Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells.

The rate of spontaneous action potentials (APs) generated by sinoatrial node cells (SANC) is regulated by local Ca release (LCR) from the sarcoplasmic reticulum via Ca release channels (ryanodine receptors, RyRs). LCR events propagate and self-organize within the network of RyR clusters (Ca release units, CRUs) via Ca-induced-Ca-release (CICR) that depends on CRU sizes and locations: While larger CRUs generate stronger release signals, the network's topology governs signal diffusion and propagation. This study used super-resolution structured illumination microscopy to image the 3D network of CRUs in rabbit SANC.

A novel conceptual model of heart rate autonomic modulation based on a small-world modular structure of the sinoatrial node.

The present view on heartbeat initiation is that a primary pacemaker cell or a group of cells in the sinoatrial node (SAN) center paces the rest of the SAN and the atria. However, recent high-resolution imaging studies show a more complex paradigm of SAN function that emerges from heterogeneous signaling, mimicking brain cytoarchitecture and function. Here, we developed and tested a new conceptual numerical model of SAN organized similarly to brain networks featuring a modular structure with small-world topology.

4π light scattering flow cytometry: enhancing the identification and characterization of individual cells.

The analysis of individual particles with complex morphologies from light scattering is crucial in disperse systems studies, such as blood cells. Characterization, which assumes determining particle characteristics, has a higher likelihood of succeeding in solving the inverse light-scattering problem if an instrument provides enough light-scattering data. In this study, we demonstrate how we extend the operating angular interval for the 4π Scanning Flow Cytometer (4πSFC), which measures angle-resolved light-scattering profiles (LSPs) of individual particles.

The Synthesis, Structure, and Luminescent Properties of TmMgBO Crystals.

TmMgBO spontaneous crystals were synthesized via the flux-growth technique from a KMoO-based solvent. The crystal structure of the compound was solved and refined within the space group 2/. The first principles calculations of the electronic structure reveal that TmMg-pentaborate with an ideal not defected crystal structure is an insulator with an indirect energy band gap of approximately 6.

Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.

Cardiac muscle contraction is initiated by an elementary Ca signal (called Ca spark) which is achieved by collective action of Ca release channels in a cluster. The mechanism of this synchronization remains uncertain. We approached Ca spark activation as an emergent phenomenon of an interactive system of release channels.

Kinetic titration method in flow cytometry for quantification of cell receptors.

For the quantitative determination of cell receptors by fluorescence flow cytometry, we proposed a new method, which takes into account the reaction kinetics. The binding reaction of the ligand with receptors begins after placing the cells in the ligand solution. In the proposed method, there are several samples with the same concentration of cells and different initial concentrations of fluorescently labeled ligand, and each sample is measured by a flow cytometer once at the time when the following condition is met: the product of the incubation time (cells with ligand) and the initial concentration of ligand is the same for all samples.

Ultraviolet light scattering scanning flow cytometry in the characterization of submicron microparticles.

Ultraviolet lasers are commonly used in flow cytometry to excite fluorochrome molecules with subsequent measurement of the specific fluorescence of individual cells. In this study, the performance of the ultraviolet light scattering (UVLS) in the analysis of individual particles with flow cytometry has been demonstrated for the first time. The main advantage of the UVLS relates to the improvement of the analysis of submicron particles due to the strong dependence of the scattering efficiency on the wavelength of the incident light.

A light scatter based model relating erythrocyte vesiculation to lifetime in circulation.

Methods for measuring erythrocyte age distribution are not available as a simple analytical tool. Most of them utilize the fluorescence or radioactive isotopes labeling to construct the age distribution and support physicians with aging indices of donor's erythrocytes. The age distribution of erythrocyte may be a useful snapshot of patient state over 120-days period of life.

Phase Relations in the O-CrO-BO ( = Gd-Lu) Ternary Oxide Systems.

In this work, isothermal sections of the O-CrO-BO ( = Gd-Lu) ternary oxide systems at 900, 1000, and 1100 °C were constructed by determining the phase relations by using a powder X-ray diffraction technique. As a result, these systems were divided into subsidiary subsystems. Two types of double borates, Cr(BO) ( = Gd-Er) and Cr(BO) ( = Ho-Lu), were observed in the investigated systems.

