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   A Statistical View on Calcium Oscillations.; ; Skupin, Alexander  et alin Advances in experimental medicine and biology (2020), 1131 Transient rises and falls of the intracellular calcium concentration have been observed in numerous cell types and under a plethora of conditions. There is now a growing body of evidence that these whole ... [more ▼] Transient rises and falls of the intracellular calcium concentration have been observed in numerous cell types and under a plethora of conditions. There is now a growing body of evidence that these whole-cell calcium oscillations are stochastic, which poses a significant challenge for modelling. In this review, we take a closer look at recently developed statistical approaches to calcium oscillations. These models describe the timing of whole-cell calcium spikes, yet their parametrisations reflect subcellular processes. We show how non-stationary calcium spike sequences, which e.g. occur during slow depletion of intracellular calcium stores or in the presence of time-dependent stimulation, can be analysed with the help of so-called intensity functions. By utilising Bayesian concepts, we demonstrate how values of key parameters of the statistical model can be inferred from single cell calcium spike sequences and illustrate what information whole-cell statistical models can provide about the subcellular mechanistic processes that drive calcium oscillations. In particular, we find that the interspike interval distribution of HEK293 cells under constant stimulation is captured by a Gamma distribution. [less ▲] Detailed reference viewed: 389 (3 UL)Calcium signaling: from single channels to pathwaysSkupin, Alexander ; in Advances in Experimental Medicine and Biology (2012), 740 Ca(2+) is not only one of the most versatile and ubiquitous second messengers but also a well-established representative example of cell signaling. The identification of most key elements involved in Ca(2 ... [more ▼] Ca(2+) is not only one of the most versatile and ubiquitous second messengers but also a well-established representative example of cell signaling. The identification of most key elements involved in Ca(2+) signaling enables a mechanistic and quantitative understanding of this particular pathway. Cellular behavior relies in general on the orchestration of molecular behavior leading to reliable cellular responses that allow for regulation and adaptation. Ca(2+) signaling uses a hierarchical organization to transform single molecule behavior into cell wide signals. We have recently shown experimentally that this organization carries single channel signatures onto the whole cell level and renders Ca(2+) oscillations stochastic. Here, we briefly review the co-evolution of experimental and theoretical studies in Ca(2+) -signaling and show how dynamic bottom-up modeling can be used to address -biological questions and illuminate biological principles of cell signaling. [less ▲] Detailed reference viewed: 102 (2 UL)Cytokine-mediated growth inhibition of human melanoma cells; ; et al in Advances in Experimental Medicine and Biology (2001), 495 Detailed reference viewed: 96 (0 UL) |
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