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Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

The spatial structure of a population is often critical for the evolution of cooperation. Here, Allen and colleagues show that when spatial structure is represented by an isothermal graph, the effective number of neighbors per individual determines whether or not cooperation can evolve.

In a randomized placebo-controlled trial in rural Niger, biannual azithromycin distribution to children 1-59 months reduced all-cause mortality. Based on serology, Arzika et al. here report a reduction of Campylobacter infection, supporting one mechanism for the intervention’s impact on mortality.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

The SPECULOOS project detected an Earth-sized planet in a short orbit around a nearby Jupiter-sized star. This planet, SPECULOOS-3 b, is one of the most promising rocky exoplanets for detailed emission spectroscopy characterization with JWST.

Year-round tracer data from the MOSAiC expedition reveal strong variability in Siberian matter dispersal along the Arctic Transpolar Drift, driven by shifting river inputs and ice–ocean exchange, underscoring complex dynamics in a changing Arctic

Phospho-MurNAc-pentapeptide translocase (MraY) is a bacterial integral membrane enzyme that is essential for peptidoglycan biosynthesis. Here the authors present the crystal structures of MraY from Aquifex aeolicus bound to caprazamycin, capuramycin and mureidomycin and discuss the implications for antibiotic development.

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.

How neural stem cells can transition between states of proliferation and quiescence is unclear. Here, the authors identify Lrig1 as a specific marker for the primed quiescent state and demonstrate that Lrig1 maintains cells in a quiescent state via modulation of the EGFR pathway.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

The phase separation of two species of associating polymers is suppressed by a magic-number effect for certain combinations of the numbers of binding sites. Here the authors use lattice simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one component has a rigid shape.

Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.

A proteogenomic profiling analysis of single cells from the blood and lymph nodes of individuals living with HIV-1 reveals that CD4⁺ memory T cells harbouring intact provirus show signatures associated with resistance to immune-mediated killing and cell survival.

Genome-wide meta-analysis with individuals of East Asian or European ancestry identifies 176 loci associated with schizophrenia. Despite consistent genetic effects across populations, polygenic risk models trained in one population have reduced performance in the other population.

After the production of double-stranded breaks in mammalian cells, ATM drives the formation of the D compartment, which regulates DNA damage-responsive genes, through the clustering of damaged topologically associating domains, with a mechanism that is consistent with polymer–polymer phase separation.

Many low- and middle-income countries, including The Gambia, had low COVID-19 vaccination coverage during the emergence of the Delta and Omicron variants. Here, the authors perform a prospective household cohort study in the Gambia to investigate the dynamics of SARS-Cov-2 infection in this setting.

Efficient statistical emulation of melting land ice under various climate scenarios to 2100 indicates a contribution from melting land ice to sea level increase of at least 13 centimetres sea level equivalent.

Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP_105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP_105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

Following the success of the inaugural games, the Microbial Olympics return with a new series of events and microbial competitors. The games may have moved to a new hosting venue, but the dedication to training, fitness, competition (and yes, education and humour) lives on.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Insecticide resistance in mosquitoes threatens the success of malaria control programmes. This study found that in different populations of a malaria mosquito species in West Africa, resistance is associated with different genes or different mutations in the same set of genes.

Understanding excitonic optical excitations is integral to improving optoelectronic and photovoltaic semiconductor devices. Here, Bennecke et al. use photoemission exciton tomography to unravel the multiorbital electron and hole contributions of entangled excitonic states in the prototypical organic semiconductor C60.

Cells sense their physical environment and reorient in response to cyclic mechanical deformation. Here the authors show that existing models do not adequately explain this phenomenon, and develop a new theory based on the active relaxation of passively stored elastic energy.

Emerging SARS-CoV-2 variants with mutations in the spike protein raise concerns regarding vaccine efficacy. Here, the authors show that two spike encoding mRNA vaccines in preclinical and clinical development protect human ACE2 mice from the B.1.351 variant of concern and ancestral B BavPat1.

Constantinides et al., perform a recall study from a British South Asian genetic cohort to explore the genetic and phenotypic risk of cholestatic liver disease. 55.6% of participants with rare heterozygous ABCB4/ABCB11 variants or a history of intrahepatic cholestasis of pregnancy showed evidence of liver involvement, highlighting the utility of genetic screening and monitoring.

Dinoflagellates are known to use dinoflagellate-viral-nucleoproteins (DVNPs) in place of histones, yet this evolutionary transition is not well understood. Here, Irwin et al. use yeast expressing DVNP to show that DVNP displaces histones and that histone reduction allows cells to cope with DVNP.

Gupta, Johnson et al. quantify the turnover rates of ~3200 E. coli proteins, demonstrating that cytoplasmic proteins are recycled when nitrogen is limited and that protein degradation rates are generally uncoupled from cell division rates.

Focusing on two ill-characterized subtypes of medulloblastoma (group 3 and group 4), this study identifies prevalent genomic structural variants that are restricted to these two subtypes and independently bring together coding regions of GFI1 family proto-oncogenes with active enhancer elements, leading to their mutually exclusive oncogenic activation.

Islands and mountaintops are often considered evolutionary dead ends. Using whole genomic data of 18 bird species and demographic models, the authors show that populations become isolated at high elevations, but disjunct montane populations maintain gene flow and thus the capacity for further colonisation.

Urban agriculture is intuitively appealing, but its carbon footprint is unclear. This analysis of case studies in the United States and northern Europe finds that food from urban agriculture is much more carbon-intensive but that circularity, such as by recycling of food waste, on long-used city plots can help urban agriculture outperform conventional agriculture.

The contribution of genetic factors to the tumour immune microenvironment (TIME) remains to be investigated. Here, the authors suggest the role of TIME eQTLs for target genes involved in reversing immune suppressive features.

Analysis of peripheral mycobacteria-reactive CD4⁺ T cell receptor sequences from individuals infected with Mycobacterium tuberculosis shows a high degree of overlap between progressors and controllers, but points to some distinct clonotypes that are enriched in either group.

Enzymes that move along DNA, such as DNA and RNA polymerases, cause the DNA ahead of them to become supercoiled. This would lead to the DNA becoming overwound, were the stress not relieved by topoisomerases. Topoisomerase inhibitors have been used as antibacterial and anticancer drugs, but the structural basis for their activity has been unclear. Here, the crystal structures are presented of a topoisomerase on DNA, either alone or in the presence of a new type of antibiotic.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Sexual size dimorphism in mammals, often linked to sexual selection, can impacts genome evolution. This study finds sexual dimorphism in body size is associated with expanded gene families for olfactory functions and contracted gene families for brain development.

Epilepsy is a brain network disorder with associated genetic risk factors. Here, the authors show that spatial patterns of transcriptomic vulnerability co-vary with structural brain network alterations in focal and generalized epilepsy.

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.

In a large single-arm phase 2 trial, the anti-PD-1 inhibitor tislelizumab combined with the next-generation BTK inhibitor zanubrutinib had an overall response rate of 58.3% and was well tolerated in patients with Richter’s transformation.

A genome-wide association study in more than 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, transancestral cohorts.