L'elogio della virt\uf9: i Cavalieri di Paolo Ligozzi e la committenza dei Saibante a San Pietro in Cariano

L'articolo analizza il programma iconografico di villa Saibante a San Pietro in Cariano (Verona), opera di Paolo Ligozzi, mettendone in evidenza il nesso con i committenti e analizzandone l'iconografia (soprattutto in relazione allo sviluppo del monumento equestre). Una delle fonti culturali alle quali si fa riferimento \ue8 il neostoicismo seicentesco, capace di spiegare alcune particolarit\ue0 iconografiche, sinora mai studiat

Social Representations of Protest and Police after the Genoa G8 Summit: A Qualitative Analysis of Activist Accounts of Events

The Genoa G8 Summit was marred by violence and conflicts between police and activists. Afterwards, these different groups constructed clashing discourses about the events. In turn, these discourses sustained different types of social representations about the nature of the conflict. Earlier analyses of hegemonic social representation examining the Italian press suggested that non-violent activists were subject to processes of delegitimisation and that they were identified with black bloc activists (Cristante, 2003; Juris, 2005; Zamperini & Botticini, 2006). Conversely, in this study we analyze activists\u2019 accounts of the protest and of the violent police repression. We examine a collection of published texts (N= 223) posted on a \u201ccyber-wall\u201d online as part of a collaborative project from three Italian media outlets: Il Manifesto, Radio Popolare, Carta. These texts represent a form of \u201ccounter-narrative\u201d produced by a stigmatized group to contest the dominant discourse, creating a tripartite of relations between non-violent activists, police and the black bloc . The analysis of these texts shows that activists represent the protest as a battle between two groups. Activists describe police as coercive, incompetent, and as the enemy. While the black bloc was perceived to have damaged the protest they were not depicted as the enemy. Cognitive, emotive and behavioral factors associated with these representations are highlighted and discussed, together with the implications for future intergroup relations between activists and the police

Reconstructed Overhanging Battlements. Executive Techniques and their Vulnerability in the Stronghold of Arquata del Tronto (Italy)

The stronghold of Arquata del Tronto was heavily damaged by earthquakes in 2016 and it drew the attention of the experts in reinforcing historic buildings. They regarded it as a case study, a predicting model of the failure in employing specific construction elements in fortified architecture, whose geometric and material data were only approximately considered. The overhanging battlement is the most seriously damaged part of the building and has raised particular attention and interest. As often happens in other castles and fortresses, it dates back to the late 19th and even more to the 20th century. A first close examination of the building’s repairs shows how the new additions, whose maintenance is difficult, ended in failure. The additions were inspired by ancient details, but nonetheless they are unreasonable from the point of view of structure and durability: they – and even more the irrational repairs of the last decades – are the principal cause of failure. Material decay – closely linked to circumstances and places – has also played a decisive role. An extensive and rigorous historical research is necessary to find the sources and to evaluate their nature and limits, as well as to relate all information to the building, thus operating in close correlation with the building archaeology, by now a so widespread and consolidated research field. Jointly, the written documents and the building itself in its historical stratification allow a better analysis of the structural behaviour , an essential step to achieve an effective restoration planning

Evaluation of Candida albicans adhesion and biofilm formation on a denture base acrylic resin containing silver nanoparticles

Aim: This study firstly evaluated the activity of a silver nanoparticle (AgNPs) solution against Candida albicans and then the effect of incorporation of AgNPs into a denture base acrylic resin on the material’s hydrophobicity, C. albicans adhesion and biofilm formation. Methods and Results: The AgNPs solution was synthesized by chemical reduction and characterized. Minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations for planktonic cells and sessile cells (MFCs) of the AgNPs solution against C. albicans were determined. Specimens (n = 360) of silver-incorporated acrylic resin at concentrations of 1000, 750, 500, 250 and 30 ppm were also prepared and stored in PBS for 0, 7, 90 and 180 days. Control was acrylic resin without AgNPs (0 ppm). After the storage periods, contact angles were measured and the specimens were used for C. albicans adherence ('37 GRAUS'; 90 min; n = 9) and biofilm formation ('37 GRAUS'; 48 h; n = 9) by XTT reduction assay. MIC, MFC and MFCs values were 3,98, 15,63 and 1000 ppm, respectively. Incorporation of AgNPs reduced the hydrophobicity of the resin. No effect on adherence and biofilm formation was observed. At 90 and 180 days of storage, there was significant increase in adherence and biofilm formation. Conclusions: Although the AgNPs solution had antifungal activity, no effect on C. albicans adherence and biofilm formation was observed after its incorporation into a denture base resin. Significance and Impact of the Study: The synthesized AgNPs solution is a promising antifungal agent, warranting investigations of more efficient methods of incorporation into denture base resins.FAPESP (08/11700-5; 08/07454-9

