Identification of Candidate Genes for Dyslexia Susceptibility on Chromosome 18

Background: Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. Methodology/Principal Findings: Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L). Conclusions: Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.Publisher PDFPeer reviewe

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Par échantillonnage aléatoire, estimation de la densité spectrale énergetique d'une fonction aléatoire Gaussienne

Nous considérons un échantillonnage aléatoire d'une fonction aléatoire gaussienne à spectre borné. Nous trouvons que, dans certaines conditions, les estimations de la densité spectrale énergétique provenant de M échantillons aléatoires sont presque aussi bonnes que celles issues de N échantillons périodiques avec N > M. Donc en utilisant la méthode aléatoire nous obtenons un gain N/M par rapport à la méthode périodique, ce gain est d'autant plus grand que le nombre d'échantillons est important

Quarter-wavelength coupled dielectric plate resonators for high selectivity TE/sub 10/-mode filters

NRC publication: Ye

Using citizen science to improve the conservation of the European Eel (Anguilla anguilla) in the Thames River Basin District

The European eel (Anguilla anguilla) is Critically Endangered under the IUCN Red List Categories and Criteria because it has markedly declined in abundance across all life-history stages in much of its natural range. Barriers to migration, such as weirs and sluices, that prevent access to upstream habitat are a key threat to eels in freshwater systems. The impact of these barriers can be partially mitigated by the installation of eel passes that restore migratory pathways. In the Thames River Basin District (Thames RBD), The Zoological Society of London and partners have added traps to monitor eel passes. Further, these organizations have developed a network of citizen scientists and stakeholder organizations that monitor eel movement through the passes. In this paper, we review how data from the Thames European Eel Project enables a better understanding of eel ecology in the Thames RBD and how these data can inform conservation management decisions. In addition, we ask whether stakeholder engagement via citizen science has informed effective conservation action for this species