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Inflammatory diseases are conditions characterized by abnormal and often excessive immune responses, leading to tissue and organ inflammation. The complexity of these disorders arises from the intricate interplay of genetic factors and immune responses, which challenges conventional therapeutic approaches. However, the field of genetic manipulation has sparked unprecedented optimism in addressing these complex disorders. This review aims to comprehensively explore the application of gene therapy and gene editing in the context of inflammatory diseases, offering solutions that range from correcting genetic defects to precise immune modulation. These therapies have exhibited remarkable potential in ameliorating symptoms, improving quality of life, and even achieving disease remission. As we delve into recent breakthroughs and therapeutic applications, we illustrate how these advancements offer novel and transformative solutions for conditions that have traditionally eluded conventional treatments. By examining successful case studies and preclinical research, we emphasize the favorable results and substantial transformative impacts that gene-based interventions have demonstrated in patients and animal models of inflammatory diseases such as chronic granulomatous disease, cryopyrin-associated syndromes, and adenosine deaminase 2 deficiency, as well as those of multifactorial origins such as arthropathies (osteoarthritis, rheumatoid arthritis) and inflammatory bowel disease. In conclusion, gene therapy and gene editing offer transformative opportunities to address the underlying causes of inflammatory diseases, ushering in a new era of precision medicine and providing hope for personalized, targeted treatments. [ABSTRACT FROM AUTHOR]

This paper describes a 2D physical model study on the hydraulic performances of composite vertical breakwaters with retreated wave walls. The research is an expansion of a previous experimental study by the same Authors: a very large number of experiments, in the order of 2,000, have been carried out by exploring and varying a wide range of wave and geometrical parameters of the structure, to investigate their effect and importance. In order to make feasible the execution of this large number of tests, a small-scale wave flume was used and regular wave conditions were reproduced. The influence of the wave wall retreat has been investigated in terms of wave-induced forces, reflection coefficients and wave overtopping discharges, comparing the hydraulic performances of structures with retreated walls with those of a flushed wall configuration under the same wave conditions. The large number of experiments allowed to formulate a detailed description of the complex phenomena at hand, providing statistical indicators that can be used as guidelines for preliminary design purposes of such structures, quantifying the relevant sources of uncertainty. The analysis confirmed and extended the previous findings and indicates that, on average, the hydraulic performances of structures with retreated crown wall vary significantly from those of flushed wall configurations. Specifically: (I) the forces acting on the wave wall increase of a factor up to 1.5, due to the occurrence of impulsive loads; (II) the forces acting on the caisson trunk decrease of a factor up to 0.91; (III) the global forces can decrease reaching a minimum reduction factor of 0.87, although some dangerous exceptions, in which equal or larger loads, than those occurring for standard flushed wall configuration, have been registered; (IV) the reflection coefficients decrease of a factor up to 0.83; (V) the wave overtopping discharges increase up to 2.55 times those with flushed walls. • New small-scale 2D experiments on vertical breakwaters with retreated walls. • A wide range of wave and geometrical parameters is systematically investigated. • Almost 2,000 regular wave tests carried out to measure hydraulic performances. • Hydraulic performances of retreated wall structures are compared, in terms of ratios, with flushed wall ones. • Statistical indicators to be used as guidelines for preliminary design are provided. [ABSTRACT FROM AUTHOR]

The traditional focus of corporate law is on aligning managers' preferences with the interests of shareholders. We show that this view is premised on two assumptions that are no longer true: first, the idea that all shareholders want to maximize the net present value of the firm's earnings per dollar invested and, second, the view that microeconomic shocks do not produce macroeconomic consequences. The rise of institutional investors undermines the first assumption: large asset managers hold the entire market and have been shown to display a preference for maximizing the value of their portfolio as a whole rather than the performance of individual companies. That is, they are portfolio, rather than firm, value maximizers. At the same time, the increasing interconnectedness of the economy, and society more broadly, undermines the second assumption. There is ample empirical evidence that microeconomic shocks to a well-identified subset of "central" firms can propagate through the existing interconnections and generate catastrophic consequences. We argue that corporate law should reflect these features of contemporary economies. On the one hand, it should aim to ensure that noncentral firms maximize their own value, despite the rise of portfolio value maximizers. On the other hand, central firms' corporate law should harness the preferences of portfolio value maximizing shareholders with the goal of minimizing the risk of catastrophic externalities like climate change or financial crises. We develop a framework to guide policymakers in the pursuit of this new, fundamental conception of corporate law and illustrate how this rewiring of corporate law could work out by taking ownership disclosure rules as an example. [ABSTRACT FROM AUTHOR]

• A nudge that does not impose any additional cost on consumers can help reducing the use of carrier bags. • Consumption of carrier bags was reduced by about 8–12% • The effect of the nudge continued even after the end of the treatment period. • Policymakers can adapt this nudge to many contexts. In this article we show that it is possible to reduce carrier bags consumption without imposing additional costs on supermarket customers. To this end, we exploit the fact that people shopping in a certain area are likely to have homogeneous preferences on certain dimensions (e.g., sport teams). We implement a simple treatment in a supermarket in Naples, Italy: whenever a customer of the supermarket buys a single-use carrier bag we donate a small sum to an institution that is likely to be perceived negatively by the customers of the supermarket (an "anti-charity"). Vice versa, whenever a customer does not purchase a bag, we donate the same amount to an association that is likely to be perceived positively by the customers of the supermarket (a "charity"). We measure the impact of the treatment with respect to the previous weeks, the corresponding weeks of the previous year and we look at the persistence of the effect. Our results show that this treatment causes a significant reduction in bags consumption without imposing monetary costs on supermarket customers. Moreover, we show that our nudge can easily be used by regulators at virtually no cost by creating multi-city tournaments. We explain how these tournaments could be arranged. [ABSTRACT FROM AUTHOR]

Landslide-generated tsunamis are a relevant hazard. Their low frequency/high consequences character and the complex phenomena related to their generation, propagation and interaction with the shore make the proper modeling of these phenomena a crucial activity to mitigate the related risk. In this article, a new numerical method for modeling tsunamis generated by granular landslides in OpenFOAM® is presented. The approach consists in modeling the granular material by using a Coulomb viscoplastic rheology (non-Newtonian rheology) implemented in the standard solver multiPhaseInterFoam. The proposed approach is simple as it only depends on few physics-based parameters, thus implying less uncertainties than dense fluid models and more flexibility and computational efficiency than Euler–Euler approaches. This numerical framework is applied to reproduce three literature benchmark landslide-tsunami cases: two-dimensional (2D) submerged as well as 2D and three-dimensional (3D) subaerial. Comparing numerical and experimental results, a good agreement is found for granular material behavior, while an overall very good (excellent in some cases) agreement is found as far as fluid behavior and waves characteristics are concerned, testifying that the momentum transfer between granular and fluid phases is well reproduced by this simple rheological model. Qualitative descriptions of the numerical results, in terms of landslide behavior, wave generation characteristics, and velocity field during the generation/propagation process are provided. Moreover, quantitative comparisons between experimental and numerical results by comparing landslide evolution, free surface elevation time series, and runup time series are presented and discussed in the article. • A new method to model tsunamis generated by granular landslides in OpenFOAM® is presented. • Granular landslides are modeled by Coulomb viscoplastic rheology in multiPhaseInterFoam. • Strengths of the approach: simple, robust and computationally efficient. • The model is validated against three literature benchmark landslide-tsunami cases. • A good agreement between numerical and experimental near-field results is found. [ABSTRACT FROM AUTHOR]

