Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

<p>Abstract</p> <p>Background</p> <p>Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2). The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade.</p> <p>Methods</p> <p>Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV) was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF₂α production. Proliferation assays were also performed in presence of different prostaglandins (PGs).</p> <p>Results</p> <p>Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor <it>in vivo </it>in skeletal muscle cells and in satellite cells and <it>in vitro </it>in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-^12,14-prostaglandin J₂(15Δ-PGJ₂), a product of COX-2-derived prostaglandin D₂, stimulated myoblast proliferation, but not PGE₂and PGF₂α.</p> <p>Conclusions</p> <p>Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.</p

teleVISE: Mobile elektronische Unterstützung für den tutoriell begleiteten Übungsbetrieb im Fach Mathematik

Die Ausbildung im Fach Mathematik stellt in vielen ingenieurtechnischen Fachrichtungen, speziell an Fachhochschulen, eine permanente Herausforderung dar. Vorkenntnisse, Motivation und Leistungen der Studierenden weisen ein breites Spektrum auf. Zur Vermittlung praxisrelevanter Mathematikkenntnisse auf hohem Niveau erweist sich Frontalunterricht alleine in der Regel als nicht ausreichend. Ziel des Projekts teleVISE ist es, eine inhaltlich-technisch-organisatorische Infrastruktur zur Intensivierung des veranstaltungsbegleitenden Übungsbetriebs im Fach Mathematik an der Hochschule Bremen aufzubauen, deren technische Unterstützung aus einer speziellen internetbasierten Lehr- und Lernumgebung besteht

Zn2+ ions inhibit gene transcription following stimulation of the Ca2+ channels Cav1.2 and TRPM3

Abstract Zinc, a trace element, is necessary for the correct structure and function of many proteins. Therefore, Zn2+ has to be taken up by the cells, using specific Zn2+ transporters or Ca2+ channels. In this study, we have focused on two Ca2+ channels, the L-type voltage-gated Cav1.2 channel and the transient receptor potential channel TRPM3. Stimulation of either channel induces an intracellular signaling cascade leading to the activation of the transcription factor AP-1. The influx of Ca2+ ions into the cytoplasm is essential for this activity. We asked whether extracellular Zn2+ ions affect Cav1.2 or TRPM3-induced gene transcription following stimulation of the channels. The results show that extracellular Zn2+ ions reduced the activation of AP-1 by more than 80% following stimulation of either voltage-gated Cav1.2 channels or TRPM3 channels. Experiments performed with cells maintained in Ca2+-free medium revealed that Zn2+ ions cannot replace Ca2+ ions in inducing gene transcription via stimulation of Cav1.2 and TRPM3 channels. Re-addition of Ca2+ ions to the cell culture medium, however, restored the ability of these Ca2+ channels to induce a signaling cascade leading to the activation of AP-1. Secretory cells, including neurons and pancreatic β-cells, release Zn2+ ions during exocytosis. We propose that the released Zn2+ ions function as a negative feedback loop for stimulus-induced exocytosis by inhibiting Ca2+ channel signaling.</jats:p

Distribution of peroxisome proliferator-activated receptors (PPARs) in human skeletal muscle and adipose tissue: relation to insulin action

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Active Learning of Intuitive Control Knobs for Synthesizers Using Gaussian Processes

Typical synthesizers only provide controls to the low-level parameters of sound-synthesis, such as wave-shapes or filter envelopes. In contrast, composers often want to adjust and express higher-level qualities, such as how ‘scary ’ or ‘steady’ sounds are perceived to be. We develop a system which allows users to directly control abstract, high-level qualities of sounds. To do this, our system learns functions that map from synthesizer control settings to perceived levels of high-level qualities. Given these functions, our system can generate high-level knobs that directly adjust sounds to have more or less of those qualities. We model the functions mapping from control-parameters to the degree of each high-level quality using Gaussian processes, a nonparametric Bayesian model. These models can adjust to the complexity of the function being learned, account for nonlinear interaction between control-parameters, and allow us to characterize the uncertainty about the functions being learned. By tracking uncertainty about the functions being learned, we can use active learning to quickly calibrate the tool, by querying the user about the sounds the system expects to most improve its performance. We show through simulations that this model-based active learning approach learns high-level knobs on certain classes of target concepts faster than several baselines, and give examples of the resulting automaticallyconstructed knobs which adjust levels of non-linear, highlevel concepts

Soziale Diagnostik in der Suchthilfe : eine geschichtliche und theoretische Herleitung

Der Beitrag beschreibt die historische Entwicklung und aktuelle Bedeutung der Sozialdiagnostik innerhalb des Handlungsfeldes der Suchthilfe

TRACKS

We combine the often opposing forces of artistic freedom and mathematical determinism to enrich a given animation or simulation of a surface with physically based detail. We present a process called tracking, which takes as input a rough animation or simulation and enhances it with physically simulated detail. Building on the foundation of constrained Lagrangian mechanics, we propose weak-form constraints for tracking the input motion. This method allows the artist to choose where to add details such as characteristic wrinkles and folds of various thin shell materials and dynamical effects of physical forces. We demonstrate multiple applications ranging from enhancing an artist's animated character to guiding a simulated inanimate object