SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

Total costs and benefits of biomass in selected regions of the European Union

The paper describes results of the BioCosts project in which a comprehensive analysis of the economic and environmental performance of the energy use of biomass was carried out for selected existing facilities throughout the European Union. It is demonstrated that the appropriately organized use of biofuels has significant environmental advantages compared to the use of fossil fuels. Mitigation of global warming is the largest single incentive to use biofuels. However, only a few technologies are economically competitive under prevailing conditions, while others lead to up to 100% higher energy production costs than fossil fuels. Employment effects of using biofuels are small but positive.http://www.sciencedirect.com/science/article/B6V2S-41JM99D-4/1/514a3253589af4590f84544e2966bcb

MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD

Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD

Systematische Darstellung der Luftreinhaltepolitik einzelner OECD-Mitgliedsländer. Länderbericht Großbritannien

The knowledge about the special structures and basic ideas of the national policies on air pollution control constitutes the precondition for an international consensus on the policy on air pollution. Therefore all important fields have been collected for the OECD United Kingdom. The aspects also include the strategies of the individual country. Clear differences become evident immission and emission standards are set up, and when the principle of prevention resp. the polluter-pays-principle is applied