This paper presents a physical model study of wave induced forces on a composite vertical breakwater, where the crown wave wall is retreated with respect to the front face of the caisson. Four different configurations (one flushed wall and three retreated wall configurations) have been tested under regular wave conditions, aiming at providing a first experimental insight on the increase/reduction of the wave loads acting on the structure. The analysis of the experimental results allows to describe the basic phenomena involved and to identify the physical/geometrical drivers, which are expected to play a role on the force increase/reduction factor. Thus, detailed processing of both forces/moments (synchronous analysis) and pressures (asynchronous analysis) on the whole structure, the wall and the caisson trunk, together with the analysis of reflection coefficients as a function of the wall position, are presented and discussed in the paper. The experimental evidences suggest that, at least for the four configurations tested, the global forces acting on the caisson vary significantly depending on the wall position, resulting in a reduction between 5% and 31% for high energy sea states. A similar behavior is found considering the global moments. Furthermore, the synchronous analysis of the forces highlighted that the physical/geometrical drivers, identified in the present study, can have both a concordant and antithetical action among them, then resulting in increasing or decreasing, respectively, forces acting on the structure, if compared with the flushed wall configuration. • New experiments on wave loads on a vertical breakwater with retreated crown wall. • Four wall configurations (one flushed and three retreated) tested under regular waves. • Basic physical phenomena involved and physical/geometrical drivers are investigated. • Physical/geometrical drivers can have concordant or antithetical action among them. • Global forces acting on the caisson vary significantly depending on the wall position. [ABSTRACT FROM AUTHOR]

The alteration in the neural circuits of both central and peripheral nervous systems is closely related to the onset of neurodegenerative disorders (NDDs). Despite significant research efforts, the knowledge regarding NDD pathological processes, and the development of efficacious drugs are still limited due to the inability to access and reproduce the components of the nervous system and its intricate microenvironment. 2D culture systems are too simplistic to accurately represent the more complex and dynamic situation of cells in vivo and have therefore been surpassed by 3D systems. However, both models suffer from various limitations that can be overcome by employing two innovative technologies: organ‐on‐chip and 3D printing. In this review, an overview of the advantages and shortcomings of both microfluidic platforms and extracellular matrix‐like biomaterials will be given. Then, the combination of microfluidics and hydrogels as a new synergistic approach to study neural disorders by analyzing the latest advances in 3D brain‐on‐chip for neurodegenerative research will be explored. [ABSTRACT FROM AUTHOR]

The recent destructive landslide tsunamis, such as the 2018 Anak Krakatau event, were fresh reminders for developing validated three-dimensional numerical tools to accurately model landslide tsunamis and to predict their hazards. In this study, we perform Three-dimensional physical modelling of waves generated by subaerial solid-block landslides, and use the data to validate two numerical models: the commercial software FLOW-3D HYDRO and the open-source OpenFOAM package. These models are key representatives of the primary types of modelling tools—commercial and open-source—utilized by scientists and engineers in the field. This research is among a few studies on 3D physical and numerical models for landslide-generated waves, and it is the first time that the aforementioned two models are systematically compared. We show that the two models accurately reproduce the physical experiments and give similar performances in modelling landslide-generated waves. However, they apply different approaches, mechanisms and calibrations to deliver the tasks. It is found that the results of the two models are deviated by approximately 10% from one another. This guide helps engineers and scientists implement, calibrate, and validate these models for landslide-generated waves. The validity of this research is confined to solid-block subaerial landslides and their impact in the near-field zone. [ABSTRACT FROM AUTHOR]

Peripheral nerve regeneration is regulated through the coordinated spatio‐temporal activation of multiple cellular pathways. In this work, an integrated proteomics and bioinformatics approach was employed to identify differentially expressed proteins at the injury‐site of rat sciatic nerve at 20 days after damage. By a label‐free liquid chromatography mass‐spectrometry (LC‐MS/MS) approach, we identified 201 differentially proteins that were assigned to specific canonical and disease and function pathways. These include proteins involved in cytoskeleton signaling and remodeling, acute phase response, and cellular metabolism. Metabolic proteins were significantly modulated after nerve injury to support a specific metabolic demand. In particular, we identified a group of proteins involved in lipid uptake and lipid storage metabolism. Immunofluorescent staining for acyl‐CoA diacylglycerol acyltransferase 1 (DGAT1) and DAGT2 expression provided evidence for the expression and localization of these two isoforms in Schwann cells at the injury site in the sciatic nerve. This further supports a specific local regulation of lipid metabolism in peripheral nerve after damage. [ABSTRACT FROM AUTHOR]

The present study was aimed at contributing to the understanding of the role of pre-service special education teachers' attachment styles and empathy dimensions in sentiments, attitudes, and concerns towards disability. Participants were 536 pre-service special education teachers (78.4% females and 21.6% males), Results of the path analysis showed that some empathy dimensions (fantasy and personal distress) played a mediating role in the association between preoccupied and fearful attachment styles and teachers' sentiments and concerns towards disability. Moreover, a direct positive association was reported from preoccupied attachment style to sentiments and concerns towards disability, from fantasy and personal distress (both dimensions of empathy) to sentiments towards disability, from personal distress to concerns towards disability, and from empathic concerns to attitudes towards disability, whereas negative relationships were found from perspective-taking to concerns and sentiments towards disability, as well as from empathic concern to sentiments towards disability. [ABSTRACT FROM AUTHOR]

Genetic defects in the nuclear encoded subunits and assembly factors of cytochrome c oxidase (mitochondrial complex IV) are very rare and are associated with a wide variety of phenotypes. Biallelic pathogenic variants in the COX11 protein were previously identified in two unrelated children with infantile-onset mitochondrial encephalopathies. Through comprehensive clinical, genetic and functional analyses, here we report on a new patient harboring novel heterozygous variants in COX11, presenting with Leigh-like features, and provide additional experimental evidence for a direct correlation between COX11 protein expression and sensitivity to oxidative stress. To sort out the contribution of the single mutations to the phenotype, we employed a multi-faceted approach using Saccharomyces cerevisiae as a genetically manipulable system, and in silico structure-based analysis of human COX11. Our results reveal differential effects of the two novel COX11 mutations on yeast growth, respiration, and cellular redox status, as well as their potential impact on human protein stability and function. Strikingly, the functional deficits observed in patient fibroblasts are recapitulated in yeast models, validating the conservation of COX11's role in mitochondrial integrity across evolutionarily distant organisms. This study not only expands the mutational landscape of COX11-associated mitochondrial disorders but also underscores the continued translational relevance of yeast models in dissecting complex molecular pathways. [ABSTRACT FROM AUTHOR]

We propose an integrable nonautonomous Lotka-Volterra model to carry out a quantitative study of the interaction among container ports located in the Le Havre-Hamburg range. We find that mutualism is emerging among the ports located in the Benelux area, but not among German ports. Moreover, we develop three alternative scenarios and find that ( i ) for mutualism to emerge no port must be too strong vis-à-vis the others; ( ii ) the kind of interaction among ports depends on their geographic location, the services they provide, and demand-side factors; and ( iii ) upgrading intermodal connections can produce externalities that are not internalized by the investing port/country. [ABSTRACT FROM AUTHOR]

