The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

A Novel Synthetic Route For Supporting Ruthenium Complexes On Functionalized Silica Gel

The immobilization of the ruthenium moiety Ru(NH3)4SO3 by reaction of trans-[Ru(NH3)4SO2(H2O)] 2+ with silica gel functionalized with 3-(1-imidazolyl)propyl groups is reported. A 60% surface coverage was obtained in the proportion of the resulting material [≡Si(CH2)3imN-Ru(NH3)4SO 3]. The anchored Ru(II) complex was characterized and its reactivity investigated. Derivatives of CO, pyrazine, and isonicotinamide have been prepared and characterized by electronic and vibrational spectroscopies, as well as by chemical means. The [≡Si(CH2)3imN-Ru(NH3)4SO 4]Cl, obtained through oxidation of the corresponding ruthenium(II) sulfite species, has been characterized and the aquo and the oxalate derivative have been synthesized. © 1993 American Chemical Society.9112982298

Controlled Study of Correlation of Biomechanical Profile of Hemiparetic Patients with Distance Travelled in Six Minutes

The six-minute walking test (6MWT) is used to assess exercise tolerance that is associated with motor function of the lower limbs in hemiparetic patients. It is suggested that, for post-stroke subjects, performance in the 6MWT may be limited by biomechanical and cardiovascular factors. Our aim is to determine the correlation between the six-minute walk distance (6MWD) and the biomechanical profile of hemiparetic patients. During this cross-sectional controlled study, 10 hemiparetic patients with heart failure underwent 6MWT (ATS protocol). Tonus (Ashworth Scale) and goniometry of the lower limbs were measured. The average of 6MWD in two tests was 279±8 m. There was a negative correlation between the degree of spasticity for both the sural triceps (r=−0.57, P&lt;0.05), quadriceps (r=−0.58, P&lt;0.05) and the limitation in ankle dorsiflexion and the 6MWD (r=−0.76, P&lt;0.05). Also, there was correlation between hip extension and ankle dorsiflexion limitations with 6MWD (r=0.66, P&lt;0.05), (r=0.77, P&lt;0.05). The negative correlation between the highest spasticity in paretic limb and the 6MWD and the correlation between the lower movement range of paretic hip and ankle suggest association with these factors and gait velocity in 6MWT. Loss percentage represents the percentage calculation between distance traveled and the distance predicted achieved by patients. In this study, the negative correlation between the percentage of loss of 6MWD and the limitation in the ankle dorsiflexion movement suggests that for a minor motion arch of the ankle, there is a higher percentage of walking distance loss foretold

Módulo de elasticidade de grãos de milho submetidos a impactos mecânicos Modulus of elasticity of shelled corn submitted to mechanical impacts

Neste trabalho investigou-se a viabilidade de se obter o módulo de compressão de grãos de milho, utilizando-se dados experimentais de força versus tempo, provenientes de testes de impacto, juntamente com uma análise estrutural elástica do processo. Os módulos de elasticidade foram determinados para grãos, a diferentes teores de umidade, submetidos a impactos de diferentes velocidades, e obtidos por um processo de otimização por meio da técnica de elementos finitos. Dois tipos de módulo foram avaliados: (a) um módulo efetivo para todo o grão e (b) um módulo para cada uma das três regiões, com diferentes características, segundo as quais o grão foi dividido. O teor de umidade e a velocidade de impacto influenciaram nos valores dos módulos. Módulos para grãos a 13,4% base úmida (b.u.) foram maiores do que para aqueles a 20,0% b.u. A análise realizada (elástica) mostrou-se ser mais adequada na obtenção de módulos de elasticidade de grãos a 13,4% b.u.; neste teor, os grãos apresentam características elásticas mais pronunciadas que quando a 20,0% b.u. e, nos grãos com altos teores de umidade, as características viscoelásticas tornam-se predominantes.<br>In this study the viability of obtaining the corn compression modulus through an elastic structural analysis was investigated using force versus time data from grain impact tests. The moduli of elasticity of shelled corn at different moisture contents submitted to various impact velocities were determined. The moduli were obtained through an optimization process using the finite element technique. Two kinds of modulus were obtained: (a) an effective modulus for the grain and (b) a modulus for each one of the three regions, with different characteristics, in which the grain was divided. The moisture content and the impact velocity affected the modulus values. The moduli values for grains at 13.4% wet basis (w.b.) were higher than those for grains at 20.0% w.b. The analysis used for the modulus seems to be more adequate for grains at 13.4% w.b. The grains at this moisture content present elastic characteristics while those at 20.0% w.b. present a viscoelastic behavior