Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease.

The SARS-CoV-2 main protease (M or Nsp5) is critical for production of viral proteins during infection and, like many viral proteases, also targets host proteins to subvert their cellular functions. Here, we show that the human tRNA methyltransferase TRMT1 is recognized and cleaved by SARS-CoV-2 M. TRMT1 installs the ,-dimethylguanosine (m2,2G) modification on mammalian tRNAs, which promotes cellular protein synthesis and redox homeostasis.

Corrigendum: Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex.

[This corrects the article DOI: 10.3389/fphar.2022.

Engineering synthetic phosphorylation signaling networks in human cells.

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression.

Resolution of selective fetal growth restriction after laser surgery for twin-to-twin transfusion syndrome can be predicted by predisease growth discordance.

Objective: To determine if the resolution of fetal growth discordance after laser surgery in pregnancies with twin-to-twin transfusion syndrome (TTTS) and coexisting selective fetal growth restriction (sFGR) can be predicted by estimated fetal weight (EFW) discordance recorded prior to the development of TTTS (pre-TTTS).

Methods: This was a single-center, retrospective analysis of prospectively collected data on monochorionic twins with concurrent TTTS and sFGR that underwent laser surgery and had available growth ultrasound records from a pre-TTTS ultrasound evaluation. Maternal demographics, pregnancy characteristics and birth outcomes were compared between three outcome groups: double twin survival with resolved sFGR determined by birth weight discordance (BWD) < 20%; double twin survival with ongoing sFGR determined by BWD ≥ 20%; and single or double fetal demise after laser surgery.

Estimated Vaccine Effectiveness for Pediatric Patients With Severe Influenza, 2015-2020.

Importance: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally.

Objective: To investigate VE in children by severity of influenza illness.

Design, Setting, And Participants: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020.