Repositório RCAAP

Development of new immunogens eliciting broadly neutralizing antibodies (bNAbs) is a main priority for the HIV-1 vaccine field. Envelope glycoproteins from non-B-non-C HIV-1clades have not been fully explored as components of a vaccine. We produced Vaccinia viruses expressing a truncated version of gp120 (gp120t) from HIV-1 clades CRF02_AG, H, J, B, and C and examined their immunogenicity in mice and rabbits. Mice primed with the recombinant Vaccinia viruses and boosted with the homologous gp120t or C2V3C3 polypeptides developed antibodies that bind potently to homologous and heterologous envelope glycoproteins. Notably, a subset of mice immunized with the CRF02_AG-based envelope immunogens developed a cross-reactive neutralizing response against tier 2 HIV-1 Env-pseudoviruses and primary isolates. Rabbits vaccinated with the CRF02_AG-based envelope immunogens also generated potent binding antibodies, and one animal elicited antibodies that neutralized almost all (13 of 16, 81.3%) tier 2 HIV-1 isolates tested. Overall, the results suggest that the novel CRF02_AG-based envelope immunogens and prime-boost immunization strategy elicit the type of immune responses required for a preventive HIV-1 vaccine.

Two contemporary 16th century authors, close to the ideas of Christian humanism, one Portuguese, Gil Vicente, the other English, Thomas More, write in the first quarter of the 16th century using the created image of a perfect principality (Castle/Kingdom and the Island of Utopia). This supposedly real archetype is revealed following exploratory land and sea voyages, depending on the case. In comparison with societies whose experience moves away from that model (European societies mainly of Portugal and England), they critically and sarcastically analyse social and mental flaws by way of the use of a carnivalesque narrative discourse. At the same time, they reveal virtues desirable in political ethics and put forward practical civic solutions to correct the regime. The comparative analysis of two testimonials from that era, Utopia by Thomas More (1516) and Frágua d’Amor (Love Forge) by Gil Vicente (c.1525), of their similarities in terms of objectives and discursive techniques but also of their own definitions of identity, enrich our knowledge of mentalities in the Modern Age.

Developing controversies from the historical past of Portugal supposedly divided into cycles of progress and decadence, historians, scholars, politicians and economists from 19th century Portugal resorted to testimonies of previous centuries to prove their theses. The testimonies selected from the 16th and 17th centuries helped them consolidate a black legend of the Portuguese Empire, mostly because of the fragmentation and lack of contextualization to which such discourses were subject. There must be a revision of contemporary concepts and interpretation that requires a close rereading and objective analysis of the discourse of 16th century authors, their complete works, deepening their philosophy of History and the factors that they valued in their time as conditions of progress and decadence, comparing them with each other and with other different testimonies.

Ao abordar o tema das práticas inanceiras na Época Moderna, pode perspectivar-se a análise sob o ângulo da história económica ou da sociologia iscal. Não faltarão, contudo, factores condicionantes sob o ângulo da contabilidade, do direito, da política e mentalidades, da história da arte e da espiritualidade. As fontes de informação da época (textuais/pictóricas) obrigam a metodologias de inquérito e a comentários próprios cujos resultados contribuirão, numa conjugação de esforços interdisciplinares, para um estudo mais aprofundado do tema. Demonstra-se neste artigo como o investigador, face a extensa bibliograia e fontes de tipologia variada, se deve colocar na encruzilhada de vários saberes para pesquisar e esclarecer o estudo do dinheiro e das suas representações, do crédito, dos mercadores e dos mercados, dos agentes de cobrança de impostos, dos poderes políticos e das avaliações sociais, inventariando, enim, e percorrendo uma série de tópicos de relexão necessários ao esclarecimento das matérias a analisar.

Estudo sobre terras e povoamento processual na capitania régia da Baía de Todos Santos criada em 1548, nomeadamente as Ilhas de Itaparica e Itamarandiba tornadas em 1556 capitania hereditária vinculada a um morgado existente no reino e a mais terras do Rio Vermelho associadas desde então às primeiras no que respeita à sucessão, segundo princípios de excepção relativamente aos Bens da Coroa. Na época e posteriormente, práticas que se procuram de aperfeiçoamento e rentabilidade, não apenas numa perspectiva económica e geopolítica, mas também de criação de novas sociedades, mistas, muito embora inspiradas por padrões mentais e de comportamento lusos. Sesmarias e aforamentos. Objectivos geoestratégicos.

