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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)
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)
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)
The expression of interleukin-2 (IL-2) is a key event in T helper (Th) lymphocyte activation, controlling both, the expansion and differentiation of effector Th cells as well as the activation of regulatory T cells. We demonstrate that the strength of TCR stimulation is translated into the frequency of memory Th cells expressing IL-2 but not into the amount(More)
Coordinated programs of gene expression during cell differentiation can be controlled by master transcription factors. The differentiation of helper T (Th) lymphocytes during the immune response has been shown to occur along alternative pathways designated as Th1 and Th2. Induction of the Th1 and Th2 pathways is associated with the conversely regulated(More)
Experimental studies have demonstrated that Ca(2+)-regulated proteins are sensitive to the frequency of Ca(2+) oscillations, and several mathematical models for specific proteins have provided insight into the mechanisms involved. Because of the large number of Ca(2+)-regulated proteins in signal transduction, metabolism and gene expression, it is desirable(More)
Eukaryotic genomes are duplicated from multiple replication origins exactly once per cell cycle. In Saccharomyces cerevisiae, a complex molecular network has been identified that governs the assembly of the replication machinery. Here we develop a mathematical model that links the dynamics of this network to its performance in terms of rate and coherence of(More)
The light response in Neurospora is mediated by the photoreceptor and circadian transcription factor White Collar Complex (WCC). The expression rate of the WCC target genes adapts in daylight and remains refractory to moonlight, despite the extraordinary light sensitivity of the WCC. To explain this photoadaptation, feedback inhibition by the WCC(More)