Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

Growth and X‑ray Diffraction Study and Specific Features of Thermal Expansion of Ba₃NbFe₃Si₂O₁₄ Single Crystal from the Langasite Family

Ba₃NbFe₃Si₂O₁₄ single crystals of promising multiferroic properties from the langasite family have been grown by floating zone melting. The accurate high-resolution X-ray diffraction studies of this crystal were performed on a diffractometer with a two-dimensional CCD detector at 293 and 90.5 K. To compensate systematic measurement errors, two data sets were obtained independently for different sample orientations at each temperature. The structure refinement was performed based on averaged data sets with the following results: space group <i>P</i>321, <i>Z</i> = 1; <i>a</i> = 8.52421(8), <i>c</i> = 5.23372(5) Å at 293 K; and <i>a</i> = 8.5211(2), <i>c</i> = 5.2243(7) Å, at 90.5 K. The <i>R</i> factors of the model structure refinement were found to be <i>R</i>/<i>wR</i> = 1.15/1.29% for 4396 independent reflections at 293 K, and <i>R</i>/<i>wR</i> = 1.13/1.35% for 4203 reflections at 90.5 K. A displacement of magnetic ion Fe³⁺ in the 3<i>f</i> site was found with reducing temperature. It was also established from comparison of the structures of Ba₃NbFe₃Si₂O₁₄ and Ba₃TaFe₃Si₂O₁₄ that the mobility of the cation in the 3<i>f</i> sites changes with an isomorphic substitution of Nb cations by Ta in the octahedral sites. This can change the characteristics of the structure and magnetic helix responsible for multiferroic properties of the iron-containing langasites. An anomaly in thermal expansion is found in the Ba₃NbFe₃Si₂O₁₄ crystal. When the temperature is reduced, the compression ratio along the <i>c</i> axis is about two times larger than that along the <i>a</i> axis, which is not typical of other langasite-family crystals