TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD

© 2016 Thorburn et al. This 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. Background Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2-/- , TLR4-/- , TLR2/4-/- and MyD88-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the suppression of asthma by S. pneumoniae, and potentially other immunoregulatory therapies

Frequency and Distribution of Refractive Error in Adult Life: Methodology and Findings of the UK Biobank Study

PURPOSE: To report the methodology and findings of a large scale investigation of burden and distribution of refractive error, from a contemporary and ethnically diverse study of health and disease in adults, in the UK. METHODS: U K Biobank, a unique contemporary resource for the study of health and disease, recruited more than half a million people aged 40-69 years. A subsample of 107,452 subjects undertook an enhanced ophthalmic examination which provided autorefraction data (a measure of refractive error). Refractive error status was categorised using the mean spherical equivalent refraction measure. Information on socio-demographic factors (age, gender, ethnicity, educational qualifications and accommodation tenure) was reported at the time of recruitment by questionnaire and face-to-face interview. RESULTS: Fifty four percent of participants aged 40-69 years had refractive error. Specifically 27% had myopia (4% high myopia), which was more common amongst younger people, those of higher socio-economic status, higher educational attainment, or of White or Chinese ethnicity. The frequency of hypermetropia increased with age (7% at 40-44 years increasing to 46% at 65-69 years), was higher in women and its severity was associated with ethnicity (moderate or high hypermetropia at least 30% less likely in non-White ethnic groups compared to White). CONCLUSIONS: Refractive error is a significant public health issue for the UK and this study provides contemporary data on adults for planning services, health economic modelling and monitoring of secular trends. Further investigation of risk factors is necessary to inform strategies for prevention. There is scope to do this through the planned longitudinal extension of the UK Biobank study

The mitochondrial genome of Parascaris univalens - implications for a “forgotten” parasite

© Jabbar et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The file attached is the Published/publisher’s pdf version of the article

Analyses of Charophyte Chloroplast Genomes Help Characterize the Ancestral Chloroplast Genome of Land Plants

The file attached is the published version of the article. Revised LorP 22/5/2017©The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]

Crystal plasticity finite element simulation of lattice rotation and x-ray diffraction during laser shock compression of tantalum

We present a crystal plasticity model tailored for high-pressure, high-strain-rate conditions that uses a multiscale treatment of dislocation-based slip kinetics. We use this model to analyze the pronounced plasticity-induced lattice rotations observed in shock-compressed polycrystalline tantalum via in situ x-ray diffraction. By making direct comparisons between experimentally measured and simulated texture evolution, we can explain how the details of the underlying slip kinetics control the degree of lattice rotation that ensues. Specifically, we show that only the highly nonlinear kinetics caused by dislocation nucleation can explain the magnitude of the rotation observed under shock compression. We demonstrate a good fit between our crystal plasticity model and x-ray diffraction data and exploit the data to quantify the dislocation nucleation rates that are otherwise poorly constrained by experiment in the dynamic compression regime

Gold catalysed synthesis of 3-alkoxyfurans at room temperature

Synthetically important 3-alkoxyfurans can be prepared efficiently via treatment of acetal-containing propargylic alcohols (obtained from the addition of 3,3-diethoxypropyne to aldehydes) with 2 mol% gold catalyst in an alcohol solvent at room temperature. The resulting furans show useful reactivity in a variety of subsequent transformations

Development of anonymous nuclear markers from Illumina paired-end data for Seychelles caecilian amphibians (Gymnophiona: Indotyphlidae)

Anonymous nuclear markers were developed for Seychelles caecilian amphibians. Using a previously published bioinformatics pipeline (developed for Roche 454 data), 36 candidate anonymous nuclear loci (ANL) of at least 180 bp length were identified from Illumina MiSeq next generation sequencing data for five Seychelles species. We designed primer pairs for the 36 candidate ANL and tested these by PCR and Sanger sequencing. Seven ANL amplified and sequenced well for at least five of the six nominal Seychelles caecilian species (in three genera), and represent potentially useful markers for systematics and conservation. © 2014 Springer Science+Business Media Dordrecht