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The identification of pathogenic mutations within prion-like domains (PrLDs) of the RNA-binding proteins hnRNPA2B1 and hnRNPA1 add to our understanding of how mutations in these proteins lead to degenerative disease, and highlight the potential importance of PrLDs in degenerative diseases of the nervous system, muscle and bone.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.

A study combining tunnelling and Andreev reflection spectroscopy with a scanning tunnelling microscope provides evidence for unconventional superconductivity in magic-angle twisted bilayer graphene.

A fresh look at whether learning alters the course of natural selection.

The human immune system naturally edits cancers of high-quality neoantigens.

Epigenetic regulators are potential therapeutic drug targets in leukemia. Here, the authors perform combinatorial CRISPR knockouts to test gene-gene pairings in leukemia cells to discover compensatory non-lethal or synergistic lethal combinations with therapeutic potential.

Passive chlorophyll fluorescence is sensitive to phytoplankton nutrient limitation, according to in-situ observations from the South Atlantic Ocean.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

Electron–electron interactions in magic-angle twisted bilayer graphene can split usually degenerate electronic bands, giving rise to a cascade of electronic transitions revealed by spectroscopy.

The [4Fe4S]²⁺ cluster-containing DNA-repair enzyme MUTYH helps safeguard the integrity of Watson–Crick base pairing and the human genetic code. The MUTYH [4Fe4S]²⁺ cluster mediates DNA redox signalling and DNA lesion identification. Now, a MUTYH pathologic variant associated with catastrophic [4Fe4S]²⁺ cluster redox degradation, impairment of DNA signalling and human colonic tumorigenesis has been identified.

The cyanobacterium Trichodesmium fixes nitrogen exclusively during the day to reduce glycogen ballast and remain buoyant in the surface ocean, where it occupies a specialized niche based on colony formation, high-light adaptation and mineral-dust utilization.

Whole-genome sequencing of haematopoietic colonies from human fetuses reveals the somatic mutations acquired by individual progenitors, which are used as barcodes to construct a phylogenetic tree of blood development.

The beta variant (B.1.351) is to date the most resistant to neutralization of the SARS-CoV-2 variants. Using nonhuman primates, Seder and colleagues demonstrate that double vaccination with a high dose of the lipid nanoparticle vaccine mRNA-1273 protects against infection with the beta variant.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

Spectroscopic study on a kagome magnet thin film uncovers the local-moment nature of the magnetism in the presence of topological flat bands, as well as a strong spin- and orbital-selective electronic correlation effect.

A multiomics single-cell atlas of the human maternal–fetal interface including the myometrium, combining spatial transcriptomics data with chromatin accessibility, provides a comprehensive analysis of cell states as placental cells infiltrate the uterus during early pregnancy.

This study finds a direct correlation between LARGE-glycan extension on dystroglycan and the protein’s capacity for extracellular matrix ligands; in regenerating mouse muscle, short LARGE-glycan polysaccharides cause various defects, including muscle dysfunction and a predisposition to dystrophy, and in muscular dystrophy patients, increased clinical severity of disease corresponds to shorter LARGE-glycans.

Kevin Campbell and colleagues identify mutations in ISPD as a cause of Walker-Warburg syndrome (WWS) using a complementation assay in fibroblasts derived from affected individuals and targeted sequencing. They find that loss-of-function mutations in ISPD disrupt dystroglycan O-mannosylation, suggesting a new disease mechanism.

Precolibactin 886 is a complex microbiome-derived metabolite implicated in colorectal cancer and produced by the clb gene cluster. A chemical synthesis and analysis of precolibactin 886 is reported which shows that its biosynthetic precursor degrades to other known clb metabolites. The data also provide insights into the structures and reactivity of advanced clb products.

Movement of secretory cargoes from the endoplasmic reticulum relies on the COPII protein complex. Here, authors combine gene editing technology with state-of-the-art fluorescence microscopy to define the native dynamics of COPII recruitment at ER subdomains for the first time.

Eutrophication has been shown to weaken diversity-stability relationships in grasslands, but it is unclear whether the effect depends on scale. Analysing a globally distributed network of grassland sites, the authors show a positive role of beta diversity and spatial asynchrony as drivers of stability but find that nitrogen enrichment weakens the diversity-stability relationships at different spatial scales.

mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.

Field-driven insulator-to-metal transition and associated colossal magnetoresistance have been reported in the magnetic nodal-line semiconductor Mn₃Si₂Te₆. Gu et al. measure infrared response across magnetic ordering and the transition, revealing a weakly metallic state instead of a traditional metallic state.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Analyses of whole-genome and RNA sequencing data from 2,733 African American, Puerto Rican and Mexican American individuals reveal ancestry-specific patterns in the genetic architecture of whole-blood gene expression.

CAR T cell success requires targeting tumors, but these cells can get trapped in other tissues, such as in the lungs, where they can cause pathology. Here, the authors use a loss-of-function CRISPR screen to identify regulators of CAR T cell tumor trafficking and engineer CAR T cells accordingly to overcome this limitation.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

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.

SpatialData is a user-friendly computational framework for exploring, analyzing, annotating, aligning and storing spatial omics data that can seamlessly handle large multimodal datasets.

Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response. This form of inactivity is a major determinant of disability. The mechanism underlying this type of fatigue remains unknown. It is shown in mice that such exaggerated fatigue is due to a lack of contraction-induced signalling from sarcolemma-localized nNOS. In addition, in patient biopsies from a large number of distinct myopathies, sarcolemmal nNOS is reduced—pointing towards a common mechanism of fatigue.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.