Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni

Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi

Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas

5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days. Weight gain was used as a sublethal endpoint, whereas survival as a lethal endpoint. Our results are the first to provide evidence for the presence of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the measured values falling below 0.03%. This is also the first study to investigate the interplay of Cd with DNA hydroxymethylation levels in a non-human animal study system. Cadmium retention in the hepatopancreas of C. aspersus increased from a dietary Cd dose of 1 milligram per kilogram dry weight (mg/kg d. wt). For the same treatment, we identified the only significant elevation in percentage of samples with detectable 5hmC levels despite the lack of significant mortalities and changes in weight gain among treatment groups. These findings indicate that 5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening a new aspect to invertebrate environmental epigenetics

The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni

BBSRC Grant (BB/K005448/1)Background The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail?s response to infection. Methodology/Principle findings Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA methyltransferase activity and 5mC binding in pigmented hybrid- compared to inbred (NMRI)- B. glabrata populations indicate a role for the snail?s DNA methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus-specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in silico predictions and whole genome BS-Seq analysis of this species? genome. Finally, we provide preliminary evidence for parasite-mediated host epigenetic reprogramming in the schistosome/snail system, as demonstrated by the increase in Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic cell line) exposure to parasite larval transformation products (LTP). Conclusions/Significance The presence of a functional DNA methylation machinery in B. glabrata as well as the modulation of these gene products in response to schistosome products, suggests a vital role for DNA methylation during snail development/oviposition and parasite interactions. Further deciphering the role of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary biology may reveal key factors associated with disease transmission and, moreover, enable the discovery of novel lifecycle intervention strategiespublishersversionPeer reviewe

Molecular dynamics study of rare earth-doped Mg-silicate nanoparticles in vitreous silica: from the preform to the fiber

International audienceA Molecular Dynamics study of rare-earth doped Mg-silicate nanoparticles in vitreous silica: from the preform to the fiber. New lasers and amplifiers still require an enhancement of the spectroscopic performance of rare-earth-doped silica optical fibers. In order to tailor their optical behavior, a route of interest consists in embedding rare-earth ions within dielectric nanoparticles in the core of optical fibers. Nanoparticles are formed through spontaneous phase separation phenomenon within a MgO–SiO2 binary melt, during melt/quench sequences of MCVD fabrication process of the preform [1][2]. Then, fibers are obtained by drawing at high temperature a preform containing nanoparticles. First report on the drawing process reveals an elongation of the nanoparticles in the drawing direction as well as a breakup of the larger ones [3]. In this Molecular dynamics study, we use a new simple transferable model [4] to show that phase separation occurring in the MgO–SiO2 binary melt, leads to separation of liquid phases with mixed composition: Si-rich Mg-poor phases on one hand, Mg-rich Si-poor phases on the other hand. These latter phases, the so-called nanoparticles, are amorphous, non spherical and exhibit a wide range of sizes. Mg-O coordination and MgO content increase with the nanoparticle size. With rare-earth doping, the larger nanoparticles are over-concentrated in luminescent ions. Due to an oxygen-rich environment in the nanoparticles, we show that the rare-earth clustering effect is greatly prevented, compared with a pure silica matrix. Finally, at high temperature, we apply a uniaxial elongation to the nanostructured preform to mimic the experimental drawing step leading to the fiber. We report here results on the effects of this drawing process on the nanoparticles characteristics

Rare-earth doped oxide nanoparticles in optical fibers

International audienceThe success of optical fibers based on silica glass are many: transmission fibers and fiber amplifiers for telecommunications, high-power fiber lasers, sensors, ... These key applications rely on the qualities of silica glass: mechanical and chemical stability, high optical damage threshold, low cost, ... However, this glass has certain characteristics (high phonon energy, low rare-earth solubility, …) which may make it less efficient compared to other types of glass. To overcome these limitations, a new family of optical fibers containing rare-earth doped oxide nanoparticles are developed. Thanks to this approach, the luminescent properties can be engineered through the composition of the nanoparticles. During this talk, we will discuss the formation of nanoparticles and the engineering of the rare-earth ions luminescent properties. These results clearly offer new possibilities for the control of the luminescent properties and the development of optical fibers with augmented properties

Tm-doped nanoparticles in optical fibers

International audienceThe success of silica-based optical fibers are many: transmission fibers and fiber amplifiers for telecommunications, high-power fiber lasers or sensors. These key applications rely on the qualities of silica glass: mechanical and chemical stability, high optical damage threshold, low cost, etc. New lasers and amplifiers based on rare-earth (RE)-doped silica optical fibers need improved spectroscopic performances : gain curve engineering, photodarkening, spectral coverage, etc. In this context, a route of interest consists of embedding the RE ions within nanoparticles of composition and structure different from those of silica. In this work, we study the properties of silica-based, MCVD-prepared fibers using LaF3:Tm3+ nanoparticles. The nanoparticles with 10-20 nm of diameter were produced by precipitation methods and were incorporated by solution doping. Through SEM analyses on preform and fiber, nanoparticles were observed across the core. As F-ions evaporate, the new phase is a La-rich silicate and its composition will be discussed based on the comparison with similar samples prepared by sol-gel. The first e-folding time of the 810-nm emission band (3H4 level) increases with the concentration of La. The best compromise between lifetime enhancement and optical attenuation corresponds to 58 μs and 0.05 dB/m, respectively. Yet, to further improve the optical properties, there is a need to limit Rayleigh scattering induced by the presence of nanoparticles. In the frame of these optical losses reductions, we propose to take advantage of the fiber drawing to tailor the size of nanoparticles. Indeed, we will report evidences that this step permits the deformation and break-up of elongated particles. The possibility of considering break-up as a way to implement size tailoring of nanoparticles will be discussed. These results clearly offer new possibilities for the control of the luminescent properties and the development of optical fibers with augmented properties

On the morphologies of oxides particles in optical fibers: Effect of the drawing tension and composition

International audienceRare-earth-doped oxide nanoparticles in the core of silica optical fibers are becoming well studied as they yield enhanced and tailorable spectroscopic and optical properties. In this paper, the evolution of particle morphology , induced by the drawing step, is studied. Indeed, during the fiber draw process, the glass flows and particles can elongate and even break-up into smaller particles through Rayleigh-Plateau instabilities. The shape of elongated particles is related to the composition as it depends on the viscosity ratio between the particle and the matrix. Moreover, a lower drawing temperature enhances the break-up phenomenon. These observations offer new possibilities for the control of the size and the shape of particles, hence performance of active optical fibers

Histone Methylome of the Human Parasite Schistosoma Mansoni

International audienc