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Stress ossidativo ed arresto cardiaco
No full textL'arresto cardiocircolatorio è un evento improvviso, caratterizzato dalla cessazione dell attività cardiaca e respiratoria, e da una rapida perdita di coscienza a seguito della conseguente interruzione della perfusione cerebrale. Lo scopo dello studio è stato la valutazione parametri di funzionalità cardiaca ed il rilascio di mediatori di stress e dell infiammazione in un modello animale di arresto cardiaco. I nostri dati dimostrano l'aumentano della perossidazione lipidica (isoprostani ed LOOH) e dello danno ossidativo del DNA nel miocardio dopo 2h e 4h dallarresto cardiaco. Simili risultati sono stati ottenuti nel rene, fegato e cervello. In particolare, nella zona CA1 dell'ippocampo abbiamo osservato una significativa perdita di neuroni ed una astrogliosi reattiva. In conclusione i nostri dati dimostrano che i livelli plasmatici e tissutali dei paprametri dello stress ossidativo sono temporaneamente alterati durante il periodo successivo alla rianimazione e correlano con l alterata funzione cardiaca
KRABBE S DISEASE MECHANISMS
No full textKrabbe disease is an autosomal recessive disorder resulting in the deficiency of galactosilcerebrosidase (GALC), a lysosomal enzyme involved in the catabolism of two lipids extremely represented during formation of myelin sheet: galactosylceramide and psychosine. Despite the GALC activity deficiency, galactosylceramide does not increase in the brain of patients, while psychosine accumulation is reported as cause of myelin-generating cells death and of severe neurodegeneration. The present work outlined a molecular explanation for how psychosine mediates a dose-dependent cell death in oligodendrocytes precursor and fibroblast cells with and without GALC mutation. In addition, it was analyzed how this mechanism may interfere in oligodendrocytes maturation. The connexins play essential roles in cell homeostasis, growth, differentiation and death. Among connexin family members, Connexin43 is recently reported as an active element in apoptosis by gap junction-dependent or -independent mechanisms. Still today, there are no scientific researches evaluating Connexin43 expression and localization in normal and in GALC mutated oligodendrocytes precursor cells. The results of this study established that the different effects of exogenous psychosine addition could be linked to different sensitivity of cell membrane. Furthermore, it was determined a primary involvement of cell proliferation and a relationship between caspase-3 activation and disturbance of membrane-activated protein involved in cellular growth and survival. Psychosine treatments resulted in proteolysis of procaspase-3 proportioned to PTEN up-expression and PI3K activity down-regulation, confirmed by Bad release, p53 enhanced levels and decrease of NF-kB. The intrinsic apoptosis activation was established. Moreover, psychosine treated oligodendrocyte precursors increased Connexin43, demonstrating preferential intracytoplasmatic localization and indicating that no gap- junction was involved. These in vitro findings were supported by examination of Connexin 43 levels in mouse brains: wild-type mouse brain proteins were compared to those ones of twitcher mouse, a natural occurring model of Krabbe disease. Reminding that Connexin43 never was found in mature oligodendrocytes, the second part of this work was pioneer in evaluating Connexin43 expression during wild-type- and GALC-mutated oligodendrocytes maturation steps without psychosine treatment. In experimental condition applied, it was verified that wild-type oligodendrocyte progenitors differentiate into a mature phenotype with loss of Connexin43. Under the same condition, GALC-mutated oligodendrocyte precursor did not express marker of maturity, they became multinuclear and Connexin43 levels remained higher than control, suggesting that psychosine is accumulating in early steps of oligodendrocyte precursor cell maturation. Taken together, these findings led to the general idea that psychosine may functionally impact cells through interference on the growth system and alteration in maturation programme, strongly related to Connexin 43 expression. Thus, the third part of this work probed the likelihood of using adipose tissue-derived mesenchymal stem cells (AT-MSCs) as source of oligodendrocytes. Two different conditioned media were used and the results demonstrated that AT-MSCs can be influenced by the environment versus a neural phenotype. For this reason, stem cells can furnish potential material for cell replacement therapy. In summary, this thesis provides a new and unexplored molecular-mechanism for understanding the appearance and maintaining Krabbe disease hallmark. This work is the first description of a potential Connexin43 involvement in oligodendrocytes maturation and psychosine-inducted toxicity
Rotational evolution between 120 Myr and 1 Gyr
