204 research outputs found

    The Immutability of Artwork in the Age of Digital Reproduction: NFT from the insiders\u27 perspective

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    A Non-Fungible Token (NFT) is a combination of a digital object and its blockchain-based certificate that promise to solve problems of authentic- ity and traceability of digital objects. Focusing on art domain, this study ex- plores the operations and implications of NFT-based digital artwork markets through the viewpoint of artists and collectors. The first data were collected in 2021 from various insiders in the NFT community: the interviewees working and earning in this market segment are the most suitable profiles to delineate the structure of these activities; their responses were analyzed against the theo- retical framework that includes the notions of digital objects and blockchain technology, outlining NFT properties. The results were consistent, showing that blockchain technology can overcome the limitations of digital objects while opening up new challenges and possible risks

    Interplay between endoplasmic reticulum (ER) stress and autophagy induces mutant p53H273 degradation

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    The unfolded protein response (UPR) is an adaptive response to intrinsic and external stressors, and it is mainly activated by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) lumen producing ER stress. The UPR signaling network is interconnected with autophagy, the proteolytic machinery specifically devoted to clearing misfolded proteins in order to survive bioenergetic stress and/or induce cell death. Oncosuppressor TP53 may undergo inactivation following missense mutations within the DNA-binding domain (DBD), and mutant p53 (mutp53) proteins may acquire a misfolded conformation, often due to the loss of the DBD-bound zinc ion, leading to accumulation of hyperstable mutp53 proteins that correlates with more aggressive tumors, resistance to therapies, and poorer outcomes. We previously showed that zinc supplementation induces mutp53 protein degradation by autophagy. Here, we show that mutp53 (i.e., Arg273) degradation following zinc supplementation is correlated with activation of ER stress and of the IRE1α/XBPI arm of the UPR. ER stress inhibition with chemical chaperone 4-phenyl butyrate (PBA) impaired mutp53 downregulation, which is similar to IRE1α/XBPI specific inhibition, reducing cancer cell death. Knockdown of mutp53 failed to induce UPR/autophagy activation indicating that the effect of zinc on mutp53 folding was likely the key event occurring in ER stress activation. Recently discovered small molecules targeting components of the UPR show promise as a novel anticancer therapeutic intervention. However, our findings showing UPR activation during mutp53 degradation indicate that caution is necessary in the design of therapies that inhibit UPR components

    Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells.

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    It is known that melanoma develops as a consequence of multifactorial alterations. To date several studies indicate the effective implication of p16 as a tumor suppressor gene with a major role in either the development or progression of human melanoma. Deregulation of melanoma cell growth has been widely associated with mutations in the p16-cyclin D/cdk4-pRb pathway. Recently anticancer therapies are focused on restoration of p16 CDK inhibitory function and other proteins unregulated in melanoma cell cycle pathway (e.g., c-myc, p27). A combined strategy for restoration of normal homeostasis in the melanoma skin with targeted delivery of apoptosis-inducing agents does not seems to be far obtained. New class of antitumoral agents are emerging: histone deacetylase (HDAC) inhibitors have attracted much interest because of their ability to arrest cell growth, induce cell differentiation, and in some cases, induce apoptosis of cancer cells. Recently, attention has been focused on the ability of HDAC inhibitors to induce perturbation in cell cycle regulatory protein (e.g., p21(CIP1)) and down-regulation of survival signalling pathway. In the present study, we have examined the effect of valproic acid (VPA) on M14 human melanoma cell line. Here we observed that VPA induces cell cycle arrest and apoptosis sensitising melanoma cells to cis-platin and etoposide treatment. IC(50) dose (2.99 mM) of VPA was able to induce G(1) arrest (up to 75%) in association with upregulation of p16, p21 and cyclin-D1 related to Rb ipo-phosphorilation. In addition VPA activated apoptosis (50%) in M14 cells, when given alone or in combination with antitumoral agents. The ability of valproic acid to reestablished the G(1) pathway in melanoma cells suggests a potential application of VPA in melanoma therapeutic protocols

    Psychological Sexual Health of People with Paraplegia

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    People with paraplegia have to fight their own and societal attitudes and stereotypes that reduce sexuality to the physiological functions of genitalia. These psychological and social limitations arise from cultural and disability models that focus sexual pleasure on phallocentric primacy, and sexual attractiveness of perfect bodies. In this chapter, we evaluate the impacts of a psychoeducational intervention in a personal growth group on the sexual life of two groups of people with spinal cord injury (SCI) and their partners, throughout their sexual interest and satisfaction, depression, and anxiety. In the first study, nonparametric statistical tests were used to compare pre- and post-outcome measures for all participants. In the second study, the grounded theory was used to explore dialogs and activities that were audiotaped during the group meetings. The participants in both groups were patients and their partners. The psychoeducational intervention was clearly effective in increasing sexual interest and satisfaction as well as the motivation and ability to enjoy sexuality. Anxiety was minimized for all participants, although it may not have been associated with the psychoeducational intervention. In addition, the intervention significantly improved the partner and patient group’s opportunity and ability to enjoy sexuality

