A cross species thermoelectric and spatiotemporal analysis of alternans in live explanted hearts using dual voltage-calcium fluorescence optical mapping.

Objective.Temperature plays a crucial role in influencing the spatiotemporal dynamics of the heart. Electrical instabilities due to specific thermal conditions typically lead to early period-doubling bifurcations and beat-to-beat alternans. These pro-arrhythmic phenomena manifest in voltage and calcium traces, resulting in compromised contractile behaviors. In such intricate scenario, dual optical mapping technique was used to uncover unexplored multi-scale and nonlinear couplings, essential for early detection and understanding of cardiac arrhythmia.Approach.We propose a methodological analysis of synchronized voltage-calcium signals for detecting alternans, restitution curves, and spatiotemporal alternans patterns under different thermal conditions, based on integral features calculation. To validate our approach, we conducted a cross-species investigation involving rabbit and guinea pig epicardial ventricular surfaces and human endocardial tissue under pacing-down protocols.Main results.We show that the proposed integral feature, as the area under the curve, could be an easily applicable indicator that may enhance the predictability of the onset and progression of cardiac alternans. Insights into spatiotemporal correlation analysis of characteristic spatial lengths across different heart species were further provided.Significance.Exploring cross-species thermoelectric features contributes to understanding temperature-dependent proarrhythmic regimes and their implications on coupled spatiotemporal voltage-calcium dynamics. The findings provide preliminary insights and potential strategies for enhancing arrhythmia detection and treatment.

Innovative Characterization of Alternans Onset and Development in Dual Voltage-Calcium Whole-Heart Optical Mapping Signals at Multiple Thermal States.

Cardiac electrical dynamics show complex space-time instabilities, like period-doubling bifurcation and beat-to-beat alternans, known to occur as pro-arrhythmic phenomena and linked to membrane voltage and intracellular calcium kinetics. Besides, cellular ionic dynamics are critically affected by temperature oscillations, further enhancing the complexity of such arrhythmias precursors that lead to irregular cardiac contraction. In this complex scenario, fluorescence dual optical mapping techniques allow the unveiling of nonlinear and multi-scale couplings. In this contribution, we propose a novel methodological analysis of synchronous dual voltage-calcium traces obtained from whole rabbit hearts for (i) detecting alternans onset and evolution, (ii) characterizing novel restitution curves, and (iii) defining spatio-temporal alternans patterns at four thermal states. We validate our approach against well-accepted analyses considering complete pacing-down restitution protocols. The proposed methodology computes integral features, e.g., area under the curve, suggesting that a novel, easy-to-use indicator, may advance predictability on alternans onset and evolution, further providing insights into spatio-temporal cardiac analyses.Clinical Relevance- This work introduces new methods for the early detection of cardiac alternans onset and development as precursors of arrhythmias and fibrillation at different temperatures.

The Direct Interaction between Two Morphogenetic Proteins Is Essential for Spore Coat Formation in Bacillus subtilis.

In Bacillus subtilis the protective layers that surround the mature spore are formed by over seventy different proteins. Some of those proteins have a regulatory role on the assembly of other coat proteins and are referred to as morphogenetic factors. CotE is a major morphogenetic factor, known to form a ring around the forming spore and organize the deposition of the outer surface layers. CotH is a CotE-dependent protein known to control the assembly of at least nine other coat proteins. We report that CotH also controls the assembly of CotE and that this mutual dependency is due to a direct interaction between the two proteins. The C-terminal end of CotE is essential for this direct interaction and CotH cannot bind to mutant CotE deleted of six or nine C-terminal amino acids. However, addition of a negatively charged amino acid to those deleted versions of CotE rescues the interaction.