248 research outputs found

    Cotton waste : its production, manipulation and uses

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    Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

    IFN-α/β Induction by dsRNA and Toll-Like Receptors Shortens Allograft Survival Induced by Costimulation Blockade: A Dissertation

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    Costimulation blockade protocols are promising alternatives to the use of chronic immunosuppression for promoting long-term allograft survival. However, the efficacy of costimulation blockade-based protocols is decreased by environmental insults such as viral infections. For example, lymphocytic choriomeningitis virus (LCMV) infection at the time of costimulation blockade treatment abrogates skin allograft survival in mice. In this dissertation, we test the hypothesis that viruses shorten allograft survival by activating the innate immune system through pattern-recognition receptors (PRRs), such as toll-like receptors (TLRs). To investigate the role of innate immunity in shortening allograft survival, costimulation blockade-treated mice were co-injected with TLR2 (Pam3Cys), TLR3 (polyinosinic:polycytidylic acid, poly(I:C)), TLR4 (lipopolysaccharide, LPS), or TLR9 (CpG DNA) agonists, followed by transplantation with skin allografts 7 days later. Costimulation blockade prolonged skin allograft survival that was shortened in mice coinjected with TLR agonists. To investigate the underlying mechanisms of this observation, we used synchimeric mice, which circulate trace populations of anti-H2b transgenic alloreactive CD8+ T cells. In synchimeric mice treated with costimulation blockade, co-administration of all four TLR agonists prevented deletion of alloreactive CD8+ T cells. These alloreactive CD8+ T cells 1) expressed the proliferation marker Ki-67, 2) upregulated CD44, and 3) failed to undergo apoptosis. We also demonstrate that costimulation blockade-treated CD8α-deficient mice exhibit prolonged allograft survival when co-injected with LPS. These data suggest that TLR agonists shorten allograft survival by impairing the apoptosis of alloreactive CD8+T cells. We further delineate the mechanism by which TLR agonists shorten allograft survival by demonstrating that LPS and poly(I:C) fail to shorten allograft survival in IFNRI- deficient mice. Interestingly, the ability of poly(I:C) to more potently induce IFN-α/β than LPS correlates with its superior abilities to shorten islet allograft survival and induce allo-specific CTL activity as measured by an in vivo cytotoxicity assay. The ability to shorten allograft survival and induce IFN-α/β is a TLR-dependent process for LPS, but is a TLR-independent process for poly(I:C). Strikingly, the injection of IFN-β impairs alloreactive CD8+T cell deletion and shortens allograft survival, similar to LPS and poly(I:C). These data suggest that LPS and poly(I:C) shorten allograft survival by inducing IFN-α/β through two different mechanisms. Finally, we present data showing that viruses (LCMV, Pichinde virus, murine cytomegalovirus and vaccinia virus) impair alloreactive CD8+T cell deletion and shorten allograft survival, in a manner comparable to LPS and poly(I:C). Similar to LPS, LCMV and MCMV exhibit an impaired ability to shorten allograft survival in MyD88-deficient mice. These data suggest that the MyD88 pathway is required for certain viruses and TLR-agonists to shorten allograft survival. In this dissertation, we present data supporting an important role for TLRs and IFN- α/β in shortening allograft induced by costimulation blockade. Our findings suggest that targeting these pathways during the peri-transplant period may enhance the efficacy of costimulation blockade protocols in the clinic

    Viral Infection: A Potent Barrier to Transplantation Tolerance

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    Transplantation of allogeneic organs has proven to be an effective therapeutic for a large variety of disease states, but the chronic immunosuppression that is required for organ allograft survival increases the risk for infection and neoplasia and has direct organ toxicity. The establishment of transplantation tolerance, which obviates the need for chronic immunosuppression, is the ultimate goal in the field of transplantation. Many experimental approaches have been developed in animal models that permit long-term allograft survival in the absence of chronic immunosuppression. These approaches function by inducing peripheral or central tolerance to the allograft. Emerging as some of the most promising approaches for the induction of tolerance are protocols based on costimulation blockade. However, as these protocols move into the clinic, there is recognition that little is known as to their safety and efficacy when confronted with environmental perturbants such as virus infection. In animal models, it has been reported that virus infection can prevent the induction of tolerance by costimulation blockade and, in at least one experimental protocol, can lead to significant morbidity and mortality. In this review, we discuss how viruses modulate the induction and maintenance of transplantation tolerance

