98 research outputs found

    The Interaction of Political, Fiscal and Financial Stability: Lessons from the Crisis

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    The current financial, economic and fiscal crisis is among other things characterised by complex interrelations between financial, fiscal, macroeconomic and political instability. One instability breeds another, with feedback loops generating self-reinforcing adverse cycles: The financial crisis triggered the ‘Great Recession’. Countermeasures by governments – to save banks and bolster up aggregate demand – ultimately jeopardized fiscal sustainability and bred the fiscal crisis. The latter in turn destabilised sovereign bond markets and banking systems in several countries. Political instability resulted from the substantial fiscal consolidations forced upon governments in the light of threatening or actual loss of access to financial market financing, and the accompanying deep recessions and sharp increase in unemployment. Political instability in turn further erodes economic and financial market confidence, thus worsening short and long-term economic and fiscal prospects, and further aggravating financial instability. In the EU and more specifically the Euro Area, multiple channels of spillovers and contagion turn the problems from purely national phenomena to ones of EU-wide and ultimately even global scope. Thus, apart from national political processes, Euro Area and EU-wide economic governance has been criticized for not addressing reform needs decisively, thus prolonging and deepening the cycle of instability

    Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response

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    Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response. Intriguingly, several infectious agents, such as Toxoplasma, Legionella, and Chlamydia, have been reported to grow within vacuoles surrounded by host mitochondria. Although many hypotheses have been proposed for the existence of host mitochondrial association (HMA), the causes and biological consequences of HMA have remained unanswered. Here we show that HMA is present in type I and III strains of Toxoplasma but missing in type II strains, both in vitro and in vivo. Analysis of F1 progeny from a type II×III cross revealed that HMA is a Mendelian trait that we could map. We use bioinformatics to select potential candidates and experimentally identify the polymorphic parasite protein involved, mitochondrial association factor 1 (MAF1). We show that introducing the type I (HMA+) MAF1 allele into type II (HMA-) parasites results in conversion to HMA+ and deletion of MAF1 in type I parasites results in a loss of HMA. We observe that the loss and gain of HMA are associated with alterations in the transcription of host cell immune genes and the in vivo cytokine response during murine infection. Lastly, we use exogenous expression of MAF1 to show that it binds host mitochondria and thus MAF1 is the parasite protein directly responsible for HMA. Our findings suggest that association with host mitochondria may represent a novel means by which Toxoplasma tachyzoites manipulate the host. The existence of naturally occurring HMA+ and HMA- strains of Toxoplasma, Legionella, and Chlamydia indicates the existence of evolutionary niches where HMA is either advantageous or disadvantageous, likely reflecting tradeoffs in metabolism, immune regulation, and other functions of mitochondria. © 2014 Pernas et al

    Phosphorylation of toxoplasma gondii secreted proteins during acute and chronic stages of infection

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    ABSTRACT The intracellular parasite Toxoplasma gondii resides within a membrane-bound parasitophorous vacuole (PV) and secretes an array of proteins to establish this replicative niche. It has been shown previously that Toxoplasma secretes kinases and that numerous proteins are phosphorylated after secretion. Here, we assess the role of the phosphorylation of strand-forming protein 1 (SFP1) and the related protein GRA29, two secreted proteins with unknown function. We show that both proteins form stranded structures in the PV that are independent of the previously described intravacuolar network or actin. SFP1 and GRA29 can each form these structures independently of other Toxoplasma secreted proteins, although GRA29 appears to regulate SFP1 strands. We show that an unstructured region at the C termini of SFP1 and GRA29 is required for the formation of strands and that mimicking the phosphorylation of this domain of SFP1 negatively regulates strand development. When tachyzoites convert to chronic-stage bradyzoites, both proteins show a dispersed localization throughout the cyst matrix. Many secreted proteins are reported to dynamically redistribute as the cyst forms, and secreted kinases are known to play a role in cyst formation. Using quantitative phosphoproteome and proteome analyses comparing tachyzoite and early bradyzoite stages, we reveal widespread differential phosphorylation of secreted proteins. While we found no direct evidence for phosphorylation playing a dominant role for SFP1/GRA29 redistribution in the cyst, these data support a model in which secreted kinases and phosphatases contribute to the regulation of secreted proteins during stage conversion. IMPORTANCE Toxoplasma gondii is a common parasite that infects up to one-third of the human population. Initially, the parasite grows rapidly, infecting and destroying cells of the host, but subsequently switches to a slow-growing form and establishes chronic infection. In both stages, the parasite lives within a membrane-bound vacuole within the host cell, but in the chronic stage, a durable cyst wall is synthesized, which provides protection to the parasite during transmission to a new host. Toxoplasma secretes proteins into the vacuole to build its replicative niche, and previous studies identified many of these proteins as phosphorylated. We investigate two secreted proteins and show that a phosphorylated region plays an important role in their regulation in acute stages. We also observed widespread phosphorylation of secreted proteins when parasites convert from acute to chronic stages, providing new insight into how the cyst wall may be dynamically regulated

