Background selection and FST: Consequences for detecting local adaptation

Background selection is a process whereby recurrent deleterious mutations cause a decrease in the effective population size and genetic diversity at linked loci. Several authors have suggested that variation in the intensity of background selection could cause variation in F_ST across the genome, which could confound signals of local adaptation in genome scans. We performed realistic simulations of DNA sequences, using recombination maps from humans and sticklebacks, to investigate how variation in the intensity of background selection affects F_ST and other statistics of population differentiation in sexual, outcrossing species. We show that, in populations connected by gene flow, Weir and Cockerham's (1984; Evolution, 38 , 1358) estimator of F_ST is largely insensitive to locus‐to‐locus variation in the intensity of background selection. Unlike F_ST, however, d_XY is negatively correlated with background selection. Moreover, background selection does not greatly affect the false‐positive rate in F_ST outlier studies in populations connected by gene flow. Overall, our study indicates that background selection will not greatly interfere with finding the variants responsible for local adaptation.     

Stretching DNA origami: effect of nicks and Holliday junctions on the axial stiffness

The axial stiffness of DNA origami is determined as a function of key nanostructural characteristics. Different constructs of two-helix nanobeams with specified densities of nicks and Holliday junctions are synthesized and stretched by fluid flow. Implementing single particle tracking to extract force–displacement curves enables the measurement of DNA origami stiffness values at the enthalpic elasticity regime, i.e. for forces larger than 15 pN. Comparisons between ligated and nicked helices show that the latter exhibit nearly a two-fold decrease in axial stiffness. Numerical models that treat the DNA helices as elastic rods are used to evaluate the local loss of stiffness at the locations of nicks and Holliday junctions. It is shown that the models reproduce the experimental data accurately, indicating that both of these design characteristics yield a local stiffness two orders of magnitude smaller than the corresponding value of the intact double-helix. This local degradation in turn leads to a macroscopic loss of stiffness that is evaluated numerically for multi-helix DNA bundles.     

P2Y2R Deficiency Attenuates Experimental Autoimmune Uveitis Development

We aimed to study the role of the nucleotide receptor P2Y₂R in the development of experimental autoimmune uveitis (EAU). EAU was induced in P2Y₂^+/+ and P2Y₂^-/- mice by immunization with IRBP peptide or by adoptive transfer of in vitro restimulated semi-purified IRBP-specific enriched T lymphocytes from spleens and lymph nodes isolated from native C57Bl/6 or P2Y₂^+/+ and P2Y₂^-/- immunized mice. Clinical and histological scores were used to grade disease severity. Splenocytes and lymph node cell phenotypes were analyzed using flow cytometry. Semi-purified lymphocytes and MACS-purified CD4⁺ T lymphocytes from P2Y₂^+/+ and P2Y₂^-/- immunized mice were tested for proliferation and cytokine secretion. Our data show that clinical and histological scores were significantly decreased in IRBP-immunized P2Y₂^-/- mice as in P2Y₂^-/- mice adoptively transfered with enriched T lymphocytes from C57Bl/6 IRBP-immunized mice. In parallel, naïve C57Bl/6 mice adoptively transferred with T lymphocytes from P2Y₂^-/- IRBP-immunized mice also showed significantly less disease. No differences in term of spleen and lymph node cell recruitment or phenotype appeared between P2Y₂^-/- and P2Y₂^+/+ immunized mice. However, once restimulated in vitro with IRBP, P2Y₂^-/- T cells proliferate less and secrete less cytokines than the P2Y₂^+/+ one. We further found that antigen-presenting cells of P2Y₂^-/- immunized mice were responsible for this proliferation defect. Together our data show that P2Y₂^-/- mice are less susceptible to mount an autoimmune response against IRBP. Those results are in accordance with the danger model, which makes a link between autoreactive lymphocyte activation, cell migration and the release of danger signals such as extracellular nucleotides.     

