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This Perspective considers the addition of ACKR1 genetic testing for identifying ACKR1/DARC-associated neutropenia in patients receiving clozapine, recommending eligibility criteria and testing strategies while estimating substantial cost savings for the UK healthcare system and enhancing equitable treatment access.

The origin and dispersal of Homo erectus, a long-lived and geographically widespread human ancestor, are unclear despite a rich fossil record. Here, the authors reconstruct the face from a Homo erectus cranium from Gona, Ethiopia, dated to 1.5-1.6 million years ago, providing insights into the evolutionary transition from early Homo to H. erectus.

Here the authors demonstrate the use of zinc isotopes (δ⁶⁶Zn) to geochemically assess trophic levels in extant and extinct sharks. They show that the Neogene megatooth shark (Otodus megalodon) and the great white shark (Carcharodon carcharias) occupied a similar trophic level.

Here, the authors show that methylphenidate alters brain organization by compressing the hierarchy between sensory and association areas. This dopamine-driven shift predicts improved attention, revealing how stimulants reorganize brain networks to enhance cognitive function.

The impact of tumour heterogeneity on metastatic potential in prostate cancer remains poorly understood. Here, the analysis of single nuclei RNA sequencing and whole-genome sequencing from samples from five patients suggests an interplay between clonal evolution and cellular plasticity driving metastatic seeding.

Geminin regulates DNA replication by binding CDT1 and preventing MCM helicase loading. Using a reconstituted system and structural modelling, the authors find geminin inhibits via steric clash with MCM, not by blocking the CDT1–MCM interface. Combined with CDK activity, it fully halts licensing.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

Previous research has suggested that pDCs are required for an effective antiviral immune response, but direct experimental evidence to support this is lacking. Here Ngo et al. develop a pDC knockin mouse model and find that pDCs are dispensable for an antiviral immune response to mouse cytomegalovirus and may be detrimental during influenza or SARS-CoV-2 infection.

The extent of the hierarchical relationship between premotor and primary motor cortices has been contested. Here, the authors show that hierarchical interactions between analogous brain regions and forelimb musculature vary substantially between two motor behaviors in mice.

In the C. elegans germline, distal niche cells provide a Notch signal to promote stem cell proliferation. Martel et al. show here that distal basement membrane type IV collagen contents positively influence the transmission of this niche signal.

Engineering of local Anopheles gambiae under containment enables the generation of a transgenic strain equipped with non-autonomous gene drive capabilities that robustly inhibits genetically diverse Plasmodium falciparum isolates obtained from naturally infected children.

HNF4A is a nuclear receptor that regulates liver lipid homeostasis. Here the authors show that HNF4A is not required for intestinal lipid metabolism but controls energy expenditure under diet induced obesity through the fat-induced release of glucose-dependent insulinotropic polypeptide.

Knowledge of how a disease spreads can lead to useful predictions to help manage and contain it. Here, Maher et al.model white-nose syndrome spreading in North American bats, and show that concentrated habitat distribution and longer winters can mediate pathogen dispersal, matching the ecological traits of bats.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Spatial transcriptomic analysis of cells in intestinal fistulae of patients with Crohn’s disease reveals the existence of specialized fistula-associated cell states with distinct signalling profiles and extracellular matrix architecture.

The role of structural variants (SVs) in Mycobacterium tuberculosis has been understudied. In this study, the authors leverage 859 high-quality, diverse, long-read assemblies to construct pangenome reference graphs (PRGs).

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

This study shows that brain connectivity changes in Huntington’s disease begin decades before symptoms, shifting from hyper- to hypoconnectivity, with links to specific neurotransmitter systems specially in granular and infragranular cortical layers.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

The white pupae (wp) phenotype has been used for decades to selectively remove females of tephritid species in genetic sexing, but the determining gene is unknown. Here, the authors show that wp phenotype is produced by parallel mutations in a Major Facilitator Superfamily domain containing gene across multiple species.

