L'itinéraire philosophique d'Hilary Putnam, des mathématiques à l'éthique

Dans cette thèse, je propose une lecture renouvelée de l’itinéraire philosophique d’Hilary Putnam concernant la problématique du réalisme. Mon propos consiste essentiellement à défendre l’idée selon laquelle il y aurait beaucoup plus de continuité, voir une certaine permanence, dans la manière dont Putnam a envisagé la question du réalisme tout au long de sa carrière. Pour arriver à une telle interprétation de son oeuvre, j’ai essentiellement suivi deux filons. D’abord, dans un ouvrage du début des années 2000, Ethics without Ontology (2004), Putnam établit un parallèle entre sa conception de l’objectivité en philosophie des mathématiques et en éthique. Le deuxième filon vient d’une remarque qu’il fait, dans l’introduction du premier volume de ses Philosophical Papers (1975), affirmant que la forme de réalisme qu’il présupposait dans ses travaux des années 1960-1970 était la même que celle qu’il défendait en philosophie des mathématiques et qu’il souhaitait défendre ultérieurement en éthique. En suivant le premier filon, il est possible de mieux cerner la conception générale que se fait Putnam de l’objectivité, mais pour comprendre en quel sens une telle conception de l’objectivité n’est pas propre aux mathématiques, mais constitue en réalité une conception générale de l’objectivité, il faut suivre le second filon, selon lequel Putnam aurait endossé, durant les années 1960-1970, le même type de réalisme en philosophie des sciences et en éthique qu’en philosophie des mathématiques. Suivant cette voie, on se rend compte qu’il existe une similarité structurelle très forte entre le premier réalisme de Putnam et son réalisme interne. Après avoir établi la parenté entre le premier et le second réalisme de Putnam, je montre, en m’inspirant de commentaires du philosophe ainsi qu’en comparant le discours du réalisme interne au discours de son réalisme actuel (le réalisme naturel du commun des mortels), que, contrairement à l’interprétation répandue, il existe une grande unité au sein de sa conception du réalisme depuis les années 1960 à nos jours. Je termine la thèse en montrant comment mon interprétation renouvelée de l’itinéraire philosophique de Putnam permet de jeter un certain éclairage sur la forme de réalisme que Putnam souhaite défendre en éthique.

Caf1A usher possesses a Caf1 subunit-like domain that is crucial for Caf1 fibre secretion

The chaperone/usher pathway controls assembly of fibres of adhesive organelles of Gram-negative bacteria. The final steps of fibre assembly and fibre translocation to the cell surface are co-ordinated by the outer membrane proteins, ushers. Ushers consist of several soluble periplasmic domains and a single transmembrane beta-barrel. Here we report isolation and structural/functional characterization of a novel middle domain of the Caf1A usher from Yersinia pestis. The isolated UMD (usher middle domain) is a highly soluble monomeric protein capable of autonomous folding. A 2.8 angstrom (1 angstrom = 0.1 nm) resolution crystal structure of UMD revealed that this domain has an immunoglobulin-like fold similar to that of donor-strand-complemented Caf1 fibre subunit. Moreover, these proteins displayed significant structural similarity. Although UMD is in the middle of the predicted amphipathic beta-barrel of Caf1A, the usher still assembled in the membrane in the absence of this domain. UMD did not bind Caf1M-Caf1 complexes, but its presence was shown to be essential for Caf1 fibre secretion. The study suggests that UMD may play the role of a subunit-substituting protein (dummy subunit), plugging or priming secretion through the channel in the Caf1A usher. Comparison of isolated UMD with the recent strcture of the corresponding domain of PapC usher revealed high similarity of the core structures, suggesting a universal structural adaptation of FGL (F(1)G(1) long) and FGS (F(1)G(1) short) chaperone/usher pathways for the secretion of different types of fibres. The functional role of two topologically different states of this plug domain suggested by structural and biochemical results is discussed.

