293 research outputs found

    Gem-induced cytoskeleton remodeling increases cellular migration of HTLV-1-infected cells, formation of infected-to-target T-cell conjugates and viral transmission

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    Efficient HTLV-1 viral transmission occurs through cell-to-cell contacts. The Tax viral transcriptional activator protein facilitates this process. Using a comparative transcriptomic analysis, we recently identified a series of genes up-regulated in HTLV-1 Tax expressing T-lymphocytes. We focused our attention towards genes that are important for cytoskeleton dynamic and thus may possibly modulate cell-to-cell contacts. We first demonstrate that Gem, a member of the small GTP-binding proteins within the Ras superfamily, is expressed both at the RNA and protein levels in Tax-expressing cells and in HTLV-1-infected cell lines. Using a series of ChIP assays, we show that Tax recruits CREB and CREB Binding Protein (CBP) onto a c-AMP Responsive Element (CRE) present in the gem promoter. This CRE sequence is required to drive Tax-activated gem transcription. Since Gem is involved in cytoskeleton remodeling, we investigated its role in infected cells motility. We show that Gem co-localizes with F-actin and is involved both in T-cell spontaneous cell migration as well as chemotaxis in the presence of SDF-1/CXCL12. Importantly, gem knock-down in HTLV-1-infected cells decreases cell migration and conjugate formation. Finally, we demonstrate that Gem plays an important role in cell-to-cell viral transmission

    Two distinct STLV-1 subtypes infecting Mandrillus sphinx follow the geographic distribution of their hosts

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    The mandrill (Mandrillus sphinx) has been shown to be infected with an STLV-1 closely related to HTLV-1. Two distinct STLV-1 subtypes (D and F) infect wild mandrills with high overall prevalence (27.0%) but are different with respect to their phylogenetic relationship and parallel to the mandrills' geographic range. The clustering of these new STLV-1mnd sequences with HTLV-1 subtype D and F suggests first, past simian-tohuman transmissions in Central Africa and second, that species barriers are easier to cross over than geographic barriers

    Adenovirus-Mediated Sensitization to the Cytotoxic Drugs Docetaxel and Mitoxantrone Is Dependent on Regulatory Domains in the E1ACR1 Gene-Region

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    Oncolytic adenoviruses have shown promising efficacy in clinical trials targeting prostate cancers that frequently develop resistance to all current therapies. The replication-selective mutants AdΔΔ and dl922–947, defective in pRb-binding, have been demonstrated to synergise with the current standard of care, mitoxantrone and docetaxel, in prostate cancer models. While expression of the early viral E1A gene is essential for the enhanced cell killing, the specific E1A-regions required for the effects are unknown. Here, we demonstrate that replicating mutants deleted in small E1A-domains, binding pRb (dl1108), p300/CBP (dl1104) and p400/TRRAP or p21 (dl1102) sensitize human prostate cancer cells (PC-3, DU145, 22Rv1) to mitoxantrone and docetaxel. Through generation of non-replicating mutants, we demonstrate that the small E1A12S protein is sufficient to potently sensitize all prostate cancer cells to the drugs even in the absence of viral replication and the E1A transactivating domain, conserved region (CR) 3. Furthermore, the p300/CBP-binding domain in E1ACR1 is essential for drug-sensitisation in the absence (AdE1A1104) but not in the presence of the E1ACR3 (dl1104) domain. AdE1A1104 also failed to increase apoptosis and accumulation of cells in G2/M. All E1AΔCR2 mutants (AdE1A1108, dl922–947) and AdE1A1102 or dl1102 enhance cell killing to the same degree as wild type virus. In PC-3 xenografts in vivo the dl1102 mutant significantly prolongs time to tumor progression that is further enhanced in combination with docetaxel. Neither dl1102 nor dl1104 replicates in normal human epithelial cells (NHBE). These findings suggest that additional E1A-deletions might be included when developing more potent replication-selective oncolytic viruses, such as the AdΔCR2-mutants, to further enhance potency through synergistic cell killing in combination with current chemotherapeutics

    STLV-1 co-infection is correlated with an increased SFV proviral load in the peripheral blood of SFV/STLV-1 naturally infected non-human primates

