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Multiple and Alternative Sites Make Tau Protein an Adaptable Sticky Surface for the SH3 Domain of Fyn Kinase
: The interaction between the microtubule associated protein Tau and the tyrosine kinase Fyn is believed to play a pivotal role in the early stage of Alzheimer's disease. Previous studies have identified the SRC Homology 3 (SH3) domain of Fyn as the binding receptor of several proline-rich motifs in Tau. However, the role of each proline-rich motif and their interplay in molecular recognition are still unclear. In this work, we investigated the mechanism of Fyn-SH3 recognition by the multiple PxxP sites inserted within the full-length Tau protein by using nuclear magnetic resonance (NMR) spectroscopy combined with computational, calorimetric and in-cell FRET (Förster resonance energy transfer) methods. Both in vitro and in-cell experiments revealed no single binding site strictly necessary for the binding. Instead, Fyn-SH3 contacts full-length Tau on multiple hot spot regions, located over a distance of 85 residues, through global moderate-to-low affinity interactions. Beyond two principal regions containing classical PxxP motifs, we identified a novel non-canonical binding site at the beginning of the microtubule binding domain. Our study indicates that multiple binding sites in Tau are involved in the interaction, making Tau an adaptable recognition surface that can function when single consensus motifs are deleted
The effects of a music training program on rhythmic skills, executive functions, and linguistic abilities in preschoolers
Introduction: Literature has explored the relationship between music/rhythmic activities and developmental domains such as cognition and language. However, few studies have considered the impact of structured music training programs on cognitive and language development in preschoolers. This study aims to investigate the role of music training in developing rhythmic abilities, executive functions, and lexical skills.
Method: Participants were 55 children (25 girls) aged between 46 and 58 months (Mage = 53.0) at the baseline and between 50 and 66 months (Mage = 57.1) at the re-test. Using a randomized pre-post-test control trial, 32 children (14 girls, training group, TG) participated in an 8-week music training program while 23 children (11 girls) acted as a comparison group (control group, CG). All the children were tested twice (pre- and post-training) using the “Rhythmic Imitation Test” (Stamback, 1980) for rhythmic skills, the “Stroop Day/Night” task (Usai et al., 2017) for inhibitory control, the “Keep in Mind” task (Usai et al., 2017) for working memory, the “Peabody Picture Vocabulary Test” (PPVT; Stella et al., 2000) for receptive vocabulary, and the “Oral Comprehension Test” (TOR; Levorato & Roch, 2007) for listening text comprehension.
Results: Repeated measures mixed ANCOVA, with parents’ education as a covariate, were run on the variables considered to assess the impact of the music training program. Data analysis revealed a significant main effect of “time” on receptive vocabulary score [F(1,41) = 13.580, p = <.001, η2 = 0.021]; a significant interaction between “time” and “group” for rhythmic abilities [F(1,36) = 4.215, p = 0.047, η2 = 0.024], for inhibitory control [F(1,40) = 9.500, p = 0.004, η2 = 0.032] and working memory [F(1,42) = 5.050, p = 0.030, η2 = 0.024]. Furthermore, partial correlations revealed that receptive vocabulary significantly correlates with rhythmic abilities (r(48) = 0.336; p = 0.032) and inhibitory control (r(49) = 0.552; p = <.001); and morphosyntax abilities with inhibitory control (r(49) = 0.379; p = 0.013) at the baseline.
