Caractérisation des interactions glycosaminoglycannes/protéines dans le but de développer des molécules d'intérêt thérapeutique : <br />exemples de l'Endocan et de l'interféron gamma

Proteoglycans are complex macromolecules which consist structurally of a core protein and one or more covalently linked glycosaminoglycan chains. Both components can interact with a variety of binding proteins known to be involved in various pathophysiological processes such as inflammation and cancer. The characterization of the specific interactions between glycosaminoglycans and their binding partners should raise new therapeutic opportunities in drug development.In this context, we first studied a recently discovered proteoglycan called endocan. By developing new processes for high yield production and purification, we have been able to further characterise the structure of endocan using different biochemical approaches and also to study the interactions with various binding partners including interferon Γ and hepatocyte growth factor. In the same time, the characterisation of the specific interaction of interferon gamma and the particular glycosaminoglycan of heparan sulphate type allowed the synthesis by sugar chemistry of glycosaminoglycan mimetics. Among these molecules, a glycoconjugate modulates the activity of the cytokine and could lead to the development of a new type of drugs.Les protéoglycannes exercent de nombreuses fonctions par le biais de leur partie protéique ou de leurs glycosaminoglycannes. La caractérisation des interactions entre les glycosaminoglycannes et des protéines a ouvert de larges champs d'applications. Dans ce cadre, deux thèmes de recherche ont été développés. Premièrement, nous nous sommes intéressés à un nouveau protéoglycanne appelé endocan. La développement des capacités de production et de purification de cette macromolécule, nous a permis par différentes approches de déterminer le profil structural de sa chaîne glycannique et de sa partie protéique, mais aussi d'étudier les interactions avec plusieurs de ses partenaires protéiques dont l'interféron Γ et l'hépatocyte growth factor, impliqués respectivement dans l'inflammation et le développement tumoral. Parallèlement, une étude structurale et fonctionnelle de l'interaction entre l'interféron gamma et des glycosaminoglycannes de type héparanes sulfates a conduit au développement de mimes oligosaccharidiques obtenus par synthèse chimique. Parmi ces molécules, certaines permettent de moduler in vitro l'activité de la cytokine, et constituent une base possible pour le développement de nouveaux médicaments

Collocated Microstrip Antennas for MIMO Systems with a Low Mutual Coupling Using Mode Confinement

WOSInternational audienceIn this paper, collocated antennas for MIMO systems are presented. The structure is composed of a dual-polarized microstrip square patch combined to a dual-polarized microstrip square ring. Consequently, four different radiation patterns are available simultaneously. With a length of about one guided wavelength, the proposed structure is well suited to reduce the MIMO terminal size. The structure operates in the 5.25 GHz band and exhibits a mutual coupling between the four input ports less than -23.5 dB in simulation and -20 dB in measurement. MIMO channel capacity measurements have been performed and demonstrate that the proposed antenna system can replace a classical system based on space diversity

Antennes co-localisées reconfigurables en fréquence pour systèmes MIMO

National audienceCe papier présente trois antennes co-localisées dont les accès présentent un découplage de l'ordre de 30dB en simulation. La diversité entre chaque antenne est assurée par une combinaison de diversité de polarisation et de rayonnement. Le dispositif a été dimensionné pour fonctionner autour de 5.25GHz avec une largeur de bande d'environ 9.8%. Toutefois, afin de répondre aux besoins actuels concernant la multiplication de fonctions au sein d'un même dispositif, une agilité en fréquence a été introduite via l'utilisation de courts-circuits étendant ainsi la bande à 33%, de 5GHz à 7GHz. La faisabilité pratique d'une telle antenne et la fiabilité des choix des différents paramètres de simulation ont été démontrés précédemment dans le cas d'une antenne cube du même type excitée par un seul monopôle

Pattern Reconfigurable Cubic Antenna

International audienceA new single-feed reconfigurable antenna for pattern diversity is presented in this paper. The proposed structure is based on a metallic cubic cavity which radiates through rectangular slots. The pattern reconfiguration is achieved with PIN diode switches by short-circuiting slots in their center. The designed antenna can switch between three different radiation patterns which radiate in a 4π steradian range and can receive any incident field polarizations. A prototype of the antenna, including PIN diodes and operating in the 5 GHz band, has been built to demonstrate the feasibility of the concept. Measurements have been conducted and three-dimensional radiation patterns are provided. Diversity performances are evaluated by calculating the envelope correlation coefficient

Investigation on Cavity/Slot Antennas for Diversity and MIMO systems: the example of a three-port antenna

International audienceThe use, as diversity antennas, of electromagnetic cavities with radiated slots etched on their faces is discussed. From this kind of geometries, many antenna configurations can be designed in order to provide uncorrelated signals. As an example, a three-port antenna which combines polarization and radiation pattern diversities is presented. The structure operates in the 5 GHz band and exhibits a coupling between input ports less than -30 dB in measurement. Envelope correlations between radiation patterns of each port are less than 0.035 which makes this structure well-suited for antenna diversity systems

Hijacking of the Pleiotropic Cytokine Interferon-γ by the Type III Secretion System of Yersinia pestis

Yersinia pestis, the causative agent of bubonic plague, employs its type III secretion system to inject toxins into target cells, a crucial step in infection establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. Upon cell contact, LcrV is also released into the surrounding medium where it has been shown to block the normal inflammatory response, although details of this mechanism have remained elusive. In this work, we reveal a key aspect of the immunomodulatory function of LcrV by showing that it interacts directly and with nanomolar affinity with the inflammatory cytokine IFNγ. In addition, we generate specific IFNγ mutants that show decreased interaction capabilities towards LcrV, enabling us to map the interaction region to two basic C-terminal clusters of IFNγ. Lastly, we show that the LcrV-IFNγ interaction can be disrupted by a number of inhibitors, some of which display nanomolar affinity. This study thus not only identifies novel potential inhibitors that could be developed for the control of Yersinia-induced infection, but also highlights the diversity of the strategies used by Y. pestis to evade the immune system, with the hijacking of pleiotropic cytokines being a long-range mechanism that potentially plays a key role in the severity of plague

Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.: HERV-W in schizophrenia and bipolar disorder

International audienceEpidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of severe psychotic disorders

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements