Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

«La relation de limitation et d’exception dans le français d’aujourd’hui : excepté, sauf et hormis comme pivots d’une relation algébrique »

L’analyse des emplois prépositionnels et des emplois conjonctifs d’ “excepté”, de “sauf” et d’ “hormis” permet d’envisager les trois prépositions/conjonctions comme le pivot d’un binôme, comme la plaque tournante d’une structure bipolaire. Placées au milieu du binôme, ces prépositions sont forcées par leur sémantisme originaire dûment métaphorisé de jouer le rôle de marqueurs d’inconséquence systématique entre l’élément se trouvant à leur gauche et celui qui se trouve à leur droite. L’opposition qui surgit entre les deux éléments n’est donc pas une incompatibilité naturelle, intrinsèque, mais extrinsèque, induite. Dans la plupart des cas (emplois limitatifs), cette opposition prend la forme d’un rapport entre une « classe » et le « membre (soustrait) de la classe », ou bien entre un « tout » et une « partie » ; dans d’autres (emplois exceptifs), cette opposition se manifeste au contraire comme une attaque de front portée par un « tout » à un autre « tout ». De plus, l’inconséquence induite mise en place par la préposition/conjonction paraît, en principe, tout à fait insurmontable. Dans l’assertion « les écureuils vivent partout, sauf en Australie » (que l’on peut expliciter par « Les écureuils vivent partout, sauf [qu’ils ne vivent pas] en Australie »), la préposition semble en effet capable d’impliquer le prédicat principal avec signe inverti, et de bâtir sur une telle implication une sorte de sous énoncé qui, à la rigueur, est totalement inconséquent avec celui qui le précède (si « les écureuils ne vivent pas en Australie », le fait qu’ils « vivent partout » est faux). Néanmoins, l’analyse montre qu’alors que certaines de ces oppositions peuvent enfin être dépassées, d’autres ne le peuvent pas. C’est, respectivement, le cas des relations limitatives et des relations exceptives. La relation limitative, impliquant le rapport « tout » - « partie », permet de résoudre le conflit dans les termes d’une somme algébrique entre deux sous énoncés pourvus de différent poids informatif et de signe contraire. Les valeurs numériques des termes de la somme étant déséquilibrées, le résultat est toujours autre que zéro. La relation exceptive, au contraire, qui n’implique pas le rapport « tout » - « partie », n’est pas capable de résoudre le conflit entre deux sous énoncés pourvus du même poids informatif et en même temps de signe contraire : les valeurs numériques des termes de la somme étant symétriques et égales, le résultat sera toujours équivalent à zéro

Le texte dans l'apprentissage de la lecture en cours préparatoire : analyse et description

Choisir un texte pour une utilisation dans lapprentissage de la lecture demande la mobilisation de plusieurs savoirs référents : les recherches sur lenseignement et lapprentissage de la lecture, la pédagogie et la didactique, mais aussi la linguistique puisque lobjet utilisé dans cet apprentissage est le texte, et enfin linformatique car il sagit de construire un environnement informatique daide à lapprentissage. La modélisation de cette décision du choix du texte montre que loutil indispensable à sa réalisation est une description-analyse du texte. Pour la constituer, il faut considérer le texte dans ses deux utilisations. Sil est support dapprentissage, il faut décrire les apprentissages quil permet de réaliser, par exemple la liste des mots comprenant le graphème à acquérir. Sil est objet dapprentissage, il faut en faire une analyse linguistique, le type, la progression thématique par exemple, et observer ce que ces particularités permettent à lapprenant. Peut-il construire, à partir, par exemple, dun schéma narratif repérable, une stratégie de compréhension ? Poser ainsi le problème du choix du texte conduit à utiliser des analyses linguistiques existantes, mais fait aussi émerger dautres questions linguistiques, comme celle de la répétition, outil très utilisé dans les albums pour enfants mais pas étudiée en tant que telle par la linguistique. De plus, lexplicitation totale dune part des connaissances mises en jeu dans cette décision, et dautre part de leur organisation rend ce savoir expert transmissible à lenseignant de cours préparatoire qui ainsi complète sa formation initiale

Poly(ionic liquid)s with controlled architectures and their use in the making of ionogels with high conductivity and tunable rheological properties

International audienceWe describe the preparation as well as the electrochemical and mechanical properties of a series of novel well-defined poly(ionic liquids) (PILs) featuring a finely tuned cross-linking ratio. We generate a variety of such PILs with various cationic moieties and cross-linking ratios starting from a common polymeric platform. Mixing those polymers with an appropriate ionic-liquid leads to ionogel electrolytes exhibiting good ionic conductivities (up to 1.2 mS cm−1 at 298 K), high electrochemical stability (up to 6 V) and a yield-stress fluid mechanical behavior, which enables their use as solid electrolytes. We demonstrate that depending on the cationic moieties, this ability to be solid at rest and reversibly fluid when sheared is obtained by two different mechanisms

Solid-state: Versus solution investigation of a luminescent chiral BINOL-derived bisphosphate single-molecule magnet

International audienceThe enantiopure coordination polymer [Dy(hfac)3((S/R)-L)]n ([(S/R)-1]n) involving a BINOL-derived bisphosphate ligand (S/R)-L is reported. Paramagnetic NMR and computational investigations demonstrated the formation of mononuclear species [(S/R)-1] in CH2Cl2 solution and its optimized structure was determined. The experimental electronic circular dichroism signals of (S/R)-L were strongly enhanced after metal coordination [(S/R)-1]. Both polymeric and mononuclear structures displayed field-induced Single-Molecule Magnet (SMM) behaviour with similar multi-relaxation processes due to the retention of crystal-field splitting determined by CASSCF calculations, despite the strong structural transformation between the two media. The HOMO ? LUMO transition of the (S)-L ligand induced the classical Dy(iii) emission at 77 K that was correlated with the magnetic properties. [(S)-1]n is described as one-dimensional assembly of chiral luminescent Single-Ion Magnets (SIMs)

Gravidity-dependent associations between interferon response and birth weight in placental malaria.

BackgroundMaternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal-fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses. However, its role in placental malaria is unknown. This study examines the cytokine responses in placental tissue from subsets of malaria-infected and uninfected women, and attempts to correlate them with particular birth outcomes.Methods40 whole placental biopsy samples were obtained from pregnant women at least 16 years of age recruited to a larger prospective chemoprevention trial against malaria. These were patients at Tororo District Hospital in Uganda, an area of high malaria endemicity where approximately 40% of women have evidence of malaria infection at delivery. They were regularly followed at a local clinic and monitored for fever, with blood smears performed then and at time of delivery to diagnose malaria infection. Placenta biopsies were taken for histological diagnosis of placental malaria, as well as quantitative PCR analysis of genes in the IFN-I pathway (IFN-β, IL-10 and MX-1). Parameters such as infant birth weight and gestational age were also recorded.ResultsHistological analysis revealed placental malaria in 18 samples, while 22 were found to be uninfected. RT-PCR analysis showed a four-fold increase in IFN-β and IL-10 expression in multigravidas with placental malaria when compared to gravidity-matched, uninfected controls. This effect was not observed in primigravidas. Interestingly, linear regression analysis showed a positive association between IFN-β levels and higher birth weights (β = 101.2 g per log2-fold increase in IFN-β expression, p = 0.042). This association was strongest in primigravidas with placental malaria (β = 339.0, p = 0.006).ConclusionsThese results demonstrate differential regulation of the IFN-I pathway in placental malaria according to gravidity, with the greatest anti-inflammatory response seen in multigravidas. The association between IFN-β levels and higher birth weight also suggests a protective role for IFN-I against fetal growth restriction in placental malaria

GPIomics:global analysis of glycosylphosphatidylinositol-anchored molecules of Trypanosoma cruzi

Glycosylphosphatidylinositol (GPI) anchoring is a common, relevant posttranslational modification of eukaryotic surface proteins. Here, we developed a fast, simple, and highly sensitive (high attomole-low femtomole range) method that uses liquid chromatography-tandem mass spectrometry (LC-MSn) for the first large-scale analysis of GPI-anchored molecules (i.e., the GPIome) of a eukaryote, Trypanosoma cruzi, the etiologic agent of Chagas disease. Our genome-wise prediction analysis revealed that approximately 12% of T. cruzi genes possibly encode GPI-anchored proteins. By analyzing the GPIome of T. cruzi insect-dwelling epimastigote stage using LC-MSn, we identified 90 GPI species, of which 79 were novel. Moreover, we determined that mucins coded by the T. cruzi small mucin-like gene (TcSMUG S) family are the major GPI-anchored proteins expressed on the epimastigote cell surface. TcSMUG S mucin mature sequences are short (56–85 amino acids) and highly O-glycosylated, and contain few proteolytic sites, therefore, less likely susceptible to proteases of the midgut of the insect vector. We propose that our approach could be used for the high throughput GPIomic analysis of other lower and higher eukaryotes

Gravidity-dependent associations between interferon response and birth weight in placental malaria.

BackgroundMaternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal-fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses. However, its role in placental malaria is unknown. This study examines the cytokine responses in placental tissue from subsets of malaria-infected and uninfected women, and attempts to correlate them with particular birth outcomes.Methods40 whole placental biopsy samples were obtained from pregnant women at least 16 years of age recruited to a larger prospective chemoprevention trial against malaria. These were patients at Tororo District Hospital in Uganda, an area of high malaria endemicity where approximately 40% of women have evidence of malaria infection at delivery. They were regularly followed at a local clinic and monitored for fever, with blood smears performed then and at time of delivery to diagnose malaria infection. Placenta biopsies were taken for histological diagnosis of placental malaria, as well as quantitative PCR analysis of genes in the IFN-I pathway (IFN-β, IL-10 and MX-1). Parameters such as infant birth weight and gestational age were also recorded.ResultsHistological analysis revealed placental malaria in 18 samples, while 22 were found to be uninfected. RT-PCR analysis showed a four-fold increase in IFN-β and IL-10 expression in multigravidas with placental malaria when compared to gravidity-matched, uninfected controls. This effect was not observed in primigravidas. Interestingly, linear regression analysis showed a positive association between IFN-β levels and higher birth weights (β = 101.2 g per log2-fold increase in IFN-β expression, p = 0.042). This association was strongest in primigravidas with placental malaria (β = 339.0, p = 0.006).ConclusionsThese results demonstrate differential regulation of the IFN-I pathway in placental malaria according to gravidity, with the greatest anti-inflammatory response seen in multigravidas. The association between IFN-β levels and higher birth weight also suggests a protective role for IFN-I against fetal growth restriction in placental malaria