Accurate Cytotoxicity and Proliferation Determination: Advantages of a High-Throughput Phenotypic Approach Over ATP Luminescence Assays.

Cell viability and proliferation assays are a fundamental tool in the drug discovery process and are used to evaluate both the antiproliferative potency and toxicity of compounds. Some lead discovery groups generate cell viability data for up to two million compounds per screen, so any method used to assess these parameters needs to deliver not only on data quality but also on throughput and assay cost per well. Most methods used to determine cell viability cannot deliver on all three of these requirements, so compromises have to be made.

Advances in laser scanning imaging cytometry for high-content screening.

The advent of high-content screening more than a decade ago remodeled drug discovery workflows by recasting the role of cell-based approaches in target identification, primary screening, lead optimization, and toxicity. The ability to identify and quantify compound effects on multiple cellular functions allows for rapid characterization of chemical libraries. Laser scanning imaging cytometry (LSIC) is one of the technologies that is being applied to a broad range of assays utilizing fluorescent labeling, at throughputs compatible with primary screening campaigns.

Subunit dimers of alpha-hemolysin expand the engineering toolbox for protein nanopores.

Staphylococcal α-hemolysin (αHL) forms a heptameric pore that features a 14-stranded transmembrane β-barrel. We attempted to force the αHL pore to adopt novel stoichiometries by oligomerizing subunit dimers generated by in vitro transcription and translation of a tandem gene. However, in vitro transcription and translation also produced truncated proteins, monomers, that were preferentially incorporated into oligomers.

Nonlinear time series analysis of food intake in the dab and the rainbow trout.

Evidence suggests that dab and rainbow trout are able to quickly adjust their food intake to an appropriate level when offered novel diets. In addition day-to-day and meal-to-meal food intake varies greatly and meal timing is plastic. Why this is the case is not clear: Food intake in fish is influenced by many factors, however the hierarchy and mechanisms by which these interact is not yet fully understood.