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Cocaine-context associations rely on nucleus accumbens neuronal ensembles with engram-like properties unique to distinct stages of memory encoding. Here the authors show that ensemble reactivation parallels recall and selectively engages transcriptional plasticity programs.

Genome-wide association studies indicate a strong genetic susceptibility to acute lymphoblastic leukaemia in children, though the effect on protein-coding genes is not fully understood. Here Xu and Zhang et al. identify a missense variant in CDKN2Awhich reduces tumour suppression.

Cryo-electron microscopy structures of three different serotonin receptors in complex with serotonin and other agonists provide insights into the role of lipids in regulating these receptors and the structural basis of ligand recognition.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

Formylpeptide receptors (FPRs) are a class of chemotactic G protein-coupled receptors (GPCRs) that recognize pathogen- and host-derived formylpeptides. Here the authors report the 3.17 Å cryo-EM structure of the human FPR2-G_i signaling complex with a bound peptide agonist and in combination with computational docking and MD simulations provide mechanistic insights into formylpeptide recognition by FPRs.

The small molecule GS-6207, which disrupts the function of the HIV capsid protein, shows potential as a long-acting therapeutic agent for the treatment and prevention of HIV infection.

In analogy with quantum Hall systems, it may be possible to find non-abelian anyons in the higher bands of Chern insulators. Now, the phase diagram of the second moiré band of twisted MoTe₂ is explored, laying the groundwork for such investigations.

The authors report a tripling in the speed of serial section transmission electron microscopy using a beam deflecting mechanism. This innovation enables the acquisition of multiple image tiles for each stage motion, yielding a net imaging rate of 0.3 gigapixels per second for millimeter-scale areas.

Xu et al. show that satellite-measured urbanicity (living in a densely populated area) is correlated with brain volume, cortical surface area and brain network connectivity in a sample of 3,867 people from China and Europe.

An approach for the design of protein pores is demonstrated by the computational design and subsequent experimental expression of both an ion-selective and a large transmembrane pore.

Typical single-cell RNAseq pipelines will subcluster homogeneous cells. Here, authors present a computational algorithm for accurately identifying cell-type marker genes in single-cell data analysis with a low false discovery rate.

Cryo-electron microscopy structures of the noradrenaline transporter in the apo state, bound to noradrenaline and bound to various antidepressants shed light on the substrate transport, molecular recognition and dimeric architecture of this protein.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

DREDge is a software tool for motion correction of high-density electrophysiology recordings. It can handle action potential or local field potential data and is demonstrated on a variety of acute or chronic recordings from humans, nonhuman primates and mice.

Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of inflammatory diseases. Here authors report a cryoelectron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, which provides insights into PACAP27 binding and VIP receptor activation.

Adhesion GPCRs involved in cell and matrix interactions signal through a distinct self-cleavage, self-activation mechanism.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Seryl-tRNA synthetase is important in vasculogenesis and contains a unique domain at its C-terminus. In this study, the unique domain is shown to target the protein to the nucleus, block expression ofvegfaand be essential for vasculogenesis in zebrafish.

The plant hormone abscisic acid (ABA) is a regulator of plant growth, development and responses to environmental stresses. Recently, the PYR/PYL/RCAR family of START proteins was found to bind ABA and mediate inactivation of downstream effectors. The crystal structures of apo and ABA-bound receptors as well as a ternary PYL2–ABA–PP2C complex is now reported and analysed, revealing a gate–latch–lock mechanism underlying ABA signalling.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

A single component built from sputtered niobium dioxide, a Mott insulator–metal transition material, can simultaneously exhibit both visible light emission and electrical threshold switching with neuron-like oscillations.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Wildfires are becoming increasingly frequent in several regions around the world due to climate change, posing serious health risks, especially for respiratory diseases. This study examines the respiratory health risk and burden of wildfire-specific PM_2.5 pollution across eight countries and territories.

A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.

Characterization of DCAF16-based BRD4 molecular glue degraders revealed a trans-labeling mechanism termed ‘template-assisted covalent modification’, which opens a new path for proximity-driven pharmacology.

Machine-learned potentials are accurate but often lack broad applicability. Here, authors develop a general-purpose neuroevolution potential for 16 metals and their alloys, achieving efficient and accurate predictions of various physical properties.

Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe.

Adenine base editing successfully corrected a MYH7 pathogenic variant that causes hypertrophic cardiomyopathy in human cardiomyocytes and a mouse model of the disease, highlighting the potential of the approach to correct monogenic variants causing cardiac disease.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

Seq2Symm is a sequence-based AI model designed to predict the symmetry of protein structures composed of identical chains, known as homo-oligomers. It surpasses existing methods in accuracy and efficiency, enabling rapid, proteome-scale predictions.

Xu et al. use single-cell transcriptomics to reveal that targeted and systemic partial reprogramming restore the production of neuronal progenitors and new neurons in old mice and show a cell-autonomous effect of reprogramming in cultures of aged neural stem cells.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Here, the authors report structures of corticotropin releasing factor receptor 2 (CRF2R) bound to agonist Urocortin 1 (UCN1) and coupled to G proteins G₁₁ and G_o, offering insight into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

The orphan GPR84 plays important roles in inflammation, fibrosis, and metabolism. Here, authors report cryo-EM structures of the receptor bound to two ligands, with insights into ligand binding and entry from the extracellular milieu.

Copper (Cu) dysregulation contributes to aging and oxidative stress. Here the authors develop imaging probes to detect labile hepatic Cu, revealing age-related increases that deplete ALDH1A1 activity, and show that chelation therapy restores Cu homeostasis, offering a potential strategy to mitigate liver aging.

The topological properties of twisted bilayer MoTe₂ are thought to stem from a spatial texture in the layer polarization of the electronic wavefunctions. This polarization is now measured using scanning tunnelling microscopy.

Exome sequence analysis of more than 5,000 schizophrenia cases and controls identifies a polygenic burden primarily arising from rare, disruptive mutations distributed across many genes, among which are those encoding voltage-gated calcium ion channels and the signalling complex formed by the ARC protein of the postsynaptic density; as in autism, mutations were also found in homologues of known targets of the fragile X mental retardation protein.

Structural studies on the complex containing G-protein-coupled receptor kinase 2 (GRK2), neurotensin receptor 1 (NTSR1), Gα_q and the arrestin-biased ligand SBI-553 provide insights into these interactions and a foundation for the design of arrestin-biased ligands for G-protein-coupled receptors.

5-hydroxytryptamine 2C receptors (5-HT2CRs) in the brain have been shown to regulate glucose homeostasis. Xu and colleagues find that 5-HT2CRs expressed specifically by hypothalamic pro-opiomelanocortin neurons are involved in the regulation of insulin sensitivity and glucose homeostasis in liver.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Cryo-EM structures of sulfated cholecystokinin 8 bound to the cholecystokinin A receptor in complex with G_s, G_i and G_q heterotrimers reveal structural determinants for G-protein coupling selectivity.