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Diet-related maternal obesity is linked to neurodevelopmental disorders in offspring, yet underlying mechanisms are unclear. Here, authors show that maternal high-fat diets trigger immune-metabolic dysregulation, elevating neurotoxic kynurenine metabolites in fetal brains, and blocking these pathways rescues social deficits in male mice, highlighting preventive strategies for neurodevelopmental disorders.

Frequent loss-of-function mutations in KEAP1, a master regulator of the NRF2 antioxidant pathway, accelerate mutant KRAS driven lung carcinogenesis, but also impose a dependency of these tumors on glutaminolysis. Using a precision medicine–based approach, this work uncovers a metabolic vulnerability of KRAS–KEAP1-mutant lung cancers that can be therapeutically exploited using currently available glutaminase inhibitors and provides a scientific rationale for patient selection in clinical trials.

Emergence of ABL1 kinase inhibitor resistant clones may cause disease relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia. Here, the authors show interleukin 7 receptor (IL7R) signaling to contribute to this resistance mechanism, and that targeting the IL7R pathway may suppress incurable drug-resistant leukemia forms.

Deubiquitinating enzymes play an essential role in myocardial hypertrophy. Here, the authors show the beneficial effects of a cardiomyocyte-derived deubiquitinating enzyme, USP13, in hypertrophic cardiomyocytes and identify a cardiomyocyte-specific USP13-STAT1 axis in regulating cardiac hypertrophy.

Structure of human nuclear pore complex in its cellular environment reveals a substantially dilated central channel and shows that its nucleoplasmic and cytoplasmic rings restrict channel dimensions and create membrane asymmetry at the inner ring.

Integrative molecular modelling of a mitochondrial crista demonstrates a pipeline for constructing biologically representative systems and addressing interactions in complex environments.

Li et al. introduced tract-geometry coupling (TGC) to quantify the coupling between white matter tracts and cortical geometry in the human brain, shedding light on how the brain’s wiring and shape evolve together and its support for behavior and growth.

Xenoturbella is a simple marine worm recently suggested to be either a deuterostome or an early branching bilaterian. Nakano et al. report the first observations of naturally spawned eggs and embryos from Xenoturbella, and uncover new insights into the evolutionary history of metazoan development.

How the abrupt warming events recorded in Greenland ice cores during the last glacial cycle have influenced the tropical climate is not well known. Here the authors present new lake sediment data from the Peruvian Andes that shows that these events resulted in rapid glacier retreat and large reductions in lake level.

Reconfigurable arrays of up to 448 neutral atoms are used to implement and combine the key elements of a universal, fault-tolerant quantum processing architecture and experimentally explore their underlying working mechanisms.

Through multimodal analyses of human cardiac tissues across different ages, Fan, Zheng, Zhan, Xu, Liu and colleagues reveal that RNA-binding protein ARID5A drives inflammaging by stabilizing the MAVS mRNA and activating the NF-κB–TBK1 pathway, and show that inactivating myocardial ARID5A attenuates cardiac senescence and functional decline.

People try to infer how others feel, with varying success. Here, the authors show that others’ feelings and our inferences can both be predicted from our brain activity, and that we are more accurate when these brain patterns align.

IL-22RA1 is highly expressed on pancreatic islets and absent on immune cells. Here, the authors investigate its role by generating animals that lack IL-22RA1 on beta cells and reveal IL22RA1 signalling is critical for insulin biosynthesis and beta-cell health, evidenced by its regulation of MHC II expression and its suppressive effect on inflammation and cellular stress.

Researchers developed a self-driving lab, including automated confocal imaging, that uses machine learning to rapidly map the phase behavior of biomolecular condensates.

This protocol describes how to isolate trophoblast from first-trimester human placentas and grow it long term in a three-dimensional organoid culture system.

Impairment of cognitive function is a common feature of many neurodevelopmental disorders. Systems genetics analysis in the brain uncovered a convergent gene network for both cognition and neurodevelopmental disorders. As the network does not recapitulate known pathways, this finding represents a new basis for understanding factors influencing normal and disordered cognition.

The Multi-Worm Tracker permits real-time, high-throughput, quantitative analysis of behavior in Caenorhabditis elegans. It should enable screens for genes implicated in complex worm behaviors. Also in this issue, Albrecht and Bargmann apply microfluidics to study worm chemosensory behavior with high spatial and temporal precision.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Cockburn et al. report that epidermal differentiation is a multi-day process through which cells undergo a continuum of transcriptional alterations initiated independently of cell cycle exit.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Schizophrenia (SZ) is a severe psychiatric disorder; unfortunately, only ~1/3 of patients respond favorably to treatment. Here, the authors reveal hyperacetylation of histone H2A.Z in SZ neurons and postmortem SZ human brain tissues. They further show BRD4 is a reader of hyperacetylated H2A.Z and treatment with bromodomain inhibitor JQ1 largely rescues abnormal gene expression associated with SZ.

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).

Structure of the Toxoplasma mitoribosome made of >50 short rRNA molecules reveals evolutionary solutions to rRNA fragmentation: addition of poly A tails to rRNAs, reused rRNA sequences, and repurposing of proteins with transcription factor domains.

In a combined analysis of two large patient cohorts, three peripheral consensus transcriptomic subtypes of sepsis are identified, which can be linked to an 18-gene classifier associated with different odds of mortality and may offer a way to tailor care for patients with sepsis.

Analysis of data on 971 bird species in natural habitat and cattle pasture in Colombia finds that near-national-scale losses of bird diversity greatly exceed losses recorded at the local scale, suggesting that extrapolations from local studies will severely underestimate biodiversity losses.

Data on beetle, bird, plant and mammal occupancy of woodland sites in UK agricultural landscapes demonstrate how contemporary spatial spillovers and legacies of past land use interact to affect species richness and community composition.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

An Antarctic glacier retreated after the loss of landfast ice at a peak rate almost an order of magnitude faster than previously recorded because of buoyancy-driven ice calving, according to an analysis of geophysical data and satellite imagery.