In this paper the Empirical Orthogonal Function (EOF) method is applied to extract from the experimental data, related to landslide-tsunamis around the coast of a conical island, the spatial modes that contribute to the wave field. For each mode the wavenumber and the frequency are calculated by analyzing the shape along the coast and the time function. The relevant modes are then compared with those obtained through numerical eigenanalysis of the long wave equation around the considered island. It was possible to associate each EOF mode with some eigenvectors and the corresponding eigenfrequencies, both on the basis of the spatial shape, the wavenumber calculated along the coast and the frequency. Results confirm that landslide-generated waves propagate along the coast as trapped edge waves and the zero-th order mode is the most important. Further of exploring the physics, it is believed that this paper can be of use as some of the most relevant and straightforward techniques for modal identification are applied to the same problem and dataset. [ABSTRACT FROM AUTHOR]

Background: Mesothelioma is a rare neoplasm which commonly develops in the pleura of people exposed to asbestos. Pericardial mesothelioma accounts for only 0.7 % of all malignant mesotheliomas and it usually presents with pericardial effusion, mimicking serositis. To date, there are approximately 200 cases of pericardial mesothelioma described in the medical literature, and little knowledge exists about the systemic manifestations of this pathology. The first and only described case of pericardial mesothelioma with autoimmune features dates back to 1984 and, in our case report, we describe the second.Case Presentation: We report a case of a 45-year-old white woman whose pericardial mesothelioma was initially misdiagnosed as pericardial involvement of an autoimmune disease (systemic lupus erythematosus). After several relapses of pericardial effusion, a computed tomography scan and a biopsy with histological analysis were performed revealing neoplastic growth.Conclusions: We describe a rare case of pericardial mesothelioma in a patient with a clinical presentation compatible with lupus serositis. Clinicians should consider malignant mesothelioma in the differential diagnosis of pericardial effusion, especially when it is recurrent and not clearly explained by other causes. Cytological samples should always be obtained and, if imaging tools are suggestive for solid processes, histological confirmation is mandatory. [ABSTRACT FROM AUTHOR]

Will coastal towns survive the rising pressure, or better, the rising sea level in future decades? Waves overtop dikes, and the overtopping flow on the crest of the dike can cause damage. Wave impacts from these overtopping flows already became of interest in coastal engineering the past few years, but very little literature and almost no design formulae are available yet for irregular waves. This paper gives such design formulae for practical use. Experimental modeling at three different scales (small, middle and large scale) has been carried out to measure such impacts. The tested geometry was a smooth sloping dike (only non-breaking waves) with a promenade at crest level and a storm wall at the end of this promenade. The outcome of this paper are three methodologies to a) calculate wave impact forces on such a storm wall as a function of the hydraulic parameters; b) determine the (Weibull) distribution of all impacts in one test, with the shape and scale parameters also linked to the hydraulic parameters; and c) to provide an indirect approach to calculate the impact forces on the storm wall. In this last approach, the (distribution of the) individual overtopping waves are linked to the (distribution of the) overtopping flow parameters, which are then linked to the (distribution of the) impact forces. Finally, the empirical formulae from the aforementioned three methodologies are compared; analogies and differences are discussed, and guidance is provided to design storm walls against post overtopping impact forces. Results show that forces from waves overtopping the dikes are in the order of 20 to 40 kN/m prototype scale in the dimensionless freeboard (R c /H m0 ) range of 1 to 2. This is (much) lower compared to impact forces on vertical walls as calculated by the Shore Protection Manual. [ABSTRACT FROM AUTHOR]

In this work, we assessed the capacity of RNA polymerases to use platinated ribonucleotides as substrates for RNA synthesis by testing the incorporation of the model compound [Pt(dien)( N7 -5′-GTP)] (dien = diethylenetriamine; GTP = 5′-guanosine triphosphate) into a natural RNA sequence. The yield of in vitro transcription operated by T7 RNA polymerase, on the LacZ ( Escherichia coli gene encoding for β-galactosidase) sequence, decreases progressively with decreasing the concentration of natural GTP, in favor of the platinated nucleotide, [Pt(dien)( N7 -5′-GTP)]. Comparison of the T7 RNA polymerase transcription activities for [Pt(dien)( N7 -5′-GTP)] compound incorporation reaction test, with respect to the effect of a decreasing concentration of natural GTP, showed no major differences. A specific inhibitory effect of compound [Pt(dien)( N7 -5′-GTP)] (which may pair the complementary base on the DNA strand, without being incorporated in the RNA by the T7 RNA polymerase) was evidenced. Our findings therefore suggest that RNA polymerases, unlike DNA polymerases, are unable to incorporate N7 -platinated nucleotides into newly synthesized nucleic acids. In this respect, specifically designed N7 -platinated nucleotides based compounds could be used in alternative to the classical platinum based drugs. This approach may offer a possible strategy to target specifically DNA, without affecting RNA, and is potentially able to better modulate pharmacological activity. [ABSTRACT FROM AUTHOR]

This article is a first application of an integrable nonautonomous Lotka–Volterra (LV) model to the study of tourism dynamics. In particular, we analyze the interaction in terms of touristic flows among three Italian regions. Confirming an hypothesis advanced by recent theoretical works, we find that these regions not only compete against each other, but at times they also proceed in mutualism. Moreover, the kind and the intensity of the interaction changes over time, suggesting that dynamic models can play a vital role in the study of touristic flows. [ABSTRACT FROM AUTHOR]

Wave overtopping is a relevant threat for rubble mound breakwaters which are designed to protect coastal areas or harbours. Currently, the wave overtopping assessment for such structures is mostly performed by using empirical formulae where hydraulic and geometric variables together with correction factors are included, such as the armour roughness. The predictive overtopping formulae for sloping structures are usually applied by assuming a constant value of this parameter based on the type of armour units, number of layers and type of core. In this paper we present a new methodology to estimate the roughness factor for rubble mound breakwaters as a function of both hydraulic and structural parameters. To this end, new physical model tests and previous results obtained from an existing database (i.e., CLASH) have been used. The new methodology to estimate the roughness factor, depending on a detailed complete geometrical representation, provides an improved prediction of the average overtopping discharge compared to the existing formulae. • New 2D physical model tests on wave overtopping: influence of the roughness factor. • Extended database to assess the performance of roughness factor existing formulae. • New method to estimate roughness factor based on geometrical and wave parameters. [ABSTRACT FROM AUTHOR]

Inflammasome complexes and their integral receptor proteins have essential roles in regulating the innate immune response and inflammation at the post-translational level. Yet despite their protective role, aberrant activation of inflammasome proteins and gain of function mutations in inflammasome component genes seem to contribute to the development and progression of human autoimmune and autoinflammatory diseases. In the past decade, our understanding of inflammasome biology and activation mechanisms has greatly progressed. We therefore provide an up-to-date overview of the various inflammasomes and their known mechanisms of action. In addition, we highlight the involvement of various inflammasomes and their pathogenic mechanisms in common autoinflammatory, autoimmune and neurodegenerative diseases, including atherosclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We conclude by speculating on the future avenues of research needed to better understand the roles of inflammasomes in health and disease. [ABSTRACT FROM AUTHOR]

