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This study introduces two new measures of brain function at the gray–white matter boundary, revealing distinct patterns of signal transmission and metabolic activity that deepen our understanding of brain organization and development.

Cells typically migrate toward stiffer substrates via durotaxis, relying on focal adhesions. Here, the authors show that confined cells can migrate up friction gradients without focal adhesions, revealing a mode of directed migration called frictiotaxis.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Variations in human brain frontoparietal functional connectivity and in signal complexity during intelligence tests relate to individual test performance. Results encourage exploring human intelligence across multiple spatial and temporal scales.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Marin-Llaurado and colleagues engineer curved epithelial monolayers of controlled geometry and develop a new technique to map their state of stress. They show that pronounced stress anisotropies influence cell alignment.

Integrins regulate haematopoietic stem cell (HSC) homeostasis and engraftment into the bone marrow (BM) niche upon transplantation. Here, the authors show that HSC quiescence and function in the BM is regulated by the interaction of PERIOSTIN and INTEGRIN αv and subsequent increase in p27Kip1.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Argonaute proteins are key effectors in the microRNA pathway. Here, the authors show that the conserved peptidase DPF-3 regulates Argonautes in C. elegans, and that loss of dpf-3 restores function and fitness in animals lacking the microRNA Argonaute ALG-1.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Using a cohort of nearly 1,000 genetically diverse mice undergoing dietary restriction over the lifespan, the authors reveal numerous insights into the interactions between the gut microbiome, host genome, diet, health and longevity.

Ageing in humans is associated with an increase in circulating methylmalonic acid, which induces expression of SOX4 and promotes tumour progression.

A study in eastern Canada finds that forest-management strategies that lead to simplified forest structure and composition have resulted in loss of breeding habitat and associated population losses for many bird species.

JWST observations of a strongly lensed low-mass galaxy in a 600-million-year-old Universe show massive star clusters (the Firefly Sparkle) cocooned in a diffuse arc in the Canadian Unbiased Cluster Survey.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Ancient, rock-derived organic matter is consumed by micro-organisms in Arctic fjord sediments despite its presumed limited bioavailability, representing a potential source of greenhouse gas emissions, according to compound-specific radiocarbon analyses of lipids from living bacteria.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

The authors test whether experience-dependent neocortical modifications need Ube3a, an ubiquitin ligase implicated in autism and Angelman syndrome, using a mouse model of Angelman syndrome. They find that experience-dependent maturation of excitatory circuits in the visual cortex is impaired in these mice and that there are deficits in plasticity. This loss of plasticity was reversible with visual deprivation.

Catalytic transformations involving main group compounds is much less developed than carbon chemistry. Here, the authors report the use of catalytic or stoichiometric tBuOK in presence of a hydrogen acceptor for efficient P–P and P–heteroatom coupling reactions.

Wrinkling of cell nuclei is associated with disease. During development, the nucleus behaves like a sheet of paper and the wrinkling amplitude can be manipulated without changing its pattern.

Observations of a 3-million-year-old pre-main-sequence star with a misaligned disk reveal a giant orbiting planet; the system is ideal for studying the early formation and migration of planets.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Wang et al. profile age-dependent miRNAomic changes in worm tissues and extracellular vesicles (EVs). They show that ageing controls miRNAs in a tissue-specific manner and their findings further suggest a complex EV-mediated miRNA trafficking network across tissues.

Human WNT10A mutations are associated with dental defects and adult onset ectodermal dysplasia. Xuet al. show that WNT10A-activated ß-catenin plays dual roles in adult epithelial progenitor proliferation and differentiation by complexing with KLF4 in differentiating, but not proliferating, cells.

D1- and D2-expressing striatal neurons encode separate parts of a learned reward distribution, paralleling modern approaches in machine learning.

New archaeological and ancient genomic data from humans in Papua New Guinea and the Bismarck Archipelago shed light on regional human admixture and genetic isolation over the past 2,500 years.

Serological profiles from two observational cohort studies in The Gambia characterize surrogates of protection against Streptococcus pyogenes and reveal an antibody response against antigens that are currently in vaccine development.

The molecular and cellular mechanisms underlying ovarian aging are incompletely understood. Here the authors provide single-nuclei RNA and ATAC-seq of human ovarian tissue from four young and four reproductively aged donors, revealing coordinated transcriptomic and epigenomic changes across cell types and highlighting a role for mTOR signaling in reproductive aging.

An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.

Shlien and colleagues report on 300 patients from the SickKids Cancer Sequencing program and identify clinically actionable variants in 56% of the patients by profiling somatic and germline data at multiple clinical time points.

Adherens junctions (AJs) mediate cell-cell adhesion between epithelial cells but tools to study their dynamic regulation are lacking. Here the authors develop an optochemical tool to stimulate the assembly of AJs through addition of a photocleavable tool and their dissociation upon exposure to light.

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.