Effects of Methyl, Ester, and Amine Surface Groups on Microbial Activity and Communities in Nitrifying Biofilms.

The objective of this study was to determine how different attachment surface chemistries affected the initial and long-term performance and microbial populations of nitrifying biofilms under well-controlled hydrodynamic mixing conditions. While much previous research has focused on the effects of surface properties such as hydrophobicity on bacterial attachment in pure cultures, this study evaluated the effects of specific functional groups on mixed culture composition and functional behavior. Three surfaces with varying hydrophobicity and charge were evaluated for biofilm community development and performance: unmodified poly(dimethylsiloxane) (PDMS), which included terminal methyl groups and was relatively hydrophobic (P-Methyl), PDMS silanized with ester groups (P-Ester), which was uncharged and relatively hydrophilic, and PDMS modified with amine groups (P-Amine), which possessed a positive charge and was the most hydrophilic.

Effects of surface skewness on local shear stresses, biofilm activity, and microbial communities for wastewater treatment.

This study's objective was to assess attachment surface skewness (asymmetric surface height variation) effects on biofilm development. 3D printed molds were used to create surfaces with 300 μm features to provide opposite skewness but identical roughness values. Surfaces with negative skewness had consistently greater nitrite oxidation and biomass growth than other surfaces during biofilm development when studied in annular bioreactor systems.

Performance and diversity responses of nitrifying biofilms developed on varied materials and topographies to stepwise increases of aeration.

Nitrifying biofilms were grown on 3D-printed nylon with three different surface characteristics (flat, millimeter-scale indentations, and indentations with activated carbon (AC) coating) and were subjected to sequentially increasing aeration-based shear to determine the interplay between surface, performance, and microbial populations towards improved design of wastewater treatment media. Biofilms were evaluated for nitrification, biomass detachment, and microbial composition based on Illumina 16s rRNA sequencing. Indentations provided greater stability over flat with respect to population diversity after detachment events but did not improve ammonia removal.

A selective prostaglandin E2 receptor subtype 2 (EP2) antagonist increases the macrophage-mediated clearance of amyloid-beta plaques.

A high-throughput screen resulted in the discovery of benzoxazepine 1, an EP2 antagonist possessing low microsomal stability and potent CYP3A4 inhibition. Modular optimization of lead compound 1 resulted in the discovery of benzoxazepine 52, a molecule with single-digit nM binding affinity for the EP2 receptor and significantly improved microsomal stability. It was devoid of CYP inhibition and was ∼4000-fold selective against the other EP receptors.

An intramolecular inverse electron demand Diels-Alder approach to annulated α-carbolines.

Intramolecular inverse electron demand cycloadditions of isatin-derived 1,2,4-triazines with acetylenic dienophiles tethered by amidations or transesterifications proceed in excellent yields to produce lactam- or lactone-fused α-carbolines. Beginning with various isatins and alkynyl dienophiles, a pilot-scale library of eighty-eight α-carbolines was prepared by using this robust methodology for biological evaluation.

Novel pyrrolidine melanin-concentrating hormone receptor 1 antagonists with reduced hERG inhibition.

We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibition.

Novel 2,3-dihydro-1,4-benzoxazines as potent and orally bioavailable inhibitors of tumor-driven angiogenesis.

Angiogenesis is vital for solid tumor growth, and its prevention is a proven strategy for the treatment of disease states such as cancer. The vascular endothelial growth factor (VEGF) pathway provides several opportunities by which small molecules can act as inhibitors of endothelial proliferation and migration. Critical to these processes is signaling through VEGFR-2 or the kinase insert domain receptor (KDR) upon stimulation by its ligand VEGF.