Nas Ordenações portuguesas e mais textos jurídicos quinhentistas incentiva-se oficiais da Justiça e da Fazenda, agentes da Casa real e do governo das cidades, vilas e lugares, naturalmente abastados, a uma conduta que não ocasione “corrupção” da Justiça régia. Estabelecem-se recompensas para denunciantes, abrandamento de pena para confissões, sanções (multas, confisco de bens, degredo) para quem presenteia e para quem recebe peitas. Conhecem-se denúncias em Cortes, em escritos e nas artes, e devassas que poderiam macular a imagem régia. Até que ponto as regras do sistema administrativo permitem aos agentes conciliar o ofício com compromissos políticos, lealdades familiares e pessoais?

Under the supervision of Rubén Cucuzza and Pablo Pineau, this work brings together in a complementary and diachronic form a set of studies drawn up by a group of eight researchers. The study consists of an introduction and twelve chapters, whose chronology is situated between the "colonial catechism" and the adoption by Parliament, in July 1952, of La Razón de Mi Vida (supposed autobiography of Eva Péron), as the sole school textbook for the final years of primary school. We are therefore before a long timescale in the history of the teaching and reading and writing, in the contexts of englightenment, liberalism and the nation-state.

This text aims to highligh the action and the social appraisal of mainly mercantile and financial negotiators in the early modern period. The historical background in which they act, that of modernity, leads us to ask questions related to eras and to shifting paradigms, given the promotion of financial and commercial practices in different European regions and their interconnection, and in a much bigger and systematic extension at intercontinental and planetary level. Hence the highlighting of novelties and continuities in the specific dynamics of merchants and in their inclination to be included in social groups, as well as in the techniques and the way they can promote new social and cultural practices as well as a new mind‐set.

Tendo por suporte textos e elaborações pictóricas, procura-se a imagem criada no século XVI que melhor traduza correntes de pensamento político, social e espiritual. Cruzam-se produções de uma centúria (das belas-artes e das belas-letras) que visam o esclarecimento de reflexões sobre o teor divino e a capacidade humana no homem, suas técnicas de organização social, suas opções de conduta moral. Confrontam-se artistas com diferente formação e experiência buscando na sua contemporaneidade confluências e dicotomias.

Atravessando vastos tempos e espaços, a simbologia da Fénix revela-se em contos lendários da China, da Índia ou da Pérsia, variando em pormenores, construindo-se um mito que o Ocidente herdou do Egipto e que ajuda a consolidar na época clássica, medieval e moderna, com projecções ainda na contemporaneidade. Será que a Fénix europeia nada tem de comum com a Fénix chinesa ou seja a Feng-Huang, para lá da criação mítica relacionada com heranças da humanidade e um inconsciente colectivo, depósito de imagens e de símbolos (Jung)? Numa comparação de pormenores acentua-se de comum a carga espiritual, da rara beleza à virtude divina, da santificação e pureza ao amor eterno, à prosperidade e boa governação, da singularidade e excelência ao renascimento e à eternidade.

The period of time in which Francisco Vitória published his discourses on the power of the Church and on the condition of the American Indian was one of tensions involving lay people, jurists and theologians. The Chamber of Conscience (Mesa da Consciência) was institutionalised in 1532 with its ethical and political dimension closely linked to the sovereign. At the same time, the changes introduced in this nation that generated an Empire and in a church that needed reform are highlighted in moralistic discourses and in texts of an ecclesial nature based on pre-tridentine guidelines. Sometimes echoes of Luther appeared to be heard in the theatre… Strong disturbances occurred all over Europe, inciting new currents of spirituality, coming from Christian humanism or Lutheranism, reactions of differing intensities, of compliance or repulsion, demanding de facto political and social readjustments. Until the institutionalisation in 1536 of the Inquisition in Portugal, an instrument of ethical and religious nature and also of social discipline, the crime of heresy was politicised in France under Francis I, the wars of religion were increasingly intense in the Germany of Charles V, and the Act of Supremacy of the English monarch irremediably divided Christianity. This communication, vis-à-vis sensitivities and concerns differing in terms of space, sought to compare attempts to address problems that were so often common and that revealed facets of a simultaneously political and confessional consciousness at the level of regional or state authorities.

