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17 results on '"Sneyd, James"'

1. Understanding broad-spike oscillations in a model of intracellular calcium dynamics

Author

Rahmani, Behnaz, Jelbart, Samuel, Kirk, Vivien, and Sneyd, James

Subjects
Mathematics - Dynamical Systems, 34C15, 34C26, 34E15, 37N25
Abstract

Oscillations of free intracellular calcium concentration are thought to be important in the control of a wide variety of physiological phenomena, and there is long-standing interest in understanding these oscillations via the investigation of suitable mathematical models. Many of these models have the feature that different variables or terms in the model evolve on very different time-scales, which often results in the accompanying oscillations being temporally complex. Cloete et al [5] constructed an ordinary differential equation model of calcium oscillations in hepatocytes in an attempt to understand the origin of two distinct types of oscillation observed in experiments: narrow-spike oscillations in which rapid spikes of calcium concentration alternate with relatively long periods of quiescence, and broad-spike oscillations in which there is a fast rise in calcium levels followed by a slower decline then a period of quiescence. These two types of oscillation can be observed in the model if a single system parameter is varied but the mathematical mechanisms underlying the different types of oscillations were not explored in detail in [5]. We use ideas from geometric singular perturbation theory to investigate the origin of broad-spike solutions in this model. We find that the analysis is intractable in the full model, but are able to uncover structure in particular singular limits of a related model that point to the origin of the broad-spike solutions.

Published
2024

2. A Ca$^{2+}$ puff model based on integrodifferential equations

Author

Hawker, Molly, Cao, Pengxing, Sneyd, James, and Siekmann, Ivo

Subjects
Quantitative Biology - Quantitative Methods
Abstract

The calcium (Ca$^{2+}$) signalling system is important for many cellular processes within the human body. Signals are transmitted within the cell by releasing Ca$^{2+}$ from the endoplasmic reticulum (ER) into the cytosol via clusters of Ca$^{2+}$ channels. Mathematical models of Ca$^{2+}$ release via inositol 1,4,5-trisphosphate receptors (IP$_{3}$R) help with understanding underlying Ca$^{2+}$ dynamics but data-driven modelling of stochastic Ca$^{2+}$ release events, known as Ca$^{2+}$ puffs, is a difficult challenge. Parameterising Markov models for representing the IP$_{3}$R with steady-state single channel data obtained at fixed combinations of the ligands Ca$^{2+}$ and inositol-trisphosphate (IP$_{3}$) has previously been demonstrated to be insufficient. However, by extending an IP$_{3}$R model based on steady-state data with an integral term that incorporates the delayed response of the channel to varying Ca$^{2+}$ concentrations we succeed in generating realistic Ca$^{2+}$ puffs. By interpreting the integral term as a weighted average of Ca$^{2+}$ concentrations that extend over a time interval of length $\tau$ into the past we conclude that the IP$_{3}$R requires a certain amount of memory of past ligand concentrations., Comment: 31 pages, 8 figures, 1 table

Published
2024

7. Calcium oscillations in HEK293 cells lacking SOCE suggest the existence of a balanced regulation of IP3 production and degradation.

Author

Octors, Clara, Yoast, Ryan E., Emrich, Scott M., Trebak, Mohamed, and Sneyd, James

Subjects
OSCILLATIONS, CALCIUM, CELL membranes, TIME series analysis, INOSITOL
Abstract

The concentration of free cytosolic Ca2+ is a critical second messenger in almost every cell type, with the signal often being carried by the period of oscillations, or spikes, in the cytosolic Ca2+ concentration. We have previously studied how Ca2+ influx across the plasma membrane affects the period and shape of Ca2+ oscillations in HEK293 cells. However, our theoretical work was unable to explain how the shape of Ca2+ oscillations could change qualitatively, from thin spikes to broad oscillations, during the course of a single time series. Such qualitative changes in oscillation shape are a common feature of HEK293 cells in which STIM1 and 2 have been knocked out. Here, we present an extended version of our earlier model that suggests that such time-dependent qualitative changes in oscillation shape might be the result of balanced positive and negative feedback from Ca2+ to the production and degradation of inositol trisphosphate. [ABSTRACT FROM AUTHOR]

Published
2024
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8. A Non-exhaustive List of Some Open Questions

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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9. Models Without Reset: Hawkes Processes

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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10. Mean Field Limits and Short-Term Synaptic Facilitation in Continuous Time Models

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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11. What Is a Stationary State in a Potentially Infinite System?

