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Post-drought rehydration triggers a preventive immune response in plants, revealing targets to enhance crop resilience by linking drought stress recovery with improved pathogen resistance.

Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.

Nimbus, a deep learning model, uses a large multiplexed imaging dataset to predict the likelihood of marker positivity in single cells.

The nuclear receptor PPARγ regulates insulin sensitivity and is the molecular target of anti-diabetic drugs. Here, Hughes et al. show demonstrate binding of synthetic PPARγ agonists to a previously unknown binding site within PPARγ and show this affects structure and function of the receptor.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

This study presents an extensive single-nucleus and spatial transcriptomic atlas of the Arabidopsis life cycle that represents ten distinct developmental time points inclusive of six diverse organs.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Colorectal cancer metastasis involves dramatic plasticity and loss of PROX1-mediated repression of non-intestinal lineages.

Rao and Cai et al. perform a detailed metabolic comparison between primary tumours from patients and their matching xenografts, which identify conserved as well as divergent metabolic patterns.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

The repressive states of peroxisome proliferator-activated receptor γ (PPARγ) are ill-defined, despite nuclear receptors being a major drug target. Here authors demonstrate multiple structurally distinct repressive states, providing a structural rationale for ligand bias in a nuclear receptor.

CD388 is a first-in-class antiviral drug–Fc conjugate engineered for extended half-life that demonstrates potent prophylactic and therapeutic efficacy against lethal influenza A and B challenge in mice.

The development of a molecularly defined spatiotemporal atlas of pathogen-infected Arabidopsis thaliana leaves reveals specific cell states that have distinct roles in plant immunity.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor. Here the authors provide insights into PPARγ activation by combining fluorine (¹⁹F) NMR and molecular dynamics simulations to characterize the nuclear receptor conformational ensemble in solution and the response of this ensemble to ligand and coregulatory peptide binding.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

New tumor epitopes are discovered by ribosome profiling and immunopeptidome mass spectrometry.

Modeling a rare bone marrow failure disorder due to haploinsufficiency for the MECOM transcription factor identifies a human hematopoietic stem cell regulatory network, which is co-opted by high-risk leukemias.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Synthetic REV-ERB agonists can alter the circadian expression of core clock genes in the hypothalami of mice, which changes the expression of metabolic genes in liver, skeletal muscle and adipose tissue, and results in increased energy expenditure.

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

Gate-tunable Andreev bound states that arise within quantum dots formed beneath superconducting contacts deposited on a graphene sheet could be useful in the development of solid-state qubits.

Central to the lineage commitment of multipotent mesenchymal stem cells is the nuclear receptor PPARγ, the master regulator of adipogenesis. Here the authors use a variety of structural approaches to rationally design PPARγ inverse agonist SR2595, and demonstrate its ability to promote osteogenesis.

Treatment responses of melanoma patients to MAPK pathway inhibitors are often limited. Here, the authors show that combining cardiac glycosides with MAPK inhibitors improves tumor regression by inducing intracellular acidification, mitochondrial calcium dysregulation, ATP depletion, and cell death.

Characterization of ten temperate mycobacteriophages reveals at least five distinct prophage-expressed viral defence systems that interfere with infection by either closely related or unrelated lytic and temperate phages.

Single-nucleus RNA-sequencing and chromatin-accessibility analyses in rice (a C₃ plant) and sorghum (a C₄ plant) provide insight into how C₄ photosynthesis evolved in bundle-sheath cells, revealing that the acquisition of ancestral cis-elements was key.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a target for insulin sensitizing drugs. Here the authors combine NMR, X-ray crystallography and MD simulations and report a structural mechanism for eliciting PPARγ inverse agonism, where coactivator binding is inhibited and corepressor binding promoted, which causes PPARγ repression.

Quantitative connectivity matrices (or connectomes) for both adult sexes of the nematode Caenorhabditis elegans are presented that encompass all connections from sensory input to end-organ output across the entire animal.

Modlin and colleagues examined the skin lesions of human leprosy patients using single-cell RNA sequencing coupled to cellular spatial mapping. Their analysis maps the architecture of granulomas in leprosy lesions from patients with leprosy with localized disease (tuberculoid leprosy, reversal reaction) to those with progressive infection (lepromatous leprosy).

Differences in MCT1 function among melanoma cells confer differences in oxidative stress resistance and metastatic potential.

Amr Sawalha and colleagues performed dense genotyping in the HLA locus followed by imputation to fine map genetic variants associated with Behçet's disease in this region. They report four independent genetic associations in the HLA region and localize the genetic association previously attributed to HLA-B*51 to a genetic variant between the HLA-B and MICA genes.

By analysing the exonuclease EXD2, Silva et al. find that it localizes to mitochondria, and that its loss alters metabolism by affecting mitochondrial translation and causes developmental delay and lifespan extension in flies.

The delivery route and dose of the BCG vaccine profoundly alters the protective outcome after Mycobacterium tuberculosis challenge in non-human primates.

Some nuclear receptors dimerize with retinoid X receptor to allow ligand-dependent signalling. Here, Kojetin et al.use structural and biophysical techniques to identify structural changes that guide these complex signalling networks.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

The small molecule Nobiletin enhances circadian rhythms and protects against obesity-associated metabolic dysfunction in mice. Here the authors test its effect on health and lifespan, reporting that circadian enhancement promotes fitness and healthy aging in metabolically challenged mice.

Synthetic biology can be used to regulate target genes and uncover gene function in physiologically relevant settings. Here Robles-Oteiza et al. describe a new recombinase-based system for conditional inactivation and inducible restoration of gene function and develop new mouse models to study p53 and Rb.

LRP5/6 is a Wnt co-receptor essential for Wnt/β-catenin signaling. X-ray crystallography and electron microscopy analyses now reveal that the LRP6 extracellular ligand-binding domain is composed of two pairs of rigid blocks connected by a short hinge. The structure of the LRP6–DKK1c complex also shows how DKK1 may potently inhibit Wnt/β-catenin signaling through its binding to these structural blocks.

Seven methods for single-cell RNA sequencing are benchmarked on cell lines, primary cells and mouse cortex.

PPM1D is a known mediator of p53 signalling, and has been linked to treatment resistance in glioma. In this work, the authors utilise genomics, proteomics, and mouse models to determine the role of PPM1D in the development of diffuse midline glioma.

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.

Constrained ligands activate a canonical ER pathway via a common structural mechanism, whereas dynamic ligands rewire the canonical pathway; DBD-dependent activity interferes with canonical ER proliferative signals and associates with a strong anti-inflammatory effect.