Population-Level Associations between Preschool Vulnerability and Grade-Four Basic Skills

Background: This is a predictive validity study examining the extent to which developmental vulnerability at kindergarten entry (as measured by the Early Development Instrument, EDI) is associated with children’s basic skills in 4th grade (as measured by the Foundation Skills Assessment, FSA). Methodology/Principal Findings: Relative risk analysis was performed on a large database linking individual-level EDI ratings to the scores the same children obtained on a provincial assessment of academic skills (FSA – Foundation Skills Assessment) four years later. We found that early vulnerability in kindergarten is associated with the basic skills that underlie populations of children’s academic achievement in reading, writing and math, indicating that the Early Development Instrument permits to predict achievement-related skills four years in advance. Conclusions/Significance: The EDI can be used to predict children’s educational trends at the population level and can help select early prevention and intervention programs targeting pre-school populations at minimum cost

EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases

EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention

A Population Genetic Approach to Mapping Neurological Disorder Genes Using Deep Resequencing

Deep resequencing of functional regions in human genomes is key to identifying potentially causal rare variants for complex disorders. Here, we present the results from a large-sample resequencing (n = 285 patients) study of candidate genes coupled with population genetics and statistical methods to identify rare variants associated with Autism Spectrum Disorder and Schizophrenia. Three genes, MAP1A, GRIN2B, and CACNA1F, were consistently identified by different methods as having significant excess of rare missense mutations in either one or both disease cohorts. In a broader context, we also found that the overall site frequency spectrum of variation in these cases is best explained by population models of both selection and complex demography rather than neutral models or models accounting for complex demography alone. Mutations in the three disease-associated genes explained much of the difference in the overall site frequency spectrum among the cases versus controls. This study demonstrates that genes associated with complex disorders can be mapped using resequencing and analytical methods with sample sizes far smaller than those required by genome-wide association studies. Additionally, our findings support the hypothesis that rare mutations account for a proportion of the phenotypic variance of these complex disorders

Lunar samples record an impact 4.2 billion years ago that may have formed the Serenitatis Basin

Impact cratering on the Moon and the derived size-frequency distribution functions of lunar impact craters are used to determine the ages of unsampled planetary surfaces across the Solar System. Radiometric dating of lunar samples provides an absolute age baseline, however, crater-chronology functions for the Moon remain poorly constrained for ages beyond 3.9 billion years. Here we present U–Pb geochronology of phosphate minerals within shocked lunar norites of a boulder from the Apollo 17 Station 8. These minerals record an older impact event around 4.2 billion years ago, and a younger disturbance at around 0.5 billion years ago. Based on nanoscale observations using atom probe tomography, lunar cratering records, and impact simulations, we ascribe the older event to the formation of the large Serenitatis Basin and the younger possibly to that of the Dawes crater. This suggests the Serenitatis Basin formed unrelated to or in the early stages of a protracted Late Heavy Bombardment

Genotypic and environmental effects on wheat technological and nutritional quality

International audienceTechnological (processing performance and end-product) and nutritional quality of wheat is in principle determined by a number of compounds within the wheat grain, including proteins, polysaccharides, lipids, minerals, heavy metals, vitamins and phytochemicals, effecting these characters. The genotype and environment is of similar importance for the determination of the content and composition of these compounds. Furthermore, the interaction between genotypes and the cultivation environment may play a significant role. Many studies have evaluated whether the genotype or the environment plays the major role in determining the content of the mentioned compounds. An overall conclusion of these studies is that except for compounds encoded by single major genes, importance of certain factors mainly depend on how wide environments and how diverse cultivars are within these comparative studies. Comparing environments all over, e.g. across Latin America, ends up with a high significance of the environment while large studies including genotypes of wide genetic background result in a significant role for the genotype. In addition, for some technological properties and components, genotype has a higher effect (e.g. grain hardness and gluten proteins), while environment influences stronger on others (e.g. protein and mineral content).Content and concentration of proteins, but also to some extent of starch, some non-starch polysaccharides and lipids, are essential in determining the technological quality of a wheat flour. For nutritional quality of the flour, the majority of the compounds are together the important determinant. Thus an increased understanding of environmental effects is essential. As to how the environment is influencing the content of the compounds, there are some differences. The protein content and composition is strongly affected by environmental factors influencing nitrogen availability and cultivar development time. However, these two factors are impacted by a range of environmental (temperature, precipitation, humidity/sun hours, etc.) and agronomic (soil properties, crop management practices such as seeding density, nitrogen fertilizer application timing and amount, etc.) components. Thus, to understand the interplay between the various environmental and agronomic factors impacting the technological quality of a wheat flour, modeling is a useful tool. Several other compounds, including minerals and heavy metals, are to a higher extent determined by site specific variation, resulting in similar rankings of entries across locations, although the total content is varying among years. The bioactive compounds and vitamins are a part of the defense mechanisms of plants and thus there is a variation in these compounds depending on prevailing biotic and abiotic stresses (heat, drought, excess rainfall, nutrition, diseases and pests). Thus, even for nutritional quality of wheat, incorporating all compounds of relevance in the evaluation would benefit from modeling tools