Noise Effects on the Complex Patterns of Abnormal Heartbeats

Patients at high risk for sudden death often exhibit complex heart rhythms in which abnormal heartbeats are interspersed with normal heartbeats. We analyze such a complex rhythm in a single patient over a 12-hour period and show that the rhythm can be described by a theoretical model consisting of two interacting oscillators with stochastic elements. By varying the magnitude of the noise, we show that for an intermediate level of noise, the model gives best agreement with key statistical features of the dynamics.Comment: 4 pages, 4 figures, RevTe

Mechanisms of Surviving Burial: Dune Grass Interspecific Differences Drive Resource Allocation After Sand Deposition

Sand dunes are important geomorphic formations of coastal ecosystems that are critical in protecting human populations that live in coastal areas. Dune formation is driven by ecomorphodynamic interactions between vegetation and sediment deposition. While there has been extensive research on responses of dune grasses to sand burial, there is a knowledge gap in understanding mechanisms of acclimation between similar, coexistent, dune-building grasses such as Ammophila breviligulata (C3), Spartina patens (C4), and Uniola paniculata (C4). Our goal was to determine how physiological mechanisms of acclimation to sand burial vary between species. We hypothesize that (1) in the presence of burial, resource allocation will be predicated on photosynthetic pathway and that we will be able to characterize the C3 species as a root allocator and the C4 species as leaf allocators. We also hypothesize that (2) despite similarities between these species in habitat, growth form, and life history, leaf, root, and whole plant traits will vary between species when burial is not present. Furthermore, when burial is present, the existing variability in physiological strategy will drive species-specific mechanisms of survival. In a greenhouse experiment, we exposed three dune grass species to different burial treatments: 0 cm (control) and a one-time 25-cm burial to mimic sediment deposition during a storm. At the conclusion of our study, we collected a suite of physiological and morphological functional traits. Results showed that Ammophila decreased allocation to aboveground biomass to maintain root biomass, preserving photosynthesis by allocating nitrogen (N) into light-exposed leaves. Conversely, Uniola and Spartina decreased allocation to belowground production to increase elongation and maintain aboveground biomass. Interestingly, we found that species were functionally distinct when burial was absent; however, all species became more similar when treated with burial. In the presence of burial, species utilized functional traits of rapid growth strategy, although mechanisms of change were interspecifically variable

The Dynamics of Sustained Reentry in a Loop Model with Discrete Gap Junction Resistance

Dynamics of reentry are studied in a one dimensional loop of model cardiac cells with discrete intercellular gap junction resistance ($R$). Each cell is represented by a continuous cable with ionic current given by a modified Beeler-Reuter formulation. For $R$ below a limiting value, propagation is found to change from period-1 to quasi-periodic ($QP$) at a critical loop length ($L_{crit}$) that decreases with $R$. Quasi-periodic reentry exists from $L_{crit}$ to a minimum length ($L_{min}$) that is also shortening with $R$. The decrease of $L_{crit}(R)$ is not a simple scaling, but the bifurcation can still be predicted from the slope of the restitution curve giving the duration of the action potential as a function of the diastolic interval. However, the shape of the restitution curve changes with $R$.Comment: 6 pages, 7 figure

Points, Walls and Loops in Resonant Oscillatory Media

In an experiment of oscillatory media, domains and walls are formed under the parametric resonance with a frequency double the natural one. In this bi-stable system, %phase jumps $\pi$ by crossing walls. a nonequilibrium transition from Ising wall to Bloch wall consistent with prediction is confirmed experimentally. The Bloch wall moves in the direction determined by its chirality with a constant speed. As a new type of moving structure in two-dimension, a traveling loop consisting of two walls and Neel points is observed.Comment: 9 pages (revtex format) and 6 figures (PostScript

Instability and Spatiotemporal Dynamics of Alternans in Paced Cardiac Tissue

We derive an equation that governs the spatiotemporal dynamics of small amplitude alternans in paced cardiac tissue. We show that a pattern-forming linear instability leads to the spontaneous formation of stationary or traveling waves whose nodes divide the tissue into regions with opposite phase of oscillation of action potential duration. This instability is important because it creates dynamically an heterogeneous electrical substrate for inducing fibrillation if the tissue size exceeds a fraction of the pattern wavelength. We compute this wavelength analytically as a function of three basic length scales characterizing dispersion and inter-cellular electrical coupling.Comment: 4 pages, 3 figures, submitted to PR

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Size-Dependent Transition to High-Dimensional Chaotic Dynamics in a Two-Dimensional Excitable Medium

The spatiotemporal dynamics of an excitable medium with multiple spiral defects is shown to vary smoothly with system size from short-lived transients for small systems to extensive chaos for large systems. A comparison of the Lyapunov dimension density with the average spiral defect density suggests an average dimension per spiral defect varying between three and seven. We discuss some implications of these results for experimental studies of excitable media.Comment: 5 pages, Latex, 4 figure

Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca(2+)/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKIIδ (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction

Metabolomics, lipidomics and proteomics profiling of myoblasts infected with Trypanosoma cruzi after treatment with different drugs against Chagas disease.

INTRODUCTION: Chagas disease, the most important parasitic infection in Latin America, is caused by the intracellular protozoan Trypanosoma cruzi. To treat this disease, only two nitroheterocyclic compounds with toxic side effects exist and frequent treatment failures are reported. Hence there is an urgent need to develop new drugs. Recently, metabolomics has become an efficient and cost-effective strategy for dissecting drug mode of action, which has been applied to bacteria as well as parasites, such as different Trypanosome species and forms. OBJECTIVES: We assessed if the metabolomics approach can be applied to study drug action of the intracellular amastigote form of T. cruzi in a parasite-host cell system. METHODS: We applied a metabolic fingerprinting approach (DI-MS and NMR) to evaluate metabolic changes induced by six different (candidate) drugs in a parasite-host cell system. In a second part of our study, we analyzed the impact of two drugs on polar metabolites, lipid and proteins to evaluate if affected pathways can be identified. RESULTS: Metabolic signatures, obtained by the fingerprinting approach, resulted in three different clusters. Two can be explained by already known of mode actions, whereas the three experimental drugs formed a separate cluster. Significant changes induced by drug action were observed in all the three metabolic fractions (polar metabolites, lipids and proteins). We identified a general impact on the TCA cycle, but no specific pathways could be attributed to drug action, which might be caused by a high percentage of common metabolome between a eukaryotic host cell and a eukaryotic parasite. Additionally, ion suppression effects due to differences in abundance between host cells and parasites may have occurred. CONCLUSION: We validated the metabolic fingerprinting approach to a complex host-cell parasite system. This technique can potentially be applied in the early stage of drug discovery and could help to prioritize early leads or reconfirmed hits for further development