Simulated micro-electrode array recordings from stem cell-derived cardiomyocytes

Human stem cell-derived cardiomyocytes (hSC-CMs) are a promising medium for cardiovascular safety assessment. The effects of pharmaceutical compounds on the electrophysiological properties of these cells can be examined using micro-electrode arrays. Biomarkers derived from the recorded field potential give an indication of the effect of the compound on the tissue, and can therefore be used to make an initial judgement of the arrhythmic risk associated with a compound.<br><br>We propose a pipeline that combines ion channel screening data, micro-electrode array recordings and simulations to understand the mechanistic effects of a compound on the electrical activity recorded in an hSC-CM monolayer. A two-dimensional system is used to model the monolayer, from which simulated field potentials and biomarkers can be extracted. Despite previous work on modelling the distinct electrophysiology of hSC-CMs, there have been few tissue simulations to date. This process is more challenging than would be expected due to the spontaneous activity of the hSC-CMs and the presence of multiple cellular phenotypes. <br><br>There are several ways of representing the atrial-like and ventricular-like hSC-CMs within the monolayer; here we consider discrete areas of each phenotype. We investigate the predicted micro-electrode array recordings with the addition of a compound by using IC50 data from ion channel screens to modulate the ionic currents in the mathematical model. <br

A diagnosis of environmental awareness in sport and sport policy

This article sheds light on the problematic, but urgent, relation between sport and its environmental effects by focusing on the development of internal policies in the Swedish sport movement as well as on external normative pressures for a sustainable environmental development. The materials in this study portray a passive (and blind) governance in relation to an official environmental policy at macro and meso levels, regardless of the manifestations of individual environmental projects in everyday sport practices. The analysis shows that the ideology of the autonomy of sport and the emphasis on self- regulation, regularly upheld by the Swedish Sports Confederation, is obsolete

TRPV6 protein expression in bone cells and tissues.

<p>A, B: TRPV6 expression in LNCaP (A) and TE-85 (B) cells. An inset image shows staining with normal goat IgG (1 µg/mL) in each cell line. The slides in A and B were processed simultaneously. C: Staining with normal goat IgG (1 µg/mL) in mouse bone. D, E: TRPV6 expression in normal murine duodenum (positive control). F-I: TRPV6 expression in normal murine bone. Tissues from 6-week old male C57Bl/6J mice were fixed in 10% buffered formalin for 48 hours. Bones were decalcified for 4 weeks in EDTA/PFA. Images are representative of three mice. Slides in C-I were processed simultaneously. Scale bar: 50 µm in all panels.</p

Primers for qPCR.

<p>1. Published by Nijenhuis <i>et al.</i>, 2003 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028166#pone.0028166-Nijenhuis1" target="_blank">[18]</a>.</p><p>2. On Demand TaqMan™ Gene Expression Assays (Applied Biosystems, Life Technologies Corporation).</p

Currents in whole cell voltage-clamped SaOS-2 and 16HBE14o- cells.

<p>A, B: typical traces obtained from the same SaOS-2 cell in 2 mM [Ca²⁺]_O without (A) and with (B) 100 µM ruthenium red. C: Currents for SaOS-2 cells (mean ± SEM; n = 5) in 2 mM [Ca²⁺]_O without (open symbols) and with (solid symbols) 100 µM ruthenium red. A straight line adequately fits both conditions (<i>P</i> = 0.21; comparison of both datasets using the extra sum of squares F-test). D: Currents for 16HBE14o- cells (mean ± SEM; n = 15) in 2 mM [Ca²⁺]_O without (open symbols) and with (solid symbols) 100 µM ruthenium red. (<i>P</i> = 0.027; extra sum of squares F-test).</p

TRPV6 mRNA expression in human and murine cells and tissues.

<p>A: Variation in reference gene expression in human cDNA templates. B: TRPV6 mRNA expression in human cells, relative to B2M. D3: 12 h with 10 nM 1,25D3. Data are individual measures with mean ± SEM. C: TRPV6 mRNA expression in murine duodenum and in primary murine calvarial osteoblasts, relative to B2M (n = 3 for duodenum and n = 4 for calvarial osteoblasts). * <i>P</i><0.05, n.s. not statistically significant.</p