Modulation of transcription factor dynamics allows versatile information transmission.

Cells detect changes in their environment and generate responses, often involving changes in gene expression. In this paper we use information theory and a simple transcription model to analyze whether the resulting gene expression serves to identify extracellular stimuli and assess their intensity when they are encoded in the amplitude, duration or frequency of pulses of a transcription factor's nuclear concentration (or activation state). We find, for all cases, that about three ranges of input strengths can be distinguished and that maximum information transmission occurs for fast and high activation threshold promoters.

Nested pool testing strategy for the diagnosis of infectious diseases.

The progress of the SARS-CoV-2 pandemic requires the design of large-scale, cost-effective testing programs. Pooling samples provides a solution if the tests are sensitive enough. In this regard, the use of the gold standard, RT-qPCR, raises some concerns.

High rates of calcium-free diffusion in the cytosol of living cells.

Calcium (Ca) is a universal second messenger that participates in the regulation of innumerous physiological processes. The way in which local elevations of the cytosolic Ca concentration spread in space and time is key for the versatility of the signals. Ca diffusion in the cytosol is hindered by its interaction with proteins that act as buffers.

Learning Brain Dynamics With Coupled Low-Dimensional Nonlinear Oscillators and Deep Recurrent Networks.

Many natural systems, especially biological ones, exhibit complex multivariate nonlinear dynamical behaviors that can be hard to capture by linear autoregressive models. On the other hand, generic nonlinear models such as deep recurrent neural networks often require large amounts of training data, not always available in domains such as brain imaging; also, they often lack interpretability. Domain knowledge about the types of dynamics typically observed in such systems, such as a certain type of dynamical systems models, could complement purely data-driven techniques by providing a good prior.

Quantification of fluctuations from fluorescence correlation spectroscopy experiments in reaction-diffusion systems.

Fluorescence correlation spectroscopy (FCS) is commonly used to estimate diffusion and reaction rates. In FCS the fluorescence coming from a small volume is recorded and the autocorrelation function (ACF) of the fluorescence fluctuations is computed. Scaling out the fluctuations due to the emission process, this ACF can be related to the ACF of the fluctuations in the number of observed fluorescent molecules.

Changes in Ca Removal Can Mask the Effects of Geometry During IPR Mediated Ca Signals.

Calcium (Ca) signals are ubiquitous. Most intracellular Ca signals involve the release of Ca from the endoplasmic reticulum (ER) through Inositol 1,4,5-Trisphosphate Receptors (IPRs). The non-uniform spatial organization of IPRs and the fact that their individual openings are coupled cytosolic Ca are key factors for the variety of spatio-temporal distributions of the cytosolic [Ca] and the versatility of the signals.

Correction: Fluctuations, Correlations and the Estimation of Concentrations inside Cells.

[This corrects the article DOI: 10.1371/journal.pone.

Fluorescence correlation spectroscopy experiments to quantify free diffusion coefficients in reaction-diffusion systems: The case of Ca^{2+} and its dyes.

Many cell signaling pathways involve the diffusion of messengers that bind and unbind to and from intracellular components. Quantifying their net transport rate under different conditions then requires having separate estimates of their free diffusion coefficient and binding or unbinding rates. In this paper, we show how performing sets of fluorescence correlation spectroscopy (FCS) experiments under different conditions, it is possible to quantify free diffusion coefficients and on and off rates of reaction-diffusion systems.

FCS experiments to quantify Ca diffusion and its interaction with buffers.

Ca signals are ubiquitous. One of the key factors for their versatility is the variety of spatio-temporal distributions that the cytosolic Ca can display. In most cell types Ca signals not only depend on Ca entry from the extracellular medium but also on Ca release from internal stores, a process which is in turn regulated by cytosolic Ca itself.

The effect of reactions on the formation and readout of the gradient of Bicoid.

During early development, the establishment of gradients of transcriptional factors determines the patterning of cell fates. The case of Bicoid (Bcd) in Drosophila melanogaster embryos is well documented and studied. There are still controversies as to whether SDD models in which Bcd is Synthesized at one end, then Diffuses and is Degraded can explain the gradient formation within the timescale observed experimentally.

Sexual pheromone modulates the frequency of cytosolic Ca bursts in .

Transient and highly regulated elevations of cytosolic Ca control a variety of cellular processes. Bulk measurements using radioactive Ca and the luminescent sensor aequorin have shown that in response to pheromone, budding yeast cells undergo a rise of cytosolic Ca that is mediated by two import systems composed of the Mid1-Cch1-Ecm7 protein complex and the Fig1 protein. Although this response has been widely studied, there is no treatment of Ca dynamics at the single-cell level.

Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action.

The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca-liberating second messenger inositol trisphosphate (IP) diffuses with a coefficient (~280 μm s) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP is generally considered a "global" cellular messenger.

Luminal Ca(2+) dynamics during IP3R mediated signals.

