1,917 research outputs found

    Vier maanden op de ARA <i>Libertad</i>

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    Specific biomarkers for C9orf72 FTD/ALS could expedite the journey towards effective therapies

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    A hexanucleotide repeat expansion in the C9orf72 gene is a common genetic cause of ALS and FTD. The repeats are translated into five different dipeptide repeat proteins (DPRs). In this issue, Lehmer et al (2017) demonstrate that one of these DPRs, poly(GP), can be measured in the CSF of individuals with C9orf72 mutations. In conjunction with the findings from another recent study (Gendron et al, 2017), these DPR biomarkers may prove to be extremely valuable in the quest for effective therapies for C9FTD/ALS

    Blood/gas partition coefficients of halothane, isoflurane and sevoflurane in horse blood

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    Background. Blood/gas partition coefficients (λb/g) for volatile agents in horse blood are reported for halothane but not for isoflurane and sevoflurane. We measured the λb/g of halothane, isoflurane and sevoflurane in the blood of fasted horses. The correlation with age, weight and some haematological and biochemical variables was studied. The temperature correction factor for isoflurane solubility was calculated. Methods. Twenty‐four horses were randomly allocated to halothane (n=8), isoflurane (n=8) or sevoflurane (n=8). Blood samples were taken after 10 h' fasting. Calculation of λb/g was based on the measurement of anaesthetic partial pressures in blood at 37 °C, which was achieved with tonometer equilibration and headspace gas chromatography. Results. Mean λb/g was 1.66 (sd 0.06) for halothane, 0.92 (0.04) for isoflurane, and 0.47 (0.03) for sevoflurane. The λb/g values were all significantly lower than in humans (P<0.001). No correlation was found between λb/g and weight, age, haematocrit, plasma triglycerides, cholesterol or total bilirubin. The change in isoflurane solubility per 1 °C temperature increase was -2.63 (0.13)%. Conclusion. The λb/g values of halothane, isoflurane and sevoflurane in fasted horses are significantly lower than those reported in humans. The λb/g for halothane in this study agrees with values reported in the literature but a positive correlation with plasma triglycerides could not be confirmed. Knowledge of λb/g can refine models of anaesthetic uptake. Br J Anaesth 2003; 91: 276-

    Guidelines for morpholino use in zebrafish

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    The zebrafish (Danio rerio) has emerged as a powerful model to study vertebrate development and disease. Its short generation time makes it amenable to genetic manipulation and analysis, and its small size and high fecundity make it especially well suited for large-scale forward genetic and chemical screens. Fast-developing zebrafish embryos are transparent, facilitating live imaging of a variety of developmental processes in wild-type and mutant animals. ... This brief document provides an updated set of guidelines regarding morpholino use in zebrafish that we anticipate will be of value for experimentalists as well as journal and grant reviewers, and decision makers

    Colonization patterns of Nematoda on decomposing algae in the estuarine environment: community assembly and genetic structure of the dominant species <i>Pellioditis marina</i>

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    We performed a field experiment in the Westerschelde Estuary (The Netherlands) to characterize the colonization dynamics of nematodes in relation to the proximity of a source population and to local environmental conditions. The effects of colonization on the population genetic structure of the dominant species, Pellioditis marina, were simultaneously investigated. Two contrasting sites, each containing four patches with defaunated algae, were sampled seven times during 1 month. Site A was situated amidst Fucus stands, which permanently harbor P. marina, while site B was approximately 100 m from any source population and experienced more stressful environmental conditions. We hypothesized that (1) colonization in site A would proceed faster than in site B and that (2) founder events and genetic bottlenecks would affect population genetic structure and differentiation at site B more than at site A. We screened 992 individuals for variation in 426 base pairs of the cytochrome oxidase c subunit 1 gene with the single-strand conformation polymorphism method. The algal deposits at site A were indeed more rapidly colonized and reached fivefold higher densities of nematodes than those in site B. Haplotype composition in site A was very similar to that of the source population, while rare haplotypes were abundant and genetic diversity was lower in site B. We conclude that founder effects and genetic bottlenecks structured the populations in site B. The genetic differences between patches in each site further indicate that effective migration in P. marina is low and that priority effects influence the genetic structure of P. marina populations