Apolipoprotein B-48: comparison of fasting concentrations measured in normolipidaemic individuals using SDS-PAGE, immunoblotting and ELISA

Raised levels of chylomicrons and chylomicron remnants, which circulate following a meal, have been implicated in the development of atherosclerosis. Apolipoprotein (apo) B-48 is exclusively associated with chylomicron particles and provides a specific direct measurement of the number of intestinally derived lipoproteins in the circulation. The quantification of apo B-48 in biological samples is difficult due to the very low concentration in plasma, structural similarity to the N-terminal 48% of apo B-100 and lack of an appropriate standard for apo B-48. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), followed by coomassie blue staining, has been used for many years to measure apo B-48 levels in triacylglycerol (TAG)-rich lipoprotein samples. The raising of antiserum to apo B-48 has led to development of more sensitive and specific methods including immunoblotting and enzyme-linked immunosorbant assays (ELISAs). This has enabled direct measurement of apo B-48 in plasma without the need for separation into TAG-rich lipoproteins. A high degree of variability was observed in the apo B-48 concentrations reported in the literature both within and between the SDS-PAGE, immunoblotting and ELISA methods. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women

Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial complince (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (sem 2.0) % at baseline and 15.5 (sem 1.1) % after isoflavone treatment compared with 12.4 (sem 1.0) % after placebo treatment (P=0.03). NOx increased from 27.7 (sem 2.7) to 31.1 (sem 3.2) mu m after isoflavones treatment compared with 25.4 (sem 1.5) to 20.4 (sem 1.1) mu m after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production

Background: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. Objective: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ER beta (AluI) and ER beta[cx] (Tsp5091), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. Design: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1;50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. Results: Isoflavones improved CRP concentrations [odds ratio (95% Cl) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ER beta AluI genotypes. Conclusion: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ER beta gene polymorphic subgroup.

Isoflavones and endothelial function

Dietary isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. Oestrogen is believed to have beneficial effects on endothelial function and may be one of the mechanisms by which premenopausal women are protected against CVD. Decreased NO production and endothelial NO synthase activity, and increased endothelin-1 concentrations, impaired lipoprotein metabolism and increased circulating inflammatory factors result from oestrogen deficiency. Oestrogen acts by binding to oestrogen receptors alpha and beta. Isoflavones have been shown to bind with greater affinity to the latter. Oestrogen replacement therapy is no longer thought to be a safe treatment for prevention of CVD; isoflavones are a possible alternative. Limited evidence from human intervention studies suggests that isoflavones may improve endothelial function, but the available data are not conclusive. Animal studies provide stronger support for a role of isoflavones in the vasculature, with increased vasodilation and endothelial NO synthase activity demonstrated. Cellular mechanisms underlying the effects of isoflavones on endothelial cell function are not yet clear. Possible oestrogen receptor-mediated pathways include modulation of gene transcription, and also non-genomic oestrogen receptor-mediated signalling pathways. Putative non-oestrogenic pathways include inhibition of reactive oxygen species production and up regulation of the protein kinase A pathway (increasing NO bioavailability). Further research is needed to unravel effects of isoflavones on intracellular regulation of the endothelial function. Moreover, there is an urgent need for adequately powered, robustly designed human intervention studies in order to clarify the present equivocal findings.

SARS coronavirus unique domain: three-domain molecular architecture in solution and RNA binding

Nonstructural protein 3 of the severe acute respiratory syndrome (SARS) coronavirus includes a "SARS-unique domain" (SUD) consisting of three globular domains separated by short linker peptide segments. This work reports NMR structure determinations of the C-terminal domain (SUD-C) and a two-domain construct (SUD-MC) containing the middle domain (SUD-M) and the C-terminal domain, and NMR data on the conformational states of the N-terminal domain (SUD-N) and the SUD-NM two-domain construct. Both SUD-N and SUD-NM are monomeric and globular in solution; in SUD-NM, there is high mobility in the two-residue interdomain linking sequence, with no preferred relative orientation of the two domains. SUD-C adopts a frataxin like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. The structures of both SUD-M (previously determined) and SUD-C (from the present study) are maintained in SUD-MC, where the two domains are flexibly linked. Gel-shift experiments showed that both SUD-C and SUD-MC bind to single-stranded RNA and recognize purine bases more strongly than pyrimidine bases, whereby SUD-MC binds to a more restricted set of purine-containing RNA sequences than SUD-M. NMR chemical shift perturbation experiments with observations of (15)N-labeled proteins further resulted in delineation of RNA binding sites (i.e., in SUD-M, a positively charged surface area with a pronounced cavity, and in SUD-C, several residues of an anti-parallel beta-sheet). Overall, the present data provide evidence for molecular mechanisms involving the concerted actions of SUD-M and SUD-C, which result in specific RNA binding that might be unique to the SUD and, thus, to the SARS coronavirus.

