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How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

In the nucleus accumbens, acetylcholine boosts dopamine release to promote effortful behaviour.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.

Conventional methods for human motion analysis using sensors tightly attached to the body are often uncomfortable. Here, the authors demonstrate motion recognition and prediction using sensors embedded in garments. The results provide guidance for the development of wearable technology integrated into everyday clothing.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Vibrio cholerae O1 outbreak strains are classified as Ogawa or Inaba serotypes, but the impact of serotype on pathogenicity is understudied. Here, the authors show that O1 antigen methylation in Ogawa strains promotes colonization and infectivity.

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.

Whether high-order frontal lobe areas receive raw speech input in parallel with early speech areas in the temporal lobe is unclear. Here, the authors show that frontal lobe areas get fast low-level speech information in parallel with temporal lobe speech areas.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

Multi-trait genome-wide analyses identify variants associated with comorbid lung diseases. Polygenic scores leveraging shared components of heritable risk improve prediction of asthma, chronic obstructive pulmonary disease and lung cancer in a multi-ancestry cohort.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuropathy.

DBiTplus represents an integrated experimental and computational workflow that unifies sequencing-based and imaging-based spatial omics, demonstrated by combining transcriptomic profiling and multiplexed protein imaging on the same tissue section.

Active galactic nuclei are surrounded by a dusty and molecular disk that fuels supermassive black holes and connects them to their host galaxies. Here, the authors show with JWST interferometric observations that most of the dust in the Circinus galaxies lies in a compact disk, while only a tiny fraction traces hot outflowing material.

Prior hypoglycemia alters the paracrine interaction between islet α and δ cells, leading to impaired counter-regulatory glucagon secretion through somatostatin hypersecretion, increasing the risk of recurrent hypoglycemia.

Structural, genetic, functional and biochemical analyses of the complex flagellar motor of Campylobacter jejuni reveal structural adaptations with an ancient origin also found more widely across bacterial species, including elements exapted from the type IV pilus machinery.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

The LGN is a critical stage between the retina and visual cortex, but the properties of human LGN neurons are not fully understood. Here the authors report that they closely resemble those in monkeys and that closure of one eye increases the activity of putative inhibitory neurons connected to that eye.

This research developed and compared firearm-specific and method-agnostic machine-learning models using data from 800,579 Army veterans, revealing that model choice and intervention thresholds impact predictive accuracy and fairness, guiding tailored suicide prevention efforts.

Some next-generation computing may be based in physical systems that respond directly and reciprocally to environmental stimuli. Here, the authors describe a photoresponsive material that autonomously performs computations with incident beams of incoherent white light.

Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

Tree cover gains in the moist tropics (1982–2015) were 56% naturally regenerated forests and 27% managed tree systems, with forest type influencing carbon recovery. Effective forest restoration requires robust tracking of forest types established by restoration efforts.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

Intense lasers enable scientists to study the behaviour of matter under extreme pressures, but obtaining information about its atomic structure is challenging. In this work, Suggit et al. demonstrate the use of white-light X-ray diffraction to probe the structure of laser-shocked copper on nanosecond timescales.

Druckman et al. document gaps in trust in scientists in the USA. People from groups less represented among scientists (for example, women and those with lower economic status) are less trusting. Increasing the representation of these groups within science increases trust.

In this phase 2 ZUMA-14 clinical trial, Strati et al. reported the safety and efficacy of axicabtagene ciloleucel plus rituximab in adult participants with chemorefractory large B cell lymphomas and compared the results with previous findings from ZUMA-1 cohort 1.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Reported detections of gases in exoplanet atmospheres, including claims of biosignatures on K2-18 b, disappear when broader models are tested, revealing that such detections often reflect modelling limits rather than real signals.

Access to green space has been a critical, and contentious, issue for neighbourhood inequality and health outcomes. This Analysis looks at how the COVID-19 pandemic interacts with availability of nature for urban residents.

Vaccines inducing mucosal immunity may provide better protection from respiratory viruses. Here, Ykema et al. demonstrate the utility of a bivalent, mucosally delivered nanostructured lipid carrier-replicon vaccine for induction of mucosal and systemic immunity and protection against morbidity and mortality from H5N1 and H7N9 influenza.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

The Zwicky Transient Facility has observed a transitioning white dwarf with two faces, with one side of its atmosphere dominated by hydrogen and the other by helium.

Authors measure plasma proteins in a cohort of hospitalised patients presenting to the emergency department with suspected infection, revealing six discrete host response clusters that were driven by pathogen exposure and organ dysfunction, and had distinct clinical characteristics, hospital courses, and responses to treatment.

Complex infectious conditions, such as sepsis, requires rapid assessment of both pathogens and host responses. Here, the authors develop MIDAS, an assay platform that profiles bacterial RNA and inflammatory proteins simultaneously in under 4 hours.

In a prospective study involving 579,583 women in multiple sites across the USA, a multistage AI-driven workflow for digital breast tomosynthesis mammograms assisted radiologists in identifying 21.6% more cancers with respect to historical data, showing no significant variation across socio-demographic and breast density subgroups.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Adjuvants are an important component of modern vaccines. Here, the authors employ a phenotypic screen of ~200k compounds and identify PVP-057, a TLR3 agonist with a simple scalable 3-step synthesis, as an adjuvant that induces durable humoral and cellular immunity to varicella-zoster virus (VZV) gE in mice.

The mediators of bone-fat axis remain largely unknown. Here, the authors show SHN3 gene-deficiency in bone can protect mouse models from weight gain driven by diet-induced obesity through secreting a bone-derived cytokine, C-fragment of SLIT2, which could stimulate adipocyte browning.

Neural circuits in adult mouse visual cortex are stabilized by astrocytes, which secrete CCN1, resulting in reduced plasticity and increased maturation of multiple cell types.

Here, the authors show that brain dynamics mature from childhood to adulthood with increased hierarchical propagation and reduced visual-somatomotor dynamics. Top-down hierarchical flow strengthens throughout this developmental period.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.