No full textIn this work the rotational evolution and the lithium depletion of low -mass stars in young stellar system is investigated, taking advantage of extensive new data sets on rotational periods that have recently became available. The rotational evolution of slow-rotating stars between 100Myr and 1 Gyr have been examined in detail, outlining a complex behaviour that claim for improved modelling of the internal angular momentum transport and of the angular momentum loss via a magnetised wind. A puzzling change in the rotation distribution vs. mass takes place at 550 Myr, which seems to contradict current theoretical models. Previous assumptions on the factorisation of the rotational dependence on time and mass do not hold in the 100 Myr - 1 Gyr time interval, which complicates somewhat the age inference from rotation. Studies based on the distribution of rotational periods of solar-type stars suggest in addition a possible link between lithium depletion and the rotational history of stars. The dispersion of lithium abundance at a given color in the Pleiades member stars have been re-examined. Once removed the mass dependence from rotation and Li-depletion a soft correlation between lithium and rotational periods in K and M type stars has been found. On the other hand, a clear and solid correlation has been found in the 0.74<=(B-V)<1.15 color range. In this (B-V) range the slower a star is the larger is the lithium depletion. A comparison and an analysis of the rotation periods and lithium depletion in young stellar association AB Doradus and the Pleiades has allowed to confirm the coevality for these two systems. A group of slow-rotating stars in AB Dor, however, have Li abundance considerably higher that suggested by the general trend, which may be indicative of differences in the rotational histories of stars belonging to the young loose association. A young nearby cluster, gamma2 Velorum, has also been analyzed, using data from the Gaia-ESO survey. This latter has evidenced the presence of two possible different populations. These populations are kinematically different eventual differences in Li abundance are found below detectability
Indagini micologiche, tassonomiche e mappatura delle Boletales sul territorio siciliano isole minori comprese
No full textIndagini micologiche sulle Boletales del territorio siciliano. L'autore descrive la presenza e la distribuzione dell'ordine delle Boletales in Sicilia, sottolineandone gli aspetti ecologici ed ambientali e delineando le caratteristiche delle più importanti specie. In particolare l'autore fa riferimento al notevole ruolo economico e gastronomico della famiglia delle Boletaceae nel patrimonio culturale siciliano, prestando una maggiore attenzione alle specie presunte tossiche e velenose
Sopravvenienze e sopravvivenze attive in esito alla cancellazione della Società dal registro delle imprese
No full textLa tesi è incentrata sulla sorte degli elementi patrimoniali attivi non liquidati che residuano a seguito dell'iscrizione della cancellazione della Società dal registro delle imprese. Dopo un iniziale excursus sulle diverse tesi avanzate in dottrina e in Giurisprudenza e dopo aver valutato l'impatto sul sistema dell'inciso iniziale dell'art. 2495, secondo comma c.c., come introdotto dalla Riforma Societaria del 2003, si analizzano i poteri di controllo dell Ufficio del registro delle imprese e le condizioni di legge per una valida richiesta d iscrizione della cancellazione della Società. Quindi, provata la natura prettamente formale del controllo dell'Ufficio e ritenuto, per l'effetto, che gli elementi patrimoniali attivi non liquidati cadano, a seguito dell'iscrizione della cancellazione dal registro delle imprese, in comunione tra i soci si individuano tanto le situazioni giuridiche che possano sussumersi nelle categorie concettuali delle "sopravvivenze" e "sopravvenienze" attive quanto la fonte del regime comunitario che su di esse si instaura avvalendosi, in tale analisi, di diverse sentenze della Cassazione, anche a Sezioni Unite, che numerose si sono susseguite nel lasso di un breve periodo di tempo a conferma dell'importanza e dell'attualità del tema trattato. Infine, analizzati i problemi pratici che pongono le sopravvivenze/sopravvenienze attive sia in tema di rappresentanza sostanziale e processuale della Società ormai cancellata che in tema di regime pubblicitario degli elementi di natura immobiliare (specie qualora i soci divenuti comproprietari intendano disporre della sopravvivenza/sopravvenienza), la tesi si conclude con l'analisi dei possibili profili di responsabilità degli ex liquidatori
Investigation on Mt. Etna dynamics by seismic and acoustic signals (August 2007 December 2010)
No full textIn order to shed light on the dynamics of the plumbing system, and define the source-mechanism of acoustic events at Mt. Etna, infrasound signals-continuously recorded by Istituto Nazionale di Geofisica and Vulcanologia- were analyzed in this thesis, jointly with some seismic signals. In particular, we focused on the period comprised between August 2007 and December 2010, during which a wide spectrum of eruptive activity occurred. Until the activation of Bocca Nuova (BN), on August 2010, the three main vents radiating infrasound were North East Crater (NEC), South East Crater (SEC), and the Eruptive Fissure of the 2008-2009 eruption (EF).
