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Controlling the reactivity of the propagating chain end in polymerization reactions is crucial for achieving well-defined polymers. Here, the authors present a strategy for processive catalytic polymerization by encapsulating catalysts for ring-opening metathesis polymerization into the sub-surface cages of a metal-organic framework.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The cell cycle regulatory E3 ligase APC/C cooperates with UBE2C to prime substrates with ubiquitin and UBE2S to extend the ubiquitin chains. Careful analysis reveals that binding of the UBE2S to APC/C accelerates the rate-limiting step of APC/C–UBE2C.

By simply deprotonating a neutral hydrogen-bond donor thiourea it is possible to generate a class of highly efficient and tunable thioimidates that can simultaneously activate a pro-nucleophile and an electrophile. These bifunctional thioimidates exhibit fast kinetics and high selectivity for ring-opening polymerizations of cyclic lactones and carbonates.

Reovirus mRNAs lack polyadenylated tails yet are efficiently translated. Here, the authors identify host protein ataxin-2-like (ATXN2L) as a mediator of reovirus nonpolyadenylated mRNA translation.

Fluorinated poly(aryl thioethers), unlike their poly(aryl ethers) counterparts, have received little attention despite excellent physical properties displayed by many polysulfides. Here the authors show a highly efficient route to fluorinated poly(aryl thioethers) via an organocatalyzed nucleophilic aromatic substitution of silyl-protected dithiols.

The structure (at ∼7-nm resolution) of a complete flagellar motor obtained in situ by electron cryotomography of intact Treponema primitia cells is presented. The stator's 16-fold symmetry and its multiple connections to the rotor, C ring and a novel P-ring-like structure are described.

Dysregulated protein levels can cause disease. The authors present a scalable platform capable of identifying small molecules that alter disease-linked target protein levels, and report >40 that increase SynGAP protein abundance, with SR1815 restoring neuronal function in Syngap1 deficient neurons.

The analysis of the energy spectrum of 36 million tritium β-decay electrons recorded in 259 measurement days within the last 40 eV below the endpoint challenges the Neutrino-4 claim.

Single-photon emitters (SPEs) in 2D semiconductors are usually affected by complex spectral profiles that limit their understanding and applications. Here, the authors combine a noncovalent surface functionalization method with localized mechanical strain to simplify the spectra and enhance the purity of SPEs in monolayer WSe₂.

Heparin-like oligosaccharides are implicated in various diseases. Hansen et al. report an efficient two-cycle [4+4+4] tetrasaccharide-iteration-based approach to synthesize a structurally defined heparin dodecasaccharide with a latent aldehyde tag for labelling and conjugation.

A compilation of wildfire records spanning six continents and 2,000 years reveals global patterns in biomass burning to be temporally linked with changes in climate, population and land use. An abrupt decline in biomass burning beginning about 150 years ago may be related to the expansion of intensive grazing, agriculture and fire management activities.

Experiments in human cortical organoid and mouse models of SYNGAP1 haploinsufficiency, which is associated with autism spectrum disorder (ASD), reveal altered cortical neurogenesis, suggesting that a non-synaptic mechanism contributes to the disorder.

Quantum error correction codes with low qubit overhead and error suppression capabilities are highly desirable for fault-tolerant quantum computing. Here, the authors introduce a family of high-rate Low Density Parity-Check quantum error correcting codes with moderate long-range connectivity and outline a near-term implementation in static neutral atom registers.

As the Plasmodium species that cause malaria replicate in the liver, Heath and colleagues designed mRNA vaccines to limit infection by inducing liver-resident memory T cells. Efficacy was observed in mice, including in hosts with previous blood-stage infection.

Biosynthesis of the strigolactones—important plant hormones—has been solved up to carlactone. Biochemical and genetic evidence now demonstrate that homologous enzymes perform two subsequent oxidations, setting the strigolactone scaffold in place.

Research shows how small nuclear RNAs act as a cellular GPS to guide endogenous RNA-modifying enzymes to their targets for site-specific RNA editing. This approach boosts efficiency and safety when editing high-complexity genes, broadening the therapeutic potential.

