Social Innovation Education. Transformierende Lernprogramme für Hochschulen

Seit einigen Jahrzehnten erleben wir, wie die Welt sich immer schneller verändert und die Komplexität der gesellschaftlichen, politischen und wirtschaftlichen Herausforderungen zunimmt. Dennoch begegnen wir den Anforderungen unserer Zeit in der Bildung und Ausbildung junger Menschen bis heute nur unzureichend. Zukünftige Generationen brauchen Handlungs- und Lösungskompetenzen, um den stetigen Wandel mitzugestalten. Sie benötigen die Fähigkeit mit unterschiedlichen Menschen zusammenzuarbeiten, zu kooperieren und verschiedene Perspektiven zu berücksichtigen. Dies erfordert Lernprogramme, die neben unternehmerischen Kompetenzen vor allem soziale-innovative, sozialunternehmerische und ethische Führungs- und Gestaltungskompetenzen fördern. Derartige Programme aus dem Bereich der noch jungen Social Innovation Education sind bisher kaum dokumentiert. Der vorliegende Sammelband soll dazu beitragen, diese Lücke zu schließen. Er lädt Bildungsverantwortliche und Lehrende sowie Praktikerinnen und Praktiker ein, sich mit transformierenden Lernprogrammen und Werkzeugen vertraut zu machen. So werden die an deutschen Hochschulen verstreuten Initiativen und Personen im Umfeld von ‚Social Innovation Education‘ sichtbar, damit diese noch besser voneinander, miteinander und füreinander lernen können

High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Connecting Countries by Electric Roads: Methodology for Feasibility Analysis of a Transnational ERS Corridor

The present study aims at discussing relevant aspects for a potential roll-out of Electric Road Systems (ERS) on transnational corridors, as well as generally for ERS introduction in Europe. Feasibility criteria have thus been developed in order to assess the following topics for specific potential ERS corridor projects: Technical aspects: Which technical prerequisites exist for ERS corridors and to which extent can they expected to be met? Environmental aspects: Which effects can be expected on key environmental indicators? Economic aspects: Can an ERS corridor pose a business case? Could it contribute to the improvement of ERS economy in general? Political aspects: Would an ERS corridor implementation make sense from a political point of view? The developed criteria may serve as a toolbox for scrutinizing future transnational ERS corridor projects. In order to illustrate their application, we used them to analyse a potential roll-out of an Electric Road System on a selected highway corridor (424 km) connecting Sweden and Germany, but mainly located on Danish territory. Based on traffic flows and patterns along the corridor route, it was found: A considerable part of the total truck mileage on the corridor is done by vehicles with a rather limited driving distance for pre- and post-haul, assuming the corridor is realized as a stand-alone project, and the CO2 emissions (well-to-wheel) of truck traffic along the corridor route can be significantly reduced if electric trucks are powered by the national electricity mixes expected for the year 2030, and even more if it would be powered purely renewable. Although a continuous ERS on the complete corridor route would not be economically feasible under current conditions, the analysis pinpoints sections along the route where the traffic volumes with a sufficient share of operation on a potential ERS are significantly higher. These sections are located in the metropolitan areas of Malmö, Copenhagen and Hamburg. For implementation, peculiarities of the local markets and regulation should be considered, as well as country-specific priorities on decarbonizing road freight transport. Additionally, the identified ERS potential for medium distances will depend on the technical and cost development of battery trucks. Our analysis also sheds some light on the role of first transnational corridors within a European roll-out strategy for ERS. Such corridor projects could help to proof the principal strengths of ERS, trigger strategic coordination between the participating countries, foster national ERS roll-out due to synergy effects with the corridor and pave the way for integration of ERS into EU legislation (e.g. AFID, TEN-T planning)Swedish-German Research Collaboration on Electric Road Systems (CollERS

Mutations in RAD21 Disrupt Regulation of APOB in Patients With Chronic Intestinal Pseudo-Obstruction

BACKGROUND & AIMS: Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. METHODS: We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. RESULTS: We identified a homozygous mutation (p. 622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p. 622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p. 622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. CONCLUSIONS: Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe