La ricerca affronta in modo unitario e nell’ottica europea i multiformi fenomeni della doppia imposizione economica e giuridica, assumendo come paradigma iniziale la tassazione dei dividendi cross-border. Definito lo statuto giuridico della doppia imposizione, se ne motiva la contrarietà all’ordinamento europeo e si indagano gli strumenti comunitari per raggiungere l’obiettivo europeo della sua eliminazione. In assenza di un’armonizzazione positiva, il risultato sostanziale viene raggiunto grazie all’integrazione negativa. Si dimostra che il riserbo della Corte di Giustizia di fronte a opzioni di politica fiscale è soltanto un’impostazione di facciata, valorizzando le aperture giurisprudenziali per il suo superamento. Questi, in sintesi, i passaggi fondamentali. Si parte dall’evoluzione delle libertà fondamentali in diritti di rango costituzionale, che ne trasforma il contenuto economico e la portata giuridica, attribuendo portata costituzionale ai valori di neutralità e non restrizione. Si evidenzia quindi il passaggio dal divieto di discriminazioni al divieto di restrizioni, constatando il fallimento del tentativo di configurare il divieto di doppia imposizione come principio autonomo dell’ordinamento europeo. Contemporaneamente, però, diventa opportuno riesaminare la distinzione tra doppia imposizione economica e giuridica, e impostare un unico inquadramento teorico della doppia imposizione come ipotesi paradigmatica di restrizione alle libertà. Conseguentemente, viene razionalizzato l’impianto giurisprudenziale delle cause di giustificazione. Questo consente agevolmente di legittimare scelte comunitarie per la ripartizione dei poteri impositivi tra Stati Membri e l’attribuzione delle responsabilità per l’eliminazione degli effetti della doppia imposizione. In conclusione, dunque, emerge una formulazione europea dell’equilibrato riparto di poteri impositivi a favore dello Stato della fonte. E, accanto ad essa, una concezione comunitaria del principio di capacità contributiva, con implicazioni dirompenti ancora da verificare. Sul piano metodologico, l’analisi si concentra criticamente sull’operato della Corte di Giustizia, svelando punti di forza e di debolezza della sua azione, che ha posto le basi per la risposta europea al problema della doppia imposizione. / In a unitary and European perspective, the research deals with the multiform phenomena of economic and juridical double taxation, by adopting cross-border dividend taxation as a paradigm. Once the juridical status of double taxation is defined, its incompatibility with European law is asserted and EU instruments to achieve the result of its elimination are examined. Lacking positive harmonization, the substantive outcome is achieved by means of negative integration. The traditional self-restraint of the European Court of Justice on the matter of tax policy choices is nothing but a formal attitude, which may be overcome starting from clues given by the Court itself in its case-law. Here are the main steps of the research. First, the evolution of fundamental freedoms into constitutional rights, transforming both their economical and juridical scope, and conferring constitutional level to the principles of neutrality and non-restriction. Secondly, the shift from the prohibition of discriminations to the prohibition of restrictions and the failure of the attempt to define the prohibition of double taxation as an autonomous principle of European law. At the same time, however, juridical and economic double taxation need to be framed in a unitary category, both being a typical example of restriction to EU freedoms. Third, the analysis focuses on the asset of judicial justifications. All the above grounds EU choices concerning the allocation of taxing rights between Member States and the allocation of liabilities for the elimination of the effects of double taxation. Therefore, the research points out a European formula for the allocation of taxing rights in favour of the State of source, as well as a EU concept of ability-to-pay, having important effects yet to be assessed. As regards the method, the analysis focuses on ECJ’s case-law and underlines its merits and weakness in preparing the EU answer to double taxation.

Il coordinamento tra sistemi impositivi è una questione originaria e tipica del diritto comunitario. La tesi ne esplora le conseguenze sotto più aspetti. / Income tax systems' co-ordination is a relatively recent issue in the globalizing economy. In fact, a tendence to tax co-ordination begins, essentially, with the EU Law. Since 2006, European Institutions feel the urgence to solve problem of double imposition and non imposition phenomena left unsolved by the member states themselves, or by means of Double Taxation Conventions (DTCs). The tax co-ordination envisages means to do so. The theme is firstly envisaged by the unilateral and bilateral perspective, underlining the deficiencies of sovereignity methods in fronting the economies' integration problems. The theme is then pointed out by the perspective of EU Law. At a first level, by considering tax systems co-ordination methods envisaged by the Directives in matter of group-taxation. Then, monitoring the outgoing of co-ordination considered by three EU Communications dated 19 December 2006 (respectively targeted to the general problem of tax co-ordination, to the co-ordination between member states upon exit taxation, to the co-ordination upon consideraton of intra-EU losses). The issue is also considered by the point of view of the European Court of Justice. In this perspective, it's relevant to estabilish whether the ECJ has the power to compel the member states to structure each other their income tax systems, based on the application of the EU freedoms, with a view – in particular – to exit taxation policies, to intra-EU losses: a theme strictly linked to the view that is optioned out for the interpretation of EU non-discrimination clause (an overall approach facing the opposite per-country approach).

Lo scopo di questa ricerca è stato quello di offrire una visione sistematica per lo studio del fenomeno della concorrenza fiscale nel quadro dell'UE. In questo modo, dopo approfondire nel concetto, gli effetti e le teorie economiche che sviluppano la concorrenza fiscale, abbiamo analizzato le condizioni generali di svolgimento della concorrenza fiscale nell'UE, con particolare attenzione alla pratica dell’arbitrio fiscale per privati ed imprese. Questo schema lo abbiamo successivamente trasferito a due campi che finora avevano ricevuto poca attenzione dottrinale: l'imposizione indiretta (IVA e accise) e la tassazione delle persone fisiche. Infine, abbiamo aggiornato lo studio dei due strumenti tradizionali di lotta contro la concorrenza fiscale dannosa: il Codice di condotta in materia di tassazione delle imprese e il regime degli aiuti di Stato. Le sfide dell'Unione europea ci impongono di prendere una visione critica che abbiamo cercato di estendere a tutto il nostro lavoro. / The objective of this research has been to offer a systematic vision for the study of the tax competition phenomena within the EU. In this way, after deepening in the concept, the effects and the economic theories that have studied tax competition, we have a developed a scheme of the general conditions for its development, with special attention to the concept of tax arbitrage. This scheme have subsequently used to study two fields that up to now had received little attention from the doctrine: the indirect taxation (VAT and excise duties) and the taxation of individuals. Finally, we have updated the analysis of the two instruments which traditionally monopolized the studies in this field: the Code of Conduct for business taxation and the State aid regime. The challenges and difficulties that the EU faces has pushed ourselves into a critical view that we have tried to extend to all our work.

Introduzione: le Coliti Microscopiche, altrimenti note come Colite Collagena e Colite Linfocitica, sono disordini infiammatori cronici del colon che causano diarrea e colpiscono più frequentemente donne in età avanzata e soggetti in terapia farmacologica. Negli ultimi anni la loro incidenza sembra aumentata in diversi paesi occidentali ma la prevalenza in Italia è ancora incerta. Scopo: il presente studio prospettico e multicentrico è stato disegnato per valutare la prevalenza delle CM in pazienti sottoposti a colonscopia per diarrea cronica non ematica. Pazienti e metodi: dal Maggio 2010 al Settembre 2010 sono stati arruolati consecutivamente tutti i soggetti adulti afferenti in due strutture dell’area metropolitana milanese per eseguire una pancolonscopia. Nei soggetti con diarrea cronica non ematica sono state eseguite biopsie multiple nel colon ascendente, sigma e retto nonché in presenza di lesioni macroscopiche. Risultati: delle 8008 colonscopie esaminate 265 sono state eseguite per diarrea cronica; tra queste, 8 presentavano informazioni incomplete, 52 riscontri endoscopici consistenti con altri disordini intestinali (i.e. IBD, tumori, diverticoliti). 205 colonscopie sono risultate sostanzialmente negative, 175 dotate di adeguato campionamento microscopico (M:F=70:105; età mediana 61 anni). L’analisi istologica ha permesso di documentare 38 nuovi casi di CM (M:F=14:24; età mediana 67.5 anni): 27 CC (M:F=10:17; età mediana 69 anni) e 11 CL (M:F=4:7; età mediana 66 anni). In altri 25 casi sono state osservate alterazioni microscopiche prive dei sufficienti requisiti per la diagnosi di CM. Conclusioni: nel presente studio l’analisi microscopica del colon ha identificato la presenza di CM nel 21,7% dei soggetti con diarrea cronica non ematica ed indagine pancolonscopica negativa. Lo studio microscopico del colon è pertanto un passo diagnostico fondamentale per il corretto inquadramento diagnostico delle diarree croniche, specialmente dopo i 60 anni di età. Ampi studi prospettici e multicentrici dovranno chiarire ruolo e peso dei fattori di rischio associati a questi disordini. / Background and aim: Microscopic colitis (MC) encompasses Lymphocytic (LC) and Collagenous colitis (CC) and is a chronic, inflammatory condition of the colon causing watery diarrhea. MC is more prevalent in elderly women and in patients taking multiple drugs. The overall incidence of MC appears to have increased in recent years and to be relatively common in subjects with chronic diarrhea; however, the prevalence of this condition in Italy is still unclear. We designed a prospective multicenter study in order to evaluate the prevalence of MC in subjects undergoing colonoscopy for chronic non-bloody diarrhea. Methods: from May 2010 to September 2012, we prospectively enrolled subjects undergoing colonscopy in the metropolitan area of Milan for chronic non-bloody diarrhea. Biopsies were obtained from any macroscopic finding detected in the course of the endoscopic and from ascending, sigmoid colon and rectum. Results: a total of 8008 colonoscopies were performed; of these, 265 were done for non-bloody diarrhea; 8 were not complete, 52 detected relevant endoscopic findings consistent with a specific diagnosis (i.e. IBD, neoplasm, diverticulitis). Colonoscopy was grossly normal in 205 subjects; microscopic analysis was available in 175 cases (M:F=70:105; median age 61 yrs). Histopathologic evaluation revealed MC in 38 patients (M:F=14:24; median age 67.5 yrs): 27 CC (M:F=10:17; mean age 69 yrs), and 11 LC (M:F=4:7; mean age 66 yrs). In 25 subjects we observed non-diagnostic changes, such as a mild increase in intraepithelial lymphocytes or a slight thickening of sub-epithelial collagen. Conclusions: in this study endoscopic biopsies allowed the diagnosis of MC in 21.7% of patients complaining non-bloody diarrhea with a normal colonoscopy. Indeed, the identification of MC is pivotal for the adequate management of chronic diarrhea, especially in elderly people. Larger multicenter prospective studies are warranted to define the real impact of this clinical entity in our country.

IL-33/ST2 axis is known to promote Th2 immune responses and has been linked to several autoimmune and inflammatory disorders, including inflammatory bowel disease (IBD), and recent evidences show that it can regulate eosinophils (EOS) infiltration and function. Based also on the well documented relationship between EOS and IBD, we assessed the role of IL-33-mediated eosinophilia and ileal inflammation in SAMP1/YitFc (SAMP) murine model of Th1/Th2 chronic enteritis, and we found that IL-33 is related to inflammation progression and EOS infiltration as well as IL-5 and eotaxins increase. Administering IL-33 to SAMP and AKR mice augmented eosinophilia, eotaxins mRNA expression and Th2 molecules production, whereas blockade of ST2 and/or typical EOS molecules, such as IL-5 and CCR3, resulted in a marked decrease of inflammation, EOS infiltration, IL-5 and eotaxins mRNA expression and Th2 cytokines production. Human data supported mice’s showing an increased colocalization of IL-33 and EOS in the colon mucosa of UC patients, as well as an augmented IL-5 and eotaxins mRNA expression, when compared to non-UC. Lastly we analyzed SAMP raised in germ free (GF) condition to see the microbiota effect on IL-33 expression and Th2 responses leading to chronic intestinal inflammation. We found a remarkable decrease in ileal IL-33 and Th2 cytokines mRNA expression as well as EOS infiltration in GF versus normal SAMP with comparable inflammatory scores. Moreover, EOS depletion in normal SAMP didn’t affect IL-33 mRNA expression. These data demonstrate a pathogenic role of IL-33-mediated eosinophilia in chronic intestinal inflammation, and that blockade of IL-33 and/or downstream EOS activation may represent a novel therapeutic modality to treat patients with IBD. Also they highlight the gut microbiota role in IL-33 production, and the following EOS infiltration in the intestinal mucosa, confirming that the microbiota is essential in mounting potent Th2 response leading to chronic ileitis in SAMP.

