112,701 research outputs found
Raw, not cropped supporting Western blot files for: Clijsters, L. ... Pagano, M. Cyclin F controls cell cycle transcriptional outputs by directing the degradation of the three activator E2Fs. Mol. Cell (2019)
No full textRaw, not cropped supporting Western blot files for: Clijsters L., Hoencamp C., Calis J., Marzio A, Handgraaf S., Cuitino M., Marzluff W., Rosenberg B., Leone G., and Pagano, M. Cyclin F controls cell cycle transcriptional outputs by directing the degradation of the three activator E2Fs. Mol. Cell (2019
Raw, not cropped supporting Western blot files for: Clijsters, L. ... Pagano, M. Cyclin F controls cell cycle transcriptional outputs by directing the degradation of the three activator E2Fs. Mol. Cell (2019)
No full textRaw, not cropped supporting Western blot files for:
Clijsters L., Hoencamp C., Calis J., Marzio A, Handgraaf S., Cuitino M., Marzluff W., Rosenberg B., Leone G., and Pagano, M.
Cyclin F controls cell cycle transcriptional outputs by directing the degradation of the three activator E2Fs.
Mol. Cell 74:1264-1277 (2019)
Presentazione del volume di M. Pagano, A. Tomeo, Capua. La seconda Roma (Napoli 2021).
No full textIntervento sul volume di M. Pagano e A. Tomeo, dal titolo "Capua. La seconda Roma" (Napoli 2021)
Pluralismo, dialogo e dimensione universale
No full textIl saggio discute i contributi e le tesi di Maurizio Pagano intorno ai temi indicati dal titolo
G-quadruplex-binding proteins and their functional relevance in human cancer cells
No full textBackground:
DNA can adopt a variety of different conformations based on particular sequence motifs and interactions with various proteins. Guanine-rich motifs can form non-canonical structures known as G-quadruplexes. The existence of such structures in vivo has been definitively proved by their direct visualization in human cells. G-quadruplex-forming sequences are located in strategic functional regions of the genome, such as telomeres and oncogene promoters, and play important roles in cancer biology.
Hypothesis:
There is compelling evidence that G-quadruplex DNA structures are strongly involved in tumorigenic processes, with regulatory functions in telomere maintenance and oncogene expression. Experimental evidences imply that an ensemble of interacting proteins modulates the formation of telomeric G-quadruplex DNA to achieve biological effects, as well as proteins are involved in the recognition of such structures in oncogene promoters to control their expression. However, most of G-quadruplex- interacting proteins, as well as their functional relevance remain elusive. The identification of those proteins is crucial to clarify the mechanisms in which G-quadruplexes are involved. These new knowledge may greatly push forward the research in this field.
Aims:
The biological functions of G-quadruplex DNA at the telomere, including its role in tumorigenic processes, are modulated by cellular factors such as proteins. Human telomeric G-quadruplexes display a large structural heterogeneity, that may influence the binding partners and, thus, have biological relevance. Therefore, the first principal aim of this project is the identification of proteins that recognize the telomeric G-quadruplex DNA in its different conformations, along with the assessment of the biological relevance of validated interactions. The second main aim is to discover the proteins that specifically bind the G- quadruplexes in selected oncogene promoters and to evaluate the functional relevance of the binding.
Experimental Design:
We have already demonstrated that the use of a chemoproteomic-driven approach represents a successful strategy for the identification of G-quadruplex-binding proteins. We also showed the effectiveness of the combined use of biophysical and biological experiments to validate the selected targets. This promising strategy will be applied to all the G-quadruplex folding topologies formed by human telomeric DNA and to selected oncogene promoter G-quadruplexes.
Expected Results:
The identification and characterization of the proteins that recognize the different G-quadruplex structures in human telomere will allow us to shed light, for the first time, on the biological relevance of the structural heterogeneity of telomeric DNA. The discovery of the binding partners of the investigated oncogene promoter G-quadruplexes, and of their role, will contribute to expand the knowledge on these DNA structures and to understand the mechanisms underlying regulation of oncogene expression.
