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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.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

AE1 is the most abundant membrane protein in erythrocytes. Here, authors report cryo-EM structures in multiple states and demonstrate the inhibitory effect of PIP2 lipids. Free energy calculations reveal the molecular mechanism for PIP₂ inhibition.

Supersonic turbulence is relevant to astrophysical plasmas with their study mostly limited to numerical simulations. Here the authors demonstrate supersonic turbulence in collisional high Mach number plasma jets generated in laboratory by using high power lasers.

CDP-alcohol phosphotransferases (CDP-APs) are critical for the biosynthesis of glycerophospholipids. Here, Clarke et al.present the first structure of an enzymatically active CDP-AP in the presence of a bound lipid substrate and propose a mechanism for substrate binding and catalysis.

Metazoans have evolved endocrine systems that signal through dimerized receptors in response to cognate hormones. These authors characterize a nematode homolog of such human receptors, presenting the cryo-EM structure of an asymmetric dimer that embodies properties of the human receptors.

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).

Researchers develop a new way to selectively remove ion channel proteins by recruiting the body’s own NEDD4-2 enzyme using custom nanobodies, offering a precise and general strategy for future drug development.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

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.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Metabolic strategies of cave microorganisms are poorly studied. Here, the authors show that cave microbes use atmospheric trace gases hydrogen, carbon monoxide and methane as energy and carbon sources, sustaining primary production and revealing how life can thrive in oligotrophic and dark ecosystems.

Cell2fate improves RNA velocity analysis of single-cell and spatial transcriptomics data by module decomposition of realistic biophysical models of transcription dynamics.

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.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

A single-cell sequencing study using more than 30,000 tumour genomes from human ovarian cancers shows that whole-genome doubling is an ongoing mutational process that drives tumour evolution and disrupts immunity.

Arboviruses transmitted by Aedes mosquitoes have an expanding global distribution and identifying areas at risk is important for public health planning. Here, the authors present global disease maps for dengue, chikungunya, Zika and yellow fever through a multi-disease ecological niche modelling approach.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

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.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

CryoDRGN-AI is a deep learning system for ab initio reconstruction of dynamic biomolecular complexes from cryo-electron microscopy and cryo-electron tomography imaging datasets.

Colour code on a superconducting qubit quantum processor is demonstrated, reporting above-breakeven performance and logical error scaling with increased code size by a factor of 1.56 moving from distance-3 to distance-5 code.

Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease.

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.

An improved structure of the TRPV3 pentamer, together with molecular dynamics simulations, provides insights into its conformation, subunit interfaces, permeability to large cations, and the mechanism of transition to the canonical tetrameric state.

The structure of the GABA_B receptor in an inactive state reveals, amongst other features, a latch between the two subunits that locks the transmembrane domain interface, and the presence of large phospholipids that may modulate receptor function.

Stb15 provides resistance to Septoria tritici blotch in wheat and encodes a G-type lectin receptor-like kinase. The three cloned Stb genes, which are effective against different pathogen isolates, encode diverse receptor-like kinases with extracellular domains potentially involved in sugar binding.

Using electron cryomicroscopy, the closed-state structure of rabbit RyR1 is determined at 4.8 Å resolution; analysis confirms that the RyR1 architecture consists of a six-transmembrane ion channel with a cytosolic α-solenoid scaffold, and suggests a mechanism for Ca²⁺-induced channel opening.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Mt Fuji’s freshwater springs were believed to be fed exclusively by shallow groundwater aquifers. Using a newly developed combination of tracer techniques, this study finds widespread vertical exchange between shallow and deeper aquifers and shows evidence of a substantial deep groundwater contribution to the springs.

Scalable quantum information processing requires controllable high-coherence qubits. Here, the authors present superconducting flux qubits with broad frequency tunability, strong anharmonicity and high reproducibility, identifying photon shot noise as the main source of dephasing for further improvements.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Cryo-electron microscopy and molecular dynamics simulations reveal how MFSD2A transports essential omega-3 fatty acids across the blood–brain and blood–retina barriers as lysolipids.