Ferroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2. We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc− or directly target GPX4, as do erastin and RSL3, respectively, or deplete GPX4 protein, as does FIN56. Instead, FINO2 causes both indirect loss of GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation. These findings suggest that endoperoxides such as FINO2 can initiate a multi-pronged mechanism of ferroptosis.

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Our study reveals a novel role for ANKRD1 as a selective regulator of PE-induced signalling whereby ANKRD1 recruits and localizes GATA4 and ERK1/2 in a sarcomeric macro-molecular complex to enhance GATA4 phosphorylation with subsequent nuclear translocation of the ANKRD1 complex to induce hypertrophic gene expression.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has expanded the utilization of telemedicine in clinical practice to minimize potential risks to both patients and providers. We aim to describe the perception of telemedicine by both surgical patients and providers to understand the preferences for future incorporation in future surgical practice. Methods An anonymous survey was administered to providers that transitioned clinic visits to telemedicine encounters since the start of the COVID-19 pandemic. In the second part of the study, patients who underwent video telemedicine appointments answered survey questions via telephone. Results Twenty-six out of 36 (72.7%) providers responded. Over 75% reported that they could effectively communicate with patients over telemedicine. Six (23.1%) reported that they could adequately assess surgical sites. Of 361 patients, 187 consented to the study (consent rate 51.8%). Among patients, the most common result to choose a telemedicine appointment was to avoid the risk of COVID-19 transmission (84, 44.9%), though the minority reported that they would choose telemedicine after the pandemic (64, 34.2%). Those patients who would choose an in-person visit were more likely to have a higher Charlson Comorbidity Score, body mass index, and use friends or family for transportation. In open-ended feedback, patients suggested that telemedicine would be better suited for long-term follow-up rather than the immediate postoperative setting. Conclusions Patients and providers reported a high degree of satisfaction using telemedicine during the COVID-19 pandemic but noted concern with limited physical examinations. Telemedicine may be suited for preoperative evaluation and medium-term and long-term postoperative follow-up for surgical patients.

Protein synthesis in eukaryotes is regulated by diverse reprogramming mechanisms that expand the coding capacity of individual genes. Here, we exploit one such mechanism termed −1 programmed ribosomal frameshifting (−1 PRF) to engineer ligand-responsive RNA switches that regulate protein expression. First, efficient −1 PRF stimulatory RNA elements were discovered by in vitro selection; then, ligand-responsive switches were constructed by coupling −1 PRF stimulatory elements to RNA aptamers using rational design and in vivo directed evolution. We demonstrate that −1 PRF switches tightly control the relative stoichiometry of two distinct protein outputs from a single mRNA, exhibiting consistent ligand response across whole populations of cells. Furthermore, −1 PRF switches were applied to build single-mRNA logic gates and an apoptosis module in yeast. Together, these results showcase the potential for harnessing translation-reprogramming mechanisms for synthetic biology, and establish −1 PRF switches as powerful RNA tools for controlling protein synthesis in eukaryotes.