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Mutations present at a low frequency in a sample are detected with high sensitivity and a low error rate.

Here, the authors provide molecular insight into the remarkable ability of Tardigrades to withstand high levels of radiation by demonstrating that their Dsup protein interacts with multiple surfaces of the nucleosome to protect the genome from oxidative DNA damage.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

tRNAs fold into defined structures and extensively interact with cellular proteins and ribosomes. Here, the authors develop a chemical mapping sequencing method to profile human tRNA structures and their interactions in cells. Their results reveal dynamic tRNA structurome and interactome in response to stress with consequences in translational regulation.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Free-standing nanoparticle superlattices offer interesting possibilities for the design of devices free from undesired effects of substrates. DNA can now be used to obtain superlattices with control over interparticle spacing, offering an alternative perspective on the synthesis of nanoparticle solids.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Gene editing approaches are widely used for correcting mutations, but their application is largely limited to cells and not living animals. Here the authors show that in vivoγPNA-mediated editing of a β-globin mutation is promoted by SCF and leads to sustained normalization of blood haemoglobin levels β-thalassemic mice.

A combination of mouse model data and data from a randomized phase 2 trial in patients with breast cancer in remission demonstrates feasibility, safety and a reduction in residual tumor cells following treatment with hydroxychloroquine and/or everolimus.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

This paper develops a multiplex RNA-seq method that reports tRNA abundance, modification, charging, and fragmentation. Results show stress-induced regulation in translational elongation and association of modification and tRNA fragment biogenesis.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Cyanuric acid, a small molecule with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) into long fibres with a unique internal structure. The association of adenine and cyanuric acid units into a hexameric rosette motif brings together poly(adenine) triplexes with subsequent cooperative polymerization.

DNA sequences from the insulin-linked polymorphic region can form non-canonical structures. Here, the authors present a structural investigation into the relationship between native sequence variants and the different structures they form.

The cocrystal structure of bacterial alarmone ZMP with its cognate riboswitch reveals how the two subdomains of the latter mediate ligand recognition. Supporting biochemical analyses show that ligand binding affinity and transcription antitermination are modulated by the interdomain linker length.

Multiresolution computational simulations generate all-atom models of a complete packaged virus particle.

A long-standing problem with the RNA-world hypothesis is that enzyme-free replication of RNA strands has not been demonstrated. Here, immobilization of a template strand and periodic replacement of a solution containing activated nucleotides allows the copying of unmodified RNA sequences containing any of the four natural nucleobases in near-quantitative yield.

Colorectal cancer is discriminated by measuring cell-free RNA methylation in plasma.

Analysis of more than 95% of each diploid human genome of a four-generation, twenty-eight-member family using five complementary short-read and long-read sequencing technologies provides a truth set to understand the most fundamental processes underlying human genetic variation.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

A survey of members of the legal profession involved in cases requiring the use of scientific experts reveals strong support for court-appointed experts – but little evidence of direct experience to back up this feeling.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Visual receptive fields are known to change positions around the time of a saccade, but the nature of this remapping is unclear. Here Neupane and colleagues show that neurons in area V4 of the visual cortex exhibit two types of remapping, one consistent with a role in maintaining perceptual stability, and a second that seems to reflect shifts of attention.

Oligonucleotide catalysts such as ribozymes and DNAzymes can cleave RNA efficiently and specifically but are typically dependent on high concentrations of divalent cations, limiting their biological applications. A modular XNAzyme catalyst composed of 2′-deoxy-2′-fluoro-β-d-arabino nucleic acid (FANA) has now been developed that can cleave long (>5 kb), highly structured mRNAs under physiological conditions and enables allele-specific catalytic RNA knockdown inside cells.

A six-letter sequencing workflow can simultaneously detect genetic and epigenetic bases.

Mutations in the gene encoding Shrm4 are associated with epilepsy and intellectual disability. The authors show that Shrm4 interacts with GABA_Breceptors and regulates tonic inhibition in the hippocampus, and knockdown of Shrm4 in rats leads to anxiety-like behaviour and seizures.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The estimation of low energies of many-body systems is a cornerstone of the computational quantum sciences. This paper demonstrates on a superconducting quantum processor that the Krylov quantum diagonalization algorithm is poised to complement its classical counterparts at the foundation of computational methods for quantum systems.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.