Biomedical subjects

Alejandra C Ventura

Publications and source records attributed to Alejandra C Ventura.

5 recordsLinked to original sources

PubMed2025

The advantage of periodic over constant signalling in microRNA-mediated regulation.

Cells may exploit oscillatory gene expression to encode biological information. Temporal features of oscillations, such as pulse frequency and amplitude, are determinant for the outcome of signalling pathways. However, little effort has been devoted to unveiling the role of pulsatility in the context of post-transcriptional gene regulation, where microRNAs act by binding to RNAs and regulate their expression. Here, we study the effects of periodic against constant microRNA synthesis within minimal microRNA-target networks. We find that there is a repressive advantage of pulsatile over constant microRNA synthesis, and that the extent of repression depends on the frequency of pulses, thus uncovering frequency preference behaviours. We show that the preference for specific input frequencies is determined by relative microRNA and target kinetic rates and can lead to exclusive frequency-dependent repression on distinct RNA species, thereby highlighting a potential mechanism of selective dynamical target regulation. Moreover, we show that frequencies observed in periodically expressed microRNAs, such as those involved in circadian rhythms and development, can be selectively favored. Our findings might have implications for experimental studies aimed at understanding how periodic patterns drive biological responses through microRNA-mediated signalling and provide suggestions for validation in synthetic networks.

MicroRNAs↗

PubMed2006

Simple data-driven models of intracellular calcium dynamics with predictive power.

Biology is complex. However, it is not clear how much of this complexity must necessarily translate into complicated mathematical models of biological processes. Simple models can be appealing to physicists but are usually deceiving for biologists. Complicated models, on the other hand, depend on too many parameters whose values are frequently unknown. Therefore, complicated models, although in principle more realistic, can lead to erroneous results if they are sensitive to these unknown parameter values. Intracellular calcium signals provide an example of utmost biological importance in which the issue of "simple vs complex" can be explored. In this paper we show that simple models describing the dynamics of intracellular calcium can be directly inferred from experimental data, without no a priori information on unknown parameters. A similar approach can be followed to study other reaction-diffusion systems. In spite of their simplicity, these models can provide quantitative information on some of the processes that shape calcium signals, such as the calcium current that underlies an experimental observation. This shows that simple models of biological systems are not limited to qualitative descriptions.

Animals↗

PubMed2006

Calcium oscillations and waves generated by multiple release mechanisms in pancreatic acinar cells.

We explore the dynamic behavior of a model of calcium oscillations and wave propagation in the basal region of pancreatic acinar cells [Sneyd, J., et al., Biophys. J. 85: 1392-1405, 2003]. Since it is known that two principal calcium release pathways are involved, inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR), we study how the model behavior depends on the density of each receptor type. Calcium oscillations can be mediated either by IPR or RyR. Continuous increases in either RyR or IPR density can lead to the appearance and disappearance of oscillations multiple times, and the two receptor types interact via their common effect on cytoplasmic calcium concentration and the subsequent effect on the total amount of calcium inside the cell. Increases in agonist concentration can stimulate oscillations via the RyR by increasing calcium influx. Using a two time-scale approach, we explain these complex behaviors by treating the total amount of cellular calcium as a slow parameter. Oscillations are controlled by the shape of the slow manifold and where it intersects the nullcline of the slow variable. When calcium diffusion is included, the existence of traveling waves in the model equation is strongly dependent on the interplay between the total amount of calcium in the cell and membrane transport, a feature that can be experimentally tested. Our results help us understand the behavior of a model that includes both receptors in comparison to the properties of each receptor type in isolation.

Calcium Signaling↗

PubMed2005

A model-independent algorithm to derive Ca2+ fluxes underlying local cytosolic Ca2+ transients.

Local intracellular Ca(2+) signals result from Ca(2+) flux into the cytosol through individual channels or clusters of channels. To gain a mechanistic understanding of these events we need to know the magnitude and spatial distribution of the underlying Ca(2+) flux. However, this is difficult to infer from fluorescence Ca(2+) images because the distribution of Ca(2+)-bound dye is affected by poorly characterized processes including diffusion of Ca(2+) ions, their binding to mobile and immobile buffers, and sequestration by Ca(2+) pumps. Several methods have previously been proposed to derive Ca(2+) flux from fluorescence images, but all require explicit knowledge or assumptions regarding these processes. We now present a novel algorithm that requires few assumptions and is largely model-independent. By testing the algorithm with both numerically generated image data and experimental images of sparklets resulting from Ca(2+) flux through individual voltage-gated channels, we show that it satisfactorily reconstructs the magnitude and time course of the underlying Ca(2+) currents.

Algorithms↗

PubMed2003

Saltatory and continuous calcium waves and the rapid buffering approximation.

Calcium waves propagate inside cells due to a regenerative mechanism known as calcium-induced calcium release. Buffer-mediated calcium diffusion in the cytosol plays a crucial role in the process. However, most models of calcium waves either treat buffers phenomenologically or assume that they are in equilibrium with calcium (the rapid buffering approximation). In this article we address the issue of whether this approximation provides a good description of wave propagation. We first compare the timescales present in the problem, and determine the situations in which the equilibrium hypothesis fails. We then present a series of numerical studies based on the simple fire-diffuse-fire model of wave propagation. We find that the differences between the full and reduced descriptions may lead to errors that are above experimental resolution even for relatively fast buffers in the case of saltatory waves. Conversely, in the case of continuous waves, the approximation may give accurate results even for relatively slow buffers.

Biophysics↗