Conclusions: These results suggest that short music training enhances rhythmic skills, executive functions, and, indirectly, language development in preschoolers. These findings can have an impact on the educational practices of preschoolers
L’uso (improprio) del virgolettato nei titoli dei quotidiani: Il caso del vaccino AstraZeneca sulla stampa italiana e britannica
Il contributo esplora l’utilizzo delle citazioni dirette tra virgolette all’interno dei ti-toli giornalistici, utilizzando come caso studio la notizia della sospensione del vaccino COVID-19 prodotto da AstraZeneca. L’analisi discorsiva di un corpus di articoli conte-nenti la parola chiave “AstraZeneca”, pubblicati tra il 14 e il 27 marzo 2021 sul Corriere della Sera e su The Times, estratti dalla banca dati NexisUni, esamina la corrispondenza tra le citazioni dirette presenti nei titoli e nei sommari degli articoli e quelle all’interno dei testi. I risultati mostrano che nella quasi totalità dei testi italiani, la citazione nel titolo non è completamente fedele a quella riportata nel testo dell’articolo, e sembra piutto-sto riassumerne i contenuti principali; tuttavia, le modifiche apportate ne modificano il significato pragmatico. Negli articoli del Times viene preferito il discorso indiretto introdotto da verba dicendi
Sensitivity to negative-feedback processing in people with Parkinson's disease and impulsive-compulsive behaviours
Biomarkers of impulsive compulsive behaviours (ICBs) in Parkinson’s disease (PD) are lacking. We combined behavioural and electrophysiological markers of sensitivity to negative feedback to address this lack of knowledge. Eighteen PD patients (ICB+, N = 8; ICB-, N = 10) underwent electroencephalography during the Balloon Analogue Risk Task (BART), a measure of risky behaviour, and the feedback-related negativity (FRN), a measure of negative feedback processing, was recorded. Participants also completed the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-rs), and underwent cognitive, affective and motivation measures. Behaviour on the BART and FRN measures did not differ between the ICB + and ICB- groups. However, a significant positive correlation was observed between the amplitude of the FRN at the Cz electrode and the BART discrepancy score when the two groups were combined into one PD group (rs(18) = 0.52, p = 0.03; 95% CI = 0.07, 0.80). No additional correlations were found between FRN amplitudes and the QUIP-rs score, nor with cognitive, affective, or motivational measures. Our findings indicate that, regardless of ICB status, PD patients may be able to process negative feedback to mitigate risky behaviour during reward-related decision-making. We observed that a higher feedback-related negativity (FRN) is linked to a decrease in risky behaviour following a balloon burst. However, due to the small sample size, these findings should be interpreted with caution. Future studies should explore both positive and negative feedback processing using a task that maintains the dynamics of the ongoing decision-making process while increasing ris
“Mothering”
This entry explores the complex interplay between mothering and religion in ancient Greece and Rome, drawing on literary, epigraphic, and archaeological evidence. Moving beyond essentialist and biological definitions of motherhood, it adopts a maternal theory framework to examine how caregiving was a collective, gendered, and culturally regulated process. It considers both normative religious prescriptions and individual maternal practices, with attention to figures such as wet-nurses, adoptive mothers, grandmothers, and other female relatives. The study emphasizes the religious agency of mothers and caregivers through votive practices, rituals, and dedications related to conception, childbirth, breastfeeding, and infant care. Furthermore, it addresses how early Christianity reshaped maternal paradigms—introducing both spiritual motherhood and conflicting ideals of femininity. By integrating archaeological material and matricentric feminist theory, this lemma aims to shift the focus from abstract models to embodied maternal experience, expanding the scope of religious history and gender studies in antiquity
Lights and shadows of microsatellite status characterization in gastrointestinal cancers in the era of cancer precision therapy
: The introduction of immunotherapy has dramatically changed the paradigm of solid tumor treatment with the creation of novel therapeutic opportunities even for tumors that currently lack valid therapeutic options in the advanced or metastatic setting. Initially, the role of deficient mismatch repair status (dMMR)/microsatellite instability (MSI) as a predictive biomarker was confined to colorectal cancer. In 2017, MSI/dMMR became the first true agnostic biomarker to stratify patient response to immune checkpoint inhibitors. MSI/dMMR evaluation is a crucial point in diagnostic-therapeutic decision-making for most gastrointestinal cancer patients and the pathologist must be responsible for the delivery of reliable reporting in this setting. The aim of this review is to summarize the current methods available in routine diagnostics for the evaluation of MSI/dMMR status, their limitations, and potential pitfalls that can be encountered. The authors also give an overview of the role of MSI/dMMR as a prognostic and predictive biomarker in gastrointestinal cancers, with a focus on non-colorectal malignancies
La Corte penale internazionale sotto assedio
