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The authors find that the insulin receptor forms dynamic clusters during insulin signaling and that these clusters become dysfunctional in insulin resistance. This dysfunction is partially rescued by metformin, a drug used to treat type 2 diabetes.

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.

The heterogeneity of whole-exome sequencing (WES) data generation methods presents a challenge to joint analysis. Here, the authors present a bioinformatics strategy to generate high-quality data from processing diversely generated WES samples, as applied in the Alzheimer’s Disease Sequencing Project.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

The switching of ferroelectric polarization is of promise for non-volatile electronic memory devices. Here, the authors show that nanodomains in a ferroelectric composite allow the arbitrary rotation of the macroscopic polarization, potentially enabling memory devices with more than two storage states.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

The sc-linker is an analysis framework that combines genome-wide association study summary statistics, epigenomics and single-cell transcriptomes to identify disease-critical cell types and cellular processes across tissues and states.

Here the authors present a deep learning framework for dementia diagnosis, which can identify persons with normal cognition, mild cognitive impairment, Alzheimer’s disease, and dementia due to other etiologies.

Changing from a five-point scale to a two-point scale for rating workers reduces racial discrimination by making customers focus on whether the work was good or bad instead of their own personal biases.

In the Arctic, the risks of the permafrost thaw are perceived differently by communities, and key hazards include infrastructure failure, mobility disruption, decreased water quality and food security, and exposure to diseases, according to a transdisciplinary analysis based on workshops and a thematic network approach.

Here the authors show that unlike IL12, IFNγ can induce a T helper 1-like state in regulatory T (T_reg) cells during viral infection in mice that suppresses effector T cell responses and memory formation.

The genome is folded in 3-dimensions, though the lack of robust ultra-resolution imaging makes this difficult to visualise. Here, the authors present 3D-EMISH that combines serial block-face scanning electron microscopy with in situ hybridization.

The authors present an integrative framework for identifying structural variants (SVs) in cancer that applies optical mapping, Hi-C, and whole-genome sequencing. They find SVs affecting distal regulatory sequences, DNA replication, and three-dimensional chromatin structure.

Three-dimensional imaging of the lingual kinematics of mice drinking from a water spout reveals that successful licks have the hallmarks of online motor control, requiring rapid adjustments controlled by anterolateral motor cortex.

Results are presented that indicate that alterations to gene regulatory three-dimensional architecture are a critical mechanism that enables structural variant-based oncogene activation in cancer genomes and sheds light on the essential elements for such gene activation events.

A genomic map of nearly 300,000 potential cis-regulatory sequences determined from diverse mouse tissues and cell types reveals active promoters, enhancers and CCCTC-binding factor sites encompassing 11% of the mouse genome and significantly expands annotation of mammalian regulatory sequences.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Induction of CD4 T follicular helper (Tfh) cells is important for antibody responses to viral infections. Here, the authors show in a rhesus macaque model of mild COVID-19 that SARS-CoV-2 infection results in transient accumulation of proliferating Tfh cells with a Th1 profile in peripheral blood and generation of germinal center Tfh cells specific for viral proteins.

The plasma membrane can expand the blades of the PIEZO1 ion channel, impacting channel activation.

The relationship between the components of repetitive head impacts and chronic traumatic encephalopathy (CTE) remains unclear. Here, the authors use American football helmet sensor data to show that duration of play, cumulative head impacts and linear and rotational accelerations are significantly associated with CTE pathology.

Indigenous-led structured decision-making workshops with local Indigenous people on Bundjalung Country in Australia identified and prioritized culturally significant species and determined Bundjalung-led actions for the management of these culturally significant entities.

Locksley et al. show tissue-specific imprinting dictates the activating receptors ILC2s express, even in germ-free mice. Skin ILC2s are preferentially activated by IL-18, and IL-18 contributes to inflammation in a mouse model of atopic dermatitis.

Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.

Here the authors show how the liver affects the immune response to pancreatic ductal adenocarcinoma and that cancer immunity and survival outcomes after surgery might be bolstered by therapeutic intervention on hepatocyte release of serum amyloid A proteins.

Analyses of real-world evidence from digital clinical practice data provide important insights for healthcare decision makers. Here, authors test reproducibility of 150 peer-reviewed studies, reporting strong reproducibility, which could be further improved through more complete reporting in future original studies

Here, the authors identify a frontostriatal circuit that is involved in regulating social interactions based on learned hierarchical relationships.

Synthetic transcriptional repressors are engineered from natural DNA-binding domains.

Building crystal structures into the electron density is an important step in protein structure solution. Here, the authors recruit online game players, students, and experienced crystallographers to compete in a competition to solve a new structure, and find that crowdsourcing model-building works.

A novel approach to analyse high-depth Hi-C data provides a comprehensive chromatin interaction map at approximately 5–10 kb resolution in human fibroblasts; this reveals that TNF-α-responsive enhancers are already in contact with target promoters before signalling and that this chromatin looping is a strong predictor of gene induction.

The noncoding RNA Xist regulates the accessibility of select chromatin regions on the inactive X chromosome (Xi) by directly inhibiting the chromosome remodeler BRG1 and by expelling it from the Xi.

Single-nucleus methyl-3C sequencing jointly interrogates 3D chromatin organization and DNA methylation in human cells, and these joint measurements more accurately distinguish different cell types than either unimodal method.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Deep learning was used to map the crown sizes of each tree in the West African Sahara, Sahel and sub-humid zone using submetre-resolution satellite imagery, revealing a relatively high density of trees in arid areas.

Jung-Hyun Lee, Jong Bhak and their colleagues report the whole-genome sequencing and de novo assembly of a male minke whale genome, as well as the genome sequences of three additional minke whales, a fin whale, a bottlenose dolphin and a finless porpoise. Their comparative analysis across cetaceans provides insights into adaptation to an aquatic lifestyle.

A lightweight, flexible technology that displays vibro-tactile patterns across large areas of the skin in single units or through a wirelessly coordinated collection of them can be used to convey map directions for road navigation, translate musical tracks into tactile patterns and reconstruct tactile sensations for feedback control of robotic prosthetics.

The Aegilops tauschii-derived leaf rust resistance gene Lr42 has been widely used for breeding resistance wheat cultivars, but the molecular basis is unknown. Here, the authors show that Lr42 encodes an NLR-type of disease resistance gene by bulked segregant mapping in Ae. tauschii and confirm its function in common wheat.

Type 2 responses can be elicited by ILC2s and T_H2 cells. Locksley and colleagues show that the epithelium-derived cytokines IL-25, IL-33 and TSLP are required for full effector activation of poised ILC2 and primed T_H2 cell populations.

Learning new associations that reappraise the behavioral significance of previously irrelevant cues requires gamma-frequency synchronization between parvalbumin interneurons in the left and right prefrontal cortex.

An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Study of structural inhomogeneities in zeolites is important but limited by conventional techniques. Here the authors employ in situ free-electron-laser-based time-resolved coherent X-ray diffraction imaging to visualize the effect of these inhomogeneities during catalytic deoxygenation of NOx.