Two-Dimensional Fluctuating Vesicles in Linear Shear Flow

The stochastic motion of a two-dimensional vesicle in linear shear flow is studied at finite temperature. In the limit of small deformations from a circle, Langevin-type equations of motion are derived, which are highly nonlinear due to the constraint of constant perimeter length. These equations are solved in the low temperature limit and using a mean field approach, in which the length constraint is satisfied only on average. The constraint imposes non-trivial correlations between the lowest deformation modes at low temperature. We also simulate a vesicle in a hydrodynamic solvent by using the multi-particle collision dynamics technique, both in the quasi-circular regime and for larger deformations, and compare the stationary deformation correlation functions and the time autocorrelation functions with theoretical predictions. Good agreement between theory and simulations is obtained.Comment: 13 pages, 7 figure

L’enseignement - apprentissage du français aux élèves rejoignants

La scolarisation des enfants de migrants pose le problème de l’acquisition de la langue scolaire et du métalangage des disciplines. Les difficultés d’enseignement - apprentissage que rencontrent élèves - rejoignants et enseignants sont à rapprocher de celles, plus générales, qui touchent les enfants francophones en situation d’échec scolaire. Des solutions pédagogiques doivent être mise en place : l’article propose quelques pistes de réflexions.The instruction of immigrant/migrant children poses the problem of classroom language and of the metalanguage of the various disciplines taught at school. The learning difficulties students joining their parents in a foreign land face and the instructional difficulties their teachers face are to be likened to the broader ones which affect french speaking students in the situation of failing in school. Pedagogical solutions must be implemented. The article proposes a few reflections along various lines of thought

Swinging and tumbling of elastic capsules in shear flow

The deformation of an elastic micro-capsule in an infinite shear flow is studied numerically using a spectral method. The shape of the capsule and the hydrodynamic flow field are expanded into smooth basis functions. Analytic expressions for the derivative of the basis functions permit the evaluation of elastic and hydrodynamic stresses and bending forces at specified grid points in the membrane. Compared to methods employing a triangulation scheme, this method has the advantage that the resulting capsule shapes are automatically smooth, and few modes are needed to describe the deformation accurately. Computations are performed for capsules both with spherical and ellipsoidal unstressed reference shape. Results for small deformations of initially spherical capsules coincide with analytic predictions. For initially ellipsoidal capsules, recent approximative theories predict stable oscillations of the tank-treading inclination angle, and a transition to tumbling at low shear rate. Both phenomena have also been observed experimentally. Using our numerical approach we could reproduce both the oscillations and the transition to tumbling. The full phase diagram for varying shear rate and viscosity ratio is explored. While the numerically obtained phase diagram qualitatively agrees with the theory, intermittent behaviour could not be observed within our simulation time. Our results suggest that initial tumbling motion is only transient in this region of the phase diagram.Comment: 20 pages, 7 figure

Effects of ultraviolet radiation on aquatic bryophytes

The depletion of the stratospheric ozone layer as a result of anthropogenic activities increases the ultraviolet-B (UV-B) irradiance at ground level. This may lead to harmful biological consequences affecting photosynthetic organisms. Mountain streams are especially exposed to a UV-B increase, and bryophytes play a key ecological role in them. In this paper, the effects of enhanced UV-B radiation on photosynthetic organisms in general and on bryophytes in particular are described. Hereafter, some results obtained by our group on the effects of UV-B on bryophytes from mountain streams are presented. Laboratory and field experiments show that these effects depend on the species, the environmental factors (such as temperature), and the origin of the samples (sun or shade conditions, low or high altitude). Among the variables measured, the maximum quantum yield of photosystem II (Fv/Fm) and the level of UV-absorbing compounds seem to be the most responsive to enhanced UV-B, but no variable responded in the same manner in every species. The potential use of aquatic bryophytes as bio-indicators of changes in ambient UV-B radiation would require an adequate selection of both variables and species. Promising variables are Fv/Fm, the concentration of UV-absorbing compounds (especially if they are analyzed individually) and DNA damage, whereas the liverwort Jungermannia exsertifolia subsp. cordifolia has been revealed to be a good bio-indicator species. Globally, the responses of aquatic bryophytes to UV-B radiation and their protecting systems are still poorly characterized, and thus further study is required under both controlled and field conditions.La degradación antropogénica de la capa de ozono estratosférico provoca un aumento de la radiación ultravioleta-B (UV-B) en la superficie de La Tierra. Esto puede causar consecuencias biológicas nocivas en los organismos fotosintéticos. Los arroyos de montaña están especialmente expuestos al aumento de UV-B, y los briófitos desempeñan un papel ecológico crucial en estos ecosistemas. En el presente artículo, se describen los efectos de un aumento de radiación UV-B sobre los organismos fotosintéticos en general y sobre los briófitos en particular. A continuación, se presentan algunos resultados obtenidos por nuestro grupo de investigación sobre los efectos de la radiación UV-B en briófitos de arroyos de montaña. Los experimentos realizados tanto en campo como en laboratorio muestran que dichos efectos dependen de la especie considerada, de los factores ambientales (como la temperatura) y de la procedencia de las muestras (aclimatadas a condiciones de sol o sombra, provenientes de baja o elevada altitud). Entre las variables analizadas, el rendimiento cuántico máximo del fotosistema II (Fv/Fm) y el nivel de compuestos absorbentes de radiación UV parecen ser las que mejor responden a un aumento de UV-B, pero ninguna variable responde de la misma manera en todas las especies. El uso potencial de los briófitos acuáticos como bioindicadores de cambios en los niveles naturales de radiación UV-B requiere una selección adecuada tanto de las variables analizadas como de las especies empleadas. Fv/Fm y la concentración de compuestos absorbentes de radiación UV (en especial si éstos son analizados individualmente), junto con los daños en el ADN, parecen ser las variables más prometedoras en este campo, mientras que la hepática Jungermannia exsertifolia subsp. cordifolia podría resultar una buena especie bioindicadora. Desde un punto de vista global, las respuestas de los briófitos acuáticos a la radiación UV-B, y los mecanismos protectores que utilizan para hacerle frente, están todavía poco caracterizados, y en consecuencia se necesita una mayor investigación en condiciones controladas y en campo

