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A Model of [Formula: see text] Dynamics in an Accurate Reconstruction of Parotid Acinar Cells.

ABSTRACT: We have constructed a spatiotemporal model of [Formula: see text] dynamics in parotid acinar cells, based on new data about the distribution of inositol trisphophate receptors (IPR). The model is solved numerically on a mesh reconstructed from images of a cluster of parotid acinar cells. In contrast to our earlier model (Sneyd et al. in J Theor Biol 419:383-393. https://doi.org/10.1016/j.jtbi.2016.04.030 , 2017b), which cannot generate realistic [Formula: see text] oscillations with the new data on IPR distribution, our new model reproduces the [Formula: see text] dynamics observed in parotid acinar cells. This model is then coupled with a fluid secretion model described in detail in a companion paper: A mathematical model of fluid transport in an accurate reconstruction of a parotid acinar cell (Vera-Sigüenza et al. in Bull Math Biol. https://doi.org/10.1007/s11538-018-0534-z , 2018b). Based on the new measurements of IPR distribution, we show that Class I models (where [Formula: see text] oscillations can occur at constant [[Formula: see text]]) can produce [Formula: see text] oscillations in parotid acinar cells, whereas Class II models (where [[Formula: see text]] needs to oscillate in order to produce [Formula: see text] oscillations) are unlikely to do so. In addition, we demonstrate that coupling fluid flow secretion with the [Formula: see text] signalling model changes the dynamics of the [Formula: see text] oscillations significantly, which indicates that [Formula: see text] dynamics and fluid flow cannot be accurately modelled independently. Further, we determine that an active propagation mechanism based on calcium-induced calcium release channels is needed to propagate the [Formula: see text] wave from the apical region to the basal region of the acinar cell.

SUBMITTER: Pages N

PROVIDER: S-EPMC6449190 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A Model of [Formula: see text] Dynamics in an Accurate Reconstruction of Parotid Acinar Cells.

Pages Nathan N Vera-Sigüenza Elías E Rugis John J Kirk Vivien V Yule David I DI Sneyd James J

Bulletin of mathematical biology 20190114 5

We have constructed a spatiotemporal model of [Formula: see text] dynamics in parotid acinar cells, based on new data about the distribution of inositol trisphophate receptors (IPR). The model is solved numerically on a mesh reconstructed from images of a cluster of parotid acinar cells. In contrast to our earlier model (Sneyd et al. in J Theor Biol 419:383-393. https://doi.org/10.1016/j.jtbi.2016.04.030 , 2017b), which cannot generate realistic [Formula: see text] oscillations with the new data ...[more]

PMID: 30644065

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Project description:Salivary gland acinar cells use the calcium ([Formula: see text]) ion as a signalling messenger to regulate a diverse range of intracellular processes, including the secretion of primary saliva. Although the underlying mechanisms responsible for saliva secretion are reasonably well understood, the precise role played by spatially heterogeneous intracellular [Formula: see text] signalling in these cells remains uncertain. In this study, we use a mathematical model, based on new and unpublished experimental data from parotid acinar cells (measured in excised lobules of mouse parotid gland), to investigate how the structure of the cell and the spatio-temporal properties of [Formula: see text] signalling influence the production of primary saliva. We combine a new [Formula: see text] signalling model [described in detail in a companion paper: Pages et al. in Bull Math Biol 2018, submitted] with an existing secretion model (Vera-Sigüenza et al. in Bull Math Biol 80:255-282, 2018. https://doi.org/10.1007/s11538-017-0370-6 ) and solve the resultant model in an anatomically accurate three-dimensional cell. Our study yields three principal results. Firstly, we show that spatial heterogeneities of [Formula: see text] concentration in either the apical or basal regions of the cell have no significant effect on the rate of primary saliva secretion. Secondly, in agreement with previous work (Palk et al., in J Theor Biol 305:45-53, 2012. https://doi.org/10.1016/j.jtbi.2012.04.009 ) we show that the frequency of [Formula: see text] oscillation has no significant effect on the rate of primary saliva secretion, which is determined almost entirely by the mean (over time) of the apical and basal [Formula: see text]. Thirdly, it is possible to model the rate of primary saliva secretion as a quasi-steady-state function of the cytosolic [Formula: see text] averaged over the entire cell when modelling the flow rate is the only interest, thus ignoring all the dynamic complexity not only of the fluid secretion mechanism but also of the intracellular heterogeneity of [Formula: see text]. Taken together, our results demonstrate that an accurate multiscale model of primary saliva secretion from a single acinar cell can be constructed by ignoring the vast majority of the spatial and temporal complexity of the underlying mechanisms.

