Site directed mutagenesis as a tool to understand the catalytic mechanism of human cytidine deaminase.

Cytidine deaminase (CDA), is one of the enzymes involved in the pyrimidine salvage pathways, which catalyzes the formation of uridine and deoxyuridine by the hydrolytic deamination of cytidine and deoxycytidine, respectively. Human CDA is a tetrameric enzyme of identical 15 kDa subunits, each containing an essential zinc atom in the active site. The substrate binds to each active site independently and the cooperativity between subunits has not been reported. CDA is able to recognize as substrates some antitumor and antiviral cytidine analogs rendering them pharmacologically inactive. In light of the role played by this enzyme, a deep knowledge of CDA active site and mechanism of catalysis is required. Site-directed mutagenesis, associated with molecular modeling studies, may be an important tool to discover the active site structure of an enzyme and consequently its mechanism of action. In this review are summarized the site-directed mutagenesis experiments performed on human CDA: through these studies it was possible to understand the role exerted by specific amino acid residues in CDA active site and in the contacts between subunits. The obtained results may open a way for designing new cytidine based drugs or more potent CDA inhibitors

PROTO-SPHERA: a magnetic confinement experiment which emulates the jet + torus astrophysical plasmas

The PROTO-SPHERA experiment, built at the CR-ENEA laboratory in Frascati, was in part inspired by the jet + torus astrophysical plasmas, a rather common morphology in Astrophysics. This paper illustrates how the said plasma morphology can be reproduced in a laboratory with the setup of the PROTO-SPHERA experiment. The experiment as such displayed the appearance and sustainment of a plasma torus around an internal magnetized plasma centerpost (jet) by self-organisation; an entirely unexplored phenomenon to date. The remarkable ideal MHD stability of the PROTO-SPHERA plasma is extremely significant, as it is obtained in a simply connected geometry, inside a perfectly insulating vacuum vessel, and without the need of a nearby stabilizing conducting shell. The concluding sections of this paper deal with application of force-free fields to the Pulsar Wind Nebulae morphology and present an extension of the well-known split-dipole model. Such an extension provides a natural description of the presence of tori around the Pulsar plasma jets. In addition, similarities and differences between the laboratory and the astrophysical jet + torus plasmas are detailed

La libertà religiosa nelle strutture carcerarie: normativa e prassi della Regione Marche.

La presente ricerca muove da una preliminare disamina dei profili generali della libertà religiosa volta a delineare i rapporti tra lo Stato italiano e le singole confessioni religiose, anche alla luce degli orientamenti maturati nel tempo dalla giurisprudenza della Corte Costituzionale, per poi affrontare il tema centrale che è quello della libertà religiosa negli istituti di prevenzione e pena.\ud Il legislatore al riguardo ha risentito dell'orientamento politico dominante che, nel tempo, ha riconosciuto una particolare tutela alla religione cattolica per poi aprirsi anche alle altre confessioni religiose.\ud Tale percorso non si è ancora completato anche perché non è ancora stato chiarito l'approccio sistemico: Legge sulla libertà religiosa o intese volte a regolare di volta in volta i rapporti con le singole confessioni religiose? \ud Allo stato attuale il dettato costituzionale - che garantisce uguale parità di trattamento a tutte le confessioni religiose nella assistenza ai detenuti – non sembra ancora completamente attuato. La figura del Cappellano carcerario è infatti istituzionalizzata e soltanto con il nuovo ordinamento penitenziario, egli è stato affrancato da compiti che poco o nulla hanno a che vedere con la pastorale carceraria come, ad esempio, la presenza nel consiglio di disciplina.\ud Le ragioni che in passato potevano essere ricondotte ad un maggior radicamento della religione cattolica nel contesto sociale italiano, e quindi anche in quello carcerario, oggi non sono più valide anche per la significativa presenza di detenuti stranieri che praticano religioni diverse dalla cattolica.\ud La piena attuazione del principio di libertà religiosa appare ancor più necessaria nelle strutture carcerarie che - privando i detenuti della libertà religiosa - impongono una convivenza forzata.\ud Ulteriore profilo di ricerca è riferito alla libertà religiosa alla luce della normativa in tema di misure alternative alla detenzione. Infatti mentre all'interno del carcere, comunque è compito dell'amministrazione dare risposte alla domanda di assistenza religiosa, non altrettanto può dirsi quando la detenzione è domiciliare. In questo ambito ci si trova in un cono d'ombra che, in assenza di una normativa di riferimento, viene affrontato e risolto non decisioni non sempre uniformi dalla competente magistratura.\ud La normativa e la prassi seguita nella Regione Marche sono in linea con l'orientamento nazionale. L'analisi riferita ai relativi istituti di prevenzione e pena ha evidenziato una disponibilità ed attenzione verso il problema che tuttavia per essere risolto necessiterebbe di un diverso approccio. Non dovrebbe essere, infatti, il singolo detenuto a richiedere assistenza religiosa diversa dalla cattolica, ma l'amministrazione dovrebbe offrire tale servizio tanto più se si pensa alla condizione di soggezione in cui versano i detenuti; in altri termini da semplice disponibilità passiva a prestare attenzione alle esigenze delle persone recluse in tema di libertà religiosa si dovrebbe passare alla completa attuazione di tutti quegli strumenti ed opportunità tali da garantire un effettivo godimento della libertà religiosa.\ud E' auspicabile quindi un percorso volto a favorire una sostanziale parità di trattamento tra confessioni religiose negli istituti di prevenzione e pena, che sappia effettivamente garantire la laicità dello Stato garantendo in tal modo la piena applicazione di un principio espressamente previsto dalla Costituzione repubblicana che ancora oggi non appare completamente attuato

