Structure and mechanism of mouse cyclase-associated protein (CAP1) in regulating actin dynamics.

Srv2/CAP is a conserved actin-binding protein with important roles in driving cellular actin dynamics in diverse animal, fungal, and plant species. However, there have been conflicting reports about whether the activities of Srv2/CAP are conserved, particularly between yeast and mammalian homologs. Yeast Srv2 has two distinct functions in actin turnover: its hexameric N-terminal-half enhances cofilin-mediated severing of filaments, while its C-terminal-half catalyzes dissociation of cofilin from ADP-actin monomers and stimulates nucleotide exchange. Here, we dissected the structure and function of mouse CAP1 to better understand its mechanistic relationship to yeast Srv2. Although CAP1 has a shorter N-terminal oligomerization sequence compared with Srv2, we find that the N-terminal-half of CAP1 (N-CAP1) forms hexameric structures with six protrusions, similar to N-Srv2. Further, N-CAP1 autonomously binds to F-actin and decorates the sides and ends of filaments, altering F-actin structure and enhancing cofilin-mediated severing. These activities depend on conserved surface residues on the helical-folded domain. Moreover, N-CAP1 enhances yeast cofilin-mediated severing, and conversely, yeast N-Srv2 enhances human cofilin-mediated severing, highlighting the mechanistic conservation between yeast and mammals. Further, we demonstrate that the C-terminal actin-binding ß-sheet domain of CAP1 is sufficient to catalyze nucleotide-exchange of ADP-actin monomers, while in the presence of cofilin this activity additionally requires the WH2 domain. Thus, the structures, activities, and mechanisms of mouse and yeast Srv2/CAP homologs are remarkably well conserved, suggesting that the same activities and mechanisms underlie many of the diverse actin-based functions ascribed to Srv2/CAP homologs in different organisms.

Sleep-disordered breathing, sleep apnea, and other obesity-related sleep disorders: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides clinicians an overview of sleep-disordered breathing, (e.g., sleep-related hypopnea, apnea), and other obesity-related sleep disorders. Methods: The scientific support for this CPS is based upon published citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: Obesity contributes to sleep-disordered breathing, with the most prevalent manifestation being obstructive sleep apnea. Obesity is also associated with other sleep disorders such as insomnia, primary snoring, and restless legs syndrome. This CPS outlines the evaluation, diagnosis, and treatment of sleep apnea and other sleep disorders, as well as the clinical implications of altered circadian system. Conclusions: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on "Sleep-Disordered Breathing, Sleep Apnea, and Other Obesity-Related Sleep Disorders" is one of a series of OMA CPSs designed to assist clinicians in the care of patients with the disease of obesity.

COVID-19 Pandemic: Clinical Nurse Specialist Practice Supporting Preparedness in the Spheres of Impact.

PURPOSE/OBJECTIVES: The goal of this article is to describe how a high-functioning clinical nurse specialist (CNS) team rapidly responded to the needs of the patients, nursing staff, and organization as a whole to address the coronavirus disease 2019 (COVID-19) crisis. DESCRIPTION OF THE PROJECT: Using the advanced practice knowledge and skills, each CNS moved effortlessly between the 3 spheres of influence, patient, nursing, and organization, to address the unique needs of the COVID-positive patient, as well as the routinely ill who still needed care during a pandemic. In addition to observing and addressing opportunities at the bedside, the CNS team was essential in the development of plans of care, crisis care standards, and a structure for critical care cross-training. OUTCOMES: Five themes essential to success were identified: a common motivation and goal, collaboration, the importance of communication in utilizing established groups to create rapid change, power of influence, and the availability of a vast number of resources including professional nursing roles. CONCLUSION: Using the expertise of a specially trained team of CNSs, an effective plan was established to ensure safe, optimal care during the COVID-19 pandemic and effectively support frontline nurses.