Use of Organosilicon Compounds towards the Rational Design of Antiparasitic and Antiviral Drugs

One of the major problems met for the conception of antiviral or antiparasitic drugs is to reach a high level of selectivity towards the pathogenic agent versus the host. We shall describe two synthetic approaches where main group organometallics have been used towards this goal. A series of nucleoside sila-analogues was synthesized as potential therapeutic agents designed to inhibit HIV Reverse Transcriptase. In a second approach novel organosilicon derivatives have been synthesized as mimics of antisense oligonucleotides

Embedded Systems Requirements Verification Using HiLeS Designer

International audienceOne of the issues related to systems design is the early verification in first design steps: system specifications verification. Nowadays, it is common to use text-based specifications to begin a system design. However, these specifications cannot be verified until a software model is made. In this work, we show how can we use HiLeS Designer to model and verify, formally and by simulation an embedded system specification. This tool makes easier to build the model, using graphical concepts which are familiar to designers. It also helps to verify formally the structure and some logical behavior, and by simulation, it is possible to verify the consistence of the embedded system specification. We model and verify System Display Selector Requirements applying HiLeS Designer

Surface specific peptide immobilization on radiografted polymers as potential screening assays for antiangiogenic immunotherapy

International audienceAngiogenesis is a key process of cancer development and metastasis. It's inhibition is an important and promising strategy to block tumor growth and invasion. One of these approaches, based on antiangiogenic immunotherapy, is the recognition of a specific region of an angiogenic growth factor, called VEGF-A, by monoclonal antibodies. Thus, we aimed to design a novel assay to screen potential monoclonal antibodies directed against VEGF-A. In a first approach, we chose to perform covalent coupling of angiogenesis active cyclopeptides onto biocompatible thermoplastic transparent PVDF films and to fully characterize the chemical structure, the surface state and the biochemical properties of the synthesized devices. Electron beam radiation created radical sites on PVDF films without adding any toxic chemicals. These primary radicals and some induced peroxides were used as initiators for acrylic acid polymerization. Under our experimental conditions, surface grafting was favoured. Functionalization of PVDF-g-PAA films with peptides via a spacer arm was possible by performing two subsequent coupling reactions. EDC was used as coupling agent. Spacer arm saturation of the film surface was achieved for 25 mol% yield meaning that one spacer arm on four carboxylic acids were covalently bound. Peptide immobilization resulted in binding 10 times less leading to a final 3 mol% yield. Binding densities are governed by their individual space requirements. Each chemical step has been followed by FTIR in ATR mode, NMR using HR MAS technique and XPS. From XPS results, a layer of peptide covered PVDF-g-PAA film surface. The amounts of covalently immobilized peptide were determined using indirect UV spectroscopy on supernatant reaction solution. Yields were correlated with high resolution NMR results. The peptide/antibody recognition validated our system showing the conservation of peptide tridimensional structure with a positive response to specific antibodies. Because of the covalent protein linkage to PVDF films, a simple cleaning with immunoaffinity chromatography buffer allows the films to be reused

Temporal dominance of sensations of peanuts and peanut products in relation to Hutchings and Lillford’s “breakdown path"

Hutchings and Lillford’s (Journal of Texture Studies, 19, 103-115, 1988) proposed a “breakdown path” whereby particle size reduction occurs through mastication in conjunction with the secretion of saliva to form a swallowable bolus. The swallowing trajectory of whole peanuts, peanut meal and peanut paste were studied with the temporal dominance of sensations technique. The sensations for whole peanuts progressed from hard, to crunchy, to chewy, to soft and ended compacted on teeth. Predictably peanut meal missed out the first two sensations, progressing from chewy, to soft and ending compacted on teeth. However peanut paste, which starts as a soft suspension with relatively little structure appears to thicken and stick to the palate during oral processing. We propose that the “hard to swallow” sensation elicited by peanut paste may be due to water absorption from the saliva as they mix in the mouth

Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function

The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38MAPK, extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38MAPK, ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phosphomimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38MAPK, ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser-115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5

Understanding the relevance of in-mouth food processing. A review of in vitro techniques

