Directing peptide crystallization through curvature control of nanotubes ‡

International audienceIn the absence of efficient crystallization methods, the molecular structures of fibrous assemblies have so far remained rather elusive. In this paper, we present a rational method to crystallize the lanreotide octapeptide by modification of a residue involved in a close contact. Indeed, we show that it is possible to modify the curvature of the lanreotide nanotubes and hence their diameter. This fine tuning leads to crystallization because the radius of curvature of the initially bidimensional peptide wall can be increased up to a point where the wall is essentially flat and a crystal is allowed to grow along a third dimension. By comparing X-ray diffraction data and Fourier transform Raman spectra, we show that the nanotubes and the crystals share similar cell parameters and molecular conformations, proving that there is indeed a structural continuum between these two morphologies. These results illustrate a novel approach to crystallization and represent the first step towards the acquisition of an Å-resolution structure of the lanreotide nanotubes β-sheet assembly

A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification

BACKGROUND: The health benefits of increased intakes of omega-3 fatty acids are well established but palatability often presents a problem. The process of emulsification is used in the food industry to provide a wider spectrum of use, often with the result of increased consumption. Moreover, as emulsification is an important step in the digestion and absorption of fats, the pre-emulsification process may enhance digestion and absorption. In this study the levels of plasma fatty acid and triacylglycerol (TAG) following the ingestion of either an oil mixture or an emulsified oil mixture have been compared. METHODS: In this randomised cross-over study, 13 volunteers received the oil mixture and 11 received the oil emulsion as part of an otherwise fat free meal. Blood samples were collected at 0, 1.5, 3, 4.5, 6, 7.5 and 9 hours after ingestion of oil, separated and stored at -20°C. Plasma triacylglycerols were assessed spectrophotometrically and fatty acids were determined by gas chromatography. Following a washout period of twenty days the procedure was repeated with the assignments reversed. RESULTS: The postprandial plasma TAG and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels for the emulsified oil group were increased significantly (P = 0.0182; P = 0.0493; P = 0.0137; P < 0.0001; P = 0.0355 respectively) compared with the non-emulsified oil group. The C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not significantly different for the oil and emulsified oil groups. CONCLUSION: Pre-emulsification of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not affect absorption of shorter chain less saturated fatty acids, suggesting that pre-emulsification of fish oils may be a useful means of boosting absorption of these beneficial fatty acids. Trial registration: Current Controlled Trials ISRCTN4320260

Ivy : un bus logiciel au service du développement de prototypes de systèmes interactifs

Ce document présente l'expérience acquise au cours du développement et de l'utilisation du bus logiciel Ivy, dans un cadre de prototypage de systèmes interactifs pour le contrôle du trafic aérien. Après une description du principe de fonctionnement de ce système, nous verrons comment cet outil a pu influer sur notre approche de problématiques IHM spécifiques comme la multimodalité, l'interaction répartie ou la mobilité. L'accent est porté sur les services rendus par ce bus pour le développement rapide de systèmes interactifs " légers ", facilement intégrables dans un banc de démonstration et basés sur la logique des langages de script. En présentant cet outil que nous utilisons depuis maintenant cinq ans, nous espérons partager ici une expérience utile pour la conception de futures architectures de systèmes interactifs à des fins de recherche prospective

Champ de pression non isotrope approchant le champ des contraintes d'indentation d'un verre

Selon Yoffe (1982), les contraintes générées lors de l'indentation d'un verre relèvent d'une «plasticité non-orthodoxe» au sens d'une déformation irréversible non isovolume. Intervient un phénomène de densification où sa définition simple d'une inclusion sphérique tronquée équivalente utilise un champ uniforme de pression non isotrope approchant celui des contraintes «élasto-pseudo-plastique-densifiant». Un tel champ se compose d'un écrasement vertical réparti sur une surface circulaire et d'une expansion radiale; il approche le champ irréversible assimilé à la superposition du champ élastique de Boussinesq (1885) et d'un champ «d'ampoule». L'approximation de cette équivalence entre champ de pression uniforme non isotrope et champ élasto-plasto-densifiant est obtenue par troncature d'une série de Fourier; nos résultats semi-analytiques s'efforcent de dépendre explicitement du coefficient de Poisson et incitent à de futurs développements expérimentaux et théoriques

Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study

International audienceABSTRACT: INTRODUCTION: Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question. METHODS: We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug. RESULTS: Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug. CONCLUSIONS: Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution

Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization

9siIn host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis.openopenSegond D; Abi Khalil E; Buisson C; Daou N; Kallassy M; Lereclus D; Arosio P; Bou-Abdallah F; Nielsen Le Roux C.Segond, D; Abi Khalil, E; Buisson, C; Daou, N; Kallassy, M; Lereclus, D; Arosio, Paolo; Bou Abdallah, F; Nielsen Le Roux, C

Confining Trypanosoma brucei in emulsion droplets reveals population variabilities in division rates and improves in vitro cultivation

Trypanosome parasites are infecting mammals in Sub-Saharan Africa and are transmitted between hosts through bites of the tsetse fly. The transmission from the insect vector to the mammal host causes a number of metabolic and physiological changes. A fraction of the population continuously adapt to the immune system of the host, indicating heterogeneity at the population level. Yet, the cell to cell variability in populations is mostly unknown. We develop here an analytical method for quantitative measurements at the single cell level based on encapsulation and cultivation of single-cell Trypanosoma brucei in emulsion droplets. We first show that mammalian stage trypanosomes survive for several hours to days in droplets, with an influence of droplet size on both survival and growth. We unravel various growth patterns within a population and find that droplet cultivation of trypanosomes results in 10-fold higher cell densities of the highest dividing cell variants compared to standard cultivation techniques. Some variants reach final cell titers in droplets closer to what is observed in nature than standard culture, of practical interest for cell production. Droplet microfluidics is therefore a promising tool for trypanosome cultivation and analysis with further potential for high-throughput single cell trypanosome analysis

Development of an innovative adenovirus-inspired self-assembling vaccine platform rapidly adaptable to coronaviruses and other emergent viruses

The COVID-19 pandemic clearly shows how emergent diseases can cause severe global health and economic problems. We must be prepared to react swiftly against new pathogenic agents and this requires the development of vaccines that are safe, efficient in the long-term and easily adaptable with a short revision time. To this end, the COVID-19 mRNA and adenoviral vector vaccines have been spectacular successes, permitting rapid vaccination across the world in an unprecedented manner. Here we report the design of a new adenovirus-derived vaccine technology based on non-infectious pseudo-viral nanoparticles from the serotype 3 human adenovirus. Each nanoparticle comprises sixty identical proteins that assemble to form a 30 nm diameter spherical particle. A sequence has been engineered into the surface of this protein that enables the display of a covalently-bound target antigens. To demonstrate the efficiency of this approach, we added the SARS-CoV 2 spike protein receptor binding domain (RBD), that interacts with host cell ACE2 receptors, to the surface of the nanoparticles. We first showed that the glycosylated RBD retained its ACE2-binding function when displayed on nanoparticles. We then measured the in vivo humoral response of our vaccine candidate in mice and observed a strong antibody response after the prime injection; further levels were achieved following a second booster injection. In mice preimmunized with underivatized adenoviral nanoparticles, we tested if adenovirus seroprevalence, as frequently observed in humans, was detrimental to the RBD-mediated protection provided by our vaccine candidate. Interestingly, a strong anti-coronaviral response was still observed suggesting that existing circulating anti-adenovirus antibodies are not deleterious to our vaccine platform. We then performed pseudo-CoV 2 neutralization assays and obtained higher ID50 values than observed with COVID-19 convalescent sera, thus showing the high potential efficacy of our vaccine platform. This new vaccine technology is a tool that is easily adaptable to future SARS-CoV 2 variants and, more generally, to future emergent viruses and pathogens

