LTR point mutations in the Tax-responsive elements of HTLV-1 isolates from HIV/HTLV-1-coinfected patients

Background: In Virology Journal 2011, 8: 535, Neto et al. described point mutations into Tax-responsive elements (TRE) of the LTR region of HTLV-1 isolates from asymptomatic carriers from Sao Paulo, Brazil, and hypothesized that the presence of the G232A mutation in the TRE-1 increase viral proliferation and consequently the proviral load (PvL), while the A184G mutation in the TRE-2 do not have such effect. Findings: We performed the real-time PCR assay (pol) and sequenced LTR region of HTLV-1 isolates from 24 HIV/HTLV-1-coinfected patients without HTLV-1-associated diseases from the same geographic area. These sequences were classified as belonging to the transcontinental subgroup A of the Cosmopolitan subtype a. The frequency of G232A mutation (16/24, 66.7%) was high as much as 61.8% reported by Neto's in HTLV-1 asymptomatic carriers with high PvL. High frequency (13/24, 54.2%) of double mutations G232A and A184G was also detected in HIV/HTLV-1-coinfected patients. We did not quantify PvL, but comparative analyses of the cycle threshold (Ct) median values of the group of isolates presenting the mutated-types sequences (Ct 33.5, n = 16) versus the group of isolates with the wild-type sequences (Ct 32, n = 8) showed no statistical difference (p = 0.4220). Conclusion: The frequencies of mutated-type sequences in the TRE-1 and TRE-2 motifs were high in HIV/HTLV-1-coinfected patients from Sao Paulo, Brazil. If these LTR point mutations have predictive value for the development of HTLV-1-associated diseases or they correspond to the subtype of virus that circulate in this geographic area has to be determined.

Tax Gene Characterization of Human T-Lymphotropic Virus Type 1 Strains from Brazilian HIV-Coinfected Patients

The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

CD3e expression in HTLV-1-infected individuals is associated with proviral load and Tax expression

Financial support: FUNDHERP, CTC, INCTC, FAPESP, CNPq and CAPES.

Ex-post Liability Rules in Modern Patent Law

This doctoral thesis examines the use of liability rules to protect patent entitlements, focusing on a specific type of rule named ex-post since it is applied and designed ex-post by a court or an agency. The research starts from the premise that patents are defined by the legal and economic scholarship as exclusive rights but nevertheless, under certain circumstances there are economic as well as other compelling reasons to transform the exclusiveness of patent rights into a right to receive compensation.

The special rights other than shares in cross-border mergers of limited liability companies within the European Union. A perspective from the Spanish Law

The present research aims to study the special rights other than shares in Spanish Law and the protection of their holders in cross-border mergers of limited liability companies within the European Union frame. Special rights other than shares are recognised as an independent legal category within legal systems of some EU Member States, such as Germany or Spain, through the implementation of the Third Directive 78/855/CEE concerning mergers of public limited liability companies. The above-cited Directive contains a special regime of protection for the holders of securities, other than shares, to which special rights are attached, consisting of being given rights in the acquiring company, at least equivalent to those they possessed in the company being acquired. This safeguard is to highlight the intimate connection between this type of rights and the company whose extinction determines the existence of those. Pursuant to the Directive 2005/56/CE on cross-border mergers of limited liability companies, each company taking part in these operations shall comply with the safeguards of members and third parties provided in their respective national law to which is subject. In this regard, the protection for holders of special rights other than shares shall be ruled by the domestic M&A regime. As far as Spanish Law are concerned, holders of these special rights are recognized a right of merger information, in the same terms as shareholders, as well as equal rights in the company resulting from the cross-border merger. However, these measures are not enough guarantee for a suitable protection, thus considering those holders of special rights as special creditors, sometimes it will be necessary to go to the general protection regime for creditors. In Spanish Law, it would involve the recognition of right to the merger opposition, whose exercise would prevent the operation was completed until ensuring equal rights.

Civil Liability as an Enforcement Tool of Securities Underwriter Gatekeeping Duty

This book is dedicated to the Law and Economics analysis of civil liability of securities underwriters for the damage caused by material misstatements of corporate information by securities issuers. It seeks to answer a series of important questions. Who the are underwriters and what is their main role in the securities offering? Why there is a need for legal intervention in the underwriting market? What is so special about civil liability as an enforcement tool? How is civil liability used in a real world and does it really reach its goals? Finally, is there a need for a change and, if so, by what means?

