Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors

Retinoic acid-related orphan receptor RORγt plays a pivotal role in the differentiation of T_H17 cells. Antagonizing RORγt transcriptional activity is a potential means to treat T_H17-related autoimmune diseases. Herein, we describe the identification of a series of diphenylpropanamides as novel and selective RORγ antagonists. Diphenylpropanamide <b>4n</b> inhibited the transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed human T_H17 cell differentiation at submicromolar concentrations

Effects of stream predator richness on the prey community and ecosystem attributes.

It is important to understand the role that different predators can have to be able to predict how changes in the predator assemblage may affect the prey community and ecosystem attributes. We tested the effects of different stream predators on macroinvertebrates and ecosystem attributes, in terms of benthic algal biomass and accumulation of detritus, in artificial stream channels. Predator richness was manipulated from zero to three predators, using two fish and one crayfish species, while density was kept equal (n = 6) in all treatments with predators. Predators differed in their foraging strategies (benthic vs. drift feeding fish and omnivorous crayfish) but had overlapping food preferences. We found effects of both predator species richness and identity, but the direction of effects differed depending on the response variable. While there was no effect on macroinvertebrate biomass, diversity of predatory macroinvertebrates decreased with increasing predator species richness, which suggests complementarity between predators for this functional feeding group. Moreover, the accumulation of detritus was affected by both predator species richness and predator identity. Increasing predator species richness decreased detritus accumulation and presence of the benthic fish resulted in the lowest amounts of detritus. Predator identity (the benthic fish), but not predator species richness had a positive effect on benthic algal biomass. Furthermore, the results indicate indirect negative effects between the two ecosystem attributes, with a negative correlation between the amount of detritus and algal biomass. Hence, interactions between different predators directly affected stream community structure, while predator identity had the strongest impact on ecosystem attributes

Novel Antibacterial Class

We report the discovery and characterization of a novel ribosome inhibitor (NRI) class that exhibits selective and broad-spectrum antibacterial activity. Compounds in this class inhibit growth of many gram-positive and gram-negative bacteria, including the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis, and are nontoxic to human cell lines. The first NRI was discovered in a high-throughput screen designed to identify inhibitors of cell-free translation in extracts from S. pneumoniae. The chemical structure of the NRI class is related to antibacterial quinolones, but, interestingly, the differences in structure are sufficient to completely alter the biochemical and intracellular mechanisms of action. Expression array studies and analysis of NRI-resistant mutants confirm this difference in intracellular mechanism and provide evidence that the NRIs inhibit bacterial protein synthesis by inhibiting ribosomes. Furthermore, compounds in the NRI series appear to inhibit bacterial ribosomes by a new mechanism, because NRI-resistant strains are not cross-resistant to other ribosome inhibitors, such as macrolides, chloramphenicol, tetracycline, aminoglycosides, or oxazolidinones. The NRIs are a promising new antibacterial class with activity against all major drug-resistant respiratory pathogens