Impact On Cancer:
The proposed project is likely to have significant impact on cancer research. Our studies will help to elucidate the role of G- quadruplexes in the control of telomere functions and oncogene expression in cancer cells. In addition to clarify the elusive biological mechanisms in which such non-canonical DNA structures are implicated, our findings will have considerable implications in the field of drug discovery. Indeed, we could exploit these protein-DNA interactions for therapeutic intervention aimed at the development of a new generation of anticancer drugs targeted at specific molecular events
Molecular mechanism of cannabinoids in cancer progression [*Pagano C. *Navarra G. co-first authors]
No full textCannabinoids are a family of heterogeneous compounds that mostly interact with receptors eliciting several physiological effects both in the central and peripheral nervous systems and in peripheral organs. They exert anticancer action by modulating signaling pathways involved in cancer progression; furthermore, the effects induced by their use depend on both the type of tumor and their action on the components of the endocannabinoid system. This review will explore the mechanism of action of the cannabinoids in signaling pathways involved in cancer prolifera-tion, neovascularisation, migration, invasion, metastasis, and tumor angiogenesis
A Cross-Cultural Experience in Tourism Studies
No full textThe present article is the result of a joint teaching experience carried out by Giovanni Ruggieri, lecturer of Tourism Economics at the University of Palermo, and Ninfa Pagano, lecturer of English language, University of Palermo; the experience was addressed to our students of Tourism Studies at the Department of Economics, University of Palermo.
The rationale at the basis of this teaching experience was to provide Italian students with extra language practice applied to more than one of their main fields of study in order to show how two different subjects, i.e. Tourism Economics and the English language, can be linked, thus working as a reinforcement for students in both areas.
Prof. Ruggieri suggested proposing to our students the reading of an article in English which focused on a comparative analysis of tourism in the Mediterranean islands; the article took into consideration aspects such as bed-place capacity and occupancy rates, strategies to develop sustainable tourism and tourism policies.
Students were asked to analyse it and parallelly to deepen the understanding of the English text through a series of language activities aiming to improve comprehension, lexis expansion and aspects of English syntax.
The objectives we set were thus twofold: improving our students’ knowledge about aspects concerning Tourism Economics while increasing their linguistic competence in English. Such cross-cultural experience has recently been introduced in Italian schools as well with the name of CLIL (Content and Language Integrated Learning). However, it had seldom been proposed at university level, so we carried it out on an experimental basis
Aptameri formanti G-quadruplex per la terapia delle malattie da prioni
No full textLe malattie da prioni, note anche come encefalopatie spongiformi trasmissibili (TSE), sono malattie neurodegenerative che colpiscono uomini e animali. Le TSE hanno suscitato grande interesse negli ultimi 25 anni a causa dell’ambigua natura dell'agente infettivo, eccezionalmente resistente, che ha generato timori di possibili epidemie. Sebbene non si siano verificati eventi catastrofici, l'attenzione per queste malattie è sempre molto elevata poiché non si è ancora in grado di bloccare o ritardare il loro esito fatale.
La patogenesi delle TSE è legata alla conversione della proteina prionica normale (PrPC), presente soprattutto nel cervello, in una forma patologica (PrPSc) che ha forte tendenza ad aggregare, causando un’ampia e progressiva degenerazione cerebrale.
Dato che la conversione di PrPC in PrPSc è un evento cruciale in tali malattie, la sua inibizione è un target ideale per una strategia terapeutica.
Con questo progetto proponiamo un approccio innovativo per realizzare un'efficace terapia anti-prione basata su aptameri in grado di legare specificamente PrPC, inibendone la conversione in PrPSc. Gli aptameri sono oligonucleotidi sintetici che legano il target con elevata affinità e specificità grazie alla loro peculiare forma tridimensionale.
Recentemente abbiamo dimostrato che alcuni oligonucleotidi formanti G-quadruplex hanno alta affinità e specificità per la PrPC in vitro e scarsa affinità per un oligomero di PrP mimico di PrPSc e che la loro struttura G-quadruplex è determinante per il riconoscimento della proteina (Nucleic Acids Res. 2013, 41:327). Inoltre, una di queste G-quadruplex ha mostrato attività anti-prione in cellule neuronali di topo infettate con agenti di TSE, il che suggerisce il loro potenziale uso nel trattamento delle malattie da prioni.
In tale ambito, il nostro progetto, frutto della stretta collaborazione del PI con il gruppo del dott. Human Rezaei (Proteins Macroassemblies and Prion diseases, INRA, Francia), mira alla scoperta di nuovi validi strumenti terapeutici contro le malattie da prioni.
I nostri sforzi si concentreranno essenzialmente su 3 Thrust:
T1. Progettazione e sintesi di oligonucleotidi ricchi in guanine aventi modifiche chimiche che assicurino proprietà farmacocinetiche e pre-organizzazione conformazionale tali da favorire il riconoscimento specifico della proteina.
T2. Caratterizzazione biofisica degli aptameri formanti G-quadruplex e selezione dei migliori ligandi della PrPC.
T3. Valutazione in vitro e in vivo dell'attività anti-prione degli aptameri selezionati.
I risultati di T2 e T3 saranno utili per progettare poi aptameri di seconda generazione, in un processo di ottimizzazioni successive.
