Ash2 acts as an ecdysone receptor coactivator by stabilizing the histone methyltransferase Trr.

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is required for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator

Chromatin proteins and RNA are associated with DNA during all phases of mitosis.

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein-DNA and RNA-DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains

Conformance Checking with Constraint Logic Programming: The Case of Feature Models

Developing high quality systems depends on developing high quality models. An important facet of model quality is their consistency with respect to their meta-model. We call the verification of this quality the conformance checking process. We are interested in the conformance checking of Product Line Models (PLMs). The problem in the context of product lines is that product models are not created by instantiating a meta-model: they are derived from PLMs. Therefore it is usually at the level of PLMs that conformance checking is applied. On the semantic level, a PLM is defined as the collection of all the product models that can be derived from it. Therefore checking the conformance of the PLM is equivalent to checking the conformance of all the product models. However, we would like to avoid this naïve approach because it is not scalable due to the high number of models. In fact, it is even sometimes infeasible to calculate the number of product models of a PLM. Despite the importance of PLM conformance checking, very few research works have been published and tools do not adequately support it. In this paper, we present an approach that employs Constraint Logic Programming as a technology on which to build a PLM conformance checking solution. The paper demonstrates the approach with feature models, the de facto standard for modeling software product lines. Based on an extensive literature review and an empirical study, we identified a set of 9 conformance checking rules and implemented them on the GNU Prolog constraints solver. We evaluated our approach by applying our rules to 50 feature models of sizes up to 10000 features. The evaluation showed that our approach is effective and scalable to industry size models

Heat conductivity of DNA double helix

Thermal conductivity of isolated single molecule DNA fragments is of importance for nanotechnology, but has not yet been measured experimentally. Theoretical estimates based on simplified (1D) models predict anomalously high thermal conductivity. To investigate thermal properties of single molecule DNA we have developed a 3D coarse-grained (CG) model that retains the realism of the full all-atom description, but is significantly more efficient. Within the proposed model each nucleotide is represented by 6 particles or grains; the grains interact via effective potentials inferred from classical molecular dynamics (MD) trajectories based on a well-established all-atom potential function. Comparisons of 10 ns long MD trajectories between the CG and the corresponding all-atom model show similar root-mean-square deviations from the canonical B-form DNA, and similar structural fluctuations. At the same time, the CG model is 10 to 100 times faster depending on the length of the DNA fragment in the simulation. Analysis of dispersion curves derived from the CG model yields longitudinal sound velocity and torsional stiffness in close agreement with existing experiments. The computational efficiency of the CG model makes it possible to calculate thermal conductivity of a single DNA molecule not yet available experimentally. For a uniform (polyG-polyC) DNA, the estimated conductivity coefficient is 0.3 W/mK which is half the value of thermal conductivity for water. This result is in stark contrast with estimates of thermal conductivity for simplified, effectively 1D chains ("beads on a spring") that predict anomalous (infinite) thermal conductivity. Thus, full 3D character of DNA double-helix retained in the proposed model appears to be essential for describing its thermal properties at a single molecule level.Comment: 16 pages, 12 figure

Automatic pathway building in biological association networks

BACKGROUND: Scientific literature is a source of the most reliable and comprehensive knowledge about molecular interaction networks. Formalization of this knowledge is necessary for computational analysis and is achieved by automatic fact extraction using various text-mining algorithms. Most of these techniques suffer from high false positive rates and redundancy of the extracted information. The extracted facts form a large network with no pathways defined. RESULTS: We describe the methodology for automatic curation of Biological Association Networks (BANs) derived by a natural language processing technology called Medscan. The curated data is used for automatic pathway reconstruction. The algorithm for the reconstruction of signaling pathways is also described and validated by comparison with manually curated pathways and tissue-specific gene expression profiles. CONCLUSION: Biological Association Networks extracted by MedScan technology contain sufficient information for constructing thousands of mammalian signaling pathways for multiple tissues. The automatically curated MedScan data is adequate for automatic generation of good quality signaling networks. The automatically generated Regulome pathways and manually curated pathways used for their validation are available free in the ResNetCore database from Ariadne Genomics, Inc. [1]. The pathways can be viewed and analyzed through the use of a free demo version of PathwayStudio software. The Medscan technology is also available for evaluation using the free demo version of PathwayStudio software

Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes in Drosophila is mediated by the epigenetic chromatin modifiers

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR\u27s target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of AHR in a living organism. Here, we examined the effects of human AHR and its ligands using transgenic Drosophila lines with an inducible human AhR gene. We found that exogenous AHR ligands can increase as well as decrease the transcription levels of the AHR target genes, including genes that control proliferation, motility, polarization, and programmed cell death. This suggests that AHR activation may affect the expression of gene networks that could be critical for cancer progression and metastasis. Importantly, we found that AHR target genes are also controlled by the enzymes that modify chromatin structure, in particular components of the epigenetic Polycomb Repressive complexes 1 and 2. Since exogenous AHR ligands (alternatively - xenobiotics) and small molecule inhibitors of epigenetic modifiers are often used as pharmaceutical anticancer drugs, our findings may have significant implications in designing new combinations of therapeutic treatments for oncological diseases. © Akishina et al

Obtención de espumas flexibles de poliuretano apartir de aceites de palma y castor modificados

Muy pocos estudios se han realizado en la obtención de espumas flexibles de poliuretano a base de aceite de palma y castor, por la gran rigidez y dureza que presentan estos productos; para mejorar estas propiedades, se modificaron mediante glicerólisis y esterificación. Se optimizaron utilizando la metodología Taguchi, las siguientes variables: relación de los reactivos, temperatura y tiempo, y en la obtención de las espumas: poliol modificado, cantidad de catalizador organométalico, amínico y cantidad de agua. Las espumas obtenidas presentan las características requeridas de confort y durabilidad, densidad, dureza, resistencia tensil, porcentaje de elongación, porcentaje de resiliencia, pruebas de espectroscopia infrarroja y resistencia a solvente y a la hidrólisi

Fibrosis-the Tale of H3K27 Histone Methyltransferases and Demethylases

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 (EZH1, EZH2), which are the alternative subunits of the Polycomb Repressive Complex 2 (PRC2) and demethylase (KDM) enzymes, Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and Lysine demethylase 6B (KDM6B), are responsible for regulating methylation status of H3K27me3. In this review, we explore how these key enzymes regulate chromatin structure to alter gene expression in fibrosis, highlighting them as attractive targets for the treatment of fibrosis

Obtención de espumas flexibles de poliuretano apartir de aceites de palma y castor modificados

Muy pocos estudios se han realizado en la obtención de espumas flexibles de poliuretano a base de aceite de palma y castor, por la gran rigidez y dureza que presentan estos productos; para mejorar estas propiedades, se modificaron mediante glicerólisis y esterificación. Se optimizaron utilizando la metodología Taguchi, las siguientes variables: relación de los reactivos, temperatura y tiempo, y en la obtención de las espumas: poliol modificado, cantidad de catalizador organométalico, amínico y cantidad de agua. Las espumas obtenidas presentan las características requeridas de confort y durabilidad, densidad, dureza, resistencia tensil, porcentaje de elongación, porcentaje de resiliencia, pruebas de espectroscopia infrarroja y resistencia a solvente y a la hidrólisi