Genome Wide Identification of Structure Variations in Five Italian Turkey Populations

Structural variants (SVs) are one of the main sources of genetic variants and have a significant impact on phenotype evolution, disease susceptibility, and environmental adaptations. We used 73 whole genome sequencing (12x) to apply a mapping approach to identify SVs in five turkey populations. A notable degree of genetic isolation was observed between the Basilicata and Apulian populations, as indicated by principal component analysis and admixture results. A total of 11,733 SVs were detected, including 6712 deletions, 2671 duplications, 1430 inversions, and 920 translocations. The Variant Effect Predictor (VEP) analysis predicted various consequences of filtered SVs as follows: intron variants (35.8%), intergenic variants (9.6%), coding sequence variants (8.3%), downstream gene variants (7.5%), and transcript ablations (7.3%). Our functional annotation of genes overlapping with SVs was mainly enriched in recognized pathways governing positive regulation of nucleoplasm, protein binding, mitochondrion, negative regulation of cell population proliferation, identical protein binding, and calcium signaling. We produced a comprehensive SV catalog utilizing unique whole-genome turkey data. This SV catalog not only increases our understanding of genetic diversity in turkeys but also enhances our knowledge of the role of SVs in their phenotypic traits

RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation

Background: RANBP9 and RANBP10, also called Scorpins, are essential components of the C-terminal to LisH (CTLH) complex, an evolutionarily conserved poorly investigated multisubunit E3 ligase. Their role in non-small cell lung cancer (NSCLC) is unknown. Methods: In this study, first we used stable loss-of function and overexpression inducible cell lines to investigate the ability of either RANBP9 or RANBP10 to form their own functional CTLH complex. Then, we probed lysates from patient tumors and analyzed data from publicly available repositories to investigate the expression of RANBP9 and RANBP10. Finally, we used inducible cell lines in vitro to recapitulate the expression observed in patients and investigate the changes of the proteome and the ubiquitylome associated with either RANBP9 or RANBP10 in NSCLC. Results: Here, we show that the two Scorpins are both expressed in NSCLC cells and that either of them can independently support the formation of the CTLH complex. Short-term experiments revealed that the RANBP9 and RANBP10 proteins balance each other in terms of expression, and the acute overexpression of one or the other results in significant reshaping of the NSCLC cell proteome and ubiquitylome. A higher RANBP9/RANBP10 ratio is associated with greater proliferation in both NSCLC cell lines and patients. Acute increased expression of RANBP10 slows NSCLC cell proliferation and decreases the level of proliferation-associated proteins, including key players in DNA replication. Conclusions: We present evidence that the Scorpins act as partial antagonists and work together as one sophisticated rheostat to modulate the CTLH complex ubiquitylation output, which regulates cell proliferation and other key biological processes in NSCLC. These results suggest that the two Scorpins can be considered as targets for the treatment of NSCLC

Youth Gangs between Crime Control and Social Inclusion: A Critical Examination of Competing Paradigms in Italy

This article critically examines the competing paradigms that have shaped the study, representation, and governance of youth gangs in Italy. Drawing on a wide body of criminological, sociological, and ethnographic literature, the paper contrasts the dominant criminological paradigm—rooted in classical traditions of social control and risk management—with the constructivist and cultural approaches that emphasise the role of social exclusion, identity negotiation, and resistance in the formation of youth street groups. The so-called baby gang phenomenon in Italy provides a revealing case study of how public discourse, media narratives, and official data converge to construct youth groups as threats to public order. This construction, in turn, legitimises repressive policies and emergency legislation, often at the expense of preventive and inclusive social measures

Riserve di attività e disciplina del contratto nel mercato finanziario

Il saggio affronta la questione delle conseguenze civilistiche della violazione delle riserve di attività nei mercati finanziari. Il tema è esaminato nella duplice prospettiva del compimento di atti riconducibili a un’attività riservata, da parte di un soggetto non abilitato, e del compimento di atti estranei a quelli tipici dell’attività riservata, da parte di un soggetto abilitato, alla luce delle disposizioni che limitano l’oggetto sociale delle società che operano nei mercati finanziari. Nell’ultima parte del lavoro è affrontato il problema dei rapporti fra la disciplina sanzionatoria che presidia le riserve di attività e la disciplina dell’atto “non conforme”

PICCOLE MOLECOLE BIOATTIVE DA SCREENING VIRTUALE DI LIBRERIE CHIMICHE PER IL TARGETING DEI MITOCONDRI NELLE MALATTIE RARE

