61 research outputs found

    Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection

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    A variety of human diseases are associated with gammaherpesviruses, including neoplasms of lymphocytes (e.g. Burkitt's lymphoma) and endothelial cells (e.g. Kaposi's sarcoma). Gammaherpesvirus infections usually result in either a productive lytic infection, characterized by expression of all viral genes and rapid cell lysis, or latent infection, characterized by limited viral gene expression and no cell lysis. Here, we report characterization of endothelial cell infection with murine gammaherpesvirus 68 (γHV68), a virus phylogenetically related and biologically similar to the human gammaherpesviruses. Endothelial cells supported γHV68 replication in vitro, but were unique in that a significant proportion of the cells escaped lysis, proliferated, and remained viable in culture for an extended time. Upon infection, endothelial cells became non-adherent and altered in size, complexity, and cell-surface protein expression. These cells were uniformly infected and expressed the lytic transcription program based on detection of abundant viral gene transcripts, GFP fluorescence from the viral genome, and viral surface protein expression. Additionally, endothelial cells continued to produce new infectious virions as late as 30 days post-infection. The outcome of this long-term infection was promoted by the γHV68 v-cyclin, because in the absence of the v-cyclin, viability was significantly reduced following infection. Importantly, infected primary endothelial cells also demonstrated increased viability relative to infected primary fibroblasts, and this increased viability was dependent on the v-cyclin. Finally, we provide evidence for infection of endothelial cells in vivo in immune-deficient mice. The extended viability and virus production of infected endothelial cells indicated that endothelial cells provided a source of prolonged virus production and identify a cell-type specific adaptation of gammaherpesvirus replication. While infected endothelial cells would likely be cleared in a healthy individual, persistently infected endothelial cells could provide a source of continued virus replication in immune-compromised individuals, a context in which gammaherpesvirus-associated pathology frequently occurs

    Effect of Audiovisual Training on Monaural Spatial Hearing in Horizontal Plane

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    The article aims to test the hypothesis that audiovisual integration can improve spatial hearing in monaural conditions when interaural difference cues are not available. We trained one group of subjects with an audiovisual task, where a flash was presented in parallel with the sound and another group in an auditory task, where only sound from different spatial locations was presented. To check whether the observed audiovisual effect was similar to feedback, the third group was trained using the visual feedback paradigm. Training sessions were administered once per day, for 5 days. The performance level in each group was compared for auditory only stimulation on the first and the last day of practice. Improvement after audiovisual training was several times higher than after auditory practice. The group trained with visual feedback demonstrated a different effect of training with the improvement smaller than the group with audiovisual training. We conclude that cross-modal facilitation is highly important to improve spatial hearing in monaural conditions and may be applied to the rehabilitation of patients with unilateral deafness and after unilateral cochlear implantation

    Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

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    Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies

    Response of Cocoa Trees (Theobroma cacao) to a 13-month Dessication Period in Sulawesi, Indonesia

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    In South-east Asia, ENSO-related droughts represent irregularly occuring hazards for agroforestry systems containing cocoa which are predicted to increase in severity with expected climate warming. To characterize the drought response of mature cocoa tree, we conducted the Sulawesi Throughfall Displacement Experiment in a shaded (Gliricidia sepium) cocoa agroforestry system in Central Sulawesi, Indonesia. Three large sub-canopy roofs were installed to reduce throughfall by about 80% over a 13-month period to test the hypotheses that (i) cocoa trees are sensitive to drought due to their shallow fine root system, and (ii)bean yield is more sensitive to drought than leaf or stem growth. As 83% of fine root (diameter 2mm) was located in the upper 40 cm of the soil, the cocoa tree examined had a very shallow root system. Cocoa and Gliricidia differed in their vertical rooting patterns, thereby reducing competition for water. Despite being exposed for several mnths to soil water contents close to the conventional wilting point, cocoa trees showed no significant decreases in leaf biomass, stem and branch wood production or fine root biomass. Possible causes are active osmotic adjusment in roots, mitigation of drought stress by shading from Gliricidia or other factors. By contrast, production of cocoa bean

    Effects of different cultivated or weed grasses, grown as pure stands or in combination with wheat, on take-all and its suppression in subsequent wheat crops

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    Grass species were grown in plots, as pure stands or mixed with wheat, after a sequence of wheat crops in which take-all (Gaeumannomyces graminis var. tritici) had developed. Annual brome grasses maintained take-all inoculum in the soil as well as wheat (grown as a continuous sequence), and much better than cultivated species with a perennial habit. Take-all developed more in wheat grown after Anisantha sterilis (barren brome) or Bromus secalinus (rye brome), with or without wheat, than in continuous grass-free wheat in the same year, where take-all decline was apparently occurring. It was equally or more severe, however, in wheat grown after Lolium perenne (rye-grass) or Festuca arundinacea (tall fescue), despite these species having left the least inoculum in the soil. It was most severe in plots where these two grasses had been grown as mixtures with wheat. It is postulated that the presence of these grasses inhibited the development of take-all-suppressive microbiota that had developed in the grass-free wheat crops. The effects of the grasses appeared to be temporary, as amounts of take-all in a second subsequent winter wheat test crop were similar after all treatments. These results have important implications for take-all risk in wheat and, perhaps, other cereal crops grown after grass weed-infested cereals or after set-aside or similar 1-year covers containing weeds or sown grasses, especially in combination with cereal volunteers. They also indicate that grasses might be used experimentally in wheat crop sequences for investigating the mechanisms of suppression of, and conduciveness to, take-all
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