188,308 research outputs found
Pharmacological and neurobiological studies on Neuropeptide S and its receptor
No full textNeuropeptide 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
Di Ruzza Renato, Halevi Joseph, De l'économie politique à l'ergologie. Lettre aux amis, Paris, L'Harmattan, 2003
No full textDi Ruzza Renato, Halevi Joseph, De l'économie politique à l'ergologie. Lettre aux amis, Paris, L'Harmattan, 2003. In: Formation Emploi. N.84, 2003. p. 104
Di Ruzza Renato, Halevi Joseph, De l'économie politique à l'ergologie. Lettre aux amis, Paris, L'Harmattan, 2003
No full textDi Ruzza Renato, Halevi Joseph, De l'économie politique à l'ergologie. Lettre aux amis, Paris, L'Harmattan, 2003. In: Formation Emploi. N.84, 2003. p. 104
Di Ruzza (F.) et Gerbier (В.). — Ski en crise, essai sur l'économie du sport.
No full textGuérin Jean-Paul. Di Ruzza (F.) et Gerbier (В.). — Ski en crise, essai sur l'économie du sport.. In: Revue de géographie alpine, tome 66, n°3, 1978. pp. 357-358
Performance Assessment of Water Distribution Systems Subject to Leakage and Temporal Variability of Water Demand
No full textA water distribution system (WDS) is designed and managed to provide a reliable water supply, that is, to properly respond towater user demand, particularly in critical operating conditions such as in times of peak demand. Therefore, the assessment of the influence ofwater demand characteristics is an essential requirement in the context of WDS reliability. In this paper the impact of the pattern of hourlydemand on WDS performance is analyzed for a system subject to aging processes and temporary pipe unavailability and affected by waterlosses with different leakage levels. The hydraulic deficit that can occur when the pressure falls below the minimum service value is used as aperformance index, and its relevance is analyzed without and with preventive maintenance. The case of the synthetic Anytown network isanalyzed, but the procedure has general validity and can be applied to any real WDS. Defined in a prescribed temporal horizon the pipereplacement prioritization without preventive maintenance, the effects of pipe substitutions are analysed as a function of different schedulingtimes to quantify the reduction of the hydraulic deficit. The results show the capability of the proposed approach to define a pipe replacementprioritization and the related scheduling time, in view of the relevance that these aspects could have in any economic analysis developed todefine a proper maintenance strategy
Molecular and Functional Characterization of Human SW 872 Adipocytes as a Model System for Testing Nutraceutical Products
No full textBackground: The availability of characterized human adipocyte cell models for in vitro studies is currently limited. They may be useful to better understand the role of dysfunctional adipocytes in the pathophysiology of cardio-metabolic diseases and to evaluate the metabolic effects of nutraceutical compounds. In this study, human liposarcoma SW 872 cells, both non-differentiated and differentiated for 7 days with 100 mM oleic acid, have been used as the model system to (1) characterize these cells, concerning metabolic, pro-inflammatory, and morphologic features, and (2) begin to evaluate the “healthy” effects of some plant-derived nutraceutical compounds. Methods: In SW 872 cells, we evaluated the accumulation of triglycerides, glucose uptake, pro-inflammatory cytokine release, and the modulation of Akt protein phosphorylation (pAkt), highlighting the differences between differentiated and non-differentiated cells. Results: Oleic-acid-differentiated SW 872 cells have a higher triglyceride content (p < 0.001) than non-differentiated cells, as well as a lower glucose uptake (p < 0.001), but a higher insulin response (p < 0.05) and a specific activation of the Akt pathway. This cell model has thus been chosen for the preliminary evaluation of the effects of some phytochemical complexes on the modulation of these molecular parameters, observing, in some instances, promising effects on the reduction in triglyceride content and pro-inflammatory cytokine release, as well as on increased glucose uptake. Conclusions: Our study suggests that the SW 872 cell model could be useful for studies regarding human adipocyte function and dysfunction, as well as studies on the effects of bioactive compounds on dysfunctional adipose tissue, which will be addressed in future research
Scienziati e artisti sotto la stessa tenda di un circo mutante