Tax Treaty Override

What exactly is tax treaty override ? When is it realized ? This thesis, which is the result of a co-directed PhD between the University of Bologna and Tilburg University, gives a deep insight into a topic that has not yet been analyzed in a systematic way. On the contrary, the analysis about tax treaty override is still at a preliminary stage. For this reason the origin and nature of tax treaty override are first of all analyzed in their ‘natural’ context, i.e. within general international law. In order to characterize tax treaty override and deeply understand its peculiarities the evaluation of the effects of general international law on tax treaties based on the OECD Model Convention is a necessary pre-condition. Therefore, the binding effects of an international agreement on state sovereignty are specifically investigated. Afterwards, the interpretation of the OECD Model Convention occupies the main part of the thesis in order to develop an ‘interpretative model’ which can be applied every time a case of tax treaty override needs to be detected. Fictitious income, exit taxes and CFC regimes are analyzed in order to verify their compliance with tax treaties based on the OECD Model Convention and establish when the relevant legislation realizes cases of tax treaty override.

Legal presumptions in national tax systems (Italy and Belgium) and in EU law

The thesis deals with the concept of presumptions, and in particular of legal presumptions, in the context of national tax systems (Italy and Belgium) and EU law. The purpose was to investigate the concept of legal presumption under a twofold comparative perspective. After having provided a general overview of the common core concept of presumption in the European context, an insight in the national approach to legal presumptions was given by examining two different national experiences, namely the Italian and Belgian tax systems. At this stage, the Constitutional framework and some of the most interesting and relevant at EU level presumptive measures were explored, with a view to underlining possible divergences and common grounds. The concept of (national) legal presumption was then investigated in the context of EU law, with the attempt to systematize under a uniform perspective a matter which has been traditionally dealt with either from the merely national point of view or, at EU level, through a fragmented form. In this instance, the EU law relevant framework and the most significant EUCJ case-law, in particular in the field of customs duties, VAT, on the issue of the repayment of taxes levied in breach of EU law and in the area of direct taxation, were examined so as to construe the overall EU approach to national legal presumptions. This was done with the finality of determining if and to what extent a common analytical framework may be identified, from which were extracted certain criteria governing the compatibility of national legal presumptions with EU law.

Il diritto alla detrazione e le frodi Iva

Il presente lavoro parte dalla constatazione che l’Imposta sul valore aggiunto è stata introdotta con lo scopo specifico di tassare il consumo in modo uniforme a livello europeo. La globalizzazione dell’economia con l’abolizione delle frontiere ha tuttavia favorito la nascita non solo di un mercato unico europeo, ma anche di “un mercato unico delle frodi”. L’esistenza di abusi e frodi in ambito Iva risulta doppiamente dannosa per l’Unione europea: tali condotte incidono quantitativamente sull'ammontare delle risorse proprie dell’Unione e sulle entrate fiscali dei singoli Stati membri nonché violano il principio di concorrenza e producono distorsioni nel mercato unico. È in questo contesto che intervengono i giudici nazionali e la Corte di Giustizia, al fine di porre un freno a tali fenomeni patologici. Quest’ultima, chiamata a far rispettare il diritto comunitario, ha sviluppato una misura antifrode e antiabuso consistente nel diniego del diritto alla detrazione qualora lo stesso venga invocato dal soggetto passivo abusivamente o fraudolentemente. Vedremo però che il problema non può essere facilmente ridotto a formule operative: al di là dello schema, fin troppo scontato, dell’operatore apertamente disonesto e degli operatori con esso dichiaratamente correi, rimane il territorio grigio dei soggetti coinvolti, qualche volta inconsapevolmente qualche volta consapevolmente, ma senza concreta partecipazione nella frode da altri orchestrata. Permane a questo punto la domanda se sia coerente - in un sistema impositivo che privilegia i profili oggettivi, prescindendo, salvo gli aspetti sanzionatori, da quelli soggettivi- negare il diritto alla detrazione Iva per asserita consapevolezza di comportamenti fraudolenti altrui o se non vi siano regole più adatte al fine di porre un freno alle frodi e dunque più conformi al principio di proporzionalità.