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Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

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

The Connectome Annotation Versioning Engine (CAVE) is a platform for proofreading, annotating and analyzing datasets reaching the petascale. Currently, CAVE is used for electron microscopy datasets, but it can potentially be used for other large-scale datasets.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The MICrONS mouse visual cortex dataset shows that neurons with similar response properties preferentially connect, a pattern that emerges within and across brain areas and layers, and independently emerges in artificial neural networks where these ‘like-to-like’ connections prove important for task performance.

The authors determine the synaptic wiring diagram of a vertebrate circuit and reveal behaviorally associated modules. A model based on this connectome predicts neural coding and dynamics that are verified with calcium imaging data.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Resistive switching is a promising technology to replace current non-volatile memory technologies such as flash. The demonstration of a fast, stable and highly scalable resistive-switching memory device represents a significant advance towards the practical implementation of this technology.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

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.

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.

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.

Aging impairs muscle and bone health, and exercise is known to mitigate this decline, partly through secreted factors. Here, the authors show that the muscle-derived factor CLCF1, which declines with age but is restored by exercise, mediates musculoskeletal benefits in aged mice.

Benchmarking of tumor subclonal reconstruction algorithms finds that interalgorithm variability overwhelms intertumor variability and identifies key quality metrics.

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.

FlyWire is an online community and a platform for proofreading electron microscopy-based connectome data of the Drosophila brain.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The spatial context of epitranscriptomic features in the tumour microenvironment remains poorly understood. Here, a method for transcriptomic and epitranscriptomic analysis of immunofluorescence-stained tissue, Select-seq, is applied to stem cell-like microniches in triple negative breast cancer.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

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.

Comparison of spontaneous canine cancers and human cancers may illuminate future therapeutic avenues. Here, genomic analyses of these tumors highlights a convergence on PI3K-Akt oncogenic pathways.

The outflow pathway of cerebrospinal fluid into lymph nodes in the neck and how non-invasive mechanical stimulation can enhance drainage and restore impaired outflow in aged mice are explored.

Changing characteristics of light-driven molecular motors during their action is an unsolved problem. Here, the authors propose to use coupling with photon confined in an optical cavity to manipulate the speed of rotation of molecular motors.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

Transcranial brain stimulation offers promising control of brain function. Here, the authors present a wireless transcranial optogenetic brain modulator for precise control of multiple brain regions, demonstrating its potential in studying complex behaviors and alleviating Parkinson’s symptoms.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Using an intrinsically stretchable nanocomposite of quantum dots, an elastomer and a hole transport polymer as an emissive layer, stretchable light-emitting diodes can be fabricated that exhibit high brightness even under 50% strain.

Excitatory neurons in the neocortex exhibit considerable morphological diversity, yet their organizational principles remain a subject of ongoing research. Here, the authors use unsupervised learning to show that most excitatory neuron morphologies in the mouse visual cortex form a continuum, with notable exceptions in deeper layers.

The availability of tracers to track the health of cells over long periods of time will be of value to optimize cell-based therapy. Here, Lee et al.design a nanoparticle that fluoresces red in living cells, but fluoresces green when cells begin to die from apoptosis or necrosis.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Hybrid entanglement between a quantum single-photon qubit state and a classical one is experimentally generated by quantum-mechanically superposing non-Gaussian operations on distinct modes. Entanglement is clearly observed between the two different types of generated states. This method provides a feasible way to generate even larger hybrid entanglement.

Automated reconstruction of dense neural networks in the ventral nerve cord of the fruit fly provides a resource for investigating the neural control of movement.

Perinuclear localization of CED-3 zymogen in C. elegans germ cells and interaction with nuclear-pore protein NPP-14 inhibit autocatalytic activation of CED-3, a central event in apoptosis.

Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.

Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.

Neural Decomposition (NEURD) is a software package that decomposes neuronal data from high-resolution electron microscopy volumes into feature-rich graph representations to facilitate analysis for neuroscience research.

Neural basis of multisensory decision-making is not fully understood. Here authors show that locomotion shifts multisensory decisions in mice from auditory to visual dominance by activating the motor cortex that inhibits auditory output to the parietal cortex. This reveals how state-dependent auditory gating shapes multisensory perception.