2,173 research outputs found

    Il Flauto Magico, TEATRO REANDANO

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    Set design & light design: Luca Ruzza in collaboration with: Bruno Capezzuoli e Barbara Renzi. Costumes: Laura Colombo. Direction: Marco Bellussi. Orchestra direction: M. Maurizio Zappellon. Production: Teatro Rendano, Internationale Stiftung Mozarteum

    Pharmacological and neurobiological studies on Neuropeptide S and its receptor

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    Neuropeptide S (NPS) is the last neuropeptide identified via reverse pharmacology techniques. NPS selectively binds and activates a previously orphan GPCR, now named NPSR, producing intracellular Ca2+ mobilization and stimulation of cAMP levels. Biological functions modulated by the NPS/NPSR system include anxiety, arousal, locomotion, food intake, learning and memory, pain and drug addiction. In our laboratories we provided further evidence that NPS injected supraspinally in mice acts as a stimulatory anxiolytic. In fact, in the mouse righting reflex (RR) test, NPS (0.01- 1 nmol, i.c.v.) was able to reduce in a dose dependent manner the percent of animals losing the RR in response to diazepam (15mg/kg, i.p.) and their sleep time. Furthermore, NPS in the same range of doses caused a significant increase in locomotor activity (LA) in mice. These effects were associated with a clear anxiolytic-like action elicited by NPS in the mouse elevated plus maze (EPM) test, open field (OF) test and stress-induced hyperthermia (SIH) assay. Thus NPS evokes an unique pattern of behavioural effects: stimulation associated with anxiolysis. To deeply investigate the biological roles played by the NPS/NPSR system the development of pharmacological (i.e. selective NPSR ligands, particularly antagonists) and genetic (i.e. receptor knockout animals) tools are needed. In collaboration with the medicinal chemistry group of the University of Ferrara, we performed a series of classical structure-activity (SAR) studies on NPS sequence. Specifically, NPS positions 2, 3, 4 and 5 were investigated in details, since they were demonstrated to be crucial for NPS bioactivity. Studies focussed on NPS position 5 led to the identification and the in vitro and in vivo pharmacological characterization of the first generation of NPSR peptide antagonists. In vitro, in HEK293 cells stably expressing the mouse NPSR, [D-Cys(tBu)5]NPS up to 100 μM did not stimulate Ca2+ mobilization but was able to counteract in a competitive manner the stimulatory action of NPS (pA2: 6.44). In vivo, in the RR test, [D-Cys(tBu)5]NPS at 10 nmol was inactive per se but dose dependently antagonized the arousal-promoting action of NPS 0.1 nmol. [D-Val5]NPS acted in vitro as a pure NPSR antagonist, with a pKB of 6.54 in inhibition experiments. In vivo, in LA test, [D-Val5]NPS at 10 nmol completely blocked the stimulatory effect evoked by NPS. In a further medicinal chemistry study, the potent NPSR antagonist [tBu-D-Gly5]NPS was identified. In vitro, [tBu-D-Gly5]NPS did not stimulate calcium mobilization but blocked the stimulant action of NPS with a pKB of 7.06 7. In vivo, in RR assay, [tBu-D-Gly5]NPS (0.1-10 nmol, i.c.v.) was inactive per se but dose dependently antagonized the arousal-promoting action of NPS 0.1 nmol. Similarly in the LA assay [tBu-D-Gly5]NPS (0.1-10 nmol, i.c.v.) was inactive per se but was able to counteract the stimulatory effect evoked by 0.1 nmol NPS in a dose dependent manner. SHA 68 has been previously identified as the first non peptide NPSR antagonist. In our laboratories we further assessed the pharmacological profile of SHA 68 in vitro and in vivo. In vitro SHA 68 was inactive per se up to 10 μM while it antagonized NPSstimulated Ca2+ mobilization in a competitive manner showing a pA2 value of 8.06. In vivo, in the mouse RR assay, SHA68 50 mg/kg i.p. fully prevented the arousal promoting action of NPS 0.1 nmol. In LA experiments, SHA 68 50 mg/kg i.p. was able to partially counteract the stimulant effects elicited by NPS 0.1 nmol. Instead, the anxiolytic-like effects of NPS 0.1 nmol in mouse OF test were slightly reduced by SHA 68. Collectively these data demonstrated the exclusive involvement of NPSR in the arousal promoting and locomotor stimulant effects of NPS. Finally, we backcrossed on the CD-1 strain the NPSR knockout mice originally generated on the 129Sv/Ev genetic background. A first phenotype analysis revealed no locomotor differences between NPSR(+/+) and NPSR(-/-) mice, with the exception of rearing behaviour that was reduced in knockout animals. Furthermore, the behaviour of NPSR(+/+) and NPSR(-/-) mice in the EPM, OF and SIH tests is superimposable. Similarly no differences were detected in the novel object recognition, forced swimming, RR and formalin assays. However, the stimulant actions of 1 nmol NPS in RR and in LA test could be detected in NPSR(+/+) but not in NPSR(-/-) mice. Collectively these data demonstrated that endogenous NPS/NPSR system does not play a role in the control of locomotion, anxiety, depression and memory, at least under the present experimental conditions. These results demonstrated that the NPS stimulant effects are selectively due to NPSR activation, corroborating the findings obtained with NPSR antagonists. In conclusion, the research activity performed during the PhD program led to the identification of the first generation of NPSR peptide antagonists. The use of these research tools in parallel with knockout studies generated converging evidence on the biological effects induced by the selective activation of NPSR

    Renal dysfunction is a confounder for plasma natriuretic peptides in detectingheart dysfunction in uremic and idiopathic dilated cardiomyopathies.

