Human embryonic stem (hES) cells originate during an embryonic period of active epigenetic remodeling. DNA methylation patterns are likely to be critical for their self-renewal and pluripotence. We compared the DNA methylation status of 1536 CpG sites (from 371 genes) in 14 independently isolated hES cell lines with five other cell types: 24 cancer cell lines, four adult stem cell populations, four lymphoblastoid cell lines, five normal human tissues, and an embryonal carcinoma cell line. We found that the DNA methylation profile clearly distinguished the hES cells from all of the other cell types. A subset of 49 CpG sites from 40 genes contributed most to the differences among cell types. Another set of 25 sites from 23 genes distinguished hES cells from normal differentiated cells and can be used as biomarkers to monitor differentiation. Our results indicate that hES cells have a unique epigenetic signature that may contribute to their developmental potential.
Embryonic stem (ES) cells are unique as they have the potential to be generated in large numbers and the ability to differentiate into the three germ layers via embryoid body (EB) formation. This property could be utilized as an index to study initial mammalian development. We have investigated the utility of a comprehensively characterized human ES (hES) cell line (ReliCellhES1) for testing the embryotoxic effects of compounds using cytotoxicity assays. Further, we performed real time gene expression analysis to check the alterations in germ layer markers expression upon drug treatment. The results show that assays using hES cells could serve as a reliable, sensitive and robust method to assess embryotoxic potential of compounds. They also provide a proof of concept that hES cells can be used as an in vitro model to demonstrate developmental toxicity, and to examine the germ layer-specific effects on differentiating EBs.
Aim The objective of this study was to find out the effect of religious fasting on intraocular pressure. Methods Intra-ocular pressure by applanation tonometer was measured four times a day in 38 healthy young adult male patients. The mean age of patients was 29 years. Body weight was measured to assess the extent of dehydration caused by fasting. Results There was a statistically significant difference between the intra-ocular pressure during fasting and the non-fasting period (P Ͻ 0.001). There was weight loss ranging from 0.4 to 1.5 kg. Conclusion Fasting alters the diurnal intraocular pressure in the study population, ie young males 22-38 years.
The development of the heart is essential for embryogenesis and precedes development of other organs. However, the mechanisms involved in embryonic cardiac development are ill-defined. Recent evidence suggests that Smad and Wnt signaling pathways are important in stem cell fate determination and their commitment to cardiovascular differentiation. We have previously reported that bone morphogenetic proteins (BMP)-2, -5, and -7 and fibroblast growth factors (FGF)-2 and -4 secreted from the adjoining endodermal cells favor cardiac differentiation in murine embryonic stem (ES) cells. Here, we demonstrate that BMP-2, -5, and -7 stimulate receptor-activated Smad1, 5, and 8, which in turn causes oligomerization of Smad4 in the nucleus. We further delineate the role of Wnt signaling pathway as evidenced by induction of Wnt3 and Wnt8b, stimulation of FRP-1, inhibition of GSK-B, accumulation of cytosolic beta-catenin, and transcription of target genes, including c-myc and cyclin-D1. We also ascertained the specificity of BMP- and Wnt-evoked activation of signaling cascades. Our data are consistent with the hypothesis that BMP-dependent activation of transcription factors including GATA-4, Nkx2.5, and MEF-2C augments cardiac differentiation mediated by cooperative control of Smad and Wnt signaling pathways. Our results provide a solid foundation for further study of the biochemistry of cardiac differentiation from stem cells.
Silicon photonics has become in the past years an important technology adopted by a growing number of industrial players to develop their next generation optical transceivers. However most of the technology platforms established in CMOS fabrication lines are kept captive or open to only a restricted number of customers. In order to make silicon photonics accessible to a large number of players several initiatives exist around the world to develop open platforms. In this paper we will present imec's silicon photonics active platform accessible through multi-project wafer runs
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