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Restricting or permitting H3K27me3 spreading concentrates or dilutes canonical PRC1 (cPRC1), respectively, which affects three-dimensional chromatin interactions. Disruption of cPRC1 compromises repression of Polycomb target genes and induces differentiation and tumor regression in H3K27M-mutant glioma.

The authors performed computational and experimental analyses to reveal how Smoothened directly inhibits PKA through an intrinsically disordered region, defining a central step in Hedgehog signaling and a mechanism of G-protein-coupled receptor–kinase regulation.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Neuromodulation via epidural electrical stimulation both below and above the lesion in three participants with complete spinal cord injury could enable respectively motor activation and sensory perception.

Guan, Ocampo and colleagues report the discovery and mechanistic dissection of Al3Cas12f, a metagenome-derived miniature nuclease that retains notable genome-editing capacity. They engineer an RKK variant, which boosts editing and helps overcome the potency threshold that has limited compact editors.

This Review discusses the unique features of the functionally versatile nuclease Cas12a, including allosteric regulation, structural elements controlling guide RNA maturation, target specificity, cis-cleavage and trans-cleavage activities and determinants of off-target cleavage. These features increase the applicability of Cas12a in biotechnology, therapeutics and molecular diagnostics

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

JWST phase-curve observations reveal that the two innermost TRAPPIST-1 planets emit thermal radiation consistent with bare rocky surfaces, indicating that both lack thick atmospheres.

Kir7.1 is an essential potassium channel. The authors report cryo-EM structures in multiple states revealing how bioactive lipids modulate Kir7.1, and define a pharmacological landscape that identifies agonists with therapeutic potential.

High-order modes of hyperbolic polaritons – hybrid light-matter interactions – in anisotropic van der Waals materials hold potential for nanophotonics applications. Here, the authors report the observation of polariton mode conversion in step-shaped terraces of hexagonal boron nitride and α-MoO3.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Extreme thermal transport in 2D materials challenges classical models. Here the authors combine microheater-based thermal control and Raman thermometry to reveal high in-plane thermal conductivity and non-diffusive phonon transport in suspended monoisotopic hBN.

Nanoscale emitters are useful for measuring biomolecular interactions, but are limited by weak signals. Here, the authors use a photonic crystal surface for 3000-fold signal enhancement, achieving single emitter sensitivity with extended on-time, and demonstrate its application in miRNA biomarker sensing.

Interface engineering is promising for advancing perovskite solar cell (PSC) performance and longevity. This Review highlights three emerging strategies for interfacial optimization in PSCs: multifunctional molecular passivation, heterostructures and self-assembled monolayers. The authors discuss relevant materials, assess their limitations and outline challenges and prospective directions for future research.

Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

Artificial reefs provide important ecosystem services in marine environments. Accurate knowledge of the area covered by such reefs can help evaluate benefits and risks of such structures. This study describes the physical footprint of artificial reefs deployed in coastal waters of the United States.

Here, Schwartz, Bravo, and Ahsan et al. show how multi-subunit fusion proteins are arranged around a crRNA in a type III CRISPR-Cas effector to cleave target RNA. Structures and molecular dynamics of this complex show three distinct active sites that can be used for programmable RNA cleavage.

The origin of continental crust is unclear. Geochemical and geophysical analyses of the Central American land bridge show that continental crust began to form there when enriched oceanic crust created above the Galápagos plume was subducted.

Exai-1, a cell-free RNA foundation model that integrates sequence, structure and expression features, advances liquid biopsy diagnostics by denoising noisy data, augmenting limited datasets and improving the generalizability of cancer detection models.

Symmetrical protein oligomers perform key structural and catalytic functions in nature, but engineering such oligomers synthetically is challenging. Now, oppositely supercharged synthetic variants of normally monomeric proteins have been shown to assemble via specific, introduced electrostatic contacts into symmetrical, highly well-defined oligomers.

RNA polymerase (Pol) I transcribes ribosomal RNA that is critically required for ribosome assembly, and the enzyme is a major determinant of protein biosynthesis and cell growth; here the crystal structure of the complete 14-subunit Pol I from yeast is determined, providing insights into its unique architecture and the possible functional roles of its components.

Vietnam has undergone a social and economic transformation since the end of the war in 1975. In this Perspective, the authors describe how the progress that has alleviated infectious disease burdens burdens associated with absolute poverty has generated new challenges linked to urbanisation, inequality, and lifestyle changes.

Chiral metamaterials present interesting ways to manipulate and distinguish between different circular polarizations of light. Zhanget al. realize chiral metamaterials that exhibit photoinduced switching between left- and right-handed circular polarization interactions at terahertz frequencies.

Acinetobacter baumannii is a multi-drug-resistant pathogen of urgent international concern. Here, the authors develop a protein subunit vaccine which prevents A. baumannii catheter-associated urinary tract infections in mice by inhibiting Abp2D, a key adhesive virulence factor.

By demonstrating a computational approach to restore the clinical efficacy of a COVID-19 antibody, the potential to rapidly update clinical antibodies is explored.

Commercially available bionic hands can replicate many movements, but controlling a multiarticulate bionic hand is not an intuitive task. Here, the authors describe the integration of proximity and pressure sensors into a commercial prosthesis to enable autonomous grasping

Cellobiohydrolases (CBHs) are critical for natural and industrial biomass degradation but their structure–activity relationships are not fully understood. Here, the authors present the biochemical and structural characterization of two CBHs, identifying protein regions that confer enhanced CBH activity.

Here, the authors show that van der Waals isotopic heterostructures based on few-layer h¹⁰BN and h¹¹BN can be tuned to modulate the energy-momentum dispersions of hyperbolic phonon polaritons, offering an alternative approach to engineer the nanophotonic properties of 2D materials.

Mutation of conserved prolines enhances correct pairing of light and heavy chains for bispecific IgG-like antibody production.

Ingo Braasch, John Postlethwait and colleagues report the genome of the spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before genome duplication. Their data provide insights into the evolution of genes involved in immunity, mineralization and development and facilitate the comparison of cis-regulatory elements between teleosts and humans.

Crystal structures of a five-protein complex comprising the inner-membrane components of the bacterial lipopolysaccharide transporter provide insight into the mechanism of extraction of lipopolysaccharide from the inner membrane and its transport to the outer membrane.

Here the authors discover a small-molecule that inhibits DNA polymerase theta by trapping the enzyme on DNA in the closed conformation. The inhibitor selectively kills BRCA-mutant cells and exhibits strong synergistic activity with PARP inhibitors.