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The APC/C ubiquitylates histones to regulate gene expression in pluripotent cells. Here, the authors pair cryo-EM and biochemical and biophysical assays to show that instead of modifying nucleosome-incorporated histones, the APC/C ubiquitylates extranucleosomal histone complexes through a mechanism that bypasses canonical substrate degrons.

Membrane proteins depend on their lipid environments. Using aquaporin as a model, the authors show that the choice of lipid bilayer fundamentally affects membrane protein structure, thermodynamics, kinetic, and function, even to the point of lipid-based inhibition.

Cell therapy to replace β-cells is a potential therapeutic avenue to treat diabetes, but the production of insulin-secreting replacement cells requires reliable tools to assess islet cellular identity. Here the authors use single-cell transcriptomics meta-analysis to construct gene sets that describe the identity of human α-, β-, γ- and δ-cells.

Virtual screening of huge libraries is successful in identifying drug leads. Here, the authors describe a computational strategy, Chemical Space Docking, which combines docking with a reaction-based search of compounds, thereby enabling the exploration of billions of compounds and beyond.

The first step of biofilm formation is a transition from a single layer of bacteria to multiple layers. Now, there is evidence that this transition is determined by the phenotypic noise associated with cell geometry and growth rate.

By single-cell mass cytometry and adoptive transfer of B cell subtypes in mice, Pattarabanjird et al. show that human CD24^hi circulating marginal zone B cells produce IgM to atherosclerosis antigens and confer atheroprotection. Blocking CD24 increased vascular inflammation in hyperlipidemic humanized mice.

This work combines nanopore native RNA sequencing with machine learning models for identifying inosine-containing sites in transcriptomes.

Successful engraftment of human hematopoietic stem cells during gene therapy requires myeloablative conditioning of the recipient, at the expense of toxicity. Authors show here that a single-dose of anti-CD117 antibody-drug conjugate achieves similar engraftment results as traditional multi-dose busulfan conditioning but preserves fertility in a non-human primate model.

Analysis of 1.32 billion records of medication data from England, Scotland and Wales reveals that the COVID-19 pandemic led to substantial declines in dispensing of antihypertensive and lipid-lowering medications, leading to increased risks for future cardiovascular disease.

Failure to account for heterogeneity in TB risk can mislead model-based evaluation of proposed interventions. Here, the authors introduce a metric to estimate the distribution of risk in populations from routinely collected data and find that variation in infection acquisition is the most impactful.

The fungal Ascomycota provide a model phylum to investigate the evolution of complex multicellularity. Here, the authors combine genome sequencing with comparative and functional genomics to identify diverse endomembrane related machineries associated with the gain and loss of fungal complexity.

The authors combine multiscale simulations with electrochemical and surface characterization to investigate the formation and dissolution kinetics of passivating oxides on Ni-Cr alloys, probing the interdependent effects of alloy composition, temperature, pH, and applied voltage.

The medicinal plant Catharanthus roseus is a source of leading anticancer drugs. The monoterpene indole alkaloid (MIA) biosynthetic pathway in C. roseus has now been analyzed using a complementary, multi-omics, single-cell approach. This identified clusters of genes involved in MIA biosynthesis and cell-type-specific partitioning in the MIA biosynthetic pathway.

Paired prime editing is used to precisely delete genomic sequences up to 10 kb.

Water electrolysis offers a promising means for green hydrogen production, however current electrolysers do not provide a competitive edge over fossil fuels. Here, authors develop a capillary-fed electrolyser setup that avoids bubble formation to achieve a high-performance, cost-competitive device.

Crystal structures of the ABC transporter MsbA in complex with two selective small-molecule antagonists reveal an unprecedented allosteric mechanism of inhibition.

This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility.

Using valley-resolved scanning tunnelling spectroscopy, twisted WSe₂ bilayers are studied, including incommensurate dodecagon quasicrystals at 30° and commensurate moiré crystals at 21.8° and 38.2°.

A protein platform rapidly develops peptide-focused major histocompatibility complex class I binders with high specificity.

Spangler et al. used a substrate inhibitor covalent conjugate strategy to solve cryo-EM structures of nucleosomes in complex with the lysine demethylase KDM2, which demonstrates that KDM2A, but not its closely related paralog, KDM2B, anchors to the acidic patch to direct histone H3K36-specific demethylation.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Epithelial tissues such as those in the gut or skin are strongly polar, generating electric fields that play a role in wound healing and nutrient transport. Changing the field direction in a layer of tissue disrupts its homeostatic stability.

