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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.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Genetic predictors of health outcomes often drop in accuracy when applied to people dissimilar to participants of large genetic studies. Here, the authors investigate the root causes and highlight open questions underlying this problem.

The authors investigate the heterogeneity of Toxoplasma bradyzoites prior to recrudescence. Tissue cysts from infected mice harbor multiple bradyzoite subtypes with distinct developmental fates as evidenced by single-bradyzoite RNAseq and FACS.

Previous studies suggested that glycogen metabolism played a role in beiging of subcutaneous adipocytes. This work identifies a β-adrenergic–driven transcriptional program that promotes glycogen synthesis and turnover during thermogenic activation of adipocytes. PGC1α and estrogen-related receptors (ERRs) cooperatively sustain this program by regulating chromatin accessibility and gene expression.

Scanning nitrogen-vacancy microscopy unveils super-moiré spin textures emerging in twisted double-bilayer CrI₃ and provides real-space evidence of antiferromagnetic Néel-type skyrmions spanning multiple moiré cells.

The inability of intrinsically photosensitive retinal ganglion cells to shift the circadian clock in the suprachiasmatic nucleus during daytime is caused by light-dependent depolarization block of these cells.

Early life RSV infection contributes to risk of childhood asthma. Here, the authors develop a statistical model to predict age at first RSV infection in the United States based on birthdate, demographics, and RSV surveillance data which could be used to identify groups at risk of chronic respiratory sequalae like asthma.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

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.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

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 distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

The Neurospora circadian clock keeps time through a negative feedback loop involving a protein complex of FRQ bound to FRH. Here, the authors show that slow, stochastic phosphorylation of these proteins dissociates and activates them via two precisely timed switches.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Disease heterogeneity complicates precision medicine, which focuses on single conditions and ignores shared mechanisms. Here the authors introduce ‘pan-disease’ analysis using a deep learning model on multi-organ data, identifying 11 AI-derived biomarkers that reveal new therapeutic targets and pathways, enhancing patient stratification for disease risk monitoring and drug discovery.

In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

Lucerastat was well-tolerated, but did not reduce neuropathic pain, abdominal pain, or diarrhea compared with placebo. Lucerastat reduced biomarkers of Fabry Disease at 6 months, and these reductions were maintained at the 18-month interim analysis.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

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.

Anti-phased changes in Antarctic Circumpolar Current strength between the Indian and Pacific sectors of the Southern Ocean occurred on orbital timescales over the past one million years, linked to glacial cycles and obliquity forcing, according to proxy records and modelling.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

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.

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.

Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

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.

Nitazenes are potent synthetic opioids that are difficult to detect. Here, authors computationally redesign a plant receptor to create sensitive sensors capable of detecting diverse nitazenes and their metabolites in biological samples.

Breeding crops with delayed senescence could plausibly increase grain yield. Here the authors show that variation at the rice SGR locus contributes to differences in senescence between indica and japonica subspecies and show that introgression can increase yield in an elite indica rice variety.

Neuronal and pharmacological analysis of rat auditory cortex reveals its direct role in regulating vocal production, identifying distinct neuron classes that predict call timing and duration and demonstrating auditory modulation of vocal behavior

Utricle, a component of the inner ear vestibular system, is essential for balance. This study maps the cells and genes in the adult human utricle. It identifies distinct non-sensory cell types and reveals early responses to damage, providing insight into potential strategies for restoring balance.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

From 2003 to 2020, the efficiency of white light-emitting diodes rose from 6% to 39%, while costs fell by 96%. Weinold et al. explore the drivers of such rapid progress to formulate lessons for future clean energy innovation.

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 platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Ma et al. developed a directed evolution method with various selection strategies for the evolution of synthetic intrinsically disordered proteins capable of forming condensates with desired properties in living cells.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

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.

The authors develop textile electronic substrates with tailored stiffness and interfacial affinities by selective and controllable laser-matter interaction, addressing the mechanical mismatch between hybrid electronics and elastic textiles.

The mediodorsal thalamus (MD) is central to flexible decision-making. Here, the authors identify MD’s unique roles in arbitrating between different reinforcement learning strategies through prefrontal-striatal brain circuits.

In this study, a post-hoc analysis of medical records for individuals being treated with Cobenfy investigates real-world effectiveness, identifying predictors of response and suggesting the existence of biologically distinct psychosis subgroups.