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    Simian T-Leukemia Virus type 1 and Simian Foamy Virus infect non-human primates. While STLV-1, as HTLV-1, causes Adult T-cell Leukemia/lymphoma, SFV infection is asymptomatic. Both retroviruses can be transmitted from NHPs to humans through bites that allow contact between infected saliva and recipient blood. Because both viruses infect CD4+ T-cells, they might interfere with each other replication, and this might impact viral transmission. Impact of STLV-1 co-infection on SFV replication was analyzed in 18 SFV-positive/STLV-1-negative and 18 naturally SFV/STLV-1 co-infected Papio anubis. Even if 9 animals were found STLV-1-positive in saliva, STLV-1 PVL was much higher in the blood. SFV proviruses were detected in the saliva of all animals. Interestingly, SFV proviral load was much higher in the blood of STLV-1/SFV co-infected animals, compared to STLV-1-negative animals. Given that soluble Tax protein can enter uninfected cells, we tested its effect on foamy virus promoter and we show that Tax protein can transactivate the foamy LTR. This demonstrates that true STLV-1 co-infection or Tax only has an impact on SFV replication and may influence the ability of the virus to be zoonotically transmitted as well as its ability to promote hematological abnormalities

    Venus transit 2004: Illustrating the capability of exoplanet transmission spectroscopy

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    The transit of Venus in 2004 offered the rare possibility to remotely sense a well-known planetary atmosphere using ground-based observations for absorption spectroscopy. Transmission spectra of Venus' atmosphere were obtained in the near infrared using the Vacuum Tower Telescope (VTT) in Tenerife. Since the instrument was designed to measure the very bright photosphere of the Sun, extracting Venus' atmosphere was challenging. CO_2 absorption lines could be identified in the upper Venus atmosphere. Moreover, the relative abundance of the three most abundant CO_2 isotopologues could be determined. The observations resolved Venus' limb, showing Doppler-shifted absorption lines that are probably caused by high-altitude winds. This paper illustrates the ability of ground-based measurements to examine atmospheric constituents of a terrestrial planet atmosphere which might be applied in future to terrestrial extrasolar planets.Comment: 7 pages, 5 figures, 1 tabl

    Earthworm management in tropical agroecosystems

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    Collaborative research in the Macrofauna project has enabled development of some techniques that presently are at different stages of advancement, from promising pilot experiments (tomato production and inoculation in plant nursery bags at Yurimaguas and in India) to the fully developed technique of massive worm production and biofertilization of tea gardens in Tamil Nadu (India) (patent deposited). Failures have also helped to gain better insight into the potential feasibility of techniques that had been considered in the objectives of this project. Endogeic earthworms (#Pontoscolex corethrurus$) may be produced in large quantities, i.e.about 12000 worms (1.6-2.8 kg live wt)/m2/year in specific culture beds using either sawdust (Yurimaguas, Peru) or a mixture of high and low quality materials (Tamil Nadu, India) mixed into soil as substrates. Cost of production of 1 kg of earthworm biomass through bed culture is about 3.6 Euro, much lower than the cost of hand collection of worms from pastures/grasslands where these species are abundant (6-125 Euro depending on the cost of labour and earthworm density). The theorical value of an active earthworm community with an average biomass of 400 kg live wt has been estimated at 1400 Euro, the price that it would cost to reintroduce an equivalent biomass produced in our culture units, indicating the cost of land restoration. Direct inoculation of earthworms in the field to improve production may only affect plant growth positively if a large biomass (greater than 30 g live wt/m2) is inoculated from the beginning. An alternative may be to concentrate the inoculum in small areas regularly distributed across the field... (D'après résumé d'auteur

    Traitement du signal audio-visuel et visiophone personne libre

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    Les informations visuelles et acoustiques sont au coeur de la (télé)communication entre les personnes. Le visage est la principale source d'information. Des techniques de détection du mouvement et de la teinte de la peau délimitent des régions d'intérêt où peuvent se trouver des visages. Un réseau de neurones détecte le visage et fournit la position et l'échelle du visage. Le visage repéré est suivi, en temps réel, par une caméra motorisée et par une antenne acoustique qui génère un lobe orientable. La prise de vue et la prise de son sont ainsi centrées en permanence sur l'utilisateur qui est libre de se déplacer et libre de tout équipement spécifique. Le traitement du signal audio-visuel sont intégrées à LISTEN, démonstrateur du visiophone "personne libre"
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