Biomedical subjects

Geneviève Dupont

Publications and source records attributed to Geneviève Dupont.

6 recordsLinked to original sources

PubMed2006

Modelling the effect of specific inositol 1,4,5-trisphosphate receptor isoforms on cellular Ca2+ signals.

BACKGROUND INFORMATION: Oscillations of cytosolic Ca2+ are well-known to rely on the regulatory properties of the InsP3R (inositol 1,4,5-trisphosphate receptor). Three isoforms of this channel have been identified. They differ in their regulatory properties by Ca2+ and InsP3. Experiments in different cell types clearly indicate that the relative amounts of each isoform affect the time course of Ca2+ changes after agonist stimulation. In the present study, we investigate whether different steady-state curves for the open probability of the InsP3Rs as a function of Ca2+ imply different dynamical behaviours when these receptors are present in a cellular environment. We therefore describe by a specific phenomenological model the three main types of curves that have been reported: (i) the classical bell-shaped curve, (ii) the bell-shaped curve that is shifted towards higher Ca2+ concentrations when InsP3 is increased, and (iii) a monotonous increasing function of cytosolic Ca2+. RESULTS: We show that, although these types of curves can be ascribed to slight differences in the channel regulation by Ca2+ and InsP3, they can indicate important variations as to the receptor role in cellular Ca2+ control. Thus the receptor associated with the classical bell-shaped curve appears to be the most robust Ca2+ oscillator. If the steady-state curve is supposed to be a monotonous increasing function of cytosolic Ca2+, the modelled receptor cannot sustain Ca2+ oscillations in the absence of Ca2+ exchanges with the extracellular medium. When the bell-shaped curve is shifted towards higher Ca2+ concentrations with increasing InsP3 levels, the model predicts that the receptor is less robust to changes in density; this receptor, however, provides a finer control of the steady-state level of Ca2+ when varying the InsP3 concentration. CONCLUSIONS: Our model allows us to propose an explanation for the experimental observations about the effect of selectively expressing or down-regulating InsP3R isoforms, as well as to make theoretical predictions.

Animals↗

PubMed2006

Did Jean Condorcet (1743-1794) commit suicide?

Condorcet was a famous French mathematician, philosopher and revolutionary. In circumstances that are still unclear, he died in a cell of the Bourg-Egalité prison on 29 March 1794. Most historians of the French Revolution accept suicide as the most likely cause of death but we cannot rule out the possibility that he died of stroke or exhaustion.

Famous Persons↗

PubMed2004

Simulation of calcium waves in ascidian eggs: insights into the origin of the pacemaker sites and the possible nature of the sperm factor.

Fertilization triggers repetitive waves of cytosolic Ca(2+) in the egg of many species. The mechanism involved in the generation of Ca(2+) waves has been studied in much detail in mature ascidian eggs, by raising artificially the level of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] or of its poorly metabolizable analogue, glycero-myo-phosphatidylinositol 4,5-bisphosphate [gPtdIns(4,5)P(2)]. Here, we use this strategy and the experimental results it provides to develop a realistic theoretical model for repetitive Ca(2+) wave generation and propagation in mature eggs. The model takes into account the heterogeneous spatial distribution of the endoplasmic reticulum. Our results corroborate the hypothesis that Ca(2+) wave pacemakers are associated with cortical accumulations of endoplasmic reticulum. The model is first tested and validated by the adequate match between its theoretical predictions and the observed effects of localized injections of massive amounts of Ins(1,4,5)P(3) analogues. In a second step, we use the model to make some propositions about the possible characteristics of the sperm factor. We find that to account for the spatial characteristics of the first series of Ca(2+) waves seen at fertilization in ascidian eggs, it has to be assumed that, if the sperm factor is a phospholipase C, it is Ca(2+)-sensitive and highly diffusible. Although the actual state of knowledge does not allow us to explain the observed relocalization of the Ca(2+) wave pacemaker site, the model corroborates the assumption that PtdIns(4,5)P(2), the substrate for phospholipase C is distributed over the entire egg. We also predict that the dose of sperm factor injected into the egg should modulate the temporal characteristics of the first, long-lasting fertilization wave.

Animals↗

PubMed2003

Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations: a simple model.

The rules that govern the activation and autophosphorylation of the multifunctional Ca2+-calmodulin kinase II (CaMKII) by Ca2+ and calmodulin (CaM) are thought to underlie its ability to decode Ca2+ oscillations and to control multiple cellular functions. We propose a simple biophysical model for the activation of CaMKII by Ca2+ and calmodulin. The model describes the transition of the subunits of the kinase between their different possible states (inactive, bound to Ca2+-CaM, phosphorylated at Thr(286), trapped and autonomous). All transitions are described by classical kinetic equations except for the autophosphorylation step, which is modeled in an empirical manner. The model quantitatively reproduces the experimentally demonstrated frequency sensitivity of CaMKII [Science 279 (1998) 227]. We further use the model to investigate the role of several characterized features of the kinase--as well as some that are not easily attainable by experiments--in its frequency-dependent responses. In cellular microdomains, CaMKII is expected to sense very brief Ca2+ spikes; our simulations under such conditions reveal that the enzyme response is tuned to optimal frequencies. This prediction is then confirmed by experimental data. This novel and simple model should help in understanding the rules that govern CaMKII regulation, as well as those involved in decoding intracellular Ca2+ signals.

Biophysical Phenomena↗

PubMed2002

Calcium wave pacemakers in eggs.

During the past 25 years, the characterization of sperm-triggered calcium signals in eggs has progressed from the discovery of a single calcium increase at fertilization in the medaka fish to the observation of repetitive calcium waves initiated by multiple meiotic calcium wave pacemakers in the ascidian. In eggs of all animal species, sperm-triggered inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] production regulates the vast array of calcium wave patterns observed in the different species. The spatial organization of calcium waves is driven either by the intracellular distribution of the calcium release machinery or by the localized and dynamic production of calcium-releasing second messengers. In the highly polarized egg cell, cortical endoplasmic reticulum (ER)-rich clusters act as pacemaker sites dedicated to the initiation of global calcium waves. The extensive ER network made of interconnected ER-rich domains supports calcium wave propagation throughout the egg. Fertilization triggers two types of calcium wave pacemakers depending on the species: in mice, the pacemaker site in the vegetal cortex of the egg is probably a site that has enhanced sensitivity to Ins(1,4,5)P(3); in ascidians, the calcium wave pacemaker may rely on a local source of Ins(1,4,5)P(3) production apposed to a cluster of ER in the vegetal cortex.

Animals↗

PubMedDate not supplied

[Pierre-Joseph Duhem (1758-1807), doctor regicide, and other National Convention physician-deputies vis-a-vis the lawsuit of Louis XVI].

On January 16, 1793, seven hundred aud forty nine deputies of the National Convention are called on to express their opinion by word of mouth about this question: "What penalty Louis, former king of the French, brought upon himself ?" Among these deputies, 47 are or were physicians : 22 vote for death without delay, 3 for suspended death sentence, 20 for indulgence (imprisonment till the peace and banishment thereafter), and 2 refuse to vote. This paper aims at summarizing the attitude of the physicians-deputies, and more specifically those of Pierre-Joseph Duhem, at the time of one of the most famous trials of the history of France.

Capital Punishment↗