Project description:The experimental value for the isospin amplitude [Formula: see text] in [Formula: see text] decays has been successfully explained within the standard model (SM), both within the large [Formula: see text] approach to QCD and by QCD lattice calculations. On the other hand within the large [Formula: see text] approach the value of [Formula: see text] is by at least [Formula: see text] below the data. While this deficit could be the result of theoretical uncertainties in this approach and could be removed by future precise QCD lattice calculations, it cannot be excluded that the missing piece in [Formula: see text] comes from new physics (NP). We demonstrate that this deficit can be significantly softened by tree-level FCNC transitions mediated by a heavy colourless [Formula: see text] gauge boson with a flavour-violating left-handed coupling [Formula: see text] and an approximately universal flavour diagonal right-handed coupling [Formula: see text] to the quarks. The approximate flavour universality of the latter coupling assures negligible NP contributions to [Formula: see text]. This property, together with the breakdown of the GIM mechanisms at tree level, allows one to enhance significantly the contribution of the leading QCD-penguin operator [Formula: see text] to [Formula: see text]. A large fraction of the missing piece in the [Formula: see text] rule can be explained in this manner for [Formula: see text] in the reach of the LHC, while satisfying the constraints from [Formula: see text], [Formula: see text], [Formula: see text], LEP-II and the LHC. The presence of a small right-handed flavour-violating coupling [Formula: see text] and of enhanced matrix elements of [Formula: see text] left-right operators allows one to satisfy simultaneously the constraints from [Formula: see text] and [Formula: see text], although this requires some fine-tuning. We identify the quartic correlation between [Formula: see text] contributions to [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]. The tests of this proposal will require much improved evaluations of [Formula: see text] and [Formula: see text] within the SM, of [Formula: see text] as well as precise tree-level determinations of [Formula: see text] and [Formula: see text]. We present correlations between [Formula: see text], [Formula: see text] and [Formula: see text] with and without the [Formula: see text] rule constraint and generalise the whole analysis to [Formula: see text] with colour ([Formula: see text]) and [Formula: see text] with FCNC couplings. In the latter case no improvement on [Formula: see text] can be achieved without destroying the agreement of the SM with the data on [Formula: see text]. Moreover, this scenario is very tightly constrained by [Formula: see text]. On the other hand, in the context of the [Formula: see text] rule [Formula: see text] is even more effective than [Formula: see text]: it provides the missing piece in [Formula: see text] for [Formula: see text]-[Formula: see text].

Project description:The Josephson effect in point contacts between an "ordinary" superconductor [Formula: see text]In[Formula: see text] ([Formula: see text]) and single crystals of the Fe-based superconductor Ba[Formula: see text]K[Formula: see text](FeAs)[Formula: see text] ([Formula: see text]), was investigated. In order to shed light on the order parameter symmetry of Ba[Formula: see text]K[Formula: see text](FeAs)[Formula: see text], the dependence of the Josephson supercurrent [Formula: see text] on the temperature and on [Formula: see text] with [Formula: see text] was studied. The dependencies of the critical current on temperature [Formula: see text] and of the amplitudes of the first current steps of the current-voltage characteristic [Formula: see text] [Formula: see text] on the power of microwave radiation with frequency [Formula: see text] were measured. It is shown that the dependencies [Formula: see text] are close to the well-known Ambegaokar-Baratoff (AB) dependence for tunnel contacts between "ordinary" superconductors and to the dependence calculated by Burmistrova et al. (Phys Rev B 91, 214501 (2015)) for microshorts between an "ordinary" superconductor and a two-band superconductor with [Formula: see text] order parameter symmetry at certain values of the transparency of boundaries and thickness of the transition layer. It is found that the dependencies [Formula: see text] cannot be approximated within the resistively shunted model using the normalized microwave frequencies [Formula: see text] with characteristic voltages [Formula: see text], [Formula: see text]-normal resistance of the contact) found from the low-voltage parts of the current-voltage characteristics. The reasons for this failure are discussed and a method is proposed for accurately determining the value of [Formula: see text], which takes into account all the features of the point contact affecting the period of the dependence [Formula: see text]. An analysis of the [Formula: see text] and [Formula: see text] dependencies shows that the superconducting current of the Josephson contacts under investigation is proportional to the [Formula: see text] of the phase difference [Formula: see text], [Formula: see text]. The implications of these results on the symmetry of the order parameter are also discussed.

Dataset Information

A Model of [Formula: see text] Dynamics in an Accurate Reconstruction of Parotid Acinar Cells.

Publications

A Model of [Formula: see text] Dynamics in an Accurate Reconstruction of Parotid Acinar Cells.

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