Design of a genetically stable high fidelity coxsackievirus B3 polymerase that attenuates virus growth in vivo

Positive strand RNA viruses replicate via a virally encoded RNA-dependent RNA polymerase (RdRP) that uses a unique palm domain active site closure mechanism to establish the canonical two-metal geometry needed for catalysis. This mechanism allows these viruses to evolutionarily fine-tune their replication fidelity to create an appropriate distribution of genetic variants known as a quasispecies. Prior work has shown that mutations in conserved motif A drastically alter RdRP fidelity, which can be either increased or decreased depending on the viral polymerase background. In the work presented here, we extend these studies to motif D, a region that forms the outer edge of the NTP entry channel where it may act as a nucleotide sensor to trigger active site closure. Crystallography, stoppedflow kinetics, quench-flow reactions, and infectious virus studies were used to characterize 15 engineered mutations in coxsackievirus B3 polymerase. Mutations that interfere with the transport of the metal A Mg2+ ion into the active site had only minor effects on RdRP function, but the stacking interaction between Phe364 and Pro357, which is absolutely conserved in enteroviral polymerases, was found to be critical for processive elongation and virus growth. Mutating Phe364 to tryptophan resulted in a genetically stable high fidelity virus variant with significantly reduced pathogenesis in mice. The data further illustrate the importance of the palm domain movement for RdRP active site closure and demonstrate that protein engineering can be used to alter viral polymerase function and attenuate virus growth and pathogenesis

Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency

RNA viruses use RNA dependent RNA polymerases to replicate their genomes. The intrinsically high error rate of these enzymes is a large contributor to the generation of extreme population diversity that facilitates virus adaptation and evolution. Increasing evidence shows that the intrinsic error rates, and the resulting mutation frequencies, of RNA viruses can be modulated by subtle amino acid changes to the viral polymerase. Although biochemical assays exist for some viral RNA polymerases that permit quantitative measure of incorporation fidelity, here we describe a simple method of measuring mutation frequencies of RNA viruses that has proven to be as accurate as biochemical approaches in identifying fidelity altering mutations. The approach uses conventional virological and sequencing techniques that can be performed in most biology laboratories. Based on our experience with a number of different viruses, we have identified the key steps that must be optimized to increase the likelihood of isolating fidelity variants and generating data of statistical significance. The isolation and characterization of fidelity altering mutations can provide new insights into polymerase structure and function1-3. Furthermore, these fidelity variants can be useful tools in characterizing mechanisms of virus adaptation and evolution4-7

A Necklace Model for Vesicles Simulations in 2D

International audienceThe aim of this paper is to propose a new numerical model to simulate 2D vesicles interacting with a newtonian fluid. The inextensible membrane is modeled by a chain of circular rigid particles which are maintained in cohesion by using two different type of forces. First, a spring force is imposed between neighboring particles in the chain. Second, in order to model the bending of the membrane, each triplet of successive particles is submitted to an angular force. Numerical simulations of vesicles in shear flow have been run using Finite Element Method and the FreeFem++[1] software. Exploring different ratios of inner and outer viscosities, we recover the well known "Tank-Treading" and "Tumbling" motions predicted by theory and experiments. Moreover, for the first time, 2D simulations of the "Vacillating-Breathing" regime predicted by theory in [2] and observed experimentally in [3] are done without special ingredient like for example thermal fluctuations used in [4]

Omeprazole Increases the Efficacy of Acyclovir Against Herpes Simplex Virus Type 1 and 2

Omeprazole was shown to improve the anti-cancer effects of the nucleoside analogue 5-fluorouracil. Here, we combined omeprazole with the antiviral nucleoside analogues ribavirin and acyclovir. Omeprazole did not affect the antiviral effects of ribavirin in non-toxic concentrations up to 80 μg/mL but increased the acyclovir-mediated effects on herpes simplex virus 1 and 2 (HSV-1 and -2) replication in a dose-dependent manner. Omeprazole alone reduced HSV-1 and -2 titers [but not HSV-induced formation of cytopathogenic effects (CPE)] at concentrations ≥40 μg/mL. However, it exerted substantially stronger effects on acyclovir activity and also increased acyclovir activity at lower concentrations that did not directly interfere with HSV replication. Omeprazole 80 μg/mL caused a 10.8-fold (Vero cells) and 47.7-fold (HaCaT cells) decrease of the acyclovir concentrations that reduced HSV-1-induced CPE formation by 50% (IC50). In HSV-2-infected cells, omeprazole 80 μg/mL reduced the acyclovir IC50 by 7.3- (Vero cells) and 12.9-fold (HaCaT cells). In HaCaT cells, omeprazole 80 μg/mL reduced the HSV-1 titer in the presence of acyclovir 1 μg/mL by 1.6 × 105-fold and the HSV-2 titer in the presence of acyclovir 2 μg/mL by 9.2 × 103-fold. The proton pump inhibitors pantoprazole, rabeprazole, lansoprazole, and dexlansoprazole increased the antiviral effects of acyclovir in a similar fashion as omeprazole, indicating this to be a drug class effect. In conclusion, proton pump inhibitors increase the anti-HSV activity of acyclovir and are candidates for antiviral therapies in combination with acyclovir, in particular for topical preparations for the treatment of immunocompromised individuals who are more likely to suffer from severe complications