400 research outputs found

    Spatial contrast sensitivity in adolescents with autism spectrum disorders

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    Adolescents with autism spectrum disorders (ASD) and typically developing (TD) controls underwent a rigorous psychophysical assessment that measured contrast sensitivity to seven spatial frequencies (0.5-20 cycles/degree). A contrast sensitivity function (CSF) was then fitted for each participant, from which four measures were obtained: visual acuity, peak spatial frequency, peak contrast sensitivity, and contrast sensitivity at a low spatial frequency. There were no group differences on any of the four CSF measures, indicating no differential spatial frequency processing in ASD. Although it has been suggested that detail-oriented visual perception in individuals with ASD may be a result of differential sensitivities to low versus high spatial frequencies, the current study finds no evidence to support this hypothesis

    Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

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    A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

    The politics of protest in newspaper campaigns: dissent, populism and the rhetoric of authenticity

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    Newspaper campaigns embody newspaper’ most emphatic claims to speak for ‘the people’, and as such are generally regarded as populist. However, they can be oppositional, engaging in dissent of one sort or another, and often assume a certain amount of political engagement with that dissent on the part of the audience. This article examines the potential of newspaper camapigns to facilitate the political engagement of citizens through the politics of protest. It draws on qualitative analysis of seven campaigns that ran in the Scottish press between 2000 and 2005, and semi-structured interviews with relevant journalists. The distinction between legitimate protest and manipulative populism is made in terms of: (a) the rhetoric and strategies of political representation, participation and influence and (b) the construction of political legitimacy in terms of the public interest and the moral authority of the ‘victim’. It is argued that populist impulses dominate, driving a tendency to use discourses of emotional authenticity and offence to legitimise demands for a plebiscitary response to popular of ‘victim’ preference and to close down controversy and debate, with the principal objective marketing the newspaper as an influential community champion

    Contribution of CTCF binding to transcriptional activity at the HOXA locus in NPM1-mutant AML cells

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    Transcriptional regulation of the HOXA genes is thought to involve CTCF-mediated chromatin loops and the opposing actions of the COMPASS and Polycomb epigenetic complexes. We investigated the role of these mechanisms at the HOXA cluster in AML cells with the common NPM1c mutation, which express both HOXA and HOXB genes. CTCF binding at the HOXA locus is conserved across primary AML samples, regardless of HOXA gene expression, and defines a continuous chromatin domain marked by COMPASS-associated histone H3 trimethylation in NPM1-mutant primary AML samples. Profiling of the three-dimensional chromatin architecture in primary AML samples with the NPM1c mutation identified chromatin loops between the HOXA cluster and loci in the SNX10 and SKAP2 genes, and an intergenic region located 1.4 Mbp upstream of the HOXA locus. Deletion of CTCF binding sites in the NPM1-mutant OCI-AML3 AML cell line reduced multiple long-range interactions, but resulted in CTCF-independent loops with sequences in SKAP2 that were marked by enhancer-associated histone modifications in primary AML samples. HOXA gene expression was maintained in CTCF binding site mutants, indicating that transcriptional activity at the HOXA locus in NPM1-mutant AML cells may be sustained through persistent interactions with SKAP2 enhancers, or by intrinsic factors within the HOXA gene cluster

    Contribution of Alaskan glaciers to sea level rise derived from satellite imagery

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    International audienceOver the last 50 years, retreating glaciers and ice caps (GIC) contributed 0.5 mm/yr to sea level rises (SLR), and one third is believed to originate from ice masses bordering the Gulf of Alaska. However, these estimates of ice wastage in Alaska are based on methods that measure a limited number of glaciers and extrapolate the results to estimate ice loss for the many thousands of others. How these methods capture the complex pattern of decadal elevation changes at the scale of individual glacier and mountain range is unclear. Here, combining a comprehensive glacier inventory with elevation changes derived from sequential digital elevation models (DEMs), we found that, between 1962 and 2006, Alaskan glaciers lost 41.9 ± 8.6 km**3/yr water equivalent (w.e.) and contributed 0.12±0.02 mm/yr to SLR. Our ice loss is 34% lower than previous estimates. Reasons for our lower values include the higher spatial resolution of our glacier inventory and the reduction of ice thinning under debris and at the glacier margins which were not resolved in earlier work. Estimates of mass loss from GIC in other mountain regions could be subject to similar revisions

    Resveratrol: A Multifunctional Compound Improving Endothelial Function: Editorial to: “Resveratrol Supplementation Gender Independently Improves Endothelial Reactivity and Suppresses Superoxide Production in Healthy Rats” by S. Soylemez et al.

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    The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression and activity of NADPH oxidases, resveratrol inhibits superoxide-mediated NO inactivation. Some resveratrol effects are mediated by sirtuin 1 (SIRT1) or estrogen receptors, respectively

    Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus

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    Background: Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings: We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical o, functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusion/Significance: Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway, Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods. © 2008 Couveur et al.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe
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