Rationale Mu opioid receptor (MOR) analgesics like morphine have high intrinsic MOR efficacy but produce side effects. Lower efficacy MOR agonists like buprenorphine can produce analgesia with improved safety. We recently described a series of novel phenylmorphan-based MOR agonists with graded MOR efficacies, including several with sub-buprenorphine efficacies, and we described their acute effectiveness in mice to produce (a)...

Over recent decades, the eastern North Pacific Ocean (ENP) has undergone significant climate-driven change, characterized by rising sea surface temperatures (SSTs), a northward expansion of the North Pacific Transition Zone (NPTZ), and more frequent marine heatwaves. Juvenile North Pacific loggerhead sea turtles ( Caretta caretta ), a highly mobile species sensitive to environmental variability, have emerged as a sentinel spec...

Rationale Opioid withdrawal is a serious obstacle to self-initiated abstinence, and previous experiences of opioid withdrawal may exacerbate the severity of subsequent incidences. Methods To study the impact of repeated opioid withdrawal episodes, we compared male and female mice after one or five cycles of fentanyl exposure and withdrawal. We selectively expressed hemagglutinin-tagged ribosomes (RiboTag) in microglia of trans...

Many nascent breeding programs aim to achieve genetic gain by crossing locally-elite germplasm, but a lack of systematic approaches to develop elite gene pools from locally adapted varieties hinders their progress. Motivated by the observation of undesirable transgressive segregation in presumed elite crosses in Senegalese cereal breeding programs, we designed approaches for de novo development of elite gene pools from locally...

The North Pacific Transition Zone (NPTZ) is known as a global marine hotspot for many endangered and commercially significant highly mobile marine species. In the last few decades, the region has undergone unprecedented physical and biological transformations in response to climate variability and change. Although it is anticipated that many highly mobile species will need to adapt and shift their distributions, current predic...

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidanc...