Biological fractionation of lithium isotopes by cellular Na/H exchangers unravels fundamental transport mechanisms.

Lithium (Li) has a wide range of uses in science, medicine, and industry, but its isotopy is underexplored, except in nuclear science and in geoscience. Li and Li isotopic ratio exhibits the second largest variation on earth's surface and constitutes a widely used tool for reconstructing past oceans and climates. As large variations have been measured in mammalian organs, plants or marine species, and as Li elicits stronger effects than natural Li (∼95% Li), a central issue is the identification and quantification of biological influence of Li isotopes distribution.

How Does Our Knowledge on the Na/H Exchanger NHE1 Obtained by Biochemical and Molecular Analyses Keep up With Its Recent Structure Determination?

Na/H exchangers are membrane transporters conserved in all living systems and therefore are assumed to be amongst the most ancestral molecular devices that equipped the first protocells. Following the cloning and sequencing of its gene, the mammalian NHE1, that regulates pH and volume in all cells, has been thoroughly scrutinized by molecular and biochemical analyses. Those gave a series of crucial clues concerning its topology, dimeric organization, pharmacological profile, regulation, and the role of key amino acids.

Intracellular pH Control by Membrane Transport in Mammalian Cells. Insights Into the Selective Advantages of Functional Redundancy.

Intracellular pH is a vital parameter that is maintained close to neutrality in all mammalian cells and tissues and acidic in most intracellular compartments. After presenting the main techniques used for intracellular an vesicular pH measurements we will briefly recall the main molecular mechanisms that affect and regulate intracellular pH. Following this we will discuss the large functional redundancy found in the transporters of H or acid-base equivalents.

Simulations of amperometric monitoring of exocytosis: moderate pH variations within the cell-electrode cleft with the buffer diffusion.

Amperometry with ultramicroelectrodes is nowadays a routine technique to investigate neurotransmitter secretion by vesicular exocytosis at the single-cell level. This electroanalytical tool allows one to understand many aspects of the vesicular release in terms of mechanisms. However, the electrochemical detection relies on the oxidation of released neurotransmitters that produce 2H and thus the possible acidification of the cell-electrode cleft.

Cavitation Mean Expectation Time in a Stretched Lennard-Jones Fluid under Confinement.

We investigate the nucleation of cavitation bubbles in a confined Lennard-Jones fluid subjected to negative pressures in a cubic enclosure. We perform molecular dynamics (MD) simulations with tunable interatomic potentials that enable us to control the wettability of solid walls by the liquid, that is, its contact angle. For a given temperature and pressure, as the solid is taken more hydrophobic, we put in evidence, an increase in nucleation probability.

Capillary bridge technique to study superhydrophobic surfaces.

We present here the use of the capillary bridge technique to study the wetting properties (advancing and receding contact angles) of transparent, textured and superhydrophobic surfaces over large wetted area. Apparent contact angles on such surfaces are classically measured using a goniometer in combination with video camera side visualization and a drop shape analysis. Recent experiments of Schellenberger et al.

Reconstructing the functional connectivity of multiple spike trains using Hawkes models.

Background: Statistical models that predict neuron spike occurrence from the earlier spiking activity of the whole recorded network are promising tools to reconstruct functional connectivity graphs. Some of the previously used methods are in the general statistical framework of the multivariate Hawkes processes. However, they usually require a huge amount of data, some prior knowledge about the recorded network, and/or may produce an increasing number of spikes along time during simulation.

Surrogate Data Methods Based on a Shuffling of the Trials for Synchrony Detection: The Centering Issue.

We investigate several distribution-free dependence detection procedures, all based on a shuffling of the trials, from a statistical point of view. The mathematical justification of such procedures lies in the bootstrap principle and its approximation properties. In particular, we show that such a shuffling has mainly to be done on centered quantities-that is, quantities with zero mean under independence-to construct correct p-values, meaning that the corresponding tests control their false positive (FP) rate.

Bubble dynamics inside an outgassing hydrogel confined in a Hele-Shaw cell.

We report an experimental study of bubble dynamics in a non-Newtonian fluid subjected to a pressure decrease. The fluid is a hydrogel, composed of water and a synthetic clay, prepared and sandwiched between two glass plates in a Hele-Shaw geometry. The rheological properties of the material can be tuned by the clay concentration.

Na(+)/H(+) antiporter (NHE1) and lactate/H(+) symporters (MCTs) in pH homeostasis and cancer metabolism.

The Na(+)/H(+)-exchanger NHE1 and the monocarboxylate transporters MCT1 and MCT4 are crucial for intracellular pH regulation, particularly under active metabolism. NHE1, a reversible antiporter, uses the energy provided by the Na(+) gradient to expel H(+) ions generated in the cytosol. The reversible H(+)/lactate(-) symporters MCT1 and 4 cotransport lactate and proton, leading to the net extrusion of lactic acid in glycolytic tumors.

Capturing intracellular pH dynamics by coupling its molecular mechanisms within a fully tractable mathematical model.

