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In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

Prime editing in mammalian cells benefits from a comprehensive list of genetic parts.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

A conserved gene regulatory network involving SOX4, SOX11 and TFAP2D shapes the development of excitatory neurons in ventrolateral pallium and their connectivity with the prefrontal cortex.

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).

Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival.

SpaGFT is a spatial omics representation method. It identifies spatially variable genes, enhances gene imputation, detects immunological regions, and characterises variations in secondary lymphoid organs. This method improves predictive power in wide downstream machine-learning tasks.

The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

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.

Genome-wide sequencing of 180 ancient individuals shows a continuous gradient of ancestry in Early-to-Mid-Holocene hunter-gatherers from the Baltic to the Transbaikal region and distinct contemporaneous groups in Northeast Siberia, and provides insights into the origins of modern Uralic and Yeniseian speakers.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Metabolites play an important role in physiology, yet the complexity of the metabolome and its interaction with disease and aging is poorly understood. Here the authors present a comprehensive atlas of the mouse brain metabolome and how it changes during aging.

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.

Gelabert et al. examine genomic and archaeological data from Europe’s earliest farming communities in Central Europe (5500–5000 bce). They find differentiated genetic networks but no evidence of unequal access to resources linked to sex or kin.

Archaeogenetic study of ancient DNA from medieval northwestern Europeans reveals substantial increase of continental northern European ancestry in Britain, suggesting mass migration across the North Sea during the Early Middle Ages.

By applying operant conditioning, behavioral manipulation, in vivo electrophysiology, computational modeling, and closed-loop optogenetics, the authors reveal a mechanism for action timing in mice mediated by the secondary auditory cortex.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Aurora, a new large-scale foundation model trained on more than one million hours of diverse geophysical data, outperforms operational forecasts in predicting air quality, ocean wave dynamics, tropical cyclone tracks and high-resolution weather.

Ancient DNA reveals how the explosive expansion of Yamnaya steppe pastoralists began with a small community north of the Black Sea speaking ancestral Indo-European, and detects genetic links with Anatolian speakers, stemming from a common Indo-Anatolian homeland in the North Caucasus–lower Volga region.

Quantitative analysis of the methylation of mouse cortical neurons that project to different cortical and subcortical target regions provides insight into genetic mechanisms that contribute to differences in cell function.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Fatty acid amide hydrolase (FAAH) is a key regulator of endocannabinoid signalling. Here, the authors develop a knock-in mouse that recapitulates a common human mutation in the FAAH gene and demonstrate parallel neural and behavioural alterations across species, suggesting a gain-of-function in fear regulation.

A large language model designed for health monitoring provides personalized sleep and fitness predictions, insights and advice.

The ventromedial nucleus of the hypothalamus is known to maintain energy homeostasis by controlling locomotor activity and thermogenesis. Here van Veen and Kammel et al. identified heterogeneous neuronal populations with sexually dimorphic gene expression and functions by using single-cell RNA analysis.

Ader et al. find a grommet-like role for ESCRTs distinct from their nuclear envelope sealing function after spindle pole body extrusion. The grommet works with spindle pole body components that establish a diffusion barrier to maintain compartmentalization.

Whole-genome sequencing analysis of 81 prehistoric individuals reveals how the genetic makeup of people from the North Pontic region was influenced by waves of migration during the Eneolithic period and Early Bronze Age.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Using focused ion beam milling and cryoelectron tomography, Tsuji et al. found actin filaments, with both cofilin-bound and canonical morphologies, within the lumen of human platelet microtubules and reconstituted these structures in vitro.

A conjugate drug consisting of GLP-1 receptor agonist and the PPARɑ/ɣ dual-agonist tesaglitazar is shown to have superior anti-diabetic effects than monotherapy.

Genome-wide analyses of ancient DNA from individuals from California and Mexico shed light on the spread of Mexican ancestry to California and how it correlates with linguistic flow.

Soil priming could release large amounts of soil C into the atmosphere. Here the authors show that experimental warming boosts soil priming and CO₂ emissions in grasslands potentially due to microbial changes. Model accuracy could be improved by incorporating these mechanisms.

Single-cell transcriptome profiling of mouse embryos and newborn pups is combined with previously published data to construct a tree of cell-type relationships tracing development from zygote to birth.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Little is known about the genetic landscape of people living in the Nile region prior to the Islamic migrations of the late 1st millennium CE. Here, the authors report genome-wide data for 66 ancient individuals to investigate the genetic ancestry of a Christian Period group from Kulubnarti.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Orphan transporters can be found in over 20 families in the SLC superfamily. Here, the authors show that human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220; while in great apes, its orthologs transport sex steroid conjugates.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.