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© 2020. Published by The Company of Biologists Ltd.Eric Olson is Professor and Chair of Molecular Biology at the University of Texas Southwestern Medical Center, USA, where he holds the Robert A. Welch Distinguished Chair in Science, the Annie and Willie Nelson Professorship in Stem Cell Research and the Pogue Distinguished Chair in Research in Cardiac Birth Defects. In 1999, he was elected to the US National Academy of Sciences and, in 2001, to the Institute of Medicine of the National Academy. He has received several awards, including the American Heart Association Research Achievement Award in 2008 and the Eugene Braunwald Academic Mentorship award in 2016. He has a lifelong interest in muscle development and disease, with a particular interest in Duchenne muscular dystrophy. In this interview, conducted at the Society for Developmental Biology's 2019 meeting in Boston, Massachusetts, USA, he discusses his experiences in academia and industry, as well as reflecting on the people and opportunities that contributed to his career. © 2020. Published by The Company of Biologists Ltd.OBJECTIVES Vulvar squamous cell carcinoma is a rare malignancy and lymph node involvement is the most significant prognostic factor. We aimed to evaluate the association between partnership status and mortality from vulvar squamous cell carcinoma, cancer stage at the time of presentation, and the decision for sentinel lymph node biopsy. METHODS The US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database was queried and different parameters were evaluated relative to partnership status. A total of 4851 patients with vulvar squamous cell carcinoma, &gt;18 years of age, who presented between January 2010 to December 2015, were analyzed. Kaplan-Meier and Cox regression analyses were used to assess survival and hazard ratio. Multinomial regression analysis and χ2 were utilized to evaluate odd ratios and significance of variables. RESULTS Most patients were unpartnered (58.5%), including never married (17.7%), divorced (13.8%), or widowed (27%). Partnered patients were mostly Caucasian CONCLUSIONS Partnership status should be considered when counseling patients for vulvar squamous cell carcinoma therapy and when recommending screening and follow-up to optimize patient care. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma. METHODS Patients with stage I endometrial cancer who underwent hysterectomy from 2004 to 2013 were identified through the National Cancer Database and classified as stage IA G1/2, stage IA G3, stage IB G1/2, and stage IB G3. Trends in use of vaginal brachytherapy and external beam radiation therapy were assessed. Overall survival was measured from surgery and estimated using the Kaplan-Meier method. The effect of radiation therapy on overall survival was assessed within each stage/grade group using Cox proportional hazards analysis in propensity-matched treatment groups. RESULTS A total of 132 393 patients met inclusion criteria, and 81% of patients had stage IA and 19% had stage IB endometrial cancer. Adjuvant therapy was administered in 18% of patients 52% received vaginal brachytherapy, 30% external beam radiation therapy, and 18% chemotherapy ±radiare shown to benefit from improved overall survival when adjuvant radiation therapy is administered. These findings demonstrate potential opportunities to reduce both overtreatment and undertreatment in stage I endometrial cancer patients. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.Folding of proteins entering the mammalian secretory pathway requires the insertion of the correct disulfides. Disulfide formation involves both an oxidative pathway for their insertion and a reductive pathway to remove incorrectly formed disulfides. Reduction of these disulfides is critical for correct folding and degradation of misfolded proteins. Previously, we showed that the reductive pathway is driven by NADPH generated in the cytosol. Here, by reconstituting the pathway using purified proteins and ER microsomal membranes, we demonstrate that the thioredoxin reductase system provides the minimal cytosolic components required for reducing proteins within the ER lumen. In particular, saturation of the pathway and its protease sensitivity demonstrates the requirement for a membrane protein to shuttle electrons from the cytosol to the ER. These results provide compelling evidence for the critical role of the cytosol in regulating ER redox homeostasis ensuring correct protein folding and facilitating the degradation of misfolded ER proteins. © 2020. Published by The Company of Biologists Ltd.Many chromatin remodeling and modifying proteins are involved in the DNA damage response by stimulating repair or inducing DNA damage signaling. [https://www.selleckchem.com/ https://www.selleckchem.com/] Interestingly, here we identified that down regulation of the H1-interacting protein SET results in increased resistance to a wide variety of DNA damaging agents. We found that this increased resistance is not the result of an inhibitory effect of SET on DNA repair, but rather the consequence of a suppressed apoptotic response to DNA damage. We further provide evidence that the histone chaperone SET is responsible for the eviction of H1 from chromatin. Knock down of H1 in SET-depleted cells resulted in re-sensitization of cells to DNA damage, suggesting that the increased DNA damage resistance in SET-depleted cells is the result of enhanced retention of H1 on chromatin. Finally, clonogenic survival assays show that SET and p53 are epistatic in attenuating DNA damage-induced cell death. Altogether, our data show a role for SET in the DNA damage response as a regulator of cell survival following genotoxic stress. © 2020. Published by The Company of Biologists Ltd.During mitotic cell division, the actomyosin cytoskeleton undergoes several dynamic changes that play key roles in progression through mitosis. While the regulators of cytokinetic ring formation and contraction are well-established, proteins that regulate cortical stability during anaphase and telophase have been understudied. Here, we describe a role for CLIC4 in regulating actin and actin-regulators at the cortex and cytokinetic cleavage furrow during cytokinesis. We first describe CLIC4 as a new component of the cytokinetic cleavage furrow that is required for successful completion of mitotic cell division. We also demonstrate that CLIC4 regulates the remodeling of sub-plasma membrane actomyosin network within the furrow by recruiting MST4 kinase and regulating ezrin phosphorylation. This work identifies and characterizes new molecular players involved in regulating cortex stiffness and blebbing during late stages of cytokinetic furrowing. © 2020. Published by The Company of Biologists Ltd.