225 research outputs found
Suppression of allergic airway inflammation by helminth-induced regulatory T cells
Allergic diseases mediated by T helper type (Th) 2 cell immune responses are rising dramatically in most developed countries. Exaggerated Th2 cell reactivity could result, for example, from diminished exposure to Th1 cell–inducing microbial infections. Epidemiological studies, however, indicate that Th2 cell–stimulating helminth parasites may also counteract allergies, possibly by generating regulatory T cells which suppress both Th1 and Th2 arms of immunity. We therefore tested the ability of the Th2 cell–inducing gastrointestinal nematode Heligmosomoides polygyrus to influence experimentally induced airway allergy to ovalbumin and the house dust mite allergen Der p 1. Inflammatory cell infiltrates in the lung were suppressed in infected mice compared with uninfected controls. Suppression was reversed in mice treated with antibodies to CD25. Most notably, suppression was transferable with mesenteric lymph node cells (MLNC) from infected animals to uninfected sensitized mice, demonstrating that the effector phase was targeted. MLNC from infected animals contained elevated numbers of CD4(+)CD25(+)Foxp3(+) T cells, higher TGF-β expression, and produced strong interleukin (IL)-10 responses to parasite antigen. However, MLNC from IL-10–deficient animals transferred suppression to sensitized hosts, indicating that IL-10 is not the primary modulator of the allergic response. Suppression was associated with CD4(+) T cells from MLNC, with the CD4(+)CD25(+) marker defining the most active population. These data support the contention that helminth infections elicit a regulatory T cell population able to down-regulate allergen induced lung pathology in vivo
Special Issue Paper
An exploratory data analysis of the temperature fluctuations in a spreading fir
Motion, flash, and flicker:A unified spatiotemporal model of perceived edge sharpening
Blurred edges appear sharper in motion than when they are stationary. We proposed a model of this motion sharpening that invokes a local, nonlinear contrast transducer function (Hammett et al, 1998 Vision Research 38 2099-2108). Response saturation in the transducer compresses or 'clips' the input spatial waveform, rendering the edges as sharper. To explain the increasing distortion of drifting edges at higher speeds, the degree of nonlinearity must increase with speed or temporal frequency. A dynamic contrast gain control before the transducer can account for both the speed dependence and approximate contrast invariance of motion sharpening (Hammett et al, 2003 Vision Research, in press). We show here that this model also predicts perceived sharpening of briefly flashed and flickering edges, and we show that the model can account fairly well for experimental data from all three modes of presentation (motion, flash, and flicker). At moderate durations and lower temporal frequencies the gain control attenuates the input signal, thus protecting it from later compression by the transducer. The gain control is somewhat sluggish, and so it suffers both a slow onset, and loss of power at high temporal frequencies. Consequently, brief presentations and high temporal frequencies of drift and flicker are less protected from distortion, and show greater perceptual sharpening
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Analyzing the transmission of wildfire exposure on a fire-prone landscape in Oregon, USA
We develop the idea of risk transmission from large wildfires and apply network analyses to understand its importance on a 0.75 million ha US national forest. Wildfires in the western US frequently burn over long distances (e.g., 20-50 km) through highly fragmented landscapes with respect to ownership, fuels,
management intensity, population density, and ecological conditions. The collective arrangement of fuel
loadings in concert with weather and suppression efforts ultimately determines containment and the
resulting fire perimeter. While spatial interactions among land parcels in terms of fire spread and intensity
have been frequently noted by fire managers, quantifying risk and exposure transmission has not
been attempted. In this paper we used simulation modeling to quantify wildfire transmission and built
a transmission network consisting of land designations defined by national forest management designations
and ownership. We then examined how a forest-wide fuel management program might change the
transmission network and associated metrics. The results indicated that the size, shape, and fuel loading
of management designations affected their exposure to wildfire from other designations and ownerships.
Manipulating the fuel loadings via simulated forest fuel treatments reduced the wildfire transmitted
among the land designations, and changed the network density as well. We discuss how wildfire transmission
has implications for creating fire adapted communities, conserving biodiversity, and resolving
competing demands for fire-prone ecosystem services.Keywords: Wildfire risk, Forest fuel treatments, Risk network, Wildfire simulation, Network analysi
Quantitative Trait Loci Associated with Milling and Baking Quality in a Soft X Hard Wheat Cross
Interclass hybridization between soft and hard wheat (Triticum aestivum L.) results in new genetic combinations of potential value
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Wildfire exposure and fuel management on western US national forests
Substantial investments in fuel management activities on national forests in the western US are part of a national strategy to reduce human and ecological losses from catastrophic wildfire and create fire resilient landscapes. Prioritizing these investments within and among national forests remains a challenge, partly because a comprehensive assessment that establishes the current wildfire risk and exposure does not exist, making it difficult to identify national priorities and target specific areas for fuel management. To gain a broader understanding of wildfire exposure in the national forest system, we analyzed an array of simulated and empirical data on wildfire activity and fuel treatment investments on the 82 western US national forests. We first summarized recent fire data to examine variation among the Forests in ignition frequency and burned area in relation to investments in fuel reduction treatments. We then used simulation modeling to analyze fine-scale spatial variation in burn probability and intensity. We also estimated the probability of a mega-fire event on each of the Forests, and the transmission of fires ignited on national forests to the surrounding urban interface. The analysis showed a good correspondence between recent area burned and predictions from the simulation models. The modeling also illustrated the magnitude of the variation in both burn probability and intensity among and within Forests. Simulated burn probabilities in most instances were lower than historical, reflecting fire exclusion on many national forests. Simulated wildfire transmission from national forests to the urban interface was highly variable among the Forests. We discuss how the results of the study can be used to prioritize investments in hazardous fuel reduction within a comprehensive multi-scale risk management framework.Keywords: Risk assessment, Wildfire exposure, Wildfire risk, Burn probability, National fores
Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease
Background
Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes.
Methods
We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants.
Results
Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects.
Conclusions
Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application
Relationship between bacterial strain type, host biomarkers, and mortality in clostridium difficile infection
Background: Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases. Methods: From September 2006 to May 2011, strains isolated from Clostridium difficile toxin enzyme immunoassay (EIA)-positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive C. difficile infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors. Results: Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%-9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P <. 0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted P =. 05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 109 neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 109 neutrophils/L in EIA-negative controls (P <. 0001) and 7.9 × 109 neutrophils/L in ST 44 (P =. 08). There were strong associations between C. difficile-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho =-0.45), and serum albumin (rho =-0.47). Biomarkers predicted 30%-40% of clade-specific mortality differences. Conclusions: C. difficile genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential
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Early retreat of the Alaska Peninsula Glacier Complex and the implications for coastal migrations of First Americans
The debate over a coastal migration route for the First Americans revolves around two major points: seafaring technology, and a viable landscape and resource base. Three lake cores from Sanak Island in the western Gulf of Alaska yield the first radiocarbon ages from the continental shelf of the Northeast Pacific and record deglaciation nearly 17 ka BP (thousands of calendar years ago), much earlier than previous estimates based on extrapolated data from other sites outside the coastal corridor in the Gulf of Alaska. Pollen data suggest an arid, terrestrial ecosystem by 16.3 ka BP. Therefore glaciers would not have hindered the movement of humans along the southern edge of the Bering Land Bridge for two millennia before the first well-recognized “New World” archaeological sites were inhabited.Keywords: First Americans, Deglaciation, Coastal migratio
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