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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).

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.

Proteins are often modified by complex carbohydrates (N-glycans). Here, authors identified gene regulators of this process and uncovered links between plasma protein Nglycosylation, metabolic and liver diseases, and anti-inflammatory proteins.

New archaeological and ancient genomic data from humans in Papua New Guinea and the Bismarck Archipelago shed light on regional human admixture and genetic isolation over the past 2,500 years.

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.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

In Arabidopsis, lateral root emergence requires the penetration of overlying tissues by stem cells deep within the root. Voß et al. reveal that changes in auxin signalling required for this process are mediated by local rephasing of the circadian clock.

Next-generation red and green G-protein-coupled receptor-based dopamine sensors with improved properties have been developed. Their performance is demonstrated in cell culture, in brain slices and in vivo in the mouse.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses.

Bacterial protein FtsZ polymerizes at mid-cell and exhibits treadmilling dynamics, driving the movement of enzymes that synthesize septal peptidoglycan. Here, McCausland et al. combine theoretical modelling with single-molecule imaging of bacteria to show that FtsZ treadmilling drives enzyme movement via a Brownian ratchet mechanism.

Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.

Spin-orbit coupling in gate-defined quantum dots in silicon metal-oxide semiconductors provides a promising route for electrical control of spin qubits. Here, the authors demonstrate that intervalley spin–orbit interaction enables fast singlet–triplet qubit rotations in this platform, at frequencies exceeding 200MHz.

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

Some of the earliest life on Earth flourished in terrestrial hot springs. Here, the authors present evidence for ca. 3.5 Ga hot spring deposits from the Dresser Formation, Pilbara Craton, Australia, that host some of the earliest known life in the form of stromatolites and other microbial biosignatures.

Charles Mullighan, Stephen Hunger, Jinghui Zhang and colleagues report a genomic analysis of 264 pediatric and young adult T-lineage acute lymphoblastic leukemia (T-ALL) samples. They identify 106 candidate driver genes, 53 of which have not been described previously in pediatric T-ALL, as well as associations between mutations and disease stage or subtype.

In the first SARS-CoV-2 challenge study in humans, 36 young, healthy adult participants were intranasally inoculated with virus and monitored for productive infection, symptoms, virus kinetics, antibody response and safety in a controlled setting.

Attempts to incorporate additional criteria into the traditional tumour-node-metastasis staging classification have often resulted in inaccuracy and confusion in the use of terminology. In this Position paper, the authors provide guidance on the consistent use of the terminology relating to cancer staging.

Superfluid ³He appears to be composed of two independent superfluid subsystems. Here the authors discuss diffusion of quasiparticles in the two-dimensional boundary superfluid.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

As the performance of silicon-based qubits has improved, there has been increasing focus on developing designs that are compatible with industrial processes. Here, Jock et al. exploit spin-orbit coupling to demonstrate full, all-electrical control of a metal-oxide-semiconductor electron spin qubit.

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.

Matthew Brown, Peter Donnelly and colleagues report results of a genome-wide association meta-analysis and follow-up study of ankylosing spondylitis. They identify three new risk variants and report a genetic interaction between ERAP1 and HLA-B27, implicating aberrant peptide handling in the pathophysiology of this disease.

A biomedical application of a nanoconjugate is now shown in vivo. Sealed carbon nanotubes filled with a radionuclide are functionalized with carbohydrate molecules without prompting cargo release. The stability and biocompatibility of the capsule together with the radioactive payload enables in vivo imaging of the system and delivery of a high-density radiodose.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.