A Role for Cross-linking Proteins in Actin Filament Network Organization and Force Generation.

The high turgor pressure across the plasma membrane of yeasts creates a requirement for substantial force production by actin polymerization and myosin motor activity for clathrin-mediated endocytosis (CME). Endocytic internalization is severely impeded in the absence of fimbrin, an actin filament crosslinking protein called Sac6 in budding yeast. Here, we combine live-cell imaging and mathematical modeling to gain new insights into the role of actin filament crosslinking proteins in force generation.

Managing violence and aggression in the emergency department.

Half of all reported violent incidents in healthcare settings occur in the emergency department (ED), so ED nurses are disproportionately affected by violence and aggression. Violence and aggression can cause physical injury, psychological harm, delays to patient care, eroded staff morale, increased sick leave and low staff retention. This article explores potential causes and risk factors for violent or aggressive behaviour from patients and visitors in the ED.

Toxicological Characterization of Exon Skipping Phosphorodiamidate Morpholino Oligomers (PMOs) in Non-human Primates.

Background: Phosphorodiamidate morpholino oligomers (PMOs) are a class of exon skipping drugs including eteplirsen, which has shown considerable promise for treatment of the degenerative neuromuscular disease, Duchenne musculardystrophy (DMD).

Objective: Toxicity studies in non-human primates (NHPs) of 12 weeks duration with two new PMOs for DMD, SRP-4045 and SRP-4053, along with results from a chronic study in NHPs of 39 weeks duration for eteplirsen, are described here.

Methods: PMOs were administered once-weekly by bolus intravenous (IV) injections to male NHPs.

Toxicogenomics: a new revolution in drug safety.

New drugs are screened for adverse reactions using a laborious, costly process and still some promising therapeutics are withdrawn from the marketplace because of unforeseen human toxicity. Novel higher throughput methods in toxicology need to be developed. These new approaches should provide more insight into potential human toxicity than current methods.