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

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

Item does not contain fulltex

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