ETS1 induction by the microenvironment promotes ovarian cancer metastasis through focal adhesion kinase

Metastatic colonization involves paracrine/juxtacrine interactions with the microenvironment inducing an adaptive response through transcriptional regulation. However, the identities of transcription factors (TFs) induced by the metastatic microenvironment in ovarian cancer (OC) and their mechanism of action is poorly understood. Using an organotypic 3D culture model recapitulating the early events of metastasis, we identified ETS1 as the most upregulated member of the ETS family of TFs in metastasizing OC cells as they interacted with the microenvironment. ETS1 was regulated by p44/42 MAP kinase signaling activated in the OC cells interacting with mesothelial cells at the metastatic site. Human OC tumors had increased expression of ETS1, which predicted poor prognosis. ETS1 regulated OC metastasis both in vitro and in mouse xenografts. A combination of ChIP-seq and RNA-seq analysis and functional rescue experiments revealed FAK as the key transcriptional target and downstream effector of ETS1. Taken together, our results indicate that ETS1 is an essential transcription factor induced in OC cells by the microenvironment, which promotes metastatic colonization though the transcriptional upregulation of its target FAK

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

CD1b tetramers identify T cells that recognize natural and synthetic diacylated sulfoglycolipids from mycobacterium tuberculosis

Mycobacterial cell wall lipids bind the conserved CD1 family of antigen-presenting molecules and activate T cells via their T cell receptors (TCRs). Sulfoglycolipids (SGLs) are uniquely synthesized by Mycobacterium tuberculosis, but tools to study SGL-specific T cells in humans are lacking. We designed a novel hybrid synthesis of a naturally occurring SGL, generated CD1b tetramers loaded with natural or synthetic SGL analogs, and studied the molecular requirements for TCR binding and T cell activation. Two T cell lines derived using natural SGLs are activated by synthetic analogs independently of lipid chain length and hydroxylation, but differentially by saturation status. By contrast, two T cell lines derived using an unsaturated SGL synthetic analog were not activated by the natural antigen. Our data provide a bioequivalence hierarchy of synthetic SGL analogs and SGL-loaded CD1b tetramers. These reagents can now be applied to large-scale translational studies investigating the diagnostic potential of SGL-specific T cell responses or SGL-based vaccines

Estimativas de ganhos genéticos por diferentes índices de seleção em três populações híbridas de batata.

O objetivo deste trabalho foi comparar a eficiência de diferentes índices de seleção de clones superiores de batata. O experimento foi realizado no campo experimental da Embrapa Clima Temperado em Pelotas-RS, na primavera de 2008. Foram estudadas três populações híbridas de batata derivadas de cruzamentos entre clones avançados do programa de melhoramento de batata da Embrapa e cultivares estrangeiras. O delineamento experimental foi blocos aumentados em quatro repetições. O uso de índices de seleção resultou em maiores estimativas de ganhos de seleção, com melhor distribuição entre os caracteres avaliados. Os melhores índices de seleção encontrados para serem utilizados em programas de melhoramento de batata são os índices multiplicativo de Subandi et al. (1973) e o índice baseado na soma de ranks proposto por Mulamba & Mock (1978)

Combining ability of potato parents for tuber appearance and tuber yield component traits

The purpose of this study was to estimate the combining ability between two groups of potato parents in early generations of selection. Twelve potato families, derived from two groups of parents crossed in a 4x3 partial diallel design, were evaluated, in a randomized complete block design with three replications. Additive effects of genes were predominant for the traits tuber shape uniformity, tuber pointiness, tuber curvature, general tuber appearance, tuber size uniformity, tuber number, total tuber yield, and average tuber weight. With regard to general combining ability, for all tuber appearance traits, the foreign parents ‘Pukara’ and ‘Asterix’, and the national parent ‘Eliza’ contributed with complementary favorable alleles. For tuber yield component traits, the foreign parent ‘Rioja’ and the national parent ‘Eliza’ were outstanding. The specific combining ability indicated ‘Pukara’/‘Eliza’ as the most promising cross for the development of superior genotypes for the traits general tuber appearance and tuber number

Hidrólise de ATP e ADP em culturas de astrócitos e linhagens de gliomas : um estudo comparativo

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