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Bilateral vestibular schwannomas (VS) are the main feature of NF2-related schwannomatosis, but the immunological landscape of VS is poorly understood. By performing imaging mass cytometry, the authors assess the cellular heterogeneity in VS tumours and reveal niche-dependent modes of T-cell regulation in these neoplasms.

The endosomal retrieval subdomain organizes recycling of endocytosed proteins. Here, using proximity proteomics, the authors reveal that this recycling subdomain regulates switching of specific RAB GTPases, a feature likely important in neuroprotection.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Spin–orbit torques in heavy metal/ferromagnetic layers have a complex dependence on the magnetization direction. This dependence can be exploited to increase the efficiency of spin–orbit torques.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.

The role of cationic intermediates in the benzylidene-directed synthesis of 1,2-cis glycosidic linkages is unclear. Now cryogenic infrared spectroscopy provides insight into the S_N1 mechanism of benzylidene-directed glycosylation reactions. The analysis reveals that cationic intermediates form anhydro cations through a two-step process, which correlates with the observed stereochemical outcome.

The identification of T cell epitopes is a critical step in understanding the immune response to infection and in designing vaccine based approaches. Here the authors introduce a frame work of antigen discovery called MHCvalidator and Epitrack to identify new antigenic features for T-cell COVID-19 vaccines and characterise a novel non-canonical epitope from a truncated Spike variant and mutation of an immunodominant epitope in the BNT162b4 vaccine.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Fine-tuning the expression of biosynthetic pathway genes is crucial to improve microbial production titres. Here, the authors present GEMbLeR, an optimization strategy to balance the expression of multiple genes simultaneously over a wide range.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

A multidimensional proteomics analysis of the interactions between around 2,000 nuclear proteins and over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states provides insights into how chromatin states are decoded by chromatin readers.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Whereas the toxic effects of ethanol are well-documented, the underlying mechanism is obscure. This study uses the eukaryotic model S. cerevisiae to reveal how exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate.

Ballistic delivery with micro/nano-particles has been successfully used to transfect plant cells, however, has failed in mammalian cells due to toxic effects. Here, the authors report on a self-assembled nano-ballistic delivery system for the delivery of functional macromolecules and demonstrate efficient transfection of mammalian cells.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The adenosine A2A receptor (A2AR) plays a crucial role in regulating inflammation and metabolism, yet the extent to which endogenous metabolites modulate its activity remains unclear. Here, the authors utilized the MIDAS platform to identify metabolites interacting with A2AR, revealing orthosteric and allosteric modulators.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

A complex containing the Par3/6 polarity proteins and the matrix receptor DDR1 modulates migration by downregulating cortical actomyosin contractility.

The RNA-binding ubiquitin E3 ligase TRIM25 plays a critical role in antiviral immunity. Here the authors identify key RNA-binding residues of TRIM25, link RNA binding to antiviral activity, reveal RNA structural and sequence preferences, and investigate binding to the viral genome.

Kevin Jacobs and colleagues report a new test statistic for detection of membership of an individual within a genome-wide association study, based on reporting of study genotype frequencies.

High-throughput automated synthesis is used to investigate the crystallization behaviour of two-dimensional (2D) halide perovskites (HPs) based on a bulky ligand cation, 3,3-diphenylpropylammonium. The solution-processed 2D HP flakes realize a moiré superlattice, indicating the formation of a twisted 2D stack via self-assembly action.

The shift in fluorescence lifetime of tumour tissue with respect to normal tissue after systemic injection of the near-infrared dye indocyanine green can be used to distinguish tumour tissue from normal tissue with high accuracy.

Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.

Oncofetal (OnF) reprogramming, driven by YAP and AP-1, induces phenotypic plasticity and therapy resistance in WNT-dependent colorectal cancer (CRC). Targeting the OnF state in combination with chemotherapy substantially attenuates tumor growth in mouse models and patient-derived CRC tumoroids.

Reanalysis of bipedal trackways from Laetoli site A in Tanzania suggest that the footprints were made by a hominin that coexisted with at least one other hominin species.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

In vitro modelling of the adipose tissue-liver axis can advance understanding and therapy of metabolic disease, including by distinguishing effects of obesity and inflammation. Here, authors develop such a system based on isogenic human iPSCs and interconnected microphysiological devices.

The protein PICALM/CALM is implicated in Alzheimer’s disease (AD) pathology, but it is unclear how. In this study, the authors show that CALM regulates clearance of the protein tau, which is also implicated in AD pathology, by facilitating endocytosis-dependent autophagy.

The complexity of fabricating and operating microfluidic devices limits their use. Walsh et al. describe a method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

A study demonstrates that sustained membrane blebs in cancer cells recruit curvature-sensing septins that form plasma membrane-proximal signalling hubs that promote cancer cell survival.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Nasopharyngeal cancer is frequently characterized by Epstein-Barr virus infection. Here, using genomic analyses, the authors find that the tumours harbour mutations in genes involved in the NF-κB signalling pathway or overexpress a viral oncoprotein, latent membrane protein 1.

A primordial carbon-to-oxygen ratio (C/O) greater than 0.8 in an exoplanet causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmospheres also can differ from those in the Solar System. The solar C/O is 0.54. This study reports an analysis of spectra from the transiting hot Jupiter WASP-12b that reveals that C/O>1 in its atmosphere, based upon the observed concentrations of the prominent molecules CO, CH₄ and H₂O.

Stable sub-cycle pulses in the mid-infrared region allow damage-free investigation of electron dynamics in solids. Here, the authors develop a suitable source to this end which is based on an optical parametric amplifier.

Haematopoiesis has high clonal diversity up to about 65 years of age, after which diversity drops precipitously owing to positive selection acting on a handful of clones that expand exponentially throughout adulthood.

A millihertz frequency X-ray quasi-periodic oscillation has been observed near the innermost orbit of an actively accreting supermassive black hole and its frequency has evolved significantly over 2 years, a phenomenon that is difficult to explain with existing models.

There has been a significant increase in the demand for face masks, but achieving a balance of breathability and effective filtration is challenging. Here, the authors report a face mask of modified cotton for the capture of bioaerosols.

Targeted protein degradation uses small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation, but only a few human E3 ligases are amenable to this strategy. Here, the authors identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12, containing an FKBP12 ligand appended with a flexible alkylamine tail that is metabolized to an active aldehyde species which recruits the SCF^FBXO22 ligase for FKBP12 degradation.

Experimental assays are used to determine if compounds cause a desired activity in cells. Here the authors demonstrate that computational methods can predict compound bioactivity given their chemical structure, imaging and gene expression data from historic screening libraries.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.