The genus Benyvirus includes the most important and widespread sugar beet viruses transmitted through the soil by the plasmodiophorid Polymyxa betae. In particular Beet necrotic yellow vein virus (BNYVV), the leading infectious agent that affects sugar beet, causes an abnormal rootlet proliferation known as rhizomania. Beet soil-borne mosaic virus (BSBMV) is widely distributed in the United States and, up to date has not been reported in others countries. My PhD project aims to investigate molecular interactions between BNYVV and BSBMV and the mechanisms involved in the pathogenesis of these viruses. BNYVV full-length infectious cDNA clones were available as well as full-length cDNA clones of BSBMV RNA-1, -2, -3 and -4. Handling of these cDNA clones in order to produce in vitro infectious transcripts need sensitive and expensive steps, so I developed agroclones of BNYVV and BSBMV RNAs, as well as viral replicons allowing the expression of different proteins. Chenopodium quinoa and Nicotiana benthamiana plants have been infected with in vitro transcripts and agroclones to investigate the interaction between BNYVV and BSBMV RNA-1 and -2 and the behavior of artificial viral chimeras. Simultaneously I characterized BSBMV p14 and demonstrated that it is a suppressor of post-transcriptional gene silencing sharing common features with BNYVV p14.

Inflammatory Bowel Diseases (IBD) are intestinal chronic relapsing diseases which ethiopathogenesis remains uncertain. Several group have attempted to study the role of factors involved such as genetic susceptibility, environmental factors such as smoke, diet, sex, immunological factors as well as the microbioma. None of the treatments available satisfy several criteria at the same time such as safety, long-term remission, histopatological healing, and specificity. We used two different approaches for the development of new therapeutic treatment for Inflammatory Bowel Disease. The first is focused on the understanding of the potential role of functional food and nutraceuticals nutrients in the treatment of IBD. To do so, we investigated the role of Curcuma longa in the treatment of chemical induced colitis in mice model. Since Curcma Longa has been investigated for its antinflammatory role related to the TNFα pathway as well investigators have reported few cases of patients with ulcerative colites treated with this herbs, we harbored the hypothesis of a role of Curcuma Longa in the treatment f IBD as well as we decided to assess its role in intestinal motility. The second part is based on an immunological approach to develop new drugs to induce suppression in Crohn’s disease or to induce mucosa immunity such as in colonrectal tumor. The main idea behind this approach is that we could manipulate relevant cell-cell interactions using synthetic peptides. We demonstrated the role of the unique interaction between molecules expressed on intestinal epithelial cells such as CD1d and CEACAM5 and on CD8+ T cells. In normal condition this interaction has a role for the expansion of the suppressor CD8+ T cells. Here, we characterized this interaction, we defined which are the epitope involved in the binding and we attempted to develop synthetic peptides from the N domain of CEACAM5 in order to manipulate it.

Il lavoro svolto durante questa tesi di dottorato pone le basi per lo sviluppo di nuove biotecnologie della micorrizazione di piante forestali con tartufi pregiati ed in particolare con Tuber magnatum. Durante questa tesi è stato possibile isolare e mantenere in coltura pura il micelio di T. magnatum, ad ottenere e descrivere le sue micorrize e quelle di altri tartufi “bianchi” (T. oligospermum, T. borchii) e a seguire l’evoluzione del micelio nel suolo utilizzando la tecnica della real time PCR. Sono stati disegnati primer specie specifici in grado di identificare T. oligospermum ed è stata verificata la possibiltà di utilizzare questi primers in PCR multiplex con quelli specifici di T. magnatum e di T. borchii già presenti in bibliografia, al fine di “scovare” sia frodi nella commercializzaione degli ascomi sia eventuali contaminazioni nelle piante micorrizate. Per migliorare lo sviluppo miceliare di tartufo abbiamo si è cercato di migliorare il mezzo nutritivo per la crescita del micelio utilizzando: fonti di carbonio diverse, estratti radicali di nocciolo e singole frazioni separate dagli stessi. Infine sono stati sviluppati protocolli di crioconservazione per miceli di tartufo. Gli estratti radicali sono in grado di stimolare le crescita miceliare del tartufo modello T. borchii e dimodificarne la morfologia ifale. Questo risultati sono stati confermati anche dall’aumento dell’espressione di geni CDC42 e Rho-GDI, due geni legati alla crescita apicale polarizzata delle ife dei funghi filamentosi. Inoltre è stato dimostrato che il mantenimento in coltura per numerosi anni dei miceli di tartufo provoca una perdita della capacità d’infettare le radici delle piante e quindi il loro potenziale utilizzo sia a scopo sperimentale sia a scopo colturale. Questo pone in risalto l’importanza della conservazione a lungo termine del materiale biologico a disposizione ed è stato dimostrato che la crioconservazione è applicabile con successo anche alle specie del genere Tuber. / In this PhD thesis we have developed new biotechnologies for the mycorrhizal synthesis of forest plants with precious truffles and in particular with T. magnatum. We have isolated and kept in pure culture the mycelium T. magnatum for the first time. We have obtained and described its mycorrhizas and the mycorrhizas of other similar white truffles (T. oligospermum, T. borchii). We have also follow the development of its mycelium in the pot using the real time PCR technique. We have designed specific primers for T. oligospermum identification and we have verified the possibility to use these primers in PCR multiplex in combination with T. magnatum and T. borchii primers reported in literature. Using these primers we are able to discover frauds in truffle commercialization or contaminations in commercial mycorrhized plants. In order to increase the growth of T. magnatum mycelium we tested different media containing different C sources , hazel root extracts and fractions of theses roots extracts. We have also developed new protocols for the cryopreservation of truffle mycelia. We found that the root extracts stimulate the mycelial growth of the model fungus T. borchii and also modify the its hyphal morphology. These results are confirmed by an increased expression of the genes CDC42 e Rho-GDI, which are involved in apical growth of filamentous fungi. Moreover we showed that long term cultivation on synthetic media (for more than 10 years) of truffle mycelia lose their infectivity and perhaps they cannot be successfully used for the commercial and experimental production of mycorrhized plants. Thus our results confirm the importance of the cryopreservation methods for long term vitality and infectivity preservation of Tuber mycelia.