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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12. Statistical Estimation of the Interaction Graph

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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13. A Discrete Time Stochastic Neural Network Model

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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14. But Time is Continuous!

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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15. Mean Field Limits for Discrete Time Stochastic Neural Network Models

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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16. A Neurophysiology Primer for Mathematicians

Author

Galves, Antonio, Löcherbach, Eva, Pouzat, Christophe, Mori, Yoichiro, Editor-in-Chief, Perthame, Benoît, Editor-in-Chief, Stevens, Angela, Editor-in-Chief, Burger, Martin, Series Editor, Chacron, Maurice, Series Editor, Diekmann, Odo, Series Editor, Layton, Anita, Series Editor, Lei, Jinzhi, Series Editor, Lewis, Mark, Series Editor, Mahadevan, L., Series Editor, Méléard, Sylvie, Series Editor, Neuhauser, Claudia, Series Editor, Othmer, Hans G., Series Editor, Peletier, Mark, Series Editor, Perelson, Alan, Series Editor, Peskin, Charles S., Series Editor, Preziosi, Luigi, Series Editor, Rubin, Jonathan E., Series Editor, Santillán Zerón, Moisés, Series Editor, Schütte, Christof, Series Editor, Sneyd, James, Series Editor, Swain, Peter, Series Editor, Tyran-Kamińska, Marta, Series Editor, Wu, Jianhong, Series Editor, Galves, Antonio, Löcherbach, Eva, and Pouzat, Christophe

Published
2024
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17. A mathematical model of ENaC and Slc26a6 regulation by CFTR in salivary gland ducts.

Author

Su S, Wahl A, Rugis J, Suresh V, Yule DI, and Sneyd J

Subjects
Mice, Animals, Cell Membrane metabolism, Epithelial Sodium Channels genetics, Epithelial Sodium Channels metabolism, Sodium metabolism, Models, Theoretical, Sulfate Transporters genetics, Sulfate Transporters metabolism, Antiporters genetics, Antiporters metabolism, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Cystic Fibrosis genetics, Cystic Fibrosis metabolism
Abstract

Cystic fibrosis (CF) is a genetic disease caused by the mutations of cystic fibrosis transmembrane conductance regulator ( CFTR ), the cystic fibrosis transmembrane conductance regulator gene. Cftr is a critical ion channel expressed in the apical membrane of mouse salivary gland striated duct cells. Although Cftr is primarily a Cl - channel, its knockout leads to higher salivary Cl - and Na + concentrations and lower pH. Mouse experiments show that the activation of Cftr upregulates epithelial Na + channel (ENaC) protein expression level and Slc26a6 (a 1Cl - :2[Formula: see text] exchanger of the solute carrier family) activity. Experimentally, it is difficult to predict how much the coregulation effects of CFTR contribute to the abnormal Na + , Cl - , and [Formula: see text] concentrations and pH in CF saliva. To address this question, we construct a wild-type mouse salivary gland model and simulate CFTR knockout by altering the expression levels of CFTR, ENaC, and Slc26a6. By reproducing the in vivo and ex vivo final saliva measurements from wild-type and CFTR knockout animals, we obtain computational evidence that ENaC and Slc26a6 activities are downregulated in CFTR knockout in salivary glands. NEW & NOTEWORTHY This paper describes a salivary gland mathematical model simulating the ion exchange between saliva and the salivary gland duct epithelium. The novelty lies in the implementation of CFTR regulating ENaC and Slc26a6 in a CFTR knockout gland. By reproducing the experimental saliva measurements in wild-type and CFTR knockout glands, the model shows that CFTR regulates ENaC and Slc26a6 anion exchanger in salivary glands. The method could be used to understand the various cystic fibrosis phenotypes.

Published
2024
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