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The Amazon faces worsening droughts, yet little is known about large-scale variation in the physiological limits of Amazon trees. Here, the authors reveal family-level conservatism in embolism resistance and estimate that Brazilian and Guiana shield forests are more resistant than Western Amazonia forests.

Here, the authors investigate the mechanism by which human aspartate/asparagine-β-hydroxylase (AspH), a 2OG-dependent oxygenase with an atypical Fe(II) coordination environment, catalyses hydroxylation of aspartate and asparagine residues in epidermal growth factor-like domains.

The pathological mechanisms underlying multiple system atrophy (MSA) remain unclear. Here, the authors show in mouse and human MSA models that α-synuclein spreads from neurons to oligodendrocytes via TLR2 leading to myelination defects, and that blocking TLR2 prevents glial cytoplasmic inclusions and myelin damage.

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.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

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.

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.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

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.

Molecular bilayer crystals of an organic semiconductor can exhibit metallic charge transport down to 8 K with an electrical conductivity of up to 245 S cm⁻¹, as well as charge carrier mobility values of more than 100 cm² V⁻¹ s⁻¹ at 20 K.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

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.

Microbial consortia offer a promising route for sustainable wastewater treatment but are often constrained by inefficient interspecies metabolic interactions. This study shows that hydrogel-defined mesospace confinement enhances interspecies cross-feeding by regulating transmembrane transport and metabolite retention, improving pathway selectivity and treatment efficiency.

Short-circuiting during fast charging through lithium dendrite intrusion into electrolytes is a major challenge in solid-state batteries. Here, using thermally annealed 3-nm-thick Ag coatings, lithium penetration into brittle electrolyte Li_6.6La₃Zr_1.6Ta_0.4O₁₂ is inhibited at local current densities of 250 mA cm⁻² due to an increase in surface fracture toughness.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Isotropic tissue magnification is integrated with matrix-assisted laser desorption/ionization mass spectrometry imaging to enable untargeted spatial proteomics at micrometre resolution and with high protein identification rates in multiple tissue types.

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.

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.

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.

An 11-qubit atom processor comprising two precision-placed nuclear spin registers of phosphorus in silicon is shown to achieve state-of-the-art Bell-state fidelities of up to 99.5%.

Hybrid gRNAs significantly increase targeted editing in the liver while simultaneously reducing unwanted bystander editing in humanized mouse models.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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 biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

A completely solid-state, single-chip, microwave-frequency surface acoustic wave phonon laser can generate coherent phonons from thermal noise or resonantly amplify injected phonons using only a direct current bias field.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

On-demand laser-induced frequency tuning of coherent magnons in a 20 nm thick magnet at room temperature is demonstrated. By tuning the laser fluence and magnetic field, red- or blueshift of the frequency up to 40% of its original value are achieved.

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.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

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.

METTL3 promotes healthy placenta function by regulating m⁶A methylation and histone epigenetics. Deficiency in METTL3 leads to premature senescence, inflammation activation of trophoblasts, contributing to pregnancy complications like preeclampsia.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

The short Argonaute-based bacterial defence system SPARDA exhibits collateral nuclease activity during phage infection. Here, the authors show that target DNA-induced filament assembly of SPARDA leads to tetramerization and activation of the DREN nuclease domain.

De novo design of Ca²⁺ channels with ion selectivity that can assemble appropriately and mediate Ca²⁺ conductance when expressed in cells is described.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.