La Corte penale internazionale si è impegnata in prima linea per individuare i responsabili delle gravi atrocità commesse nel contesto del conflitto armato russo-ucraino ed israelo-palestinese. A seguito dei mandati internazionali di arresto emessi nei confronti di Vladimir Putin e Benjamin Netanyahu la Corte ha, però, subito notevoli attacchi e ritorsioni. E’ davvero a rischio il suo operato
Il progetto MelArete: a scuola di amicizia e gratitudine
Il capitolo presenta in sintesi la struttura del percorso educativo previsto dal progetto MelArete 2 sull'amicizia e la gratitudine. Vengono descritti tipologie di attività e strumenti educativi utilizzati
Pilot-Scale Acidogenic Fermentation of Reground Pasta Byproduct for Polyhydroxyalkanoate Production with Mixed Microbial Cultures
The production of polyhydroxyalkanoates (PHAs) has been herein investigated by using an organic acid mixture originated from a pilot-scale acidogenic fermentation (AF) of reground pasta (RP) byproduct. The pilot-scale AF process was conducted either under no pH control or with the pH maintained at a value of 5.90, with the two obtained fermented mixtures termed RP-fermented 1 and RP-fermented 2, respectively. The fermented mixtures were fed to a lab-scale sequencing batch reactor (SBR), operated at short hydraulic retention time (HRT, 0.5 days) and sludge retention time (SRT, 1 day) and at two values of the applied organic loading rate (OLR) of 2.12 gCODACIDS/Ld and 4.25 gCODACIDS/Ld. During all of the SBR operating conditions, a high selective microbial pressure was established, as confirmed by both the microbiology analysis and the detected values of the storage yield (which reached a maximum value of 0.68 +/- 0.04 CODPHA/CODACIDS). A poly(hydroxybutyrate/hydroxyvalerate) copolymer and a poly(hydroxybutyrate/hydroxyvalerate/hydroxyhexanoate) terpolymer were produced with the RP-fermented 1 and RP-fermented 2 streams, respectively. When the OLR of 2.12 gCODACIDS/Ld was applied to the SBR, the stored copolymer and terpolymer presented very similar molecular weights of 339 and 389 kDa, respectively
Nanocarriers for nutraceutical molecules from sustainable sources: development and characterization
More than one-third of food is wasted alongside the food chain.
Despite national policies trying to reduce its production through laws, incentives, sensibilization, and education campaigns, food waste is a persistent issue with notable ethical, environmental, and economic repercussions.
Polyphenols are a large class of organic compounds involved in several biological mechanisms. Many experimental studies hint toward their preventive capacity against several non-communicable illnesses, such as cardiovascular and neurodegenerative diseases, cancer, diabetes, and osteoporosis, fueling the great interest in this topic. Abundant in fruits and vegetables, these bioactives can also be found in food waste, which may represent a precious and exploitable source.
Red cabbage (Brassica oleracea L. var. Capitata f. rubra) is a cruciferous vegetable known for its bright color and nutritional value. An abundant part of this plant, mainly composed of slightly damaged leaves and stems, is often discarded, even if still valid from a nutraceutical point of view. The water-soluble pigments in this food and in its by-product, known as anthocyanins, can be used as a natural dye, health promotor, and food sensor against spoilage.
Similarly, the olive oil production chain offers notable sources of valorisable food waste. Extra-virgin Olive Oil is considered one of the main promoters of the many health benefits of the Mediterranean Diet. Its nutritional profile is characterized by an elevated concentration of monounsaturated fatty acids but also by a minor heterogeneous component containing several polar phenolic compounds, particularly hydroxytyrosol, tyrosol, and oleuropein, which have been considered by the European Food Safety Authority, capable of preventing blood lipid oxidation. However, not many olive oils can grant such a high content of phenols.
The most significant part of these hydrophilic molecules (> 98%) remains in the by-product, i.e., the olive mill waste. From a circular economy perspective, many food by-products could be valorized through polyphenol extraction, stabilization, and employment. However, despite many experimental studies imputing preventive capacities to these molecules against several diseases, they are inherently fragile and challenging to be extracted from their matrices, hampering their industrial employment.
In this scenario, nanoencapsulation can aid in tackling several problems, such as protecting these molecules against degradation or boosting viability and functionality, offering a semi-finished product exploitable to enhance foods and feeds.
This project, conducted in collaboration with the company ECSIN EcamRicert SRL led by the expertise of Dr. Federico Benetti acting as industrial co-supervisor, aimed to develop and characterize nanoencapsulation approaches tailored for food application. In compliance with the principles of green chemistry and circular economy, model payloads, i.e., polyphenols-rich extracts prepared from red cabbage wasted leaves and olive pomace, were studied, characterized, and encapsulated into nanoparticles prepared with two different approaches: complex coacervation and ionotropic gelation, using, at the best of our possibilities, green procedures and food-grade waste-valorized wall materials.
After a brief introduction in which the food waste problem is discussed and the legal framework surrounding novel food and encapsulation regulations is defined, the encapsulation process, the bioactives of interest, the encapsulation matrices used in this project, and the procedures attempted throughout the doctoral program will be thoroughly discussed