Structural Studies of RNA-dependent RNA polymerases

Most RNA viruses possess an RNA-dependent RNA polymerase (vRdRP), responsible for viral genome replication and transcription. Furthermore, a number of eukaryotic organisms, including plants, fungi, protozoa and some metazoans, produce cellular RdRPs (cRdRPs) involved in RNA silencing mechanisms. One of the best studied vRdRPs is that of the dsRNA bacteriophage Φ6. Structures of Φ6 RdRP (Φ6pol) in complex with RNA oligonucleotides revealed the basis for template specificity: the extra hydroxyl group leads to additional RNA-protein interactions, further stabilizing the template. Structures of "manganese-free" Φ6pol and a mutated form of the protein with lower affinity for the ion (E491Q mutant) provided some hints to the role of manganese. The structure of a complex of Φ6pol with RNA oligonucleotides and GTP with the catalytic magnesium ions substituted by calcium ions shows a distorted geometry of the initiation competent state, providing a molecular explanation of the calcium inhibitory effect. Finally, the structure of a mutated form of the protein (628QYKW632-SG mutant) prone to back-priming initiation revealed a set of contacts important for de novo initiation. Considering the high structural homology of Φ6pol with other vRdRPs, particularly from (+)ssRNA Hepatitis C Virus (HCV), insights into the mechanistic and structural details of Φ6pol are thought to be relevant to the general understanding of vRdRPs. The dimeric structure of QDE-I, an RdRP from the fungus Neurospora crassa involved in RNA silencing, revealed a surprising similarity at the active site level to multi subunit DNA-dependent RNA polymerases (DdRPs). This implies a close evolutionary relationship between these erzymes and a possible connection between RNA silencing pathways and primordial RNA polymerisation mechanisms. Furthermore, an analysis based on the structures of several template dependent polymerases suggests that they have emerged more than once over the course of evolution

Optimization of β-cyclodextrin-based extraction of antioxidant and anti-browning activities from thyme leaves by response surface methodology

Thyme (Thymus vulgaris) has been demonstrated to extend the shelf-life of food products, being also a potential source of bioactive compounds. The aim of this research was to optimize the ultrasound assisted extraction employing β-cyclodextrin aqueous solutions as no-contaminant technology and Response Surface Methodology to obtain thyme extracts with the maximum antioxidant capacity. The optimal extraction conditions were: a solution of β-ciclodextrin 15 mM, an ultrasonic treatment time of 5.9 min at a temperature of 36.6 °C. They resulted in an extract with a polyphenolic content of 189.3 mg GAE/mL, an antioxidant activity (DPPH[rad]) of 14.8 mg GAE/mL, and ferric reducing/antioxidant power (FRAP) of 3.3 mg GAE/mL. Interestingly, the extract demonstrated to inhibit the production of Maillard browning products and can be considered a potential antiglycant agent. The obtained data is important for developing eco-friendly technologies in order to obtain natural antioxidant extracts with a potential inhibitory capacity of Maillard glycation reaction.Fil: Favre, Leonardo Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; ArgentinaFil: dos Santos, Cristina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Lopez Fernandez, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Mazzobre, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; ArgentinaFil: Buera, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentin

Divesture/acquisition analysis: PT/Telefónica/VIVO case study

The main objective of this master thesis is to evaluate the impact of events/announcements in the market capitalization of companies involved and to test market efficiency. Acquisitions, mergers and divestures are strategies followed by companies in order to adjust to economic and political changes and explore opportunities to develop capabilities in new environments. In this study it is analyzed the impact of selling the stake held in Vivo by PT to Telefónica in the market capitalization of the both companies. Additionally it was applied the event study methodology suggested by Mackinlay et al. (1997). This methodology can be used to measure the impact of a specific event on the market capitalization of companies with the purpose to test market efficiency in capital markets. In this study were detected abnormal returns in every events in analysis, with special focus on event 2 and 3, that correspond respectively, to the day 1st June 2010 (day in which Telefónica launched the second offer in order to acquire Vivo, for the amount of €6.5 bn) and the day 30th June 2010 (day when the General Board Meeting occurred and the Portuguese government used the golden share in order to block the operation).O principal objectivo desta tese de mestrado é avaliar o impacto dos eventos/anúncios na capitalização bolsista das empresas de forma a testar a eficiência dos mercados. As aquisições, fusões e desinvestimentos são estratégias levadas a cabo pelas empresas de forma a ajustarem-se ás mudanças económicas e políticas para assim desenvolverem novas capacidades que lhes permitam aproveitar as oportunidades que existem na envolvente. Neste estudo analisa-se o impacto que a venda da participação da PT na Vivo, á Telefónica, teve na capitalização bolsista de ambas as empresas. Adicionalmente, é também aplicada a metodologia do estudo de eventos sugerida por Mackinlay et al. (1997). Esta metodologia tem como objectivo medir o impacto de um evento/anúncio específico na capitalização bolsista das empresas, estando desta forma a testar a eficiência dos mercados de capitais. Neste estudo detectaram-se rentabilidades anómalas em todos os eventos em análise, com especial incidência no evento 2 e 3, que correspondem respectivamente, ao dia 1 de Junho de 2010 (dia em que a Telefónica lançou a segunda oferta com o objectivo de adquirir a participação detida pela PT na Vivo pelo montante de €6.5 bn) e ao dia 30 de Junho de 2010 (dia em que ocorreu a Assembleia Geral de Accionistas da PT em que foi usada a Golden Share por parte do Governo Português de forma a bloquear a operação)

