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Intercellular Ca2+ waves in astrocytes are thought to serve as a pathway of long-range signaling. The waves can propagate by the diffusion of molecules through gap junctions and across the extracellular space. In rat striatal astrocytes, the gap-junctional route was shown to be dominant. To analyze the interplay of the processes involved in wave(More)
T cell antigen receptor (TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck. Here we showed that catalytically active Lck was present in unstimulated naive T cells and thymocytes and was readily detectable in these cells in lymphoid organs. In naive T cells up to approximately 40% of total Lck(More)
Hepatocytes respond with repetitive cytosolic calcium spikes to stimulation by vasopressin and noradrenalin. In the intact liver, calcium oscillations occur in a synchronized fashion as periodic waves across whole liver lobules, but the mechanism of intercellular coupling remains unclear. Recently, it has been shown that individual hepatocytes can have very(More)
This review provides a comparative overview of recent developments in the modelling of cellular calcium oscillations. A large variety of mathematical models have been developed for this wide-spread phenomenon in intra- and intercellular signalling. From these, a general model is extracted that involves six types of concentration variables: inositol(More)
During the past 20 years the EU legislation for the notification of chemicals has focussed on new chemicals and at the same time failed to cover the evaluation of existing chemicals in Europe. Therefore, in a new EU chemicals policy (REACH, Registration, Evaluation and Authorization of Chemicals) the European Commission proposes to evaluate 30,000 chemicals(More)
Intercellular regenerative calcium waves in systems such as the liver and the blowfly salivary gland have been hypothesized to spread through calcium-induced calcium release (CICR) and gap-junctional calcium diffusion. A simple mathematical model of this mechanism is developed. It includes CICR and calcium removal from the cytoplasm, cytoplasmic and(More)
Hormones that act through the calcium-releasing messenger, inositol 1,4,5-trisphosphate (IP3), cause intracellular calcium oscillations, which have been ascribed to calcium feedbacks on the IP3 receptor. Recent studies have shown that IP3 levels oscillate together with the cytoplasmic calcium concentration. To investigate the functional significance of this(More)
Cytokines are pleiotropic and readily diffusible messenger molecules, raising the question of how their action can be confined to specific target cells. The T cell cytokine interleukin-2 (IL-2) is essential for the homeostasis of regulatory T (Treg) cells that suppress (auto)immunity and stimulates immune responses mediated by conventional T cells. We(More)
The white-collar complex (WCC), the core transcription factor of the circadian clock of Neurospora, activates morning-specific expression of the transcription repressor CSP1. Newly synthesized CSP1 exists in a transient complex with the corepressor RCM1/RCO1 and the ubiquitin ligase UBR1. CSP1 is rapidly hyperphosphorylated and degraded via UBR1 and its(More)
NFAT transcription factors are activated through dephosphorylation by the phosphatase calcineurin. Experimental data show that 13 conserved phosphorylation sites conspire to control the transition between an inactive and an active conformation. We propose a quantitative model of the underlying molecular mechanisms that may generally apply to highly(More)