427 research outputs found
Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model
Background
Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation.
Methods
Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells.
Results
Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals.
Conclusions
Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.n
Hydrodynamic Description of Granular Convection
We present a hydrodynamic model that captures the essence of granular
dynamics in a vibrating bed. We carry out the linear stability analysis and
uncover the instability mechanism that leads to the appearance of the
convective rolls via a supercritical bifurcation of a bouncing solution. We
also explicitly determine the onset of convection as a function of control
parameters and confirm our picture by numerical simulations of the continuum
equations.Comment: 14 pages, RevTex 11pages + 3 pages figures (Type csh
Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10
Type I interferon (IFN) α/β is critical for host defense. During endotoxicosis or highly lethal bacterial infections where systemic inflammation predominates, mice deficient in IFN-α/β receptor (IFNAR) display decreased systemic inflammation and improved outcome. However, human sepsis mortality often occurs during a prolonged period of immunosuppression and not from exaggerated inflammation. We used a low lethality cecal ligation and puncture (CLP) model of sepsis to determine the role of type I IFNs in host defense during sepsis. Despite increased endotoxin resistance, IFNAR−/− and chimeric mice lacking IFNAR in hematopoietic cells display increased mortality to CLP. This was not associated with an altered early systemic inflammatory response, except for decreased CXCL10 production. IFNAR−/− mice display persistently elevated peritoneal bacterial counts compared with wild-type mice, reduced peritoneal neutrophil recruitment, and recruitment of neutrophils with poor phagocytic function despite normal to enhanced adaptive immune function during sepsis. Importantly, CXCL10 treatment of IFNAR−/− mice improves survival and decreases peritoneal bacterial loads, and CXCL10 increases mouse and human neutrophil phagocytosis. Using a low lethality sepsis model, we identify a critical role of type I IFN–dependent CXCL10 in host defense during polymicrobial sepsis by increasing neutrophil recruitment and function
Application of Quadratic Constitutive Relation to One- Equation k-kL Turbulence Model
This paper analyzes the accuracy of the recently developed one-equation k-kL turbulence model with Quadratic Constitutive Relation (QCR) compared to the linear Boussinesq relation and Algebraic Reynolds Stress Model (ARSM). The computational results in several benchmark cases from NASA TMR are compared to other widely used one equation turbulence models with QCR, such as Spalart-Allmaras model (SA), Wray-Agarwal model (WA) and SST k-ω model. In particular, one-equation k-kL-QCR model shows good accuracy with experimental data for supersonic flow in a square duct where the effect of QCR is clearly visible in capturing the secondary flow vortices which is not feasible with the any standard model without QCR. In addition, both one-equation k-kL and one-equation k- kL-QCR models show better accuracy for subsonic separated flow in 3D NASA Glenn S- duct compared to other one-equation models. Other test cases show little difference in the results obtained without and with QCR
Characterization of the S = 9 excited state in Fe8Br8 by Electron Paramagnetic Resonance
High Frequency electron paramagnetic resonance has been used to observe the
magnetic dipole, M = 1, transitions in the excited
state of the single molecule magnet FeBr. A Boltzmann analysis of the
measured intensities locates it at 24 2 K above the ground
state, while the line positions yield its magnetic parameters D = -0.27 K, E =
0.05 K, and B = -1.3 10 K. D is thus smaller by 8%
and E larger by 7% than for . The anisotropy barrier for is
estimated as 22 K,which is 25% smaller than that for (29 K). These
data also help assign the spin exchange constants(J's) and thus provide a basis
for improved electronic structure calculations of FeBr.Comment: 7 pages, Figs included in text, submitted to PR
Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor
As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR)
exerts an important role in immune regulation besides its requirement for
xenobiotic metabolism. Transcriptional activation of AhR target genes is
counterregulated by the AhR repressor (AhRR) but the exact function of the
AhRR in vivo is currently unknown. We here show that the AhRR is predominantly
expressed in immune cells of the skin and intestine, different from other AhR
target genes. Whereas AhRR antagonizes the anti-inflammatory function of the
AhR in the context of systemic endotoxin shock, AhR and AhRR act in concert to
dampen intestinal inflammation. Specifically, AhRR contributes to the
maintenance of colonic intraepithelial lymphocytes and prevents excessive IL-
1β production and Th17/Tc17 differentiation. In contrast, the AhRR enhances
IFN-γ-production by effector T cells in the inflamed gut. Our findings
highlight the physiologic importance of cell-type specific balancing of
AhR/AhRR expression in response to microbial, nutritional and other
environmental stimuli
Unconstraining the Unhiggs
We investigate whether or not perturbative unitarity is preserved in the
Unhiggs model for the scattering process of heavy quarks and longitudinal gauge
bosons . With the Yukawa coupling given in the
original formulation of the Unhiggs model, the model preserves unitarity for
Unhiggs scaling dimensions . We examine the LHC phenomenology that
is implied by the Unhiggs model in this parameter range in detail and discuss
to what extent the LHC can test if an excess is measured in the
phenomenologically clean channel in the future or if the LHC measurement
remains consistent with the background. We then make use of the AdS/CFT
correspondence to derive a new Yukawa coupling that is conformally invariant at
high energies, and show that with this Yukawa coupling the theory is unitary
for .Comment: 19 pages, 10 figures; typos corrected, version published by PR
Semiconductive and Photoconductive Properties of the Single Molecule Magnets Mn-Acetate and FeBr
Resistivity measurements are reported for single crystals of
Mn-Acetate and FeBr. Both materials exhibit a
semiconductor-like, thermally activated behavior over the 200-300 K range. The
activation energy, , obtained for Mn-Acetate was 0.37 0.05
eV, which is to be contrasted with the value of 0.55 eV deduced from the
earlier reported absorption edge measurements and the range of 0.3-1 eV from
intramolecular density of states calculations, assuming = , the
optical band gap. For FeBr, was measured as 0.73 0.1 eV,
and is discussed in light of the available approximate band structure
calculations. Some plausible pathways are indicated based on the crystal
structures of both lattices. For Mn-Acetate, we also measured
photoconductivity in the visible range; the conductivity increased by a factor
of about eight on increasing the photon energy from 632.8 nm (red) to 488 nm
(blue). X-ray irradiation increased the resistivity, but was insensitive
to exposure.Comment: 7 pages, 8 figure
DEAF1 is a Pellino1-interacting protein required for interferon production by Sendai virus and double-stranded RNA
Double-stranded (ds) RNA of viral origin, a ligand for Melanoma Differentiation-associated gene 5 (MDA5) and Toll-Like Receptor 3 (TLR3), induces the TANK-Binding Kinase 1 (TBK1)-dependent phosphorylation and activation of Interferon Regulatory Factor 3 (IRF3) and the E3 ubiquitin ligase Pellino1, which are required for interferon β (IFNβ) gene transcription. Here, we report that Pellino1 interacts with the transcription factor Deformed Epidermal Autoregulatory Factor 1 (DEAF1). The interaction is independent of the E3 ligase activity of Pellino1, but weakened by the phosphorylation of Pellino1. We show that DEAF1 binds to the IFNβ promoter and to IRF3 and IRF7, that it is required for the transcription of the IFNβ gene and IFNβ secretion in MEFs infected with Sendai virus or transfected with poly(I:C). DEAF1 is also needed for TLR3-dependent IFNβ production. Taken together, our results identify DEAF1 as a novel component of the signal transduction network by which dsRNA of viral origin stimulates IFNβ production
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