Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, “outrunning” the host’s immune response in demyelinating plaques, thus continuously eliciting new lesions

Human alveolar progenitors generate dual lineage bronchioalveolar organoids

Mechanisms of epithelial renewal in the alveolar compartment remain incompletely understood. To this end, we aimed to characterize alveolar progenitors. Single-cell RNA-sequencing (scRNA-seq) analysis of the HTII-280(+)/EpCAM(+) population from adult human lung revealed subclusters enriched for adult stem cell signature (ASCS) genes. We found that alveolar progenitors in organoid culture in vitro show phenotypic lineage plasticity as they can yield alveolar or bronchial cell-type progeny. The direction of the differentiation is dependent on the presence of the GSK-3β inhibitor, CHIR99021. By RNA-seq profiling of GSK-3β knockdown organoids we identified additional candidate target genes of the inhibitor, among others FOXM1 and EGF. This gives evidence of Wnt pathway independent regulatory mechanisms of alveolar specification. Following influenza A virus (IAV) infection organoids showed a similar response as lung tissue explants which confirms their suitability for studies of sequelae of pathogen-host interaction

Guiding principles for the development and application of solid-phase phosphorus adsorbents for freshwater ecosystems

While a diverse array of phosphorus (P)-adsorbent materials is currently available for application to freshwater aquatic systems, selection of the most appropriate P-adsorbents remains problematic. In particular, there has to be a close correspondence between attributes of the P-adsorbent, its field performance, and the management goals for treatment. These management goals may vary from a rapid reduction in dissolved P to address seasonal enrichments from internal loading, targeting external fluxes due to anthropogenic sources, or long term inactivation of internal P inventories contained within bottom sediments. It also remains a challenge to develop new methods and materials that are ecologically benign and cost-effective. We draw on evidence in the literature and the authors’ personal experiences in the field, to summarise the attributes of a range of P-adsorbent materials. We offer 'guiding principles' to support practical use of existing materials and outline key development needs for new materials

De la filiation en droit français, autrichien et allemand (Les conflits de lois en matière de fond et de procédure)

Firsching K. De la filiation en droit français, autrichien et allemand (Les conflits de lois en matière de fond et de procédure). In: Revue internationale de droit comparé. Vol. 25 N°1, Janvier-mars 1973. pp. 17-51

Copper porphyry exploration: Combination of X-ray investigations with other methods

International audienceCopper porphyries represent complex alteration zones, hosting variable grades of Cu-(Au-Mo), but also Pb, Zn, Te, Bi and Ag. Processing of these ores becomes more difficult and more expensive as metal grades are lower and highly variable. Reducing the operational costs while increasing the resource efficiency at constant production is the challenge for the mining industries. Samples from specific alteration zones of the Niaz porphyry copper (Mo)-deposit in NW Iran were analyzed by different methods (e.g. scanning electron microscopy (SEM), dual energy (DE) and multi energy (ME) X-ray transmission (XRT) as well as X-ray computed tomography (CT)). The alteration zones are potassic-phyllic, propylitic, phyllic-argillic and peripheral skarn. The propylitic alteration zone is characterized by a coarse-grained diorite composed of feldspars, amphiboles, epidotes, biotite, chlorite, and minor calcite. Ore phases are pyrite, molybdenite, galena Te-Bi phases and sphalerite. The phyllic-argillic mineralized zone is represented by a microgranular quartz-diorite composed of quartz, feldspars, amphibole, biotite, kaolinite and rare siderite. Ore phases are various Cu-sulfides. The peripheral part of the porphyry is a coarse-grained skarn composed of chlorite, amphibole, garnet, epidote, rare diopside, quartz calcite and apatite in the matrix and veins. Ore phases are chalcopyrite, pyrite, Ag-sulfides and Te-Bi clusters attached to galena. Analysis of reconstructed three-dimensional CT volume data revealed structural information as well as two or three different groups of elements (low, medium and high effective atomic number). With these data, in combination with other methods, mine-geologists can assign grey values to minerals based on densities. Thus, it is possible to locate rapidly mineralization in the alteration zones for unknown samples. With XRT, fractions of heavy and light materials can be revealed in two-dimensional radiographs. While CT is useful for a small selection of samples as it is time consuming, XRT can be used in real-time on conveyor belts