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Design, synthesis and biological evaluation of new H2S-releasing rivastigmine derivatives as neuroprotective molecules
No full textAlzheimer's disease (AD) represents one of the main challenges for the 21st century medical research as no disease-modifying agent has been successfully progressed to the market, while the number of people affected by AD is estimated to grow exponentially over the next years. The complex network of triggering factors involved in the insurgence and progression of AD can be rightly addressed as one of the main reasons behind the difficulty in identifying new pharmacological approaches. For this reason, the discovery and development of drugs endowed with pleiotropic activity remain the most valuable, but at the same time challenging, approaches to tackle down AD. Interestingly, the combination of active pharmacophores through molecular hybridization - or Multi-Target Directed Ligand strategy (MTDL) - has not been explored enough for this disease, despite proving to be a successfully strategy in other field, such as oncology. To contribute to the development of new strategies against AD, we decided to explore the hybridization of the marketed drug rivastigmine - prescribed to ameliorate AD symptomatology - with moieties capable to release hydrogen sulfide (H2S), a gasotransmitter with a key role in the neurological physiology of ageing. In particular, we identified compound 1, as a potent small molecule capable of inhibit AChE, preventing inflammation and ROS production in cultured neurons and microglia, triggering autophagy response and blocking A(3 fibrils propagation. Interestingly, the beneficial effects observed in vitro have been confirmed in vivo, since the rivastigmine derivative 1 improved the lifespan in a Caenorhabditis elegans model of AD
Breakwaters impact marine turtle nesting activity
No full textCoastal erosion is a significant environmental issue, exacerbated by human activities and rising sea levels due to climate change. One of the measures developed to counteract erosion worldwide is the use of breakwaters: structures designed to protect coastlines from the force of waves. While effective, these structures can negatively impact natural habitats, including those of marine turtles. There are concerns that breakwaters may obstruct both female turtles trying to reach beaches to nest and hatchlings attempting to reach the open sea. However, information on these impacts is limited and often confounded by other environmental factors. This study aims to assess the possible impact of breakwaters on marine turtle nesting activity by taking advantage of a particular circumstance at a major nesting site (Chrysochou Bay, Cyprus), where nesting activity was monitored before (2015–2017) and after (2019–2021) the installation of 10 breakwaters. A total of 5405 nests were recorded over these periods. Despite a general increase in nest numbers in the rest of Chrysochou Bay, a marked decrease was observed landward of the breakwaters. Our findings provide conclusive evidence that emerged breakwaters impact marine turtle nesting activity
Protocol for the extraction of human auditory ossicles in bioarchaeology
No full textThis protocol describes standardised procedures for locating, extracting, documenting, and storing auditory ossicles (malleus, incus, and stapes) from archaeological human skeletal remains while minimising damage surrounding cranial structures and ensuring proper contextual documentation
Predictive prioritization of enhancers associated with pancreatic disease risk
No full textGenetic and epigenetic variation in enhancers is associated with disease susceptibility; however, linking enhancers to target genes and predicting enhancer dysfunction remain challenging. We mapped enhancer-promoter interactions in human pancreas using 3D chromatin assays across 28 donors and five cell types. Using a network approach, we parsed these interactions into enhancer-promoter tree models, enabling quantitative, genome-wide analysis of enhancer connectivity. A machine learning algorithm built on these trees estimated enhancer contributions to cell-type-specific gene expression. To test predictions, we perturbed enhancers in primary human pancreas cells with CRISPR interference and quantified effects at single-cell resolution using RNA fluorescence in situ hybridization (FISH) and high-throughput imaging. Tree models also annotated germline risk variants linked to pancreatic disorders, connecting them to candidate target genes. For pancreatic ductal adenocarcinoma risk, acinar regulatory elements showed greater variant enrichment, challenging the ductal cell-of-origin view. Together, these datasets and models provide a resource for studying pancreatic disease genetics
