Analysis of mixtures of drugs/chemicals along a fixed-ratio ray without single-chemical data to support an additivity model

This article presents and illustrates an approach to designing and analyzing studies involving mixtures/combinations of drugs or chemicals along fixed-ratio rays of the drugs or chemicals for generalized linear models. When interest can be restricted to a specific ray, we consider fixed-ratio ray designs to reduce the amount of experimental effort. When a ray design is used, we have shown that the hypothesis of additivity can be rejected when higher order polynomial terms are required in the total dose-response model. Thus, it is important that we have precise parameter estimates for these higher order polynomial terms in the linear predictor. We have developed methodology for finding a D _s -optimal design based on this subset of the terms in the linear predictor.     

Evaluation of restoration success in alluvial grasslands under contrasting flooding regimes

Along the northern Upper Rhine, Germany, large-scaled restoration attempts aiming at the recovery of species-rich alluvial meadows from ex-arable fields were evaluated. We analysed floristic composition, soil nutrient status and biomass production of old and newly established meadows with respect to their position in both, the recent functional flood-plain and the fossil flood-plain compartment which is protected from flooding by a dyke. It is hypothesised that restoration in terms of species-enrichment will be more successful in the functional floodplain due to the input of propagules in the course of flooding events.Generally, we found great floristic differences between old and new meadows, independent of their position in the floodplain. After 15-20 years of restoration management, the floristic structure of new meadows was still dominated by sown grasses and a high proportion of ruderal and arable species, whereas target species of flood-meadows largely failed to establish in both compartments. Old and new meadows differed only slightly in the environmental variables, while measured significant differences in plant available phosphorus and biomass yield were revealed between floodplain compartments.The results indicated a minor effect of edaphic site conditions on the low restoration success and limited dispersal and recruitment were revealed to be the main constraints for restoration. We found no evidence that species enrichment is enhanced in the functional floodplain via the input of diaspores by flooding. Our results strongly suggest that dispersal limitation of target species is unlikely to be overcome merely by the restoration of more natural flooding conditions.     

Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming

Upon maturation, dendritic cells (DCs) acquire the unique ability to activate na?ve T cells. We used time-lapse video microscopy and two-photon imaging of intact lymph nodes to show that after establishing initial contact between their dendrites and na?ve T lymphocytes, mature DCs migrate toward the contacted lymphocytes. Subsequently, the DCs tightly entrap the T cells within a complex net of membrane extensions. The Rho family guanosine triphosphatases Rac1 and Rac2 but not Rho itself control the formation of dendrites in mature DCs, their polarized short-range migration toward T cells, and T cell priming.     

A 5-micron-bright spot on Titan: evidence for surface diversity

Observations from the Cassini Visual and Infrared Mapping Spectrometer show an anomalously bright spot on Titan located at 80 degrees W and 20 degrees S. This area is bright in reflected light at all observed wavelengths, but is most noticeable at 5 microns. The spot is associated with a surface albedo feature identified in images taken by the Cassini Imaging Science Subsystem. We discuss various hypotheses about the source of the spot, reaching the conclusion that the spot is probably due to variation in surface composition, perhaps associated with recent geophysical phenomena.     

Disulfide isomerization after membrane release of its SAR domain activates P1 lysozyme

The P1 lysozyme Lyz is secreted to the periplasm of Escherichia coli and accumulates in an inactive membrane-tethered form. Genetic and biochemical experiments show that, when released from the bilayer, Lyz is activated by an intramolecular thiol-disulfide isomerization, which requires a cysteine in its N-terminal SAR (signal-arrest-release) domain. Crystal structures confirm the alternative disulfide linkages in the two forms of Lyz and reveal dramatic conformational differences in the catalytic domain. Thus, the exported P1 endolysin is kept inactive by three levels of control-topological, conformational, and covalent-until its release from the membrane is triggered by the P1 holin.     

Direct measurements of the convective recycling of the upper troposphere

We present a statistical representation of the aggregate effects of deep convection on the chemistry and dynamics of the upper troposphere (UT) based on direct aircraft observations of the chemical composition of the UT over the eastern United States and Canada during summer. These measurements provide unique observational constraints on the chemistry occurring downwind of convection and the rate at which air in the UT is recycled. These results provide quantitative measures that can be used to evaluate global climate and chemistry models.     

Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants

Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.