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Massively parallel reporter assays across five cell types identify thousands of causal, noncoding regulatory variants among 220,000 loci, revealing diverse regulatory mechanisms shaping complex traits and disease.

Interleukin (IL)-1β has been shown to promote tumour growth in non-small cell lung cancer (NSCLC). Here the authors show using chemo-immunotherapy resistant mouse tumour models that IL-1β improves CD8 T cell recruitment in a CXCL10-dependent manner and IL-1β therapy could be a useful adjunct to chemotherapy and anti-PD-1.

Using food residues on pottery vessels and dental calculus, and faunal remains, Casanova et al. find evidence that Neolithic communities in Iran were milking goats or sheep as early as the seventh millennium BC.

Reconstructing microbial genomes from 820 reef-building corals collected at 99 reefs across 32 islands throughout the Pacific Ocean highlights the importance of conserving coral reefs as vital reservoirs of molecular diversity.

Huot et al. investigate the differences in natural killer (NK) cells in lymph nodes during pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infection of cynomolgus macaques and African green monkeys (AGMs), respectively. Their findings suggest that NK cells are specifically recruited to follicles in AGMs and regulate SIV replication in the lymph node.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Yakut communities, with Trans-Baikal admixture during the Mongol expansion, preserved genomic diversity and oral microbiomes despite the Russian conquest, which introduced cereals, pathogens and Christianity, whereas marital practices preserved low consanguinity except in one late case of traditional shamanism.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Enantioconvergent reactions convert both enantiomers of a racemic starting material into a single enantioenriched product. All currently known enantioconvergent processes necessitate the loss or partial loss of the racemic substrate’s stereochemical information. Now, an alternative approach has been developed that proceeds with full retention of the racemic substrate’s configuration.

Algorithms and bots are capable of performing some behaviours at human or super-human levels. Humans, however, tend to trust algorithms less than they trust other humans. The authors find that bots do better than humans at inducing cooperation in certain human–machine interactions, but only if the bots do not disclose their true nature as artificial.

Proximity-ligation-based sequencing from 111 samples and 5 environments reveals that a substantial proportion of phages infect multiple species.

Environmental metagenomic explorations show that Mirusviricota lineages lack essential replication and transcription genes and contain spliceosomal introns, suggesting nuclear reproduction.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Here, Alcala and colleagues present a multi-omics analysis of these tumours, revealing distinct molecular and prognostic subgroups.

Mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA–processing complex, cause an autoinflammatory syndrome due to enhanced interferon signaling mediated by the cGAS–STING pathway, showing an essential role for nuclear histones in suppressing the immunogenicity of self-DNA.

Here, the authors leverage data from the Tara Oceans expeditions to perform a phylogeny-guided plastid genome-resolved metagenomic survey and provide 660 non-redundant plastid genomes from marine algae. They identify a rare, deep branching plastid lineage of nano-sized algae, describing their diversity, phylogeny, distribution and relevance to our understanding of plastid endosymbioses.

The ComFC protein is essential for natural transformation, a process that plays a major role in the spread of antibiotic resistance genes. Here the authors show that ComFC is a membrane-associated protein that participates in the transport of DNA through the cell membrane and the handling of the single-stranded DNA once delivered into the cytoplasm.

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.

In the Earth's history, the timing of oceanic large-scale events of oxygen depletion remains poorly understood. Here, the authors show that palaeogeography was a major preconditioning factor during the Cretaceous, implying that thresholds to shift toward a global anoxia are likely to be much higher at present.

Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe.

In a mouse model of prostate cancer, neural progenitors from the central nervous system that express doublecortin infiltrate tumours and metastases, and can generate new adrenergic neurons in tumours.

From sugar beets to TV screens, François-Xavier Coudert explores the history, applications and perils of the Scottish element, strontium

The association between obesity and breast cancer biology remains understudied in humans. Here, using a large retrospective data collection, the authors identify obesity associated changes in the genomic, transcriptomic profile, and the tumor microenvironment of primary untreated breast tumors.

The high observed abundance of atmospheric methanol over remote oceans is still not well-explained. Here the authors use quantum calculations and atmospheric modelling to show the reaction of methyl peroxy and hydroxyl radicals is a major methanol source (115 Tg/yr), comparable to global terrestrial emissions.

The global distribution of nearly all extant reptile species reveals richness patterns that differ spatially from that of other taxa. Conservation prioritization should specifically consider reptile distributions, particularly lizards and turtles.

Chromosome ends must be protected from fusion by NHEJ despite Ku binding to telomeres. Here, the authors show that at telomeres yeast Rap1 inhibits Ku’s translocation on DNA, preventing NHEJ and protecting telomeres without displacing Ku.

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 newly compiled atlas of species-wide structural variants and gene-based and graph pangenomes derived from highly complete assemblies of genomes from 1,086 natural isolates enable integrative genome-scale studies of Saccharomyces cerevisiae.

Processes involved in diploidization after whole genome duplication is poorly understood. Here, the authors explore the genome history of Sporobolus alterniflorus and S. maritimus, two related polyploid grasses, considered as ecosystem engineers in saltmarshes.

Despite being an important driver of a subset of medulloblastomas, efforts to therapeutically target Sonic Hedgehog (SHH) signaling, such as with the use of Smoothened (SMO) inhibitors, have had limited success. Here, the authors find that SHH medulloblastomas are sensitive to netrin-1 inhibition and investigate netrin-1 as a mechanism of resistance to SMO inhibition.

Hybridizations between different wild species and subspecies within Musa genus lead to the origin of current banana cultivars with different ploidy level and constitution. Here, the authors assemble seven genomes from different ancestral genetic groups and show the speciation process is accompanied by chromosome rearrangements.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

The gut microbiota may contribute to depression, but the underlying mechanism is not well understood. Here the authors use a mouse model of stress induced depression to demonstrate that behavioural changes conferred by fecal transplant from stressed to naïve mice require the endocannabinoid system.

Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.

The control of translation during mitosis has an important role in cancer cell biology. Here the authors report that in mitotically arrested cancer cells, redistribution of ribosomes towards upstream open reading frames results in enhanced presentation of immunogenic peptides on cancer cell surface.

Genes encoding the class A auxin-response factor group of plant transcriptional activators reside in constitutively open chromatin, enabling their continual regulation by transcriptional repressors to modulate auxin signalling throughout development.

Artificial intelligence is now superior to humans in many fully competitive games, such as Chess, Go, and Poker. Here the authors develop a machine-learning algorithm that can cooperate effectively with humans when cooperation is beneficial but nontrivial, something humans are remarkably good at.

Genomes of nine brown algal species with different sex determination systems show that U/V sex chromosomes evolved 450–224 Ma and show remarkable conservation of genes within the sex-determining region despite independent expansions of the sex locus in each lineage.

Bacteria have evolved numerous innate and adaptive defence mechanisms. Here, Beavogui et al characterise the impact of biogeography, genetic mobility, and clustering in defense islands, on the defence systems of soil, marine, and human gut bacterial populations genomes.

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.