Low levels of vitamin D are related to muscle weakness, poor balance, and higher risk of falls, and can therefore have a major impact on performance and safety at work. Little knowledge exists on the association between work environment and vitamin D status. This study evaluates vitamin D status in shift workers. In this cross-sectional study, led during early springtime, 96 male shift workers at an engineering factory in Northern Italy, and 100 male daily workers operating nearby, participated. 25-OH vitamin D concentration, anthropometric indexes, fasting glycemia and triglycerides were detected. 51 shift workers underwent anamnesis collection on lifestyle and habits and determination of heel bone mineral density. Vitamin D levels were lower in shift workers than daily ones (13.4 ± 5.3 ng/mL versus 21.9 ± 10.7 ng/mL, p < 0.001). Linear regression analysis adjusted for age, body mass index and smoking habits confirms a statistically significant association between shift work and vitamin D levels ( p < 0.0001). An association trend between cigarette smoking and low vitamin D values was found. No significant association was detected between the heel bone mineral density values and vitamin D levels or smoking habits. In conclusion, this cross-sectional study highlights the high prevalence of vitamin D deficit among shift workers compared with daily ones. [ABSTRACT FROM AUTHOR]

Due to the risk of severe vaccine-associated adverse events, yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease. From September 2008 through June 2009, two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deaths (case-fatality, 43%) in the southern state of Rio Grande do Sul and 28 cases with 11 deaths (39%) in Sao Paulo state. Epizootic deaths of non-human primates were reported before and during the outbreak. Over 5.5 million doses of yellow fever vaccine were administered in the two most affected states. Vaccine-associated adverse events were associated with six deaths due to acute viscerotropic disease (0.8 deaths per million doses administered) and 45 cases of acute neurotropic disease (5.6 per million doses administered). Yellow fever vaccine recommendations were revised to include areas in Brazil previously not considered at risk for yellow fever. Author Summary: Yellow fever is a viral hemorrhagic disease transmitted by mosquitos, endemic in tropical regions of Africa and South America. Large urban outbreaks of yellow fever have been eliminated in the Americas, where most yellow fever cases result from human exposure to jungle or forested environments. Vaccination is effective but carries a risk of potentially fatal adverse events in a small number of vaccinees. In a large country such as Brazil, vaccination is recommended only in areas where there is a risk of exposure to yellow fever virus. We describe two outbreaks of yellow fever in areas without yellow fever vaccine recommendations. Numerous epizootics, or die-offs of non-human primates, were reported from areas with human cases. In response to the outbreaks and epizootic activity, over five million doses of vaccine were administered in previously unvaccinated populations, resulting in vaccine associated adverse events, six of which were fatal. The outbreaks resulted in expansion of areas with yellow fever vaccine recommendations, and highlight the need for safer yellow fever vaccines. [ABSTRACT FROM AUTHOR]

Human genes for passive, ion-coupled transporters and exchangers are included in the so-called solute carrier (SLC) gene series, to date consisting of 52 families and 398 genes. Teleost fish genes for SLC proteins have also been described in the last two decades, and catalogued in preliminary SLC-like form in 50 families and at least 338 genes after systematic GenBank database mining (December 2010-March 2011). When the kinetic properties of the expressed proteins are studied in detail, teleost fish SLC transporters always reveal extraordinary 'molecular diversity' with respect to the mammalian counterparts, which reflects peculiar adaptation of the protein to the physiology of the species and/or to the environment where the species lives. In the case of the H+-oligopeptide transporter PEPT1(SLC15A1), comparative analysis of diverse teleost fish orthologs has shown that the protein may exhibit very eccentric properties in terms of pH dependence (e.g. the adaptation of zebrafish PEPT1 to alkaline pH), temperature dependence (e.g. the adaptation of icefish PEPT1 to sub-zero temperatures) and/or substrate specificity (e.g. the species-specificity of PEPT1 for the uptake of l-lysine-containing peptides). The revelation of such peculiarities is providing new contributions to the discussion on PEPT1 in both basic (e.g. molecular structure-function analyses) and applied research (e.g. optimizing diets to enhance growth of commercially valuable fish). [ABSTRACT FROM AUTHOR]

Due to the risk of severe vaccine-associated adverse events, yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease. From September 2008 through June 2009, two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deaths (case-fatality, 43%) in the southern state of Rio Grande do Sul and 28 cases with 11 deaths (39%) in Sao Paulo state. Epizootic deaths of non-human primates were reported before and during the outbreak. Over 5.5 million doses of yellow fever vaccine were administered in the two most affected states. Vaccine-associated adverse events were associated with six deaths due to acute viscerotropic disease (0.8 deaths per million doses administered) and 45 cases of acute neurotropic disease (5.6 per million doses administered). Yellow fever vaccine recommendations were revised to include areas in Brazil previously not considered at risk for yellow fever. [ABSTRACT FROM AUTHOR]

Adaptation of organisms to extreme environments requires proteins to work at thermodynamically unfavorable conditions. To adapt to subzero temperatures, proteins increase the flexibility of parts of, or even the whole, 3D structure to compensate for the lower thermal kinetic energy available at low temperatures. This may be achieved through single-site amino acid substitutions in regions of the protein that undergo large movements during the catalytic cycle, such as in enzymes or transporter proteins. Other strategies of cold adaptation involving changes in the primary amino acid sequence have not been documented yet. In Antarctic icefish (Chionodraco hamatus) peptide transporter 1 (PEPT1), the first transporter cloned from a vertebrate living at subzero temperatures, we came upon a unique principle of cold adaptation. A de novo domain composed of one to six repeats of seven amino acids (VDMSRKS), placed as an extra stretch in the cytosolic COOH-terminal region, contributed per se to cold adaptation. VDMSRKS was in a protein region uninvolved in transport activity and, notably, when transferred to the COOH terminus of a warm-adapted (rabbit) PEPT1, it conferred cold adaptation to the receiving protein. Overall, we provide a paradigm for protein cold adaptation that relies on insertion of a unique domain that confers greater affinity and maximal transport rates at low temperatures. Due to its ability to transfer a thermal trait, the VDMSRKS domain represents a useful tool for future cell biology or biotechnological applications. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the mediating role of problem-solving coping strategies in the relationship between thinking styles (legislative, executive, and judicial) and teachers' attitudes towards distance education (difficulties related to distance education and efficacy in distance education). The study sample consisted of 556 special education teachers, 122 males (21.9%) and 434 females (78.1%), with an average age of 37.90 years (SD = 7.12). The results confirmed the role of problem-solving coping as a mediator for legislative thinking style on difficulties related to distance education. Furthermore, the findings indicated a positive relationship between judicial style and efficacy in distance education. The results of this study highlight the importance of developing specific special education teacher trainings to promote positive attitudes towards distance education. [ABSTRACT FROM AUTHOR]

