Phenotype Screening of an Azole-bisindole Chemical Library Identifies URB1483 as a New Antileishmanial Agent Devoid of Toxicity on Human Cells

none11sìWe report the evaluation of a small library of azole-bisindoles for their antileishmanial potential, in terms of efficacy on Leishmania infantum promastigotes and intracellular amastigotes. Nine compounds showed good activity on L. infantum MHOM/TN/80/IPT1 promastigotes with IC50 values ranging from 4 to 10 μM. These active compounds were also tested on human (THP-1, HEPG2, HaCaT, and human primary fibroblasts) and canine (DH82) cell lines. URB1483 was selected as the best compound, with no quantifiable cytotoxicity in mammalian cells, to test the efficacy on intracellular amastigotes. URB1483 significantly reduced the infection index of both human and canine macrophages with an effect comparable to the clinically used drug pentamidine. URB1483 emerges as a new anti-infective agent with remarkable antileishmanial activity and no cytotoxic effects on human and canine cells.openDiotallevi, Aurora; Scalvini, Laura; Buffi, Gloria; Pérez-Pertejo, Yolanda; De Santi, Mauro; Verboni, Michele; Favi, Gianfranco; Magnani, Mauro; Lodola, Alessio; Lucarini, Simone; Galluzzi, LucaDiotallevi, Aurora; Scalvini, Laura; Buffi, Gloria; Pérez-Pertejo, Yolanda; De Santi, Mauro; Verboni, Michele; Favi, Gianfranco; Magnani, Mauro; Lodola, Alessio; Lucarini, Simone; Galluzzi, Luc

Synthesis and Biological Evaluation of a γ-Cyclodextrin-based Formulation of the Anticancer Agent 5,6,11,12,17,18,23,24-Octahydrocyclododeca[1,2-b:4,5-b’:7,8-b’’:10,11-b’’’]tetraindole (CTet)

none10sìopenLucarini, Simone; DE SANTI, Mauro; Antonietti, Francesca; Brandi, Giorgio; Diamantini, Giuseppe; Fraternale, Alessandra; Paoletti, MARIA FILOMENA; Tontini, Andrea; Magnani, Mauro; Duranti, AndreaLucarini, Simone; DE SANTI, Mauro; Antonietti, Francesca; Brandi, Giorgio; Diamantini, Giuseppe; Fraternale, Alessandra; Paoletti, MARIA FILOMENA; Tontini, Andrea; Magnani, Mauro; Duranti, Andre

Whole-Genome Sequencing Characterization of Virulence Profiles of Listeria monocytogenes Food and Human Isolates and In Vitro Adhesion/Invasion Assessment

none13sìListeria monocytogenes (Lm) is the causative agent of human listeriosis. Lm strains have different virulence potential. For this reason, we preliminarily characterised via Whole-Genome Sequencing (WGS) some Lm strains for their key genomic features and virulence-associated determinants, assigning the clonal complex (CC). Moreover, the ability of the same strains to adhere to and invade human colon carcinoma cell line Caco-2, evaluating the possible correspondence with their genetic virulence profile, was also assessed. The clinical strains typed belonged to clonal complex (CC)1, CC31, and CC101 and showed a very low invasiveness. The Lm strains isolated from food were assigned to CC1, CC7, CC9, and CC121. All CC1 carried the hypervirulence pathogenicity island LIPI-3 in addition to LIPI-1. Premature stop codons in the inlA gene were found only in Lm of food origin belonging to CC9 and CC121. The presence of LIPI2_inlII was observed in all the CCs except CC1. The CC7 strain, belonging to an epidemic cluster, also carried the internalin genes inlG and inlL and showed the highest level of invasion. In contrast, the human CC31 strain lacked the lapB and vip genes and presented the lowest level of invasiveness. In Lm, the genetic determinants of hypo- or hypervirulence are not necessarily predictive of a cell adhesion and/or invasion ability in vitro. Moreover, since listeriosis results from the interplay between host and virulence features of the pathogen, even hypovirulent clones are able to cause infection in immunocompromised people.openGiuditta Fiorella Schiavano * , Collins Njie Ateba , Annalisa Petruzzelli , Veronica Mele , Giulia Amagliani , Fabrizia Guidi , Mauro De Santi , Francesco Pomilio , Giuliana Blasi , Antonietta Gattuso , Stefania Di Lullo , Elena Rocchegiani, Giorgio BrandiSchiavano, GIUDITTA FIORELLA; Njie Ateba, Collins; Petruzzelli, Annalisa; Mele, Veronica; Amagliani, Giulia; Guidi, Fabrizia; DE SANTI, Mauro; Pomilio, Francesco; Blasi, Giuliana; Gattuso, Antonietta; Di Lullo, Stefania; Rocchegiani, Elena; Brandi, Giorgi

