Chapter La riforma delle risorse proprie e la possibile introduzione di un tributo europeo

In the European Union, negotiations on the financial perspectives and the determination of the Union's own resources focus mainly on the amount of the individual states' contributions, and much less on the Union's fiscal competence. This weakens the Union's ability to conduct ambitious long-term policies, potentially mortgaging its very raison d'être. Recent developments related to the COVID-19 crisis (and beyond) seem to open a window for future changes. The European tax is an issue that provokes a wide debate at both the European and national levels, and not only of a political nature, between sovereignists and federalists, but also on the technical-legal-constitutional modalities that such a change would imply. For this reason, it is useful to present a structured analysis first of the financial instruments assigned to the EU, then of a reform of own resources and, finally, of the possibility of envisaging the birth of a European tax, albeit with an awareness of the limits of such a reform with regard to the current constitutional set-up of the European Union. Consequently, it will also be necessary to ask what kind of tax would be appropriate for this purpose

Abus de droit en droit européen - divergences ou convergences des concepts et politiques?

The fight against tax fraud and avoidance has become one of the main drivers of EU legislation and continues to influence the shaping of the case-law of the European Court of Justice in tax matters. The concept of abuse plays a key role in the interpretation of EU primary and secondary law and is even referred to in a number of provisions of EU tax legislation (harmonization directives, administrative cooperation and exchange of information). However, after almost 25 years of application by European and domestic courts and tax authorities, this apparently unifying function of the concept of abuse in tax matters raises a number of unresolved issues, creating significant legal uncertainty for taxpayers. The conference will gather together academics, public officials and practitioners to discuss the most recent issues concerning the prohibition of abuse in tax matters, as regards the application of fundamental freedoms, the EU corporate tax directives, including the recent Pillar 2 directive and the Unshell directive proposal, VAT and customs, exchange of information,. The conference will also address the latest implications of the notion of abuse of law on corporate tax planning and tax competition among Member States in the context of the international initiatives aiming at curbing base erosion and profit shifting (BEPS) and improving global tax transparency (exchange of information).16. Peace, justice and strong institution

The Future of EU Tax Harmonisation

Since the treaty of Rome, the European Union has been granted harmonization powers in the field of taxation. As for indirect taxes first and then direct taxes, directives have been adopted, mainly in order to facilitate free movement of taxpayers within the internal market and to fight against tax fraud and avoidance. Recent developments, such as the OECD BEPS initiative and the creation of a global forum on taxation issues, in particular relating to digitalization, Brexit and the financial and environmental crisis, along with the structural difficulty to reach unanimous agreement in key areas such as corporate taxation, are influencing the way tax legislation is proposed and passed at the EU level. At the eve of a new term for the European Commission, Council and Parliament, it may be time to re-think the purpose and the means of harmonization in the field of taxation. The morning session will address general issues such as the origin and purpose of EU harmonization, the current legal framework for the adoption of EU tax rules, in particular the principles of proportionality and subsidiarity and the peculiarities of the decision making process. Finally, the relationship between tax harmonization and the reform of the EU budget will be discussed. The second session will be devoted to corporate taxation, including its digital dimension. The possibility of a comprehensive harmonization of corporate tax along the lines of the CCCTB project will be assessed taking into account international developments. The other issues addressed in this session are the compatibility between the EU harmonization process (and more broadly EU law) and the BEPS project as regards the fight against tax avoidance and finally the potential harmonization a EU level of rules regarding digital economy

Sorafenib induces variations of the DNA methylome in HA22T/VGH human hepatocellular carcinoma-derived cells

Abstract. Sorafenib is currently used to treat advanced and/or unresectable hepatocellular carcinoma (HCC), but the increase of the median survival was only 3 months. Moreover, sorafenib has severe side effects and patients develop resistance quickly. Epigenetic alterations such as DNA methylation play a decisive role in the development and progression of HCC. To our knowledge, there are no studies that analysed the global DNA methylation changes in HCC cells treated with sorafenib. Using MeDip-chip technologies, we found 1230 differentially methylated genes in HA22T/VGH cells treated with sorafenib compared to untreated cells. Gene ontology and pathway analysis allowed identifying several enriched signaling pathways involved in tumorigenesis and cancer progression. Among the genes differentially methylated we found genes related to apoptosis, angiogenesis and invasion, and genes belonging to pathways known to be deregulated in HCC such as RAF/MEK/ERK, JAK-STAT, PI3K/AKT/mTOR and NF-κB. Generally, we found that oncogenes tended to be hypermethylated and the tumor suppressor genes tended to be hypomethylated after sorafenib treatment. Finally, we validated MeDip-chip results for several genes found diffedifferentially methylated such as BIRC3, FOXO3, MAPK3, SMAD2 and TSC2, using both COBRA assay and direct bisulfite sequencing and we evaluated their mRNA expression. Our findings suggest that sorafenib could affect the methylation level of genes associated to cancer-related processes and pathways in HCC cells, some of which have been previously described to be directly targeted by sorafenib

Exome sequencing in schizophrenic patients with high levels of homozygosity identifies novel and extremely rare mutations in the GABA/glutamatergic pathways

Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state. A recent study showed a suggestive enrichment of long ROHs in schizophrenic patients, suggesting that recent inbreeding could play a role in the disease. To better understand the impact of autozygosity on schizophrenia risk, we selected, from a cohort of 180 Italian patients, seven subjects with extremely high numbers of large ROHs that were likely due to recent inbreeding and characterized the mutational landscape within their ROHs using Whole Exome Sequencing and, gene set enrichment analysis. We identified a significant overlap (17%; empirical p-value = 0.0171) between genes inside ROHs affected by low frequency functional homozygous variants (107 genes) and the group of most promising candidate genes mutated in schizophrenia. Moreover, in four patients, we identified novel and extremely rare damaging mutations in the genes involved in neurodevelopment (MEGF8) and in GABA/glutamatergic synaptic transmission (GAD1, FMN1, ANO2). These results provide insights into the contribution of rare recessive mutations and inbreeding as risk factors for schizophrenia. ROHs that are likely due to recent inbreeding harbor a combination of predisposing low-frequency variants and extremely rare variants that have a high impact on pivotal biological pathways implicated in the disease. In addition, this study confirms that focusing on patients with high levels of homozygosity could be a useful prioritization strategy for discovering new high-impact mutations in genetically complex disorders