An annotation-free method for evaluating privacy protection techniques in videos

While several privacy protection techniques are pre- sented in the literature, they are not complemented with an established objective evaluation method for their assess- ment and comparison. This paper proposes an annotation- free evaluation method that assesses the two key aspects of privacy protection that are privacy and utility. Unlike some existing methods, the proposed method does not rely on the use of subjective judgements and does not assume a spe- cific target type in the image data. The privacy aspect is quantified as an appearance similarity and the utility aspect is measured as a structural similarity between the original raw image data and the privacy-protected image data. We performed an extensive experimentation using six challeng- ing datasets (including two new ones) to demonstrate the effectiveness of the evaluation method by providing a per- formance comparison of four state-of-the-art privacy pro- tection techniques.

A new member of the ribbon-helix-helix transcription factor superfamily from the plant pathogen Xanthomonas axonopodis pv. citri

XACb0070 is an uncharacterized protein coded by the two large plasmids isolated from Xanthomonas axonopodis pv. cirri, the agent of citrus canker and responsible for important economical losses in citrus world production. XACb0070 presents sequence homology only with other hypothetical proteins belonging to plant pathogens, none of which have their structure determined. The NMR-derived solution structure reveals this protein is a homodimer in which each monomer presents two domains with different structural and dynamic properties: a folded N-terminal domain with beta alpha alpha topology which mediates dimerization and a long disordered C-terminal tail. The folded domain shows high structural similarity to the ribbon-helix-helix transcriptional repressors, a family of DNA-binding proteins of conserved 3D fold but low sequence homology: indeed XACb0070 binds DNA. Primary sequence and fold comparison of XACb0070 with other proteins of the ribbon-helix-helix family together with examination of the genes in the vicinity of xacb0070 suggest the protein might be the component of a toxin-antitoxin system. (C) 2010 Elsevier Inc. All rights reserved.

Variação, contato e mudança linguística em Moçambique e Cabo Verde : A concordância variável de número em sintagmas nominais do português

This study investigates variable noun phrase number agreement (VNA) in two second language varieties of Portuguese, spoken in Maputo, Mozambique and in Mindelo, Cape Verde. Quantitative VARBRUL analysis is carried out based on recordings made in Maputo and Mindelo 2007 and 2008. Previous quantitative studies on VNA in varieties of Brazilian Portuguese (Guy, 1981; Lopes, 2001; Andrade, 2003) as well as on VNA in first and second language varieties of Portuguese from São Tomé (Baxter, 2004; Figueiredo, 2008, 2010) indicate contact between Portuguese and African languages as the main origin of this phenomenon. VNA in Brazilian Portuguese is, however, interpreted by Scherre (1988) and Naro & Scherre (1993, 2007) as the result of language internal drift. Varieties of Portuguese from Mozambique and Cape Verde are particularly interesting to contrast in order to investigate influences from African languages on VNA, as in Mozambique Bantu languages are first languages of the vast majority of Portuguese speakers, whereas in Cape Verde, practically all Portuguese speakers are first language speakers of Cape Verdean Creole, whose substrates are West African, and not Bantu, languages. Comparison is also made with previous studies from Brazil and São Tomé. The results of this study comment previously postulated explanations for VNA in Portuguese in various ways. The analysis of the variables onset age and age stratum indicates that VNA in the analyzed varieties is a phenomenon linked to the acquisition of Portuguese as a second language and/or language contact rather than the result of internal drift. The fact that all the compared varieties tend to mark plural on pre-head components contradicts Bantu transfer as an explanation for this pattern, and raises the need to also consider more general explanations based on language contact. The basic structural similarity between the compared varieties suggests the existence of a grammatical restructuring continuum.

Potassium channel modulation by a toxin domain in matrix metalloprotease

Peptide toxins found in a wide array of venoms block K+ channels, causing profound physiological and pathological effects. Here we describe the first functional K+ channel-blocking toxin domain in a mammalian protein. MMP23 (matrix metalloprotease 23) contains a domain (MMP23TxD) that is evolutionarily related to peptide toxins from sea anemones. MMP23TxD shows close structural similarity to the sea anemone toxins BgK and ShK. Moreover, this domain blocks K+ channels in the nanomolar to low micromolar range (Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4, in decreasing order of potency) while sparing other K+ channels (Kv1.2, Kv1.5, Kv1.7, and KCa3.1). Full-length MMP23 suppresses K+ channels by co-localizing with and trapping MMP23TxD-sensitive channels in the ER. Our results provide clues to the structure and function of the vast family of proteins that contain domains related to sea anemone toxins. Evolutionary pressure to maintain a channel-modulatory function may contribute to the conservation of this domain throughout the plant and animal kingdoms.