Engagement of CD99 activates distinct programs in Ewing sarcoma and macrophages

Ewing sarcoma (EWS) is the second most common pediatric bone tumor. The EWS tumor microenvironment is largely recognized as immune-cold, with macrophages being the most abundant immune cells and their presence associated with worse patient prognosis. Expression of CD99 is a hallmark of EWS cells, and its targeting induces inhibition of EWS tumor growth through a poorly understood mechanism. In this study, we analyzed CD99 expression and functions on macrophages and investigated whether the concomitant targeting of CD99 on both tumor and macrophages could explain the inhibitory effect of this approach against EWS. Targeting CD99 on EWS cells downregulated expression of the "don't eat-me" CD47 molecule but increased levels of the "eat-me" phosphatidyl serine and calreticulin molecules on the outer leaflet of the tumor cell membrane, triggering phagocytosis and digestion of EWS cells by macrophages. In addition, CD99 ligation induced reprogramming of undifferentiated M0 macrophages and M2-like macrophages toward the inflammatory M1-like phenotype. These events resulted in the inhibition of EWS tumor growth. Thus, this study reveals what we believe to be a previously unrecognized function of CD99, which engenders a virtuous circle that delivers intrinsic cell death signals to EWS cells, favors tumor cell phagocytosis by macrophages, and promotes the expression of various molecules and cytokines, which are pro-inflammatory and usually associated with tumor regression. This raises the possibility that CD99 may be involved in boosting the antitumor activity of macrophages

Defects in III-N LEDs: experimental identification and impact on electro-optical characteristics

III-N light-emitting-diodes (LEDs) are subject of intense investigations, thanks to their high efficiency and great reliability. The quality of the semiconductor material has a significant impact on the electro-optical performance of LEDs: for this reason, a detailed characterization of defect properties and the modeling of the impact of defects on device performance are of fundamental importance. This presentation addresses this issue, by discussing a set of recent case studies on the topic; specifically, we focus on the experimental characterization of defects, and on the modeling of their impact on the electro-optical characteristics of the devices

Quali strumenti giuridici statali e regionali per le comunit\ue0 patrimoniali?

The Framework Convention on the Value of Cultural Heritage for Society (Faro Convention, 2005) recognizes a central role to heritage communities in the process of identification, study, interpretation, protection, conservation and presentation of the cultural heritage. As a signatory State of the Convention (signed on 27th February 2013, still waiting for ratification), Italy has in any case to ensure its contribution to the safeguarding of the tangible and intangible cultural heritage by adequate policies. Currently, a State law providing a general regulation of the participation of civil society to the protection and the enhancement of cultural heritage in the Italian legal system has not been adopted yet. Nevertheless, communities, groups and individuals have a wide range of instruments available, which can be drawn by an accurate interpretation of the Constitution and of many State and regional laws. In the long run, the persistent lack of common rules on this subject may be a source of uncertainty, capable of weakening, instead of strengthening, the role of heritage communities, in contrast with the principles of the Faro Convention

