Metabolic Diseases: a differential diagnosis of primary progressive multiple sclerosis

Objectives: The overall aim of our research project is to develop a Next Generation Sequencing strategy to identify metabolic disorders in 104 patients with a presumptive diagnosis of primary progressive MS.We would like to thank to MERCK, SA and NORTE2020 (NORTE-01-0246-FEDER-000014) for funding this Project.N/

Garantizar el orden: debates sobre el derecho de revolución y el federalismo en el Congreso Nacional durante la intervención a Corrientes de 1878

El trabajo revisa la coyuntura política de finales de la década de 1870 y analiza las alternativas que signaron la "Conciliación de los partidos" planteada por el presidente Nicolás Avellaneda. El trabajo da cuenta de las tensiones que atravesaban el escenario político y de los diversos actores que allí intervenían abordando un caso particular: los conflictos suscitados en la provincia de Corrientes por la elección de gobernador. Allí las controversias derivaron en un enfrentamiento armado que provocó la intervención federal y suscitó intensos debates parlamentarios sobre las características del régimen federal y la legitimidad de las acciones armadas. A través de dicha polémica se advierte el difícil equilibrio que exigía la federación en tanto modelo de estado y régimen de gobierno. La vigencia efectiva del principio de soberanía popular entraba en tensión con los resguardos de autonomía consagrados por el pacto federal cuando una disputa electoral derivaba en una acción armada. En esas circunstancias se planteaba un interrogante clave: ¿quién era el garante del orden constitucional? Ese interrogante involucraba un abanico de cuestiones que expresaban las indeterminaciones acerca del federalismo y la situación de ´provisionalidad´ de algunas instituciones claves no sólo del ámbito nacional sino también de los espacios provinciales.Fil: Cucchi, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; ArgentinaFil: Navajas, Maria José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; Argentin

A escolha apesar da (in)comensurabilidade: Controvérsias e tomada de decisão pública acerca do desenvolvimento territorial sustentável

