The PHF21B gene is associated with major depression and modulates the stress response

Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.M-L Wong, M Arcos-Burgos, S Liu, J I Vélez, C Yu, B T Baune, M C Jawahar, V Arolt, U Dannlowski, A Chuah, G A Huttley, R Fogarty, M D Lewis, S R Bornstein, and J Licini

Metabolomics Reveals Minor Tambjamines in a Marine Invertebrate Food Chain

Metabolomics analysis detected tambjamine alkaloids in aqueous and EtOAc extracts of the marine invertebrates Virididentula dentata, Tambja stegosauriformis, Tambja brasiliensis, and Roboastra ernsti. Among several tambjamines, the new amino acid derivatives tambjamines M-O (17-19) were identified by Marfey's advanced analysis, UPLC-MS/MS analyses, and total synthesis. The tambjamine diversity increased from the bryozoan V. dentata to its nudibranch predators T. stegosauriformis and T. brasiliensis and attained a higher diversity in R. ernsti, the nudibranch that preys upon T. stegosauriformis and T. brasiliensis. The total tambjamine content also increases among the trophic levels, probably due to biomagnification. Tambjamines A (1), C (3), and D (4) are the major metabolites in the tissues of V. dentata, T. stegosauriformis, T. brasiliensis, and R. ernsti and are likely the main chemical defenses of these marine invertebrates

Estudo exploratório do uso da vinhaça ao longo do tempo: II. Características da cana-de-açúcar Exploratory study of the stillage use along the time: II. Characteristics of the sugarcane crop

O presente trabalho foi realizado em Cidade Gaúcha, PR, e teve como objetivo avaliar a resistência mecânica do solo, compactação, níveis de cálcio, magnésio e potássio, além da saturação de bases no solo e a densidade de raízes de cana-de-açúcar fertirrigados com vinhaça durante 1, 2, 3, 4, 12 e 20 anos e em uma área que não recebeu aplicação. A compactação foi avaliada com um penetrômetro de cone até 0,50 m de profundidade; a cada 0,02 m as análises químicas foram realizadas em amostras de solo coletadas entre 0 e 0,20 e 0,20 e 0,40 m de profundidade e a densidade de raízes avaliada com a pesagem de massa seca das raízes extraídas de monólitos de solos retirados a cada 0,10 m de profundidade, até 0,50 m. A maior resistência mecânica do solo ocorreu na área com vinte anos de aplicação de vinhaça. A concentração de cálcio decresceu após 2 anos de aplicação de vinhaça, acompanhando a fertilidade atual dos solos, não tendo ligação direta com a produtividade; já a concentração de potássio no solo apresentou relação direta com a produtividade; A quantidade de raízes no perfil do solo aumentou com o tempo de aplicação de vinhaça.<br>This work was conducted in the Cidade Gaúcha PR, with the objective to evaluate the mechanical resistance of soil, the levels of calcium, magnesium, potassium, base saturation in the soil, the roots distribution and yield of sugarcane fertigated with wastewater (stillage) of sugarcane industry for 1, 2, 3, 4, 12 and 20 consecutive years and a control without application. The soil compaction was evaluated with penetrometer cone to 0.50 m depth in intervals of 0.02 m. The results of chemical analysis of soil samples collected between the depths of 0 to 0.20 and 0.20 to 0.40 m were evaluated. The root density was evaluated with the weight of the dry matter of roots with the monolith method retreats to each 0.10 m depths to 0.50 m. The high soil mechanical resistance occurred where wastewater of sugarcane industry was applied for 20 years. The concentration of calcium decreased after two years of application of wastewater, accompanying the fertility of the soils not showing direct connection with the productivity as well as the magnesium. The concentration of the potassium in soil presented linear relation with the productivity. The roots of the sugarcane presented a direct relation with the application time of wastewater of sugarcane industr