Jails are high-risk settings for transmission of pathogens. Here, the authors use genomic and epidemiological data to investigate the bacterial and clinical factors affecting transmission of MRSA in jails and impacts on wider community transmission dynamics.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Observations from the JWST MIRI/LRS show the detection of SO₂ spectral features in the 5–12-μm transmission spectrum of the hot, Saturn-mass exoplanet WASP-39b, suggesting that photochemistry is a key process in high-temperature exoplanet atmospheres.

Uterine perivascular cells were identified as progenitors for endometrial re-epithelialization via mesenchymal-to-epithelial transition, whereby cellular quiescence and activation were mediated via Notch signaling and estrogen, respectively.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

In this phase 1 trial, treatment of patients with fibrolamellar hepatocellular carcinoma with a therapeutic peptide vaccine targeting the fusion kinase DNAJB1–PRKACA, which is the driver of the disease, together with nivolumab and ipilimumab, was safe and led to encouraging preliminary clinical responses, and translational analysis showed activation of immune responses.

By unifying data from engineered β-barrel nanopores and supported by modelling, it is demonstrated that the lumen charge in a β-barrel nanopore governs rectification and voltage-driven gating, with applications in computing using nanofluidic synapses.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

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.

Transitioning from spores to hyphae is crucial for host invasion by the plant pathogenic fungus Zymoseptoria tritici. Here, the authors show that the spore-to-hypha transition is enhanced by wheat leaf surface compounds and is regulated by the white-collar complex, which integrates light with biotic and abiotic cues to allow host invasion through open stomata.

The impact of prior infection on the immune response to COVID-19 vaccination has not been fully characterised. Here, the authors use data from ~100,000 adults in the UK and find that a single vaccine dose in those with prior infection produces a comparable or stronger response to two doses in those without infection.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Using data from 142,238 Mass General Brigham Biobank participants, researchers explored population history and social and genetic risk factors for disease in Greater Boston. The study links genetics and context to guide equitable precision health.

Haines et al. developed an MEK–RAF molecular glue called IK-595 that blocks MAPK pathway activation in RAS-mutant and BRAF-mutant cancer cells. IK-595 exhibited high tolerability and strong antitumor effects in preclinical models across cancer types.

The warm Earth-sized planet LHS 475 b is validated and characterized with two transits observed by the JWST. The absence of evident spectroscopic features excludes a substantial hydrogen envelope and indicates that LHS 475 b has either little or no atmosphere or an optically thick cloud deck at high altitudes.

Creating multimaterial objects through vat photopolymerization is challenging due to difficulty transitioning between liquid resins and processing incompatibility between material classes. Here the authors develop infusion multimaterial actinic spatial control additive manufacturing, which uses dual wavelength light projection to create distinct material regions that can be selectively infused with a variety of organic and metallic materials.

Insecticide resistance can limit the effectiveness of insecticide-treated nets for malaria prevention, but other factors such as access and durability also contribute. Here, the authors quantify impacts of this ‘cascade’ of factors using a mathematical model.

The corpus callosum is essential for coordinating sensorimotor, associative and executive functions. Here, the authors show a GWAS of corpus callosum morphology implicates prenatal growth pathways, immune-driven thinning, and genetic overlap with cortical and neuropsychiatric traits.

Understanding tumor heterogeneity and its impact on prostate cancer progression remains elusive. Here, single nucleus snATAC and snRNA sequencing of a multi-loci sampled cohort of advanced prostate cancer patients identifies an inflammatory-like state underlying metastatic dissemination to the lymph nodes.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

The authors used data from the ABCD Study to examine the effects of prenatal cannabis exposure on neuroimaging metrics and mental health in adolescents.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

Researchers reveal widespread, newly formed seafloor seeps along Antarctica’s Ross Sea coast. Methane-rich flows alter local ecosystems and may influence warming. The drivers remain unknown, warranting coordinated study.

The timing of respiratory syncytial virus seasonal epidemic peaks in Japan shifted in 2016-17. Here, the authors use mathematical modelling to evaluate the hypothesis that this change in timing may be due to an increase in use of childcare facilities following a policy change