A comparison between terrestrial and satellite microwave links as opportunistic rainfall sensors
No full textIn the last decades, both the backhauling links of terrestrial wireless networks (Commercial Microwave Links, CMLs) and the downlink of satellite broadcasting/broadband services (Satellite Microwave Links, SML) operating in the Ku-band and above, say >10 GHz, revealed themselves as effective opportunistic systems for rainfall sensing. CMLs and SMLs exhibit, indeed, features that make them suitable to complement conventional measurements carried out by rain gauge networks, weather radars, and Earth observation satellites. Based on the experience achieved by several research Italian teams active since 2017, this paper compares CMLs and SMLs as opportunistic rainfall sensors from different perspectives. In detail, we will address technical aspects (complexity of data acquisition and processing), performance (spatio-temporal resolution, accuracy, sensitivity and benefits brought by AI techniques), data accessibility and ownership, and deployment and operational costs. Finally, the perspectives of such opportunistic sensors as operational tools are also assessed in accordance with the evolution of wireless networks: as for CMLs, fiber backhauling and the shift towards mmW bands, whereas for SMLs, the deployment of large and mega constellations of LEO satellites
Accessibility to Clinical Care for People with ASD: Design and Integration of the ACCESS Technological Tools
No full textThe Medical Impact of Hepatitis D Virus Infection in Natives and Immigrants: The Italian Paradigm
No full textBackground and Aim: Ongoing migratory flows are reconstituting the hepatitis D virus (HDV) reservoir in Italy. We aimed to characterise the current clinical and virologic features of HDV infection in both native Italians and migrants. Methods: We enrolled 515 hepatitis B surface antigen (HBsAg)-positive patients with detectable anti-HDV antibodies from 32 Italian centres between August 2022 and July 2024; all patients underwent centralised virologic assessment. Results: Overall, 432 out of 515 (83.9%) patients were HDV-RNA-positive (4.39, 1.30–5.82 Log IU/mL; 99.0% HDV genotype-1). HDV-RNA levels correlated with ALT (rs = 0575, 0.514–0.630) and hepatitis B core-related antigen (rs = 0.521, 0.455–0.581). Native Italians (n = 317; 61.6%) were older than migrants (n = 198; 38.4%) (median age: 60, 55–65 vs. 46, 39–54 years; p < 0.001) and were more frequently male (68.1% vs. 49.5%; p < 0.001), with a higher prevalence of liver cirrhosis (70.3% vs. 50.5%; p < 0.001) and hepatocellular carcinoma (14.8% vs. 0.5%; p < 0.001). Among Italians, 223 (70.3%) had liver cirrhosis, 46 (14.5%) had chronic hepatitis D (CHD) without cirrhosis and 48 (15.1%) exhibited inactive/minimal disease with low viremia (≤ 3 Log IU/mL). Among migrants, 100 (50.5%) had liver cirrhosis, 58 (29.3%) had CHD and 40 (20.2%) showed inactive/minimal disease with low viremia (≤ 3 Log IU/mL). Conclusions: The current clinical landscape of chronic HDV infections in Italy is heterogeneous, changing the perspective of CHD as uniformly severe; although cirrhosis remains common, a substantial proportion of both native Italians and migrants present with milder forms of disease
X-Ray micro-tomography unveils the internal features of volcanic ash aggregates
No full textVolcanic ash aggregation occurs during transport in the atmosphere when individual ash particles collide and stick together. It significantly impacts ash residence time in the atmosphere, with major consequences for hazard assessment and ash dispersal forecasts. Nonetheless, aggregation processes are still not adequately parametrized, mostly due to the low preservation potential of most aggregate types. We present here the first, detailed structural and morphological characterization of the major aggregate types, combining an innovative field collection strategy, which allows for the original aggregate structure to be preserved at deposition, coupled to X-Ray micro-tomography. Resulting observations together with weather information, allowed for the structure of fragile ash clusters and of the elusive cored Ash Pellets (cAP1s) to be fully resolved and their genesis to be better described. The collected dataset represents a fundamental advancement towards a comprehensive characterization of the principal aggregate categories, which is key to accurately interpreting and modelling the process of volcanic ash aggregation and dispersal