No full textOgni punto è un punto d'incontro. Ogni filo è un percorso di vita e di ricerca, che dall'interiorità dell'anima si dipana e si interseca con altri fili di luce tessendo la trama dell'esistenza. Il senso di questo tessere e intrecciarsi di fili, che crea forme e colori in modo apparentemente casuale, spesso rimane oscuro. Eppure tutte le volte ci sorprende, perché inaspettata e misteriosa è la creazione in ogni sua diversa manifestazione. "Trame di meraviglia. Studi in onore di Silvia Carandini", prodotto in un crogiolo alchemico per mescolanza e amalgama di discipline e di esperienze diverse, è un libro che nasce per essere un dono a una persona speciale.Each point is a meeting point. Each thread is a path of life and research, which from the interior of the soul descends and intersects with other waves of light weaving the plot of existence. The sense of this weave and threading of threads, which creates shapes and colors seemingly casual, often remains obscure. And yet every now and then we are surprised, because unexpected and mysterious is the creation in every different manifestation. Silvia Carandini's "Stunning Textures", produced in an alchemical crucible for mixing and amalgamation of different disciplines and experiences, is a book that is born to be a gift to a special person
Linear and cyclic peptides as substrates for lyn tyrosine kinase
No full textTwo Tyr residues are supposed to play a crucial role in the regulation of protein tyrosine kinases of the Src family. Autophosphorylation of Src Tyr416 correlates with enzyme activation, while phosphorylation of C-terminal Tyr527 by Csk gives rise to inactive forms of Src kinases. It has previously been demonstrated that the Src-like tyrosine kinase expressed by the oncogene lyn displays a particularly high affinity (Km20 μm) toward the dimeric linear and cyclic derivatives of the heptapeptide H-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-OH which reproduces the main autophosphorylation site of most of the Src enzymes. Under the experimental conditions used only one Tyr residue of the dimeric sequence can be phosphorylated [P. Ruzza, A. Calderan, B. Filippi, B. Blondi, A. Donella Deana, L. Cesaro, L. A. Pinna & G. Borin (1995) Int. J. Peptide Protein Res. 45, 529-539]. The present study addresses the problem of the efficiency displayed by Lyn towards the two Tyr residues located at positions 5 and 12 of the dimeric peptide. To this purpose, two tetradecapeptides were synthesized by the classical solution method, each containing one of the two Tyr residues alternatively replaced by Phe, and the corresponding univocal cyclic form. A possible correlation between the different structural properties induced by the modifications of the native sequence and the ability of the peptides to act as Lyn substrates was noted. The kinetic data obtained indicate that Lyn phosphorylates the residues located at different positions in the two linear analogues differently. In particular, while the Tyr5, Phe12 derivative presents a Kmvalue similar to those obtained for the dimeric linear and cyclic unmodified analogues, the Kmvalue of the Phe5, Tyr12 derivative is two-fold higher than those found for the above-mentioned peptides. Moreover, as previously reported for the linear and cyclic dimeric forms of the native sequence, in the mono-tyrosine containing series of dimers the still conformationally flexible cyclic derivative shows a phosphorylation efficiency two-fold higher than those found for the linear derivatives. © 1998 European Peptide Society and John Wiley & Sons, Ltd
A New Analysis of the Three-Body Problem
No full textIn 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
Losses Identification in Uncalibrated Water Distribution Networks: A Case Study
No full textIn a real water distribution network, district metering for the identification of losses cannot always be successfully applied due to the limited number of discharge measurements or poor district identification. In such cases network models should be a valuable aid, but uncertainties on the demand distribution and on the pipe roughness, as well as the unknown location of losses, thwart their calibration. This study suggests and applies in a real case a procedure based on data assimilation techniques (Kalman-filter based) to identify the spatial distribution of leaks and to calibrate, at the same time, the pipe roughness
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