The role of cytosolic Ca(2+) on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca(2+) signals has been studied at large both experimentally and by modeling. The role of luminal Ca(2+) has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca(2+) release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca(2+) simultaneously in Xenopus laevis oocytes.

Fluctuations, Correlations and the Estimation of Concentrations inside Cells.

Information transmission in cells occurs quite accurately even when concentration changes are "read" by individual binding sites. In this paper we study ligand number and site occupancy fluctuations when ligands diffuse and react going beyond the analyses that focus on their asymptotic decay. In this way we show that, for immobile binding sites, fluctuations in the number of bound molecules decay on a relatively fast scale before the asymptotic behavior kicks in.

Ca²⁺ images obtained in different experimental conditions shed light on the spatial distribution of IP₃ receptors that underlie Ca²⁺ puffs.

Many intracellular Ca(2+) signals involve Ca(2+) release from the endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors (IP3Rs). The open probability of IP3Rs depends on cytosolic Ca(2+) so that these signals involve Ca(2+)-induced Ca(2+)-release (CICR). IP3Rs are organized in clusters.

How long should a system be observed to obtain reliable concentration estimates from the measurement of fluctuations?

The interior of cells is a highly fluctuating environment. Fluctuations set limits to the accuracy with which endogenous processes can occur. The physical principles that rule these limits also affect the experimental quantification of biophysical parameters in situ.

Messages do diffuse faster than messengers: reconciling disparate estimates of the morphogen bicoid diffusion coefficient.

The gradient of Bicoid (Bcd) is key for the establishment of the anterior-posterior axis in Drosophila embryos. The gradient properties are compatible with the SDD model in which Bcd is synthesized at the anterior pole and then diffuses into the embryo and is degraded with a characteristic time. Within this model, the Bcd diffusion coefficient is critical to set the timescale of gradient formation.

Fluorescence fluctuations and equivalence classes of Ca²⁺ imaging experiments.

Ca²⁺ release into the cytosol through inositol 1,4,5-trisphosphate receptors (IP₃Rs) plays a relevant role in numerous physiological processes. IP₃R-mediated Ca²⁺ signals involve Ca²⁺-induced Ca²⁺-release (CICR) whereby Ca²⁺ release through one open IP₃R induces the opening of other channels. IP₃Rs are apparently organized in clusters.

Buffer regulation of calcium puff sequences.

Puffs are localized Ca(2 +) signals that arise in oocytes in response to inositol 1,4,5-trisphosphate (IP3). They are the result of the liberation of Ca(2 +) from the endoplasmic reticulum through the coordinated opening of IP3 receptor/channels clustered at a functional release site. The presence of buffers that trap Ca(2 +) provides a mechanism that enriches the spatio-temporal dynamics of cytosolic calcium.

From free to effective diffusion coefficients in fluorescence correlation spectroscopy experiments.

Diffusion is one of the main transport processes that occur inside cells determining the spatial and time distribution of relevant action molecules. In most cases these molecules not only diffuse but also interact with others as they get transported. When these interactions occur faster than diffusion the resulting transport can be characterized by "effective diffusion coefficients" that depend on both the reaction rates and the "free" diffusion coefficients.

Intracellular calcium signals display an avalanche-like behavior over multiple lengthscales.

Many natural phenomena display "self-organized criticality" (SOC), (Bak et al., 1987). This refers to spatially extended systems for which patterns of activity characterized by different lengthscales can occur with a probability density that follows a power law with pattern size.

Mean field strategies induce unrealistic non-linearities in calcium puffs.

Mean field models are often useful approximations to biological systems, but sometimes, they can yield misleading results. In this work, we compare mean field approaches with stochastic models of intracellular calcium release. In particular, we concentrate on calcium signals generated by the concerted opening of several clustered channels (calcium puffs).

Custom-made modification of a commercial confocal microscope to photolyze caged compounds using the conventional illumination module and its application to the observation of Inositol 1,4,5-trisphosphate-mediated calcium signals.

The flash photolysis of "caged" compounds is a powerful experimental technique for producing rapid changes in concentrations of bioactive signaling molecules. These caged compounds are inactive and become active when illuminated with ultraviolet light. This paper describes an inexpensive adaptation of an Olympus confocal microscope that uses as source of ultraviolet light the mercury lamp that comes with the microscope for conventional fluorescence microscopy.

Optical techniques provide information on various effective diffusion coefficients in the presence of traps.

In many cell-signaling pathways information is transmitted via the diffusion of messenger molecules. In most cases, messengers react with other substances and diffuse at the same time. Effective diffusion coefficients may be introduced to characterize the net transport rate that results from the combined effect of these two processes.

Stochastic fire-diffuse-fire model with realistic cluster dynamics.

Living organisms use waves that propagate through excitable media to transport information. Ca2+ waves are a paradigmatic example of this type of processes. A large hierarchy of Ca2+ signals that range from localized release events to global waves has been observed in Xenopus laevis oocytes.