    Reasonable potential for GHG savings by anaerobic biomethane in Germany and UK derived from economic and ecological analyses

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    This study introduces a new approach to estimate biomethane market potential by analysing biogas markets and their relative environmental and economic advantages. This potential is then combined with greenhouse gas emission values for different feedstock shares (farm-fed and waste-fed systems) and different application share to determine the possible contribution of biomethane to national greenhouse gas emission saving goals. Markets that are considered are Germany and the UK being the biggest emitters of CO2eq in the European Union. The current use was compared with the scenarios (i) market projection, derived from literature study and (ii) reasonable potential, derived from environmental and economic calculations. The current market status is presented to show the past market development until the present date and associated greenhouse gas savings. Additionally the potential of biomethane to contribute to greenhouse gas emission savings is extensively described. Results indicate that the share of application in Germany is more environmental beneficial than the one in the UK achieving higher greenhouse gas savings at comparable feed-in level. In contrast, the UK has a higher share of waste-fed systems to produce biomethane. The use of biomethane in CHP plants achieves the highest GHG emission savings and if organic waste is used as feedstock the possible savings are even higher. With an increase of biomethane used in CHP plants and a decrease of biomethane used for direct heating the savings in the UK could increase up to 52%. Current savings of 2446 kt CO2eq (Germany) and 606 kt CO2eq (UK) can be extended to 4483 kt CO2eq (Germany) and 1443 kt CO2eq (UK) respectively. Scenario results were determined based on the environmental and economic advantageousness development of the existing biogas market. In this way positive future market development as well as improved shares of feedstock and application can contribute to further greenhouse gas emission savings of Germany and the UK

    Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice

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    Allograft transplantation requires chronic immunosuppression, but there is no effective strategy to evaluate the long-term maintenance of immunosuppression other than assessment of graft function. The ability to monitor naive alloreactive T cells would provide an alternative guide for drug therapy at early, preclinical stages of graft rejection and for evaluating tolerance-inducing protocols. To detect and quantify naive alloreactive T cells directly ex vivo, we used the unique ability of naive T cells to rapidly produce TNF-alpha but not IFN-gamma. Naive alloreactive T cells were identified by the production of TNF-alpha after a 5-hour in vitro stimulation with alloantigen and were distinguished from effector/memory alloreactive T cells by the inability to produce IFN-gamma. Moreover, naive alloreactive T cells were not detected in mice tolerized against specific alloantigens. The frequency of TNF-alpha-producing cells was predictive for rejection in an in vivo cytotoxicity assay and correlated with skin allograft rejection. Naive alloreactive T cells were also detected in humans, suggesting clinical relevance. We conclude that rapid production of TNF-alpha can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection

    Adipose Tissue-Derived Mesenchymal Stem Cells Increase Skin Allograft Survival and Inhibit Th-17 Immune Response

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    Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4+ regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4+ T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation

    Warm Dust and Spatially Variable PAH Emission in the Dwarf Starburst Galaxy NGC 1705

