We have developed a method combining microinjection and automated fluorescence microscopy to continuously assess the degradation rate, subcellular localization and intracellular concentration of protein analytes at the single-cell level. Cells are unperturbed and grown in unaltered environmental conditions and show high viability. The injection of analytes at defined ratios and concentrations allows for a clearly defined starting point of degradation, without the entanglement of biosynthesis/uptake, often encountered in existing methods.
View Article and Find Full Text PDFMutated KRAS proteins are frequently expressed in some of the most lethal human cancers and thus have been a target of intensive drug discovery efforts for decades. Lately, KRAS(G12C) switch-II pocket (SII-P)-targeting covalent small molecule inhibitors have finally reached clinical practice. Sotorasib (AMG-510) was the first FDA-approved covalent inhibitor to treat KRAS(G12C)-positive nonsmall cell lung cancer (NSCLC), followed soon by adagrasib (MRTX849).
View Article and Find Full Text PDFBackground: The population health burden of adverse childhood experiences (ACEs) reflects a critical need for evidence-based provider training. Rural children are also more likely than urban children to have any ACEs. A large proportion of providers are unaware of the detrimental effects of ACEs.
View Article and Find Full Text PDFBackground: Adverse childhood experiences (ACEs) are pervasive and well-recognized as having lasting deleterious effects on the physical and mental health of those who experience them, particularly with accumulated exposure.
Objective: This study seeks to identify the perspectives of interprofessional health providers on their personal and professional experiences with ACEs, ACEs screening, how to work with people with ACEs, and make recommendations for the field.
Participants And Setting: Sixty-two health professionals and PhD students who completed at least one module of an online course and at least one of the accompanying discussion board sub-prompts.