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    Clin Chem. 2007 Dec;53(12):2097-104. Epub 2007 Oct 12. Renal dysfunction is a confounder for plasma natriuretic peptides in detecting heart dysfunction in uremic and idiopathic dilated cardiomyopathies. Codognotto M, Piccoli A, Zaninotto M, Mion M, Plebani M, Vertolli U, Tona F, Ruzza L, Barchita A, Boffa GM. Source Division of Nephrology, University Hospital, University of Padova, Italy. Abstract BACKGROUND: The diagnostic value of natriuretic peptides in uremic cardiomyopathy has not been defined, nor has the effect of a hemodialysis (HD) session on peptides. METHODS: We performed an observational study of 100 white adult outpatients in New York Heart Association class I-II, with neither diabetes nor ischemic heart disease, 50 of whom had idiopathic dilated cardiomyopathy (DCM) and 50 of whom had uremic cardiomyopathy and were undergoing HD. We measured plasma N-terminal proB-type natriuretic peptide (NT-proBNP), BNP, and atrial natriuretic peptide (ANP) both before and after a dialysis session. Doppler echocardiograms were evaluated. We performed multiple regression analysis on the logarithm of peptide concentrations using clinical, laboratory, and echocardio-Doppler data as explanatory variables. RESULTS: Mean peptide concentrations were higher in the HD group, with an HD:DCM ratio of 25 for NT-proBNP and 5 for BNP and ANP. Peptides were correlated with each other (r > 0.85). After HD, NT-proBNP significantly increased by 14%, BNP decreased by 17%, and ANP decreased by 56%. Predialysis concentrations correlated with postdialysis values (r > 0.85). A multiple regression equation significantly fitted the observed peptide concentrations, both pre- and postdialysis, using the same set of 4 variables: disease group (DCM or HD), diastolic pattern, left atrial volume, and body mass index. CONCLUSIONS: Renal dysfunction was a confounder for natriuretic peptides, which were present in higher concentrations in the uremic patients with milder cardiac dysfunction than in those with idiopathic DCM without renal dysfunction. Left diastolic function pattern and atrial volume were cardiac determinants of peptide concentrations in DCM and HD

    Storie degli spazi teatrali. Secondo volume.

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    Il secondo volume espone la storia degli spazi teatrali dai teatri d'oriente fino alle Feste e gli spazi teatrali della francia del XVII sec

    Storie degli spazi teatrali. Primo volume. Dai teatri dell'antichità al Rinascimento

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    Storia degli spazi teatrali dal teatro di Atene, i teatri nel Medioevo, la scena europea nel '500, la scena italiana e le feste teatrali nel '500. Il primo volume della collana Storie degli Spazi teatrali esplora il concetto di scenografia urbana come prospettiva progettuale per intervenire sugli spazi pubblici della città. Viene approfondito il concetto di “culturalizzazione dello spazio”, fornendo ampio spazio ad un’analisi del rapporto luogo-comunità-pratiche. Il volume intende fornire un’approccio integrato alle problematiche emergenti della città ed è volto a ripensare i contenuti dello spazio pubblico in stretto rapporto con il mondo sensibile degli abitanti. il rapporto tra arte e città, a partire dagli spazi delle origini nell'antica Grecia fino all’arte pubblica seicentesca. La città come sistema in continua evoluzione viene analizzata e rappresentata in maniera inedita dall’artista che cerca di rendere visibili contraddizioni, problematiche e risorse. Dalla rappresentazione della città, all’interazione con gruppi e comunità, la storia delle pratiche artistiche inferisce sempre più con i grandi processi di trasformazione del territorio contemporaneo, talvolta influenzandone processi e politiche

    Brezin-Gross-Witten tau function and isomonodromic deformations

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    The Brezin-Gross-Witten tau function is a tau function of the KdV hierarchy which arises in the weak coupling phase of the Brezin-Gross-Witten model. It falls within the family of generalized Kontsevich matrix integrals, and its algebro-geometric interpretation has been unveiled in recent works of Norbury. This tau function admits a natural extension, called generalized Brezin-Gross-Witten tau function. We prove that the latter is the isomonodromic tau function of a 2 × 2 isomonodromic system and consequently present a study of this tau function purely by means of this isomonodromic interpretation. Within this approach we derive effective formulae for the generating functions of the correlators in terms of simple generating series, the Virasoro constraints, and discuss the relation with the Painlevé XXXIV hierarchy

    Numerical studies to detect chaotic motion in the full planar averaged three-body problem

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    In this paper, the author deals with a well-known problem of Celestial Mechanics, namely the three-body problem. A numerical analysis has been done in order to prove existence of chaotic motions of the full-averaged problem in particular configurations. Full because all the three bodies have non-negligible masses and averaged because the Hamiltonian describing the system has been averaged with respect to a fast angle. A reduction of degrees of freedom and of the phase-space is performed in order to apply the notion of covering relations and symbolic dynamics

    A New Analysis of the Three-Body Problem

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    In the recent papers [5, 18], respectively, the existence of motions where the perihelions afford periodic oscillations about certain equilibria and the onset of a topological horseshoe have been proved. Such results have been obtained using, as neighbouring integrable system, the so-called two-centre (or Euler) problem and a suitable canonical setting proposed in [16, 17]. Here we review such results.</p

    Preface

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    This volume contains the detailed text of the major lectures delivered during the I-CELMECH Training School 2020 held in Milan, whose aim was to present a contemporary review of recent results in the field of Celestial Mechanics, with special emphasis on theoretical aspects. In fact, the modern developments of Celestial Mechanics have their roots in the mathematics of Hamiltonian perturbation theory and of the dynamical system
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