In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally differentiated somatic cells to a pluripotent stem cell state. The resulting induced pluripotent stem cells (iPSCs) made a paradigm shift in the field, further nailing down the disproval of the long‐held dogma that differentiation is unidirectional. The prospect of using iPSCs for patient‐specific cell‐based therapies has been enticing. This promise, however, has been questioned in the last two years as several studies demonstrated intrinsic epigenetic and genomic anomalies in these (...) cells. Here, we not only review the recent critical studies addressing the genome integrity during the reprogramming process, but speculate about the underlying mechanisms that could create de novo genome damage in iPSCs. Finally, we discuss how much an elevated mutation load really matters considering the safety of future therapies with cells heavily cultured in vitro. (shrink)

The recent ability to inactivate specific genes in mice has significantly accelerated our understanding of molecular, cellular, and even behavioral aspects of normal and disease processes. However, this ability has also demonstrated the extreme complexity of genetic determination in mammals, in particular, that genes in the same family or pathway can be functionally redundant and that a given gene often has multiple roles. Thus, inactivation of a gene often does not indicate its complete spectrum of functions. To circumvent this problem, (...) many new tools and novel applications of classic techniques have been developed to place spatial and temporal restrictions on the genomic alterations. These approaches include chimera and mosaic studies, organ transplantation, complementation assays, dominant negative mutants, conditional gene knockouts, and lineage-specific gene rescue. Not only has this opened up more sophisticated ways to make genomic alterations, but it has provided the opportunity to create animal models for sporadic human genetic diseases. BioEssays 20:200–208, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

There are several reasons to explore the role theater played in the life of Søren Kierkegaard and in the inspiration for his works. There are probably more reasons to analyze the role Kierkegaard played for theater, both as a source of inspiration and as a thinker reflecting on different facets of drama, performance, and acting. In the present study I focus on the diversity and complexity of Kierkegaard’s views on theater to elaborate on the possible connections and types of influence (...) he exercised on stage artists and theorists, shaping our contemporary theater theories. Approaches include literature, philosophy, theology, staging, acting, audience, and the history of theater, both in Kierkegaard’s times and later. (shrink)