    EPR analysis of cyanide complexes of wild-type human neuroglobin and mutants in comparison to horse heart myoglobin

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    Electron paramagnetic resonance (EPR) data reveal large differences between the ferric (C-)cyanide complexes of wild-type human neuroglobin (NGB) and its H64Q and F28L point mutants and the cyanide complexes of mammalian myo-and haemoglobin. The point mutations, which involve residues comprising the distal haem pocket in NGB, induce smaller, but still significant changes, related to changes in the stabilization of the cyanide ligand. Furthermore, for the first time, the full C hyperfine tensor of the cyanide carbon of cyanide-ligated horse heart myoglobin (hhMb) was determined using Davies ENDOR (electron nuclear double resonance). Disagreement of these experimental data with earlier predictions based on C NMR data and a theoretical model reveal significant flaws in the model assumptions. The same ENDOR procedure allowed also partial determination of the corresponding C hyperfine tensor of cyanide-ligated NGB and H64QNGB. These C parameters differ significantly from those of cyanide-ligated hhMb and challenge our current theoretical understanding of how the haem environment influences the magnetic parameters obtained by EPR and NMR in cyanide-ligated haem proteins

    Investigating the ecology and evolution of cryptic marine nematode species through quantitative real-time PCR of the ribosomal ITS region

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    The presence of morphologically similar but genetically distinct species has impacted biogeographical and ecological paradigms. In marine sediments, free-living nematodes form one of the most abundant and diverse faunal groups. Inferring the importance of nematode diversity for ecosystem functioning requires species-level identification, which is hampered by the lack of easily observable diagnostic characters and the presence of cryptic species. New techniques are urgently needed to adequately study the ecology and evolution of cryptic species. The aim of the present study was to evaluate the potential of a quantitative real-time PCR (qPCR) assay using the internal transcribed spacer (ITS) region of the ribosomal DNA to detect and quantify cryptic species of the R. (P.) marina complex. All primer pairs proved to be highly specific, and each primer pair was able to detect a single juvenile in a pool of 100 nematodes. Ct values were significantly different between developmental stages for all species except for PmIII. Despite differences between developmental stages, a strong correlation was observed between the amount of extracted DNA and the number of nematodes present. Relative and absolute quantification estimates were comparable and resulted in strong positive correlations between the qPCR estimate and the actual number of nematodes present in the samples. The qPCR assay developed here provides the ability to quickly identify and quantify cryptic nematode species and will facilitate their study in laboratory and field settings

    Radiation-Hydrodynamics with MPI-AMRVAC: Flux-Limited Diffusion

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    Radiation controls the dynamics and energetics of many astrophysical environments. To capture the coupling between the radiation and matter, however, is often a physically complex and computationally expensive endeavour. We develop a numerical tool to perform radiation-hydrodynamics simulations in various configurations at an affordable cost. We build upon the finite volume code MPI-AMRVAC to solve the equations of hydrodynamics on multi-dimensional adaptive meshes and introduce a new module to handle the coupling with radiation. A non-equilibrium, flux-limiting diffusion approximation is used to close the radiation momentum and energy equations. The time-dependent radiation energy equation is then solved within a flexible framework, accounting fully for radiation forces and work terms and further allowing the user to adopt a variety of descriptions for the radiation-matter interaction terms (the 'opacities'). We validate the radiation module on a set of standard testcases for which different terms of the radiative energy equation predominate. As a preliminary application to a scientific case, we calculate spherically symmetric models of the radiation-driven and optically thick supersonic outflows from massive Wolf-Rayet stars. This also demonstrates our code's flexibility, as the illustrated simulation combines opacities typically used in static stellar structure models with a parametrised form for the enhanced line-opacity expected in supersonic flows. This new module provides a convenient and versatile tool to perform multi-dimensional and high resolution radiative-hydrodynamics simulations in optically thick environments with the MPI-AMRVAC code. The code is ready to be used for a variety of astrophysical applications, where a first target for us will be multi-dimensional simulations of stellar outflows from Wolf-Rayet stars.Comment: 14 pages, 10 figures Submitted to A&
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