    Biblioteche, infrastrutture culturali e polifunzionalità: una mappatura data driven

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    Il contributo affronta un tema ancora poco discusso e che sembra invece centrale per immaginare quali trasformazioni interesseranno le biblioteche nel prossimo futuro. Si tratta del concetto di polifunzionalità. A partire dall’analisi dei dati delle prime tre edizioni del Censimento dell’Istat, questo concetto è stato approfondito in relazione alle caratteristiche delle biblioteche italiane e grazie a un approccio data driven ne viene offerta una dettagliata geografia che rispecchia le variazioni avvenute tra il 2020 e il 2022. È stata quindi ricostruita la fisionomia della polifunzionalità delle biblioteche prima e dopo la pandemia da Covid-19. Presentando i risultati di un’indagine in corso, è stato anche possibile affiancare a questo approfondimento una mappatura dei cosiddetti ‘nuovi centri culturali multidisciplinari e indipendenti’ che sono ampiamente diffusi a livello nazionale e che sembrano contraddistinguersi proprio per la loro polifunzionalità. Mettendo a confronto visioni e analisi diverse, si è voluto dare avvio a una riflessione anche di tipo comparativo tra le biblioteche polifunzionali e i nuovi centri culturali per rintracciare le caratteristiche che li rendono dei luoghi della contemporaneità

    Biblioteche, infrastrutture culturali e polifunzionalità. Una mappatura data driven

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    Il contributo affronta un tema ancora poco discusso e che sembra invece centrale per immaginare quali trasformazioni interesseranno le biblioteche nel prossimo futuro. Si tratta del concetto di polifunzionalità. A partire dall’analisi dei dati delle prime tre edizioni del Censimento dell’Istat, questo concetto è stato approfondito in relazione alle caratteristiche delle biblioteche italiane e grazie a un approccio data driven ne viene offerta una dettagliata geografia che rispecchia le variazioni avvenute tra il 2020 e il 2022. È stata quindi ricostruita la fisionomia della polifunzionalità delle biblioteche prima e dopo la pandemia da Covid-19. Presentando i risultati di un’indagine in corso, è stato anche possibile affiancare a questo approfondimento una mappatura dei cosiddetti ‘nuovi centri culturali multidisciplinari e indipendenti’ che sono ampiamente diffusi a livello nazionale e che sembrano contraddistinguersi proprio per la loro polifunzionalità. Mettendo a confronto visioni e analisi diverse, si è voluto dare avvio a una riflessione anche di tipo comparativo tra le biblioteche polifunzionali e i nuovi centri culturali per rintracciare le caratteristiche che li rendono dei luoghi della contemporaneità

    Autoantibodies against the glial glutamate transporter GLT1/EAAT2 in Type 1 diabetes mellitus-Clues to novel immunological and non-immunological therapies

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    : Islet cell surface autoantibodies were previously found in subjects with type 1 diabetes mellitus (T1DM), but their target antigens and pathogenic mechanisms remain elusive. The glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2) is expressed on the membrane of pancreatic β-cells and physiologically controls extracellular glutamate concentrations thus preventing glutamate-induced β-cell death. We hypothesized that GLT1 could be an immunological target in T1DM and that autoantibodies against GLT1 could be pathogenic. Immunoprecipitation and ELISA experiments showed that sera from T1DM subjects recognized GLT1 expressed in brain, pancreatic islets, and GLT1-transfected COS7-cell extracts. We validated these findings in two cohorts of T1DM patients by quantitative immunofluorescence assays. Analysis of the combined data sets indicated the presence of autoantibodies against GLT1 in 32 of the 87 (37%) T1DM subjects and in none of healthy controls (n = 64) (p < 0.0001). Exposure of pancreatic βTC3 cells and human islets to purified IgGs from anti-GLT1 positive sera supplemented with complement resulted in plasma membrane ruffling, cell lysis and death. The cytotoxic effect was prevented when sera were depleted from IgGs. Furthermore, in the absence of complement, 6 out of 16 (37%) anti-GLT1 positive sera markedly reduced GLT1 transport activity in βTC3 cells by inducing GLT1 internalization, also resulting in β-cell death. In conclusion, we provide evidence that GLT1 is a novel T1DM autoantigen and that anti-GLT1 autoantibodies cause β-cell death through complement-dependent and independent mechanisms. GLT1 seems an attractive novel therapeutic target for the prevention of β-cell death in individuals with diabetes and prediabetes
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