2176 research outputs found
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Politiche pubbliche per l'irrigazione nel Mezzogiorno tra '800 e '900
No full textPolitiche legislative italiane, dall'Unità al Fascismo, in materia di irrigazion
Caratterizzazione funzionale della proteina SHOC2 e della sua forma miristilata implicata nella sindrome di Mazzanti
No full textCPTH6,an histone acetyltransferase, shows anti-tumor properties
No full textRecent studies strongly support the histone acetylation as a promising therapeutic target. Although a growing body of evidence demonstrates a direct relationship between histone acetyltransferases (HAT) activity and development or progression of cancer disease, only limited progress has been made in the field of HAT inhibitors. This study identifies the thiazole derivative 3-methyl-cyclopentylidene-[4-(4’-chlorophenyl)thiazol-2yl)hydrazone (CPTH6) as a novel HAT inhibitor in a panel of solid and hematologic tumor cell lines. CPTH6 leads to an inhibition of Gcn5 and pCAF HAT activity. Moreover, it inhibits H3/H4 histones and α-tubulin acetylation of acute myeloid leukemia cell (AML) line U-937. Concentration- and time-dependent inhibition of cell viability, paralleled by accumulation of cells in the G0/G1 phase and depletion from the S/G2M phases, was observed. The role of mitochondrial pathway on CPTH6-induced apoptosis was shown, being a decrease of mitochondrial membrane potential and the release of cytochrome c, from mitochondria to cytosol, induced by CPTH6. Also the involvement of Bcl-2 and Bcl-xL on CPTH6-induced apoptosis was found after over-expression of the two proteins in leukemia cells. Solid tumor cell lines from several origins were shown to be differently sensitive to CPTH6 treatment in terms of cell viability and a correlation between the inhibitory efficacy on H3/H4 histones acetylation and cytotoxicity was found. Differentiating effect on leukemia and neuroblastoma cell lines was also induced by CPTH6. Moreover, CPTH6 treatment induced, in a dose-dependent manner, a significant increase of the membrane-bound form of microtubule-associated protein 1 light chain 3 (LC3B-II) levels and the appearance of typical LC3B-II-associated autophagosomal puncta. We found that the effect of CPTH6 on autophagy developed through a non-canonical mechanism that did not require beclin-1-dependent nucleation, but involved Atg-7-mediated elongation of autophagosomal membranes. Strikingly, a combined treatment of CPTH6 with late-stage autophagy inhibitors, such as chloroquine and bafilomycin A1, demonstrates that under basal condition CPTH6 reduces autophagosome turnover through an impairment of their degradation pathway. According to these results, CPTH6 induced enhancement of autophagy substrate p62 and NBR1 protein levels confirms a blockage of autophagic cargo degradation. In addition, CPTH6 inhibited autophagosome maturation and compounds having high structural similarities with CPTH6 produced similar effects on the autophagic pathway. Finally, the evidence that CPTH6 treatment decreased α-tubulin acetylation and failed to increase autophagic markers in cells in which acetyltransferase ATAT1 expression was silenced indicates a possible role of α-tubulin acetylation in CPTH6-induced alteration in autophagy. Overall, CPTH6 could be a valuable agent for the treatment of cancer and should be further studied as a possible antineoplastic agent
Studio del ruolo dei polimorfismi a singolo nucleotide rs12979860 e rs8099917 dell’IL28B in una coorte di pazienti italiani con infezione cronica da virus dell’epatite C sottoposti a terapia interferonica
No full text"La costruzione dell''infermiera moderna. Genere, biopolitica, immaginario nel primo trentennio del Novecento'"
No full textQuesta ricerca ricostruisce il contrastato processo di costruzione dell'assistenza infermieristica come una "professione femminile" nel primo trentennio del novecento. La figura dell'"infermiera moderna" è paradigmatica delle trasformazioni che in quel periodo hanno attraversato le biopolitiche di gestione dei corpi, della popolazione e della salute pubblica
Application of Medicinal Chemistry Methods on Different Classes of Drugs
No full textThe present doctoral thesis is the result of the work carried out during the three
years of my PhD scholarship at the Rome Center for Molecular Design laboratory
(RCMD, Department of Chemistry and Drug Technologies, Sapienza University of
Rome), under the supervision of Prof. Rino Ragno. The research activity was
focused mainly on the design, optimization and application of computational