Report of the project BECOM This project is meant to explore decision making devices (namely instruments and procedures) and their role in dealing with conflicts between (incommensurable) values as they arise in the process of public decision-making concerning the sustainability of projects with major impact on environment. With the European Union Directive 2001/42/EC the assessment procedure known as Strategic Environmental Assessment (SEA) became a major instrument for implementing sustainable territorial development policies in the EU. Public decision is thus called to translate into practice the goal of territorial sustainable development - a guiding principle of public action that requires the composition of different and often contrasting definitions concerning desirable common goods to pursue (O'Neill 2007). However, the directive does not contain any indication in respect to the way in which this composition should be achieved, leaving thus room for controversies and varied, context-dependent, arrangements. In the literature concerned with public decision, the necessity to compose normative conflicting stances is addressed differently according to the approach to choice adopted. Two approaches, a monistic approach and a pluralistic approach, may be singled out as end points of a continuum. Both approaches have informed the definition of specific devices (instruments and procedures) to help public decision.The monistic approach to composition relies on commensurability. It has its basis in utilitarianism and its most sophisticated and influential contemporary applied form in cost-benefit analysis (Pearce et al. 2006; Posner 2004). According to this approach the resolution of conflicts of value requires their reduction to a common measure through which different values can be traded off with one another (Espeland and Stevens 1998). On the contrary, the pluralistic approach, supported by different theoretical traditions among which pragmatism stands out, claims that public choice may be rational in spite of value conflicts and incommensurability (Richardson 2002). Integrated and multicriteria approaches are devices of decision that try to operationalize the pluralistic approach to public decision. The project combines two different but interwoven explorations. The first is meant to analyse the translation of the monistic and the pluralistic approaches into "devices of decision" (cost-benefit analysis; integrated and multicriteria approaches). In particular, we aim at investigating how these devices (instruments and procedures) deal, technically, with value incommensurability and "moral difficulty", as well as with the epistemic uncertainty characterizing environmental issues. The second axis is devoted to the observation of how these devices have been enacted in controversies concerning large infrastructural projects, specifically airports, in two cases: the decision on the location of the new Lisbon airport and the decision on the extension of Milan airport. Through a comparative approach (Italy and Portugal) we are interested in addressing the role played by political cultures in the way these devices are implemented (Jasanoff 2007). In treating these tools and models of decision-making as specific socio-technical tools we are rejoining Science and Technology Studies (STS) in one of its recent trends of development: the move from studying how "hard" sciences participate in the shaping of our world in common towards studying, with the same purpose, the role of economics and social sciences (Callon 1998). The aim of the project is not advancing a formal model for decision making in socio-technical controversies involving value conflicts and incommensurability. Our contribution is rather directed towards a better understanding of how devices supporting public decision address issues of incommensurability in situations of normative and epistemic uncertainty. In particular, on the basis of the research results, we will work at pointing out some features of the devices (instruments and procedures) best suited to help transforming incommensurability in an opportunity for democratic debate concerning collective goals and means to pursue them. The theoretical and empirical exploration we propose is meant to develop a critical analysis of both the relevance of devices of decision in shaping public decision processes in socio-technical controversies and the pros and cons of the specific way in which they help in dealing with normative and epistemic uncertainty.Relatorio do projeto BECOM Este projecto pretende explorar dispositivos (instrumentos e procedimentos) de tomada de decisão e o papel que desempenham no modo como os conflitos entre valores (incomensuráveis) são geridos nos processos de tomada de decisão pública a respeito da sustentabilidade de projectos com impactos importantes no ambiente. Com a Directiva da União Europeia 2001/42/EC o procedimento de avaliação conhecido como Avaliação Ambiental Estratégica (AAE) tornou-se um importante instrumento das políticas de desenvolvimento territorial sustentável na UE. Com esta directiva os decisores públicos são chamados a traduzir na prática o objectivo de desenvolvimento territorial sustentável - um princípio orientador da acção pública que requer a composição de definições diversas e muitas vezes contrastantes dos bens comuns que é desejável perseguir (O'Neil 2007). Contudo, a directiva não contem nenhuma indicação a respeito do modo como esta composição deve ser conseguida, deixando espaço para controvérsias e arranjos variados, dependentes do contexto. Na bibliografia respeitante à tomada de decisão pública, a necessidade de compor dimensões conflituais do ponto de vista normativo é tratada de forma distinta consoante a abordagem à escolha adoptada. É possível identificar, como extremos de um continuum , duas abordagens: a abordagem monistica e abordagem pluralista. Ambas constituem fundamento para a definição de dispositivos (instrumentos e procedimentos) de apoio à tomada de decisão. A abordagem monista assenta na comensurabilidade. Com origem no utilitarismo e a sua forma contemporânea aplicada mais sofisticada e influente é a análise custo-benefício (OECD 2006; Posner 2004). De acordo com esta abordagem a resolução de conflitos de valor requer a redução de todos os valores a uma métrica comum que possibilite trade-offs entre eles (Espeland and Stevens 1998). A abordagem pluralista, apoiada em diferentes tradições teóricas, entre as quais se destaca o pragmatismo, defende, pelo contrário, que a escolha pública pode ser racional apesar dos conflitos de valores e da incomensurabilidade (Richardson 2002). As abordagens multicritértio e integradas são dispositivos de tomada de decisão que procuram operacionalizar a abordagem pluralista de tomada de decisão. Este projecto combina duas linhas de exploração diferentes mas inter-relacionadas. A primeira é dirigida à análise da tradução das abordagens monista e pluralista em "dispositivos de decisão" (análise custo-benefício; abordagens multicritério e integradas). Em particular, pretendemos investigar o modo como estes dispositivos (instrumentos e procedimentos) lidam com a incomensurabilidade e a "dificuldade moral", assim como com a incerteza epistémica que caracteriza as questões ambientais. O segundo eixo é dedicado à observação do modo como estes dispositivos têm sido operacionalizados em controvérsias respeitantes a grandes projectos infra-estruturais, especificamente aeroportos, em dois casos: a decisão acerca da localização do novo aeroporto de Lisboa e a decisão acerca do alargamento do aeroporto de Milão. Através de uma abordagem comparativa (Itália e Portugal) o nosso interesse dirige-se também à influência que as culturas políticas têm no modo como estes dispositivos são usados na prática (Jasanoff 2007). Tratando estas ferramentas e modelos de tomada de decisão como ferramentas sócio-técnicas especificas seguimos os Estudos de Ciência e Tecnologia numa das suas recentes tendências de desenvolvimento: a deslocação do estudo acerca do modo com as ciências "duras" participam na definição do nosso mundo comum para o estudo, feito com o mesmo objectivo, do papel da economia e das ciências sociais (Callon 1998). O objectivo do projecto não é propor um modelo formal de tomada de decisão em controvérsias sócio-tecnicas que envolvem conflitos de valor e incomensurabilidade. A nossa contribuição será antes dirigida a uma melhor compreensão do modo como os dispositivos de apoio à tomada de decisão lidam com a questão da incomensurabilidade em situações de incerteza normativa e epistémica. Procuraremos, em particular, com base nos resultados da pesquisa, assinalar algumas características dos dispositivos (instrumentos e procedimentos) que melhor contribuem para transformar a incomensurabilidade numa oportunidade para o debate democrático a respeito dos objectivos comuns e dos meios para os realizar. A exploração teórica e empírica que propomos pretende desenvolver uma análise crítica quer da influência dos dispositivos de tomada de decisão sobre os processos de tomada de decisão pública em controvérsias sócio-técnicas, quer das vantagens e inconvenientes dos modos específicos como eles ajudam a lidar com a incerteza normativa e epistémica