SLC15A4/PHT1 is an endolysosome-resident carrier of oligopeptides and histidine recently come into view as a key path marker of immune/autoimmune/inflammatory pathways in immune cells. Yet, its emerging role in inflammatory processes directly targeting the gastrointestinal epithelial layer, as in the multifactorial pathophysiology of inflammatory bowel disease (IBD), is poorly investigated. Here, the first identification of SLC15A4/PHT1 gene products in human colonic epithelium of ulcerative colitis (UC) patients is reported, showing protein primarily localized in intracellular vesicle-like compartments. Qualitative and quantitative immunohistochemical analyses of colon biopsies revealed overexpression of SLC15A4/PHT1 protein product in the epithelial layer of UC patients. Results were successfully mirrored in vitro, in spontaneously differentiated enterocyte-like monolayers of Caco-2 cells specifically exposed to DSS (dextran sodium sulphate) to mimic IBD inflammatory onsets. SLC15A4/PHT1 expression and cellular localization were characterized confirming its (dys)regulation traits in inflamed vs. healthy epithelia, strongly hinting the hypothesis of SLC15A4/PHT1 increased function associated with epithelial inflammation in IBD patients. [ABSTRACT FROM AUTHOR]

Abstract: Changes in the mitochondrial DNA (mtDNA) population, together with the expression of a set of genes involved in mtDNA replication and transcription and genes encoding for components of OxPhos complexes, were studied during zebrafish development from early embryo to larval stages. The mtDNA copy number, measured from 1h post-fertilization to the adult stage, significantly decreased over time, suggesting that mtDNA replication is not active in early zebrafish embryos and that, as in mammals, there occurs partition of the maternal mtDNA copies. Zebrafish genes involved in mtDNA replication (i.e. catalytic subunit of the mtDNA polymerase γ, mitochondrial deoxyribonucleoside kinase) are expressed late in embryo development, further supporting the notion that there is no replication of mtDNA in the early stages of zebrafish development. Notably, as from 4days post-fertilization, marked expression of “replication genes” was observed in the exocrine pancreas. Interestingly, the mtDNA helicase, also involved in mtDNA replication, was detected early in development, suggesting diverse regulation of this gene. On the other hand, zebrafish mtDNA transcription genes (i.e. mtDNA-directed RNA polymerase, mitochondrial transcription factor A) were ubiquitously expressed in the early stages of development, suggesting that mitochondrial transcription is already active before mtDNA replication. This hypothesis of early activation of mtDNA transcription fits in with the high early expression of structural OxPhos genes, suggesting that an active OxPhos system is necessary during early embryogenesis. As well as providing the first description of mtDNA distribution during zebrafish development, the present study also represents a step toward the use of Danio rerio as a model for investigation of mitochondrial metabolism and disease. [Copyright &y& Elsevier]

The initial observation of peptide absorption in fish intestine dates back to 1981, when, in rainbow trout ( Oncorhynchus mykiss), the rate of intestinal absorption of the dipeptide glycylglycine (Gly-Gly) was compared in vivo with the rate of absorption of its component amino acid glycine (Gly). The description of the identification of the underlying mechanisms that allow di- and tripeptide transport across the plasma membranes in fish was provided in 1991, when the first evidence of peptide transport activity was reported in brush-border membrane vesicles of intestinal epithelial cells of Mozambique tilapia ( Oreochromis mossambicus) by monitoring uptake of radiolabelled glycyl-l-phenylalanine (Gly-l-Phe). Since then, the existence of a carrier-mediated, H+-dependent transport of di- and tripeptides (H+/peptide cotransport) in the brush-border membrane of fish enterocytes has been confirmed in many teleost species by a variety of biochemical approaches, providing basic kinetics and substrate specificities of the transport activity. In 2003, the first peptide transporter from a teleost fish, i.e. the zebrafish ( Danio rerio) PEPtide transporter 1 (PEPT1), was cloned and functionally characterized in the Xenopus laevis oocyte expression system as a low-affinity/high-capacity system. PEPT1 is the protein in brush-border membranes responsible for translocation of intact di- and tripeptides released from dietary protein by luminal and membrane-bound proteases and peptidases. The transporter possesses affinities for the peptide substrates in the 0.1–10 mM range, depending on the structure and physicochemical nature of the substrates. After the molecular and functional characterization of the zebrafish transporter, the interest in PEPT1 in teleost fish has increased and approaches for cloning and functional characterization of PEPT1 orthologues from other fish species, some of them of the highest commercial value, are now underway. In this paper, we provide a brief overview of the transport of di- and tripeptides in teleost fish intestine by recalling the bulk of biochemical, biophysical and physiological observations collected in the pre-cloning era and by recapitulating the more recent molecular and functional data. [ABSTRACT FROM AUTHOR]

The initial observation of peptide absorption in fish intestine dates back to 1981, when, in rainbow trout ( Oncorhynchus mykiss), the rate of intestinal absorption of the dipeptide glycylglycine (Gly-Gly) was compared in vivo with the rate of absorption of its component amino acid glycine (Gly). The description of the identification of the underlying mechanisms that allow di- and tripeptide transport across the plasma membranes in fish was provided in 1991, when the first evidence of peptide transport activity was reported in brush-border membrane vesicles of intestinal epithelial cells of Mozambique tilapia ( Oreochromis mossambicus) by monitoring uptake of radiolabelled glycyl-l-phenylalanine (Gly-l-Phe). Since then, the existence of a carrier-mediated, H+-dependent transport of di- and tripeptides (H+/peptide cotransport) in the brush-border membrane of fish enterocytes has been confirmed in many teleost species by a variety of biochemical approaches, providing basic kinetics and substrate specificities of the transport activity. In 2003, the first peptide transporter from a teleost fish, i.e. the zebrafish ( Danio rerio) PEPtide transporter 1 (PEPT1), was cloned and functionally characterized in the Xenopus laevis oocyte expression system as a low-affinity/high-capacity system. PEPT1 is the protein in brush-border membranes responsible for translocation of intact di- and tripeptides released from dietary protein by luminal and membrane-bound proteases and peptidases. The transporter possesses affinities for the peptide substrates in the 0.1-10 mM range, depending on the structure and physicochemical nature of the substrates. After the molecular and functional characterization of the zebrafish transporter, the interest in PEPT1 in teleost fish has increased and approaches for cloning and functional characterization of PEPT1 orthologues from other fish species, some of them of the highest commercial value, are now underway. In this paper, we provide a brief overview of the transport of di- and tripeptides in teleost fish intestine by recalling the bulk of biochemical, biophysical and physiological observations collected in the pre-cloning era and by recapitulating the more recent molecular and functional data. [ABSTRACT FROM AUTHOR]

Sulfate plays an essential role during growth, development and cellular metabolism. In this study, we characterized the function and structure of the zebrafish (Danio rerio) Na+-sulfate cotransporter 1 (NaS1) cDNA and gene (slc13a1). Zebrafish NaS1 encodes a protein of 583 amino acids with 13 putative transmembrane domains. Expression of zebrafish NaS1 protein in Xenopus oocytes led to Na+-sulfate cotransport, which was significantly inhibited by thiosulfate, selenate, molybdate, and tungstate. Zebrafish NaS1 transport kinetics were: Vmax = 1,731.670 ± 92.853 pmol sulfate/oocyte · hour and Km = 1.414 ± 0.275 mM for sulfate and Vmax = 307.016 ± 32.992 pmol sulfate/ oocyte· hour, Km = 24.582 ± 4.547 mM and n (Hill coefficient) = 1.624 ± 0.354 for sodium. Zebrafish NaS1 mRNA is developmentally expressed in embryos from day 1 postfertilization and in the intestine, kidney, brain, and eye of adult zebrafish. The zebrafish NaS1 gene slc13a1 contains 15 exons spanning 8,716 bp. Characterization of the zebrafish NaS1 contributes to a greater understanding of sulfate transporters in a well-defined genetic model and will allow the elucidation of evolutionary and functional relationships among vertebrate sulfate transporters. [ABSTRACT FROM AUTHOR]

Background: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than 50 documented cases in English medical literature, the diagnosis and management of adrenal LMS remain challenging. The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers and report our specific case. Methods: A systematic review of the literature was conducted using PubMed, Web of Science, Google Scholar, and Scopus databases, up to December 2020. The search utilized MeSH terms such as "Adrenal Gland Neoplasms," "Leiomyosarcoma," "Adrenalectomy," and "Smooth Muscle Tumor." The inclusion criteria focused on studies reporting patients with a histopathological diagnosis of adrenal leiomyosarcoma. The PRISMA guidelines were followed to ensure a comprehensive analysis. Results: Out of 63 identified studies, 43 met the inclusion criteria and were reviewed. These studies highlighted the rarity and aggressive behavior of adrenal leiomyosarcoma. Surgical excision remains the cornerstone of treatment, often complemented by adjuvant therapies. The reviewed case involved a 52-year-old woman who underwent a right laparoscopic adrenalectomy for a 9 × 7 × 6 cm grade 3 leiomyosarcoma. Despite subsequent adjuvant chemotherapy, hepatic metastases were detected, illustrating the aggressive nature of the disease. The literature underscores the importance of histopathological analysis and long-term surveillance for managing disease progression. Conclusions: Optimal management of adrenal leiomyosarcoma requires a multidisciplinary approach and meticulous follow-up. The rarity of the disease poses challenges for standardizing treatment, but surgical excision and tailored adjuvant therapies show promise. Further research is essential to refine treatment strategies and improve prognosis for this rare malignancy. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs–macrophage communication is pivotal. Here, we focus on extracellular vesicle (EVS)-mediated communication and, in particular, we analyze the response of macrophages. NSC-34 cells transfected with mutant SOD1 (G93A, A4V, G85R, G37R) and differentiated towards MN-like cells, and Raw 264.7 macrophages are the cellular models of the study. mSOD1 NSC-34 cells release a high number of vesicles, both large-lEVs (300 nm diameter) and small-sEVs (90 nm diameter), containing inflammation-modulating molecules, and are efficiently taken up by macrophages. RT-PCR analysis of inflammation mediators demonstrated that the conditioned medium of mSOD1 NSC-34 cells polarizes Raw 264.7 macrophages towards both pro-inflammatory and anti-inflammatory phenotypes. sEVs act on macrophages in a time-dependent manner: an anti-inflammatory response mediated by TGFβ firstly starts (12 h); successively, the response shifts towards a pro-inflammation IL-1β-mediated (48 h). The response of macrophages is strictly dependent on the SOD1 mutation type. The results suggest that EVs impact physiological and behavioral macrophage processes and are of potential relevance to MN degeneration. [ABSTRACT FROM AUTHOR]

In this paper, an extended numerical analysis of the "confined-crest impact" (hereinafter referred as "C–CI"), induced by non-breaking waves on recurved parapet walls, is presented to better understand the physics and characteristics of this impulsive wave phenomenon, which significantly depends on the geometry of the parapet (here made by a sector of circumference) as well as on non-breaking wave steepness. A dimensional analysis of the forces has been carried out and used to analyse the results obtained by numerical CFD computations. The numerical simulations, performed for different radii of curvature, opening angles and incoming wave characteristics (changing both the wave height H and wave period T), have shown that the maximum impulsive pressure: (i) takes place on the top of the recurved parapet and decreases moving towards the S W L , where it tends to vanish; (ii) tends to decrease as the radii of curvature and the incoming wave characteristics (wave height H and period T) increase. However, this reduction in the maximum pressure, is always accompanied by an increase of the forces acting on the recurved parapet and a decrease of the wave overtopping volumes. Moreover, the maximum wave induced pressures have been examined by means of regular and irregular wave conditions in order to analyse the possibility of schematising the effects (i.e. forces) of an irregular sea state with those of a regular one, providing an equivalent force and therefore saving computational time. Based on the new results, a schematization of the pressure diagram induced by the C–CI impact has been proposed, used to extend the Goda-Takahashi pressure diagrams, valid for vertical walls in non-breaking wave conditions, including recurved walls. - The effects induced by the Confined-Crest Impact on recurved parapets in nonbreaking wave conditions are investigated in this study. - A large number of numerical tests, by varying the geometrical parameters of the recurved parapet and the wave conditions, have been carried out. - A dimensional analysis highlights the close dependence of the Confined-Crest Impact on the dimensionless parameter Hl L 2 . - Large impulsive forces induced by the Confined-Crest Impact occur in the upper part of the structure, avove the SWL. - A new method to calculate the pressure on vertical breakwaters with revurved parapets is proposed in order to provide a simple design tool. [ABSTRACT FROM AUTHOR]

The paper investigates on the hydro-acoustic waves propagation caused by the underwater earthquake, occurred on 6 February 2012, between the Negros and Cebu islands, in the Philippines. Hydro-acoustic waves are pressure waves that propagate at the sound celerity in water. These waves can be triggered by the sudden vertical sea-bed movement, due to underwater earthquakes. The results of three dimensional numerical simulations, which solve the wave equation in a weakly compressible sea water domain are presented. The hydro-acoustic signal is compared to an underwater acoustic signal recorded during the event by a scuba diver, who was about 12 km far from the earthquake epicenter. [ABSTRACT FROM AUTHOR]

In this article, we apply an integrable nonautonomous Lotka–Volterra model to study the relationship between oil and renewable energy stock prices between 2006 and 2016. The advantage of this innovative approach is that it allows us to study the simultaneous interaction among n stock indices at any point in time. In line with previous studies, we find that the relationship between oil and renewables is characterized by major structural breaks taking place in 2008 and around 2013. The first structural break might be caused by the financial crisis, whereas more studies are required to advance a hypothesis on the causes behind the second structural break. Our main finding is that oil is always in a predator–prey relationship with wind, whereas it proceeds in mutualism with solar after 2012. Moreover, we find that solar and wind proceed in mutualism between 2008 and 2013 but have a rivalrous interaction before (competition) and after (predator–prey) that period. We explore the possible reasons behind these patterns and their policy implications. [ABSTRACT FROM AUTHOR]

