Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line.

The signaling pathways triggered by adherence of Candida albicans to the host cells or extracellular matrix are poorly understood. We provide here evidence in C. albicans yeasts of a p105 focal adhesion kinase (Fak)-like protein (that we termed CaFak), antigenically related to the vertebrate p125Fak, and its involvement in integrin-like-mediated fungus adhesion to vitronectin (VN) and EA.hy 926 human endothelial cell line. Biochemical analysis with different anti-chicken Fak antibodies identified CaFak as a 105-kDa protein and immunofluorescence and cytofluorimetric analysis on permeabilized cells specifically stain C. albicans yeasts; moreover, confocal microscopy evidences CaFak as a cytosolic protein that colocalizes on the membrane with the integrin-like VN receptors upon yeast adhesion to VN. The protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A strongly inhibited C. albicans yeast adhesion to VN and EA.hy 926 endothelial cells. Moreover, engagement of alpha v beta 3 and alpha v beta 5 integrin-like on C. albicans either by specific monoclonal antibodies or upon adhesion to VN or EA.hy 926 endothelial cells stimulates CaFak tyrosine phosphorylation that is blocked by PTK inhibitor. A role for CaFak in C. albicans yeast adhesion was also supported by the failure of VN to stimulate its tyrosine phosphorylation in a C. albicans mutant showing normal levels of CaFak and VNR-like integrins but displaying reduced adhesiveness to VN and EA.hy 926 endothelial cells. Our results suggest that C. albicans Fak-like protein is involved in the control of yeast cell adhesion to VN and endothelial cells

Social Innovation and Environmental Sustainability in Social Housing Policy: Learning from two Experimental Case Studies in Italy

Il capitolo esamina in maniera critica l’approccio e le soluzioni proposte dal social housing come risposta in termini sostenibili all’emergenza abitativa con cui le città contemporanee e, in particolare le città italiane, si confrontano. In una prospettiva più ampia, si evidenzia come l’housing sia diventato in Europa “difficile” e come le fasce più povere della popolazione rischiano di restare drammaticamente escluse dal diritto alla casa. Considerando l’housing nella sua dimensione processuale, l’attenzione si focalizza su due casi di studio in Italia che propongono un nuovo modo di vivere la città, in cui l’abitare sociale presenta standard elevati ma accessibili a tutti. Lo Sharing hotel residence di Torino e lo Zoia social housing di Milano coniugano l’housing ad altre misure espressioni di innovazione sociale, in un regime di sostenibilità e avanguardia edilizia. Si tratta di due esempi di interesse che includono categorie come la temporaneità, la flessibilità, l’integrazione delle misure. Il primo intervento risponde a una domanda abitativa temporanea da parte di nuclei fragili; il secondo mira alla costruzione di un quartiere liminale inglobato solo di recente nella trama urbana milanese. Gli obiettivi che, seppure in modo diverso, le due esperienze tentano di realizzare riguardano la qualità sociale, progettuale, architettonica e ambientale.This book chapter critically examines approaches and solutions developed by social housing to sustainably respond to the housing emergency plaguing contemporary cities and Italian cities in particular. In a broader perspective, we also investigate how housing has become "difficult" in Europe and the poorest segments of the population run the risk of having their right to housing dramatically denied. Analysing housing in terms of its procedural dimension, we focus on two Italian case studies that evoke a new way of inhabiting the city, cases in which high standards characterized social housing and yet remains accessible to all. The Sharing hotel residence in Turin and Zoia social housing in Milan combine housing with other socially innovative measures in a framework of sustainability and avant-garde construction. These are significant examples that speak to issues such as temporariness, flexibility and the coordination of measures. These two cases both pursued objectives having to do with social, planning, architectural and environmental quality, albeit each in their own way. There are by now numerous examples of social housing in Europe and these have recently attracted growing interest in Italy as well; in this country, however, such projects represent valid instances of experimentation but are not at all widespread

Il diritto ad una città giusta. Percorsi per uscire dalla crisi del valore

Roma sta soffrendo duramente le conseguenze economiche della pandemia: una tempesta perfetta sulla quale occorre intervenire. È però necessario andare oltre le congiunture per comprendere le ragioni strutturali di una crisi più che decennale le cui radici – storiche, economiche, politiche – sono ben precedenti, e le cui implicazioni più insidiose sono sociali e territoriali. Il contributo analizza il quadro della situazione e propone un’idea alternativa e radicale di economia urban

Synthesis and biological evaluation of new asymmetrical bisintercalators as potential antitumor drugs

The good results obtained in the past decade with various types of potential bisintercalating agents, e. g., LU 79553, DMP 840, BisBFI, MCI3335, WMC-26, BisAC, BisPA, and the asymmetrical derivative WMC-79 ( Chart 1), prompted us to investigate a new series of asymmetrical bisintercalators, compounds 1a-t ( Chart 2), which can combine the potentiality of bisintercalation with a possible different mechanism of action due to two diverse chromophores. The DNA-binding properties of these compounds have been examined using fluorometric techniques: target compounds are excellent DNA ligands, with a clear preference for binding to AT-rich duplexes. In vitro cytotoxicity of these derivatives toward human hormone-refractory prostate adenocarcinoma cell line (PC-3) is described. Apoptosis assays of four selected compounds are also reported. Very potent cytotoxic compounds, some of them capable of inducing early apoptosis, have been identified

Synthesis and antitumor evaluation of bis aza-anthracene-9,10-diones and bis aza-anthrapyrazole-6-ones

The good results obtained as potential antitumor drugs with aza-anthracenediones and aza-anthrapyrazoles, e.g. pixantrone, 1a, and 1b (Chart 1), prompted us to design and synthesize a series of symmetrical bis derivatives, compounds 7-10 (Chart 1). These compounds are dimers of different aza-anthracenedione and aza-anthrapyrazolone monomers connected by the linker found to be the most appropriate among potential bis intercalators synthesized by us. The DNA-binding properties of bis derivatives 7 and 8 have been examined using fluorometric techniques: these target compounds are excellent DNA ligands, with a clear binding site preference for AT-rich duplexes. In vitro cytotoxic activity of all target compounds 7-10 and of reference compound pixantrone toward human cancer adenocarcinoma cell line HT29 is also described. Two selected compounds have been investigated for their capacity of inducing early apoptosis

The protozoan toxin climacostol inhibits growth and induces apoptosis of human tumor cell lines

Climacostol (5-(Z)-non-2-enyl-benzene-1,3-diol) is a natural toxin isolated from the freshwater ciliated protozoan Climacostomum virens and belongs to the group of resorcinolic lipids,compounds that showantimicrobial, antiparasitic and antitumor activities.We investigated the cytotoxic activity of the chemically synthesized toxin on: (1) human tumor squamous carcinoma A431 cells, (2) human promyelocytic leukaemia HL60 cells, and (3) human non-tumor endothelial EA.hy926 cells. The results showed that climacostol effectively inhibited the growth of tumor cell lines in a dose-dependent manner by inducing programmed cell death, with non-tumor cells proving significantly more resistant to the toxin