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    We present Spitzer observations of the dwarf starburst galaxy NGC 1705 obtained as part of SINGS. The galaxy morphology is very different shortward and longward of ~5 microns: short-wavelength imaging shows an underlying red stellar population, with the central super star cluster (SSC) dominating the luminosity; longer-wavelength data reveals warm dust emission arising from two off-nuclear regions offset by ~250 pc from the SSC. These regions show little extinction at optical wavelengths. The galaxy has a relatively low global dust mass (~2E5 solar masses, implying a global dust-to-gas mass ratio ~2--4 times lower than the Milky Way average). The off-nuclear dust emission appears to be powered by photons from the same stellar population responsible for the excitation of the observed H Alpha emission; these photons are unassociated with the SSC (though a contribution from embedded sources to the IR luminosity of the off-nuclear regions cannot be ruled out). Low-resolution IRS spectroscopy shows moderate-strength PAH emission in the 11.3 micron band in the eastern peak; no PAH emission is detected in the SSC or the western dust emission complex. There is significant diffuse 8 micron emission after scaling and subtracting shorter wavelength data; the spatially variable PAH emission strengths revealed by the IRS data suggest caution in the interpretation of diffuse 8 micron emission as arising from PAH carriers alone. The metallicity of NGC 1705 falls at the transition level of 35% solar found by Engelbracht and collaborators; the fact that a system at this metallicity shows spatially variable PAH emission demonstrates the complexity of interpreting diffuse 8 micron emission. A radio continuum non-detection, NGC 1705 deviates significantly from the canonical far-IR vs. radio correlation. (Abridged)Comment: ApJ, in press; please retrieve full-resolution version from http://www.astro.wesleyan.edu/~cannon/pubs.htm

    The Nature of Infrared Emission in the Local Group Dwarf Galaxy NGC 6822 As Revealed by Spitzer

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    We present Spitzer imaging of the metal-deficient (Z ~30% Z_sun) Local Group dwarf galaxy NGC 6822. On spatial scales of ~130 pc, we study the nature of IR, H alpha, HI, and radio continuum emission. Nebular emission strength correlates with IR surface brightness; however, roughly half of the IR emission is associated with diffuse regions not luminous at H alpha (as found in previous studies). The global ratio of dust to HI gas in the ISM, while uncertain at the factor of ~2 level, is ~25 times lower than the global values derived for spiral galaxies using similar modeling techniques; localized ratios of dust to HI gas are about a factor of five higher than the global value in NGC 6822. There are strong variations (factors of ~10) in the relative ratios of H alpha and IR flux throughout the central disk; the low dust content of NGC 6822 is likely responsible for the different H alpha/IR ratios compared to those found in more metal-rich environments. The H alpha and IR emission is associated with high-column density (> ~1E21 cm^-2) neutral gas. Increases in IR surface brightness appear to be affected by both increased radiation field strength and increased local gas density. Individual regions and the galaxy as a whole fall within the observed scatter of recent high-resolution studies of the radio-far IR correlation in nearby spiral galaxies; this is likely the result of depleted radio and far-IR emission strengths in the ISM of this dwarf galaxy.Comment: ApJ, in press; please retrieve full-resolution version from http://www.astro.wesleyan.edu/~cannon/pubs.htm

    A process-based model of conifer forest structure and function with special emphasis on leaf lifespan

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    We describe the University of Sheffield Conifer Model (USCM), a process-based approach for simulating conifer forest carbon, nitrogen, and water fluxes by up-scaling widely applicable relationships between leaf lifespan and function. The USCM is designed to predict and analyze the biogeochemistry and biophysics of conifer forests that dominated the ice-free high-latitude regions under the high pCO2 “greenhouse” world 290–50 Myr ago. It will be of use in future research investigating controls on the contrasting distribution of ancient evergreen and deciduous forests between hemispheres, and their differential feedbacks on polar climate through the exchange of energy and materials with the atmosphere. Emphasis is placed on leaf lifespan because this trait can be determined from the anatomical characteristics of fossil conifer woods and influences a range of ecosystem processes. Extensive testing of simulated net primary production and partitioning, leaf area index, evapotranspiration, nitrogen uptake, and land surface energy partitioning showed close agreement with observations from sites across a wide climatic gradient. This indicates the generic utility of our model, and adequate representation of the key processes involved in forest function using only information on leaf lifespan, climate, and soils
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