1-D Modeling of the Screw-Pinch Plasma in PROTO-SPHERA

A simple steady-state model for a 3-species mixture (ions, electrons, and neutrals) in a screw-pinch plasma configuration is developed. The model is applied to the central plasma column of the PROTO-SPHERA experiment. Degree of ionization, azimuthal current density, and azimuthal ion velocity are calculated. Full ionization is found at plasma temperatures above 1.5 eV, with neutrals confined in an outer shell where radial plasma flow develops and drives both azimuthal current and azimuthal flow

Analytical calculation of boozer magnetic coodinates for axysimmetric MHD equilibria

Associazione EURATOM-ENEA- sulla FusioneConsiglio Nazionale delle Ricerche (CNR). Biblioteca Centrale / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

The effects of low voltage electrical stimulation on donkey meat

The effects of early post-mortem low voltage electrical stimulation (28 V, 60 Hz) on biochemical changes and on final tenderness in Longissimus Thoracis et Lumborum (LTL) muscle from donkey carcasses was studied. ES significantly accelerated the glycolytic process only during the first hours post-mortem, with a faster pH fall at 1, 3 and 6 h post-mortem, and a reduction in ATP content at 3 and 6 h post-mortem. The activities of μ-calpain and calpastatin were reduced (P < 0.05) by the treatment in the first 6 h post-mortem. Tenderness was improved (P < 0.05) at 4 and 7 days post-mortem by the application of ES. Muscle colour (L*) was lighter (P < 0.05) in stimulated carcasses

Ideal MHD stability calculations in presence of magnetic separatrices

12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France)The use of magnetic coordinates, in which field lines are straight, defines the simplest approach to the numerical study of the ideal MHD stability of magnetoplasma equilibria: it allows the use of 1-dimensional radial Finite Elements, while adopting a Fourier decomposition in the poloidal angle. However the magnetic coordinates become singular in presence of magnetic separatrices. This difficulty becomes particularly relevant in the stability analysis of a simply connected axisymmetric plasmas (Flux-Core-Spheromak or Chandrasekhar-Kendall-Furth configurations), which embed a magnetic separatrix with regular X-points (B!=0) and are bounded by an edge magnetic separatrix that includes a part of the symmetry axis (R=0) and is limited by two singular X-points (B=0). The approach taken in the present paper is that of maintaining the 1-dimensional radial Finite Elements, while using an asymptotic analysis of the perturbed plasma displacement near the separatrices. The permissible asymptotic limits for the perturbed displacement are derived: they have simple analytical expressions in Boozer magnetic coordinates. An intensified numerical radial mesh following Boozer magnetic coordinates is set up near the magnetic separatrices; it requires: a logarithmic fit to the rotational transform near the embedded magnetic separatrix; a minimum distance between the radial mesh and both separatrices; finally an extended spectrum of poloidal mode numbers in the Boozer angle. The numerical results are compared "a posteriori" with the permissible asymptotic limits for the perturbed displacement. The radial displacement variable (radial contravariant component of the perturbed displacement) is found to be always near to its most unstable asymptotic limit, while the full range of permissible asymptotic behaviours can be obtained for the binormal and parallel displacement variables (which are combinations of the poloidal and toroidal contravariant components of the perturbed displacement)

Antioxidant Properties of Donkey Milk

In the present work the well-known beneficial donkey’s milk (DM) characteristics to human health have been investigated, focusing the attention on anti-oxidant properties. For this purpose, vitamin C, lactoferrin, lactoperoxidase activity and total antioxidant power (PAO) were determined on milk whereas the reactive oxygen metabolites (ROM) and PAO concentrations were evaluated on blood. The trial was carried out on 10 pluriparous jennets. Sterile blood and milk samples were collected during three different periods of lactation. Microbiological tests, SCC (by a fluoro-optoelettronic method), PAO and ROM determinations were performed by commercial kits. Quantitative determination of lactoferrin from DM was determined by an HPLC method, lactoperoxidase activity was evaluated by a continuous spectrophotometric method, vitamin C content determination was performed using a commercial kit. The obtained data were subjected to the analysis of variance (ANOVA, SPSS). Mean values of the investigated param - eters±standard errors were calculated. No significant differences were observed for ROM, SCC and neither blood or milk PAO (respectively, 4.45±0.1 mmol/L; 50.9±19.9¥103/mL; 166.2±4.1 and 55.5±3.2 μmol HClO/mL). The fresh DM contains 57 mg/L of vitamin C, similar to that of human milk but higher compared with that of cow’s milk. The lactoferrin concentration in DM is 0.080±0.0035 g/L, very close to that obtained for mare, bovine but lower if compared with human milk. Mature DM contains low but detectable LPO activity (0.11±0.027 mg/L) similarly to value obtained from human milk. Concluding, for the first time were determined the PAO and ROM reference range in DM, furthermore the high content of vitamin C in DM confirms the important nutritional characteristics of this product