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Imaging of the mantle transition zone beneath the Lesser Antilles shows a basalt-rich region within the subducting slab near the proposed location of a subducted extinct spreading ridge, implying ancient tectonics play a role in influencing slab trajectories.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Verhaege et al. identify a conserved fibroblast barrier population at the base of the choroid plexus that compartmentalizes brain–CSF interfaces and is disrupted by inflammation, revealing a new site of central nervous system immune entry and barrier regulation.

Serpentine subducted below the Lesser Antilles volcanic arc supplies water to the arc, controlling the location of seismicity, volcanic productivity and thickness of crust.

To humanize models of liver metabolic disease research, authors develop a microfluidic platform leveraging human hepatic spheroids integrated with microvasculature and circulating monocytes to model hepatic insulin resistance.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

With its attribution to Paranthropus, a 2.6-million-year-old partial mandible expands the range of the genus into the Afar region of Ethiopia and adds to our understanding of hominin evolution in eastern Africa.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

APOBEC deaminases restrict retroviruses but can also mutate human DNA. Here, the authors show that cancerassociated APOBEC3s with low RNA binding, known to enter the nucleus, are selectively recognized by E3 ligases and degraded, eliminating harmful nuclear enzymes, and limiting genome mutation.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

ADGRL4 is a cancer-implicated adhesion GPCR whose ability to couple to G proteins had been unclear. Here, authors show that ADGRL4 weakly engages Gq and determine its 3.1 Å active-state structure, revealing its mechanism of activation.

Floquet engineering is often limited by weak light–matter coupling and heating. Now it is shown that exciton-driven fields in monolayer semiconductors produce stronger, longer-lived Floquet effects and reveal hybridization linked to excitonic phases.

Understanding species’ spatiotemporal dynamics is key to predicting their responses to climate change. Here, the authors combine landscape genomics, demographic reconstructions, and species distribution models to assess lineage-specific responses to past and future climate in a migratory raptor.

CELSR1 is a core component of the tissue/planar cell polarity pathway. Here, the authors report a CELSR1-related disorder featuring brain malformations, neurodevelopmental delay and epilepsy, and use mice to explore the pathophysiological mechanisms.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Ramaglia and colleagues show that aberrant formation of B cell-rich lymphoid structures in the brain meninges is associated with high CXCL13:BAFF ratios. Inhibiting the kinase BTK reduces the lymphotoxin signaling needed to sustain such structures, lowers CXCL13:BAFF ratios and reduces cortical tissue injury.

The links between meat production and immunity in cattle can affect agricultural production. Here, Li et al. identify genetic and environmental factors that shape immune responses in cattle, which can guide breeding for improved health.

The ageing process leads to cellular changes that disrupt the intricate axis between the nervous and vascular systems that governs cardiac function. In this Review, Wagner and Dimmeler describe the crucial role of neurovascular ageing in cardiac dysfunction and explore the therapeutic potential of targeting the cardiac neurovascular unit to develop interventions for ageing populations.

Sambaquis are archaeological shellmounds found in Brazil. Here, the authors use archaeological and molecular methods to show southern right whale, humpback whale, and dolphin were exploited 5000 years ago by Sambaqui groups to manufacture whale-bone harpoons and other artefacts.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Shroom3 genetic variants increase Shroom3 levels and promote kidney fibrosis but reduce proteinuria, complicating Shroom3 targeting for precision medicine. Here, the authors show increased fibrosis mediated by Shroom3–Rock signaling and blocking this interaction genetically or with new compounds reduces tubular Rock activation and fibrosis.

Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNA^Ala mutation (m.5019A>G) in mice and demonstrate that macrophages carrying this mutation display altered function and metabolism in vitro, along with increased type I IFN release following LPS challenge in vivo.

The authors theoretically delineate the maximal increases in tree growth that can be expected from increases in plant intrinsic water-use efficiency, which increases with rising CO₂. They highlight environmental and physiological limits on growth in the context of experimental data.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

Soil microorganisms play a crucial role in maintaining ecosystem functioning across diverse environments. This study shows that soil properties and specific microbial taxa jointly shape ecosystem functioning across European soils.

Patients with primary mitochondrial disease manifesting cardiomyopathy are twice as likely to die compared to those without cardiomyopathy. Here, the authors show that a modest increase in cardiac mitochondrial energetics via gene therapy can significantly improve cardiac function and is effective in treating mitochondrial cardiomyopathy.

The authors previously pinpointed OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. Here, the authors identify increased IL-18Rα expression on CD8⁺ T cells, which acquire a reduced cytotoxic signature, correlates with severe respiratory viral infection of influenza A virus, RSV and COVID-19.

Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the import of PTS2-containing proteins.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Nuclear pore complexes control selective transport between the nucleus and cytoplasm. Here, the authors show how FG-Nups and transport receptors form a dynamic interface that enables selective and efficient transport.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

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.

Dysfunctionality of T lymphocytes has been implicated in cancer and infection, however, the role of CD4 T cells remains understudied. The authors here generate a TCR transgenic mouse model for the study of dysfunctional CD4 T cells directed against a tumor-specific antigen, which can be reinvigorated by checkpoint blockade and vaccination.

Human–artificial intelligence (AI) dialogues can meaningfully impact voters’ attitudes towards presidential candidates and policy, demonstrating the potential of conversational AI to influence political decision-making.

There are several semiempirical models to predict which elements will form stable compounds, but their applicability is limited. Here, the authors develop a simple model to this aim throughout the periodic table requiring only two parameters fitting.