Novel urinary protein biomarkers for the detection of acute renal damage, recently accepted by the U.S. Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan), now have to be validated in practice. Limited data regarding the performance of these acute markers after subacute or subchronic treatment are publicly available. To increase the area of applicability of these markers, it is important to evaluate the ability to detect them after 28 days of treatment or even longer. Wistar rats were treated with three doses of cisplatin, vancomycin, or puromycin to induce renal damage. Twelve candidate proteins were measured by Luminex xMAPbased WideScreen assays, MesoScale Discovery-based MULTI-SPOT technology, or RENA-strip dipstick assay after 28 days. Treatment with all three model compounds resulted in a dose-dependent increase in urinary biomarkers, specific for the observed areas within the nephron, determined histopathologically. The most promising biomarkers in this study were NGAL, Kim-1, osteopontin, clusterin, RPA-1, and GSTYb1, detected by multiplexing technologies. The RENA-strip dipstick assay delivered good diagnostic results for vancomycin-treated but not for cisplatin-or puromycin-treated rats. Taken together, the data show that these new biomarkers are robust and measurable for longer term studies to predict different types of kidney toxicities.
In this article, we argue that the spatial environment of everyday interaction has to be understood as a social construct. Co-participants in an interaction make use of the spatial affordances of the interactional architecture around them, and at the same time they interactionally create and maintain spatial configurations. In that sense, they can be argued to be "doing space". Concerning face-to-face interaction, we distinguish between heavily structured material settings that are custom-built for specific types of institutionalized interactions, such as lecture theatres, assembly halls or service encounters; moderately structured settings, such as restaurants, staff rooms or museums; and weakly structured settings, such as public town squares or other settings which provide only minimal assumptions about the interactions that may take place there and their spatial configurations. We extend this analysis to different forms of interaction on interactive multimodal platforms (IMP), where the complexities increase with the different spatial levels of the physical computer screen, the many different spatial levels depicted there, and the increasing difficulties for the interactants to navigate and negotiate the different levels of doing space.
Inducible gene expression is a powerful tool for basic research, gene therapy and biotechnology, whose utility depends in part on consistent levels of induction regardless of metabolic status or physiological context. Here we examined the inducibility of the ecdysone receptor-based RheoSwitch mammalian inducible expression system in proliferating cells and in cell cycle-arrested cells. We found that both contact inhibition and growth arrest subsequent to serum deprivation dramatically reduced the levels of induction of reporter genes that could be achieved in 3T3 fibroblasts but in not NMuMG mammary epithelial cells. These data have implications for the use of the RheoSwitch system in inducible gene expression applications.
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