Suchergebnisse

One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer. ; The research leading to these results has received funding from the German Research Foundation (SCHA 1933/1-1), the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013–2017', SEV-2012-0208, the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreements n° HEALTH-F4-2011-278568 (PRIMES), from the Spanish Ministerio de Economía y Competitividad (Plan Nacional BIO 2012-39754) and the/nEuropean Fund for Regional Development (EFRD).

Im Februar 2009 trat die EU-Richtlinie zur Einbeziehung des internationalen Luftverkehrs in den EU-Emissionshandel mit CO2-Zertifikaten (EU-ETS) in Kraft. Ab dem Jahre 2012 werden für praktisch alle in der EU startenden und landenden Flüge Zertifikate erforderlich sein. Die Erstzuteilung von Emissionszertifikaten an Fluggesellschaften wird auf einem sogenannten Benchmark basieren, der durch die Division der CO2-Emissionen des Zeitraums 2004 bis 2006 durch die Verkehrsleistung des Jahres 2010 berechnet wird. Die vorliegende Untersuchung stellt ein empirisches Simulationsmodell zur Abschätzung der Effekte des EU-Emissionshandels (EU-ETS) für den Luftverkehr vor. Mit Hilfe dieses Modells werden aktuelle und zukunftsbezogene CO2-Emissionen und Verkehrsleistungen des europäischen Luftverkehrs geschätzt. Weiterhin werden die ökonomischen Effekte des EU-Emissionshandels auf den Luftverkehrssektor insgesamt, auf ausgewählte Gruppen von Fluggesellschaften sowie auf die EU-Mitgliedstaaten analysiert und erörtert. Im Ergebnis kann gezeigt werden, dass einzelne Gruppen von Fluggesellschaften und EU-Mitgliedstaaten ganz unterschiedlich von der neuen EU-Gesetzgebung betroffen sein werden. ; In February 2009, the EU Directive for the inclusion of international aviation into the EU emission trading with allowances for CO2 (EU-ETS) came into force. From 2012, virtually all flights landing and departing in the EU will be required to hold and surrender allowances. The initial allocation of allowances to individual aircraft operators will be based on a benchmark, which is calculated by dividing the CO2 emissions for the period from 2004 to 2006 by the reported revenue ton kilometres of the year 2010. In this article, an empirical model for the estimation of the effects of the EU-ETS for aviation is presented. With this model, current and future CO2 emissions and revenue ton kilometres of European aviation are estimated. Furthermore, the economic effects of the EU-ETS on air transport in general, on airline business models and on EU Member States are analysed and interpreted. As a result, it is shown that individual airline business models and EU Member States are quite differently affected by the new EU legislation.

The increasing number of experimentally detected interactions between proteins makes it difficult for researchers to extract the interactions relevant for specific biological processes or diseases. This makes it necessary to accompany the large-scale detection of protein-protein interactions (PPIs) with strategies and tools to generate meaningful PPI subnetworks. To this end, we generated the Human Integrated Protein-Protein Interaction rEference or HIPPIE (http://cbdm.uni-mainz.de/hippie/). HIPPIE is a one-stop resource for the generation and interpretation of PPI networks relevant to a specific research question. We provide means to generate highly reliable, context-specific PPI networks and to make sense out of them. We just released the second major update of HIPPIE, implementing various new features. HIPPIE grew substantially over the last years and now contains more than 270 000 confidence scored and annotated PPIs. We integrated different types of experimental information for the confidence scoring and the construction of context-specific networks. We implemented basic graph algorithms that highlight important proteins and interactions. HIPPIE's graphical interface implements several ways for wet lab and computational scientists alike to access the PPI data. ; German Research Foundation [SCHA 1933/1-1]; Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017' [SEV-2012-0208]; European Union Seventh Framework Programme (FP7/2007-2013) [n° HEALTH-F4-2011-278568 (PRIMES)]; Spanish Ministerio de Economía y Competitividad [Plan Nacional BIO2012-39754]; European Fund for Regional Development (EFRD). Funding for open access charge: University of Mainz.

DNA methylation is an epigenetic mechanism known to affect gene expression and aberrant DNA methylation patterns have been described in cancer. However, only a small fraction of differential methylation events target genes with a defined role in cancer, raising the question of how aberrant DNA methylation contributes to carcinogenesis. As recently a link has been suggested between methylation patterns arising in ageing and those arising in cancer, we asked which aberrations are unique to cancer and which are the product of normal ageing processes. We therefore compared the methylation patterns between ageing and cancer in multiple tissues. We observed that hypermethylation preferentially occurs in regulatory elements, while hypomethylation is associated with structural features of the chromatin. Specifically, we observed consistent hypomethylation of late-replicating, lamina-associated domains. The extent of hypomethylation was stronger in cancer, but in both ageing and cancer it was proportional to the replication timing of the region and the cell division rate of the tissue. Moreover, cancer patients who displayed more hypomethylation in late-replicating, lamina-associated domains had higher expression of cell division genes. These findings suggest that different cell division rates contribute to tissue- and cancer type-specific DNA methylation profiles. ; German Research Foundation [SCHA 1933/1-1]; European Union Seventh Framework Programme [FP7/2007-2013] under grant agreements [HEALTH-F4-2011-278568 (PRIMES)]; Spanish Ministry of Economy, Industry and Competitiveness (MEIC) [BFU2015-63571-P] and to the EMBL partnership; the European Regional Development Fund (ERDF/FEDER); Centro de Excelencia Severo Ochoa and the support of the CERCA Programme/Generalitat de Catalunya. Funding for open access charge: Spanish Ministry of Economy, Industry and Competitiveness (MEIC) [BFU2015-63571-P].