Citrus psorosis virus movement protein contains an aspartic protease required for autocleavage and the formation of tubule-like structures at plasmodesmata

Plant virus cell-to-cell movement is an essential step in viral infections. This process is facilitated by specific virus-encoded movement proteins (MPs), which manipulate the cell wall channels between neighboring cells known as plasmodesmata (PD). Citrus psorosis virus (CPsV) infection in sweet orange involves the formation of tubule-like structures within PD, suggesting that CPsV belongs to "tubuleforming" viruses that encode MPs able to assemble a hollow tubule extending between cells to allow virus movement. Consistent with this hypothesis, we show that the MP of CPsV (MPCPsV) indeed forms tubule-like structures at PD upon transient expression in Nicotiana benthamiana leaves. Tubule formation by MPCPsV depends on its cleavage capacity, mediated by a specific aspartic protease motif present in its primary sequence. A single amino acid mutation in this motif abolishes MPCPsV cleavage, alters the subcellular localization of the protein, and negatively affects its activity in facilitating virus movement. The amino-terminal 34-kDa cleavage product (34KCPsV), but not the 20-kDa fragment (20KCPsV), supports virus movement. Moreover, similar to tubule-forming MPs of other viruses, MPCPsV (and also the 34KCPsV cleavage product) can homooligomerize, interact with PD-located protein 1 (PDLP1), and assemble tubule-like structures at PD by a mechanism dependent on the secretory pathway. 20KCPsV retains the protease activity and is able to cleave a cleavage-deficient MPCPsV in trans. Altogether, these results demonstrate that CPsV movement depends on the autolytic cleavage of MPCPsV by an aspartic protease activity, which removes the 20KCPsV protease and thereby releases the 34KCPsV protein for PDLP1-dependent tubule formation at PD. IMPORTANCE Infection by citrus psorosis virus (CPsV) involves a self-cleaving aspartic protease activity within the viral movement protein (MP), which results in the production of two peptides, termed 34KCPsV and 20KCPsV, that carry the MP and viral protease activities, respectively. The underlying protease motif within the MP is also found in the MPs of other members of the Aspiviridae family, suggesting that protease-mediated protein processing represents a conserved mechanism of protein expression in this virus family. The results also demonstrate that CPsV and potentially other ophioviruses move by a tubule-guided mechanism. Although several viruses from different genera were shown to use this mechanism for cell-to-cell movement, our results also demonstrate that this mechanism is controlled by posttranslational protein cleavage. Moreover, given that tubule formation and virus movement could be inhibited by a mutation in the protease motif, targeting the protease activity for inactivation could represent an important approach for ophiovirus control.Fil: Robles Luna, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Peña, Eduardo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Borniego, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Heinlein, Manfred. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; FranciaFil: Garcia, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentin

CHARACTERIZATION OF TEMPORAL RAINFALL DISTRIBUTION IN FLORIANÓPOLIS, SANTA CATARINA, BRAZIL

Temporal rainfall distribution is an important information for the preparation of the design hyetograph, directly influencing peak flow. This study analyzes the temporal rainfall distribution of Florianópolis city. We used rainfall data from 1986 to 2012 obtained from the Brazilian National Meteorological Institute (code 83897). Heavy rainfall events were classified and individualized, and intensities were determined at each 5% interval of the duration. Rainfall was classified in Huff quartiles and identified by season and duration. Rainfall accumulation curves in the 10-90 percentiles were determined as well as 50% probability curves for each season and duration. The results showed that type I rainfall is the most frequent and that summer rains have a more anticipated pattern. Important differences were found between rainfall durations. The advance coefficient varies with rainfall duration, and averaged 0.38

Identification of a novel human E-Cadherin splice variant andassessment of its effects upon EMT-related events

Epithelial Cadherin (E-cadherin) is involved in calcium-dependent cell-cell adhesion and signal transduction. The E-cadherin decrease/loss is a hallmark of Epithelial to Mesenchymal Transition (EMT), a key event in tumor progression. The underlying molecular mechanisms that trigger E-cadherin loss and consequent EMT have not been completely elucidated. This study reports the identification of a novel human E-cadherin variant mRNA produced by alternative splicing. A bioinformatics evaluation of the novel mRNA sequence and biochemical verifications suggest its regulation by Nonsense-Mediated mRNA Decay (NMD). The novel E-cadherin variant was detected in 29/42 (69%) human tumor cell lines, expressed at variable levels (E-cadherin variant expression relative to the wild type mRNA = 0.05-11.6%). Stable transfection of the novel E-cadherin variant in MCF-7 cells (MCF7Ecadvar) resulted in downregulation of wild type E-cadherin expression (transcript/protein) and EMT-related changes, among them acquisition of a fibroblastic-like cell phenotype, increased expression of Twist, Snail, Zeb1, and Slug transcriptional repressors and decreased expression of ESRP1 and ESRP2 RNA binding proteins. Moreover, loss of cytokeratins and gain of vimentin, N-cadherin and Dysadherin/FXYD5 proteins was observed. Dramatic changes in cell behavior were found in MCF7Ecadvar, as judged by the decreased cell-cell adhesion (Hanging-drop assay), increased cell motility (Wound Healing) and increased cell migration (Transwell) and invasion (Transwell w/Matrigel). Some changes were found in MCF-7 cells incubated with culture medium supplemented with conditioned medium from HEK-293 cells transfected with the E-cadherin variant mRNA. Further characterization of the novel E-cadherin variant will help understanding the molecular basis of tumor progression and improve cancer diagnosis.Fil: Matos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Marin Briggiler, Clara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giustina, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Furlong, Laura Ines. Universitat Pompeu Fabra; EspañaFil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

ONG de mulheres e a luta contra a violência contra as mulheres e crianças no seio da família: o contributo da UMAR

Galvão Walnice Nogueira. Patrick Chabal et al., The postcolonial literature of Lusophone Africa. In: Lusotopie, n°6, 1999. Dynamiques religieuses en lusophonie contemporaine. p. 532