Oxidative stress and signaling through EGFR and PKA pathways converge on the nuclear transport factor RanBP1.

Nuclear protein trafficking requires the soluble transport factor RanBP1. The subcellular distribution of RanBP1 is dynamic, as the protein shuttles between the nucleus and cytoplasm. To date, the signaling pathways regulating RanBP1 subcellular localization are poorly understood. During interphase, RanBP1 resides mostly in the cytoplasm. We show here that oxidative stress concentrates RanBP1 in the nucleus, and our study defines the underlying mechanisms. Specifically, RanBP1's cysteine residues are not essential for its oxidant-induced relocation. Furthermore, our pharmacological approaches uncover that signaling mediated by epidermal growth factor receptor (EGFR) and protein kinase A (PKA) control RanBP1 localization during stress. In particular, pharmacological inhibitors of EGFR or PKA diminish the oxidant-dependent relocation of RanBP1. Mutant analysis identified serine 60 and tyrosine 103 as regulators of RanBP1 nuclear accumulation during oxidant exposure. Taken together, our results define RanBP1 as a target of oxidative stress and a downstream effector of EGFR and PKA signaling routes. This positions RanBP1 at the intersection of important cellular signaling circuits.

Equal Opportunity: Women Representation on Editorial Boards and Authorship of Editorials in Gastroenterology and Hepatology Journals.

INTRODUCTION: The proportion of women editorial board members and authors of editorials in major gastroenterology journals is not known. METHODS: We determined the sex of editorial board members (n = 2,282) and authors of editorials (n = 1,705) across 6 journals from 1985 to 2020 at 5-year intervals. RESULTS: The proportion of women editorial board members increased from 2.9% in 1985 to 19.8% in 2020 (P < 0.0001) and women authors of editorials increased from 0% in 1985 to 22.2% in 2020 (P < 0.0001). DISCUSSION: The proportion of women represented over time has improved, but opportunities likely exist to improve further.

Unexpected BP Sensitivity to Angiotensin II in a Patient With Coronavirus Disease 2019, ARDS, and Septic Shock.

We report the case of an 88-year-old man with coronavirus disease 2019 (COVID-19) who presented with ARDS and septic shock. The patient had exquisite BP sensitivity to low-dose angiotensin II (Ang-2), allowing for rapid liberation from high-dose vasopressors. We hypothesize that sensitivity to Ang-2 might be related to biological effect of severe acute respiratory syndrome coronavirus 2 infection. The case is suggestive of a potential role for synthetic Ang-2 for patients with COVID-19 and septic shock. Further studies are needed to confirm our observed clinical efficacy.

Comparison of Phenotypes and Risk Factors for Esophageal Adenocarcinoma at Present vs Prior Decades.

BACKGROUND & AIMS: The incidence of esophageal adenocarcinoma (EAC) has increased over the past decades. It is unclear if this increase is the result of a new cancer phenotype or an increase in risk factors for EAC. We aimed to compare risk factors, the proportions of intestinal and nonintestinal phenotypes of EAC, and survival times of patients during the 2009 to 2012 time period vs the 1996 to 1997 time period. METHODS: We performed a retrospective single-center cohort study of 829 patients with EAC from the time periods of 1996 to 1997 and 2009 to 2012. Baseline characteristics were compared using χ2 analysis for categoric variables and the Student t test for continuous variables. The Cox proportional hazards model was used to compare 5-year survival. RESULTS: We included 149 patients from the 1996 to 1997 time period and 680 patients from the 2009 to 2012 time period. There was no significant difference between the cohorts in terms of age at cancer presentation, sex, or history of smoking (P > .05). Gastroesophageal reflux symptoms were absent in almost half of the patients from each time period (P = .46). Intestinal metaplasia was identified in esophageal tumor tissues from 48.3% of patients with EAC in the 1996 to 1997 time period and in 49.9% of patients in the 2009 to 2012 time period (P = .45). Patients from each time period presented with similar-stage cancer (P = .25), most at stage III (43% in the 1996-1997 period and 37.8% in the 2009-2012 period). Having EAC during the period of 1996 to1997 was associated with an increased risk of death (hazard ratio, 1.6; 95% CI, 1.3-2.0; P = .001), compared with the 2009 to 2012 time period, in a univariate model (adjusted hazard ratio, 1.7; 95% CI, 1.4-2.1; P < .001) after we controlled for sex, age at diagnosis, tumor stage, and presence of intestinal metaplasia. CONCLUSIONS: In a comparison of patients with EAC from the time periods of 1996 to 1997 vs 2009 to 2012, we found similar and persistent proportions of tumor phenotypes, characterized by a lack of intestinal metaplasia or heartburn symptoms. The lack of symptoms could contribute to our continued inability to identify incident cancers and/or improve patient survival.