Tale progetto è centrato su un argomento di estremo interesse che rappresenta un intricato enigma lungi dall'essere risolto. Siamo convinti che i nostri studi contribuiranno ad ampliare le attuali conoscenze sulle TSE e a fornire nuovi candidati farmaci contro tali devastanti malattie ancora non sconfitte
Benzo-fused nitroheterocycles via benzannulation with nitro-1,3-butadienes: synthesis and application.
No full textNitroindoles, despite their scanty occurrence in nature, are attractive reactive intermediates in organic synthesis thanks to the coupling of the properties of the nitro group and of the indole moiety.[1] While nitration of the pyrrole nucleus can be easily achieved, nitration on the benzene ring represents a more challenging target. Ex-novo construction of the pyrrole onto a functionalized benzene derivative is, by far, the synthetic strategy most frequently exploited to access indole nitrated on the benzene ring. Herein, we expand the synthetic access to such nitroindoles reporting an original protocol based on the ex-novo construction of the benzene ring onto pyrrole employing mono- or dinitro-1,3-butadienes as powerful C4 benzannulating agents. This appealing, metal-free process characterized by high atom economy and mild reaction conditions allows to synthesize nitroindoles characterized by patterns of substitution not easy to be obtained otherwise.[2] Such unusual substitution patterns have demonstrated to be promising for further elaborations, i.e. the application of the classic Cadogan reaction conditions in order to access pyrrolocarbazoles with a rarely reported ring fusion.[3]
A very interesting side project regarded the synthesis of a series of atropisomeric naphthyl nitroindoles with two stereogenic axes originated from steric hindrances forcing the naphthyl groups out of the indole plane; the asymmetry of the indole “spacer” makes both the syn and anti diastereoisomers entail an atropisomeric pair. A stereodynamic analysis of such new atropisomeric nitroindoles has been done resolving atropisomers by chiral HPLC and determining their absolute configuration and the rotational barriers of the indole–naphthyl axes.[4]
This work, within an Erasmus+ project, demonstrates also the photochemical activity of electron donor-acceptor (EDA) complexes providing a way to generate radicals under mild conditions. This strategy has recently found application in chemical synthesis. Reported methods classically relied on the formation of intermolecular EDA complexes. Herein, we further expand the synthetic utility of this strategy demonstrating that indole-tethered ynones form an intramolecular electron donor-acceptor complex that can undergo visible-light-induced charge transfer to promote thiyl radical generation from thiols.[5] This initiates a novel radical chain sequence, based on dearomatizing spirocyclization with concomitant C–S bond formation. Sulfur-containing spirocycles are formed in high yields using this simple and mild synthetic protocol, in which neither transition metal catalysts nor photocatalysts are required. The proposed mechanism is supported by various mechanistic studies, and the unusual radical initiation mode represents only the second report of the use of an intramolecular electron donor-acceptor complex in synthesis.
[1] G. W. Gribble, in Prog. Heterocycl. Chem., Vol. 31, Elsevier, 2020, pp. 83-117.
[2] A. Pagano, M. Mancinelli, L. Bianchi, G. Giorgi, M. Maccagno, G. Petrillo, C. Tavani, Tetrahedron 2019, 75, 4506-4515.
[3] A. Benzi, L. Bianchi, M. Maccagno, A. Pagano, G. Petrillo, C. Tavani, Molecules 2019, 24, 3802.
[4] A. Pagano, E. Marotta, A. Mazzanti, G. Petrillo, C. Tavani, M. Mancinelli, Synlett 2018, 29, 2161-2166.
[5] H. E. Ho, A. Pagano, J. A. Rossi-Ashton, J. R. Donald, R. G. Epton, M. J. James, P. O'Brien, R. J. K. Taylor, W. P. Unsworth., Chem. Sci. 2020, DOI: 10.1039/c9sc05311e
EU Cohesion-Policies and Metropolitan Areas
No full textAbstractThe European Union has allocated a considerable part of cohesion-policies funds to urban development, recognising urban areas as key-components for social and economic development. They represent at the same time the engine of economy and the social unrest - such as poverty, unemployment and exclusion - the environmental concerns - such as pollution, resource management, urban planning to the maximum extent. Hence there is the need of a sustainable, functional and flexible urban approach to the development, which can meet the different local needs, overcoming metric definitions to classify the manifold connotations of urban agglomerations, characterized by a close network of formal, informal, concrete and virtual relations extending beyond geographic and administrative boundaries to reach an easy territorial management according to the principle of a variable geometry. Only taking up the challenge of an integrated approach, in order to realize a smart sustainable and inclusive society, the European urban network can become a catalyst of innovation and creativity. The Metropolitan City plays a primary role in terms of attractiveness and allocation of resources for development. It can also be a suitable reference framework for the economic recovery with the aim of defining and address the development in relation to the typical features in order to make it competitive both at national and international level
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