Background: Dystroglycanopathy (α-DG) is a relatively common, clinically and genetically heterogeneous category of congenital forms of muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) associated with hypoglycosylated α-dystroglycan. To date, mutations in at least 19 genes have been associated with α-DG. One of them, GMPPB, encoding the guanosine-diphosphate-mannose (GDP-mannose) pyrophosphorylase B protein, has recently been associated with a wide clinical spectrum ranging from severe Walker-Warburg syndrome to pseudo-metabolic myopathy and even congenital myasthenic syndromes. We re-sequenced the full set of known disease genes in 73 Italian patients with evidence of either reduced or nearly absent α-dystroglycan to assess genotype-phenotype correlations in this cohort. We used innovative bioinformatic tools to calculate the effects of all described GMPPB mutations on protein function and attempted to correlate them with phenotypic expressions.Results: We identified 13 additional cases from 12 families and defined seven novel mutations. Patients displayed variable phenotypes including less typical pictures, ranging from asymptomatic hyperCKemia, to arthrogryposis and congenital clubfoot at birth, and also showed neurodevelopmental comorbidities, such as seizures and ataxic gait, as well as autism-spectrum disorder, which is seldom described in clinical reports of dystroglycanopathies. We also demonstrated that few mutations recur in the Italian GMPPB-mutated population and that alterations of protein stability are the main effects of GMPPB missense variants.Conclusion: This work adds to the data on genotype-phenotype correlations in α-DG and offers new bionformatic tools to provide the conceptual framework needed to understand the complexity of these disorders. [ABSTRACT FROM AUTHOR]

In this article, we study spillovers in political trust between the national parliaments of 15 Member States and the European Commission, the European Parliament and the European Central Bank in the period 2000–2015. We show that in most instances spillovers between the national parliaments and the European Commission and the European Parliament are bidirectional, asymmetric, and change over time and place. A corollary of these findings is that simultaneously achieving high level of trust in institutions at different levels of governance may require a deeper understanding of the complex inter-institutional relationships that exist in the EU multilevel governance setting. [ABSTRACT FROM AUTHOR]

Background: Yellow fever (YF) is a severe, infectious, but non-communicable arboviral hemorrhagic disease. In the last decades, yellow fever virus (YFV) infections have been prevalent in endemic areas in Brazil, affecting human and non-human primate (NHP) populations. Monitoring of NHP infection started in 1999, and reports of epizootic diseases are considered important indicators of viral transmission, particularly in relation to the sylvatic cycle. This study presents the monitoring of YFV by real-time RT-PCR and the epidemiological findings related to the deaths of NHPs in the south-eastern states and in the north-eastern state of Bahia, during the outbreak of YF in Brazil during 2017 and 2018. Methods: A total of 4198 samples from 2099 NHPs from south-eastern and north-eastern Brazilian states were analyzed by real-time reverse transcription polymerase chain reaction (rtRT-PCR). Results: A total of 4198 samples from 2099 NHPs from south-eastern and north-eastern Brazilian states were collected between 2017 and 2018. The samples were subjected to molecular diagnostics for YFV detection using real-time reverse transcription polymerase chain reaction (rtRT-PCR) techniques. Epizootics were coincident with human YF cases. Furthermore, our results showed that the YF frequency was higher among marmosets (Callithrix sp.) than in previous reports. Viremia in species of the genus Alouatta and Callithrix differed greatly. Discussion: Our results indicate a need for further investigation of the role of Callithrix spp. in the transmission cycles of YFV in Brazil. In particular, YFV transmission was observed in a region where viral circulation has not been recorded for decades and thus vaccination has not been previously recommended. Conclusions: This highlights the need to straighten epizootic surveillance and evaluate the extent of vaccination programmes in Brazil in previously considered "YFV-free" areas of the country. [ABSTRACT FROM AUTHOR]

The current cross-sectional study aimed to increase the knowledge about socio-cognitive skills of preservice special education teachers that may affect their ethnic prejudices. In particular, the purpose of the study was to analyze the mediating role of empathy dimensions in the relationship between affective theory of mind and blatant and subtle prejudices. Participants included 531 Italian preservice special education teachers (76.4% females and 22.4% males), with an average age of 34.79 (SD = 6.10). Data were collected during the 2020–2021 academic year and all participants were administered, via the Google Form, the Reading the Mind in the Eyes test, Interpersonal Reactivity Index, and Subtle and Blatant Prejudice Scale. Path analysis showed that perspective taking and empathic concern play mediating roles in the relationship between the ability to infer people’s feelings and blatant and subtle prejudices. In addition, direct relations from affective theory of mind to ethnic prejudice and from empathic abilities to ethnic prejudice were found. These findings suggest that affective theory of mind and empathy are two cognitive-social skills involved in the expression of prejudice. The limitations and implications of the study were discussed. [ABSTRACT FROM AUTHOR]

Introduction Pyruvate dehydrogenase complex (PDH) deficiency (Online Mendelian Inheritance in Man # 312170) is a relatively common mitochondrial disorder, caused by mutations in the X-linked PDHA1 gene and presenting with a variable phenotypic spectrum, ranging from severe infantile encephalopathy to milder chronic neurological disorders. Isolated peripheral neuropathy as predominant clinical presentation is uncommon. Results We report on a patient, now 21 years old, presenting at the age of 2 years with recurrent symmetric weakness as first symptom of a PDH deficiency. Neurophysiological evaluation proving a sensory-motor polyneuropathy with conduction blocks and presence of elevated cerebrospinal fluid proteins, suggested a chronic inflammatory demyelinating polyneuropathy. The evidence of high serum lactate and the alterations in oxidative metabolism in muscle biopsy pointed toward the final diagnosis. After starting nutritional supplements, no further episodes occurred. A hemizygous mutation in PDHA1 (p.Arg88Cys) was identified. This mutation has been previously described in five patients with a similar phenotype. A three-dimensional reconstruction demonstrated that mutations affecting this arginine destabilize the interactions between the subunits of the E1 complex. Conclusion We summarize the clinical and genetic characteristics of one patient with PDH deficiency presenting isolated peripheral nervous system involvement. This study highlights that the diagnosis of PDH deficiency should be considered in children with unexplained peripheral neuropathy, even with features suggestive of acquired forms, especially in case of early onset and limited response to treatment. A simple analysis of lactic acid could help to target the diagnosis. In addition, we suggest that the residue Arg88 is the most frequently involved in this specific phenotype of PDH deficiency. [ABSTRACT FROM AUTHOR]

The resistance demonstrated by many microorganisms towards conventional antibiotics has stimulated the interest in alternative antimicrobial agents and in novel approaches for prevention of infections. Silver, a natural braod-spectrum antimicrobial agent known since antiquity, has been widely employed in biomedical field due to its recognized antibacterial, antifungal and antiviral properties. In this work, antibacterial silver coatings were deposited on absorbable surgical sutures through the in situ photo-chemical deposition of silver clusters. Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX) and thermo-gravimetric analysis (TGA) were performed in order to investigate the presence and distribution of the silver clusters on the substrate. The amounts of silver deposited and released by the silver treated sutures were calculated through Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS), and the results were related to the biodegradation of the material. The microbiological properties and the potential cytotoxicity of the silver-treated sutures were investigated in relation with hydrolysis experiments, in order to determine the effect of the degradation on antibacterial properties and biocompatibility. [ABSTRACT FROM AUTHOR]

The relevant adsorption of cis -[Pt(NH 3 ) 2 (P 2 O 7 )] 2 − ( phosphaplatin ) on hydroxyapatite nanocrystals (nHAP) was observed and studied in water suspension. Phosphaplatin cytotoxicity, which is very low for HeLa, MCF-7 and HS-5 cell lines could be enhanced, reaching that of cisplatin , by interaction with solid nHAP. This effect stems from nHAP ability to catalyze the phosphaplatin hydrolysis, producing the same hydrolytic species responsible for cisplatin antitumor activity. [ABSTRACT FROM AUTHOR]