Location and spectral analyses carried out on the infrasound signals, revealed the numerical dominance and the steadiness of NEC events, radiating almost continuously acoustic energy, oppositely to SEC and EF. Furthermore, NEC events most relevant changes (spectral and amplitude variation) occurred systematically after the renewal of activity at SEC or at the EF. This evidence led us to infer the existence of a persistent link among their feeding system, and confirm the presence of a double resonance model for NEC events. Successively, events from EF were gathered and analyzed in detail through high precision location methods, allowing to define the cyclic activation of an highest altitude vent along the fissure, likely corresponding to the arrival of new batch of magma, rich in volatiles.
During 2010, instead, Mt. Etna eruptive style was different, being characterized by a total number of roughly 35 minor ash emissions from SEC, BN and NEC. Three main episodes are here analyzed, by studying the morphological and compositional features of the sampled ash and the seismic and acoustic signals radiated during those events. Different conditions were deduced for the craters. In particular, for SEC and BN the presence of material plugging the upper conduit was inferred, while data shows that NEC was characterized by open conduit conditions.
Finally, a dataset of acoustic signals, regarding few days of explosive activity occurring at Mt. Yasur (Vanuatu) was analyzed. Indeed, the comparison with other volcanic environments is fundamental in order to widen the knowledge on the volcanic phenomena. Mt. Yasur data, revealed completely different features, suggesting that different source dynamics were active. Furthermore, the existence of propagation effects, affecting the signals´ characteristics and due to the topography is discussed
"Study of novel pathogenic mechanism in Huntington disease"
No full textHuntington Disease (HD) is a neurodegenerative disorder resulting from the expansion of polyglutamine stretch in the huntingtin protein (Htt). Mutant Htt (mHtt) leads to progressive impairment of several molecular pathways that have been linked to disease pathogenesis. Defects in
the production of neurotrophic factors have been described as important determinants contributing to the development of HD. In addition to others, production of transforming growth factor-beta1 (TGF-beta1) is also deregulated in HD and shows a variable profile during disease course. TGF-beta1 levels have been reported to be markedly reduced before and at the time of HD onset in both central (human post-mortem cortex) and peripheral (serum) districts and returned to normal levels with disease severity. We have discovered that the abnormal production of peripheral TGF-beta1 depends on the changes in the percentage of TGF-beta1-producing macrophages along HD. Variation in the number of TGF-beta1-producing macrophags resulted from differential activation state of the same cells, which displayed phenotypic and functional heterogeneity throughout the clinical course of HD. Similar to the periphery, TGF-beta1 levels varied in human post-mortem brain with HD
neuropathological changes. Our study highlights an interesting link between periphery and central compartment and underlines the potential of TGF-beta1 as a possible early disease marker suitable for prediction of disease onset in HD
Role of Dopamine D3 receptor in the regulation of memory related genes
No full textDopamine is postulated to be a key neurotransmitter that mediates human memory via signaling in the striatum, hippocampus and prefrontal cortex. The effects of dopaminergic system crucially depend on the different subtype of dopamine receptors involved and the brain regions in which they are activated. D3 receptors (D3R) are more selectively expressed in the limbic regions, which are associated with cognitive and emotional functions. However, few studies have focused on the effect of D3R deficiency on learning and memory processes and underlying molecular events. To elucidate the potential role of D3R in associative learning and underlying molecular events, we used D3R knockout (D3-/-) mice in order to explore the intracellular signaling pathways using Passive avoidance (PA) tasks. In the first study we evaluated the