Nicolas Wieder

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In this study, we numerically analyzed the nonlinear Ca(2+)-dependent gating dynamics of a single, nonconducting inositol 1,4,5-trisphosphate receptor (IP₃R) channel, using an exact and fully stochastic simulation algorithm that includes channel gating, Ca(2+) buffering, and Ca(2+) diffusion. The IP₃R is a ubiquitous intracellular Ca(2+) release channel(More)
In this article, we present an overview of simulation strategies in the context of subcellular domains where calcium-dependent signaling plays an important role. The presentation follows the spatial and temporal scales involved and represented by each algorithm. As an exemplary cell type, we will mainly cite work done on striated muscle cells, i.e. skeletal(More)
In simulations of chemical systems, the main task is to find an exact or approximate solution of the chemical master equation (CME) that satisfies certain constraints with respect to computation time and accuracy. While Brownian motion simulations of single molecules are often too time consuming to represent the mesoscopic level, the classical Gillespie(More)
Calcium ions play a key role in subcellular signaling as localized transients of the intracellular calcium concentration modify the activity of ion channels, enzymes and transcription factors, among others. The intracellular calcium concentration is inherently noisy, as diffusion, the transient binding to and dissociation from buffer molecules and(More)
With more than 6,000 new pediatric patients with treatment-resistant nephrotic syndrome in the US each year alone, the unmet need for novel, podocyte-specific therapies is substantial. Recently, the established therapeutic benefit of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) was used as a starting point to gain(More)
The upregulation of chaperones such as the 78-kDa glucose-regulated protein (GRP78; also referred to as BiP or HSPA5) is part of the adaptive cellular response to endoplasmic reticulum (ER) stress. GRP78 is widely used as a marker of the unfolded protein response, associated with sustained ER stress. Here, we report the discovery of a proteostatic mechanism(More)
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