102,412 research outputs found
Affinity of the anthracycline antitumor drugs Doxorubicin and Sabarubicin for human telomeric G-quadruplex structures
Combining various techniques in solution we proved that Doxorubicin, also called Adriamycin, and Sabarubicin, also known as MEN 10755, bind to the human telomeric sequence, 5'-d[GGG(TTAGGG)(3)]-3' (21-mer), assuming a G-quadruplex structure in the presence of K(+). Complexes of drugs with the 21-mer in 1 : 1 and 2 : 1 stoichiometry coexist in solution. Association constants were obtained from titration experiments and confirmed by isothermal titration calorimetry. The fluorescence of the drugs was quenched upon complexation. UV circular dichroism (CD) spectra of the complexes were characterized by the G-quadruplex signal and indicated that drug binding influences the equilibrium between quadruplex conformations. The visible CD spectra were exclusively due to the drug and show differences in the complexation modes of the two drugs. Spectroscopic and thermodynamic parameters of the 1 : 1 complexes point to drug stacking with the G-quadruplex top or bottom tetrad. Thermodynamic data suggests that the binding of the second drug molecule in the 2 : 1 complex may occur in a groove. Complexation caused a small increase in the thermal stability of the G-quadruplex main conformation, shifting T(m) from 62 to 67 °C
Delay-induced rebounds in CO2 emissions and critical time-scales to meet global warming targets
ISSN:2328-427
The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?
Human telomeric DNA with hundreds of repeats of the 5’-TTAGGG-3’ motif plays a crucial role in several biological processes. It folds into G-quadruplex (G4) structures and features a pocket at the interface of two contiguous G4 blocks. Up to now no structural NMR and crystallographic data are available for ligands interacting with contiguous G4s. Naphthalene diimide monomers and dyads were investigated as ligands of a dimeric G4 of human telomeric DNA comparing the results with those of the model monomeric G4. Time-resolved fluorescence, circular dichroism, isothermal titration calorimetry and molecular modeling were used to elucidate binding features. Ligand fluorescence lifetime and induced circular dichroism unveiled occupancy of the binding site at the interface. Thermodynamic parameters confirmed the hypothesis as they remarkably change for the dyad complexes of the monomeric and dimeric telomeric G4. The bi-functional ligand structure of the dyads is a fundamental requisite for binding at the G4 interface as only the dyads engage in complexes with 1 : 1 stoichiometry, lodging in the pocket at the interface and establishing multiple interactions with the DNA skeleton. In the absence of NMR and crystallographic data, our study affords important proofs of binding at the interface pocket and clues on the role played by the ligand structure
Media Relations in English Football Clubs
External corporate communications are regarded as a vital function for both the
everyday running and the long-term success of the sport industry in general and the
football industry in particular. However, the examination of media relations in
football, especially in regards to traditional media, appears to attract little research,
regardless of its great impact on corporate reputation and image management. This
study examines how media relations are managed, by investigating the current
practice in English Premier League clubs. The analysis of the practices employed in
the clubs underlines the disparity within them, which is further highlighted by the
various Communications and Media departments’ structures encountered. From
building formal relations between the clubs and traditional media, to developing
clubs’ own media to exclude traditional media from the communications process, or
even sustaining informal personal relations between clubs’ employees and members
of the media, this study illustrates the key media relations practices encountered
within English football clubs
Le bonifiche agrarie di Cà Corniani
Il contributo descrive la nascita del centro agricolo di Cà Corniani e ne individua i tratti salienti per poter proporre delle linee di recupero
Il Borgo Littorio di Candiana
Il contributo illustra la storia insediativa e la struttura del Borgo Littorio individuandone le linee guida per il recupero
Il riuso del patrimonio storico-industriale: strumenti, best practices e casebook
Il contributo offre una carrellata di best practices e casi studio relativi ai sistemi insediativi dedicati alla produzione ed al lavoro ed i paesaggi che li rappresentano al fine di individuare delle possibili soluzioni per questi particolari insediamenti che costituiscono un patrimonio imprescindibile nel paesaggio veneto. I casi analizzati sono riferiti ad azioni appropriate per la salvaguardia attiva, recupero e rigenerazione di tali sistemi. Azioni che non si esauriscono in una mera salvaguardia ma propongono linee guida per un ripristino ove possibile e comunque tali da conservarne e tramandarne la memoria
Valdagno, la Città Sociale ed altre istituzioni paternalistiche della Manifattura Marzotto
Il contributo analizza il sistema insediativo della Città Sociale connesso alla fabbrica tessile Marzotto, ne mette a fuoco la tipologia urbana e territoriale al fine di comprenderne e definirne le problematiche urbanistiche, le dinamiche di sviluppo ed il rapporto con il territorio cercando di individuare delle possibili vie per il recupero insediativo e la valorizzazione
La riforma agraria nel Delta padano: paesaggi agrari ed infrastrutturazione del territorio
Il contributo descrive come la riforma agraria nel Delta padano fosse riuscita a creare una struttura insediativa a livello territoriale, ne individua i tratti salienti, gli elementi che le hanno sancito il progressivo abbandono e propone alcune possibili linee di intervento volte al recupero degli insediamenti
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