132 research outputs found

    Variation in the responses of wild species of duck, gull, and wader to inoculation with a wild-bird-origin H6N2 low pathogenicity avian influenza virus

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    There is poor understanding of host responses to avian influenza virus (AIV) infection in wild birds, with most experimental studies using captive-bred birds and highly pathogenic AIVs that have an early endpoint. The objective of this study was to experimentally assess antibody responses and patterns of viral excretion in wild birds challenged with a low pathogenicity AIV. Ruddy turnstones (Arenaria interpres), silver gulls (Chroicocephalus novaehollandiae), and wandering whistling ducks (Dendrocygna arcuata) were challenged with a H6N2 virus, and blood, cloacal, and oropharyngeal (OP) swabs were analyzed from each bird over 28 days, with serology conducted on the ducks for a further 7 mo. Nineteen of 22 birds showed evidence of infection, with respiratory infection prevalent in the turnstones and gulls as mostly low titer viral excretion to 4 days postinoculation (DPI) with gastrointestinal replication detected in only one turnstone. In AIV naive ducks, there was gastrointestinal tropism with moderately high titer viral excretion via the cloaca to 6 DPI and low-grade OP viral excretion to 4 DPI. The hemagglutination inhibition antibody response was poor in the ducks, declining from 19 to 56 DPI, with higher titer responses in the gulls and turnstones. All infected birds responded with elevated nucleoprotein antibodies (in competitive enzyme-linked immunosorbent assay) by 7-10 DPI, and in the ducks these waned slowly after 42 DPI and were long-lived to at least 8 mo. The interspecies variability in response was consistent with a subtype that had adapted well in ducks, while the response of the turnstones may have been influenced by preexisting immunity to AIV. These findings provide insight into AIV infection dynamics in wild birds and highlight the need for further research

    Utilizing image texture to detect land-cover change in Mediterranean coastal wetlands

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    Land-use/cover change dynamics were investigated in a Mediterranean coastal wetland. Change Vector Analysis (CVA) without and with image texture derived from the co-occurrence matrix and variogram were evaluated for detecting land-use/cover change. Three Landsat Thematic Mapper (TM) scenes recorded on July 1985, 1993 and 2005 were used, minimizing change detection error caused by seasonal differences. Images were geometrically, atmospherically and radiometrically corrected. CVA without and with texture measures were implemented and assessed using reference images generated by object-based supervised classification. These outputs were used for cross-classification to determine the ‘from–to’ change used to compare between techniques. The Landsat TM image bands together with the variogram yielded the most accurate change detection results, with Kappa statistics of 0.7619 and 0.7637 for the 1985–1993 and 1993–2005 image pairs, respectively

    The genetic architecture of the human cerebral cortex

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    INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

    On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

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    A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

    Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

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    We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

    Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees

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    A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants

    Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

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    Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction
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