    High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors

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    <p>Abstract</p> <p>Background</p> <p>DNA of the polyomaviruses WU (WUPyV) and KI (KIPyV) and of human bocavirus (HBoV) has been detected with varying frequency in respiratory tract samples of children. However, only little is known about the humoral immune response against these viruses. Our aim was to establish virus-specific serological assays and to determine the prevalence of immunoglobulin G (IgG) against these three viruses in the general population.</p> <p>Methods</p> <p>The capsid proteins VP1 of WUPyV and KIPyV and VP2 of HBoV were cloned into baculovirus vectors and expressed in Sf9 insect cells. IgG antibodies against WUPyV VP1, KIPyV VP1, and HBoV VP2 were determined by immunofluorescence assays in 100 plasma samples of blood donors.</p> <p>Results</p> <p>The median age of the blood donors was 31 years (range 20 - 66 yrs), 52% were male. 89% of the samples were positive for WUPyV IgG (median age 31 yrs, 49.4% male), 67% were positive for KIPyV IgG (median age 32 yrs, 46.3% male), and 76% were positive for HBoV IgG (median age 32 yrs, 51.3% male). For WUPyV and HBoV, there were no significant differences of the seropositivity rates with respect to age groups or gender. For KIPyV, the seropositivity rate increased significantly from 59% in the age group 20 - 29 years to 100% in the age group > 50 years.</p> <p>Conclusions</p> <p>High prevalences of antibodies against WUPyV, KIPyV, and HBoV were found in plasma samples of healthy adults. The results indicate that primary infection with these viruses occurs during childhood or youth. For KIPyV, the seropositivity appears to increase further during adulthood.</p

    CFD Prediction of Tip Vortex Aging in the Wake of a Multi-MW Wind Turbine

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    Abstract In the present study, prediction from high-fidelity Computational Fluid Dynamics (CFD) simulations of the tip vortex aging in the near-wake of a multi-MW wind turbine is evaluated and compared to in-situ measurements as well as results of a semi-empirical model. Optimized tip vortex refinement is also introduced to investigate the influence of the grid topology on the vortex evolution. The grid refinement affects only the vortex core size and a reduction of the core radius by a factor of 3.4 was achieved with the chosen parameters. On the refined setup, vortex core sizes and strength are comparable with in-situ Unmanned Aircraft System (UAS) based measurements at 0.5 rotor radius downstream of the wind turbine. A comparison of the aging function with a semi-empirical vortex helix model shows a good agreement with the refined CFD results, but the core size predicted by the model is smaller than in simulations and experiments.</jats:p

    Manufacturing bio-based fiber-reinforced polymer composites: process performance in RTM and VARI processes

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    The utilization of bio-based materials for the manufacturing of fiber-reinforced polymer composites is gaining importance under the sustainability paradigm. The identification of suitable process parameters and limited process reproducibility remain among the major challenges to enhance the industrial application potential of bio-based composites. This is especially relevant, as the manufacturing process influences composite quality, economic performance and environmental impacts. This study compares Resin Transfer Molding and Vacuum Assisted Resin Infusion for two sets of process parameters in order to manufacture a composite plate consisting of a flax-fiber textile impregnated with a partially bio-based epoxy matrix. Process quality is described through statistical analysis of processing and composite properties, and performance in terms of process replicability and reliability using performance estimates. Processing parameters were selected to depict a range of manufacturing scenarios that were suitable for the selected bio-based material system from curing for 180 min at 60 °C to curing for 30 min at 100 °C. For an identical set of process conditions, Resin Transfer Molding outperforms Vacuum Assisted Resin Infusion in terms of tensile and flexural characteristics. Conversely, the latter shows the strongest fiber-matrix adhesion and the most homogeneous impregnation. Whereas manufacturing at lower temperature leads to positive effects on composite quality, higher processing temperature with shorter curing cycles achieve highest process performance in terms of Pp and Ppk indices. An additional annealing at 120 °C neither increases composite quality nor reduces manufacturing-induced variability. Results depend on processing differences and indicators to determine process performance, as well as methodological choices
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