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Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Number of IL-9-expressing ILC2s are elevated in patients with inflammatory arthritis during remission, and these cells are critical in mice for the resolution of inflammatory arthritis via regulatory T cell induction. Delivery of DNA minicircles encoding IL-9 into inflamed joints ameliorates mouse experimental arthritis, suggesting possible therapeutic applications.

Despite archaeobotanical evidence for domesticated cereals, organic residue evidence is scarce. Here, the authors identify cereal-specific markers in pottery from Scottish ‘crannogs’, revealing the presence of cereals in Neolithic pottery which might have been mixed with dairy products as a milk-based gruel.

The highest tensile strength biomaterial known exists in limpet teeth and replicating this material is of interest. Here, the authors report on the ex vivo growth of teeth and use of isolated limpet tissue and cells providing foundations for the development of this high-tensile biomaterial.

Individually addressable ‘T centre’ photon-spin qubits are integrated in silicon photonic structures and their spin-dependent telecommunications-band optical transitions characterized, creating opportunities to construct silicon-integrated, telecommunications-band quantum information networks.

Obstructive lung diseases are a frequent cause of morbidity worldwide. Here, the authors identify the endocannabinoid anandamide (AEA) as an airway relaxant under physiological and pathophysiological conditions that can be locally applied to the lung as an aerosol in mice.

A central concept for characterising phase-separating systems is the phase diagram but generation of such diagrams for biomolecular systems is typically slow and low-throughput. Here the authors describe PhaseScan, a combinatorial droplet microfluidic platform for high-resolution acquisition of multidimensional biomolecular phase diagrams.

Proteomics can be used to refine cancer classification. Here, the authors characterise chronic lymphocytic leukaemia patients by proteogenomics, and identified a subtype of patients with poor prognosis associated with aberrant B cell receptor signalling.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Cryo-electron microscopy structures of Staphylococcus aureus BlaR1 reveal dynamic signalling states regulating broad spectrum β-lactam antibiotic resistance through cleavage of the transcriptional repressor BlaI and induced expression of the β-lactamase blaZ and the β-lactam-resistant cell-wall transpeptidase mecA.

Aircraft measurements over the Amazon show that new particle formation in the upper troposphere emerges when isoprene, emitted by forests, undergoes oxidation in the presence of nitrogen oxides produced by lightning.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

Ribosomally synthesized and post-translationally modified peptides are a source of antimicrobials. Here, the authors report a platform for the rapid evaluation and characterization of biosynthetic gene clusters that enables the identification of 30 structurally diverse modified peptides, including three showing antimicrobial activities.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

Analyses of five treponemal genomes representing ancient relatives of Treponema pallidum suggest that this pathogen originated in the Americas.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

Current approaches for volumetric super-resolution microscopy can yield large and complex PSF spatial footprints. Here, the authors show a super-resolution microscopy approach using a hexagonal microlens array, which offers speed improvements in volumetric imaging compared to other single-molecule methods.

Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.

Calcium difluoride is a source of fluorochemicals, but the reactivity of Ca–F moieties is not well understood. Now a library of molecular Ca–F complexes featuring unique structural motifs has been synthesized, including via fluorochemical defluorination. Studies of mono- and dinuclear systems provided structure–activity relationships for E–F bond formation.

Polyketide macrolides are of interest for drug discovery but their inherent structural and stereochemical complexity hinders the exploration of related regions of chemical space more broadly. Here, the authors designed in silico and synthesized a library of tetrahydrofuran-containing polyketide macrolides, and screened them against a panel of biological assays, identifying biologically active library members.

The authors employ cryo-ET to study the structure of the palisade layer of the mature vaccinia virus core in isolation, as well as inside infected cells, revealing that it is composed of A10 protein trimers.

The T cell receptor β-chain is expressed in two isoforms, TRBC1 and TRBC2, with clonally expanded mature T cell lymphomas expressing one of them exclusively, while healthy T cells randomly express either TRBC1 or TRBC2. Here authors show structure-based design of a TRBC2-specific antibody, and depletion of malignant T cells carrying TRBC1 or TRBC2 with CAR-T cells against the cognate receptor chain in murine models.

The ubiquitous second messenger c-di-GMP regulates many biological processes in bacteria, including cell cycle, motility, virulence and biofilm formation. Here, Kaczmarczyk et al. develop a c-di-GMP biosensor that enables dynamic real-time tracking of c-di-GMP levels in individual living cells.

Ten stars in the Large Magellanic Cloud exhibit very low elemental abundances, suggesting that they have experienced enrichment by the earliest generations of stars only. These stars provide a window into a distant region of the high-redshift universe.

Myotonic dystrophy type 2 is characterized by large CCUG repeats in the CNBP gene that result in myopathy. Here, the authors show that recognition of aberrant protein translation derived from these repeats leads to ER stress and mitochondrial DNA release, leading to cGAS/STING activation and type-I IFN responses.

Investigations show that all the second-generation stars in the globular cluster NGC 6752 fail to reach the asymptotic giant branch (AGB) phase; every AGB star in the sample has a low sodium abundance, indicating that they are exclusively first-generation stars.

The aboveground carbon stock of a montane African forest network is comparable to that of a lowland African forest network and two-thirds higher than default values for these montane forests.

Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.

This study presents the first annual update of the indicator framework developed by the Food Systems Countdown Initiative, published in Nature Food in 2023. Almost half of all indicators show some desirable trends. Governance and resilience indicators were revealed as the most connected across themes, constituting entry points for transformative change.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Stegouros elengassen, an ankylosaur from the late Cretaceous of Chile, has a large tail weapon, named a macuahuitl after the Aztec club, with a frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

PMOs (phosphorodiamidate morpholino oligomers) have huge potential for antisense therapy but complex and slow synthesis limits application. Here, the authors report the development of automated flow synthesis methods which reduce nucleobase coupling times from hours to minutes removing human errors and allow for high-throughput production.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

NOTUM from Apc-mutant cells acts as a key mediator during the early stages of mutation fixation and drives the formation of intestinal adenomas.

Rinkevich and colleagues show that preexisting matrix is transferred by neutrophils across organs into injured sites in a manner dependent on integrin activation.

Some cholesterol-lowering drugs can increase the risk of type 2 diabetes, but the mechanism behind this is not fully understood. Here the authors show that there is a single genetic regulatory module that influences both cholesterol levels and glucose levels, providing a link between cholesterol levels and diabetes.

AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.

Evidence of ostrich eggshell artefacts, long-distance transport of marine shells and heat treatment of stone tools in a marginal southern African environment 92–80 thousand years ago suggests that innovation among early human groups was sensitive to ecological variation.

Reduction of systemic autoimmunity using TNF blockers may also reduce inflammatory diseases in other organs. Here, the authors use a patient database and scRNA-seq to link autoimmune diseases to benign prostatic hyperplasia (BPH), and demonstrate that prostatic hyperplasia is reduced by TNF blockers in humans and mice.

The mechanisms by which cells determine their position within the 3D space are poorly understood. Research in salamanders offers fresh insights into this question, uncovering Tig1 as a central determinant of proximo-distal identity in regeneration.

Magnetic skyrmions are chiral spin structures that can form two-dimensional lattices. Here, the authors show how lattice domains grow under the influence of pinning effects in a non-flat energy landscape and that magnetic field oscillations help to stabilize order.

Lineage tracing of human stem cells is achieved by measuring fluctuating DNA methylation.

TOI-500 hosts at least four planets, the innermost of which is an Earth-sized ultra-short-period body with a density similar to Earth. The architecture of the TOI-500 system can be explained by a slow, secular, low-eccentricity migration scenario.