Canonical RAS signaling, including PI3K/AKT- and RAF/MEK-dependent activities, results mainly from RAS•GTP interaction with its effectors at the plasma membrane. Here, we identified a fundamental, oncogenic, noncanonical RAS•GTP activity that increases XPO1-dependent export of nuclear protein cargo into the cytoplasm and is independent of PI3K/AKT and RAF/MEK signaling. This RAS-dependent step acts downstream from XPO1 binding to nuclear protein cargo and is mediated by a perinuclear protein complex between RAS•GTP and RanGAP1 that facilitates hydrolysis of Ran•GTP to Ran•GDP, which promotes release of nuclear protein cargo into the cytoplasm.
View Article and Find Full Text PDFAntimicrob Steward Healthc Epidemiol
October 2024
Background: infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods: A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI.
Background: The aim of this study was to elicit clinicians' perspectives to help reduce antibiotic prescribing for asymptomatic bacteriuria and improve a patient-centered educational brochure for older adults with urinary tract infections or asymptomatic bacteriuria.
Methods: Between October 2023 and April 2024, we conducted semi-structured qualitative interviews of clinicians who treat patients aged ≥65 years for urinary tract infections or bacteria in the urine, at infectious disease clinics, community senior living facilities, memory care clinics, and general practice. We developed an interview guide based on a behavior change framework and thematically analyzed written transcripts of audio-recorded interviews using inductive and deductive coding techniques.