Pathways of mutagenesis are induced in microbes under adverse conditions controlled by stress responses. Control of mutagenesis by stress responses may accelerate evolution specifically when cells are maladapted to their environments, i.e. are stressed. Stress-induced mutagenesis in the Escherichia coli Lac assay occurs either by ‘point’ mutation or gene amplification. Point mutagenesis is associated with DNA double-strand-break (DSB) repair and requires DinB error-prone DNA polymerase and the SOS DNA-damage- and RpoS general-stress responses. We report that the RpoE envelope-protein-stress response is also required. In a screen for mutagenesis-defective mutants, we isolated a transposon insertion in the rpoE P2 promoter. The insertion prevents rpoE induction during stress, but leaves constitutive expression intact, and allows cell viability. rpoE insertion and suppressed null mutants display reduced point mutagenesis and maintenance of amplified DNA. Furthermore, σE acts independently of stress responses previously implicated: SOS/DinB and RpoS, and of σ32, which was postulated to affect mutagenesis. I-SceI-induced DSBs alleviated much of the rpoE phenotype, implying that σE promoted DSB formation. Thus, a third stress response and stress input regulate DSB-repair-associated stress-induced mutagenesis. This provides the first report of mutagenesis promoted by σE, and implies that extracytoplasmic stressors may affect genome integrity and, potentially, the ability to evolve.
Editors of medical and scientific journals select and develop the research and opinion articles that are published, with important implications for research, patient care, and policy.Despite widespread stated commitments to promote diversity among editorial staff, there is little information about the composition of editorial teams. We developed and administered a survey to assess the diversity of editors at leading medical and scientific journals.Methods | The survey, based on prior studies 1 and input from content experts, had questions about demographics and professional characteristics (eAppendix in the Supplement).Beginning in June of 2020, we used the Web of Science 2020 Journal Citation Reports 2 and expert opinion to select 25 medical and scientific journals (17 based in the US and 8 in Europe) with impact factors greater than 10; namely, the Ameri-
all medical publications, than advancing the science and art of medicine and the betterment of public health. Today, and for the future, these goals will be accomplished by championing diversity, equity, and inclusion in all aspects of clinical care, biomedical research, health policy, and society.
We undertook a cross-sectional survey of a random sample of thoracic oncologists from the American Society of Clinical Oncology clinical directory to characterize whether prognostic uncertainty has increased and if tolerance of uncertainty is associated with prognostic discussion practices. We also assessed the Physicians' Reactions to Uncertainty Scale and presented a vignette about an incurable patient with uncertain life expectancy. One hundred and ninety-two of 438 surveys (43.8%) were received. Of the respondents, 52.1% agreed "there is more prognostic uncertainty in the management of lung cancer now than 10 years ago," and 37.4% noted difficulty "staying up-to-date."In multivariable analyses, physician-reported anxiety about uncertainty (p = .05) and reluctance to disclose uncertainty (p = .04) were inversely associated with reporting having prognostic discussions with most patients. For the vignette, 92.1% reported they would discuss incurability, but only 76.3% said they would discuss the patient's life expectancy. Our data suggest prognostic uncertainty has increased in thoracic oncology and oncologists' tolerance of uncertainty may affect discussion practices. The Oncologist 2021;26:e1480-e1482 12. Mack JW, Weeks JC, Wright AA et al. Endof-life discussions, goal attainment, and distress at the end of life: Predictors and outcomes of receipt of care consistent with preferences.
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