[EN] Oral processing of food is the first step in the eating process. Although the food undergoes a number of changes during mastication that influence the subsequent steps, this stage has very often been neglected in studies of digestion, bioavailability, flavor release, satiety potential, glycemic index determination, etc. The present review draws on different sources such as nutrition, medicine, phoniatry and dentistry to explain some in vitro oral processing methods and techniques that could be transferred to food technology studies to mimic in vivo comminution, insalivation, and bolus formation, describing, as a necessary reference, the respective in vivo physiological processes they attempt to imitate. Developing a deeper understanding of all the aspects of in-mouth process will help food technologists to give this crucial step the necessary attention its due importance and to consider better ways to incorporate it into their studies.The authors wish to acknowledge the financial support of the Spanish Government (project AGL2012-36753-C02) and gratefully acknowledge the financial support of EU FEDER funds. Mary Georgina Hardinge assisted with the translation and corrected the English text.Morell Esteve, P.; Hernando Hernando, MI.; Fiszman, SM. (2014). Understanding the relevance of in-mouth food processing. A review of in vitro techniques. Trends in Food Science and Technology. 35(1):18-31. https://doi.org/10.1016/j.tifs.2013.10.005S183135

France mirroring England : poetics of hybridization in French theater (1590-1640)

La France entretient avec son voisin anglais, entre le milieu du XVIe siècle et le début des années 1640, deséchanges constants, tant d’un point de vue politique que culturel. Malgré les troubles religieux et les guerres qui agitentl’Europe occidentale durant cette période, en dépit également des barrières linguistiques, un grand nombre devoyageurs, de diplomates, d’intellectuels et d’écrivains n’hésitent pas à traverser les frontières. Ces passeurs quittent laFrance pour se rendre de l’autre côté de la Manche : ils y apprennent éventuellement la langue anglaise, effectuent desmissions diverses et surtout ils se font les acteurs de la relation culturelle entre les deux pays. Imprimés et traductions detextes religieux, scientifiques ou littéraires, mais aussi troupes théâtrales circulent ainsi de l’Angleterre vers la France,empruntant parfois des détours inattendus. L’étude s’attache dans un premier temps à passer en revue ces différentstypes de contacts et de transferts culturels, en particulier en ce qui concerne l’influence de la littérature anglaise sur lethéâtre français.Cette influence se manifeste par ailleurs à travers des conceptions et des pratiques hybrides du théâtre.Poétiques du mélange, du métissage et de l’hybridation formelle et générique sont caractéristiques du théâtre anglais dela période élisabéthaine et jacobéenne. Des auteurs comme Marlowe, Greene, Shakespeare ou Webster expérimentent eneffet des formules dramatiques qui invitent à reconsidérer et relativiser les catégories poétiques traditionnelles. Si latragédie, la comédie ou la tragi-comédie ne sont pas absentes en tant que dénominations génériques, elles sont lessupports et les instruments de combinaisons et de mélanges multiples et variés. Ce faisant, les différentes modalités dumélange et de l’hybridation dans le théâtre anglais permettent de jeter un regard différent sur la production dramatiqueen France entre la fin du XVIe siècle et le début du XVIIe siècle. En effet, les pièces composées pendant cette périodelongtemps méconnue du théâtre français, attestent d’une hybridité aussi marquée que celle des pièces anglaises, et ellestémoignent de la grande diversité des formes et des genres dramatiques. Ce théâtre, qui ne se conforme pas encore auxcatégories critiques et aux principes dramatiques formulés par les théoriciens et commentateurs d’Aristote, secaractérise par son irrégularité, la porosité de ses catégories génériques et par un souci de s’adapter aux contraintes de lavie théâtrale.L’étude s’attache dans un dernier temps à poser les prémisses d’une analyse plus approfondie des liensorganiques entre le théâtre médiéval et populaire et le théâtre français à l’aube du XVIIe siècle. Ainsi, ce que nousappelons « théâtre monstre », parce qu’il a partie liée avec la figure politique, symbolique et esthétique du monstre etses différentes déclinaisons, nous permet de rapprocher, en France et en Angleterre, des pièces qui se caractérisent parleur a-normalité, leur ludisme et leur métathéâtralité, loin de la tradition aristotélicienne et de ses contraintes. Noussommes amené ainsi à considérer le théâtre français selon sa diversité géographique et linguistique, ainsi que du pointde vue de ses continuités historiques.France maintains with its English neighbor, between the mid-sixteenth century and the early 1640’s, constantrelationships, both political and cultural. Despite the religious troubles and the wars shaking the western Europe duringthis period, despite linguistic barriers, many travelers, diplomats, intellectuals and writers cross the frontiers. Thesecultural travelers leave France to go abroad, to the other side of the Channel : they eventually learn the Englishlanguage, carry out various missions and, above all, they become the actors of the cultural relationship between the twocountries.This influence is also evident through conceptions and hybrid practices of theater. Poetics of mixing, of formaland generic hybridizations are characteristic of the English theater during the Elizabethan and Jacobean period. Authorslike Marlowe, Greene, Shakespeare and Webster experiment new dramatic formulas that invite us to reconsider andrelativize the traditional poetic categories. Tragedy, comedy or tragicomedy are not absent as generic designations, butthey are the medias and instruments of combinations, and of multiple and various blends. Thus, the different ways ofmixing and mingling in the English theater make possible a different look at the dramatic production in France duringthe late XVIth and early 17th century. Indeed, the plays written during this long unrecognized period of the Frenchtheater, show a hybridity as marked as in the English plays and they reflect the great diversity of forms and dramaticgenres. This theater, which does not conform to the critical categories and dramatic principles formulated by theoristsand commentators of Aristotle, is characterized by its irregularity, the porosity of its generic categories and by a desireto adapt to the constraints of the theatrical life.Finally, the study focuses on the premises of a more thorough analysis of organic links between the medievaland popular theater and the French theater at the dawn of the 17th century. Thus, what we call « monster theater »,because of its bounds with the political, symbolic and aesthetic figure of the monster and its various configurations,allows us to compare, in France and England, plays that are characterized by their ab-normality, their playful dimensionand their metatheatrality, far away from the Aristotelian tradition and its constraints. In this way, we are led to considerthe French theater according to its geographical and linguistic diversity, but also from the perspective of its historicalcontinuities

Les vies françaises de l’Arcadia : du roman de Sir Philip Sidney à ses adaptations dramatiques en France

Dans les années 1580, Sir Philip Sidney s’attelle à l’écriture de son oeuvre majeure, l’Arcadia, vaste roman pastoral dont la composition inachevée s’étale sur plusieurs années, et la publication posthume. Sa diffusion à l’étranger, et notamment en France, est rapide et l’Arcadia fait en effet l’objet dès le début du XVIe siècle de plusieurs traductions, grâce à plusieurs érudits français qui n’hésitent pas à traverser la Manche pour affiner leur compréhension de la langue anglaise. Par ailleurs, le roman pastoral est adapté à trois reprises sur les scènes françaises, entre le tout début du XVIIe siècle et 1642, par successivement Galaut, La Calprenède et Mareschal. Ainsi, se dessinent des trajectoires littéraires et des continuités dramatiques singulières, qui conduisent à interroger tout à la fois les mécanismes de l’adaptation théâtrale et les fondements historiques des transferts culturels entre la France et l’Angleterre. In the 1580s, Sir Philip Sidney set about writing his major work, Arcadia. The unfinished composition of this huge pastoral romance stretched over several years, and it was published posthumously. Its dissemination abroad, and notably in France, was rapid. Arcadia was in fact translated several times from the beginning of the seventeenth century, thanks to a handful of French scholars who readily crossed the channel to refine their understanding of the English language. Moreover, the pastoral romance was adapted three times for the French stage between the outset of the seventeenth century and 1642, by Galaut, La Calprenède and Mareschal successively. Thus literary trajectories and singular dramatic continuities emerge, which lead to the questioning of both the mechanisms of theatrical adaption and the historical foundations of cultural transfers between France and England