Political theorists, theologians, jurists, men of letters, spoke during the early modern Era about uses and abuses of authority. Offences, vices and crimes of rulers or ruling elites are subject to consideration, by revisiting, in texts and images, the conduct of the political body and the repercussions in the social body, which tolerates them or cooperates with them. The construction shows itself as particularly creative, along with written works which are the inheritance and update of interpretations on the foundations and mechanisms of power, the emblematic with its symbols and enigmatic messages that also cover those subjects. It is, hereby, covered a fertile field of creativity and fantasy, inspired by ancient and modern sources, which combines inscriptio with pictura and with subscriptio, in a dialectical and intelligent articulation, challenging the reader to seek the senses of the enigma. We are faced with a literature largely spread during the Renaissance, which evolves through successive editions and translations, revisiting texts in prose or verse and recreating engravings according to the geographical and epochal vicissitudes. From Alciato to Ripa, imagery manifests a unique intelligence game.

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the Gquartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4’-(4,4’-(1,3-phenylene)bis(1H1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) (1 d) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.

Aims To understand whether the variability found in the proteome of Helicobacter pylori relates to the genomic methylation, virulence and associated gastric disease. Methods and Results We applied the Minimum‐Common‐Restriction‐Modification (MCRM) algorithm to genomic methylation data of 30 Portuguese H. pylori strains, obtained by genome sensitivity to Type II restriction enzymes' digestion. All the generated dendrograms presented three clusters with no association with gastric disease. Comparative analysis of two‐dimensional gel electrophoresis (2DE) maps obtained for total protein extracts of 10 of these strains, representative of the three main clusters, revealed that among 70 matched protein spots (in a universe of 300), 16 were differently abundant (P <0·05) among clusters. Of these, 13 proteins appear to be related to the cagA genotype or gastric disease. The abundance of three protein species, DnaK, GlnA and HylB, appeared to be dictated by the methylation status of their gene promoter. Conclusions Variations in the proteome profile of strains with common geographic origin appear to be related to differences in cagA genotype or gastric disease, rather than to clusters organized according to strain genomic methylation. Significance and Impact of the Study The simultaneous study of the genomic methylation and proteome is important to correlate epigenetic modifications with gene expression and pathogen virulence.

Genome Inspector (GIN) is a new interactive web-based application for exploring bacterial genomes designed to provide users with a wide choice of options to facilitate the process of designing DNA primers for isolating genes from similar bacterial species and strains. GIN employs a project-based approach in which users can select any given set of available genomes and perform a comprehensive bioinformatics analysis. Currently, it encompasses the full set of annotated bacterial genomes available on GenBank, a total of 4300 files corresponding to over 740,000 annotated genes. GIN allows new data to be added directly from GenBank as it is being generated, as well as new genome uploading for personal analysis. The application interfaces were designed with potential users in mind to assist with their most common research goals. Users can visually explore full circular genomes, search for similar regions in other species and strains, and visualize amplified genomic regions for several strains simultaneously. This interactive tool allows for dynamic graphical exploration and refinement of search and exploration criteria. Furthermore, it includes a multiple alignment algorithm (MUSCLE) to help researchers in the process of designing primers. GIN is free and publicly available at http://gin.ul.pt/GIN2/index.php.

Mediante a observação de construções discursivas do século XVI, de diferente natureza, desde obras do teatro de Gil Vicente (1502-1536) a testemunhos de confissões realizadas no âmbito da Visitação inquisitorial à Baía em 1591-1592, salienta-se a existência de sedimentos mentais e resíduos culturais que permanecem e se adaptam a novos contextos epocais e espaciais. Visões de estatuto social e de práticas de sociabilidade, marginalizações e estigmas, adaptações vivenciais, desenvolvem-se no Brasil, uns herdados da sociedade europeia outros condicionados a formas culturais mescladas no novo mundo. Geram-se duplas identidades ou fenómenos de transfusão de resíduos ou mesmo de sincretismos. Seja como for, a residualidade evidencia-se na longa ou na curta duração, originando uma sociedade reformulada pelos seus particularismos.

Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit to the host. Probiotics are not part of the current treatment therapies prescribed for Helicobacter pylori eradication, but there are numerous studies, most of them using probiotics as adjuvants to therapy, showing a reduction of side effects in the greater majority of cases. The probiotics administered vary hugely in the composition of microorganisms used, as well as the duration and mode of administration, which renders the comparison difficult. However, the most used probiotics for H. pylori infection are composed of Lactobacillus, Bifidobacterium, Saccharomyces, and Streptococcus. The mode of action of these probiotics relies on competition for nutrients and for adhesion to cell receptors, antimicrobial activity, and modulation of the immune system and microbiota.