The paradigm shift: Heartbeat initiation without "the pacemaker cell".

The current dogma about the heartbeat origin is based on "the pacemaker cell," a specialized cell residing in the sinoatrial node (SAN) that exhibits spontaneous diastolic depolarization triggering rhythmic action potentials (APs). Recent high-resolution imaging, however, demonstrated that Ca signals and APs in the SAN are heterogeneous, with many cells generating APs of different rates and rhythms or even remaining non-firing (dormant cells), i.e.

Adenosine reduces sinoatrial node cell action potential firing rate by uncoupling its membrane and calcium clocks.

The spontaneous action potential (AP) firing rate of sinoatrial nodal cells (SANC) is regulated by a system of intracellular Ca and membrane ion current clocks driven by Ca-calmodulin-activated adenylyl cyclase-protein kinase-A signaling. The mean AP-cycle length (APCL) and APCL variability inform on the effectiveness of clock coupling. Endogenous ATP metabolite adenosine binds to adenosine receptors (A, A) that couple to G protein-coupled receptors, reducing spontaneous AP firing rate G signaling that activates I.

Disorder in Ca2+ release unit locations confers robustness but cuts flexibility of heart pacemaking.

Excitation-contraction coupling kinetics is dictated by the action potential rate of sinoatrial-nodal cells. These cells generate local Ca releases (LCRs) that activate Na/Ca exchanger current, which accelerates diastolic depolarization and determines the pace. LCRs are generated by clusters of ryanodine receptors, Ca release units (CRUs), residing in the sarcoplasmic reticulum.

Functional Heterogeneity of Cell Populations Increases Robustness of Pacemaker Function in a Numerical Model of the Sinoatrial Node Tissue.

Each heartbeat is initiated by specialized pacemaker cells operating within the sinoatrial node (SAN). While individual cells within SAN tissue exhibit substantial heterogeneity of their electrophysiological parameters and Ca cycling, the role of this heterogeneity for cardiac pacemaker function remains mainly unknown. Here we investigated the problem numerically in a 25 × 25 square grid of connected coupled-clock Maltsev-Lakatta cell models.

Erythrocyte lysis and angle-resolved light scattering measured by scanning flow cytometry result to 48 indices quantifying a gas exchange function of the human organism.

Molecular/cell level of gas exchange function assumes the accurate measurement of erythrocyte characteristics and rate constants concerning to molecules involved into the CO /O transport. Unfortunately, common hematology analyzers provide the measurement of eight indices of erythrocytes only and say little about erythrocyte morphology and nothing about rate constants of cellular function. The aim of this study is to demonstrate the ability of the Scanning Flow Cytometer (SFC) in the complete morphological analysis of mature erythrocytes and characterization of erythrocyte function via measurement of lysing kinetics.

New Carbon-Mineral Sorbent Based on Aluminum Oxide, Polydimethylsiloxane, and Single-Wall Carbon Nanotubes: Assessment of the Effect on Erythrocytes In Vitro.

A comparative study of the effect of a sorbent with nanotubes (AlO@ WCNT-PDMS) and a carbon-mineral sorbent (AlO@C) on the parameters of human erythrocytes was carried out. Using scanning flow cytometry, the morphological and functional parameters of venous blood erythrocytes as well as drainage blood after its perfusion through columns with sorbents were determined. The compared samples AlO@SWCNT-PDMS and AlO@C are similar by their effect on the morphological and functional parameters of erythrocytes.

Phosphoprotein Phosphatase 1 but Not 2A Activity Modulates Coupled-Clock Mechanisms to Impact on Intrinsic Automaticity of Sinoatrial Nodal Pacemaker Cells.

Spontaneous AP (action potential) firing of sinoatrial nodal cells (SANC) is critically dependent on protein kinase A (PKA) and Ca/calmodulin-dependent protein kinase II (CaMKII)-dependent protein phosphorylation, which are required for the generation of spontaneous, diastolic local Ca releases (LCRs). Although phosphoprotein phosphatases (PP) regulate protein phosphorylation, the expression level of PPs and phosphatase inhibitors in SANC and the impact of phosphatase inhibition on the spontaneous LCRs and other players of the oscillatory coupled-clock system is unknown. Here, we show that rabbit SANC express both PP1, PP2A, and endogenous PP inhibitors I-1 (PPI-1), dopamine and cyclic adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (DARPP-32), kinase C-enhanced PP1 inhibitor (KEPI).

