A magnanimidade da teoria: interpretar a ética em teoria da literatura

Tese de doutoramento, Teoria da Literatura, Universidade de Lisboa, Faculdade de Letras, 2003Um dos pressupostos desta tese consiste na ideia segundo a qual o pensamento ético só adquire propriedade conceptual se preliminarmente pudermos definir ‘acção’. Como se procura demonstrar no capítulo I, saber o que é uma acção não se constitui, no entanto, como tarefa que descobre e estabelece propriedades intrínsecas e estáveis, mas como descrição de certas ocorrências, nos termos das pessoas que procuram explicar e descrever acções. Assim, o pensamento ético é algo que se constitui a partir da coerência e racionalidade de certas descrições de acções particulares e não um sistema de regras ou prescrições. Defende-se que a coerência estrutural destas descrições determina não apenas a consideração moral das acções, mas também a possibilidade do conhecimento entre as pessoas e a certeza, mais poética do que epistemológica, da sua existência. Se uma certa estabilidade do texto ético e uma certeza suficiente acerca do conhecimento humano dependem da configuração mais ou menos padronizada das acções humanas e do funcionamento mental, assumem especial relevância cognitiva e ética os casos e fenómenos de irracionalidade na realização de acções e formação de crenças. De facto, como se sugere no capítulo II, estes casos suscitam perplexidades éticas e cognitivas e assinalam o carácter provisório e conceptualmente circunscrito das nossas descrições sobre acções e pessoas, no contexto restrito do pensamento filosófico e ético. Importa por isso considerar outros textos em que a acção se constitui como motivo de estrutura argumentativa e objecto de análise. A consideração da tragédia e, sobretudo, a análise da teorização poética de Aristóteles acerca do texto trágico formam o capítulo III desta tese. A determinação ética da argumentação técnica da Poética é tão relevante para o entendimento da tragédia quanto, para a ética, conduta moral e compreensão da irracionalidade, é de absoluta pertinência uma particular descrição da acção trágica e da peculiaridade de certas actividades interpretativas exigidas não só por esse entendimento trágico de acção, mas por qualquer texto.ABSTRACT - One of the central ideas of this thesis is that ethical thinking acquires conceptual accuracy only when we can define ‘action’. As it is suggested in chapter I, to know what an action is is not, nevertheless, an activity which finds and establishes intrinsic and stable properties, but a description of some phenomena, in the vocabulary of those who seek to explain and to describe actions. Thus, ethical thinking is derived from the coherence and rationality of descriptions of particular actions and is not, therefore, a system of rules and prescriptions. It is argued that the structural coherence of these descriptions determines not only the moral apprehension of actions, but also the possibility of knowledge of persons and the assurance, more poetical than epistemological, of their existence. If a certain stability of the ethical text and a sufficient certainty about human knowledge depend on a more or less standard configuration of human actions and of mental functioning, then irrational episodes and phenomena in action and belief assume a particular cognitive and ethical relevance. As proposed in chapter II, these cases excite some ethical and cognitive perplexities and show the provisional and conceptually circumscribed character of our descriptions of actions and persons, in the strict realm of philosophy and ethics. It is necessary, therefore, to consider other texts in which action is constituted as the cause for the argumentative structure and object of analysis. The consideration of tragedy and, mostly, of the treatment of the tragic text in Aristotle’s Poetics constitutes an important part of this task and is sketched in chapter III. The ethical influence of the technical arguments of the Poetics is therefore relevant to the understanding of tragedy. A particular description of tragic action and of the specificity of interpretative activities is required not only by the understanding of action in tragedy as by the description of ethical patterns of moral behaviour and the comprehension of irrationality in any text.Fundação Calouste Gulbenkian: Bolsa de Curta Duraçã

Peptide:lipid ratio and membrane surface charge determine the mechanism of action of the antimicrobial peptide BP100. Conformational and functional studies