Neste estudo, partirei do princípio de que o livro é central na alfabetização escolar e de que a regimentalização da escola, inerente e necessária à República, teve uma política concertada sobre a leitura, o livro e muito particularmente sobre o livro escolar. Essa intervenção foi no sentido da actualização, científica e pedagógica, e da conciliação de um ideário de progresso e patriotismo. Prosseguia assim a centralidade de uma escolarização e de uma aculturação assentes no livro, revista com o Iluminismo de Estado e regulamentada pelos Liberais. Para além dos aspectos político-pedagógicos, em virtude dos quais, a leitura e o livro (particularmente o livro escolar) estiveram inseridos na alçada do Conselho Superior de Instrução Pública, concretava-se, nas sucessivas Comissões técnicas, que o substituíram, a idiossincrasia entre a república das letras e a república de cidadãos, cumprindo a escola uma função pragmática e legitimadora da hierarquia e da constituição sociopolítica.

Nas vésperas da instalação da Inquisição em Portugal, inquietavam-se os ânimos de cristãos-velhos e de conversos, provocando exaltações e revoltas, por palavras e acções, nas ruas e em Cortes. Tal facto despertaria indubitavelmente a atenção das instâncias régias. Num meio particularmente sensível à jurisdição régia e à disciplina social, o das finanças públicas, as fontes igualmente revelam tensões na década de 30 de Quinhentos. Muitos oficiais das finanças distribuídos pelo reino são conversos, ocupando lugares que vão desde a alta tesouraria do reino ou da alfândega de Lisboa a ofícios de almoxarife, contador ou recebedor das sisas de diversos lugares. Os documentos registados na Chancelaria Régia revelam, entre outros fenómenos, o da clandestinidade judaica e os sentimentos de ameaça, o medo e a fuga, a denúncia, assim como o espoletar de acções de inquirição e de redistribuição de ofícios, acompanhadas de repercussões no campo social, económico e de justiça. Este artigo visa apontar hiatos na historiografia sobre o período moderno e, futuramente, conduzir a investigações sistemáticas e aprofundadas no âmbito da história económica, social e das mentalidades.

Polycyclic Aromatic Hydrocarbons (PAHs) are persistent pollutants normally found in the environment as complex mixtures. Although several individual PAHs are classified as mutagenic and carcinogenic pollutants, the interaction effects between compounds in a mixture may trigger different toxicological mechanisms and, consequently, yield different effects to organisms which are not accounted for in risk assessment guidelines. Given the ubiquity of PAHs, understanding the mechanistic features of their mixtures is a pressing research need. Therefore, the present work aimed to disclose the interaction effects of three PAHs with different carcinogenic potential and chemical structure, in primary hepatocyte cells of gilt-headed seabreams (Sparus aurata). Hepatocytes were exposed to Phenanthrene (Phe), Benzo[a]pyrene (B[a]P) and Benzo[b]fluoranthene (B[b]F) and their mixtures at different proportions and several cellular responses were analyzed: cellular viability, CYP1A1 activity (EROD assay) and protein expression level (Western blot); transcript (mRNA) levels of CYP1A1, EPXH1 and GST-3 (qRT-PCR); genotoxic effects (DNA strand breakage) by the Comet assay. Results show that B[a]P induced CYP1A1 gene and protein expression increasing its activity and, therefore, increasing the production of metabolites that trigger genotoxic DNA damage (%). Most importantly, mixtures containing Phe and B[a]P increased even further CYP1A1 mRNA levels and DNA damage (up to 70 %) which suggests that, although Phe is considered a non-carcinogenic PAH, it potentiates CYP1A1 synthesis induced by B[a]P, increasing its genotoxicity. These findings indicate that the upregulation of CYP1A1 by carcinogenic PAHs will not weaken even when in mixtures with non-carcinogenic PAHs. On contrary, non-carcinogenic PAHs may potentiate the genotoxic effect of carcinogenic PAH and therefore mixture composition should be taken in account when assessing PAH toxicity. In fact, our results point to the need of redefining Environmental Risk Assessment protocols for mixtures of carcinogenic pollutants.