Archivio Istituzionale della Ricerca- Università del Piemonte Orientale
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Ligand-induced conformations and dynamic allosteric motions of IDO1 affecting the recruitment of a protein signaling partner
No full textIndoleamine 2,3-dioxygenase 1 (IDO1) is a moonlight protein endowed with catalytic and signaling functions. It plays a pivotal role in the immune breaking mechanism leading to immunosuppression in cancer microenvironment. Intense research efforts have been devoted to designing catalytic inhibitors for developing immunotherapies, yet neglecting the enzyme’s signaling function. A few IDO1 inhibitors have reached the clinical stage, including navoximod, epacadostat and linrodostat. Using second harmonic generation analysis (SHG) and molecular dynamics simulations, here we show that these clinical inhibitors can induce distinct allosteric motions in the enzyme that affect the stability of the transient signaling complex between IDO1 and Src tyrosine kinase. Next generation sequencing demonstrates that, despite sharing a similar ability to inhibit the enzyme’s catalytic function, all three catalytic inhibitors modulate the IDO1’s signaling function in different ways, regulating distinct transcriptomes in SKOV3 cells. (Figure presented.
Monetary policy, income distribution and semi‐autonomous demand in the US
No full textWe empirically explore the role of monetary and distribution shocks on semi-autonomous demand under a supermultiplier framework. We use quarterly data for the United States from 1968 to 2022 and apply a SVAR model to investigate the effect of changes in financial and distributive variables on autonomous expenditure. We find that: (i) the federal funds rate has a negative and statistically significant effect on autonomous expenditure; (ii) a positive shock in the wage share (WS) has a negative effect on non-revolving consumer credit (CC) and a transitory positive effect on induced consumption; (iii) a positive shock in aggregated autonomous demand has a positive, persistent, and significant effect on induced consumption and, output, as well as on the adjusted WS; (iv) a positive shock in private residential investment has a positive, persistent and statistically significant effect on other autonomous components of demand and output; (v) while residential investment positively influences CC and durable consumption, the inverse does not hold
Optimizing Care Practice: Reducing Unplanned Hospitalizations among Nursing Home Residents
No full textIntroduzione: I residenti delle Residenze Sanitarie Assistenziali (RSA) rappresentano una popolazione vulnerabile, frequentemente soggetta a trasferimenti ospedalieri, talvolta potenzialmente evitabili. Tuttavia, la definizione di “evitabilità” è eterogenea e spesso non tiene conto della complessità clinica dei residenti o delle risorse. Obiettivo: Approfondire la comprensione e supportare lo sviluppo di strategie volte a ridurre le ospedalizzazioni potenzialmente evitabili tra gli anziani delle RSA. Metodi: Sono stati condotti tre studi: 1) Revisione sistematica con metanalisi sull'efficacia degli interventi di miglioramento qualità nel ridurre il ricorso ai servizi ospedalieri; (2) Studio coorte prospettico della durata di 12 mesi (maggio 2023-giugno 2024) in 9 RSA piemontesi su trasferimenti urgenti e fattori associati; (3) Studio osservazionale retrospettivo sugli accessi in Pronto Soccorso (PS) da RSA prima, durante e post pandemia. Risultati: 1) Gli interventi di miglioramento della qualità riducono significativamente le ospedalizzazioni per tutte le cause (RR 0.60, IO 95% 0.41). 2) Sono stati inclusi 644 residenti, dei quali 206 (32%) trasferiti al PS, con un'incidenza di 4,49 per 100 residenti-mese (IO 95%: 3,86 - 5,08). I trasferimenti con manifestazioni precoci hanno maggiore probabilità di ricevere assistenza medica e infermieristica, ma sono più spesso associati a ricoveri e a decessi in ambito ospedaliero. Il rischio di trasferimento è più elevato per chi ha patologie respiratorie, cardiache, vascolari, epatiche o dipendenza funzionale nell’ alimentazione.3) Analizzati 2.071 accessi al PS tra il 2019 e 2022. Dopo il primo anno di pandemia, gli accessi per patologie respiratorie sono diminuiti ma sono aumentati significativamente quelli per disturbi mentali e fratture, come possibile conseguenza delle misure di isolamento. Conclusioni: Servono strategie per riconoscere e gestire precocemente il deterioramento clinico nelle RS
