1,888 research outputs found
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IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction.
Emerging evidence suggests that the T helper 17 (T(H)17) subset of αβ T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the αvβ8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin αvβ8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle
Anomalous metamagnetism in the low carrier density Kondo lattice YbRh3Si7
We report complex metamagnetic transitions in single crystals of the new low
carrier Kondo antiferromagnet YbRh3Si7. Electrical transport, magnetization,
and specific heat measurements reveal antiferromagnetic order at T_N = 7.5 K.
Neutron diffraction measurements show that the magnetic ground state of
YbRh3Si7 is a collinear antiferromagnet where the moments are aligned in the ab
plane. With such an ordered state, no metamagnetic transitions are expected
when a magnetic field is applied along the c axis. It is therefore surprising
that high field magnetization, torque, and resistivity measurements with H||c
reveal two metamagnetic transitions at mu_0H_1 = 6.7 T and mu_0H_2 = 21 T. When
the field is tilted away from the c axis, towards the ab plane, both
metamagnetic transitions are shifted to higher fields. The first metamagnetic
transition leads to an abrupt increase in the electrical resistivity, while the
second transition is accompanied by a dramatic reduction in the electrical
resistivity. Thus, the magnetic and electronic degrees of freedom in YbRh3Si7
are strongly coupled. We discuss the origin of the anomalous metamagnetism and
conclude that it is related to competition between crystal electric field
anisotropy and anisotropic exchange interactions.Comment: 23 pages and 4 figures in the main text. 7 pages and 5 figures in the
supplementary materia
The Human Microbiome Project: A Community Resource for the Healthy Human Microbiome
The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. Microbial ecologists, realizing that >99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ [5], primarily by sequencing the 16S ribosomal RNA gene (16S) as a phylogenetic and taxonomic marker to identify members of microbial communities [6]. The need to develop corresponding new methods for culture-independent studies [7],[8] in turn precipitated a sea change in the study of microbes and human health, inspiring the new term “metagenomics" [9] both to describe a technological approach—sequencing and analysis of the genes from whole communities rather than from individual genomes—and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions [10] culminated in a National Academy of Science report [11], which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.National Institutes of Health (U.S.) (grant U54HG004969)National Institutes of Health (U.S.) (grant U54HG004973)National Institutes of Health (U.S.) (grant U54AI084844)National Institutes of Health (U.S.) (grant U01HG004866)National Institutes of Health (U.S.) (grant R01HG005969)National Institutes of Health (U.S.) (grant R01HG004872)United States. Army Research Office (grant W911NF-11-1-0473)National Science Foundation (U.S.) (NSF DBI-1053486)Howard Hughes Medical Institute (Early Career Scientist
Ferromagnetic ordering along the hard axis in the Kondo lattice YbIr3Ge7
Ferromagnetic Kondo lattice compounds are far less common than their
antiferromagnetic analogs. In this work, we report the discovery of a new
ferromagnetic Kondo lattice compound, YbIr3Ge7. Like almost all ferromagnetic
Kondo lattice systems, YbIr3Ge7 shows magnetic order with moments aligned
orthogonal to the crystal electric field (CEF) easy axis. YbIr3Ge7 is unique in
that it is the only member of this class of compounds that crystallizes in a
rhombohedral structure with a trigonal point symmetry of the magnetic site, and
it lacks broken inversion symmetry at the local moment site. AC magnetic
susceptibility, magnetization, and specific heat measurements show that
YbIr3Ge7 has a Kondo temperature TK = 14 K and a Curie temperature TC = 2.4 K.
Ferromagnetic order occurs along the crystallographic [100] hard CEF axis
despite the large CEF anisotropy of the ground state Kramers doublet with a
saturation moment along [001] almost four times larger than the one along
[100]. This implies that a mechanism which considers the anisotropy in the
exchange interaction to explain the hard axis ordering is unlikely. On the
other hand, the broad second-order phase transition at TC favors a
fluctuation-induced mechanism
CeIrGe: a local moment antiferromagnetic metal with extremely low ordering temperature
CeIrGe is an antiferromagnetic metal with a remarkably low ordering
temperature = 0.63 K, while most Ce-based magnets order between 2
and 15 K. Thermodynamic and transport properties as a function of magnetic
field or pressure do not show signatures of Kondo correlations, interaction
competition, or frustration, as had been observed in a few antiferromagnets
with comparably low or lower . The averaged Weiss temperature
measured below 10 K is comparable to suggesting that the RKKY
exchange coupling is very weak in this material. The unusually low
in CeIrGe can therefore be attributed to the large Ce-Ce bond length of
about 5.7 {\AA}, which is about 1.5 {\AA} larger than in the most Ce-based
intermetallic systems.Comment: 4 figure
Prediction of Emerging Technologies Based on Analysis of the U.S. Patent Citation Network
The network of patents connected by citations is an evolving graph, which
provides a representation of the innovation process. A patent citing another
implies that the cited patent reflects a piece of previously existing knowledge
that the citing patent builds upon. A methodology presented here (i) identifies
actual clusters of patents: i.e. technological branches, and (ii) gives
predictions about the temporal changes of the structure of the clusters. A
predictor, called the {citation vector}, is defined for characterizing
technological development to show how a patent cited by other patents belongs
to various industrial fields. The clustering technique adopted is able to
detect the new emerging recombinations, and predicts emerging new technology
clusters. The predictive ability of our new method is illustrated on the
example of USPTO subcategory 11, Agriculture, Food, Textiles. A cluster of
patents is determined based on citation data up to 1991, which shows
significant overlap of the class 442 formed at the beginning of 1997. These new
tools of predictive analytics could support policy decision making processes in
science and technology, and help formulate recommendations for action
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Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions
A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions
Does Chlorhexidine Bathing in Adult Intensive Care Units Reduce Blood Culture Contamination? A Pragmatic Cluster-Randomized Trial
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