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Eredità in Architettura
No full textLa cultura architettonica del Novecento costituisce ancora oggi un repertorio vivo di principi e visioni capace di orientare il progetto contemporaneo. L’eredità non è intesa come ripetizione di modelli, ma come dispositivo attivo di trasformazione: l’esistente diventa matrice critica per interventi di rifunzionalizzazione, riscrittura e adattamento, in equilibrio tra permanenza e innovazione. La mostra Eredità in Architettura mette a confronto le ricerche di Atelier(s) Alfonso Femia e Park, evidenziando approcci distinti ma convergenti nell’interpretare il patrimonio come risorsa per la città contemporanea. Attraverso strategie di riqualificazione degli involucri, integrazioni volumetriche e aggiornamenti tipologici, i progetti presentati dimostrano come la tutela possa estendersi alla capacità dell’opera di adattarsi nel tempo. In dialogo con il pensiero di Renato De Fusco, emerge una visione del progetto come pratica critica e responsabile, fondata su un movimento continuo tra passato e presente, capace di generare nuove possibilità per l’architettura italiana
Generalizing two families of scattered quadrinomials in
No full textIn recent years, several efforts have focused on identifying new families of scattered polynomials. Currently, only three families in are known to exist for infinitely many values of and : (i) pseudoregulus-type monomials, (ii) Lunardon-Polverino-type binomials, and (iii) a family of quadrinomials studied in a series of papers. In this work, we provide sufficient conditions under which these quadrinomials, denoted by , are scattered. Our results both include and generalize those obtained in previous studies. We also investigate the equivalences between the previously known families of scattered polynomials and those in this new class
Proteotoxic stress triggers TFEB- and TFE3-mediated autophagy and lysosomal biogenesis via non-canonical MTORC1 inactivation
No full textProteotoxic stress, arising from conditions that cause misfolded protein accumulation, is closely linked to the pathogenesis of multiple diseases. Macroautophagy/autophagy activation is considered a compensatory mechanism to maintain protein homeostasis, but the underlying regulatory mechanisms remain incompletely understood. Here, we show that proteotoxic stress induced by proteasome inhibition, puromycin treatment, or polyglutamine-expanded HTT (huntingtin) expression promotes nuclear accumulation of TFEB and TFE3, key regulators of lysosomal biogenesis and autophagy. Mechanistically, TFEB activation under proteotoxic stress occurs independently of canonical MTORC1 inactivation mediated by TSC2 or ATF4. Instead, it involves non-canonical inhibition of MTORC1 via RRAG GTPases. Proteotoxic stress disrupts the RRAGC-TFEB interaction, preventing TFEB recruitment to lysosomes and subsequent MTORC1 phosphorylation. An activated RRAGC mutant rescues impaired lysosomal localization and nuclear accumulation of TFEB, while co-overexpression of FLCN and FNIP2, a GAP for RRAGC, partially restores stress-induced TFEB dephosphorylation. In addition, proteasome inhibition activates non-canonical autophagy. Deletion of ATG16L1 or ATG5, which known blocks Atg8-family protein lipidation and sequesters the FLCN-FNIP2 complex, partially abolishes proteotoxic stress-induced TFEB dephosphorylation and nuclear accumulation. Together, these findings demonstrate that proteotoxic stress triggers both non-canonical autophagy and TFEB-mediated canonical autophagy, with Atg8-family protein lipidation contributing to TFEB activation. Our results provide novel insights into how proteotoxic stress engages non-canonical MTORC1 inhibition and TFEB activation, thereby enhancing understanding of cellular adaptation to proteotoxic stress. Abbreviations: ALP, autophagy-lysosomal pathway; ATF4, activating transcription factor 4; Baf A1, bafilomycin A1; CHX, cycloheximide; BTZ, bortezomib; CFZ, carfilzomib; CQ, chloroquine; CTSB, cathepsin B; CTSD, cathepsin D; DQ-BSA, dequenched-bovine serum albumin; EIF4EBP1/4EBP1, eukaryotic translation initiation factor 4E binding protein 1; ER, endoplasmic reticulum; MAP1LC3B/LC3B, microtubule associated protein 1 light chain 3 beta; MG132, carbobenzoxy-Leu-Leu-leucinal; MTORC1, mechanistic target of rapamycin kinase complex 1; RPS6KB1/p70, ribosomal protein S6 kinase B1; RRAG, Ras related GTP binding; SQSTM1/p62, sequestosome 1; TFE3, transcription factor E3; TFEB, transcription factor EB; TSC2, TSC complex subunit 2; tfLC3, tandem fluorescent LC3; UPS, ubiquitin-proteasome system
Digital electronics upgrade of the INDRA 4π charged particle detection array and resulting performance improvements