The global increase in population aging has led to a rise in neurodegenerative diseases (NDs), posing significant challenges to public health. Developing selective and specific biomarkers for early diagnosis and drug development is crucial addressing the growing burden of NDs. In this context, the RNA-binding protein TDP-43 has emerged as a promising biomarker for amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and TDP-43-associated proteinopathies. However, existing detection methods suffer from limitations such as cost, complexity, and operator dependence. Here, we present a novel electrochemical biosensor integrated into a lab-on-chip (LoC) platform to detect TDP-43. The sensor utilizes electrosynthesized polypyrrole derivatives with carboxylic groups for transducer functionalization, enabling targeted immobilization of TDP-43 antibodies. Differential pulsed voltammetry (DPV) is used for the indirect detection and quantification of TDP-43. The chip exhibits rapid response, good reproducibility, a linear detection range, and sensitivity from 0.01 ng/mL to 25 ng/mL of TDP-43 protein concentration with a LOD = 10 pg/mL. Furthermore, successful TDP-43 detection in complex matrices like serum of ALS patients and healthy individuals demonstrates its potential as a point-of-care diagnostic device. This electrochemical biosensor integrated into a chip offers good sensitivity, rapid response, and robust performance, providing a promising avenue for advancing neurodegenerative disease diagnostics and therapeutic development. [Display omitted] • An innovative chip-based electrochemical sensor designed for the detection and quantification of TDP-43 have been proposed. • By leveraging the technique of electrochemical polymerization we have achieved precise chemical binding of TDP-43 antibodies. • Highly sensitive TDP-43 protein detection down to 10 pg/mL and exceptionally rapid response time of around 10 s was achieved. • Lab-on-chip devices can be used for large-scale screening of TDP-43-related disorders from easily accessible biological fluids [ABSTRACT FROM AUTHOR]

• Surveillance of deaths in NHPs is a key point for the prevention of YF in humans. • Determination of hepatic pathological features are crucial for screening YF in NHPs. • YF-associated hepatic injuries may vary between South American NHPs genera. • Humans and NHPs show marked differences in the set of YF-associated hepatic lesions. The early detection and diagnosis of deaths in free-ranging non-human primates (NHPs) are key points for the surveillance of Yellow Fever (YF) in Brazil. The histopathological identification of infectious diseases remains very useful and reliable in the screening and detection of emerging zoonotic diseases such as YF. We surveyed data records and liver slides stained with hematoxylin and eosin from the Epizootics Surveillance Network to control YF, Ministry of Health of Brazil, to evaluate histopathological hallmarks for the diagnosis of the YF virus infection. We selected natural fatal cases in NHPs from the genera Alouatta spp., Callithrix spp., and Sapajus spp. with a positive immunohistochemical assay for YF in liver samples. Our findings showed the full-spectrum YF-associated hepatic lesions in all NHPs, but some histopathological findings differed in the distribution and intensity between the three genera. In our study, South American NHPs showed significant differences in the YF-associated hepatic histopathological features compared to fatal cases reported in humans. [Display omitted] [ABSTRACT FROM AUTHOR]

The image recapitulates the interplay between neuronal and vascular systems by highlighting the cellular players involved in the molecular signalling in the context of Amyotrophic Lateral Sclerosis. [Display omitted] The neurovascular system (NVS) is a complex anatomic-functional unit that synergically works to maintain organs/tissues homeostasis of the entire body. NVS alterations have recently emerged as a common distinct feature in the pathogenesis of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Despite their undeniable involvement, neurovascular signalling pathways remain still far unknown in ALS. This review underlines the importance of endothelial, mural, and fibroblast cells as novel targets for ALS investigation and identifies in the interplay between neuronal and vascular systems the way to disclose novel molecular mechanisms behind the pathogenesis of ALS. [ABSTRACT FROM AUTHOR]

Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals. [ABSTRACT FROM AUTHOR]

Leptospirosis is a zoonotic neglected disease of worldwide public health concern. Leptospira species can infect a wide range of wild and domestic mammals and lead to a spectrum of disease, including severe and fatal forms. Herein, we report for the first time a fatal Leptospira interrogans infection in a free‐ranging nonhuman primate (NHP), a black‐tufted marmoset. Icterus, pulmonary haemorrhage, interstitial nephritis, and hepatocellular dissociation were the main findings raising the suspicion of leptospirosis. Diagnostic confirmation was based on specific immunohistochemical and PCR assays for Leptospira species. Immunolocalization of leptospiral antigens and identification of pathogenic species (L. interrogans species) were important for better understanding the pathogenesis of the disease. One Health–related implications of free‐ranging NHPs in anthropized areas and transmission dynamics of human and animal leptospirosis are discussed. [ABSTRACT FROM AUTHOR]

Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer’s Disease (AD). However, its direct impact on the dynamics of AD-related fibril formation remains uninvestigated. We considered the effects of carnosine on the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of Aβ1-42 fibrillogenesis in vitro and differences in the aggregation state of Aβ1-42 small pre-fibrillar structures (monomers and small oligomers) in the presence of carnosine. in silico molecular docking supported the experimental data, calculating possible conformational carnosine/Aβ1-42 interactions. Overall, our results suggest an effective role of carnosine against Aβ1-42 aggregation. [ABSTRACT FROM AUTHOR]

We report the molecular and functional characterisation of a novel peptide transporter from zebrafish, orthologue to mammalian and avian PEPT1. Zebrafish PEPT1 is a low-affinity/high-capacity system. However, in contrast to higher vertebrate counterparts in which maximal transport activity is independent of extracellular pH, zebrafish PEPT1 maximal transport rates unexpectedly increase at alkaline extracellular pH. Zebrafish pept1 is highly expressed in the proximal intestine since day 4 post-fertilisation, thus preceding functional maturation of the gut, first feeding and complete yolk resorption. Zebrafish PEPT1 might help to understand the evolutionary and functional relationships among vertebrate peptide transporters. Moreover, zebrafish pept1 can be a useful marker for screening mutations that affect gut regionalisation, differentiation and morphogenesis. [Copyright &y& Elsevier]

Understanding the complex communication between different cell populations and their interaction with the microenvironment in the central and peripheral nervous systems is fundamental in neuroscience research. The development of appropriate in vitro approaches and tools, able to selectively analyze and/or probe specific cells and cell portions (e.g., axons and cell bodies in neurons), driving their differentiation into specific cell phenotypes, has become therefore crucial in this direction. Here we report a multi-compartment microfluidic device where up to three different cell populations can be cultured in a fluidically independent circuit. The device allows cell migration across the compartments and their differentiation. We showed that an accurate choice of the device geometrical features and cell culture parameters allows to (1) maximize cell adhesion and proliferation of neuron-like human cells (SH-SY5Y cells), (2) control the inter-compartment cell migration of neuron and Schwann cells, (3) perform long-term cell culture studies in which both SH-SY5Y cells and primary rat Schwann cells can be differentiated towards specific phenotypes. These results can lead to a plethora of in vitro co-culture studies in the neuroscience research field, where tuning and investigating cell–cell and cell–microenvironment interactions are essential. [ABSTRACT FROM AUTHOR]