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We demonstrate that the transmembrane protease TMPRSS2 is a receptor for coronavirus HKU1; it triggers HKU1-mediated cell–cell fusion and viral entry by binding to both HKU1A and HKU1B spikes.

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

Using a cryogenic 300-mm wafer prober, a new approach for the testing of hundreds of industry-manufactured spin qubit devices at 1.6 K provides high-volume data on performance, allowing optimization of the complementary metal–oxide–semiconductor (CMOS)-compatible fabrication process.

This study shows a viable pathway to the efficient deployment of state-of-the-art large language models using mixture of experts on 3D analog in-memory computing hardware.

The authors provide cryo-EM reconstructions of human transfer RNA splicing endonuclease during substrate recognition, rationalizing disease-relevant mutations.

Many synthetic DNA nanomachines have been developed and demonstratedin vitro, but their use in living organisms has not been reported. Now, a DNA nanomachine, the I-switch, is used to map spatiotemporal pH changes associated with endosomal maturation within coelomocytes of Caenorhabditis elegans.

Peter Donnelly and colleagues report fine mapping of 14 susceptibility loci in 8,000 cases and controls for type 2 diabetes, coronary artery disease and Graves' disease. They apply a new Bayesian method for analysis of fine-mapping data sets, using this to define sets of SNPs likely to contain causal disease-associated variants.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Measurements combined with post-processing of their outcomes can be used to prepare ordered quantum states. It has been shown that they can drive a Nishimori phase transition into a disordered state even in the presence of quantum errors.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

The combination of mathematical modelling of tumour tissue, optical imaging of cleared tumours from animal models, and in vivo imaging of vascular perfusion in tumours predicts the tumour uptake and distribution of specific therapeutic agents.

TimeLapse-seq chemically recodes labeled s⁴U nucleosides to a cytidine derivative and monitors transcriptional dynamics.

A crystal structure of the RNA aptamer Mango bound to a thiazole orange–derived fluorophore reveals a three-tiered G-quadruplex structure, which, together with three flap-like nucleotides, constrains the fluorophore into its active conformation.

X-ray crystallography and NMR analysis demonstrate that, contrary to previous observations, ^fC does not significantly alter DNA structure, thus suggesting an alternative basis for recognition of ^fC-DNA by epigenome-modifying enzymes.

Stewart Cole and colleagues report the genome sequence and comparative analyses of Brazilian, Indian, North American and Thai strains of Mycobacterium leprae, the etiologial agent of leprosy. They define 16 sub-types of M. leprae and examine their geographical distribution.

Superconducting qubits are used to demonstrate features of quantum fault tolerance, making an important step towards the realization of a practical quantum machine.

The determination of RNA structures within high-molecular weight protein-RNA complexes in non-crystalline state is technically challenging. Here, the authors describe a solid-state NMR protocol for the determination of RNA structures at high resolution.

The final state of self-assembled systems is determined by both their thermodynamic and kinetic pathways. Di Michele et al.develop a strategy to realize predesigned amorphous structures of complex DNA colloidal mixtures by selectively activating local inter- or intra-species interactions upon freezing.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

The standard current–phase relation in tunnel Josephson junctions involves a single sinusoidal term, but real junctions are more complicated. The effects of higher Josephson harmonics have now been identified in superconducting qubit devices.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Single Nucleotide Polymorphisms (SNPs) affect cellular regulatory networks, and SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Here the authors introduce iSNP, a precision medicine pipeline that combines genomics and network biology approaches to uncover patient specific pathways affected in complex diseases.

A combination of gentle stimulated emission depletion microscopy imaging and deep-learning-based improvements in signal-to-noise ratio enables high-resolution reconstruction of neuronal architecture in living tissue.

Therapeutics that target long non-coding RNAs (lncRNAs) are promising treatments for cancer. In this Review, the authors discuss how technological advances have helped improve drug discovery pipelines for lncRNAs and overview their strengths and challenges as oncological therapeutics.

Fluorogenic RNA aptamers have been used for RNA imaging, but folding and fluorescence stability often limited their use in high resolution applications. Here the authors present an array of stably folding Mango II aptamers for imaging of coding and non-coding RNAs at single-molecule resolution, in both live and fixed cells.

Metal-mediated base pairs expand the repertoire of nucleic acid structures and dynamics. Here, the authors prepared a metallo-DNA duplex including two C-Hg(II)-T base pairs separated by six normal Watson-Crick base pairs and investigated its solution structure and dynamics using NMR spectroscopy.

A map of fitness consequence scores is generated for 246 rice genome region classes inferred from nine functional genomic and epigenomic datasets, which illuminates the evolutionary forces associated with genome diversity and guides crop breeding.

Patients’ selection is particularly important in cancer treatment. Here the authors present a proof-of-principle methodology that could be potentially important in assisting therapeutic decisions in the treatment of breast cancer patients.

NMR-based structural analysis of the RNA duplex formed by SMN2 exon 7 and U1 snRNA reveals that the splicing modifier SMN-C5 pulls the bulged adenine into the RNA helix base stack and transforms the weak 5ʹ splice site of SMN2 exon 7 into a stronger one.

Mathematical models are used to predict malaria burden to inform disease control efforts. Here, Cameron et al. use Bayesian statistics to calibrate previous models against a data set of age-structured prevalence and incidence, generating stratified forecasts of the prevalence–incidence relationship.

Exhausted CD8⁺ T cells with diminished effector functions accumulate in tumors. Here, the authors show that hypoxia induces a suppressive phenotype in exhausted T cells and that interfering with hypoxia-mediated CD39 expression limits immunosuppression in the tumor and augments immunotherapy, resulting in arrest of tumor growth.

SwitchSeeker combines computational and experimental techniques to identify functional RNA structural switches. Applied to the human transcriptome, it identified a novel RNA switch in the 3ʹUTR of RORC, linked to nonsense-mediated decay.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Integrative analysis of copy number and gene expression in 2,000 primary breast tumours with long-term clinical follow-up revealed putative cis-acting driver genes, novel subgroups and trans-acting aberration hotspots that modulate subgroup-specific gene networks.

During DNA recombination, two DNA molecules become covalently linked in a four-way structure known as a Holliday junction, which stays connected until the structure is dissolved by the protein resolvase. Although structures of a naked Holliday junction have been obtained, it has been difficult to solve the structure of resolvase sitting in a Holliday junction. This is one of two papers that use two different phage resolvases to solve the structure of resolvase sitting in a Holliday junction.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.