Investigating Neophobia Towards New Food Technologies in Italy: The CoNF&TTI Cross-Sectional Study
Get PDFBackground/Objectives: Food technology neophobia (FTN), defined as the reluctance to accept or consume foods produced with novel or emerging food technologies, represents a psychological barrier to the adoption of sustainable and innovative dietary practices. This cross-sectional study investigated the prevalence of food technology neophobia and its associated factors among Italian university students. Methods: A total of 1788 undergraduates from 13 universities completed a validated online questionnaire between February and October 2024. The instrument included the Food Technology Neophobia Scale (FTNS), environmental attitude items, and demographic and dietary questions. Results: The mean FTNS score was 51.2 ± 14.0, suggesting moderate levels of neophobia. Multivariate logistic regression identified several factors inversely associated with neophobia: male gender (OR = 0.73, p = 0.003), paternal university education (OR = 0.73, p = 0.024), studying in Northern Italy (OR = 0.64, p < 0.001), dietary supplement use (OR = 0.74, p = 0.003), and pro-environmental attitudes (OR = 0.97, p < 0.001). Conversely, being a commuter student was associated with increased neophobia (OR = 1.29, p = 0.031). Conclusions: These findings highlight the influence of socio-demographic, behavioral, and attitudinal factors on the acceptance of new food technologies. Tailored strategies are recommended to address FTN in specific subgroups, particularly among female, commuter, and Southern Italian students, to enhance receptivity to food innovation and support sustainable dietary transitions
Electrochemical impedance behavior and corrosion resistance of amorphous 316-type stainless steel microfibers in saline environment
Get PDFThe resistance of commercial stainless steel (SS) types in harsh environments is problematic because of the breakdown of the passive chromium oxide layer. This study aims to improve the corrosion resistance and passivation properties of commercial SS by producing fully amorphized 316 SS microfibers with multi-nozzle melt-spinning. Electrochemical tests in 3.5 wt% NaCl shows a low current density of 0.77 × 10–5 A cm–2 under ambient conditions, which increases slightly to 1.0 × 10–5 A cm–2 as the temperature rises to 50 °C. Sample electrochemically tested at 25°C also shows a current density at the level of 10–4 A cm–2 with long-term stability, and minor metastable pitting due to metal-Cl─ ion interactions is observed for the sample at 50 °C until 1.5 V. Electrochemical impedance spectroscopy before and after polarization at 50 °C shows an increase in both charge transfer resistance and double-layer admittance, suggesting double-layer formation on the outer surface due to Cl─ ion accumulation. Cross-sectional investigation by scanning transmission electron microscopy–electron energy loss spectroscopy corroborates the homogenous bulk composition and Fe-rich, Ni and Cr-containing amorphous oxide (<200 nm), both of which contribute to the corrosion resistance and passivation properties compared to nanocrystalline SS counterparts
A Comprehensive Study of the Sc(III)–OPC2A–Fluoride Interaction: Equilibrium, Kinetics, and 44Sc-Labeling
No full textMacrocyclic ligands are essential for metal coordination in biomedical applications owing to the high thermodynamic stability and inertness of their complexes. In our current study, we have investigated the Sc(III)-OPC2A2–-F–system for potential diagnostic and theranostic applications (based on18F and44Sc PET, and44Sc/47Sc matched isotopic pair, respectively). Results of equilibrium studies confirmed the formation of a stable [Sc(OPC2A)]+complex (logK[Sc(OPC2A)]= 16.72(4)) in a reaction that proceeds through the formation and rearrangement of an “out of cage” intermediate. The decomplexation reaction follows a kobs= k1[H+] + k2[H+]2rate law returning a t1/2= 0.37 h in 1 M HCl, and an unmeasurable long t1/2at pH = 7.4. The [Sc(OPC2A)F] mixed complex is remarkably stable; logK[Sc(OPC2A)F]= 4.54(8) and moderately inert against F–- exchange, with kd298= 16.5 s–1and activation parameters ΔH‡= 78 ± 1 kJ·mol–1, ΔS‡= 42 ± 4 J·mol–1K–1, and ΔG‡298= 66 ± 1 kJ·mol–1. The [44Sc]Sc(III)-labeled [Sc(OPC2A)]+forms at 95 °C within 10 min but requires purification. The complex is stable in rat blood serum, and toward transmetalation and transchelation processes. Consequently, the OPC2A is an excellent ligand platform for Sc(III) complexation and is recommended for further in vivo studies
