Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. © 2013 Brandler et al.

Uncertainty and the influence of group norms in the attitude-behaviour relationship

Two studies were conducted to examine the impact of subjective uncertainty on conformity to group norms in the attitude-behaviour context. In both studies, subjective uncertainty was manipulated using a deliberative mindset manipulation (McGregor, Zanna, Holmes, & Spencer, 2001). In Study 1 (N = 106), participants were exposed to either an attitude-congruent or an attitude-incongruent in-group norm. In Study 2(N = 83), participants were exposed to either a congruent, incongruent, or an ambiguous in-group norm. Ranges of attitude-behaviour outcomes, including attitude-intention consistency and change in attitude-certainty, were assessed. In both studies, levels of group-normative behaviour varied as a function of uncertainty condition. In Study 1, conformity to group norms, as evidenced by variations in the level of attitude-intention consistency, was observed only in the high uncertainty condition. In Study 2, exposure to an ambiguous norm had different effects for those in the low and die high uncertainty conditions. In the low uncertainty condition, greatest conformity was observed in the attitude-congruent norm condition compared with an attitude-congruent or ambiguous norm. In contrast, individuals in the high uncertainty condition displayed greatest conformity when exposed to either an attitude-congruent or an ambiguous in-group norm. The implications of these results for the role of subjective uncertainty in social influence processes are discussed. © 2007 The British Psychological Society.

Majority versus minority influence and prediction of behavioral intentions and behavior

Two experiments examined the effects of majority and minority influence on attitude-consistent behavioral intentions. In the first experiment, when attitudes were changed via minority influence there was a greater likelihood to engage in an attitude-consistent behavioral intention than when attitudes were changed via majority influence. This suggests that minority influence leads to stronger attitudes (based on systematic processing) that are more predictive of behavioral intentions, while attitude change via majority influence is due to compliance through non-systematic processing. Further support for this interpretation comes from the finding that the amount of message-congruent elaboration mediated behavioral intention. When there was no attitude change, there was no impact on behavioral intention to engage in an attitude-consistent behavior. Experiment 2 explored the role of personal relevance of the topic and also included a real behavioral measure. When the topic was of low personal relevance, the same pattern was found as Experiment 1. When the topic was of high personal relevance, thus increasing the motivation to engage in systematic processing, attitudes changed by both a majority and minority source increased behavioral intention and actual behavior. The results are consistent with the view that both majorities and minorities can lead to different processes and consequences under different situations. © 2006 Elsevier Inc. All rights reserved.

Matrix-free mass spectrometric imaging using laser desorption ionisation Fourier transform ion cyclotron resonance mass spectrometry

Mass spectrometry imaging (MSI) is a powerful tool in metabolomics and proteomics for the spatial localization and identification of pharmaceuticals, metabolites, lipids, peptides and proteins in biological tissues. However, sample preparation remains a crucial variable in obtaining the most accurate distributions. Common washing steps used to remove salts, and solvent-based matrix application, allow analyte spreading to occur. Solvent-free matrix applications can reduce this risk, but increase the possibility of ionisation bias due to matrix adhesion to tissue sections. We report here the use of matrix-free MSI using laser desorption ionisation performed on a 12 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. We used unprocessed tissue with no post-processing following thaw-mounting on matrix-assisted laser desorption ionisation (MALDI) indium-tin oxide (ITO) target plates. The identification and distribution of a range of phospholipids in mouse brain and kidney sections are presented and compared with previously published MALDI time-of-flight (TOF) MSI distributions.

Cataract, macular characteristics and assessing lens opacities

Age-related macular degeneration and cataract are very common causes of visual impairment in the elderly. Macular pigment optical density is known to be a factor affecting the risk of developing age-related macular degeneration but its behaviour due to light exposure to the retina and the effect of macular physiology on this measurement are not fully understood. Cataract is difficult to grade in a way which reflects accurately the visual status of the patient. A new technology, optical coherence tomography, which allows a cross sectional slice of the crystalline lens to be imaged has the potential to be able to provide objective measurements of cataract which could be used for grading purposes. This thesis set out to investigate the effect of cataract removal on macular pigment optical density, the relationship between macular pigment optical density and macular thickness and the relationship between cortical cataract density as measured by optical coherence tomography and other measures of cataract severity. These investigations found: 1) Macular pigment optical density in a pseudophakic eye is reduced when compared to a fellow eye with age related cataract, probably due to differences in light exposure between the eyes. 2) Lower macular pigment optical density is correlated with thinning of the entire macular area, but not with thinning of the fovea or central macula. 3) Central macular thickness decreases with age. 4) Spectral domain optical coherence tomography can be used to successfully acquire images of the anterior lens cortex which relate well to slit lamp lens sections. 5) Grading of cortical cataract with spectral domain optical coherence tomography instruments using a wavelength of 840nm is not well correlated with other established metrics of cataract severity and is therefore not useful as presented as a grading method for this type of cataract.