No full textINDRA is a 4π charged particle detection array in use since 1993 for the study of nuclear collisions at bombarding energies from a few 10s to a few 100s of MeV/nucleon. Originally equipped with custom electronics using the VXI standard, the entire acquisition system was recently upgraded to a fully digital system using commercially-available modules supplied by mesytec GmbH & Co. KG. At the same time, both low and high voltage supplies and all cabling and signal routing outside of the reaction chamber have also been replaced. The new electronics were used for the first time in 2022 in an experiment at GANIL coupling INDRA with 12 blocks of FAZIA telescopes placed at forward angles. The full details of the upgraded system, and the resulting improvements in performance, stability, dead time and identification capabilities are presented in this article
Green metabolic engineering of Synechocystis sp. PCC 6803 for efficient production and sustainable extraction of β-cryptoxanthin and zeaxanthin
No full textBackground: β-xanthophylls, such as zeaxanthin and β-cryptoxanthin, display significant bioactive properties including anti-oxidant, anti-inflammation and anti-cancer activities. These properties spur their widespread use in food, animal feed, cosmetic and pharmaceutic sectors. However, commercial carotenoids are dominantly manufactured by chemical synthesis, posing environmental pollution. A minor fraction is sourced from plants and algae, a process often hampered by low yields and high costs. Consequently, microbial biosynthesis has emerged as a promising alternative for producing these high-value compounds. Results: Here, we engineered the photosynthetic microorganism Synechocystis sp. PCC 6803 for efficient production of zeaxanthin and β-cryptoxanthin by two different strategies. In the first strategy, the gene crtO for echinenone biosynthesis and crtD involved in the myxoxanthophyll biosynthesis were inactivated, which increased the amount of zeaxanthin and β-cryptoxanthin by approximately 30% and 60%, respectively, reaching 1.3 mg/g DCW and 0.15 mg/g DCW in the double mutant ΔcrtO/crtD compared to wild type. The second strategy combined the replacement of the native β-carotene hydroxylase with a heterologous, high-efficiency plant enzyme and further improvement of precursor supply. The final strain oxBDI produced 5 mg/g DCW zeaxanthin and 1.5 mg/g DCW β-cryptoxanthin, fivefold and 18-fold higher than wild type, respectively, representing 80% of the total carotenoids produced. In addition, no significant difference was observed in the growth rate between transgenic strains and wild type under standard lab conditions, suggesting the applicability of this biotechnology strategy. Moreover, we explored the use of natural deep eutectic solvents (NADESs) as a green alternative for β-xanthophylls extraction from the engineered cyanobacteria using a simplified procedure. The NADES composed of food-grade menthol and acetic acid (1:1) achieved the highest efficiency, recovering 3.5 mg/g DCW of zeaxanthin and 1.2 mg/g DCW of β-cryptoxanthin, about 50% higher than the conventional solvent acetone, highlighting the strong potential of NADES as a green and safe solvent for carotenoid recovery from cyanobacteria. Conclusions: Taken together, our work reveals an efficient biotechnological strategy for production of zeaxanthin and β-cryptoxanthin, and a novel and efficient NADES-based method for eco-friendly recovery of high-value carotenoids. Graphical abstract: [Image: see text] Supplementary information: The online version contains supplementary material available at 10.1186/s12934-025-02918-3
Valorization of grape pomace through alginate-pectin beads cross-linked with Ca2+ and Fe3+ for the stabilization and delivery of antioxidant polyphenols
No full textGrape pomace (GP), a winemaking by-product, is rich in polyphenols with antioxidant activity, but is prone to degradation. In this study, ethanolic extracts of GP were encapsulated in polysaccharide-based beads to enhance stability and enable controlled release. Alginate, low-methoxyl pectin, and an 80/20 pectin-alginate blend were cross-linked with Ca2+ or Fe2+ at two concentrations (4% and 8% w/v) to systematically adjust the network structure and release behavior. All formulations achieved high loading efficiencies (87-95%), but release and antioxidant performance were strongly matrix-dependent. The Pectin-Ca2+ beads, which contained 75% GP extract (formulation T), showed the highest efficacy, reducing intracellular ROS in HaCaT cells by up to 78%. Thermal analysis suggested that Fe2+ crosslinking enhanced solid-state stability through polymer-ion and metal-polyphenol interactions. These results demonstrate that tuning polysaccharide composition and crosslinking chemistry allows simultaneous control of polyphenol release and stabilization, providing a rational design framework for GP-based functional ingredients