The brown rot fungi belong to a group of fungal pathogens that causes considerable damage to cultivated fruits trees, particularly stone fruits and apples in the temperate regions of the World and during the postharvest with an important economic impact. In particular in Italy, it is important to monitor the Monilinia population to control economic losses associated to the peach and nectarine market. This motivates the research steps presented in this dissertation on Monilinia Italian isolates. The Monilinia species collected from stone fruits have been identified using molecular analysis based on specific primers. The relevant role of M. fructicola was confirmed and, for the first time, it was found also on apple fruits. To avoid the development of resistant strains and implement valid treatment strategies, the understanding of the fruit natural resistance during different developmental stages and the assessment of the Monilinia sensitivity/resistance to fungicides are required. The relationship between the inhibition spots and the phenolic compounds in peach fruit peel was highlighted in this research. Three methods were used to assess isolate resistance/sensitivity, the amended medium, the Spiral Gradient Endpoint Method (SGD) and the Alamar Blue method. The PCR was used to find possible mutation points in the b-tubulin gene that is responsible for fungicide resistance. Interestingly, no mutation points were observed in resistant M. laxa isolates, suggesting that the resistance could be stimulated by environmental factors. This lead to the study of the effect of the temperature on the resistance and the preliminary results of in vitro tests showed that maximum inhibition was observed at 30°C.

In questo lavoro si analizza l’imposizione indiretta nel commercio elettronico; l’analisi si è basata sullo studio della normativa Comunitaria (Direttive Europee ) e la legislazione e Italiana, esponendo anche le differenze con il profilo legislativo brasiliano (softwares e libri).Esposti i contributi delle istituzione internazionali (conferenze ed/o proposte della Unione Europea) per l’inquadramento tipologico e fiscale del commercio elettronico, sono stati analizzati i profili generali dell’istituto della stabile organizzazione ai fini dell’imposizione dell’IVA e al commercio elettronico, distinguendo anche tra le transazioni elettroniche considerabili come cessione di beni e quelle considerabili prestazioni di servizi, in base alla materialità o alla dematerializzazione del bene scambiato. Anche il principio di territorialità nelle prestazioni di servizi è stato analizzato tramite analisi dei regimi ordinario e speciale riguardanti gli operatori extracomunitari. / In this work we analyze the indirect taxation in e-commerce, the analysis was based on the study of EC regulations (EU Directives) and the Italian legislation and, exposing the differences with the legislative Brazilian (softwares and books). Exposed the contributions of the international institution (conferences and / or proposals by the European Union) for the classification of types of e-commerce and taxation, we have analyzed the general aspects of the institute of the permanent establishment for tax purposes of VAT and e-commerce , distinguishing between electronic transactions also consider them as sale of goods and the considerable services, according to the material or the dematerialization of the exchanged item. The principle of territoriality in the provision of services was analyzed by analysis of ordinary and special regimes relating to non-EU operators