644 research outputs found

    Pathology of myelinated axons in the PLP-deficient mouse model of spastic paraplegia type 2 revealed by volume imaging using focused ion beam-scanning electron microscopy

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    Advances in electron microscopy including improved imaging techniques and state-of-the-art detectors facilitate imaging of larger tissue volumes with electron microscopic resolution. In combination with genetic tools for the generation of mouse mutants this allows assessing the three-dimensional (3D) characteristics of pathological features in disease models. Here we revisited the axonal pathology in the central nervous system of a mouse model of spastic paraplegia type 2, the Plp−/Y mouse. Although PLP is a bona fide myelin protein, the major hallmark of the disease in both SPG2 patients and mouse models are axonal swellings comprising accumulations of numerous organelles including mitochondria, gradually leading to irreversible axonal loss. To assess the number and morphology of axonal mitochondria and the overall myelin preservation we evaluated two sample preparation techniques, chemical fixation or high-pressure freezing and freeze substitution, with respect to the objective of 3D visualization. Both methods allowed visualizing distribution and morphological details of axonal mitochondria. In Plp−/Y mice the number of mitochondria is 2-fold increased along the entire axonal length. Mitochondria are also found in the excessive organelle accumulations within axonal swellings. In addition, organelle accumulations were detected within the myelin sheath and the inner tongue. We find that 3D electron microscopy is required for a comprehensive understanding of the size, content and frequency of axonal swel- lings, the hallmarks of axonal pathology

    “Angular resolution expected from iCHORD orientation maps through a revisited ion channeling model”

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    International audienceCrystalline orientation maps are obtained in a Focused Ion Beam (FIB) microscope using the ion CHanneling ORientation Determination (iCHORD) method, which relies on the channeling phenomenon observed in ion-induced secondary electron images. The current paper focuses on the angular resolution that can be expected from such orientation maps, obtained using a revisited ion channeling model. A specific procedure was developed to evaluate the angular resolution, based on the distribution of orientation errors when evaluating controlled sample disorientation. The main advantage is that no external reference is required. An angular resolution of 1° is obtained on a nickel based sample using standard acquisition conditions. This value fulfills most of the needs in terms of microstructural characterization usually carried out by Electron Back Scattered Diffraction

    dynamic Flux Balance Analysis of the Metabolism of Microalgae under a Diurnal Light Cycle

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    Microalgae have received much attention in the context of renewable fuel production, due to their ability to produce in high quantities carbon storage molecules such as lipids and carbohydrates. Despite significant research effort over the last decade, the production yields remain low and need to be optimized. For that, a thorough understanding of carbon storage metabolism is necessary. This paper develops a constrained metabolic model based on the dFBA framework to represent the dynamics of carbon storage in microalgae under a diurnal light cycle. The main assumption here is that microalgae adapt their metabolism in order to optimize their production of functional biomass (proteins, membrane lipids, DNA, RNA) over a diurnal cycle. A generic metabolic network comprised of 160 reactions representing the main carbon and nitrogen pathways of microalgae is used to characterize the metabolism. The optimization problem is simplified by exploiting the right kernel of the stoichiometric matrix, and transformed into a linear program by discretizing the differential equations using a classical collocation technique. Several constraints are investigated. The results suggest that the experimentally observed strategy of accumulation of carbon storage molecules during the day, followed by their depletion during the night may indeed be the optimal one. However, a constraint on the maximal synthesis rate of functional biomass must be added for consistency with the biological observations

    Do state and trait measures measure states and traits? The case of community-dwelling caregivers of older adults

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    Spielberger’s state and trait anxiety and anger scales are widely used and documented, but there is little or no direct evidence that they actually measure their respective state and trait aspects as was intended. We conducted latent state-trait analyses on data collected from 310 community-dwelling caregivers of older adult care recipients and found that (a) both state and trait scales reflected a mixture of state and trait aspects of their latent constructs, (b) state scales reflected more state-like variance than did corresponding trait scales, but (c) both state and trait scales were dominated by stable trait-like variance. Follow-up bivariate latent state-trait analyses indicated that correlations between trait components of anger and anxiety correlated more strongly with trait components of caregiver–care recipient mutually communal behavior and care recipient problem behavior than did state–state component correlations. Implications for the measurement of state and trait components of psychological constructs are discussed

    Macromolecular and electrical coupling between inner hair cells in the rodent cochlea

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    Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers presynaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding

    Functional behaviour of TiO2films doped with noble metals

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    To evaluate the effects of different concentrations of noble metal in a TiO2 matrix, different films of both Ag:TiO2 and Au:TiO2 systems were prepared. Mechanical and tribological characterization was carried out to evaluate the coatings response as a function of the noble metals composition and (micro)structure of the films. The overall set of results indicates that the amorphous films reveal better results than the crystalline ones. For the amorphous samples, the reduced Young’s modulus and the adhesion critical loads followed similar tendencies in both sets of films. Wear rates were similar for all samples except for the one with the highest silver content. To improve brittleness of TiO2 films, the results seem to indicate that a slight metal doping is preferred, and Au showed to be a better choice than Ag. In fact, the sample with the lowest Au content revealed a better mechanical behaviour than the pure TiO2 film.This research was sponsored by FEDER funds through the COMPETE program (Programa Operacional Factores de Competitividade) and by FCT (Fundação para a CiĂȘncia e a Tecnologia), under the projects PEST-C/FIS/UI607/2013 and PEst-C/EME/UI0285/2013. The authors also acknowledge the financial support by the project Nano4color – Design and develop a new generation of color PVD coatings for decorative applications (FP7 EC R4SME Project No. 315286)

    Applying cumulative effects to strategically advance large-scale ecosystem restoration

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    International efforts to restore degraded ecosystems will continue to expand over the coming decades, yet the factors contributing to the effectiveness of long-term restoration across large areas remain largely unexplored. At large scales, outcomes are more complex and synergistic than the additive impacts of individual restoration projects. Here, we propose a cumulative-effects conceptual framework to inform restoration design and implementation and to comprehensively measure ecological outcomes. To evaluate and illustrate this approach, we reviewed long-term restoration in several large coastal and riverine areas across the US: the greater Florida Everglades; Gulf of Mexico coast; lower Columbia River and estuary; Puget Sound; San Francisco Bay and Sacramento–San Joaquin Delta; Missouri River; and northeastern coastal states. Evidence supported eight modes of cumulative effects of interacting restoration projects, which improved outcomes for species and ecosystems at landscape and regional scales. We conclude that cumulative effects, usually measured for ecosystem degradation, are also measurable for ecosystem restoration. The consideration of evidence-based cumulative effects will help managers of large-scale restoration capitalize on positive feedback and reduce countervailing effects

    ENTRAP and its potential interaction with European networks

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    AbstractENTRAP comprises a pan-European cooperation of leading scientific institutions and regulatory bodies in the field of nuclear-waste characterization and its quality assurance for the safe disposal of radioactive waste. Here, the scope of this cooperation is presented and explained and links or interfaces for a potential collaboration with partners fulfilling tasks of IDG-TP are pursued
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