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Distal gene regulation is increasingly recognised as a major contributor to complex trait variability. Here, the authors show that a heritable, biologically interpretable transcriptome signature driven by distal regulation predicts metabolic traits across mice and humans.

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.

Experimental systems in which non-trivial topology is driven by spontaneous symmetry breaking are rare. Now, topological gaps resulting from two excitonic condensates have been demonstrated in a three-dimensional material.

Widely cited studies have claimed that musical training is associated with enhanced neural encoding for sound at early stages of the auditory system. Results from this large-scale multisite study do not support this earlier claim.

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).

The intermediate states of the epithelial-to-mesenchymal transition (EMT) in cancer require further molecular characterisation. Here, the authors develop a method to evaluate EMT transformation and trajectories in cancer transcriptomics data, characterising EMT macro-states, including a hybrid state, and EMT hallmarks.

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.

Engineered polyketide synthases (PKSs) have great potential as biocatalysts for the synthesis of chemically challenging molecules. Here the authors show a retrobiosynthesis approach to design and construct PKSs to produce a series of valerolactams for biopolymer production.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The authors model subglacial water flow in East Antarctica and show significant drainage reorganization from 34 Mya to the present and forward to 2100 CE. These drainage networks affect ice dynamics, ice shelf melt, and resulting sea level change.

The authors describe a sensory circuit involving the medial septum (MS), where MS glutamatergic neurons integrate food odours to prime satiety and regulate nutrient intake.

Studies on the essentiality of Ku in human cells reveal that Ku interacts with diverse double-stranded RNA molecules, including antisense Alu, and enables tolerance of Alu sequence expansion in primates.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

Whether and how parvalbumin-expressing neural population from Basal forebrain (BFPVNs) nuclei play a role in associative learning are not fully understood. Here authors show that BFPVNs mediate aversive associative learning via playing crucial roles in encoding outcome-related information.

Receptor tyrosine kinase (RTK)–Ras oncogenes have now been shown to reprogram normal primary human and mouse cells into tumour precursors by empowering cellular mechanotransduction, in a process requiring permissive extracellular-matrix rigidity and intracellular YAP/TAZ/Rac mechanical signalling sustained by activated oncogenes.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Microplastics have spread across the globe and reached even the most remote locations, but an understanding of their origins remains largely elusive. Here the authors quantify and characterise microplastics across the North Pole, finding that synthetic fibers like polyester are dominant and likely sourced from the Atlantic Ocean.

Gomez-Salinero, Itkin et al. demonstrate the cooperative role of two ETS transcriptor factors, ERG and Fli1, in the active maintenance of endothelial cell homeostatic function. Loss of these two genes in adult mice leads to multi-organ failure, hyperinflammation, systemic thrombosis and death. In vitro, expression of both ERG and FLI1 induces human adult non-vascular mesenchymal stromal cells to acquire endothelial-like properties. In humans, several cardiovascular disorders and inflammatory-related diseases are linked to mutations in both genes.

Tumour-derived prostaglandin E₂, signaling through its receptors EP₂ and EP₄, is shown to restrain the responses of tumour-infiltrating stem-like TCF1⁺CD8⁺ T lymphocytes, and modulation of T cell EP₂ and EP₄ can restore anticancer immunity.

AAV vectors are a promising gene delivery vehicle but have a limited DNA packaging capacity. Here, the authors identify cellular restriction factors whose temporary inhibition significantly enhances transduction efficiency of oversized transgenes split into dual AAV vectors.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Together with the fatty-acid-binding protein  FABP5, the cytoskeletal organizer TAGLN2 is an essential factor for fatty acid uptake, mitochondrial respiration and anticancer function in CD8⁺ T cells.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

Whole-genome sequence data for 108 individuals representing 28 language groups across Australia and five language groups for Papua New Guinea suggests that Aboriginal Australians and Papuans diverged from Eurasian populations approximately 60–100 thousand years ago, following a single out-of-Africa dispersal and subsequent admixture with archaic populations.

Faecal carbon:nitrogen measurements and manipulation of nitrogen availability via diet and host secretions in a murine model suggest that intestinal nitrogen limitation occurs due to host absorption and microbial use, leading to benefits for specific taxa.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

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.

Regiospecific cyclizations of reactive poly-β-keto intermediates are known to lead to the structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs), but questions about the process remain. The crystal structure and mutational studies of a dissected product template monodomain from PksA, the NR-PKS that initiates the biosynethesis of the hepatocarcinogen aflatoxin B₁, are now presented.

Leptosphaeria maculans is a plant pathogen that causes stem canker of oilseed rape. Rouxel et al. sequence and describe the key features of the L. maculansgenome, including partitioning into AT-rich blocks that are enriched in effector genes and transposable elements affected by repeat-induced point mutation.

Acquired drug resistance is common during chemotherapy. Here, the authors describe the structural basis and molecular mechanism by which allosteric and clinically approved, ATP-competitive inhibitors of EGFR synergize to overcome resistance in lung cancer.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

Neural processing speed slows with age, but the relationship between this slowing and brain atrophy is unknown. Here, authors show that age-related functional brain differences in auditory and visual processing are partly due to structural differences in the distinct brain regions underlying these processes.

Randomised controlled experiments are the gold standard for scientific inference, but environmental and social scientists often rely on different study designs. Here the authors analyse the use of six common study designs in the fields of biodiversity conservation and social intervention, and quantify the biases in their estimates.

Here the authors propose an RNA interference-based switch for dynamic control of AAV transgene expression. In this approach, transgene expression may be silenced by RNAi and subsequently recovered using REVERSIR oligonucleotides.

Multitrait genome-wide analysis of glaucoma and related phenotypes identifies new risk loci and enables development of a polygenic risk score to predict disease susceptibility and key clinical outcomes.

A weaker ocean gyre in the Pine Island Bay, suppressed by higher sea-ice concentration over the ocean near the Thwaites Eastern Ice Shelf, allows more meltwater to enter the sub-ice-shelf cavity. This increases the ocean temperature beneath the ice.

The human monoclonal antibody S2X259 cross-reacts with spike proteins from all clades of sarbecovirus, and provides prophylactic and therapeutic protection in vivo against parental SARS-CoV-2 and emerging variants of concern.

There are currently two types of antiviral drugs – neutralizing antibodies and small molecule inhibitors. Here, the authors report the development of bicyclic peptides that combine the advantages of both and show their antiviral capacity against SARS-CoV-2 in vitro as well as in small animal models.