Endogenous driving and synchronization in cardiac and uterine virtual tissues: bifurcations and local coupling

Cardiac and uterine muscle cells and tissue can be either autorhythmic or excitable. These behaviours exchange stability at bifurcations produced by changes in parameters, which if spatially localized can produce an ectopic pacemaking focus. The effects of these parameters on cell dynamics have been identified and quantified using continuation algorithms and by numerical solutions of virtual cells. The ability of a compact pacemaker to drive the surrounding excitable tissues depends on both the size of the pacemaker and the strength of electrotonic coupling between cells within, between, and outside the pacemaking region. We investigate an ectopic pacemaker surrounded by normal excitable tissue. Cell–cell coupling is simulated by the diffusion coefficient for voltage. For uniformly coupled tissues, the behaviour of the hybrid tissue can take one of the three forms: (i) the surrounding tissue electrotonically suppresses the pacemaker; (ii) depressed rate oscillatory activity in the pacemaker but no propagation; and (iii) pacemaker driving propagations into the excitable region. However, real tissues are heterogeneous with spatial changes in cell–cell coupling. In the gravid uterus during early pregnancy, cells are weakly coupled, with the cell–cell coupling increasing during late pregnancy, allowing synchronous contractions during labour. These effects are investigated for a caricature uterine tissue by allowing both excitability and diffusion coefficient to vary stochastically with space, and for cardiac tissues by spatial gradients in the diffusion coefficient

Multi-scale approaches for the simulation of cardiac electrophysiology: I – sub-cellular and stochastic calcium dynamics from cell to organ

Computational models of the heart at multiple spatial scales, from sub-cellular nanodomains to the whole-organ, are a powerful tool for the simulation of cardiac electrophysiology. Application of these models has provided remarkable insight into the normal and pathological functioning of the heart. In these two articles, we present methods for modelling cardiac electrophysiology at all of these spatial scales. In part one, presented here, we discuss methods and approaches for modelling sub-cellular calcium dynamics at the whole-cell and organ scales, valuable for modelling excitation–contraction coupling and mechanisms of arrhythmia triggers

Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes

This study aimed to simulate ventricular responses to elevations in myocyte pacing and adrenergic stimulation using a novel electrophysiological rat model and investigate ion channel responses underlying action potential (AP) modulations. Peak ion currents and AP repolarization to 50% and 90% of full repolarization (APD50-90) were recorded during simulations at 1–10 Hz pacing under control and adrenergic stimulation conditions. Further simulations were performed with incremental ion current block (L-type calcium current, ICa; transient outward current, Ito; slow delayed rectifier potassium current, IKs; rapid delayed rectifier potassium current, IKr; inward rectifier potassium current, IK1) to identify current influence on AP response to exercise. Simulated APD50-90 closely resembled experimental findings. Rate-dependent increases in IKs (6%–101%), IKr (141%–1339%), and ICa (0%–15%) and reductions in Ito (11%–57%) and IK1 (1%–9%) were observed. Meanwhile, adrenergic stimulation triggered moderate increases in all currents (23%–67%) except IK1. Further analyses suggest AP plateau is most sensitive to modulations in Ito and ICa while late repolarization is most sensitive to IK1, ICa, and IKs, with alterations in IKs predominantly stimulating the greatest magnitude of influence on late repolarization (35%–846% APD90 prolongation). The modified Leeds rat model (mLR) is capable of accurately modeling APs during physiological stress. This study highlights the importance of ICa, Ito, IK1, and IKs in controlling electrophysiological responses to exercise. This work will benefit the study of cardiac dysfunction, arrythmia, and disease, though future physiologically relevant experimental studies and model development are required

Galactic stellar haloes in the CDM model

We present six simulations of galactic stellar haloes formed by the tidal disruption of accreted dwarf galaxies in a fully cosmological setting. Our model is based on the Aquarius project, a suite of high-resolution N-body simulations of individual dark matter haloes. We tag subsets of particles in these simulations with stellar populations predicted by the galform semi-analytic model. Our method self-consistently tracks the dynamical evolution and disruption of satellites from high redshift. The luminosity function (LF) and structural properties of surviving satellites, which agree well with observations, suggest that this technique is appropriate. We find that accreted stellar haloes are assembled between 1 < z < 7 from less than five significant progenitors. These progenitors are old, metal-rich satellites with stellar masses similar to the brightest Milky Way dwarf spheroidals (107–108 M⊙). In contrast to previous stellar halo simulations, we find that several of these major contributors survive as self-bound systems to the present day. Both the number of these significant progenitors and their infall times are inherently stochastic. This results in great diversity among our stellar haloes, which amplifies small differences between the formation histories of their dark halo hosts. The masses (∼ 108–109 M⊙) and density/surface-brightness profiles of the stellar haloes (from 10 to 100 kpc) are consistent with expectations from the Milky Way and M31. Each halo has a complex structure, consisting of well-mixed components, tidal streams, shells and other subcomponents. This structure is not adequately described by smooth models. The central regions (<10 kpc) of our haloes are highly prolate (c/a∼ 0.3), although we find one example of a massive accreted thick disc. Metallicity gradients in our haloes are typically significant only where the halo is built from a small number of satellites. We contrast the ages and metallicities of halo stars with surviving satellites, finding broad agreement with recent observations

A New Relativistic High Temperature Bose-Einstein Condensation

We discuss the properties of an ideal relativistic gas of events possessing Bose-Einstein statistics. We find that the mass spectrum of such a system is bounded by $\mu \leq m\leq 2M/\mu _K,$ where $\mu$ is the usual chemical potential, $M$ is an intrinsic dimensional scale parameter for the motion of an event in space-time, and $\mu _K$ is an additional mass potential of the ensemble. For the system including both particles and antiparticles, with nonzero chemical potential $\mu ,$ the mass spectrum is shown to be bounded by $|\mu |\leq m\leq 2M/\mu _K,$ and a special type of high-temperature Bose-Einstein condensation can occur. We study this Bose-Einstein condensation, and show that it corresponds to a phase transition from the sector of continuous relativistic mass distributions to a sector in which the boson mass distribution becomes sharp at a definite mass $M/\mu _K.$ This phenomenon provides a mechanism for the mass distribution of the particles to be sharp at some definite value.Comment: Latex, 22 page

Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation

Endothelial cells line all blood vessels, where they coordinate blood vessel formation and the blood-tissue barrier via regulation of cell-cell junctions. The nucleus also regulates endothelial cell behaviors, but it is unclear how the nucleus contributes to endothelial cell activities at the cell periphery. Here, we show that the nuclear-localized linker of the nucleoskeleton and cyto-skeleton (LINC) complex protein SUN1 regulates vascular sprouting and endothelial cell-cell junction morphology and function. Loss of murine endothelial Sun1 impaired blood vessel formation and destabilized junctions, angiogenic sprouts formed but retracted in SUN1-depleted sprouts, and zebrafish vessels lacking Sun1b had aberrant junctions and defective cell-cell connections. At the cellular level, SUN1 stabilized endothelial cell-cell junctions, promoted junction function, and regulated contractility. Mechanistically, SUN1 depletion altered cell behaviors via the cytoskeleton without changing transcriptional profiles. Reduced peripheral microtubule density, fewer junction contacts, and increased catastrophes accompanied SUN1 loss, and microtubule depolymerization phenocopied effects on junctions. Depletion of GEF-H1, a microtubule-regulated Rho activator, or the LINC complex protein nesprin-1 rescued defective junctions of SUN1-depleted endothelial cells. Thus, endothelial SUN1 regulates peripheral cell-cell junctions from the nucleus via LINC complex-based microtubule interactions that affect peripheral microtubule dynamics and Rho-regulated contractility, and this long-range regulation is important for proper blood vessel sprouting and junction integrity

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Early carboniferous brachiopod faunas from the Baoshan block, west Yunnan, southwest China

38 brachiopod species in 27 genera and subgenera are described from the Yudong Formation in the Shidian-Baoshan area, west Yunnan, southwest China. New taxa include two new subgenera: Unispirifer (Septimispirifer) and Brachythyrina (Longathyrina), and seven new species: Eomarginifera yunnanensis, Marginatia cylindrica, Unispirifer (Unispirifer) xiangshanensis, Unispirifer (Septimispirifer) wafangjieensis, Brachythyrina (Brachythyrina) transversa, Brachythyrina (Longathyrina) baoshanensis, and Girtyella wafangjieensis. Based on the described material and constraints from associated coral and conodont faunas, the age of the brachiopod fauna from the Yudon Formation is considered late Tournaisian (Early Carboniferous), with a possibility extending into earlyViseacutean.<br /