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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.

Smc5/6 association with DNA junctions can support genomic functions. Here, the authors show that Smc5/6 junction polarity preferences, targeting, and dwell times are determined by its structural modules as well as the RPA and PCNA genomic factors.

Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

Here, the authors develop AMPLiT a tool for screening antimicrobial peptides in metagenomic datasets, and apply it to human coprolite metagenomes, finding that Segatella copri, an ancient prevalent human gut bacterium declined in modern populations, harbors unexplored antimicrobial reservoir, offering an alternative approach against modern pathogenic infections.

This work demonstrates the first miniature RF filter combining ultrawide tunability (4–18 GHz) and high nonreciprocity, achieving low loss, zero static power, and compact size (1 cc).

Language is often thought to be represented through hierarchically structured units. Nielsen and Christiansen find that non-hierarchical structures are present across reaction-time tasks, eye-tracked reading and natural conversation.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

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.

Bark decomposition could significantly affect global carbon and nutrient cycling. Here, the authors report the global trend of bark decomposition rates, identify the key drivers in different climate regions, and predict the response of bark decomposition to future climate change.

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.

Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

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.

Natural variation in hecw-1 encoding an E3 ubiquitin ligase influences the avoidance of pathogenic bacteria by Caenorhabditis elegans and forms a molecular basis for behavioural variation.

When a wave packet traces a conical intersection, its phase must change a sign. The authors show direct experimental and computational evidence of this geometric phase effect for the hydrogen exchange reaction H + D₂ → HD + D.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Influenza A virus infection causes a dramatic upregulation of ADP-ribosylation that as part of the cellular antiviral response, a process that is counteracted by the viral NS1 protein.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Carnitine uptake by OCTN2 supports fatty acid metabolism. Here, authors report cryo-EM structures of human OCTN2, revealing the mechanism of sodium ion-dependent carnitine transport and providing insight into disease-associated variants.

The endoplasmic-reticulum (ER) transmembrane protein IRE1 mitigates ER stress through kinase-ribonuclease and scaffolding activities. However, a significant nonenzymatic IRE1 dependency has been shown in cancer. Here, the authors design a proteolysis-targeting chimera (PROTAC) to fully disrupt cellular IRE1 protein, selectively blocking growth of IRE1-dependent cancer cells.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Zonal positioning in the liver determines whether the CTNNB1 oncogene can induce liver cancer.

Extrachromosomal circular DNAs (ecDNAs) are prevalent in human cancers and are thought to drive tumor evolution and drug resistance by amplifying oncogenes. Here, authors develop ec3D to reconstruct three-dimensional ecDNA structures, revealing how their spatial organization rewires regulatory circuits.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Here, the authors reveal how twisting MoSe₂/WS₂ layers controls exciton behaviour. Combining theory and ultrafast spectroscopy, they show that lattice reconstruction creates distinct bright and long-lived excitons without hybridization effects.

With rich, multi-layered baseline data and long-term follow-up through linkage, the HELIOS Study provides a resource to investigate the behavioural, environmental, genomic, and molecular factors impacting health in Asian populations.

The authors report the discovery of charge order with onset temperature of 800 K in the kagome superconductor YRu₃Si₂. In addition, they observe time-reversal symmetry breaking below 25 K, field-induced magnetism below 90 K and bulk multi-gap superconductivity below 3.4 K.

Zierer et al. engineered cassava to express a modified potassium channel that enhances sugar flow, improving the yield and drought resilience. This strategy offers a route to increase cassava productivity in tropical regions.

ATP synthase powers cells by converting proton translocation into energy. Here, authors reveal distinct structural features of the P. aeruginosa ATP synthase that regulate activity and may serve as targets for new antimicrobial therapies.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Two impact-melt fragments in Chang’e-6 lunar soils reveal that the Apollo basin was formed at ~4.16 Ga, implying a non-cataclysmic late heavy bombardment on the Moon between 3.8 and 4.0 Ga.

This study reports that the gene SMPED1, located in a previously identified dichogamy-determining region in Alpinia species, controls the timing of sex-organ synchrony, improving our understanding of the evolutionary mechanisms of plant sexual diversity.

An outstanding question regarding cuprate superconductors is how the Fermi liquid behaviour of their normal state breaks down. Chang et al. conduct a systematic ARPES study of how the Fermi liquid quasiparticle excitations break down in momentum space, and find it to be highly anisotropic in La_2−xSr_xCuO₄.

Cap-independently translated mRNAs could expand the scope of mRNA therapies, but yield limited protein, and existing enhancement strategies are imperfect. Here, the authors install a 5′-end modification that both boosts efficiency and facilitates in-depth characterisation of these mRNAs.

A combination of genome-wide functional screening, imaging and chromatin profiling identifies a new class of highly prevalent genomic elements that help retain extrachromosomal DNA copies in dividing cells and persist across generations.

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.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

The application of astatine, one of the rarest elements on the earth, in the treatment of cancer requires a better understanding of its chemistry. Rothe et al. report the first measurement of the ionization potential of astatine, against which high-level quantum calculations are benchmarked.

A dipolar-passivation strategy enables all-perovskite tandem solar cells with a power conversion efficiency of over 30%.

Quantifying the degree of correlation required to drive a Mott insulator transition is a crucial aspect in understanding and manipulating correlated electrons. Here, the authors introduce a thallium-based cuprate system and use resonant inelastic X-ray scattering, combined with Hubbard-Heisenberg modeling, to establish a universal relation between electron interactions and magnon dispersion, suggesting optimal superconductivity at intermediate correlation strength.

The interplay between competing orders in high-temperature superconductors can be tuned by the application of magnetic fields. Here, Chang et al. report high field induced three-dimensional charge density wave in underdoped YBa₂Cu₃O_6.67, which suggests Fermi surface reconstruction due to competing orders.