Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Psicología deportiva. desarrollo – objeto – ubicación – tareas – resultados de investigación

La Psicología Deportiva es presentada como ciencia independiente, pero aún muy joven. Psicología Deportiva es de comprenderse no sólo como una forma de la Psicología aplicada (Psicología en el deporte), sino también como Psicología del Deporte, que ha desarrollado su propia teoría y métodos específicos deportivos. Su objeto de investigación son las acciones deportivas, las que son analizadas en su estructura básica.Adicionalmente se presenta en sus múltiples interrelaciones, hacia la Psicología (como ciencia madre), hacia otras Ciencias del Deporte (como ciencias paralelas) y hacia la Práctica Deportiva (como campo deaplicación).Sus tareas más importantes se dejan resumir en tareas de la investigación, aplicación y transmisión de conocimientos. Finalizando se da una corta visión sobre algunos resultados de investigación entre otros del ámbito de la investigación de la motivación y personalidad, de la investigación del stress y entrenamiento y de la sensomotricidad

Prion protein M129V polymorphism affects retrieval-related brain activity

The prion protein Met129Val polymorphism has recently been related to human long-term memory with carriers of either the 129MM or the 129MV genotype recalling 17% more words than 129VV carriers at 24 h following learning. Here, we sampled genotype differences in retrieval-related brain activity at 30 min and 24 h following learning. Furthermore, genotype groups were compared regarding grey matter concentrations and cognitive profiles. We used event-related functional magnetic resonance imaging (fMRI) during a word recognition task on 12 Met/Met carriers, 12 Val/Met carriers, and 12 Val/Val carriers. These groups were matched for retrieval performance, gender, age, education, and other memory-related genetic polymorphisms. Although retrieval performance was matched, Val carriers exhibited enhanced retrieval-related brain activity at 30 min and 24 h following learning. At both time lags, correlations between retrieval-related brain activity and retrieval success were negative for Val homozygotes (the more activity, the worse retrieval success), while correlations showed no significance or were positive for Met homozygotes and heterozygotes. These results suggest a less economic use of retrieval-related neural resources in Val relative to Met carriers. Furthermore, Val carriers exhibited higher neocortical grey matter concentrations compared to Met carriers. When controlling for grey matter concentration, genotype effects in retrieval-related brain activity remained significant. Val and Met carriers yielded comparable brain activations for correct rejections of non-studied words and for working memory, which speaks to the specificity of the genotype effect. Findings suggest that the prion protein Met129Val polymorphism affects neural plasticity following learning at a time-scale of minutes to hours

Longitudinal assessment of amyloid pathology in transgenic ArcAβ mice using multi-parametric magnetic resonance imaging

Magnetic resonance imaging (MRI) can be used to monitor pathological changes in Alzheimer's disease (AD). The objective of this longitudinal study was to assess the effects of progressive amyloid-related pathology on multiple MRI parameters in transgenic arcAβ mice, a mouse model of cerebral amyloidosis. Diffusion-weighted imaging (DWI), T1-mapping and quantitative susceptibility mapping (QSM), a novel MRI based technique, were applied to monitor structural alterations and changes in tissue composition imposed by the pathology over time. Vascular function and integrity was studied by assessing blood-brain barrier integrity with dynamic contrast-enhanced MRI and cerebral microbleed (CMB) load with susceptibility weighted imaging and QSM. A linear mixed effects model was built for each MRI parameter to incorporate effects within and between groups (i.e. genotype) and to account for changes unrelated to the disease pathology. Linear mixed effects modelling revealed a strong association of all investigated MRI parameters with age. DWI and QSM in addition revealed differences between arcAβ and wt mice over time. CMBs became apparent in arcAβ mice with 9 month of age; and the CMB load reflected disease stage. This study demonstrates the benefits of linear mixed effects modelling of longitudinal imaging data. Moreover, the diagnostic utility of QSM and assessment of CMB load should be exploited further in studies of AD

Scatter plots of K^trans, v_e and magnetic susceptibility as a function of age for of wild type (WT) and arcAβ (ArcAβ) mice.

<p><i>Cp/lgp</i> denotes caudate putamen and lateral globus pallidus.</p

Scatter plots of apparent diffusion coefficient (ADC), index of diffusion anisotropy (IDA) and T₁ relaxation times as a function of age for wild type (WT) and transgenic arcAβ (ArcAβ) mice.

<p><i>Cp/lgp</i> denotes caudate putamen and lateral globus pallidus.</p

Horizontal GRE magnitude images, susceptibility weighted images and quantitative susceptibility maps of a 21 month old arcAβ mouse.

<p>Suspected microbleeds are indicated by white arrows, while structures corresponding to vessel cross-sections are indicated by red arrows. The scale bar indicates 1 mm. Topography of cerebral microbleeds (CMBs) of a an arcAβ mouse with high CMB load at 13 (A), 18 (B) and 21 (C) months of age. Average projections of the registration template over an acquired slab of 2.1 mm thickness. The brain regions affected are predominantly the cortex and olfactory bulb and to a lesser extent the hippocampus. The CMB load increases with increasing age. The frequency of overlapping CMBs in 3D assessed at a single time point is indicated by the colour bar.</p

Examples on region-of-interest (ROI) delineating different anatomical regions.

<p>T₂-weighted spin echo images of the mouse brain acquired at 9.4T in sagittal (A), axial (B–D) and horizontal (E) orientation. ROIs were identified for the olfactory bulb (<i>ob</i>), cerebral cortex (<i>cortex</i>), caudate putamen and lateral globus pallidus (<i>cp/lgp</i>), hippocampus (<i>hc</i>), corpus callosum (<i>cc</i>), fimbria hippocampi (<i>fimbria</i>) and ventricles (<i>csf</i>).</p