SOX2 is required for the maintenance of glioblastoma stem cells (GSCs). Here the authors identify that the RING family E3 ubiquitin ligase TRIM26 promotes SOX2 stability in a non-canonical ligase-independent manner and thus, increases the tumorigenicity of GSCs.

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.

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.

The Lewis acidity of a compound can be manipulated using a light-sensitive molecular switch

Two ‘outrigger’ telescopes were added to CHIME, leading to the localization at detection of FRB 20210603A. The burst originated from deep within the star-forming disk of its host galaxy.

SPNS2 exports S1P and FTY720-P to control immune cell migration. Here, the authors use cryo-EM, immunofluorescence, in vitro binding and in vivo S1P export, and MD simulations to uncover the mechanisms of SPNS2’s transport and inhibition.

Many emerging SARS-CoV-2 variants partially escape the humoral immune response. Here, Liu et al. characterize 28 antibodies from BA.4/5 breakthrough infections and find attrition of neutralization and complete loss of function for variants with Spike mutations at positions 455 and 456.

TRIM23 is identified as an essential regulator of virus-induced autophagy that mediates restriction to several RNA and DNA viruses. K27-mediated ubiquitylation activates TRIM23 GTPase activity, triggering its relocalization and selective autophagy.

Shen et al. report a method for multiplexing isogenic iPSCs for single-cell RNA-seq. With it, they created an atlas of in vitro differentiation and identified TMEM88 as a regulator of cardiovascular development, impacting blood pressure in adult mice.

Malaria parasites invade erythrocytes to proliferate, but visualizing this rapid process is challenging. Here the authors use live imaging and genome-editing of P. knowlesi to dissect invasion and establish the roles of two vital parasite proteins.

NinaB is an isomerooxygenase that generates visual chromophore (11-cis-retinal) from carotenoid substrates. Here Solano et al. reveal the structural basis for NinaB isomerase activity, providing new insights into the evolution of visual chromophore synthesis by carotenoid cleavage enzymes.

This study has developed the first small molecule NEDD8-activating enzyme (NAE) inhibitor, which induces cancer cell death and exerts anti-tumour activity in preclinical mouse models. This work establishes NAE as an anti-cancer target and may lead to new anti-cancer therapeutics.

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.

Dynamic nanodomains in lead halide perovskites, dictated by A-site cations, crucially affect the optoelectronic properties by modulating electronic disorder and consequently enabling better solar cells and optoelectronic devices.

Tripartite ATP-independent periplasmic (TRAP) transporters use an extra substrate binding protein to transport a variety of substrates in bacteria and archaea. Here the authors use a disulfide engineering approach to lock the TRAP transporter HiSiaPQM from H. influenzae in different conformational states for characterisation.

Multiproxy SST reconstructions of the Western Pacific Warm Pool show cooling over the entire last 10 Ma. High latitude Pacific Ocean SSTs are shown to be amplified, warming 2.4 °C per 1° of warming in the WPWP. This is reproduced by climate models.

Allosteric control of metabotropic glutamate receptor is of therapeutic value in the treatment of neurological disorders. Here, using cryoEM, the authors describe the diversity of positive allosteric modulation on the metabotropic glutamate receptor, mGlu₅.

Serological detection of antibodies against SARS-CoV-2 can help establish rates of seroconversion. Here the authors develop a red cell agglutination test to detect antibodies against the receptor binding domain for distribution free of charge to qualified research groups.

Whether and how highly penetrant NDD (neurodevelopmental disorder) genes such as Syngap1 regulate sensorimotor integration are not fully understood. This study shows that Syngap1 expression in cortical projection neurons promotes cognitive abilities in mice through forming distributed networks that integrate sensory information with motor signals, a dynamic process required for perception and attention.

Proteomics can define features of proteome foldedness by assessing the reactivity of surface exposed amino acids. Here, the authors show that such exposure patterns yield insight to structural changes in chaperones as they bind to unfolded proteins in urea-denatured mammalian cell lysate.

The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing.

The engineering of biomimetic materials is accelerated by combining high-throughput RNA sequencing and proteomics.