Tracking Ca2+ Dynamics in NOD Mouse Islets During Spontaneous Diabetes Development.

Unlabelled: The mechanisms accounting for the functional changes of α- and β-cells over the course of type 1 diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female nonobese diabetic (NOD) mice during the development of spontaneous diabetes. We showed that, during the phases of islet inflammation, 8 mmol/L glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at substimulatory 4 and 6 mmol/L glucose.

High-resolution analysis of the cytosolic Ca events in β cell collectives in situ.

The release of peptide hormones is predominantly regulated by a transient increase in cytosolic Ca concentration ([Ca]). To trigger exocytosis, Ca ions enter the cytosol from intracellular Ca stores or from the extracellular space. The molecular events of late stages of exocytosis, and their dependence on [Ca], were extensively described in isolated single cells from various endocrine glands.

Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels.

Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover immediate energy needs by unlocking internal nutrient reserves. The stimulation of α2-adrenergic receptors on the plasma membrane of beta cells reduces their excitability and insulin secretion mostly through diminished cAMP production and downstream desensitization of late step(s) of exocytotic machinery to cytosolic Ca concentration ([Ca]). In most studies unphysiologically high adrenaline concentrations have been used to evaluate the role of adrenergic stimulation in pancreatic endocrine cells.

pH-Dependence of Glucose-Dependent Activity of Beta Cell Networks in Acute Mouse Pancreatic Tissue Slice.

Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function. To explain this effect, a number of mechanisms was proposed involving both extracellular and intracellular targets and pathways. Here, we focus on reassessing the influence of extracellular pH on glucose-dependent beta cell activation and collective activity in physiological conditions.

The microdynamics shaping the relationship between democracy and corruption.

Physics has a long tradition of laying rigorous quantitative foundations for social phenomena. Here, we up the ante for physics' forays into the territory of social sciences by (i) empirically documenting a tipping point in the relationship between democratic norms and corruption suppression, and then (ii) demonstrating how such a tipping point emerges from a micro-scale mechanistic model of spin dynamics in a complex network. Specifically, the tipping point in the relationship between democratic norms and corruption suppression is such that democratization has little effect on suppressing corruption below a critical threshold, but a large effect above the threshold.

Autopoietic Influence Hierarchies in Pancreatic β Cells.

β cells are biologically essential for humans and other vertebrates. Because their functionality arises from cell-cell interactions, they are also a model system for collective organization among cells. There are currently two contradictory pictures of this organization: the hub-cell idea pointing at leaders who coordinate the others, and the electrophysiological theory describing all cells as equal.

β Cells Operate Collectively to Help Maintain Glucose Homeostasis.

Residing in the islets of Langerhans in the pancreas, β cells contribute to glucose homeostasis by managing the body's insulin supply. Although it has been acknowledged that healthy β cells engage in heavy cell-to-cell communication to perform their homeostatic function, the exact role and effects of such communication remain partly understood. We offer a novel, to our knowledge, perspective on the subject in the form of 1) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and 2) empirical data analysis that reveals a qualitative shift in the cross-correlation structure of measured signals below and above the threshold glucose concentration.

Corrigendum: Random Matrix Analysis of Ca Signals in β-Cell Collectives.

[This corrects the article DOI: 10.3389/fphys.2019.

Random Matrix Analysis of Ca Signals in β-Cell Collectives.

Even within small organs like pancreatic islets, different endocrine cell types and subtypes form a heterogeneous collective to sense the chemical composition of the extracellular solution and compute an adequate hormonal output. Erroneous cellular processing and hormonal output due to challenged heterogeneity result in various disorders with diabetes mellitus as a flagship metabolic disease. Here we attempt to address the aforementioned functional heterogeneity with comparing pairwise cell-cell cross-correlations obtained from simultaneous measurements of cytosolic calcium responses in hundreds of islet cells in an optical plane to statistical properties of correlations predicted by the random matrix theory (RMT).

Collective Behavior of Social Bots Is Encoded in Their Temporal Twitter Activity.

Computational propaganda deploys social or political bots to try to shape, steer, and manipulate online public discussions and influence decisions. Collective behavior of populations of social bots has not been yet widely studied, although understanding of collective patterns arising from interactions between bots would aid social bot detection. In this study, we show that there are significant differences in collective behavior between population of bots and population of humans as detected from their Twitter activity.

Collective Sensing of β-Cells Generates the Metabolic Code.

Major part of a pancreatic islet is composed of β-cells that secrete insulin, a key hormone regulating influx of nutrients into all cells in a vertebrate organism to support nutrition, housekeeping or energy storage. β-cells constantly communicate with each other using both direct, short-range interactions through gap junctions, and paracrine long-range signaling. However, how these cell interactions shape collective sensing and cell behavior in islets that leads to insulin release is unknown.

Functional connectivity in islets of Langerhans from mouse pancreas tissue slices.

We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets.

Optimal network configuration for maximal coherence resonance in excitable systems.

We analyze the coherence resonance phenomenon in an ensemble of noise-driven excitable neurons giving special attention to the role of the interaction topology. The neural architecture is modeled using a spatially embedded network in which we can tune the network organization between scale-free-like with dominating long-range connections and a network with mostly adjacent neurons connected. We found that besides an optimal noise intensity, also an optimal network configuration exists at which the largest average coherence of noise-induced spikes is achieved.

Fractional calculus applied to the analysis of spectral electrical conductivity of clay-water system.

The analysis of the low-frequency conductivity spectra of the clay-water mixtures is presented. The frequency dependence of the conductivity is shown to follow the power-law with the exponent n=0.67 before reaching the frequency-independent part.