NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length.

Deficiency of NEIL3, a DNA repair enzyme, has significant impact on mouse physiology, including vascular biology and gut health, processes related to aging. Leukocyte telomere length (LTL) is suggested as a marker of biological aging, and shortened LTL is associated with increased risk of cardiovascular disease. NEIL3 has been shown to repair DNA damage in telomere regions .

AMICI: high-performance sensitivity analysis for large ordinary differential equation models.

Summary: Ordinary differential equation models facilitate the understanding of cellular signal transduction and other biological processes. However, for large and comprehensive models, the computational cost of simulating or calibrating can be limiting. AMICI is a modular toolbox implemented in C++/Python/MATLAB that provides efficient simulation and sensitivity analysis routines tailored for scalable, gradient-based parameter estimation and uncertainty quantification.

Ryanodine receptor dispersion disrupts Ca release in failing cardiac myocytes.

Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters.

Simple T-Wave Metrics May Better Predict Early Ischemia as Compared to ST Segment.

There is pressing clinical need to identify developing heart attack (infarction) in patients as early as possible. However, current state-of-the-art tools in clinical practice, underpinned by the evaluation of elevation of the ST segment of the 12-lead electrocardiogram (ECG), do not identify all patients suffering from lack of blood flow to the heart muscle (cardiac ischemia), worsening the risk for further adverse events and patient outcome overall. In this study, we aimed to explore and compare the portions of cardiac repolarization in the ECG that best capture the electrophysiological changes associated with ischemia.

Slow Calcium-Depolarization-Calcium waves may initiate fast local depolarization waves in ventricular tissue.

Intercellular calcium waves in cardiac myocytes are a well-recognized, if incompletely understood, phenomenon. In a variety of preparations, investigators have reported multi-cellular calcium waves or triggered propagated contractions, but the mechanisms of propagation and pathological importance of these events remain unclear. Here, we review existing experimental data and present a computational approach to investigate the mechanisms of multi-cellular calcium wave propagation.

Instabilities of the resting state in a mathematical model of calcium handling in cardiac myocytes.

We analyze a recently published model of calcium handling in cardiac myocytes in order to find conditions for the presence of instabilities in the resting state of the model. Such instabilities can create calcium waves which in turn may be able to initiate cardiac arrhythmias. The model was developed by Swietach, Spitzer and Vaughan-Jones in order to study the effect, on calcium waves, of varying ryanodine receptor (RyR)-permeability, sarco/endoplasmic reticulum calcium ATPase (SERCA) and calcium diffusion.

Note on a possible proarrhythmic property of antiarrhythmic drugs aimed at improving gap-junction coupling.

Reduced conduction velocity (CV) in the myocardium is well known to increase the probability of arrhythmia and can be caused by structural changes, reduced excitability of individual myocytes, or decreased electrical coupling in the tissue. Recently, investigators have developed antiarrhythmic drugs that target the connections between individual myocytes with the goal of restoring tissue CV, specifically through increasing gap-junction coupling. In a simple but qualitatively relevant mathematical model, we show here that the introduction of a drug that improves intercellular conductance will indeed increase the CV.

On the frequency of automaticity during ischemia in simulations based on stochastic perturbations of the Luo-Rudy 1 model.

Aims: To compute the effects of parameter perturbations for single ischemic cardiac cells, and to determine how perturbations influenced the tendency for the cells to undergo spontaneous depolarization (automaticity) during 20 min of acute ischemia.

Methods: A modified Luo-Rudy 1 cell model was used. Since the range of biological variation and measurement errors is largely unknown, we conducted our study of the consequences of perturbations under the assumption that cell model parameters have a normal distribution with a 10% standard deviation.

On the computational complexity of the bidomain and the monodomain models of electrophysiology.

The bidomain model, coupled with accurate models of cell membrane kinetics, is generally believed to provide a reasonable basis for numerical simulations of cardiac electrophysiology. Because of changes occurring in very short time intervals and over small spatial domains, discretized versions of these models must be solved on fine computational grids, and small time-steps must be applied. This leads to huge computational challenges that have been addressed by several authors.

Simulation of ST segment changes during subendocardial ischemia using a realistic 3-D cardiac geometry.

The mechanisms underlying the ST segment shifts associated with subendocardial ischemia remain unclear. The aim of this paper is to shed further light on the subject through numerical simulations of these shifts. A realistic three-dimensional model of the ventricles, including fiber rotation and anisotropy, is embedded in a nonhomogeneous torso model.

An operator splitting method for solving the bidomain equations coupled to a volume conductor model for the torso.

In this paper we present a numerical method for the bidomain model, which describes the electrical activity in the heart. The model consists of two partial differential equations (PDEs), which are coupled to systems of ordinary differential equations (ODEs) describing electrochemical reactions in the cardiac cells. Many applications require coupling these equations to a third PDE, describing the electrical fields in the torso surrounding the heart.