176 research outputs found

    Coronary sinus sampling of cytokines after heart transplantation: Evidence for macrophage activation and interleukin-4 production within the graft

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    AbstractObjectives. This study was undertaken to evaluate the organ-specific release of cytokines after heart transplantation and to assess any correlation with transplant rejection. This cytokine profile should document the relative activation of mononuclear cell subsets within the graft.Background. Up to 60% of mononuclear cell infiltrating the cardiac allograft during rejection are macrophages, but their rote is undetermined. The T lymphocytes are activated, but the activity of specific T cell subsets is not known. We sought to assess for the first time in humans the in vivo activation of mononuclear cell subsets by measuring coronary sinus cytokine levels after heart transplantation.Methods. Palred superior vena cava and coronary sinus serum samples were assayed for interkeukin (IL)-2, IL-4 and IL-6, soluble IL-2 receptors, tumor necrosis factor-alpha and neopterin in 10 patients at the time of 40 routine endomyocardial biopsy procedures. All cytokine measurements were made by using enzyme-linked immunosorbent assay; neopterin was measured by using radioimmunoassy.Results. Interleukin-2 levels were not detectable (<0.8 U/ml) in either the superior vena cava or the coronary sinus in the presence or absence of rejection. Interleukin-2 receptor levels were uniformly elevated to 1,283 U/ml in the superior vena cava and to 1,232 U/ml in the coronary sinus, with no correlation with rejection severity. Interleukin-4 levels were consistently higher in coronary sinus serum than in peripheral blood (229 vs. 61 pg/ml, p < O.0005), but there was no relation with rejection. Interleukin-6 levels were higher in the coronary sinus than in me superior vena cava (200 vs. 120 pg/mi, p < 0.05). Tumor necrosis factor-alpha showed consistently elevated levels in coronary sinus serum (68 vs. 17 pg/ml, p < 0.0005), with no relation with rejection. Neopterin, which is produced only by activated macro-phages, was also consistently elevated in the coronary sinus (2.5 vs. 2.2 nmol, p = 0.08).Conclusions. The cardiac allograft is a major source of cyto-kines after heart transplantation. The cytokine profile allows the activity of subsets of the mononuclear cell infiltrate to be investigated. Elevated coronary sinus activity of the macrophage specific metabolite neopterin suggests macrophage activation within the allograft. This possibility is supported by elevated coronary sinus levels of tumor necrosis factor-alpha and IL-6. The T lymphocytes are activated, as evidenced by high soluble IL-2 receptor levels, but IL-2 production was suppressed by conventional immunosup-pressive therapy. Coronary sinus IL-4 levels represent T helper-2 cell activation within the graft despite immunosuppression. We could find no temporal relation between the coronary sinus or superior vena cava cytokine concentration or profile and severity of rejection on concurrent biopsy studies

    Light induced calcium binding to mangrove PS II particles

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    AbstractA combination calcium selective and oxygen electrode system was used to measure the Ca2+ and O2 concentrations of a solution surrounding mangrove PS II particles. Concomitant uptake of Ca2+ and oxygen evolution in the light were observed. The Ca2+ bound during the light was released in a subsequent dark period. The Ca2+ binding was dependent on both chlorophyll and Ca2+ concentrations. Up to 3000 Ca2+ were calculated to be bound per reaction centre

    ThX - a next-generation probe for the early detection of amyloid aggregates.

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    Neurodegenerative diseases such as Alzheimer's and Parkinson's are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, the improved optical properties (extinction coefficient, quantum yield and brightness) of ThX can be used to monitor structural differences in oligomeric species, not observed via traditional ThT imaging

    Future global climate: scenario-based projections and near-term information

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    This chapter assesses simulations of future global climate change, spanning time horizons from the near term (2021–2040), mid-term (2041–2060), and long term (2081–2100) out to the year 2300. Changes are assessed relative to both the recent past (1995–2014) and the 1850–1900 approximation to the pre-industrial period

    The Macromolecular Basis of Phytoplankton C:N:P Under Nitrogen Starvation

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    Biogeochemical cycles in the ocean are strongly affected by the elemental stoichiometry (C:N:P) of phytoplankton, which largely reflects their macromolecular content. A greater understanding of how this macromolecular content varies among phytoplankton taxa and with resource limitation may strengthen physiological and biogeochemical modeling efforts. We determined the macromolecular basis (protein, carbohydrate, lipid, nucleic acids, pigments) of C:N:P in diatoms and prasinophytes, two globally important phytoplankton taxa, in response to N starvation. Despite their differing cell sizes and evolutionary histories, the relative decline in protein during N starvation was similar in all four species studied and largely determined variations in N content. The accumulation of carbohydrate and lipid dominated the increase in C content and C:N in all species during N starvation, but these processes differed greatly between diatoms and prasinophytes. Diatoms displayed far greater accumulation of carbohydrate with N starvation, possibly due to their greater cell size and storage capacity, resulting in larger increases in C content and C:N. In contrast, the prasinophytes had smaller increases in C and C:N that were largely driven by lipid accumulation. Variation in C:P and N:P was species-specific and mainly determined by residual P pools, which likely represent intracellular storage of inorganic P and accounted for the majority of cellular P in all species throughout N starvation. Our findings indicate that carbohydrate and lipid accumulation may play a key role in determining the environmental and taxonomic variability in phytoplankton C:N. This quantitative assessment of macromolecular and elemental content spanning several marine phytoplankton species can be used to develop physiological models for ecological and biogeochemical applications

    Farmed Mussels: A Nutritive Protein Source, Rich in Omega-3 Fatty Acids, with a Low Environmental Footprint

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    OThe world’s ever-growing population presents a major challenge in providing sustainable food options and in reducing pressures on the Earth’s agricultural land and freshwater resources. Current estimates suggest that agriculture contributes ~30% of global greenhouse gas (GHG) emissions. Additionally, there is an increased demand for animal protein, the production of which is particularly polluting. Therefore, the climate-disrupting potential of feeding the planet is likely to substantially worsen in the future. Due to the nutritional value of animal-based protein, it is not a simple solution to recommend a wholesale reduction in production/consumption of animal proteins. Rather, employing strategies which result in the production of low carbon animal protein may be part of the solution to reduce the GHGs associated with our diets without compromising diet quality. We suggest that farmed mussels may present a partial solution to this dilemma. Mussel production has a relatively low GHG production and does not put undue pressure on land or fresh water supplies. By drawing comparisons to other protein sources using the Australian Food and Nutrient Database and other published data, we demonstrate that they are a sustainable source of high-quality protein, long-chain omega-3 fatty acids, phytosterols, and other key micronutrients such as B-12 and iron. The aim of this review is to summarise the current knowledge on the health benefits and potential risks of increasing the consumption of farmed mussels

    Researching the use of force: The background to the international project

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    This article provides the background to an international project on use of force by the police that was carried out in eight countries. Force is often considered to be the defining characteristic of policing and much research has been conducted on the determinants, prevalence and control of the use of force, particularly in the United States. However, little work has looked at police officers’ own views on the use of force, in particular the way in which they justify it. Using a hypothetical encounter developed for this project, researchers in each country conducted focus groups with police officers in which they were encouraged to talk about the use of force. The results show interesting similarities and differences across countries and demonstrate the value of using this kind of research focus and methodology
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