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Untreated, postconsumer-PET from 51 different thermoformed products can all be almost completely degraded by FAST-PETase in 1 week and PET can be resynthesized from the recovered monomers, demonstrating recycling at the industrial scale.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Knee osteoarthritis has a sex-specific phenotype with post-menopausal persons experiencing the highest incidence. Here the authors investigate the underlying mechanisms in a mouse model of menopause and find that the loss of 17β-estradiol and progesterone enhanced susceptibility to senescence, extracellular matrix disassembly and cartilage degradation.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

Previously, the small molecule inhibitor of transcriptional enhanced associate domain (TEAD) MGH-CP1 has been described in stem cells. Here, the authors demonstrate the utility of MGH-CP1 in cancer therapy and find treatment to increase Akt pathway activation via TEAD-Vgll3 activation, presenting a rationale for combination with Akt inhibition.

B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.

Spatiotemporal transcriptomes during multicellular development of Bacillus subtilis swarms reveal supra-generational cooperation.

Acute Myeloid Leukemia (AML) develops following multiple mutations of differing impact. Here, the authors show that activating mutations of CSF3R co-operate with loss-of-function mutations of CEBPA to promote AML development through an enhancer-dependent mechanism.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

Antibodies can have synergistic effects, but mechanisms are not well understood. Here, Ragotte et al. identify three antibodies that bind neighbouring epitopes on CyRPA, a malaria vaccine candidate, and show that lateral interactions between the antibodies slow dissociation and inhibit parasite growth synergistically.

Following the building principles of crown ethers for cation encapsulation, inverse crowns are rings of metals that bind anions. Now a redox-active inverse crown ether featuring Na⁺ cations and Mg⁰ has been shown to reduce epoxides, N₂O, S₈ or O₂ by combining anion complexation by the ring of metal cations with the reducing power of Mg⁰.

Human motor adaptation reaches an upper limit. Albert et al. report that this limit is linked to implicit learning. When perturbations are variable, the adaptation limit decreases as subconscious learning systems become less sensitive to error.

Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.

The transfer of nuclear chromatin to the cytoplasm drives the pro-aging inflammatory phenotype of senescent cells. Here, Miller et al. show that this process is suppressed by p53 and that activation of p53 reverses some features of aging in vivo.

Mast cells are shown to function as sensor cells linking antigen recognition in type 2 immunity to antigen-specific avoidance behaviour, preventing immune activation and inflammation.

High-concentration lithium polysulfides in lean electrolyte lithium–sulfur batteries hinder stable cycling. Here, authors introduce a reversible calcium additive that regulates polysulfides chemistry and catalyzes sulfur redox reactions, improving energy density with stable cycling.

Nanopore sequencing technology generates longer reads than current technologies, but with more errors. Here, the authors develop new analytical tools to improve accuracy and evaluate the potential of nanopore sequencing for clinical human genomics.

Global temperature fluctuations during the last 2,000 years caused consistent changes in ocean evaporation and atmospheric moisture condensation processes, reflected in coherent water isotope signals in a large compilation of proxy records.

Arany and colleagues integrate metabolomics data, tissue RNA-sequencing data and proteomics data from explanted hearts of patients with end-stage heart failure to provide a comprehensive ‘multi-omic’ evaluation of the metabolic pathways affected by heart failure.

The APOE4 allele is a major genetic risk factor for the development of late-onset Alzheimer’s disease (AD). In this manuscript, Butovsky and colleagues suggest that APOE4 impairs the microglial response in AD by inducing TGFβ-mediated checkpoints.

The clinical detection of fluorescent protoporphyrin IX during glioma-resection surgery can be improved via a microscope that pairs stimulated Raman histology and two-photon excitation fluorescence microscopy.

In glioblastoma, malignant cells can escape surgical resection by migrating into the surrounding healthy brain tissue. Here, the authors use spatial transcriptomics to characterise the tumour core and infiltrated brain regions in glioblastoma, and show shifts in malignant cell composition and molecular pathways with potential clinical implications.

Cephalopods are an enigmatic animal group with complex and adaptive behaviors such as camouflage; however the genetic basis for these traits is not well understood. Here the authors reveal a set of cephalopod-restricted rearranged genomic loci, involving known neuronal regulators but also unexpected gene families, that confer topological organization and gene regulation.

HPV’s E6 protein promotes cancer by degrading p53. This study reveals the cryoEM structure of HPV16 E6 in complex with E6AP and p53, highlighting their picomolar affinity and large protein-protein interaction interface.

Structural studies show how the PfRCR complex of Plasmodium falciparum forms a bridge between erythrocyte and parasite membranes, and how PfCyRPA-binding antibodies neutralize invasion through a steric mechanism, opening the way to new approaches in rational vaccine design.

Tools to simultaneously trace multiple neuronal projections and/or profile projection neurons for multi-modal investigations are lacking. Here authors introduce Projection-TAGs, a retrograde AAV platform to enable multiplexed spatial neuroanatomical studies, high-throughput multi-modal (transcriptional, and epigenetic) profiling of projection neurons using various commercial assays.

