipids, and prostaglandins, along with the identification of novel congeners, in sea pens.

Nowadays, control is pervasive in vehicles, and a full and accurate knowledge of vehicle states is crucial to guarantee safety levels and support the development of Advanced Driver-Assistance Systems (ADASs). In this scenario, real-time monitoring of the vehicle sideslip angle becomes fundamental, and various virtual sensing techniques based on both vehicle dynamics models and data-driven methods are widely presented in the literature. Given the need for on-board embedded device solutions in autonomous vehicles, it is mandatory to find the correct balance between estimation accuracy and the computational burden required. This work mainly presents different physical KF-based methodologies and proposes both mathematical and graphical analysis to explore the effectiveness of these solutions, all employing equal tire and vehicle simplified models. For this purpose, results are compared with accurate sensor acquisition provided by the on-track campaign on passenger vehicles; moreover, to truthfully represent the possibility of using such virtual sensing techniques in real-world scenarios, the vehicle is also equipped with low-end sensors that provide information to all the employed observers.

PurposeThis study aimed to provide an exploratory analysis of digitalization processes in small professional service firms (SPSFs) by examining their main drivers and barriers and their impact on customer management practices, considering the intra-organizational, inter-organizational and service offering dimensions.Design/methodology/approachThis study adopted a qualitative, exploratory and inductive research methodology based on in-depth interviews with 19 owners or consultants of small tax/accounting firms, focusing on the role of digitalization in their internal and external processes.FindingsThe findings reveal external and internal barriers to and drivers of digitalization, as well as its effects on customer management practices. They also reveal the emergence of tensions related to the intra-organizational, inter-organizational and service offering dimensions.Originality/valueThis work contributes to the research on the role of digital technologies in the professional service sector, with a focus on SPSFs, which has thus far received limited attention. This research highlights the complexity of combining increasingly standardized processes and services with the need to maintain flexibility and informality in internal and external interactions.

The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne’s muscular dystrophy. In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles. Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice. In conclusion, our study uncovers a PAX7–CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies. The regenerative capacity of muscle stem cells is impaired in Duchenne muscular dystrophy (DMD). Here, the authors show that the endocannabinoid receptor CB1 is activated by PAX7 in muscle stem cells, and that pharmacological inhibition of CB1 promotes stem cell activation and ameliorates symptoms in DMD mouse models.

By mass spectrometry analysis of mouse Cystic Fibrosis Transmembrane-conductance Regulator (mCFTR) expressed in yeast we have detected 21 phosphopeptides accounting for 22 potential phospho-residues, 12 of which could be unambiguously assigned. Most are conserved in human CFTR (hCFTR) and the majority cluster in the Regulatory Domain, lying within consensus sequences for PKA, as identified in previous mammalian studies. This validates our yeast expression model. A number of phospho-residues were novel and human conserved, notably mouse Ser670, Ser723, Ser737, and Thr1467, that all lie in acidic sequences, compatible with their phosphorylation by protein kinase CK2. Thr1467 is localized in the C-terminal tail, embedded in a functionally important and very acidic sequence (EETEEE) which displays an optimal consensus for protein kinase CK2. Herein, we show that Thr1467, homologous to human Thr1471 is readily phosphorylated by CK2. Indeed a 42 amino acid peptide encompassing the C-terminal segment of human CFTR is readily phosphorylated at Thr1471 with favorable kinetics (Km 1.7 µM) by CK2 holoenzyme, but neither by its isolated catalytic subunit nor by other acidophilic Ser/Thr kinases (CK1, PLK2/3, GCK/FAM20C). Our finding that by treating CFTR expressing BHK cells with the very specific CK2 inhibitor CX4945, newly synthesized wild type CFTR (and even more its Phe508del mutant) accumulates more abundantly than in the absence of CK2 inhibitor, supports the conclusion that phosphorylation of CFTR by CK2 correlates with decreased stability of the protein.

The aviation sector is firmly committed to reducing harmful emissions and electric propulsion promises to tackle both pollution and noise at the same time. More Electric Aircrafts are progressively giving way to full electric aircraft that are expected to represent the next revolution in aviation. As is known, electric propulsion can be based on different electrochemical sources; nowadays, the widely used systems are developed on lithium battery packs, especially in automotive, where requirements in terms of gravimetric and volumetric energy densities are not so stringent compared to the aeronautical sector. Systems based on hydrogen fuel cells exhibit better performance in terms of range and endurance. In this article, a numerical study is presented on a lightweight electric aircraft, whose battery-based architecture is converted to a fuel cell-based architecture with the contribution of a battery pack that essentially intervenes in the take-off phase and, in addition, of a pack of ultracapacitors to prevent high discharge rate of the battery. The final intent is to explore the range extension without an increase in maximum take-off weight. The lumped parameter numerical models of the two propulsion systems have been developed in Simcenter Amesim where a set of simulations has been launched. It is shown that even under the constraint on the maximum take-off weight a significant extension of the range is obtained when adopting an electric propulsion system based on hydrogen fuel cells.

Group B streptococcus (GBS) infection remains a leading cause of sepsis, pneumonia, and meningitis in infants. Rates of GBS early onset disease have declined following the widcespread use of intrapartum antibiotic prophylaxis; hence, late-onset infections (LOGBS) are currently a common presentation of neonatal GBS dicsease. The pathogenesis, mode of transmission, and risk factors associated with LOGBS are unclear, which interfere with effective prevention efforts. GBS may be transmitted from the mother to the infant at the time of delivery or during the postpartum period via contaminated breast milk, or as nosocomial or community-acquired infection. Maternal GBS colonization, prematurity, young maternal age, HIV exposure, and ethnicity (Black) are identified as risk factors for LOGBS disease; however, further studies are necessary to confirm additional risk factors, if any, for the implementation of effective prevention strategies. This narrative review discusses current and previous studies that have reported LOGBS. Few well-designed studies have described this condition; therefore, reliable assessment of maternal GBS colonization, breastfeeding, and twin delivery as risk factors for LOGBS remains limited. Keywords: neonatal sepsis, prevention, infant, meningitis, CC17