The cecropin-melittin hybrid antimicrobial peptide BP100 (H-KKLFKKILKYL-NH2) is selective for Gram-negative bacteria, negatively charged membranes, and weakly hemolytic. We studied BP100 conformational and functional properties upon interaction with large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs, containing variable proportions of phosphatidylcholine (PC) and negatively charged phosphatidylglycerol (PG). CD and NMR spectra showed that upon binding to PG-containing LUVs BP100 acquires a-helical conformation, the helix spanning residues 3-11. Theoretical analyses indicated that the helix is amphipathic and surface-seeking. CD and dynamic light scattering data evinced peptide and/or vesicle aggregation, modulated by peptide: lipid ratio and PG content. BP100 decreased the absolute value of the zeta potential () of LUVs with low PG contents; for higher PG, binding was analyzed as an ion-exchange process. At high salt, BP100-induced LUVS leakage requires higher peptide concentration, indicating that both electrostatic and hydrophobic interactions contribute to peptide binding. While a gradual release took place at low peptide:lipid ratios, instantaneous loss occurred at high ratios, suggesting vesicle disruption. Optical microscopy of GUVs confirmed BP100-promoted disruption of negatively charged membranes. the mechanism of action of BP100 is determined by both peptide:lipid ratio and negatively charged lipid content While gradual release results from membrane perturbation by a small number of peptide molecules giving rise to changes in acyl chain packing, lipid clustering (leading to membrane defects), and/or membrane thinning, membrane disruption results from a sequence of events large-scale peptide and lipid clustering, giving rise to peptide-lipid patches that eventually would leave the membrane in a carpet-like mechanism. (C) 2014 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Institut Nacional de Ciencia e Tecnologia de fluidos complexos (INCTFCx)Nude de Apoio Pesquisa de Fluidos Complexos (NAPFCx)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ São Paulo, Inst Chem, Dept Biochem, BR-05513970 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Med Biochem, Nucl Magnet Resonance Natl Ctr, Rio de Janeiro, BrazilEmbrapa Recursos Genet & Biotecnol, BR-70770917 Brasilia, DF, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, BrazilFAPESP: 2007/50970-5FAPESP: 2013/08166-5Web of Scienc

In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.São Paulo Research Foundation grants: (2011/24038-1 [MRDL], 2009/08559-1 [HBdS], CAPES/IGC 04/ 2012 [MRDL, CET])

Selective oxidation of glucose to glucuronic acid by cesium-promoted gold nanoparticle catalyst

International audienc

Dehydration Determines Hydrotropic Ion Affinity for Zwitterionic Micelles

Specific ion effects in zwitterionic micelles, especially for anions, are evident in reaction kinetics, zeta potential, and critical micelle concentration measurements. However, anion adsorption to zwitterionic micelles does not produce significant changes in shape, aggregation number, or interfacial hydration. Here we used molecular dynamics simulation of systems containing sulfobetaine zwitterionic micelles of N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (DPS) and nine different salts to explore ion adsorption in terms of group dehydration. Our results, in line with those obtained for cationic micelles, showed that the adsorption degree of anions containing both hydrophobic and hydrophilic portions, i.e., hydrotropes, were correlated with the ion dehydration and were governed mainly by the hydrophobic portion dehydration upon adsorption

Interfacial concentrations of chloride and bromide and selectivity for ion exchange in vesicles prepared with dioctadecyldimethylammonium halides, lipids, and their mixtures

The local concentrations of chloride, Cl b, and bromide, Br b, in the interface of vesicles prepared with dioctadecyldimethylammonium chloride, DODAC, or bromide, DODAB, dipalmitoylphosphatidylcholine, DPPC, dimyristoylphosphatidylcholine, DMPC, and mixtures of DMPC, DPPC, and DODAC were determined by chemical trapping by analyzing product yields from spontaneous dediazoniation of vesicle-bound 2,6-dimethyl-4-hexadecylbenzenediazonium ion. The values of Cl b and Br b in DODAC and DODAB vesicles increase with vesicle size, in agreement with previous data showing that counterion dissociation decreases with vesicle size. Addition of tetramethylammonium chloride displaces bromide from the DODAB vesicular interface. The value for the selectivity constant for Br/Cl exchange at the DODAB vesicular interface obtained by chemical trapping was ∼2.0, well within values obtained for comparable amphiphiles. In vesicles of DPPC the values of Cl b were very sensitive to the nature of the cation and decreased in the order Ca 2+ > Mg 2+ > Li + > Na + > K + = Cs + = Rb + ≥ +. The effect of the cation becomes more important as temperature increases above the phase transition temperature, T m, of the lipid. The values of Cl b increased sigmoidally with the mol % of DODAC in vesicles prepared with DODAC/lipid mixtures. In sonicated vesicles prepared with DODAC and DMPC (or DPPC), the values of Cl b reach local concentrations measured for the pure amphiphile at 80 mol % DODAC. These results represent the first extensive study of local concentration of ions determined directly by chemical trapping in vesicles prepared with lipids, synthetic ampliiphiles, and their mixtures