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Here, the authors mapped signal flow over days from intracranial brain recordings in humans. Across vigilance stages, limbic structures sent twice as many signals as they received from the neocortex, challenging the long-standing hypothesis of flow reversal in sleep.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

varVAMP is open-source software for designing primers for tiled-amplicon sequencing and qPCR. It simplifies primer design for viral pathogens with high genomic variability by including sequence variations into primer sequences.

A microRNA (miR-203) that promotes differentiation of stratified epithelial stem cells by restricting their proliferation and inducing cell cycle exit is identified. One of its targets is p63, which regulates stem cells maintenance in skin, and it is shown that miR2-3 works by repressing p63 expression.

The study reveals strikingly different nonlinear Rabi splitting dynamics in MoSe₂ monolayers and (Ga,In)As quantum wells, highlighting the pivotal role of Coulomb interactions in shaping light–matter coupling in two-dimensional semiconductors.

Susac syndrome is an inflammatory pathology of the brain endothelium. Here the authors show that the pathology is driven by CD8 T cells attacking the endothelium, and that blocking T cell-endothelial adhesion ameliorates the disease in a mouse model, and associates with improved clinical score in 4 patients.

The authors present a characterization of complex X-linked lncRNA loci with sex- and allele-specific epigenetic signatures that serve as a platform for the largest chromatin structures in mammals, thereby elucidating diverse phenotypes and combinatorial effects on autosomes.

Translation efficiency can be affected by mRNA stability and secondary RNA structures. Here the authors reveal that loss of DHX36 helicase activity leads to an accumulation of translationally inactive target mRNAs with G-rich structures in untranslated regions.

Identifying biomarkers associated with risk of severe COVID-19 disease could inform clinical management. Here, the authors identify a long noncoding RNA associated with severe disease using data from three European countries, and validate their finding in data from Canada.

Targeted nanodrug delivery is crucial to treat respiratory diseases, but profiling the delivery and dynamics of nanoparticles (NPs) within the lung is a challenging task. Here, the authors present LungVis 1.0, an AI-driven 3D imaging ecosystem to profile inhaled substances in distinct lung regions while uncovering the role of tissue-resident macrophages in the fate of NPs.

How the substrate specificity of fatty aldehyde dehydrogenase (FALDH) towards long-chain aldehydes is achieved is an unresolved question. Here the authors present a crystal structure of human membrane-bound FALDH and find that it contains a ‘gatekeeper’ helix that directs substrate specificity towards long-chain fatty aldehydes.

Neumüller and colleagues identify and characterize potent HER2 exon 20 insertion-selective inhibitors with efficacy, which preserve wild-type epidermal growth factor receptor signaling in preclinical models of non-small cell lung cancer in vivo.

Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.

Stb15 provides resistance to Septoria tritici blotch in wheat and encodes a G-type lectin receptor-like kinase. The three cloned Stb genes, which are effective against different pathogen isolates, encode diverse receptor-like kinases with extracellular domains potentially involved in sugar binding.

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.

In this work, the authors report NMR lipids Databank to promote decentralised sharing of biomolecular molecular dynamics (MD) simulation data with an overlay design. Programmatic access enables analyses of rare phenomena and advances the training of machine learning models.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Understanding the sudden regime shifts leading to epileptic seizures is crucial for developing preventive measures. This research reveals that subtle dynamical changes can indicate impending seizures, and highlights the effectiveness of active probing over passive recording in assessing neural excitability in hippocampal circuits.

Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies which destabilize cell adhesion of keratinocytes. The phosphodiesterase 4 inhibitor apremilast prevents skin blistering by stabilizing the keratin filament anchorage of desmosomes.

While current COVID-19 vaccines provide certain protection, more effective vaccination strategies are still desirable. Here the authors show, using mouse vaccination models, that priming with a systemic mRNA and boosting with an intranasal adenoviral vector vaccine induces comprehensive T cell and mucosal immunity.

Researchers demonstrate the feasibility of BB84 quantum key distribution between a plane and a ground station. Establishing a stable, low-noise quantum communication channel with the plane moving at 290 km/h over a distance of 20 km (4 mrad s⁻¹), the results are representative for typical communication links to satellites.

Implementation of a genomics-informed prebreeding strategy in a global winter wheat collection enhances the use of genebank accessions and uncovers the value of genetic resources for wheat improvement.

The fine fraction of the last glacial dust in Europe mainly originates from a remote source, potentially Northern Africa, based on an analysis of isotopic samples from 15 sites and Earth system model simulations.

A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.

A chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia cells.

D-lactic acidosis typically occurs in the context of short bowel syndrome; excess D-lactate is produced by intestinal bacteria. Here, the authors identify two point mutations in the human lactate dehydrogenase D (LDHD) gene that cause enzymatic loss of function and are associated with elevated plasma D-lactate.

The mechanisms that sustain the self-renewal and expansion of cancer cells with tumour initiating potential are not completely understood. Here the authors show that the transcription factor, Sox2, marks tumour initiating cells in cutaneous squamous cell carcinomas and is required for their expansion.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

HMBG1 is a protein expressed in natural killer cells and is important in immunosurveillance. In this study, the authors show that HMGB1 binds to and inhibits PKM2, resulting in a block in aerobic glycolysis and ultimately cell death.

Immune receptor FLS2 perceives flagellin epitopes from many bacterial pathogens, but not from well-known Agrobacterium tumefaciens. The authors find a natural FLS2 in a wild grape species that can perceive this modified flagellin.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

Macrophage-specific genetic ablation of the EMT inducer ZEB1 reveals its pivotal role in intracellular cytokine trafficking, boosting cytotoxic T cell abundance and immune responses, thereby reducing tumor growth and metastatic colonization in mice.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.