Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

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

Resposta diferencial de espécies e de híbridos de citros à leprose Differential response of citrus species and hybrids to leprosis

O objetivo deste trabalho foi buscar novas fontes de resistência à leprose-dos-citros, no Banco Ativo de Germoplasma do Centro APTA Citros Sylvio Moreira, Instituto Agronômico, em Cordeirópolis, SP. Foram utilizadas plantas obtidas por sementes de 26 acessos, infectadas com o vírus da leprose-dos-citros (Citrus leprosis virus - CiLV), por meio do seu vetor Brevipalpus phoenicis. O aparecimento de lesões, a partir de 21 dias após a inoculação, foi observado em 11 dos genótipos testados (42,3%). Quinze espécies, entre elas Citrus pennivesiculata e C. celebica, comportaram-se como altamente resistentes, enquanto outras, como C. keraji, foram mais suscetíveis que o padrão C. sinensis. Os dados mostraram grande variação de respostas de Citrus spp. à leprose, com elevado número de espécies resisentes, que podem ser utilizadas como fonte de resistência à doença em programas de melhoramento.<br>The objective of this work was to prospect for new sources of resistance to leprosis in the Citrus Germplasm Bank of Centro APTA Citros Sylvio Moreira, Instituto Agronômico, in Cordeirópolis, SP, Brazil. Plants obtained through seeds from 26 citrus accessions were mite-infected with Citrus leprosis virus (CiLV). Typical lesions started to appear in 11 genotypes (42.3% of the tested accessions) 21 days after inoculation. Fifteen species, among them Citrus pennivesiculata and C. celebica, behaved as highly resistant, while other genotypes, as C. keraji, were more susceptible than the standard C. sinensis. The data showed a wide variation in the response of Citrus spp. to leprosis, with a large number of resistant species, wich can be used as source of resistance to this disease, in breeding programs

Variação temporal de larvas de Chironomidae (Diptera) no Alto Rio Paraguai (Cáceres, Mato Grosso, Brasil Temporal variation of Chironomidae larvae (Diptera) in the Upper Paraguay River (Cáceres, Mato Grosso, Brazil

A composição das assembléias de Chironomidae e os possíveis fatores ambientais que influenciam a distribuição temporal deste grupo no alto rio Paraguai, em Cáceres, foram abordados no presente estudo durante o período de novembro de 2004 a outubro de 2005. Para considerar a diversidade de habitats na região, selecionamos nove pontos amostrais, onde coletamos 2988 indivíduos, distribuídos em 34 espécies pertencentes a oito tribos de três subfamílias. Os gêneros Labrundinia sp.1, Polypedilum (Asheum) e Polypedilum (Tripodura) estiveram presentes em quase todos os meses amostrados. A maior riqueza e abundância foram registradas no período de seca, revelando Polypedilum como o gênero mais expressivo. Ficou evidente o efeito das vaiáveis ambientais sobre os atributos da diversidade do alto rio Paraguai.<br>The aim of this study is to determine the influence of environmental variables on the time distribution of assemblages of Chironomidae in the Upper Paraguay River. The samples were collected from November 2004 to October of 2005. To consider the diversity of habitats in the region, nine different sampling points were sampled and 2988 individuals were collected, distributed in 34 species, eight tribes and three subfamilies. The genus Labrundinia sp.1, Polypedilum (Asheum) and Polypedilum (Tripodura) occurred almost every month during the study. Richness and abundance were higher during the dry period of the year, and the genus Polypedilum was the most abundant. There was evident the effect of the environmental variables on the attributes of diversity in the Upper Paraguay River