4,761 research outputs found
IFN-gamma is associated with risk of Schistosoma japonicum infection in China.
Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-gamma production were associated with reduced risk of infection
An Efficient Data Structure for Dynamic Two-Dimensional Reconfiguration
In the presence of dynamic insertions and deletions into a partially
reconfigurable FPGA, fragmentation is unavoidable. This poses the challenge of
developing efficient approaches to dynamic defragmentation and reallocation.
One key aspect is to develop efficient algorithms and data structures that
exploit the two-dimensional geometry of a chip, instead of just one. We propose
a new method for this task, based on the fractal structure of a quadtree, which
allows dynamic segmentation of the chip area, along with dynamically adjusting
the necessary communication infrastructure. We describe a number of algorithmic
aspects, and present different solutions. We also provide a number of basic
simulations that indicate that the theoretical worst-case bound may be
pessimistic.Comment: 11 pages, 12 figures; full version of extended abstract that appeared
in ARCS 201
Phenotypic and functional modulation of porcine monocyte-derived dendritic cells for foot-and-mouth disease virus
Dendritic cells (DCs) play an important role in inducing primary antigen-specific immune responses to viral antigens. In this study, the peripheral blood monocyte-derived (PBMC) were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. After 6 days of culture, immature monocyte-derived dendritic cells (Mo-DCs) were generated. The addition of lipopolysaccharide (LPS) during differentiation of Mo-DCs enhanced their ability to stimulate allogeneic mixed lymphocyte reaction (MLR) and alter their ability to produce cytokines. Then, we investigated the interaction between foot-and-mouth disease virus (FMDV) and porcine Mo-DCs in vitro and confirmed that the immunological phenotype and function of porcine Mo-DCs were modulated during FMDV infection. A down-regulated expression of MHC II and CD1 were observed at 48 h post FMDV infection. In addition, the infected porcine Mo-DCs exhibited ultrastructural morphological changes, FMDV-infected porcine Mo-DCs failed to stimulate T cell proliferation in vitro. Moreover, infection of porcine Mo-DCs in vitro induced the secretion of IFN-γ and the suppressive cytokine IL-10 in porcine Mo-DCs. Results indicated that the down-regulation of MHC II and CD1 molecules and the increased secretion of the IFN-γ and IL-10 cytokines might be the mechanisms that FMDV uses to evade the host immune responses.Key words: Dendritic cells, foot-and-mouth disease virus, MHC II, modulation, cytokines
Learning and Matching Multi-View Descriptors for Registration of Point Clouds
Critical to the registration of point clouds is the establishment of a set of
accurate correspondences between points in 3D space. The correspondence problem
is generally addressed by the design of discriminative 3D local descriptors on
the one hand, and the development of robust matching strategies on the other
hand. In this work, we first propose a multi-view local descriptor, which is
learned from the images of multiple views, for the description of 3D keypoints.
Then, we develop a robust matching approach, aiming at rejecting outlier
matches based on the efficient inference via belief propagation on the defined
graphical model. We have demonstrated the boost of our approaches to
registration on the public scanning and multi-view stereo datasets. The
superior performance has been verified by the intensive comparisons against a
variety of descriptors and matching methods
Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65.
Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis
MemBrain: Improving the Accuracy of Predicting Transmembrane Helices
Prediction of transmembrane helices (TMH) in α helical membrane proteins provides valuable information about the protein topology when the high resolution structures are not available. Many predictors have been developed based on either amino acid hydrophobicity scale or pure statistical approaches. While these predictors perform reasonably well in identifying the number of TMHs in a protein, they are generally inaccurate in predicting the ends of TMHs, or TMHs of unusual length. To improve the accuracy of TMH detection, we developed a machine-learning based predictor, MemBrain, which integrates a number of modern bioinformatics approaches including sequence representation by multiple sequence alignment matrix, the optimized evidence-theoretic K-nearest neighbor prediction algorithm, fusion of multiple prediction window sizes, and classification by dynamic threshold. MemBrain demonstrates an overall improvement of about 20% in prediction accuracy, particularly, in predicting the ends of TMHs and TMHs that are shorter than 15 residues. It also has the capability to detect N-terminal signal peptides. The MemBrain predictor is a useful sequence-based analysis tool for functional and structural characterization of helical membrane proteins; it is freely available at http://chou.med.harvard.edu/bioinf/MemBrain/
R-process enrichment from a single event in an ancient dwarf galaxy
Elements heavier than zinc are synthesized through the (r)apid and (s)low
neutron-capture processes. The main site of production of the r-process
elements (such as europium) has been debated for nearly 60 years. Initial
studies of chemical abundance trends in old Milky Way halo stars suggested
continual r-process production, in sites like core-collapse supernovae. But
evidence from the local Universe favors r-process production mainly during rare
events, such as neutron star mergers. The appearance of a europium abundance
plateau in some dwarf spheroidal galaxies has been suggested as evidence for
rare r-process enrichment in the early Universe, but only under the assumption
of no gas accretion into the dwarf galaxies. Cosmologically motivated gas
accretion favors continual r-process enrichment in these systems. Furthermore,
the universal r-process pattern has not been cleanly identified in dwarf
spheroidals. The smaller, chemically simpler, and more ancient ultra-faint
dwarf galaxies assembled shortly after the first stars formed, and are ideal
systems with which to study nucleosynthesis events such as the r-process.
Reticulum II is one such galaxy. The abundances of non-neutron-capture elements
in this galaxy (and others like it) are similar to those of other old stars.
Here, we report that seven of nine stars in Reticulum II observed with
high-resolution spectroscopy show strong enhancements in heavy neutron-capture
elements, with abundances that follow the universal r-process pattern above
barium. The enhancement in this "r-process galaxy" is 2-3 orders of magnitude
higher than that detected in any other ultra-faint dwarf galaxy. This implies
that a single rare event produced the r-process material in Reticulum II. The
r-process yield and event rate are incompatible with ordinary core-collapse
supernovae, but consistent with other possible sites, such as neutron star
mergers.Comment: Published in Nature, 21 Mar 2016:
http://dx.doi.org/10.1038/nature1742
Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity
The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions
Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.
PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils
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