5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme

5-hydroxymethylcytosine is a new epigenetic modification deriving from the oxidation of 5-methylcytosine by the TET hydroxylase enzymes. DNA hydroxymethylation drives DNA demethylation events and is involved in the control of gene expression. Deregulation of TET enzymes causes developmental defects and is associated with pathological conditions such as cancer. Little information thus far is available on the regulation of TET activity by post-translational modifications. Here we show that TET1 protein is able to interact with PARP-1/ARTD1 enzyme and is target of both noncovalent and covalent PARylation. In particular, we have demonstrated that the noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP-1/ARTD1 independently of DNA breaks. Collectively, our results highlight a complex interplay between PARylation and TET1 which may be helpful in coordinating the multiple biological roles played by 5-hydroxymethylcytosine and TET proteins

Outdoor education as a way of life

The lockdown, resulting from the pandemic, has clearly highlighted the need to rethink and relocate the human dimension; mutability and complexity make our reference systems precarious, making certainties now acquired waver. Education emerges in the front line with its contradictions and urgencies. It is necessary to think of school as an educational community capable of mediating and activating educational and training strategies that allows one to breathe, and have an encounter between the nerve centres of post-modernity, where awareness and re-appropriation of one's own identity emerge through forms of creativity. School, as a physical place leaves room for new territories of conquest where education in the open air appears to be the anchor of salvation. From the analysis of the most recent studies it is clear what the benefits of outdoor education are: physical, cognitive and socio-affective. An outdoor education experience can stimulate a more holistic educational process: the aim of this analysisis to show the evidence of this opinion and observe the development of empathic and socio-relational skills to cope with a new humanism. In fact, outdoor education is experiential education that refers to learning by doing and allows the practice of a specific case related to a real problem in order to enhance motivation, divergent thinking and the personal handling of the proposed cognitive problem. We do not want to present the outdoors as a temporary alternative, aimed at solving problems, but as a practice, a physical and metaphysical space to live in, a mental habit. Outdoor education should become a lifestyle, a mental form that allows us to be inside creative spaces and outside of often pre-established and stereotyped network

Profili, competenze, percezioni delle professioni dell'area politico-sociale dal punto di vista dei datori di lavoro

Il saggio riferisce i risultati di una ricerca condotta dalle autrici fra il 2015 e il 2016 all'interno di un gruppo di lavoro del Prin 2010/2011 "Le professioni dello spazio pubblico oltre la crisi". Nello specifico, il campo di azione dell'indagine qui narrata è circoscritto al match tra le organizzazioni produttive e i laureati di tre settori disciplinari delle scienze sociali emblematici delle professioni dello spazio pubblico: Scienze Politiche, Sociologia, Comunicazione. Il punto di vista indagato è quello dei potenziali stakeholder di queste lauree, dirigenti e manager di imprese, enti pubblici e organizzazioni non profit. Il corpus empirico è costituito da una ventina di interviste realizzate per l'occasione ad testimoni privilegiati di enti nazionali e internazionali

L'immagine della fede sul piccolo schermo. Le rubriche religiose televisive

L’impatto, i legami e l’influenza della cultura cattolica sulle trasmissioni televisive sono un ambito da tempo studiato e ampiamente documentato. Tuttavia come effettivamente siano costruite, program­mate e coordinate le singole trasmissioni religiose della televisione pubblica italiana è un argomento ancora in gran parte sconosciuto. Questo saggio vuole analizzare le trasmissioni religiose della televisio­ne italiana fino al 1970, ponendo attenzione non tanto ai contenuti quanto alla complessa storia media­le in cui si trovano inserite e alla forte consapevolezza che rivelano delle caratteristiche del linguaggio audiovisivo, della forza dell'immagine televisiva e della cultura visuale in cui si trova inserita. The impact, ties and influence of the Catholic culture on the Italian television is widely documented and has been the subject of a vast scholarship. However, no specific attention has been paid so far on how religious programs were actually conceived, programmed and coordinated. Rather than focusing on the contents, this essay aims to analyze the complex media history embedded in the religious shows broadcasted by RAI until 1970. As such, the article highlights how these productions demonstrate high-skilled notions of audio-visual language as well as their awareness of the power of television images and visual culture

Role of Integrase Acetylation in HIV-1 Replication Cycle and Search for Acetylation Inhibitors

HIV-1 integrase catalyzes the integration of the viral DNA into the genome of the host cells. This irreversible event is crucial to the pathogenesis of the infection and complicates its eradication both by the immune systems and by pharmacological treatments. The mode of action of this viral enzyme is still not completely characterized, although full understanding of some key aspects, as the mechanism of integration site selection, are relevant both for the development of new anti-integrase drugs and for potential application of HIV-derived vectors for gene therapy. Our group has demonstrated that integrase is post-translationally acetylated by two cellular histone-acetyl transferases (HATs), chromatin-modifying enzymes whose major role is that of transcriptional co-activators. Integrase acetylation is important for the viral infectivity and interaction with HATs might be one of the determinants of HIV-1 preferential integration in actively transcribed genomic regions. Integrase is a poorly exploited target of anti-HIV drugs, while traditional therapies based on combinations of reverse transcriptase inhibitors and protease inhibitors are facing the rapid diffusion of multi-drugs resistant viral variants. This pushes research towards new drugs and new targets, including integrase and, even better, its interactions with cellular cofactors like, for instance, HATs. This thesis deals with the selection of novel inhibitors of integrase acetylation, to be used as lead compound for the development of new generation anti-integrase drugs. A selective inhibitor of integrase acetylation was identifyied through in vitro screening of a library of synthetic compounds, designed based on the structures of natural HAT inhibitors. Structure-Activity-Relationships (SAR) studies led to the rational design of a smaller set of compounds, whose activity was tested with in vitro and in vivo assays. Finally, one molecule was chosen for further studies with HIV-1 derived lentiviral vectors. This cinnamoil compound was able to inhibit integrase acetylation in the virus and reduced viral integration in infected cells. In a reciprocal experiment, viral vectors containing hyper-acetylated integrase were generated by trans-incorporation of fusion integrase-HAT proteins, or of isolated HAT domains. The enhanced infectivity of these virions confirmed the role of acetylation for integrase function