Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Silyl Enol Ether Prins Cyclization: Diastereoselective Formation of Substituted Tetrahydropyran-4-ones

A diastereoselective synthesis of <i>cis</i>-2,6-disubstituted tetrahydropyran-4-ones was developed. The key step of this methodology, a silyl enol ether Prins cyclization, was promoted by a condensation reaction between a hydroxy silyl enol ether and an aldehyde to afford substituted tetrahydropyran-4-ones. The cyclization was tolerant of many functional groups, and the modular synthesis of the hydroxy silyl enol ether allowed for the formation of more than 30 new tetrahydropyran-4-ones with up to 97% yield and >95:5 dr. The cyclization step forms new carbon–carbon and carbon–oxygen bonds, as well as a quaternary center with good diastereoselectivity. The method provides a versatile route for the synthesis of substituted tetrahydropyrans

MUSE: A second-generation integral-field spectrograph for the VLT

The Multi Unit Spectroscopic Explorer (MUSE) is a second-generation instrument in development for the Very Large Telescope (VLT) of the European Southern Observatory (ESO), due to begin operation in 2011/12. MUSE will be an extremely powerful integral-field spectrograph fed by a new multiple-laser adaptive optics system on the VLT. In its usual operating mode, MUSE will, in a single observation, produce a 3-dimensional data cube consisting of 90,000 R 3000 spectra, each covering a full spectral octave (480-930 nm), and fully sampling a contiguous 1×1 arcmin2 field with 0.2×0.2 arcsec2 apertures. A high-resolution mode will increase the spatial sampling to 0.025 arcsec per pixel. MUSE is built around a novel arrangement of 24 identical spectrographs (each comparable to a 1st generation VLT instrument), which are fed by a set of 24 precision image slicers. MUSE is designed for stability, with only 2 modes, and virtually no moving parts, allowing very long exposures to be accumulated. Together with high throughput, this ensures that MUSE will have extreme sensitivity for observing faint objects. We overview the technical and scientific aspects of MUSE, highlighting the key challenges for dealing with the unprecedented quantity and complexity of the data, and the integration with the VLT adaptive optics facility (AOF) - a key development on the path to extremely large telescopes (ELTs). © 2008 Springer-Verlag Berlin Heidelberg