A translational study demonstrates the role of myeloid inflammatory cells in driving disease progression and treatment resistance in prostate cancer and shows that these cells can be targeted therapeutically.

Innate IL-17-producing T cells—in particular, adipose γδ17 T cells—are enriched in molecular-clock genes, and the circadian expression of IL-17A and RORγt by these cells has a role in maintaining local homeostasis and regulating lipogenesis.

Monocytes participate in plaque formation, and adapt to metabolic changes to alter their functions. Here the authors show, using genetic mouse models and functional analyses, that Glut1-mediated glucose metabolism is important for regulating monocyte homeostasis and migration, but curiously has no impact on atherosclerotic plaque formation.

How various factors dynamically influence neuronal variability is a longstanding question. Here, the authors build an encoding model to partition variability, revealing heterogeneous source contributions to individual units and state-dependent changes of variability across the visual hierarchy.

Identification of a hyperstable boronate enables automated lego-like synthesis to access a wider range of three-dimensionally complex small organic molecules rich in Csp³–C bonds. 

The authors present structures of plant polerovirus ^NRTD proteins that protrude from the viral capsid and show that the purified ^NRTD can inhibit insect transmission and act as a bioinsecticide, providing a blueprint for control of related viruses.

Mammalian DNA replication relies on various helicases and nucleases to ensure accurate genetic duplication, but how these enzymes are properly directed is unclear. Here, the authors identify USP50 as a key protein for promoting ongoing replication, restarting stalled forks, maintaining telomeres, and ensuring cell survival.

Immunosuppressive tumour immune microenvironments (TME) limit the success of immune checkpoint blockade (ICD). Here, the authors develop a hyaluronic acid-bilirubin nanoparticle (HABN) capable of inducing immunogenic cell death in tumour cells and altering the TME, resulting in increased sensitivity to ICB (anti-PD-L1) in preclinical models of colorectal cancer and breast cancer.

Acetic acid efficiently depolymerizes aliphatic and aromatic epoxy-amine thermosets used in carbon fibre-reinforced polymers (CFRPs) to yield recoverable monomers and pristine carbon fibres, which, based on process modelling, techno-economic analysis and life cycle assessment, could enable industrial recycling of CFRPs.

Ionizing radiation from cosmic rays has been identified as a source of correlated errors in superconducting qubits, but a direct demonstration of this link has been lacking. Here the authors measure the coincidence between correlated errors and incident cosmic rays in a chip with 10 transmon qubits.

Partial antagonists of the ER transmembrane kinase/endoribonuclease IRE1ɑ were identified that preserve splicing of downstream RNA substrates such as XBP1, enabling cellular survival.

The authors show that anxiety-like behavior in mice varies based on striatal D1/D2 receptor ratios. Elevated D1/D2 ratios enhanced alcohol relief, risk-avoidance, and persistent drinking, suggesting anxiety may predispose individuals to alcohol use disorder (AUD).

A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions.

Sharpe et al. find that prior reward-learning experience can prime reward circuits to encode fear memories. This suggests prior experience can shape the way we learn, opening the neural boundaries for learning about particular types of information.

Analysis of more than 95% of each diploid human genome of a four-generation, twenty-eight-member family using five complementary short-read and long-read sequencing technologies provides a truth set to understand the most fundamental processes underlying human genetic variation.

Ependymoma is a tumor of the brain or spinal cord with the two most common and aggressive types mainly occurring in children. Here the authors employ 3D genomics and epigenomics to reveal targets for aggressive ependymoma tumors in children.

The authors develop multimodal machine learning models to infer metastatic recurrence risk for early-stage, hormone receptor-positive breast cancer from H&E images using >6000 cases across three centers, outperforming a nomogram and unimodal methods.

This Perspective discusses approaches to generate ultimate genotypes, combining the best chromosome segments in livestock and crop populations, to increase key production, sustainability and welfare traits, compared with the current best individuals.

Chloride regulation is important for setting GABAergic reversal potential, though tools to manipulate chloride levels are limited. Here, the authors combine Archaerhodopsin with a chloride channel opsin to generate an optogenetic chloride extrusion strategy, ‘Cl-out’, which they demonstrate in hippocampal slices.

Astroviruses are the leading cause of pediatric diarrhea, but which cells are the main targets in the gut remains unclear. Here, using an in vivo model of murine astrovirus, the authors show that the virus infects goblet cells and that this alters mucus production and increases mucus-associated bacterial communities in the gut.

The elongation factor Elf1 functions in transcription coupled-nucleotide excision repair (TC-NER), but the mechanism by which yeast Elf1 promotes repair was unclear. Here, the authors show that Elf1 promotes TC-NER by binding TFIIH through a conserved sequence motif in its C-terminal domain.

A neuroimaging study using repeated transcranial magnetic stimulation on unmedicated patients with depression reveals a link between response in the subgenual anterior cingulate cortex and clinical improvement.

Neural coding for motion direction has been studied intensively in the visual cortex of non-human primates. Here, the authors establish an origin for direction selectivity in the retina of the macaque monkey.