Extended Data Table News Today

The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens1–6. Despite advances in treatment with immune checkpoint inhibitors7–10, there is an unmet need in the treatment of MSI cancers11–14. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative...

RAS oncogenes (collectively NRAS, HRAS and especially KRAS) are among the most frequently mutated genes in cancer, with common driver mutations occurring at codons 12, 13 and 611. Small molecule inhibitors of the KRAS(G12C) oncoprotein have demonstrated clinical efficacy in patients with multiple cancer types and have led to regulatory approvals for the treatment of non-small cell lung cancer2,3. Nevertheless, KRASG12C mutations account for only around 15% of KRAS-mutated cancers4,5, and there a...

OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1–3, playing critical roles in plant4–7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In lipo...

The emergence of biopolymer building blocks is a crucial step during the origins of life1–6. However, all known formation pathways rely on rare pure feedstocks and demand successive purification and mixing steps to suppress unwanted side reactions and enable high product yields. Here we show that heat flows through thin, crack-like geo-compartments could have provided a widely available yet selective mechanism that separates more than 50 prebiotically relevant building blocks from complex ...

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1–5, give rise to highly divergent lineages6–8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 indiv...

Molecular ions are ubiquitous and play pivotal roles1–3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4–6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9–11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even b...

To run large-scale algorithms on a quantum computer, error-correcting codes must be able to perform a fundamental set of operations, called logic gates, while isolating the encoded information from noise1–8. We can complete a universal set of logic gates by producing special resources called magic states9–11. It is therefore important to produce high-fidelity magic states to conduct algorithms while introducing a minimal amount of noise to the computation. Here we propose and impleme...

Gram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer membrane that blocks the entry of most antibiotics. The impenetrable nature of the outer membrane is due to the presence of a large, amphipathic glycolipid called lipopolysaccharide (LPS) in its outer leaflet1. Assembly of the outer membrane requires transport of LPS across a protein bridge that spans from the cytoplasmic membrane to the cell surface. Maintaining out...

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to de...

In a series of studies, researchers found that personal biases significantly influence how individuals remember the COVID-19 pandemic, which could potentially shape historical narratives and impact future pandemic policies. They suggest that recognizing these biases is crucial for developing long-term strategies that maintain societal trust and cohesion.