Mechanism of reduction of virus release and cell-cell fusion in persistent canine distemper virus infection

Canine distemper virus (CDV), a mobillivirus related to measles virus causes a chronic progressive demyelinating disease, associated with persistence of the virus in the central nervous system (CNS). CNS persistence of morbilliviruses has been associated with cell-to-cell spread, thereby limiting immune detection. The mechanism of cell-to-cell spread remains uncertain. In the present study we studied viral spread comparing a cytolytic (non-persistent) and a persistent CDV strain in cell cultures. Cytolytic CDV spread in a compact concentric manner with extensive cell fusion and destruction of the monolayer. Persistent CDV exhibited a heterogeneous cell-to-cell pattern of spread without cell fusion and 100-fold reduction of infectious viral titers in supernatants as compared to the cytolytic strain. Ultrastructurally, low infectious titers correlated with limited budding of persistent CDV as compared to the cytolytic strain, which shed large numbers of viral particles. The pattern of heterogeneous cell-to-cell viral spread can be explained by low production of infectious viral particles in only few areas of the cell membrane. In this way persistent CDV only spreads to a small proportion of the cells surrounding an infected one. Our studies suggest that both cell-to-cell spread and limited production of infectious virus are related to reduced expression of fusogenic complexes in the cell membrane. Such complexes consist of a synergistic configuration of the attachment (H) and fusion (F) proteins on the cell surface. F und H proteins exhibited a marked degree of colocalization in cytolytic CDV infection but not in persistent CDV as seen by confocal laser microscopy. In addition, analysis of CDV F protein expression using vaccinia constructs of both strains revealed an additional large fraction of uncleaved fusion protein in the persistent strain. This suggests that the paucity of active fusion complexes is due to restricted intracellular processing of the viral fusion protei

Process Development for Batch Production of Micro-Milling Tools Made of Silicon Carbide by Means of the Dry Etching Process

Downsized and complex micro-machining structures have to meet quality requirements concerning geometry and convince through increasing functionality. The development and use of cutting tools in the sub-millimeter range can meet these demands and contribute to the production of intelligent components in biomedical technology, optics or electronics. This article addresses the development of double-edged micro-cutters, which consist of a two-part system of cutter head and shaft. The cutting diameters are between 50 and 200 μm. The silicon carbide cutting heads are manufactured from the solid material using microsystem technology. The substrate used can be structured uniformly via photolithography, which means that 5200 homogeneous micro-milling heads can be produced simultaneously. This novel batch approach represents a contrast to conventionally manufactured micro-milling cutters. The imprint is taken by means of reactive ion etching using a mask made of electroplated nickel. Within this dry etching process, characteristic values such as the etch rate and flank angle of the structures are critical and will be compared in a parameter analysis. At optimal parameters, an anisotropy factor of 0.8 and an etching rate of 0.34 µm/min of the silicon carbide are generated. Finally, the milling heads are diced and joined. In the final machining tests, the functionality is investigated and any signs of wear are evaluated. A tool life of 1500 mm in various materials could be achieved. This and the milling quality achieved are in the range of conventional micro-milling cutters, which gives a positive outlook for further development

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

The genome of <i>Prasinoderma coloniale</i> unveils the existence of a third phylum within green plants

Genome analysis of the pico-eukaryotic marine green algaPrasinoderma colonialeCCMP 1413 unveils the existence of a novel phylum within green plants (Viridiplantae), the Prasinodermophyta, which diverged before the split of Chlorophyta and Streptophyta. Structural features of the genome and gene family comparisons revealed an intermediate position of theP. colonialegenome (25.3 Mb) between the extremely compact, small genomes of picoplanktonic Mamiellophyceae (Chlorophyta) and the larger, more complex genomes of early-diverging streptophyte algae. Reconstruction of the minimal core genome of Viridiplantae allowed identification of an ancestral toolkit of transcription factors and flagellar proteins. Adaptations ofP. colonialeto its deep-water, oligotrophic environment involved expansion of light-harvesting proteins, reduction of early light-induced proteins, evolution of a distinct type of C(4)photosynthesis and carbon-concentrating mechanism, synthesis of the metal-complexing metabolite picolinic acid, and vitamin B-1, B(7)and B(12)auxotrophy. TheP. colonialegenome provides first insights into the dawn of green plant evolution. Genome analysis of the pico-eukaryotic marine green algaPrasinoderma colonialeCCMP 1413 unveils the existence of a novel phylum within green plants (Viridiplantae), the Prasinodermophyta, which diverged before the split of Chlorophyta and Streptophyta

Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj

Nuclear shadowing is observed in the per-nucleon cross-sections of positive muons on carbon, calcium and lead as compared to deuterium. The data were taken by Fermilab experiment E665 using inelastically scattered muons of mean incident momentum 470 GeV/c. Cross-section ratios are presented in the kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj decreases, the size of the shadowing effect, as well as its A dependence, are found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.

Evaluating the Effect of Tissue Anisotropy on Brain Tumor Growth using a Mechanically-coupled Reaction-Diffusion Model

Glioblastoma (GBM), the most frequent malignant brain tumor in adults, is char- acterized by rapid growth and healthy tissue invasion. Long-term prognosis for GBM remains poor with median overall survival between 1 y to 2 y [15]. GBM presents with different growth phenotypes, ranging from invasive tumors without notable mass-effect to strongly displacing lesions. Biomechanical forces, such as those resulting from displacive tumor growth, shape the tumor environment and contribute to tumor progression [9]. We present an extended version of a mechanically–coupled reaction-diffusion model of brain tu- mor growth [1] that simulates tumor evolution over time and across different brain regions using literature-based parameter estimates for tumor cell proliferation, as well as isotropic motility, and mechanical tissue properties. This model yielded realistic estimates of the mechanical impact of a growing tumor on intra-cranial pressure. However, comparison to imaging data showed that asymmetric shapes could not be reproduced by isotropic growth assumptions. We modified this model to account for structural tissue anisotropy which is known to affect the directionality of tumor cell migration and may influence the mechanical behavior of brain tissue. Tumors were seeded at multiple locations in a human MR-DTI brain atlas and their spatio-temporal evolution was simulated using the Finite-Element Method. We evaluated the impact of tissue anisotropy on the model’s ability to reproduce the aspherical shapes of real pathologies by comparing predicted lesions to publicly available GBM imaging data. We found the impact on tumor shape to be strongly location dependent and highest for tumors located in brain regions that are characterized by a single dominant white matter direction, such as the corpus callosum. However, despite strongly anisotropic growth assumptions, all simulated tumors remained more spherical than real lesions at the corresponding location and similar volume. This finding is in agreement with previous studies [17, 6] suggesting that anisotropic cell migration along white matter fiber tracks is not a major determinant of tumor shape in the setting of reaction-diffusion based tumor growth models and for most locations across the brain