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Pluripotent embryonic stem cells (ESCs) are characterised by their capacity to self-renew indefinitely while maintaining the potential to differentiate into all cell types of an adult organism. Both the undifferentiated and differentiated states are defined by specific gene expression programs that are regulated at the chromatin level. Here, we have analysed the contribution of the H3K27me2- and H3K27me23-specific demethylases KDM6A and KDM6B to murine ESC differentiation by employing the GSK-J4 inhibitor, which is specific for KDM6 proteins, and by targeted gene knockout (KO) and knockdown. We observe that inhibition of the H3K27 demethylase activity induces DNA damage along with activation of the DNA damage response (DDR) and cell death in differentiating but not in undifferentiated ESCs. Laser microirradiation experiments revealed that the H3K27me3 mark, but not the KDM6B protein, colocalise with γH2AX-positive sites of DNA damage in differentiating ESCs. Lack of H3K27me3 attenuates the GSK-J4-induced DDR in differentiating Eed-KO ESCs. Collectively, our findings indicate that differentiating ESCs depend on KDM6 and that the H3K27me3 demethylase activity is crucially involved in DDR and survival of differentiating ESCs.

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Internationalizing higher education is considered to be a major goal for universities in Germany and many medical students aspire to include international experiences into their academic training. However, the exact meaning of "internationalizing" medical education is still poorly defined, just as is the possible pedagogic impact and effects. Against this background, this article presents the special track curriculum on global health (in German: Schwerpunktcurriculum Global Health, short: SPC) at Justus Liebig University Giessen, which was established in 2011 as a comprehensive teaching program to integrate international perspectives and activities systematically into the clinical years of the medical curriculum. The report of the structure, content, didactic principles and participants' evaluations of the SPC is embedded into a larger discussion of the pedagogic value of a broad and interdisciplinary perspective on "global health" in medical education, that explicitly includes attention for health inequities, social determinants of health and the cultural dimensions of medicine and health abroad and "at home" (e.g. in relation to migration). We conclude that if properly defined, the emerging field of "global health" represents a didactically meaningful approach for adding value to medical education through internationalizing the curriculum, especially in regard to themes that despite of their uncontested value are often rather weak within medical education. The concrete curricular structures, however, have always to be developed locally. The "SPC" at Giessen University Medical School is only one possible way of addressing these globally relevant issues in one particular local academic setting.

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The solution structures of ion pairs formed by quarternary ammonium ions derived from quinine alkaloid with small hard anions (BH(4)(-) or Cl(-)) in CDCl(3) have been characterized by nuclear magnetic resonance methods. Structural observations have been correlated with the sense of asymmetric induction observed in the phase-transfer reduction of 9-anthryl trifluoromethyl ketone by borohydride (BH(4)(-)) when catalyzed by the quaternary N-benzylquinine ammonium ion. From interionic nuclear Overhauser effects (NOEs), it appears that the BH(4)(-) ion occupies two of the four trigonal pyramidal sites formed by substituents of the quarternary nitrogen of the catalyst cation. One of these sites is in close proximity to the cation's hydroxyl group that is strictly required for asymmetric induction in the model reaction, while the other site is near the vinyl group on the cation. The vinyl group does not appear to be important for determining the sense or extent of asymmetric induction. Using energy-minimized structures derived from NMR data, it was predicted that the N-(9-methyleneanthryl)quinine-quarternary ammonium catalyst would give improved asymmetric induction in the model reaction due to a preferred anion occupancy at the site near the hydroxyl group. An improvement in enantiomeric excess (ee) is observed using the anthryl-modified catalyst, and NMR studies on the modified catalyst confirm the predicted change in anion binding site occupancies. The changes in site occupancies determined by NMR can be fitted to a simple kinetic model that correctly predicts the extent of change in ee.