Multienzyme engineering in the cellar: Versatile biotechnological potential of pectolytic-based clarification enzymes in rosé winemaking
No full textCommercial pectolytic enzymes are widely used in winemaking for must clarification, but their side activities remain scarcely explored. The present study evaluated three commercial clarification enzymes (E1, E2, E3) for their collateral activities and their technological impact in both laboratory-scale and pilot-scale rosé winemaking. Enzymatic assays revealed that E1 exhibited the broadest and most intense accessory activity profile, including significant hemicellulolytic and glycosidase activities. Laboratory trials highlighted beneficial side effects, including increased yeast assimilable nitrogen and decreased calcium ions, an impact of potential interest for calcium tartrate stabilization. Pilot-scale rosé winemaking with Bombino nero and Primitivo grapes demonstrated that clarification enzymes can significantly modulate rosé wine composition, affecting colour indices and volatile profiles in a cultivar-dependent manner. Commercial pectolytic preparations can be considered versatile enzymatic cocktails that can be tailored to grape properties to optimise wine complexity and stability, moving beyond basic clarification toward multienzyme engineering
Amphiphile-drug interplay: Enhanced solubility and drug-tailored self-assembly for delivery applications
No full textDuring the last three decades, the design of refined nanosized drug delivery systems employed peculiar temperature-responsive synthetic copolymers, Pluronics, capable to mimic biological systems. Biocompatibility and biodegradability, along with the possibility of opportunely tailoring the desired features of these macromolecules, can be exploited to develop carriers able to improve the solubility and the bioavailability of hydrophobic drugs. As passive agents, Pluronics have a high drug loading capacity in water and low immunogenicity, but they can also play a more active role by reacting to temperature changes. Within specific ranges of concentration, Pluronic aqueous solutions can be injected in liquid form and become soft solids at body temperature, allowing to modulate the drug release. The presence of additives can modify the thermal response of Pluronic molecules in water, possibly sensitizing the system to other stimuli (e.g., pH). In this work, the addition of hydrophobic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) – ibuprofen (IBU), ibuprofen sodium salt (IBUNa), diclofenac potassium (DK) – in a 45 wt% Pluronic F68 aqueous solution was investigated by rheology, Differential Scanning Calorimetry (DSC), surface tension and wettability measurements. Pluronic F68 significantly increased the solubility of the drug in water. The thermo-reversible, self-assembling process was followed and phase transitions were identified through rheological oscillatory and steady measurements and calorimetric evaluations at different drug concentrations and temperatures. The effect of pH was also discussed by varying the drug type and its concentration. Lastly, empirical phase diagrams for the drug/Pluronic aqueous solutions were built
Tutor della dottoranda dott.ssa Brigitta Marieclaire Catalano – Dottorato di Ricerca “Diritti umani. Teoria, storia e prassi, LXI ciclo
No full textSelective Delivery of Anticancer Natural G-Quadruplex Ligands by the AT11 Aptamer for Gastric Cancer Treatment
No full textSearching for G-quadruplex-selective ligands as anticancer agents, we recently identified the natural compounds bulbocapnine, chelidonine, dicentrine, ibogaine, and rotenone as novel interactors of G-quadruplexes. Herein, to investigate their ability to interact with a specific carrier for selective delivery to cancer cells, the dimeric G-quadruplex-forming aptamer AT11 was used as a model. NMR spectroscopy, molecular modeling, circular dichroism, and fluorescence spectroscopy allowed the preferential interaction to be proven with the 3′-end G-quartet for bulbocapnine, chelidonine, dicentrine, and ibogaine, whereas with the 5′-end G-quartet region for rotenone. The anticancer activity of the AT11/natural compounds complexes was evaluated on gastric cancer cells using the free aptamer and free natural compounds as controls. Notably, all complexes caused a significant decrease in cancer cell viability, also producing synergistic effects. Remarkably, no relevant effects were detected on noncancerous cells, denoting the importance of delivering the natural compounds by AT11 G-quadruplex to obtain selective antiproliferative effects on cancer vs. normal cells