Impact of the Pandemic on NonInfected Cardiometabolic Patients: A Survey in Countries of Latin America—Rationale and Design of the CorCOVID LATAM Study

Background: The first case of coronavirus 2019 (COVID-19) in Latin America was detected on February 26th, 2020, in Brazil. Later, in June, the World Health Organization announced that the focus of the outbreak had shifted to Latin America, where countries already had poor control of indicators of noncommunicable diseases (NCDs). Concerns about coronavirus infection led to a reduced number of visits and hospitalizations in patients with NCDs, such as cardiovascular disease, diabetes, and cancer. There is a need to determine the impact of the COVID-19 pandemic on patients who have cardiometabolic diseases but do not have clinical evidence of COVID-19 infection. Methods: The CorCOVID LATAM is a cross-sectional survey of ambulatory cardiometabolic patients with no history or evidence of COVID-19 infection. The study will be conducted by the Interamerican Society of Cardiology. An online survey composed of 38 questions using Google Forms will be distributed to patients of 13 Latin American Spanish-speaking countries from June 15th to July 15th, 2020. Data will be analyzed by country and regions. Seven clusters of questions will be analyzed: demographics, socioeconomic and educational level, cardiometabolic profile, lifestyle and habits, body-weight perception, medical follow-up and treatments, and psychological symptoms. Results: Final results will be available upon completion of the study. Conclusions: The present study will provide answers regarding the impact of the COVID-19 pandemic on noninfected cardiometabolic patients. Data on this topic are scarce, as it is an unprecedented threat, without short-term solutions.Fil: Lopez Santi, Ricardo. Hospital Italiano de La Plata; ArgentinaFil: Piskorz, Daniel Leonardo. No especifíca;Fil: Marquez, Manlio F.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Ramirez Ramos, Cristhian. Centro de Medicina del Ejercicio y Rehabilitación Cardíaca; ColombiaFil: Renna, Nicolas Federico. Hospital Espanol de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ibarrola, Martin. No especifíca;Fil: Wyss, Fernando Stuardo. Servicios y Tecnología Cardiovascular de Guatemala; GuatemalaFil: Naranjo Dominguez, Adrián. Instituto de Cardiologia y Cirugia Cardiovascular; CubaFil: Perez, Gonzalo Emanuel. No especifíca;Fil: Farina, Juan María. No especifíca;Fil: Forte, Ezequiel. Centro Diagnóstico Cardiovascular; ArgentinaFil: Juarez Lloclla, Jorge Paul. Hospital de Apoyo II Santa Rosa; PerúFil: Flores de Espinal, Emma. Hospital Nacional San Juan De Dios; El SalvadorFil: Puente Barragan, Adriana. Instituto Mexicano del Seguro Social; MéxicoFil: Ruise, Mauro Gabriel. Clínica Yunes; ArgentinaFil: Delgado, Diego. University of Toronto; CanadáFil: Baranchuk, Adrian. Queens University; Canad

Citizens of Europe

Il titolo della collana esprime la volont\ue0 di approfondire i profili legati al processo di integrazione europeo, non ignorandone i risvolti pi\uf9 discutibili e burocratici ma sapendo guardare al di l\ue0 di essi, nella logica che traspare dal gioco di assonanze indicato dal titolo. In questo terzo volume Citizens of Europe, dedicato ai temi delle identit\ue0 e della cittadinanza culturale, viene in rilievo la tensione tra i limiti delle politiche, culturali e di cittadinanza, perseguite dalla UE e l\u2019imporsi progressivo \u2013 malgrado le cupe ombre proiettate dalla drammatica attualit\ue0 \u2013 di una pi\uf9 ampia nozione di \u2018cittadinanza d\u2019Europa\u2019, scandita in particolare da quei recenti strumenti giuridici del Consiglio d\u2019Europa attraverso i quali l\u2019afflato europeo, non imprigionato nelle pastoie dei meccanismi della EU citizenship, si sviluppa pi\uf9 significativamente