3,854 research outputs found
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Comparative Study Of The Influence Of Natural Convection On Directional Solidification Of Al-3.5 Wt% Ni And Al-7 Wt% Si Alloys
No full textWe present numerical simulations of thermosolutal convection for directional solidification of Al-3.5 wt% Ni and Al-7 wt% Si. Numerical results predict that fragmentation of dendrite arms resulting from dissolution could be favored in Al-7 wt% Si, but not in Al-3.5 wt% Ni. Corresponding experiments are in qualitative agreement with the numerical predictions. Distinguishing the two fragmentation mechanisms, namely dissolution and remelting, is critical during experiments on earth, when fluid flow is dominant. (C) 2007 COSPAR. Published by Elsevier Ltd. All rights reserved
Hysteresis phenomenon and wetting characteristics of molten Sn-3.0 wt.%Ag-0.5 wt.%Cu on different tilting substrates
No full textThe hysteresis phenomenon and wetting characteristics of molten Sn-3.0 wt.%Ag-0.5 wt.%Cu on wetting and non-wetting tilting substrates at different temperatures were investigated. The viewpoint on negative interfacial tension was proposed in this paper to explain the spreading and wetting behaviors for sample on different tilted substrates. The critical sliding angle was defined as limited tilting angle of surface at which the molten drop slid down and the upper and lower contact angles of molten drop were measured as the advancing and receding contact angles, respectively. Wetting experiments were performed to determine how contact angle and contact hysteresis on alumina and oxygen-free copper tilting substrates changed with temperature. Static, limited tilting, advancing and receding contact angles on two kinds of substrates were measured at different temperatures. In general, both negative interfacial tension and hysteresis for sample on copper were much larger than that on alumina over the range of temperatures studied, indicating better wettability but worse motion characteristics for the former. It was due to the larger adhesion between solid and liquid than the cohesion of liquid, the negative interfacial tension and the acute contact angle. (C) 2009 Elsevier B.V. All rights reserved
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
No full textDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
Solutal Convection of Liquid Al-3.5 wt%Li during Its Upward Solidification
No full textThe onset of solutal convection during the directional solidification of Bridgman type of liquid Al-3.5 wt%Li is studied. Based on the analysis of a liquid-inhomogeneous-porous-double-layer system, a bimodal feature of neutral stability curve is found. The pulling rate is ascertained as the governing parameter for the mode transition, i.e., it determines whether the microstructure in the mushy layer is related to convection after the system destabilizes
Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals
No full textA dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-FcγRIIB receptor complex that activated β-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor κB. MUC2 induced additional conditioning signals in intestinal epithelial cells. Thus, mucus does not merely form a nonspecific physical barrier, but also constrains the immunogenicity of gut antigens by delivering tolerogenic signals10.1126/science.123791
5' and 3' region variability in th edopamine transporter gene (slc6a3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study.
No full textThe dopamine transporter gene (SLC6A3) is a candidate gene for Parkinson's disease (PD) on the basis of its critical role in dopaminergic neurotransmission. Previously, we identified 22 SNPs in the 5' region of SLC6A3, which segregate as eight haplotypes that differ in transcriptional activity when transfected in rat dopamine-producing cells. In the present work from a case-control study size of 293 cases and 395 controls, we employed a cladistic approach to examine gene-disease association. First, we found strong evidence of balancing selection in this region, as determined by a Tajima's D statistic of 2.97 (P < 0.001). Second, we found that the eight haplotypes fit into two main clades and that diplotypes of these clades were marginally associated with PD. Then, after we classified cases and controls by the number of risk alleles, accounting for the well-known 3' region VNTR polymorphism, we found that having two or more risk alleles resulted in a modest but significant increase in PD risk [odds ratio=1.58; 95% confidence interval (CI): 1.03-2.40]. Finally, we detected a significant interaction between occupational pesticide exposure in men and the number of risk alleles. Among pesticide-exposed subjects, the odds ratio for having two or more risk alleles was 5.66 (95% CI: 1.73-18.53). Thus, allelic variants in SLC6A3, which affect gene expression, are associated with PD in this population and may interact with occupational pesticide exposure to increase PD risk
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