Effect of Chemical Stabilizers on the Thermostability and Infectivity of a Representative Panel of Freeze Dried Viruses

As a partner of the European Virus Archive (EVA) FP7 project, our laboratory maintains a large collection of freeze-dried viruses. The distribution of these viruses to academic researchers, public health organizations and industry is one major aim of the EVA consortium. It is known that lyophilization requires appropriate stabilizers to prevent inactivation of the virus. However, few studies have investigated the influence of different stabilizers and lyophilization protocols on the thermostability of different viruses. In order to identify optimal lyophilization conditions that will deliver maximum retention of viral infectivity titre, different stabilizer formulations containing trehalose, sorbitol, sucrose or foetal bovine serum were evaluated for their efficacy in stabilizing a representative panel of freeze dried viruses at different storage temperatures (-20°C, +4°C and +20°C) for one week, the two latter mimicking suboptimal shipping conditions. The Tissue Culture Infectious Dose 50% (TCID₅₀) assay was used to compare the titres of infectious virus. The results obtained using four relevant and model viruses (enveloped/non enveloped RNA/DNA viruses) still serve to improve the freeze drying conditions needed for the development and the distribution of a large virus collection.     

Les assemblages lithiques des niveaux du Paléolithique moyen de l’Abri des Pêcheurs (Ardèche, Sud-Est de la France): Des occupations néandertaliennes récurrentes dans un « fossé »

The Abri des Pêcheurs has yielded an extraordinary sequence with Middle and Upper Palaeolithic levels. Humans came and stayed in a ditch-cave that has been filled in along time. During Middle Palaeolithic occupations, they used first quartz, and this site is the only case in this area. Assemblages show similar technological behaviour along time. Flint is few employed and arrived as flakes from different areas if we consider its geological variety. Functions of the site are not well established. The base of the sequence has yielded sediments with a mixing of ibex, carnivore bones and artefacts. The study of the lithic assemblages brings information on the processing systems used on quartz and flint during occupations which left few evidence and used local stones while flint is available not far from the site. Hypothesis on short and specialized occupations is discussed.     

Fast inference of interactions in assemblies of stochastic integrate-and-fire neurons from spike recordings

We present two Bayesian procedures to infer the interactions and external currents in an assembly of stochastic integrate-and-fire neurons from the recording of their spiking activity. The first procedure is based on the exact calculation of the most likely time courses of the neuron membrane potentials conditioned by the recorded spikes, and is exact for a vanishing noise variance and for an instantaneous synaptic integration. The second procedure takes into account the presence of fluctuations around the most likely time courses of the potentials, and can deal with moderate noise levels. The running time of both procedures is proportional to the number S of spikes multiplied by the squared number N of neurons. The algorithms are validated on synthetic data generated by networks with known couplings and currents. We also reanalyze previously published recordings of the activity of the salamander retina (including from 32 to 40 neurons, and from 65,000 to 170,000 spikes). We study the dependence of the inferred interactions on the membrane leaking time; the differences and similarities with the classical cross-correlation analysis are discussed.     

Polyamines promote the development of embryonal-suspensor masses and the formation of somatic embryos in <Emphasis Type="Italic">Picea glehnii</Emphasis>

Effects of polyamines on the development of embryonal-suspensor masses (ESMs) and the formation of somatic embryos were examined in an effort to improve the frequency of somatic embryogenesis in Picea glehnii. Exogenous spermidine at 100 and 300 μM promoted the elongation of suspensors and the formation of somatic embryos. Exogenous putrescine at 100 μM increased the number of somatic embryos and decreased the time required for formation of somatic embryos. Thus, exogenous polyamines improved the maturation capacity of ESMs and promoted the formation of somatic embryos in P. glehnii. Light microscopy revealed that ESMs with high maturation capacity consisted of the three following cells: round or oval cells, elongated cells, and protean cells. These components might be related to the capacity for formation of somatic embryos.