We describe the construction of a fully tractable mathematical model for intracellular pH. This work is based on coupling the kinetic equations depicting the molecular mechanisms for pumps, transporters and chemical reactions, which determine this parameter in eukaryotic cells. Thus, our system also calculates the membrane potential and the cytosolic ionic composition.

A dynamical model for the Utricularia trap.

We propose a model that captures the dynamics of a carnivorous plant, Utricularia inflata. This plant possesses tiny traps for capturing small aquatic animals. Glands pump water out of the trap, yielding a negative pressure difference between the plant and its surroundings.

Prediction of local pH variations during amperometric monitoring of vesicular exocytotic events at chromaffin cells.

Electrochemical monitoring of the exocytosis process is generally performed through amperometric oxidation of the electroactive messengers released by single living cells. Herein, we consider the vesicular release of catecholamines by chromaffin cells. Each exocytotic event is thus detected as a current spike whose morphology (intensity, duration, area, etc.

Invariance of exocytotic events detected by amperometry as a function of the carbon fiber microelectrode diameter.

Etched carbon fiber microelectrodes of different radii have been used for amperometric measurements of single exocytotic events occurring at adrenal chromaffin cells. Frequency, kinetic, and quantitative information on exocytosis provided by amperometric spikes were analyzed as a function of the surface area of the microelectrodes. Interestingly, the percentage of spikes with foot (as well as their own characteristics), a category revealing the existence of sufficient long-lasting fusion pores, was found to be constant whatever the microelectrode diameter was, whereas the probability of overlapping spikes decreased with the electrode size.

Ex vivo activities of beta-lapachone and alpha-lapachone on macrophages: a quantitative pharmacological analysis based on amperometric monitoring of oxidative bursts by single cells.

ARTIFICIAL SYNAPSES FOR FEMTOMOLAR DETECTION: Amperometry at platinized carbon fibre electrodes has been used to unravel the complexity of beta-lapachone's effects on cellular oxidative stress. Alpha-lapachone, the pharmacologically inactive para-quinone isomer, did not display such characteristics, but over longer incubation periods both quinones induced apoptosis. The observed effects were interpreted in terms of two mechanisms involving opposite reactivities of quinones in living cells.

Regulation of exocytosis in chromaffin cells by trans-insertion of lysophosphatidylcholine and arachidonic acid into the outer leaflet of the cell membrane.

Vesicular exocytosis is an important complex process in the communication between cells in organisms. It controls the release of chemical and biochemical messengers stored in an emitting cell. In this report, exocytosis is studied amperometrically (at carbon fiber ultramicroelectrodes) at adrenal chromaffin cells, which release catecholamines after appropriate stimulation, while testing the effects due to trans-insertion of two exogenous compounds (lysophosphatidylcholine (LPC) and arachidonic acid (AA)) on the kinetics of exocytotic events.

Nitric oxide release during evoked neuronal activity in cerebellum slices: detection with platinized carbon-fiber microelectrodes.

Nitric oxide is an important biological messenger that particularly induces the relaxation of smooth muscle cells surrounding vessels, and, hence, controls the flow of blood. This mechanism is essential for brain function, and its fine control, termed functional hyperemia, is supposed to be realized by certain neurons that may release bursts of NO*. The aim of the present study is to examine the advantages of platinized carbon-fiber microelectrodes (5-7 microm tip diameter) for the direct and in situ electrochemical detection of NO* released by neurons into ex vivo cerebellum slices.

Correlation between vesicle quantal size and fusion pore release in chromaffin cell exocytosis.

A significant number of exocytosis events recorded with amperometry demonstrate a prespike feature termed a "foot" and this foot has been correlated with messengers released via a transitory fusion pore before full exocytosis. We have compared amperometric spikes with a foot with spikes without a foot at chromaffin cells and found that the probability of detecting a distinct foot event is correlated to the amount of catecholamine released. The mean charge of the spikes with a foot was found to be twice that of the spikes without a foot, and the frequency of spikes displaying a foot was zero for small spikes increasing to approximately 50% for large spikes.

Molecular dynamics simulations of the lipid bilayer edge.

Phospholipid bilayers have been intensively studied by molecular dynamics (MD) simulation in recent years. The properties of bilayer edges are important in determining the structure and stability of pores formed in vesicles and biomembranes. In this work, we use molecular dynamics simulation to investigate the structure, dynamics, and line tension of the edges of bilayer ribbons composed of pure dimyristoylphosphatidylcholine (DMPC) or palmitoyl-oleoylphosphatidylethanolamine (POPE).

Dynamics of full fusion during vesicular exocytotic events: release of adrenaline by chromaffin cells.

Vesicular exocytosis is important in the communication between cells in complex organisms. It controls the release of specific chemical or biochemical messengers stored in the emitting cell, which elicit a response upon detection by the target cells. Secretion of a messenger molecule (a neurotransmitter) was measured electrochemically, which allowed the quantification of cellular events and the validation of current physicochemical models.