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2 results

  • Chapter 6 - Intracellular Mechanisms

  • David Sterratt, University of Edinburgh, Bruce Graham, University of Stirling, Andrew Gillies, Psymetrix Limited, Gaute Einevoll, Norwegian University of Life Sciences (NMBU), David Willshaw, University of Edinburgh
  • Book:
    Principles of Computational Modelling in Neuroscience
    Published online:
    07 October 2023
    Print publication:
    05 October 2023, pp 145-184

  • Summary

    Intracellular molecular signalling plays a crucial role in modulating ion channel dynamics, synaptic plasticity and, ultimately, the behaviour of the whole cell. In this chapter, we investigate ways of modelling intracellular signalling systems. We focus on calcium, as it plays an extensive role in many cell functions. Included are models of intracellular buffering systems, ionic pumps and calcium-dependent processes. This leads us to outline other intracellular signalling pathways involving more complex enzymatic reactions and cascades. We introduce the well-mixed approach to modelling these pathways and explore its limitations. Rule-based modelling can be used when full specification of a signalling network is infeasible. When small numbers of molecules are involved, stochastic approaches are necessary and we consider both population-based and particle-based methods for stochastic modelling. Movement of molecules through diffusion must be considered in spatially inhomogeneous systems.

  • An agent-based model of exposure to human toxocariasis: a multi-country validation

  • K. KANOBANA, B. DEVLEESSCHAUWER, K. POLMAN, N. SPEYBROECK
  • Journal:
    Parasitology / Volume 140 / Issue 8 / July 2013
    Published online by Cambridge University Press:
    10 April 2013, pp. 986-998

  • Seroprevalence data illustrate that human exposure to Toxocara is frequent. Environmental contamination with Toxocara spp. eggs is assumed to be the best indicator of human exposure, but increased risk of exposure has also been associated with many other factors. Reported associations are inconsistent, however, and there is still ambiguity regarding the factors driving the onset of Toxocara antibody positivity. The objective of this work was to assess the validity of our current conceptual understanding of the key processes driving human exposure to Toxocara. We constructed an agent-based model predicting Toxocara antibody positivity (as a measure of exposure) in children. Exposure was assumed to depend on the joint probability of 3 parameters: (1) environmental contamination with Toxocara spp. eggs, (2) larvation of these eggs and (3) the age-related contact with these eggs. This joint probability was linked to processes of acquired humoral immunity, influencing the rate of antibody seroreversion. The results of the simulation were validated against published data from 5 different geographical settings. Using simple rules and a stochastic approach with parameter estimates derived from the respective contexts, plausible serological patterns emerged from the model in nearly all settings. Our approach leads to novel insights in the transmission dynamics of Toxocara.