Mozambique: The Rise of a Micro Dual State

The decade from 1990 to 2000 was a period of sustained political activity in Africa, leading towards democratisation. Under this scope, Mozambique is widely seen as one paradigmatic success story. Yet, the country’s multiparty democratic system remains challenged by a strong authoritarianism that hampers open deliberation in political public discourse. This paper discusses some reasons for this democratic hold-up in Mozambique’s political and social transition within the broad and ongoing democratisation process in Sub-Saharan Africa. With an emphasis on the analysis of the political situation in the northern town of Angoche, this article argues that the persistence of central government authoritarianism is a reminder of a political liberalisation without democratising the political systems. Indeed, local municipal officials are now elected and receive revenue transfers, but remain limited by other measures.2 The central state successfully resists attempts to devolve broader decision-making authority to municipalities. Far from the ideal Weberian type of state bureaucracy, public administration is highly politicised in the sense that the building up of the administrative capacities of the state are seen as a way of consolidating the political leverage of the ruling party – Frelimo. The paper defends, however, that indeed, a detailed analysis of the public political actions at local level, between distinct political structures, shows that successive authoritarian regimes have not totally erased the freedom of speech and thought, even if they have relegated opposition to ever more marginal spaces.La décennie 1990/2000 a été caractérisée en Afrique par une activité politique soutenue orientée vers la démocratisation. Dans ce cadre, le Mozambique est plutôt vu comme une réussite paradigmatique. Or, ce système démocratique de multipartisme continue à afficher des velléités d’un fort autoritarisme peu propice au relèvement du niveau de la réflexion dans le discours politique public. Cette étude s’interesse aux raisons de ce blocage démocratique du processus de transition politique et social au Mozambique dans le cadre plus général du processus de démocratisation en cours en Afrique au sud du Sahara. En s’appuyant en particulier sur l’analyse de la situation politique de la ville d’Angoche, située au nord du pays, l’étude estime que le fait que le gouvernement central persiste dans l’autoritarisme est assez révélateur d’une libéralisation politique non suivie de la démocratisation des systèmes politiques. En effet, si les fonctionnaires municipaux locaux sont maintenant élus et reçoivent des fonds de transfert, ils restent, en revanche, limités par d’autres mesures.2 Le gouvernement central résiste avec succès à toute tentative d’élargir le mandat des municipalités en matière de prise de décision. Loin du modèle idéal wébérien de bureaucratie d’Etat, l’administration publique est fortement politicisée, en ce sens que le renforcement des capacités administratives de l’Etat est perçue comme un moyen de renforcer l’influence politique du parti au pouvoir – Frelimo. L’étude défend le fait qu’une analyse exhaustive des actions politiques publiques au niveau local, entre des structures politiques bien distinctes, montre que les régimes autoritaires successifs n’ont pas totalement supprimé la liberté d’expression et de pensée même s’ils ont repoussé l’opposition encore plus loin dans les espaces marginaux

Hearing protection : selection factors and risks of excessive attenuation

Currently, noise exposure in the occupational setting continues to be a problem in industrialized countries, not only because this is the most common occupational disease in these countries, but also because it is transversal to all activity sectors, including leisure activities. Exposure to high noise levels can affect the hearing system. For this reason, the legislation requires that the employer implements a set of measures to protect the exposed worker, and as last solution the use of individual hearing protection. However, what occurs in practice and in the majority of cases is the adoption of the use of hearing protection, at the expense of collective protective measures. Nevertheless, not always their selection is made of the most efficient manner. Excessive attenuation of the protectors, as well as the existence of sectors where impulsive noise is produced, are currently the main concerns of safety technicians