Opportunities and insights from pharmaceutical companies on the current use of new approach methodologies in nonclinical safety assessment.

Sharing New Approach Methodology (NAM)-based regulatory experiences is crucial for improving human risk assessment and reducing animal use in drug safety testing. To foster broader adoption, the Biotechnology Innovation Organization surveyed companies about NAM usage and collected case studies showcasing NAM-based regulatory filings for biotherapeutics, where NAMs replaced large animal studies for safety assessment. These scientifically justified approaches were generally accepted by global health authorities, particularly in the context of species relevance limitations, prior target modulation experience, and/or when addressing severe disease.

An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins.

The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear.

Behavioral activation for smoking cessation in veterans with posttraumatic stress disorder: A randomized clinical trial.

Introduction: Certain psychiatric populations have especially low smoking cessation rates. This highlights the need to identify smoking treatments that increase cessation rates by addressing factors thought to impede their success. Behavioral activation (BA) targets anhedonia (i.

Variation in wood density across South American tropical forests.

Wood density is a critical control on tree biomass, so poor understanding of its spatial variation can lead to large and systematic errors in forest biomass estimates and carbon maps. The need to understand how and why wood density varies is especially critical in tropical America where forests have exceptional species diversity and spatial turnover in composition. As tree identity and forest composition are challenging to estimate remotely, ground surveys are essential to know the wood density of trees, whether measured directly or inferred from their identity.

Tropical forests in the Americas are changing too slowly to track climate change.

Understanding the capacity of forests to adapt to climate change is of pivotal importance for conservation science, yet this is still widely unknown. This knowledge gap is particularly acute in high-biodiversity tropical forests. Here, we examined how tropical forests of the Americas have shifted community trait composition in recent decades as a response to changes in climate.