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Here, in a cross-sectional study of 209 individuals living in communities with contrasting Schistosoma mansoni endemicity in Uganda, the authors identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

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.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

Using cryo-EM, the authors identified 42 MIPs, including outer junction protein CFAP77 and outer dense fibers, in native doublet microtubules of Tetrahymena thermophila. Knockout of CFAP77 reduced ciliary beat frequency and led to outer junction damage.

The R21/Matrix-M vaccine, but not the ME-TRAP vaccine, was protective against intradermal challenge with Plasmodium falciparum sporozoites, while neither was protective against direct venous inoculation, potentially explaining previously observed differences in protection.

An implantable vagus nerve-targeted device safely reduces disease activity and joint damage in rheumatoid arthritis, offering a new nondrug treatment for patients who do not respond to or cannot tolerate medication.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

The impact of negative energy balance on dopamine transmission is unclear. Here, authors show that the ABA model disrupts dopamine transmission via loss of GABAergic control over VTA dopamine neurons contributing to the development of hyperactivity.

This study shows that optimally sized nanocarriers reach Duchenne muscular dystrophy muscle primarily through transcytosis, where they can deliver tamoxifen to improve muscle health and strength in mice.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the functional loss of the tumor suppressor gene neurofibromin, that can lead to the development of benign and malignant tumors. Here the authors describe the development of an adeno-associated virus vector for NF1 gene replacement therapy of NF1 related tumors, showing tropism and anti-tumor activity in preclinical models

This study introduces P3T-Net, a pseudo-3D deep learning model that enables accurate and efficient cross-domain transfer of large 3D material images, improving image quality and ensuring image consistency across diverse imaging conditions.

Triple artemisinin-based combination therapies, including mefloquine–piperaquine (MQ–PPQ), may delay emergence of multidrug-resistant strains. Here the authors show that resistance to mefloquine alone reduces the efficacy of the MQ-PPQ combination therapy, and that the interaction between the two drugs further inhibits piperaquine’s activity.

Microbial alcohol production from waste gases could enable sustainable carbon cycling. Now, the tungsten-dependent aldehyde:ferredoxin oxidoreductase from the gas-converting bacterium Clostridium autoethanogenum has been biochemically and structurally characterized. This monomeric enzyme is responsible for acetate reduction to acetaldehyde, the key step of ethanol production in this industrial microorganism.

The mechanism(s) controlling CD8+ virtual memory T cell (TVM) development are still under investigation. Here, using uninfected or IAV-challenged Ikzf3-deficient mice, the authors identify the transcription factor Aiolos as a negative regulator of TVM cell development by repressing Eomes and IL-15/STAT5 signaling.

Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.

Optimizing Raman spectrometer designs for use in extreme environments can enable acquisition of critical information that may not be accessible in situ by humans. Technology advancements currently being made for space exploration can be exploited in order for such spectrometers to be used in dangerous terrestrial environments.

In this work, authors present a personalized phage therapy regimen targeting Staphylococcus aureus, which led to complete lesion removal, a six-month flare-free period and improved quality-of-life in a Hidradenitis Suppurativa (HS) patient.

The recent developments in artificial intelligence (AI) have created both intrigue and apprehension in the world of research. In this Viewpoint, we asked 12 experts in the field of metabolism to share their — differing — opinions on the use of AI in pre-clinical and clinical metabolic research.

Photonic processors are limited by the bulkiness of discrete components and wiring complexity. An experiment now demonstrates a reprogrammable two-dimensional waveguide that performs neural network inference through multimode wave propagation.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

This special issue is our ‘message in a bottle’ from the troubled ship of science. We urge readers to find it. Open it. Act on its contents.

Neurocognitive impairment and premature aging often occur in childhood survivors of cancer. Here, the authors investigate the link between biological markers of age and neurocognitive functioning in survivors of childhood cancer who received either central nervous system (CNS)-targeted or non-CNS-targeted therapy.

Telomerase recruitment to telomeres is a tightly regulated process which is stimulated by replication stress. Here, the authors identify that nuclear filamentous actin is important for interaction between telomerase and telomeres, ultimately facilitating productive telomere extension by telomerase.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

The COVID-19 vaccine rollout saw large global disparities in the introduction, scale-up, and evaluation of immunisation programmes. Here, the authors systematically quantify these disparities through linkage of public data sources.

In this study, the authors present antimalarial drug resistance surveillance data from Uganda over the period 2019-2024. They measure ex vivo susceptibility to nine standard antimalarials in 1,114 isolates and characterise sequences of markers of drug susceptibility.

This work experimentally demonstrates that light-field spatial modulation can be harnessed to substantially increase the forces used to optically levitate nanoparticles in vacuum.

Zarkali and colleagues studied brain connectivity in 108 people with Lewy body disease. They found distinct structural cortical reorganisation linked to cognitive, not motor symptoms and implicated excitatory RORB4 neurons in dementia-associated changes.

Respect for what you and your colleagues bring to the table is vital to successful integration, says Melissa T. Miller.

A neural implant with a subnanolitre-volume can provide year-long in vivo recordings in awake mice.

Synovial sarcoma (SS) is a difficult-to-treat cancer, driven by the fusion oncoprotein SS18::SSX. SS18::SSX alters the BAF (mammalian SWI/SNF) chromatin remodelling complex to create an oncogenic transcriptome. Here, the authors identify SS18::SSX-driven SMARCE1 SUMOylation as a therapeutic vulnerability in SS and show that SUMOylation inhibition stabilizes the cBAF complex, inducing cell death and sensitization of SS to chemotherapy.

Five leading researchers provide their perspectives on our current understanding of pioneer factors and their important gene regulatory roles in cell differentiation, cell fate determination and reprogramming.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The quantum noise of Kerr combs is found to exhibit oscillatory lattice dynamics through state transitions, with implications for squeezing and comb formation.

Several 17B-HSD13 variants have been identified as protective against NASH/MASH. However the protein’s endogenous function is unknown. Here authors describe sulfonamide-based inhibitors and synthetic substrates, then apply to multiple cellular systems revealing that the most prevalent IsoD variant maintains NAD-dependent catalytic activity.

We are leading Nature on a journey to help decolonize research and forge a path towards restorative justice and reconciliation.

TIRTL-seq is an innovative method that allows efficient and cost-effective identification of αβ TCR clones from millions of T cells with the aid of a pairing algorithm called T-SHELL, which provides high accuracy and throughput in sequencing paired TCR clones.

E. coli sequence type 131 is a significant cause of community-onset infection. Here, the authors perform a prospective household-based cohort study in Singapore including samples from humans, companion animals, the environment, and food, to characterise transmission and carriage dynamics.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

We have all heard the cliché; hormones make us unreliable and unpredictable. However, in this issue of Nature Neuroscience, Golden et al. show that higher states of endogenous estrogen enhance reward prediction errors in sophisticated ways, which promotes adaptive behavior and improves performance.

Elective surgical hubs in England aim to improve efficiency, reduce cancellations, and enhance patient and staff experiences by focusing on High-Volume, Low Complexity (HVLC) surgeries. Here, the authors show that new hubs significantly increased HVLC surgery rates and established hubs demonstrated resilience during the Covid-19 pandemic.