expression levels of APP and NF1, two genes implicated in cognitive function, in wild-type (WT) and D3-/- mice subjected to the single trial step-through PA paradigm. Results showed that acquisition of behavioral task leads to increased expression levels of D3Rs and NF1, but not of APP in hippocampus of WT mice, suggesting that hippocampal D3Rs might be relevant to NF1 transcriptional regulation in the hippocampus. In the second study we tested the involvement of signaling molecules MAPKs, Akt and CREB to assess whether their phosphorylation levels were affected by PA in wild-type (WT) and D3-/- mice hippocampi. Increased phosphorylation levels of CREB and ERK were detected in D3-/- mice performing PA task, while Akt activation was observed in D3-/- mice, but not in response to PA. Results suggest that D3R inactivation might improve cognitive performance in mice through the induction of hippocampal CREB activity, preferentially via ERK signaling. The aim of third work was determine whether D3R deletion influences baseline tPA expression/activity in prefrontal cortex and hippocampus, and subsequently elucidate the potential underlying mechanisms mediated by D3R to regulate CREB activity in tPA. Results revealed that in prefrontal cortex and hippocampus of D3-/- mice, tPA, mBDNF and the expression ratio of plasmin/plasminogeno both mRNA and protein expression levels were significantly increased as compared to the WT mice. Datas showed increased Akt, DARPP-32 and GSK-3B phospshorylation in D3-/- mice, suggesting that this pathaways is involved in raised tPA expression in D3-/- mice
Problemi giuridici del lavoro transnazionale in edilizia
No full textLa tutela dei diritti sociali all'interno dell'Unione Europea, di fronte alla crisi economica e finanziaria che oramai da anni attanaglia l'Europa e buona parte del mondo occidentale, richiede agli studiosi del diritto un surplus di attenzione.
Il presente elaborato ha come fine quello di tentare di fornire un contributo alla risoluzione dell'annoso problema dell'obbligatorietà o meno dell'iscrizione alle casse edili italiane delle imprese edili straniere operanti in Italia, riportando le problematiche generali attinenti il lavoro transnazionale al circoscritto ambito del lavoro transnazionale in edilizia
Gli investimenti in ICT quali scelte strategiche per il miglioramento delle performance aziendali
No full textLa ricerca persegue l obiettivo di analizzare la presenza, l entità e le caratteristiche delle correlazioni tra gli investimenti in ICT e le performance finali di profitto, di rischio di credito e di patrimonializzazione nella doppia prospettiva teorica dell IT Paradox e del Capital Deepening. La prima, fa riferimento al paradosso secondo cui all aumentare delle dotazioni di capitale tecnologico si manifesti un pay-off inversamente correlato (o non correlato) nelle misure di output prescelte; la seconda, postula l ipotesi secondo cui all aumentare degli investimenti pro-capite per lavoratore del fattore di produzione K (il capitale) si possa generare uno speculare miglioramento dell output finale in termini quantitativi e/o qualitativi. Il campione statistico osservato è composto dal 91% dei gruppi bancari italiani nel periodo 2007 2011. La metodologia di ricerca si esplica in dodici modelli di regressione lineare calcolati con la tecnica dei minimi quadrati e le variabili dipendenti individuate riguardano i tradizionali indici di profitto ROE e ROA, il "rischio di credito" e i solvency ratios Total Capital Ratio e Tier1 Capital Ratio; in aggiunta, per colmare le istanze evidenziate dalla letteratura, si è strutturato un ulteriore indice di profitto dato dalla raccolta diretta normalizzata al total asset (RDN). I risultati ottenuti sono eterogenei in quanto in linea con gli assunti dell IT Paradox in relazione alle performance sulla RDN, il rischio di credito e i solvency ratios mentre, viceversa, emergono chiare correlazioni dirette e statisticamente significative tra le dotazioni tecnologiche e le misure di profitto ROE e ROA. Con riguardo alla letteratura sul Capital Deepening, non risultano confermati i presupposti teorici in termini di produttività per dipendente e investimenti tecnologici per motivi di significatività statistica se non in determinati casi e per ammontari comunque contenuti