La disfunzione mitocondriale assume un ruolo centrale nella fisiopatologia di numerosi disturbi metabolici rari, spesso derivanti da mutazioni in geni nucleari o mitocondriali che codificano proteine mitocondriali essenziali. Queste patologie, frequentemente classificate come malattie orfane, necessitano di nuove e significative sfide nella ricerca e nello sviluppo terapeutico. Negli ultimi tre decenni, strategie come il “drug repurposing” e la modulazione mirata di proteine mitocondriali sono emerse come possibili approcci terapeutici. Tra le varie analisi effettuate, la ricerca sulla Carnitina O-Acetiltransferasi (CRAT) ha permesso lo sviluppo di una pipeline volta a identificare nuovi modulatori selettivi per le varianti di CRAT. CRAT, enzima cruciale nel metabolismo mitocondriale, è implicato nella patologia della sindrome di Leigh quando sono presenti specifiche varianti. Il nostro approccio ha integrato analisi di docking in silico e screening virtuale di librerie chimiche per predire piccole molecole ad alta affinità per CRAT, seguite da validazione in vitro. Questa metodologia ha permesso di individuare specifiche piccole molecole modulatrici in grado di agire selettivamente contro la proteina mutata e patogenica CRAT p.Tyr110Cys, dimostrando la sinergia tra previsioni computazionali e successiva validazione sperimentale. Il caso di CRAT sottolinea la necessità di studiare le relazioni struttura-funzione nelle proteine mitocondriali, evidenziando che la localizzazione e l'impatto specifico delle mutazioni devono essere attentamente valutati prima di procedere con lo sviluppo di farmaci o con l'uso di terapie antiossidanti sinergiche. La localizzazione delle mutazioni può dare indicazioni sull’efficacia dei trattamenti somministrati, incluse terapie antiossidanti o basate su cofattori, oppure evidenziare eventuali effetti collaterali e non desiderati. Capire con precisione il ruolo dei siti mutati permette una maggiore ottimizzazione degli interventi terapeutici e una predizione dei risultati a seguito del trattamento. I nostri risultati evidenziano anche il ruolo più ampio che assumono le proteine mitocondriali come bersagli farmacologici, in condizioni caratterizzate da stress ossidativo, omeostasi energetica non funzionante, e disfunzione mitocondriale, tra cui sindrome metabolica, malattie legate all'invecchiamento e malattie cardiovascolari. L’avanzamento nella metodologia sia in silico che in vitro per indagare e modulare le funzioni mitocondriali apre nuove e promettenti strade per il trattamento di patologie correlate ad una corretta funzionalità mitocondriale.Mitochondrial dysfunction is central to the pathophysiology of numerous rare metabolic disorders, often stemming from mutations in nuclear or mitochondrial genes that encode essential mitochondrial proteins. These disorders, frequently categorized as orphan diseases, face significant research and therapeutic development challenges. Over the past three decades, strategies such as drug repurposing and targeted modulation of mitochondrial proteins have emerged as viable therapeutic pathways. Among the various performed analyses, research on Carnitine O-Acetyltransferase (CRAT) has enabled the development of a pipeline aimed at identifying new selective modulators for CRAT variants. CRAT, a critical enzyme in mitochondrial metabolism, is implicated in the pathology of Leigh syndrome when specific variants are present. Our approach integrated in silico docking analyses and virtual screening of chemical libraries to predict high-affinity small molecules for CRAT, followed by in vitro validation. This methodology uncovered selective small-molecule modulators effective against the pathogenic CRAT variant p.Tyr110Cys, demonstrating the synergy between computational predictions and experimental verification. The case of CRAT underscores the necessity of studying structure-function relationships in mitochondrial proteins, emphasizing that the localization and specific impact of mutations must be thoroughly assessed before advancing drug development or employing synergistic antioxidant therapies. The localization of mutations can influence whether administered treatments, including antioxidants or cofactor-based strategies, achieve their intended efficacy or pose risks due to unintended interactions. Such precision in understanding mutation sites helps optimize therapeutic interventions and predict treatment outcomes. Our findings also highlight the broader relevance of mitochondrial proteins as pharmacological targets for conditions marked by oxidative stress, disrupted energy homeostasis, and mitochondrial dysfunction, such as metabolic syndrome, age-related disorders, and cardiovascular diseases. Advancing in silico and in vitro techniques to probe and modulate mitochondrial functions offers promising new avenues for treating pathologies reliant on mitochondrial health

Does Disinformation Toward Women Politicians Reflect Gender Stereotypes? Exploring the Role of Leaders’ Political Orientations

The recent literature highlights the importance of implementing ad hoc media literacy initiatives to counter sexist stereotypical representations in social media, particularly within the political field. To this end, the present study focuses on false and misleading contents (information disorders) about female politicians, since they can reflect gender stereotypes, portraying women as unfit for political roles. Thus, our exploratory study aims to analyze the stereotype content of information disorders targeting Italian female politicians, following classic models of stereotype content. Furthermore, it seeks to explore the role played by the type of information disorder and the political orientation of the targeted leaders. A database of 120 information disorders have been collected, codified, and analyzed. The results highlight that information disorders predominantly target the dimension of communion. Focusing on the types of information disorders, fabricated and misleading content appears to be associated with the professional and private life domains, primarily conveying communion-based stereotypical representations of politicians. Satirical and parodic contents, on the other hand, were associated with the esthetic domain, conveying agency-based stereotypical representations, with a particular focus on politicians’ physical competence. Regarding political orientation, a “Stereotyping from my eyes” effect was observed: communion-based stereotypical content prevails in information disorders targeting conservative leaders, while progressive leaders are stereotyped concerning the agency dimension. This effect may reveal a difference between conservative and progressive audiences in their adherence to traditional gender roles

Detection of the Geminga pulsar at energies down to 20 GeV with the LST-1 of CTAO

Context. Geminga is the third gamma-ray pulsar firmly detected by imaging atmospheric Cherenkov telescopes (IACTs) after the Crab and the Vela pulsars. Most of its emission is expected at tens of giga-electronvolts, and, out of the planned telescopes of the upcoming Cherenkov Telescope Array Observatory (CTAO), the Large-Sized Telescopes (LSTs) are the only ones with optimised sensitivity at these energies. Aims. We aim to characterise the gamma-ray pulse shape and spectrum of Geminga as observed by the first LST (hereafter LST-1) of the Northern Array of CTAO. Furthermore, this study confirms the great performance and the improved energy threshold of the telescope, as low as 10 GeV for pulsar analysis, with respect to current-generation Cherenkov telescopes. Methods. We analysed 60 hours of good-quality data taken by the LST-1 between December 2022 and March 2024 at zenith angles below 50 degrees. Additionally, a new Fermi-LAT analysis of 16.6 years of data was carried out to extend the spectral analysis down to 100 MeV. Lastly, a detailed study of the systematic effects was performed. Results. We report the detection of Geminga in the energy range between 20 and 65 GeV. Of the two peaks of the phaseogram, the second one, P2, is detected with a significance of 12.2 sigma, while the first (P1) reaches a significance level of 2.6 sigma. The best-fit model for the spectrum of P2 was found to be a power law with a spectral index of Gamma = (4.5 +/- 0.4(stat))(-0.6sys)(+0.2)(sys), compatible with the previous results obtained by the MAGIC Collaboration. No evidence of curvature is found in the LST-1 energy range. The joint fit with Fermi-LAT data confirms a preference for a sub-exponential cut-off over a pure exponential, even though both models fail to reproduce the data above several tens of giga-electronvolts. The overall results presented in this paper prove that the LST-1 is an excellent telescope for the observation of pulsars, and improved sensitivity is expected to be achieved with the full CTAO Northern Array

Older Patients with Elevated Pre-sepsis PTFV1 Demonstrate Greater Occurrence of Atrial Fibrillation and Worse In-Hospital Outcomes

Background: Elevated P-wave terminal force in lead V1 (PTFV1) >5000 μV*ms is a predictor of atrial fibrillation and stroke in a general population. The risk for atrial fibrillation and ischemic stroke is high in sepsis but predictors are lacking. Objectives: Analysis of a prospective, observational cohort study with subjects categorized by PTFV1 (lower and higher than 5000 μV*ms) cutoffs and by age (older and younger than 60 years old). Methods: Of the 360 consented sepsis patients, 273 had evaluable pre-sepsis electrocardiograms (ECG). PTFV1 was measured by 3 independent and blinded assessors using the Mitutoyo 500-195-30CAL Absolute Digimatic Caliper on the last available ECG before sepsis onset. Patient characteristics and outcomes were compared between lower (PTFV1 < 5,000 μV*ms) and higher PTFV1 (PTFV1 > 5,000 μV*ms), and older and younger patients with elevated pre-sepsis PTFV1. Results: The median age was 63 years [IQR 53, 71], 44% women. Median of the last ECG prior to sepsis-onset was 1 day [IQR, 0, 9]. 32% of individuals had pre-sepsis PTFV1 > 5,000 μV*ms, and were mostly females. Older patients with PTFV1 > 5,000 μV*ms had greater pre-sepsis left atrial diameter, more in-hospital new-onset atrial fibrillation, greater Charlson Comorbidity Index score, and worse clinical trajectory, compared to younger patients with PTFV1 > 5,000 μV*ms. Conclusions: Older individuals with elevated pre-sepsis PTFV1 had greater occurrence of AF and worse outcomes during sepsis. Future studies will test pre-sepsis PTFV1 as a predictor of in-hospital and longitudinal outcomes in older sepsis patients at risk of atrial fibrillation, stroke and frailty

Jerome and Florus

This paper explores the presence of Florus in Jerome’s works, with particular focus on the Vitae monachorum. Scholars of the Vita Pauli and Vita Malchi have identified passages where Jerome would employ words or expressions from Florus (no such evidence appears in the Vita Hilarionis). The significance of these lexical borrowings is assessed here. Jerome’s knowledge extends not only to Florus’ Epitome, but also to the fragmentary treatise Vergilius orator an poeta (whose attribution to the same Florus remains debated). If intertextual analysis allows for the investigation of an author’s engagement with another one, there are indications that Jerome may have been familiar with this text as well. This paper provides a comparative analysis of passages in Jerome and Florus, discussing lexical borrowings, sources, rhetorical features, and individual words and expressions, including those drawn from other authors and works

Il vescovo Sabino

Una sintesi della figura del vescovo Sabino, delle sue iniziative costruttive a Canosa e nel territorio, del suo ruolo nella Chiesa d'Occidente e dei suoi rapporti con l'Orient