strategies to derive quantitative structure-activity relationships (QSAR, 3-D
QSAR, and COMBINE) on different molecular classes of current interest, such as:
opioid receptor antagonists (OPAs), Hepatitis C Virus NS5B-Polymerase
Inhibitors (NS5B-NNIs), Hystone Deacetylase Inhibitors (HDACIs), Anti-
tubercular agents, vascular endothelial growth factor receptor-2 (VEGFR-2)
inhibitors, HSP90 inhibitors, HIV-1 reverse transcriptase inhibitors (NNRTIs),
Bovine Serum Amine Oxidase (BSAO) substrates, etc... Moreover two research
periods abroad were performed: the first framed in a LLP Erasmus program
collaboration, was conducted for six months at the Laboratoire d'Ingénierie et
Moléculaire Pharmacologique Biochimie (LIMBP) of the Université de Lorraine
Metz (France), directed by Prof. Gilbert Kirsch, and characterized by the
application of organic synthesis to obtain new thienopyrimidinone derivatives as
potential inhibitors of vascular endothelial growth factor receptor-2 (VEGFR-2);
the second took place, for three months, at the Department of Biochemistry and
Molecular Biophysics in Washington University School of Medicine in Saint Louis
(MO, USA), under the supervision of Prof. Garland R. Marshall, investigating the
activity profile of new Histone Deacetylases (HDACs) inhibitors by the application
of the Mobility Shift Assay Technology. Main purpose of this doctoral thesis is to highlight the activities carried out in the different research projects, the applied methodologies and the obtained results. The text starts describing those studies whose results were published in scientific journals (chapters I-VI): the author decided to omit some procedural details, completely reported in the published papers, that would make the text too long, tedious and redundant; therefore readers who want to delve these aspects can also refer to Chapter XII in which is possible to read the original papers; on the contrary for studies that have not yet been published, as those characterizing the Chapters VII and VIII, discussion is adequately detailed. Chapters IX and X report the scientific activities carried out in France and in USA respectively; Chapter XI summarizes all the scientific activities accomplished during the entire PhD course, whereas Chapter XII, as mentioned, contains the published articles."Progetti per Avvio alla Ricerca" prot. C26N12JZC
Con gli occhi dell'Occidente. L'immagine politica e politologica delle nuove democrazie. Il caso ucraino
No full textRational Points on Modular Curves
No full textI explain a way to compute Fourier coefficients of modular forms associated to normalizer of non-split Cartan subgroups of GL(2,Z/pZ) and how, using these coefficients, one can compute explicit equations of modular curves associated to same subgroup. I attached some tables containing some examples of results of this method
Service Continuity in Complex Power Systems: Safety, Operation and Maintenance
No full textThe research aims to define electrical architectures based on the rationalization of the distribution structure and of power sources with the achievement of the primary objectives of service continuity, power quality, safety and safe maintenance.
The thesis consists of two parts: the first part deals with the architecture impact on a complex system analyzing the system configuration and operational safety aspects. New developments and methodologies are presented in the study of critical systems. A theory of complex systems for safety, operation and maintenance aspects is defined that enables to assist the management of the system throughout its whole life cycle and allows an implementation of programming languages.
The second part refers to specific issues of mission critical power systems, data centers and hospitals especially. Several measurements were performed in laboratory and on field to analyze sneaky critical cases for the service continuity and the integrity of these strategic power systems
Procedimento legislativo e forma di governo nell'esperienza costituzionale italiana
No full textLa tesi indaga le relazioni intercorrenti tra il procedimento legislativo ordinario e i concreti assetti della forma di governo italiana. Lo studio parte dal concetto di teoria generale di 'procedimento' per poi soffermarsi sulle peculiarità strutturali di quello legislativo, analizzandone la genesi in assemblea costituente e l'evoluzione sul piano regolamentare. Ci si interroga, infine, sul procedimento quale strumento per misurare le prestazioni democratiche della forma di governo italiana nell'ambito della forma di Stato costituzionale democratica