131 research outputs found

    An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection

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    TNF is an essential player in infections with Leishmania major, contributing to the control of the inflammatory lesion and, to a lesser degree, to parasite killing. However, the relative contribution of the soluble and transmembrane forms of TNF in these processes is unknown. To investigate the role of transmembrane TNF (mTNF) in the control of L. major infections, mTNF-knock-in (mTNF(Delta/Delta)) mice, which express functional mTNF but do not release soluble TNF, were infected with L. major, and the development of the inflammatory lesion and the immune response was compared to that occurring in L. major-infected TNF(-/-) and wild-type mice. mTNF(Delta/Delta) mice controlled the infection and resolved their inflammatory lesion as well as wild-type mice, a process associated with the early clearance of neutrophils at the site of parasite infection. In contrast, L. major-infected TNF(-/-) mice developed non-healing lesions, characterized by an elevated presence of neutrophils at the site of infection and partial control of parasite number within the lesions. Altogether, the results presented here demonstrate that mTNF, in absence of soluble TNF, is sufficient to control infection due to L. major, enabling the regulation of inflammation, and the optimal killing of Leishmania parasites at the site of infection

    Macrophages induce neutrophil apoptosis through membrane TNF, a process amplified by Leishmania major

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    Neutrophils are recruited to the site of parasite inoculation within a few hours of infection with the protozoan parasite Leishmania major. In C57BL/6 mice, which are resistant to infection, neutrophils are cleared from the site of s.c. infection within 3 days, whereas they persist for at least 10 days in susceptible BALB/c mice. In the present study, we investigated the role of macrophages (MPhi) in regulating neutrophil number. Inflammatory cells were recruited by i.p. injection of either 2% starch or L. major promastigotes. Neutrophils were isolated and cultured in the presence of increasing numbers of MPhi. Extent of neutrophil apoptosis positively correlated with the number of MPhi added. This process was strictly dependent on TNF because MPhi from TNF-deficient mice failed to induce neutrophil apoptosis. Assays using MPhi derived from membrane TNF knock-in mice or cultures in Transwell chambers revealed that contact with MPhi was necessary to induce neutrophil apoptosis, a process requiring expression of membrane TNF. L. major was shown to exacerbate MPhi-induced apoptosis of neutrophils, but BALB/c MPhi were not as potent as C57BL/6 MPhi in this induction. Our results emphasize the importance of MPhi-induced neutrophil apoptosis, and membrane TNF in the early control of inflammation

    Cluster algebras of infinite rank

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    Holm and Jørgensen have shown the existence of a cluster structure on a certain category D that shares many properties with finite type A cluster categories and that can be fruitfully considered as an infinite analogue of these. In this work we determine fully the combinatorics of this cluster structure and show that these are the cluster combinatorics of cluster algebras of infinite rank. That is, the clusters of these algebras contain infinitely many variables, although one is only permitted to make finite sequences of mutations. The cluster combinatorics of the category D are described by triangulations of an ∞-gon and we see that these have a natural correspondence with the behaviour of Plücker coordinates in the coordinate ring of a doubly-infinite Grassmannian, and hence the latter is where a concrete realization of these cluster algebra structures may be found. We also give the quantum analogue of these results, generalising work of the first author and Launois. An appendix by Michael Groechenig provides a construction of the coordinate ring of interest here, generalizing the well-known scheme-theoretic constructions for Grassmannians of finite-dimensional vector spaces

    Etudes structurales par diffusion des rayons X d'assemblées de nanotubes de carbone alignés (relation avec les mécanismes de croissance et les propriétés physiques)

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    Ce travail montre comment l'outil d'investigation qu'est la diffusion des rayons X permet d'obtenir différentes informations structurales sur les assemblées macroscopiques de nanotubes de carbone.Des tapis de nanotubes multiparois (nanotubes perpendiculaires à un substrat, synthétisés par dépôt chimique en phase vapeur catalysé, au Laboratoire Francis Perrin à Saclay), des fibres de nanotubes (synthétisées par filage dans un bain coagulant de polymère, au Centre de Recherche Paul Pascal à Bordeaux) et des échantillons de peapods (molécules de fullerènes encapsulées à l'intérieur de nanotubes) ont été étudiés.Nous avons montré que les tapis de nanotubes croissent par la base, à partir de particules catalytiques dont nous avons déterminé la nature : particules d'oxyde de fer, magnétite ou maghémite. L'étude quantitative de la distribution d'orientation des nanotubes montre qu'il est possible d'obtenir de très bonnes valeurs d'alignement des nanotubes. Un axe de croissance cristallographique préférentiel des nanofils métalliques encapsulés dans les nanotubes a été déterminé.Dans les fibres, l'alignement des nanotubes le long de l'axe de la fibre est amélioré par des traitements d'allongement post-synthèse : nous avons quantifié et modélisé cette amélioration. L'amélioration des propriétés mécaniques (module d'Young et contrainte à la rupture) avec l'alignement des nanotubes est étudié. Pour les échantillons de peapods , nous montrons que la diffusion des rayons X permet de déterminer le taux de remplissage des nanotubes et la distance entre fullerènes à l'intérieur des nanotubes. L'intérêt d'aligner les peapods au sein d'échantillons macroscopiques est souligné.The present work shows how X-ray scattering technique allows one to get structural information on carbon nanotube macroscopic assemblies.Carpets of multi-wall nanotubes (nanotubes aligned perpendicularly to a substrate synthesized by catalytic chemical vapor deposition, at Laboratoire Francis Perrin at Saclay), fibers of nanotubes (synthesized by wet spinning process in a coagulating polymer bath, at Centre de Recherche Paul Pascal at Bordeaux) and peapods samples (fullerene molecules encapsulated inside the nanotubes) were studied.We show that for nanotube carpets, the growth mechanism of the nanotubes is a root growth mechanism and the nature of the catalytic particles responsible of the nucleation of the nanotubes are iron oxide: magnetite or maghemite. Quantitative study of the nanotubes orientational distribution allows us to show that very good alignments can be obtained in carpets. A preferential crystallographic growth axis is determined for the metallic nanowires encapsulated inside the nanotubes.For nanotube fibers, post-synthesis stretching treatments allow one to get better alignment of the nanotubes along the fiber axis : we quantify and model the improvement of alignment. The improvement of mechanical properties such as Young modulus and tensile strength with nanotube alignment is studied.In peapods samples, modeling of the experimental results allows one to determine the filling rate and the distance between fullerene molecules. The advantages of aligned peapods samples are underlined.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

    Integration of Complex Optical Functionality in a Production CMOS Process

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    Optical functionality has been developed within the confines of an existing CMOS process. As of this writing, 10Gigabit modulators, electrically tunable optical filters, waveguides, and grating coupler technology have been successfully implemented alongside the existing transistors in the Freescale Hip7SOI process. This technology will be used to manufacture high bandwidth optical interconnections directly on silicon chips, allowing a new type of network and computing infrastructure to be developed. This work is covered in two distinct phases. First, the exploratory work done to gain experience with high index contrast silicon waveguides primarily served to uncover challenges related with simulation of these devices, and with the practical limitations of efficiently coupling the resulting waveguide devices with the outside world. The second phase began as the grating coupler emerged to address the coupling challenge. It became feasible to conceive of a commercially viable technology based on silicon photonics. The coupler has been evolved to a high level, currently achieving coupling loss of less than 1dB. Once the light is on chip, filtering and modulation technology are implemented. The reverse-biased plasma dispersion modulator has a 3dB roll-off of 10GHz, and an insertion loss less than 5dB. Optical filters based on ring resonators, arrayed waveguide gratings, and interleavers have all been implemented, often with world record performance, and many of the devices have been made electronically tunable to compensate for manufacturing variations and environmental excursions. Finally, circuitry has been designed and constructed on the same die with the optical functionality, fully demonstrating the ability to achieve monolithic integration of these devices.</p

    The Dixmier-Moeglin equivalence and a Gel'fand-Kirillov problem for Poisson polynomial algebras

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    The structure of Poisson polynomial algebras of the type obtained as semiclassical limits of quantized coordinate rings is investigated. Sufficient conditions for a rational Poisson action of a torus on such an algebra to leave only finitely many Poisson prime ideals invariant are obtained. Combined with previous work of the first-named author, this establishes the Poisson Dixmier-Moeglin equivalence for large classes of Poisson polynomial rings, including semiclassical limits of quantum matrices, quantum symplectic and euclidean spaces, quantum symmetric and antisymmetric matrices. For a similarly large class of Poisson polynomial rings, it is proved that the quotient field of the algebra (respectively, of any Poisson prime factor ring) is a rational function field F(x(1), ..., x(n)) over the base field (respectively, over an extension field of the base field) with {x(i),x(j)} = lambda(ij)x(i)x(j)for suitable scalars lambda(ij), thus establishing a quadratic Poisson version of the Gel'fand-Kirillov problem. Finally, partial solutions to the isomorphism problem for Poisson fields of the type just mentioned are obtained

    High Intralesional Interleukin‐10 Messenger RNA Expression in Localized Cutaneous Leishmaniasis Is Associated with Unresponsiveness to Treatment

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    International audienceThe intralesional expression of cytokines (interleukin [IL]-4, IL-13, IL-10, and interferon-gamma) was analyzed in 65 patients with localized cutaneous leishmaniasis due to Leishmania guyanensis before specific treatment with pentamidine isethionate. The local expression of IL-10 was significantly higher in patients who responded poorly to treatment than in patients whose lesions were regressing. When an IL-10 level >10 (ratio of the concentration of IL-10 [pg/microL] to that of beta-actin [pg/microL]) was used as an indicator of treatment failure, the sensitivity of this test was 78.6, and the specificity was 72.5. Thus, high intralesional expression of IL-10 might predict a poor response to conventional treatment

    The murine model of infection with Leishmania major and its importance for the deciphering of mechanisms underlying differences in Th cell differentiation in mice from different genetic backgrounds

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    Mice from the majority of inbred strains are resistant to infection by Leishmania major, an obligate intracellular protozoan parasite of macrophages in the mammalian host. In contrast, mice from BALB strains are unable to control infection and develop progressive disease. In this model of infection, genetically determined resistance and susceptibility have been clearly shown to result from the appearance of parasite-specific CD4+ T helper 1 or T helper 2 cells, respectively. This murine model of infection is considered as one of the best experimental systems for the study of the mechanisms operating in vivo at the initiation of polarised T helper 1 and T helper 2 cell maturation. Among the several factors influencing Th cell development, cytokines themselves critically regulate this process. The results accumulated during the last years have clarified some aspects of the role played by cytokines in Th cell differentiation. They are providing critical information that may ultimately lead to the rational devise of means by which to tailor immune responses to the effector functions that are most efficient in preventing and/or controlling infections with pathogens

    Development of a fish-based index (FBI) of biotic integrity for French lakes using the hindcasting approach

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    [Departement_IRSTEA]Eaux [TR1_IRSTEA]QUASAREInternational audienceThe European Water Framework Directive clearly indicates that fish is one of the quality elements to be considered for the assessment of lentic systems. However, few fish-based indices (FBIs) of biotic integrity have been developed for lakes so far. Hence, the aim of our study was to develop such a tool for French lakes. Fish surveys, lakes natural environmental parameters, catchment-scale anthropogenic pressures, and local pressures were collected for 67 reservoirs and 24 natural lakes throughout France. After assigning fish species into trophic, reproductive, and tolerance guilds, we derived a set of metrics reflecting complementary aspects of community functioning and condition. Other community-level traits such as richness and evenness were added. These metrics were modeled vs. natural environmental variables and pressures. Reference conditions at each site were then assessed using hindcasting modeling. Separate indices were eventually obtained for natural and artificial lakes by combining selected metrics. Fifteen out of 73 candidate fish metrics, covering all three groups of functional traits, displayed a significant response to anthropogenic pressures. After removal of the redundant traits, the final indices for natural lakes and reservoirs included three and six metrics, respectively. Agricultural-related impacts were prominent for reservoirs, whereas for natural lakes urban and local pressures displayed the most significant effects
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