The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Microbiota-gut-brain axis as a regulator of reward processes.

Our gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e. eating, social or sexual behaviours) and non-natural reinforcers (drug addiction behaviours including those relevant to alcohol, psychostimulants, opioids and cannabinoids). We will integrate preclinical and clinical evidence suggesting that the microbiota-gut-brain axis could be implicated in the development of disorders associated with alterations in the reward system and how it may be targeted as a promising therapeutic strategy

International thought in the Lula era Pensamento internacional na era Lula

In the last fifty years, Brazil began a rapid process of structural transformation, following the first stage of industrial development in the 1930s. Currently the country integrates the small group of countries which evolved from an initial peripheral and subordinate insertion dating back to the nineteenth century, part of the most dynamic segment of the semiperiphery. But this category, intermediate between the "maturity" and "backwardness", according Modernization theorists, or between the "center" and "periphery", as theorists of the Dependence defend, has undergone a process of overcoming considerable positive progress in the direction of the group of states that dominate the current world system. In this way, during the years 2003-2010, foreign policy, along with the formulation of a new regionalism as a strategy of global integration and a new ideal model of State, has been a key factor<br>Nos últimos 50 anos, o Brasil passou por um processo de rápidas transformações estruturais, seguidas do primeiro estágio de desenvolvimento industrial nos anos 30. Atualmente, o Brasil integra um pequeno número de países que saiu da condição de periferia e subordinação do século XIX para um grupo mais dinâmico de semi-periferia. Porém, essa é uma categoria intermediária entre maturidade e atraso, de acordo com teóricos da modernização; ou uma categoria entre centro e periferia, segundo teóricos da Dependência. Esse é um estágio do processo de superação de progressivas considerações positivas na direção de um grupo de Estados que dominam o sistema mundial atual. Nesse sentido, durante os anos 2003- 2010, a política externa tem se tornado um fator fundamental, junto com sua formulação de um novo regionalismo como estratégia de integração global e um novo modelo de Estad