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.

Detailed analyses pairing deep phenotyping and molecular profiles reveal mediating roles of plasma lipids in genetic and environmental factors associated with autism-related traits in children.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

FAM111A is a serine protease important for DNA replication and antiviral defense. Here, the authors report that the FAM111A dimerization is crucial for its proteolytic activity and for promoting DNA replication at trapped topoisomerase I.

Cell extrusion regulates monolayer cell density and is critical in maintaining epithelia integrity, which has implications in homeostasis, development, and cancer progression. Here the authors describe how monolayer integrate mechanical signals from tissue mechanics, cell-cell adhesion, cell-substrate adhesion and cytoskeleton coordinate cell extrusion.

Unbiased screening for insect gene function has been largely restricted to Drosophila. Here, Schmitt-Engel et al. perform an unbiased large-scale RNAi screen in the red flour beetle Tribolium castaneumto identify putative gene functions.

The mechanism of how plant growth is controlled during the reproductive phase is not well understood. Now a study reveals a new miRNA-dependent module integrating auxin signalling and developmental pathways to promote Arabidopsis fruit morphogenesis.

Tin based perovskites are easily oxidized, which generates large density of defects and compromised the solar cell efficiency. Here Nakamura et al. add metallic tin nanoparticles in the precursor solution to suppress tin (IV) impurities and enable high efficiency tin based perovskite solar cells.

It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.

Batteries with solid polymer electrolytes face challenges in electrochemical stability and compatibility with high-voltage cathodes. Chunsheng Wang and colleagues have developed a polymer blend with a high Li salt concentration that enhances the stability of solid polymer electrolytes and achieves promising electrochemical performance in full-cell applications.

In one-dimensional systems, electronic interactions lead to a breakdown of Fermi liquid theory and the formation of a Tomonaga Luttinger Liquid (TLL), as recently reported in the helical edge states of quantum spin Hall insulators. Here, the authors show that the many-body interactions in the helical TLL of 1T’- WTe2 can be effectively controlled by the dielectric screening via the substrate.

Motivational states play a key role in memory formation. Here, the authors show that curiosity engages reward circuitry to promote a hippocampal state conducive to the formation of new memories.

Experiments using high-intensity X-ray pulses incident on high-pressure hydrocarbons suggest that diamond formation can occur at shallower depths in icy planets and may play a role in the internal convection that generates their magnetic fields.

A combination of in situ hybridization and a proximity ligation assay allows the visualization of histone modifications at single genomic loci with single-cell resolution in fixed tissue.

Monolithic 3D integration of electronics based on fully 2D materials is demonstrated in the performance of artificial intelligence tasks.

The roles of extracellular RNAs present in bacterial biofilms are poorly understood. Here, Mugunthan et al. show that specific mRNAs associate with extracellular DNA in the matrix of bacterial biofilms, facilitating the formation of viscoelastic networks.

The galectin family of secreted lectins are important regulators of immune cell function; however, their role in B cell responses is poorly understood. Here, the authors identify IgM-BCR as a ligand for galectin-9. In resting naive cells, they show that galectin-9 mediates a close association between IgM and CD22.

Using mouse lines in which subsets of neurons are genetically labelled, the authors provide generalized anatomical rules for connections within and between the cortex and thalamus.

Cryptococcus neoformans is an opportunistic fungal pathogen which primarily affects people with immune defects including those living with HIV. Here, the authors sequence and analyze genomes of 699 isolates, and identify recent population expansion driven by three phylogenetic groups.

The SARS-CoV-2 main protease (M^pro) is one of two cysteine proteases essential for viral replication. Here, the authors determine the crystal structure of an M^pro acyl intermediate with its native C-terminal autocleavage sequence and the structure of a product bound active site mutant (C145A), which are of interest for antiviral drug development.

Ros et al. show that the ER-resident chaperone calnexin (Cnx) and its partner ERp57 are trafficked to cell surface invadosomes and induce ECM degradation, promoting tumour invasiveness.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Morphometric analyses of hominid teeth from Early to Middle Pleistocene Java reveal that Meganthropus was a Pleistocene Indonesian hominid distinct from Pongo, Gigantopithecus and Homo, and that molars previously assigned to Homo erectus are more likely to belong to Meganthropus.