Les disparités territoriales dans l'accès aux formations d'élite: La situation des Pays de la Loire au regard des autres régions françaises

La formation des élites demeure un sujet controversé entre les partisans de la suppression des grandes écoles, de leur fusion au sein des universités ou de leur maintien. Alors que dans la plupart des autres pays l’Université assure seule la formation des élites, le système français est organisé de telle sorte qu’une partie des futures élites administratives, managériales, intellectuelles, politiques et scientifiques est sélectionnée, préparée et formée dans des structures non universitaires : les « grandes écoles » et les classes préparatoires aux grandes écoles (CPGE). Autre particularité du système : ces classes préparatoires relèvent de l’enseignement supérieur alors qu’elles se situent dans des établissements d’enseignement secondaire. Instituées au XVIIIe siècle (Belhoste, 2003), elles accueillent actuellement 81135 étudiants, soit 3,5% des étudiants (RERS, 2010). Leur représentation n’a quasiment pas évolué depuis 1970 (3,8%), malgré une croissance forte des effectifs, notamment durant la période 1985-1995 avec la création de nouvelles divisons, essentiellement dans les filières scientifiques et dans une moindre mesure, économiques et commerciales.Ces classes suscitent de vives critiques : plus coûteuses – le coût moyen d’un préparationnaire était en 2007 de 15080 euros contre 9120 euros pour un étudiant des universités – , faisant preuve d’une faible ouverture sociale (Euriat et Thélot, 1995 ; Duru-Bellat et Kieffer, 2008) – 51,1% d’enfants de cadre supérieur en 2009 vs 29,7% à l’Université – , territorialement inéquitables (Bodin, 2007) – les effectifs sont concentrés en Ile-de-France et dans les grandes métropoles régionales – et d’une « productivité » moyenne (Michaut, à paraître) – sur 100 néo-inscrits en CPGE scientifiques , seuls 50% intégreront une grande école en deux années de préparation et la situation est bien plus problématique dans la filière littéraire avec seulement 8% d’intégrés (Lemaire, 2008). A l’inverse, les « gardiens du temple » défendent un modèle d’excellence à la française qui favorise l’apprentissage de certaines compétences chez les étudiants, leur assurant ainsi une meilleure insertion professionnelle et de meilleurs salaires (Adangnikou, 2007 ; Giret, 2009).Les recherches se sont, jusqu’à présent, essentiellement focalisées sur le territoire national, sans faire apparaitre les éventuelles spécificités des « prépas de proximité » ou des CPGE des établissements privés. De même, les caractéristiques, les conditions de travail et les représentations des enseignants qui font souvent figure d’élites dans le corps professoral du secondaire ont été peu étudiées. Ce rapport offre des éléments de réponse en s’appuyant sur les recherches entreprises par des chercheurs du Centre de recherche en éducation de Nantes (CREN-Université de Nantes), du Centre Nantais en sociologie (CENS-Université de Nantes), du Laboratoire de Recherche en Education et Formation (LAREF-Université Catholique de l’Ouest), du Laboratoire d'Economie et de Sociologie du Travail (LEST-CNRS) et de l’Observatoire sociologique du changement (OSC- Sciences.Po). Il éclaire également les débats sur les projets de réformes en cours (30% de boursiers en CPGE, dispositif d’ouverture sociale) et aborde de nouvelles problématiques, notamment l’endorecrutement des établissements.La recherche est articulée autour de quatre axes :- les disparités territoriales de recrutement des classes préparatoires aux grandes écoles ;- les conditions d’études et les parcours scolaires des étudiants des filières d’excellence ;- Les stratégies des personnels des lycées ;- Les politiques d'ouverture sociale et les dispositifs innovants de l’Education nationale, des collectivités territoriales et des établissements d'enseignement