Ateismo, Naturalismo e Clandestinità: il Colloquium Heptaplomeres di Jean Bodin e la sua fortuna in Francia e Germania (XVII - XVIII secolo)
No full textThis doctoral project investigates the reception and circulation of Jean Bodin’s thought in France and Germany from the late Renaissance to the early eighteenth century, with particular attention to the fortune of the Colloquium Heptaplomeres. The dissertation is structured in three parts, each devoted to a distinct phase in the dissemination and interpretation of Bodin’s intellectual legacy. The first part reconstructs the initial two phases of Bodin’s reception. The first period, from 1577 to 1613, is marked by accusations of ambiguity and heterodoxy leveled against Bodin by French and Italian Catholic theologians. The second, between 1627 and 1683, begins with the discovery and circulation of the Colloquium, which helped to consolidate Bodin’s role in debates on freedom of conscience, the relationship between religion and politics, and criticism of Christian dogma. The second part focuses on a philosophical analysis of the Colloquium, examining its structure and content while highlighting its affinities with libertine and anti-Christian currents of early modernity. This analysis reveals a consistent alignment with the concerns raised by Bodin’s critics, given the presence of numerous heterodox elements and an orientation that borders on atheism. The third and final part explores the third phase of Bodin’s reception, triggered by the publication of De naturalismo (1683) by Johann Diecmann, a prominent Lutheran theologian in the German academic context of the late seventeenth and early eighteenth centuries. Although conceived as a refutation, Diecmann’s work contributed to the dissemination of the Colloquium in Germany. His inclusion of several excerpts from Bodin’s dialogue in De naturalismo sparked the curiosity of readers and increased the demand for new manuscript copies. This dynamic encouraged further – albeit unsuccessful – attempts at publication, ultimately reinforcing the Colloquium’s reputation as a clandestine and controversial text
Exploring the Association of Migraine Susceptibility SNPs With the Risk of Chronic Migraine
Get PDFBackground: Although robust genetic markers for episodic migraine (EM) have been identified, variants associated with chronic migraine (CM) are still unknown. Given the potential pathophysiologic overlap between EM and CM, we investigated whether six single nucleotide polymorphisms (SNPs), robustly associated with EM susceptibility (LRP1 rs11172113, PRDM16 rs10797381, FHL5 rs7775721, TRPM8 rs10166942, near TSPAN2 rs2078371 and MEF2D rs1925950) also play a role in the risk of developing CM. Methods: A total of 200 EM and 202 CM participants were prospectively included. Genotyping of selected SNPs was performed by TaqMan real-time PCR in 192 individuals with EM and 198 with CM who consented to genetic analysis. A validation group of 312 healthy individuals was used. Genetic associations were assessed by logistic regression using dominant, recessive, and allelic models. Results: In multivariable logistic regression analysis, LRP1 rs11172113 T>C and (near) TSPAN2 rs2078371 T>C were nominally associated with CM. However, only the association for LRP1 rs11172113 survived Bonferroni correction, with carriers of the minor C allele (genotypes T/C or C/C) having a lower risk of CM compared to wild-type homozygous subjects (OR: 0.38; 95% CI: 0.20–0.71; p-value: 0.0025). This protective effect was also observed in the analysis comparing CM participants with healthy controls. Conclusion: Carriers of the minor allele of LRP1 rs11172113 have a reduced risk of CM. However, further large-scale studies, ideally with a multicentre design, are warranted to confirm the association between LRP1 rs11172113 and CM. Significance Statement: This study identified an association between the minor allele of LRP1 rs11172113 (low-density lipoprotein receptor-related protein 1, a receptor with key roles in lipid metabolism, vascular integrity, and inflammation control) and a reduced risk of chronic migraine. These findings support the hypothesis that episodic and chronic migraine share genetic risk factors and suggest a potential protective role for this variant