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Summary: The RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins that are involved in gene-expression regulation; however, their in vivo targets and activities in biological processes such as cell differentiation, which requires reprogramming of gene-expression programs at multiple levels, are not well characterized. Here, we uncovered a mechanism by which DDX5 and DDX17 cooperate with heterogeneous nuclear ribonucleoprotein (hnRNP) H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms. We then observed that downregulation of DDX5 and DDX17 protein expression during myogenesis and epithelial-to-mesenchymal transdifferentiation contributes to the switching of splicing programs during these processes. Remarkably, this downregulation is mediated by the production of miRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins “master orchestrators” of differentiation that dynamically orchestrate several layers of gene expression. [Copyright &y& Elsevier]

Abstract: We report on the initial growth mechanisms of Ge on LaAlO3(001), a crystalline oxide with a high dielectric constant (high-κ material). Chemical and structural properties were investigated in situ, through X-ray photoelectron spectroscopy and reflection high-energy electron diffraction, and ex situ by using high-resolution transmission electron microscopy. Ge was deposited by molecular beam epitaxy at 600°C on a c(2×2) reconstructed LaAlO3(001) surface. At this temperature, a Volmer–Weber growth mode is observed due to a lower LaAlO3(001) surface free energy. It is characterized by the immediate formation of crystalline nano-islands. The Ge islands are relaxed and present an abrupt interface with the substrate. Some of them exhibit a preferential relationship in their heteroepitaxy, where the Ge(001) planes are parallel to the LaAlO3(001) ones, but rotated by 45° in the [001] direction. An additional rotation of 6° with respect to the growth axis is also observed, which compensates partially for the strain produced by the high lattice parameter mismatch (∼5%) between the semiconductor and the oxide. [Copyright &y& Elsevier]

In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n = 99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S high patients were found to be younger than TET2 low patients without a difference in the rate of complete remission. However, TET2E2S high patients exhibited a significantly lower CIR (p < 10 −4 ). TET2E2S and FLT3-ITD , but not age or NPM1 mutation status were independent prognostic factors for DFS and event-free survival (EFS), while TET2E2S was the sole prognostic factor that we identified for overall survival (OS). In both the intermediate-1 and favorable ELN genetic categories, TET2E2S remained significantly associated with prolonged survival. There was no correlation between TET2E2S status and outcomes in 34 additional AML patients who were unfit for IC. Therefore our results suggest that assessments of TET2 exon 2 splicing status might improve risk stratification in CN-AML patients treated with IC. [ABSTRACT FROM AUTHOR]

Abstract: Genes are important in defining genetic variability, but they do not constitute the largest component of genomes, which in most organisms contain large amounts of various repeated sequences including transposable elements (TEs), which have been shown to account for most of the genome size. TEs contribute to genetic diversity by their mutational potential as a result of their ability to insert into genes or gene regulator regions, to promote chromosomal rearrangements, and to interfere with gene networks. Also, TEs may be activated by environmental stresses (such as temperature or radiation) that interfere with epigenetic regulation systems, and makes them powerful mutation agents in nature. To understand the relationship between genotype and phenotype, we need to analyze the portions of the genome corresponding to TEs in great detail, and to decipher their relationships with the genes. For this purpose, we carried out comparative analyses of various natural populations of the closely-related species Drosophila melanogaster and Drosophila simulans, which differ with regard to their TE amounts as well as their ecology and population size. [Copyright &y& Elsevier]