Multichannel biomedical time series clustering via hierarchical probabilistic latent semantic analysis

Biomedical time series clustering that automatically groups a collection of time series according to their internal similarity is of importance for medical record management and inspection such as bio-signals archiving and retrieval. In this paper, a novel framework that automatically groups a set of unlabelled multichannel biomedical time series according to their internal structural similarity is proposed. Specifically, we treat a multichannel biomedical time series as a document and extract local segments from the time series as words. We extend a topic model, i.e., the Hierarchical probabilistic Latent Semantic Analysis (H-pLSA), which was originally developed for visual motion analysis to cluster a set of unlabelled multichannel time series. The H-pLSA models each channel of the multichannel time series using a local pLSA in the first layer. The topics learned in the local pLSA are then fed to a global pLSA in the second layer to discover the categories of multichannel time series. Experiments on a dataset extracted from multichannel Electrocardiography (ECG) signals demonstrate that the proposed method performs better than previous state-of-the-art approaches and is relatively robust to the variations of parameters including length of local segments and dictionary size. Although the experimental evaluation used the multichannel ECG signals in a biometric scenario, the proposed algorithm is a universal framework for multichannel biomedical time series clustering according to their structural similarity, which has many applications in biomedical time series management.

Dietary sources, current intakes, and nutritional role of omega-3 docosapentaenoic acid

Fish oils and long-chain omega-3 fatty acids are well recognized for their critical role in human diets. Docosapentaenoic acid (DPA, 22:5n-3) has always been a part of healthy nutrition, since infants obtain almost as much DPA as DHA from human milk. Fish oil supplements and ingredients, oily fish, and grass-fed beef can serve as the primary DPA sources for the general population. Although the DPA levels in fish oils are substantially lower than those of EPA and DHA, concentrated DPA products are now becoming commercially available, and DPA-based drugs are under development. Epidemiological studies show that similar to eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic (DHA, 22:6n-3) acids, DPA is linked to various improvements in human health, perhaps owing to its structural similarity to the other two molecules. Studies in mammals, platelets, and cell cultures have demonstrated that DPA reduces platelet aggregation, and improves lipid metabolism, endothelial cell migration, and resolution of chronic inflammation. Further, other in vivo and in vitro studies have shown that DPA can improve neural health. A human supplementation trial with 99.8% pure DPA suggested that it serves as a storage depot for EPA and DHA in the human body. Future randomized controlled human trials with purified DPA will help clarify its effects on human health. They may confirm the available evidence pointing to its nutritional and biological functions, unique or overlapping with those of EPA and DHA.

Determinação de motivos de ligação à quitina em vicilinas de Canavalia ensiformis e Vigna unguiculata através de métodos in silico e relação com suas toxicidades para o bruquídeo Callosobruchus maculatus (Coleoptera:Bruchidae)

Chitin is an important structural component of the cellular wall of fungi and exoskeleton of many invertebrate plagues, such as insects and nematodes. In digestory systems of insects it forms a named matrix of peritrophic membrane. One of the most studied interaction models protein-carbohydrate is the model that involves chitin-binding proteins. Among the involved characterized domains already in this interaction if they detach the hevein domain (HD), from of Hevea brasiliensis (Rubber tree), the R&R consensus domain (R&R), found in cuticular proteins of insects, and the motif called in this study as conglicinin motif (CD), found in the cristallography structure of the β-conglicinin bounded with GlcNac. These three chitin-binding domains had been used to determine which of them could be involved in silico in the interaction of Canavalia ensiformis and Vigna unguiculata vicilins with chitin, as well as associate these results with the WD50 of these vicilins for Callosobruchus maculatus larvae. The technique of comparative modeling was used for construction of the model 3D of the vicilin of V. unguiculata, that was not found in the data bases. Using the ClustalW program it was gotten localization of these domains in the vicilins primary structure. The domains R&R and CD had been found with bigger homology in the vicilins primary sequences and had been target of interaction studies. Through program GRAMM models of interaction ( dockings ) of the vicilins with GlcNac had been gotten. The results had shown that, through analysis in silico, HD is not part of the vicilins structures, proving the result gotten with the alignment of the primary sequences; the R&R domain, although not to have structural similarity in the vicilins, probably it has a participation in the activity of interaction of these with GlcNac; whereas the CD domain participates directly in the interaction of the vicilins with GlcNac. These results in silico show that the amino acid number, the types and the amount of binding made for the CD motif with GlcNac seem to be directly associates to the deleterious power that these vicilins show for C. maculatus larvae. This can give an initial step in the briefing of as the vicilins interact with alive chitin in and exert its toxic power for insects that possess peritrophic membrane

Efeito anti-inflamatório do heparinóide isolado do camarão Litopenaeus vannamei sobre a peritonite aguda

In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis