Distinct expression profiles of TGF-β1 signaling mediators in pathogenic SIVmac and non-pathogenic SIVagm infections

BACKGROUND: The generalized T-cell activation characterizing HIV-1 and SIVmac infections in humans and macaques (MACs) is not found in the non-pathogenic SIVagm infection in African green monkeys (AGMs). We have previously shown that TGF-β1, Foxp3 and IL-10 are induced very early after SIVagm infection. In SIVmac-infected MACs, plasma TGF-β1 induction persists during primary infection [1]. We raised the hypothesis that MACs are unable to respond to TGF-β1 and thus cannot resorb virus-driven inflammation. We therefore compared the very early expression dynamics of pro- and anti-inflammatory markers as well as of factors involved in the TGF-β1 signaling pathway in SIV-infected AGMs and MACs. METHODS: Levels of transcripts encoding for pro- and anti-inflammatory markers (tnf-α, ifn-γ, il-10, t-bet, gata-3) as well as for TGF-β1 signaling mediators (smad3, smad4, smad7) were followed by real time PCR in a prospective study enrolling 6 AGMs and 6 MACs. RESULTS: During primary SIVmac infection, up-regulations of tnf-α, ifn-γ and t-bet responses (days 1–16 p.i.) were stronger whereas il-10 response was delayed (4(th )week p.i.) compared to SIVagm infection. Up-regulation of smad7 (days 3–8 p.i.), a cellular mediator inhibiting the TGF-β1 signaling cascade, characterized SIV-infected MACs. In AGMs, we found increases of gata-3 but not t-bet, a longer lasting up-regulation of smad4 (days 1–21 p.i), a mediator enhancing TGF-β1 signaling, and no smad7 up-regulations. CONCLUSION: Our data suggest that the inability to resorb virus-driven inflammation and activation during the pathogenic HIV-1/SIVmac infections is associated with an unresponsiveness to TGF-β1

Thermomechanical Simulation of PET Stretch/Blow Molding

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Etude et modélisation de l’étirage/soufflage de bouteilles en P.E.T

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Viscoelastic Simulation of P.E.T Stretch/Blow Molding

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Villeneuve d'Ascq, rue du 8 mai 1945 : occupation domestique des Ier/IIe siècle

Rapport de diagnostic archéologique de 144 p., 51 fig., 8 annexes et 2 tableaux

Viscoelastic simulation of PET stretch/blow molding process

International audienceIn the stretch/blow molding process of poly(ethylene terephthalate) (PET) bottles, various parameters such as displacement of the stretch rod, inflation pressure, and polymer temperature distribution, have to be adjusted in order to improve the process. An axisymmetric numerical simulation code has been developed using a volumic approach. The numerical model is based on an updated-Lagrangian finite element method together with a penalty treatment of mass conservation. An automatic remeshing technique has been used. In addition, a decoupled technique has been developed in order to compute the viscoelastic constitutive equation. Successful stretch/blow molding simulations have been performed and compared to experiments

Two Human Immunodeficiency Virus Vaccinal Lipopeptides Follow Different Cross-Presentation Pathways in Human Dendritic Cells

An efficient vaccine against human immunodeficiency virus (HIV) must induce good cellular immune responses. To do this, it must be processed and presented by dendritic cells, which are required for primary T-lymphocyte stimulation. We have previously shown that a model lipopeptide containing a short epitopic peptide from HIV-1 was endocytosed and presented in association with major histocompatibility complex class I molecules by human dendritic cells to specific CD8(+) T lymphocytes, but the cross-presentation pathway needed to be precisely determined. We have studied a longer lipopeptide (Pol(461-484)) and another lipopeptide (Nef(66-97)) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol(461-484) lipopeptide was internalized by endocytosis, as assessed by confocal microscopy. The lipopeptides were processed by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201-restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope, respectively. Presentation of both lipopeptides was inhibited by brefeldin A. Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome-specific inhibitor, but not by monensin. This shows that it gained access to the cytosol to be digested by the proteasome. In contrast, presentation of the Nef lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a classical inhibitor of acid-dependent endosomal enzyme activity, indicating an endocytic processing pathway yielding to major histocompatibility complex class I-restricted presentation. Therefore, the two lipopeptides followed different cross-presentation pathways, both resulting in efficient presentation to CD8(+) T lymphocytes

The depositional record of the French Flemish Coastal plain since antiquity: Impacts of land reclamation in a tide‐dominated estuary

International audienceAbstract The French Flemish Coastal Plain, which extends from Denmark to France, is characterised by a topography close to sea level and protected by a system of coastal dunes. Quaternary sediments, comprised of marine, estuarine and continental deposits, accumulated by infilling and then prograding above a network of incised valleys. This study focusses on the Holocene infill of the Denna palaeoestuary, south‐west to Dunkerque. Surface geophysics (electrical conductivity and ground‐penetrating radar) and vibrocore data are used to reconstruct the landscape evolution during the last stages of sedimentation. The conductivity map highlights the last network of tidal channels, ditches and dikes of the eastern side of the palaeoestuary. Over the upper 4 m of the infill, the ground‐penetrating radar profiles show two superimposed units. The bottom unit is composed of meandering channel bars and the top unit of flat strata intersected by sparse channels, mostly infilled in place. The sediment analysis of the vibrocores shows a predominantly sandy filling of marine to estuarine origin, evidenced by sponge spicules and a fauna of bivalves and foraminifera adapted to brackish settings. The uppermost deposit exhibits an oxidation profile which marks the groundwater zone transition. Clayey sediments are also present, infilling the uppermost channels and ditches dug during reclamation, in increasing proportions towards the axis of the estuarine palaeovalley. The tidal signature of sedimentary dynamics is evidenced by heterolithic facies in some channel fills and tidal rhythmites infilling scour depressions linked to dike breaching. The abrupt decrease in channel dynamics across the unit boundary, although sedimentation remained sandy in the upper unit, coincides with the development of embankment of the estuarine border and is tentatively interpreted as a result of reclamation

Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS

T cell activation levels in HIV infection are predictive of AIDS progression. We searched for the immunological correlates of protection against disease progression by studying the early stages of nonpathogenic SIV infection in African green monkeys (SIVagm). The African green monkeys (AGMs) displayed high peak viremias and a transient decline in levels of blood CD4(+) and CD8(+) T cells between days 5 and 17 after infection. A concomitant increase in levels of CD4(+)DR(+), CD8(+)DR(+), and CD8(+)CD28(–) cells was detected. After the third week, T cell activation returned to baseline levels, which suggested a protective downregulation of T cell activation. A very early (24 hours after infection) and strong induction of TGF-β1 and FoxP3 expression was detected and correlated with increases in levels of CD4(+)CD25(+) and CD8(+)CD25(+) T cells. This was followed by a significant increase in levels of IL-10, whereas IFN-γ gene upregulation was more transient, and levels of TNF-α and MIP-1α/β transcripts did not increase in either blood or tissues. The profiles were significantly different during primary SIV infection in macaques (SIVmac); that is, there was a delayed increase in IL-10 levels accompanied by moderate and persistent increases in TGF-β levels. Together, our data show that SIVagm infection is associated with an immediate antiinflammatory environment and suggest that TGF-β may participate in the generation of Tregs, which may prevent an aberrant chronic T cell hyperactivation