University of Tübingen

About: University of Tübingen is a education organization based out in Tübingen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 40555 authors who have published 84108 publications receiving 3015320 citations. The organization is also known as: Eberhard Karls University & Eberhard-Karls-Universität Tübingen.

Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma

Abstract: Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.

Multiplex Human Papillomavirus Serology Based on In Situ-Purified Glutathione S-Transferase Fusion Proteins,

Abstract: Background: More than 100 different human papillomaviruses (HPVs) can cause proliferative diseases, many of which are malignant, such as cervical cancer. HPV serology is complex because infection and disease lead to distinct type-specific antibody responses. Using bead-based technology, we have developed an assay platform that allows the simultaneous detection of antibodies against up to 100 in situ affinity–purified recombinant HPV proteins. Methods: Twenty-seven HPV proteins were expressed as glutathione S -transferase fusion proteins and affinity-purified in one step by incubation of glutathione-displaying beads in bacterial lysate. Spectrally distinct bead sets, each carrying one particular antigen, were mixed, incubated with serum, and differentiated in a flow cytometer-like analyzer (xMAP; Luminex Corp). Antibodies bound to the antigens were detected via fluorescent secondary reagents. We studied 756 sera from 2 case-control studies of cervical cancer. Results: Glutathione S -transferase fusion proteins bound with high affinity to glutathione-displaying beads ( K d = 6.9 × 10−9 mol/L). The dynamic range of multiplex serology covered 1.5 orders of magnitude, and antibodies were detected at serum dilutions >1:1 000 000. Imprecision (median CV) was ≤5.4%, and assay reproducibility was high ( R 2 = 0.97). Results on clinical samples showed high concordance with ELISA (κ = 0.846), but multiplex serology exhibited increased detection of weak antibody responses. Antibodies to the E6 oncoproteins of the rare HPV types 52 and 58 were associated with cervical cancer ( P <0.001). Conclusion: Multiplex serology enables antibody analyses of large numbers of sera against up to 100 antigens in parallel and has the potential to replace ELISA technology.

A systemic and cognitive view on collaborative knowledge building with wikis

Abstract: Wikis provide new opportunities for learning and for collaborative knowledge building as well as for understanding these processes. This article presents a theoretical framework for describing how learning and collaborative knowledge building take place. In order to understand these processes, three aspects need to be considered: the social processes facilitated by a wiki, the cognitive processes of the users, and how both processes influence each other mutually. For this purpose, the model presented in this article borrows from the systemic approach of Luhmann as well as from Piaget’s theory of equilibration and combines these approaches. The model analyzes processes which take place in the social system of a wiki as well as in the cognitive systems of the users. The model also describes learning activities as processes of externalization and internalization. Individual learning happens through internal processes of assimilation and accommodation, whereas changes in a wiki are due to activities of external assimilation and accommodation which in turn lead to collaborative knowledge building. This article provides empirical examples for these equilibration activities by analyzing Wikipedia articles. Equilibration activities are described as being caused by subjectively perceived incongruities between an individuals’ knowledge and the information provided by a wiki. Incongruities of medium level cause cognitive conflicts which in turn activate the described processes of equilibration and facilitate individual learning and collaborative knowledge building.

Gender Diversity in the Boardroom and Firm Performance: What Exactly Constitutes a 'Critical Mass'?

Abstract: The under-representation of women on boards is a heavily discussed topic – not only in Germany. Based on critical mass theory and with the help of a hand-collected panel data set of 151 listed German firms for the years 2000-2005, we explore whether the link between gender diversity and firm performance follows a U-shape. Controlling for reversed causality, we find evidence for gender diversity to at first negatively affect firm performance and – only after a “critical mass” of about 30 percent women has been reached – to be associated with higher firm performance than completely male boards. Given our sample firms, the critical mass of 30 percent women translates into an absolute number of about three women on the board and hence supports recent studies on a corresponding “magic number” of women in the boardroom.