Ca and Membrane Potential Transitions During Action Potentials Are Self-Similar to Each Other and to Variability of AP Firing Intervals Across the Broad Physiologic Range of AP Intervals During Autonomic Receptor Stimulation.

Ca and transitions occurring throughout action potential (AP) cycles in sinoatrial nodal (SAN) cells are cues that (1) not only regulate activation states of molecules operating within criticality (Ca domain) and limit-cycle ( domain) mechanisms of a coupled-clock system that underlies SAN cell automaticity, (2) but are also regulated by the activation states of the clock molecules they regulate. In other terms, these cues are both causes and effects of clock molecular activation (recursion). Recently, we demonstrated that Ca and transitions during AP cycles in single SAN cells isolated from mice, guinea pigs, rabbits, and humans are self-similar (obey a power law) and are also self-similar to -species AP firing intervals (APFIs) of these cells , to heart rate , and to body mass.

Blood platelet quantification by light scattering: from morphology to activation.

Analysis of blood platelets encounters a number of different preanalytical issues, which greatly decrease the reliability and accuracy of routine clinical analysis. Modern hematology analyzers determine only four parameters relating to platelets. Platelet shape and dose-dependent activation parameters are outside the scope of commercial instruments.

Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species.

Objectives: The purpose of this study was to discover regulatory universal mechanisms of normal automaticity in sinoatrial nodal (SAN) pacemaker cells that are self-similar across species.

Background: Translation of knowledge of SAN automaticity gleaned from animal studies to human dysrhythmias (e.g.

cAMP-Dependent Signaling Restores AP Firing in Dormant SA Node Cells via Enhancement of Surface Membrane Currents and Calcium Coupling.

Action potential (AP) firing rate and rhythm of sinoatrial nodal cells (SANC) are controlled by synergy between intracellular rhythmic local Ca releases (LCRs) ("Ca clock") and sarcolemmal electrogenic mechanisms ("membrane clock"). However, some SANC do not fire APs (dormant SANC). Prior studies have shown that β-adrenoceptor stimulation can restore AP firing in these cells.

[Accuracy assessment of the blood glucose meter «Satellite Express» for glycemic control in children with diabetes].

Background: Monitoring glycemic control in diabetes includes daily measurements of glucose levels at home, along with periodic monitoring of glycemia indicators on the whole. The main purpose of monitoring glycemic control is to accurately and authentically assess the glycemic level reached by each patient in order to ensure the glycemic goals achievement. Glycemic control assessment at a certain point in time is best achieved by self-monitoring the level of glucose in the blood, in that allows you to assess the presence of hyperglycemia and hypoglycemia to optimize the treatment strategy.

Synchronized Cardiac Impulses Emerge From Heterogeneous Local Calcium Signals Within and Among Cells of Pacemaker Tissue.

Objectives: This study sought to identify subcellular Ca signals within and among cells comprising the sinoatrial node (SAN) tissue.

Background: The current paradigm of SAN impulse generation: 1) is that full-scale action potentials (APs) of a common frequency are initiated at 1 site and are conducted within the SAN along smooth isochrones; and 2) does not feature fine details of Ca signaling present in isolated SAN cells, in which small subcellular, subthreshold local Ca releases (LCRs) self-organize to generate cell-wide APs.

Methods: Immunolabeling was combined with a novel technique to detect the occurrence of LCRs and AP-induced Ca transients (APCTs) in individual pixels (chronopix) across the entire mouse SAN images.

Crystal Chemistry of High-Temperature Borates.

In recent years borate-based crystals has attracted substantial interest among the research community. The overall importance of this family of materials is reflected in miscellaneous articles and several reviews that have been published over the years. Crystalline borate materials exhibit numerous interesting physical properties, which make them promising for further practical applications.