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The mechanisms that regulate the initiation of DNA replication in archaea are poorly understood. Here, Dhanaraju et al. identify a sequence element and its interacting protein required for DNA replication initiation in the model archaeon Sulfolobus islandicus.

An extinct prehistoric plague lineage of Yersinia pestis has been documented from Central Europe to Asia during the Late Neolithic and Bronze Age. Here, Swali et al. show that this lineage spread to Europe’s northwestern periphery by sequencing three ~4000 year-old Yersinia pestis genomes from Britain.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

In a randomized controlled trial in individuals with persistent atrial fibrillation, an individualized ablation procedure, in which areas with abnormal electrophysiological characteristics—as detected by an AI algorithm—were targeted for ablation, led to improved efficacy for reducing arrhythmia recurrence at 12 months following the ablation procedure.

Single-cell RNA-sequencing analysis of embryogenesis and X chromosome inactivation in the opossum (Monodelphis domestica) resolves the developmental trajectory of a marsupial, and sheds light on the evolution of embryogenesis in mammals.

Stochastic nucleation prevents the repeatable multi-level response of phase change materials in integrated photonics. Here the authors circumvent this issue with a method using deterministic amorphization via spatially controlled microheater hotspots.

A study examines the diversity of extrachromosomal DNA elements in cancer, and provides details on the frequency and origin of extrachromosomal DNA and its role in the development of different types of cancer.

FOS has been linked to bone tumour pathogenesis, and viral homologue v-fos causes osteosarcoma in mice. Here, the authors report rearrangement of FOS and its paralogue FOSB in osteoblastoma and osteoid osteoma, revealing human bone tumours that are defined by mutations of FOS and FOSB.

This work integrates duplex sequencing with cost-effective Ultima sequencing to enhance the accuracy of whole-genome circulating cell-free DNA profiling.

Here, the authors show that there is a pretumorigenic T_H17 subset in the intestines that can convert to being tumorigenic under the control of KLF6 and that this process can be prevented by TGFβ1 production from intestinal epithelial cells.

Food biodiversity is likely to benefit both human health and agrifood systems. To assess food biodiversity, this epidemiological study proposes the use of dietary species richness, which is highly heterogeneous—both between and within countries—and is associated with lower rates of mortality in Europe and similar levels of micronutrient adequacy in low- and middle-income countries, as opposed to other classical indices.

A late onset of inner-core growth is inferred from ultra-low palaeomagnetic field strengths about 565 million years ago, as measured in magnetic inclusions in Ediacaran crystals.

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).

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Although the search for new zeolites has traditionally been based on trial-and-error approaches, more rational methods are now available. Using the principle of inverse sigma transformation, the reactivity of framework germanium atoms in strong mineral acid has now been exploited to selectively remove germanium from a germanosilicate zeolite.

High intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer cells.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Fendt and colleagues find that pre-metastatic niche formation and a high-fat diet increase palmitate availability in future organs of metastases and show that breast cancer cells use palmitate to generate acetyl-CoA, acetylate the NF-κB subunit p65 and induce pro-metastatic signaling.

In this study, Leventhal et al. integrate multi-omic data from human and Drosophila models of Alzheimer’s disease to define regulators of age-associated neurodegeneration in Alzheimer’s disease and the pathways through which they act.

If left unrepaired, meiotic DSBs are toxic to mammalian cells, thus oocytes in which DSBs persist are eliminated by the DNA-damage checkpoint. Here the authors provide insights into the roles of PUMA, NOXA and BAX during DNA damage checkpoint that eliminates Dmc1^−/− and Msh5^−/− oocytes.

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A₂, thereby enhancing the immune response against metastasis.

Herpes simplex virus 1 (HSV-1) is a neurotropic virus that often cause pain via the induction of ulcer or blisters. Here the authors show, in mouse models of HSV-1 infection, that the pain-perceiving nociceptor Nav_1.8⁺ neurons contribute to regulating both innate and adaptive immune responses against HSV-1, thereby offering a potential target for therapy.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Mucosal immunisation is important for initiating mucosal CD8⁺ T­cell responses but mucosal recruitment of protective CD8⁺ T cells can also be induced by skin immunisation. Here the authors examine the underlying mechanism and report a novel role for ILC1 recruiting CD8⁺ T cells to the mucosa after skin immunisation.

It is unknown if the inhalation route (nasal or oral) of particulate matter (PM) air pollution affects cognition. Here the authors show PM exposure impaired selective attention and emotion recognition but not working memory or vigilance, with no mediation by inhalation.

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.

DNA transfer between two bacterial cells is mediated by the conjugative type 4 secretion systems (T4SSs). Here, the authors report the structure of a complete T4SS outer-membrane core complex (OMCC), revealing distinct C17 and C13 symmetries of its central inner and peripheral outer ring regions, respectively.

Gonadal fate in mammals is determined during embryogenesis and is actively maintained in adulthood. This study shows that E3-SUMO ligase activity of TRIM28 is required for ovarian identity maintenance and testicular-specific gene repression in mouse adult ovary; in its absence, ovarian granulosa cells transdifferentiate to Sertoli cells.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.