Characterization of an Unusual Fluoride-Resistant Streptococcus mutans Isolate

A fluoride-resistant Streptococcus mutans isolate NCH105 was characterized and compared with wild-type strain UA130. The growth and lactic acid production of strain NCH105 were found to be unaffected by the presence of fluoride at the initial medium pH values of 6.5 and 6. In addition, NCH105 was found to be capable of lowering the pH of the medium to approximately 5.5, which is the critical level where enamel demineralization begins in vivo. Lactic acid production, glucose uptake at pH 6.5 and 6, as well as ATPase activity at pH 5 were found to be unaffected by fluoride. Finally, strain NCH105 is capable of binding as well as the wild-type bacterium to artificial tooth pellicles. These results are unusual when compared with previously isolated fluoride-resistant mutants and suggest that NCH105 may have the ability to colonize the tooth surface and initiate dental caries.     

Prey refugia and the distributions of two Sonoran Desert cacti

Summary Two small Sonoran Desert cacti, Mammillaria microcarpa and Echinocereus englemannii, are commonly found beneath canopies of the larger, tree-like cactus Opuntia fulgida. The mechanism leading to this distribution pattern is incidental to the mode of reproduction in O. fulgida. Opuntia fulgida propagates by means of easily-detached, spine-covered stem joints that accumulate beneath the parent plant. These accumulations of spines apparently deter mammalian herbivores that otherwise consume succulent tissues of the smaller cacti. Such incidental effects are little studied, but they may contribute substantially to structure within plant communities.     

High-Resolution Fractionation of Signaling Endosomes Containing Different Receptors

Receptor endocytosis is regulated by ligand binding, and receptors may signal after endocytosis in signaling endosomes. We hypothesized that signaling endosomes containing different types of receptors may be distinct from one another and have different physical characteristics. To test this hypothesis, we developed a high-resolution organelle fractionation method based on mass and density, optimized to resolve endosomes from other organelles. Three different types of receptors undergoing ligand-induced endocytosis were localized predominately in endosomes that were resolved from one another using this method. Endosomes containing activated receptor tyrosine kinases (RTKs), TrkA and EGFR, were similar to one another. Endosomes containing p75^NTR (in the tumor necrosis receptor superfamily) and PAC1 (a G-protein-coupled receptor) were distinct from each other and from RTK endosomes. Receptor-specific endosomes may direct the intracellular location and duration of signal transduction pathways to dictate response to signals and determine cell fate.     

Macrocyclic pyrrolobenzodiazepine dimers as antibody-drug conjugate payloads

Macrocyclic pyrrolobenzodiazepine dimers were designed and evaluated for use as antibody-drug conjugate payloads. Initial structure–activity exploration established that macrocyclization could increase the potency of PBD dimers compared with non-macrocyclic analogs. Further optimization overcame activity-limiting solubility issues, leading to compounds with highly potent (picomolar) activity against several cancer cell lines. High levels of in vitro potency and specificity were demonstrated with an anti-mesothelin conjugate.