525 research outputs found
Il contributo degli indicatori di performance all'aziendalizzazione delle produzioni sanitarie
No full textRuoli e funzioni delle donne nelle minoranze dal Medioevo all’età contemporanea, in Nuove frontiere per la storia di genere (panel tematico)
No full textLa curatela riguarda la sezione sul ruolo e la funzione delle donne nelle minoranze dal medioevo all'età contemporanea. Le curatrici sono state anche le organizzatrici del panel
Ruoli e funzioni delle donne nelle minoranze dal Medioevo all’età contemporanea: introduzione.
No full textL ́introduzione presenta criticamente le ragioni che hanno portato all ́organizzazione del panel, lo stato della ricerca sulle donne appartenenti alle minoranze, e discute il contenuto dei singoli contributi
In vitro modelling and characterization of cells involved in Gaucher Disease-related bone defects
No full textGaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the acid β-glucosidase encoding gene (GBA1), resulting in deficient activity of acid β-glucosidase (GCase) and the subsequent accumulation of glucosylceramide (GlcCer) within lysosomes. Up to 90% of GD patients report bone symptoms that severely reduce their quality of life. The molecular basis of bone involvement in GD is unclear. However, several lines of evidence suggest that both osteoblasts and osteoclasts play a role in the process, whereas almost no information is available about cartilage cells.
For these reasons, the general objective of this project was to explore the role played by different cells in GD bone pathology. Specifically, we (1) developed GD models of osteoclasts, osteoblasts, and chondrocytes (GBA KO cells) by using CRISPR/Cas technology to knock out (KO) the GBA1 gene in continuous cell lines relevant to study bone pathophysiology, (2) characterized the different features of wild-type (wt) and GBA KO cells, and (3) examine cell-to-cell interactions.
Firstly, we modelled GD monocytes using the THP-1 cell line. We observed increased osteoclastogenesis of THP-1 GBA KO compared with THP-1 wt. As the number of differentiated osteoclasts was reduced by providing THP-1 GBA KO with the recombinant GCase, an inhibitor of GlcCer synthesis, or an anti-inflammatory compound, we demonstrated that lipid accumulation and inflammation play a central role in this process.
Secondly, we modelled GD osteoblasts using the osteosarcoma cell line SaOS and characterized these cells in terms of type I collagen, which is produced by osteoblasts and is the main constituent of the organic component of bone extracellular matrix (ECM), and alkaline phosphatase (ALP), an enzyme required for the formation of hydroxyapatite crystals, which represent the inorganic component of bone ECM. Compared with SaOS wt, SaOS GBA KO showed a slight decrease in ALP mRNA expression and calcium deposition, and a significant decrease in type I collagen mRNA expression and deposition. Moreover, we performed the miRNA profile of these cells in cell lysates and exosomal preparations using NGS technology. Among the significantly up- and down-regulated candidates, we focused on miR-488-3p, which was strongly overexpressed by GBA KO cells.
We further validated the overexpression of miR-488-3p in primary osteoblasts treated with the GCase inhibitor CBE to mimic GD. Furthermore, to characterize the functional impact of miR-488-3p overexpression, we transfected it into SaOS wt and we showed that it downregulates the expression of ALP- and collagen type I-encoding genes, probably by downregulating their transcription factor RUNX2. Taken together, these data suggest an impairment of matrix deposition by GD osteoblasts that can be explained, at least in part, by the action of the overexpressed miR-488-3p.
Thirdly, we model GD chondrocytes using the C28I2 cell line. As we found decreased expression of collagen type II- and increased expression of collagen type X- encoding genes in GBA KO cells, we hypothesize changes in matrix composition and a different fate of GD chondrocytes compared with normal cells. In addition, these cells release more interleukin-8 and attract more neutrophils than wt: these observations may explain the pain experienced by GD patients.
Finally, we examined the role of GD osteoblasts and chondrocytes in osteoclastogenesis. We found increased osteoclastogenesis when the conditioned medium (CM) of SaOS GBA KO cells was used to differentiate THP-1 wt, likely due to increased release of the receptor activator of NF-kB ligand (RANKL). Furthermore, in a preliminary experiment, we found a similar trend in osteoclast formation when C28I2 GBA KO-CM was used, suggesting a possible role of GD chondrocytes in enhancing osteoclastogenesis.
In conclusion, we provide evidence for the role of osteoclasts, osteoblasts, and chondrocytes in GD
La valutazione dell'efficacia dei contributi de minimis alle imprese: un approccio basato sul Regression Discontinuity Design
No full textQuesto lavoro espone i risultati di una valutazione di tipo controfattuale degli effetti degli aiuti de minimis a piccole imprese, sia nuove che esistenti, erogati in un comune della Sardegna. Le modalità di implementazione della politica e le caratteristiche dell’intervento indicano la metodologia del Fuzzy RD come quella più adatta in questo contesto. L’analisi è stata effettuata su un insieme di 174 imprese. I risultati indicano che, tra le imprese che hanno effettuato l’investimento con successo, l’impatto dell’intervento è stato positivo e significativo. Tuttavia, la variazione aggiuntiva dell’occupazione è limitata, circa 7 addetti in più. In generale, la presenza di un campione piccolo e del fenomeno della ubbidienza imperfetta suggeriscono di leggere questo risultato con cautela e non permettono di generalizzare il risultato per politiche simili applicate in ambito nazionale o regionale.This paper investigates the effect of a policy aimed at supporting small firms, the De Minimis aid Program, in the Italian region of Sardinia. Both the characteristics and the way the policy has been implemented suggest the use of the Fuzzy RD methodology as the most suitable in this context. The analysis is carried out on a group of 174 small firms. The results show that the impact of the program is positive and significant but only for one of three waves of the Program. Moreover, they also suggest that, in this case, the estimated additional variation in employment is small, approximately 7 additional employees. Overall, the presence of both small sample problems and imperfect compliance imply that the results may suffer from problems of limited external validity and should be read with caution
Repertoires of knowledge practices: Social movements in times of crisis
No full textPurpose: Starting from the assumption that knowledge becomes all the more important for movements in times of crisis, as old structures are challenged and new ones envisaged and proved feasible, the purpose of this paper is to suggest ways to expand the toolkit of social movement studies in order to empirically address knowledge practices as a meaningful part of contemporary progressive activism. Design/methodology/approach: The authors start by arguing that, in their effort to pursue or resist social and political changes, contemporary progressive social movements form collective spaces of knowledge production that are true laboratories for innovation. For this reason, the authors begin by making a case for accounting more explicitly for knowledge production within social movement studies - not as a substitution for but, rather, as a necessary complement to current cultural approaches. Building on extant literature on the nexus between movements and knowledge, the authors then outline the peculiarities of movement knowledge. Findings: On these bases, the authors outline the core components of what the authors call repertoires of knowledge practices - that is, the set of practices that foster the coordination of disconnected, local, and highly personal experiences and rationalities within a shared cognitive system able to provide movements and their supporters with a common orientation for making claims and acting collectively to produce social, political, and cultural changes. Originality/value: The authors conclude by identifying some promising avenues of research to further develop the understanding of movement practices of knowledge production and transmission. © 2017, © Emerald Publishing Limited
Digital Media and Knowledge Production Within Social Movements: Insights From the Transition Movement in Italy
No full textsponsorship: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This article grounds in research activites carried out in the period 2016-2017 within the framework of the project "MAKERS- Movements as knowledge producers and learning spaces in the digital age" funded by the Scuola Normale Superiore. (Scuola Normale Superiore)status: Publishe
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