Rationale Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain. Objective Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays. Methods Cell-based a...

The identification and removal of host cell proteins (HCPs) from biologic products is a critical step in drug development. Despite recent improvements to purification processes, biologics such as monoclonal antibodies, enzyme replacement therapies, and vaccines that are manufactured in a range of cell lines and purified using diverse processes may contain HCP impurities, making it necessary for developers to identify and quant...

Summary Since a key requirement of known life forms is available water (water activity; a w ), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on E arth inhabited high‐salt environments, suggesting an ability to withstand low water‐activity. The lower limit of wat...

Low genetic heterozygosity is associated with loss of fitness in many natural populations. However, it remains unclear whether the mechanism is related to general (i.e. inbreeding) or local effects, in particular from a subset of loci lying close to genes under balancing selection. Here we analyse involving heterozygosity–fitness correlations on neonatal survival of California sea lions and on susceptibility to hookworm ( Unci...