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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).

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.

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.

Electrical excitability in neuroendocrine SCLC cells promotes tumour progression through action potential firing, increasing ATP demand and oxidative phosphorylation dependency, whereas non-neuroendocrine cells provide metabolic support, driving a tumour-autonomous cycle that enhances tumorigenesis and metastasis.

Arabinonucleic acid (ANA) Watson-Crick base-pair with RNA/DNA and can evolve to display enzyme-like function. Here, the authors now identify a prebiotic pathway that yields the complete set of Watson-Crick base-pairing purine and pyrimidine ANA nucleosides.

Malaria chemoprevention is used for young children, but resistance mutations raise concerns on efficacy. In this analysis of trials across Africa, the authors show that prevention treatment protects >42 days against susceptible parasites but <12 days against highly resistant strains highlighting the importance of genomic surveillance for chemoprevention strategies.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

2-aminothiazole — a hybrid of prebiotic amino acid and nucleotide precursors — sequentially accumulates and purifies glycolaldehyde and glyceraldehyde from complex mixtures in the order required for ribonucleotide synthesis, dynamically resolves glyceraldehyde from its ketose-isomer dihydroxyacetone, and provides the first strategy to select natural amino acids from abiotic aldehydes and ketones.

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

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Lung adenocarcinomas frequently harbour KRAS mutations, of which a subset are characterized by co-mutation of KEAP1. Here the authors show, in mice, that Kras^G12D mutant tumours are metabolically distinct, with a bronchiolar cell-of-origin.

Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

The authors have previously demonstrated the neutralising capacity of their nanoparticle vaccine, as well as showing protection of non-human primates from SARS-CoV-2 WA-1 infection. In this work, they investigate the ability of their vaccine candidate to neutralise SARS-CoV-2 variants of concern, and protect animals from other sarbecoviruses.

Last year, three Earth-sized planets were discovered to be orbiting the nearby Jupiter-sized star TRAPPIST-1; now, follow-up photometric observations from the ground and from space show that there are at least seven Earth-sized planets in this star system, and that they might be the right temperature to harbour liquid water on their surfaces.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.

Plasmodium vivax, the leading cause of human malaria in Asia and Latin America, is thought to have an Asian origin. Here, the authors show that wild chimpanzees and gorillas in Africa are infected with parasites that are closely related to P. vivax, indicating an African origin for this species.

Variation in antibody levels elicited by the COVID-19 vaccine ChAdOx1 nCov-19 is linked to specific major histocompatibility complex class II alleles, providing insight into the breadth of immune response among vaccinated individuals.

The cyanobacterium Trichodesmium fixes nitrogen exclusively during the day to reduce glycogen ballast and remain buoyant in the surface ocean, where it occupies a specialized niche based on colony formation, high-light adaptation and mineral-dust utilization.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

Dick et al. show that in youth, post-traumatic stress related to Hurricane Irma was predicted by self-reported direct and media exposure. Furthermore, neural responses in brain regions associated with anxiety conferred particular vulnerability to media exposure.

An integrated genomic analysis of 456 human pancreatic ductal adenocarcinomas identifies four subtypes defined by transcriptional expression profiles and show that these are associated with distinct histopathological characteristics and differential prognosis.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

At some stage in the origin of life, an information-carrying polymer must have formed by purely chemical means. That polymer might have been RNA, but until now this theory has been hampered by a lack of evidence for a plausible route in which the ribonucleotides could have formed on prebiotic Earth. Here, just such a route is reported.

Phosphate is critical for all life on Earth but its origins have remained enigmatic. Experiments indicate that phosphate may have been abundant in ancient Fe-rich seawater, providing a crucial ingredient for the origins of life on Earth.

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.

A genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis captures the codevelopment of embryonic tissue and extra-embryonic endoderm and mesoderm niche with early haematopoiesis, with potential for drug testing and disease modelling.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

This study reports a global analysis of binding sites for over 200 RNA-binding proteins (RBPs) from 24 species; conserved RNA-binding motifs are identified, and their analysis allows prediction of interaction sites based on the sequence of the RNA-binding domain alone.

All anxiety disorders are characterized by sleep disruption. Ben Simon et al. develop a neural framework of sleep-loss-induced anxiety, one that emphasizes NREM sleep as a therapeutic target for anxiety amelioration.

One theory for the abiogenesis of RNA involves ligation of shorter oligomers that are observed after dry-state condensation of mononucleotides. Here, the chemo- and regioselective acetylation of (oligo)nucleotides in water under prebiotically plausible conditions is described. This remarkable selectivity permits the rapid template-directed ligation of oligomers to favour extant 3′,5′-linkages.

Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic infection.

Single cell data provides cellular resolution on gene expression, but is rarely mined for isoforms. Analysis of 3' isoforms across ~250 Drosophila cell types reveals the cellular bases for numerous tissue-specific 3' programs, identifies new 3' programs, and nominates candidate trans-acting factors

Seamounts that have subducted beneath a mantle wedge allow the study of trace element recycling and mantle flow in subduction zones. Here, a geochemical analysis of central Tonga–Kermadec arc lavas suggests primarily trench-normal mantle flow in the mantle wedge beneath the central Tonga–Kermadec arc.

Do people think that behaviour is due to genetics, regardless of whether it’s good or bad? Here Lebowitz et al. find that people think prosocial behaviour is more influenced by genetics than antisocial behaviour; this asymmetry seems to be motivated by people’s desire to blame wrongdoers.