Multitarget CFTR Modulators Endowed with Multiple Beneficial Side Effects for Cystic Fibrosis Patients: Toward a Simplified Therapeutic Approach

Cystic fibrosis (CF) is a multiorgan disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR). In addition to respiratory impairment due to mucus accumulation, viruses and bacteria trigger acute pulmonary exacerbations, accelerating disease progression and mortality rate. Treatment complexity increases with patients’ age, and simplifying the therapeutic regimen represents one of the key priorities in CF. We have recently reported the discovery of multitarget compounds able to “kill two birds with one stone” by targeting F508del-CFTR and PI4KIIIβ and thus acting simultaneously as CFTR correctors and broad-spectrum enterovirus (EV) inhibitors. Starting from these preliminary results, we report herein a hit-to-lead optimization and multidimensional structure–activity relationship (SAR) study that led to compound 23a. This compound showed good antiviral and F508del-CFTR correction potency, additivity/synergy with lumacaftor, and a promising in vitro absorption, distribution, metabolism, and excretion (ADME) profile. It was well tolerated in vivo with no sign of acute toxicity and histological alterations in key biodistribution organs

A New Strategy for Glioblastoma Treatment: In Vitro and In Vivo Preclinical Characterization of Si306, a Pyrazolo[3,4-d]Pyrimidine Dual Src/P-Glycoprotein Inhibitor

20siopenOverexpression of P-glycoprotein (P-gp) and other ATP-binding cassette (ABC) transporters in multidrug resistant (MDR) cancer cells is responsible for the reduction of intracellular drug accumulation, thus decreasing the efficacy of chemotherapeutics. P-gp is also found at endothelial cells' membrane of the blood-brain barrier, where it limits drug delivery to central nervous system (CNS) tumors. We have previously developed a set of pyrazolo[3,4-d]pyrimidines and their prodrugs as novel Src tyrosine kinase inhibitors (TKIs), showing a significant activity against CNS tumors in in vivo. Here we investigated the interaction of the most promising pair of drug/prodrug with P-gp at the cellular level. The tested compounds were found to increase the intracellular accumulation of Rho 123, and to enhance the efficacy of paclitaxel in P-gp overexpressing cells. Encouraging pharmacokinetics properties and tolerability in vivo were also observed. Our findings revealed a novel role of pyrazolo[3,4-d]pyrimidines which may be useful for developing a new effective therapy in MDR cancer treatment, particularly against glioblastoma.openFallacara, Anna Lucia; Zamperini, Claudio; Podolski-Renić, Ana; Dinić, Jelena; Stanković, Tijana; Stepanović, Marija; Mancini, Arianna; Rango, Enrico; Iovenitti, Giulia; Molinari, Alessio; Bugli, Francesca; Sanguinetti, Maurizio; Torelli, Riccardo; Martini, Maurizio; Maccari, Laura; Valoti, Massimo; Dreassi, Elena; Botta, Maurizio; Pešić, Milica; Schenone, SilviaFallacara, Anna Lucia; Zamperini, Claudio; Podolski-Renić, Ana; Dinić, Jelena; Stanković, Tijana; Stepanović, Marija; Mancini, Arianna; Rango, Enrico; Iovenitti, Giulia; Molinari, Alessio; Bugli, Francesca; Sanguinetti, Maurizio; Torelli, Riccardo; Martini, Maurizio; Maccari, Laura; Valoti, Massimo; Dreassi, Elena; Botta, Maurizio; Pešić, Milica; Schenone, Silvi

Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEADbox polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target

The Salmonella enterica Pan-genome

Salmonella enterica is divided into four subspecies containing a large number of different serovars, several of which are important zoonotic pathogens and some show a high degree of host specificity or host preference. We compare 45 sequenced S. enterica genomes that are publicly available (22 complete and 23 draft genome sequences). Of these, 35 were found to be of sufficiently good quality to allow a detailed analysis, along with two Escherichia coli strains (K-12 substr. DH10B and the avian pathogenic E. coli (APEC O1) strain). All genomes were subjected to standardized gene finding, and the core and pan-genome of Salmonella were estimated to be around 2,800 and 10,000 gene families, respectively. The constructed pan-genomic dendrograms suggest that gene content is often, but not uniformly correlated to serotype. Any given Salmonella strain has a large stable core, whilst there is an abundance of accessory genes, including the Salmonella pathogenicity islands (SPIs), transposable elements, phages, and plasmid DNA. We visualize conservation in the genomes in relation to chromosomal location and DNA structural features and find that variation in gene content is localized in a selection of variable genomic regions or islands. These include the SPIs but also encompass phage insertion sites and transposable elements. The islands were typically well conserved in several, but not all, isolates—a difference which may have implications in, e.g., host specificity