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Many human antibodies that neutralize Zika virus recognize quaternary epitopes on the envelope (E) protein. Here, Metz et al. engineer stable recombinant homodimers of Zika virus E protein and show that it induces neutralizing antibodies in mice that recognize similar epitopes as human antibodies from Zika infected people.

The human ATP-binding cassette transporter ABCG2 plays critical roles in anticancer resistance but the molecular mechanism of ABCG2-mediated substrate transport remains enigmatic. Here authors use extensive mutagenesis and molecular dynamics simulations to reveal a mechanistic basis for the function of the di-leucine valve and the roof organization in the transport cycle.

Iron coordination complexes can be used to gain insight on biologically relevant iron-oxygen compounds generated in iron metalloenzymes. Here, the authors characterise a μ-1,2-hydroperoxo Fe^IIIFe^III and a μ-1,2-peroxo Fe^IVFe^III, and study their reactivity in C-H activation.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Whilst superlattices containing thin films of 5d transition metal oxides are expected to yield strong interfacial coupling, only weak effects have been observed. Here, the authors report strong coupling between 3d SrMnO₃ and 5d SrIrO₃due to the interplay of strong Coulomb and spin orbit interactions.

Mass spectrometry (MS) involves ionization of analytes with spectra dependent upon the mass-to-charge ratio. Here, the authors demonstrate that MS based on nanoelectromechanical systems gives results that are independent of the charge state and allow the mass spectrum of neutral species to be obtained.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

Three-terminal memtransistors can improve the neuromorphic performance of conventional two-terminal memristors. Here, the authors report the fabrication of high-yield large-scale crossbar array architectures incorporating up to 2,048 2D MoS₂ memtransistors per array, showing low-power memory and image recognition applications.

Lu et al. perform systematic functional analyses using data from the TRACERx cohort of patients with non-small-cell lung cancer and delineate how FAT1 regulates homologous recombination repair, chromosomal instability and whole-genome doubling with distinct mechanisms.

An in situ only fabrication process for networks of topological insulator–superconductor Josephson junctions with high interface transparency is introduced, which holds some potential for the production of future topological quantum computing networks.

Antimicrobial resistance continues to be a critical One Health challenge, despite research and policy progress. Building on the past decade of research, this Perspective provides an integrative roadmap for addressing antimicrobial resistance by leveraging the complexities of human and environment interactions.

The bacterial diterpene synthase CotB2 catalyses the cyclisation of geranylgeranyl diphosphate to cyclooctat-9-en7-ol. Here the authors present various CotB2 structures including a trapped abrupt reaction product that were used for molecular dynamic simulations and allowed them to model all intermediates along the reaction cascade.

Supercapacitors are fast-charging energy-storage devices. However, an understanding of how structure impacts high-power energy storage is still lacking. Here pulsed-field-gradient nuclear magnetic resonance measurements show that the pore network tortuosity, rather than traditional porosity analyses, in porous carbon dictates the speed of supercapacitor charging.

Otu2-driven deubiquitylation of ribosomal protein eS7 impacts translational efficiency. Here, the authors provide the molecular basis for recognition of monoubiquitinated eS7 on 40S and give mechanistic insights into Otu2’s role in translation reset.

The ATPase UAP56 acts as an ATP-gated molecular switch that directs mRNA ribonucleoprotein complexes from TREX to nuclear-pore-complex-anchored TREX-2 complexes for mRNA export from the nucleus.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

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.

Leukapheresis is prohibitive in newborns due to the large extracorporeal volume. Here, the authors develop a microfluidic device to perform leukapheresis on whole blood at clinically relevant flow rates and show its safety and efficacy in animals.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

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

Here, Chi et al. report cryo-EM structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic T1 domain, which allows the interactions with the C-terminal axonal targeting motif and key components of the gating machinery. These findings provide insights into the functional relevance of previously unknown interdomain interactions in Kv3 channels and may guide the design of new pharmaceutical drugs.

There is no consensus on a potential primary cause of spatio-temporal biodiversity patterns. Here the authors combine a macroecological model and global climate simulations to suggest that niche-environment interaction may have driven marine biodiversity trajectory during the Phanerozoic.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with novel topologies is of both fundamental and practical interest but the construction of highly crystalline 3D COF remains challenging. Here, the authors report highly crystalline 3D COFs with pto and mhq-z topologies by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains.

X-ray crystallography, solution NMR and biochemical and cell-based analyses reveal a model where catalytically repressed receptor tyrosine kinases accomplish activation loop (A-loop) tyrosine transphosphorylation.

The local X-ray-induced dynamics that occur in protein crystals during serial femtosecond crystallography (SFX) measurements at XFELs are not well understood. Here the authors performed a time-resolved X-ray pump X-ray probe SFX experiment, and they observe distinct structural changes in the disulfide bridges and peptide backbone of proteins; complementing theoretical approaches allow them to further characterize the details of the X-ray induced ionization and local structural dynamics.

Patients with Huntington’s disease carrying the FAN1 R507H mutation have earlier than predicted onset of motoric symptoms. This study provides mechanistic insight into the interactions that may promote CAG repeat expansion. FAN1 R507 interacts with PCNA D232 and this interaction is impaired for FAN1 R507H, resulting in reduced FAN1 activity.

Three structures of the eukaryotic small ribosomal subunit in complex with initiator tRNA, mRNA and the initiation factors eIF1 and eIF1A have been solved; these structures offer insight into the contributions of the initiation factors, the mechanism by which mRNA is scanned, and the interactions that occur in the ribosome’s P site.

Glycosylation of human IgG antibodies in bacterial hosts has proven challenging. Here, the authors identify a bacterial enzyme enabling E. coli to glycosylate IgGs at native sites, thereby advancing therapeutic antibody development in this host.

Researchers developed a programmable metamaterial that enables real-time shaping of low-frequency vibrations. Using simple, off-the-shelf components, it unlocks applications ranging from refreshable multi-touch tactile displays to analog computing.

Cross-study analysis defines fecal microbial species associated with colorectal cancer.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Protein/protein interaction (PPI) interfaces have emerged as drug targets to develop medications with less side effects. Here, Dvorak et al. show that small molecule targeting of PPIs in the brain is an approach for psychiatric drug discovery.

It is unclear how cell compartmentalization emerged in prebiotic conditions. Now it is shown that a temperature gradient in a confined space can bring the core components of a cell together.

The sorting and assembly machinery (SAM) mediates mitochondrial β-barrel protein folding and membrane insertion. A cryo-EM structure of the yeast SAM complex bound to an early eukaryotic β-barrel intermediate reveals a multipoint guidance mechanism.

In this Review, Kahne and colleagues discuss how lipopolysaccharide (LPS) is transported across the cellular envelope and inserted into the outer membrane of Gram-negative bacteria. They propose a new model, which explains how energy from the cytoplasm is used to power LPS transport to the cell surface.

Large variability of wood carbon fractions in different trees can lead to an error of up to 8.9% in carbon estimates for forests, according to an analysis of wood carbon data across global forested biomes.

Many recent studies have explored the response of magnetic systems to circularly polarised light. To achieve this, typically experiments use a birefringent crystal. Here, Yang et al show that any small error in the alignment of the crystal can result in a beam shift, and this shift can lead to spurious signals similar yet unrelated to the electron spin.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

The Rbfox family of developmentally important splicing factors controls alternative splicing in a tissue-specific manner. Genome-wide analyses now show that more than half of Rbfox-binding sites are located distally from exons, that these distal sites are conserved and functionally important, and that long-range RNA-RNA secondary structures mediate distal splicing regulation by Rbfox.