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Although CTCF is a well-established 3D chromatin organizer in multicellular eukaryotes, relatively little is known about its male germ cell-specific paralogue, BORIS. Here the authors investigate how CTCF and BORIS interact and compensate in the male germline of mice to ensure appropriate activation of spermatogenesis-specific genes.

Xie and colleagues show that MRI-based brain function maps can identify patient-specific abnormalities in temporal lobe epilepsy, track how they spread along brain networks, and help diagnose, lateralize seizure focus, and predict surgical outcomes.

In this work, a library of several hundred million compounds was computationally docked to a cryoEM structure of the orphan G protein-coupled receptor GPR139, leading to the discovery of a potent agonist with in vivo effects and insights into GPR139 signalling.

This study defines the consequences of ARID1A and ARID1B loss in dedifferentiated or undifferentiated endometrial carcinoma, finding that altered SWI/SNF chromatin remodeler complex subtypes support oncogenesis, informing potential therapeutic opportunities.

Royer and colleagues find a principal dimension of neural dynamic similarity dissociating unimodal and association cortices. Systematic variations in local and macroscale constraints across the cortex also followed this pattern.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

Shaking evoked by wet fur or plumage is reproduced by a synthetic agonist of the cold and menthol receptor TRPM8, in rats, mice, and chickens. In water sprayed mice, the onset of the shaking behavior depends on water temperature and TRPM8 expression.

HippoMaps provides an open-source resource for studying the human hippocampus at different scales and with different modalities such as histology, fMRI, structural MRI and EEG.

EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Hydrofunctionalization of α-olefins with mineral acids usually proceeds with Markovnikov selectivity. Now, a strategy based on synergistic phase transfer and photoredox catalysis is developed to facilitate anti-Markovnikov addition of aqueous hydrochloric and nitric acid to unactivated alkenes.

Functional imaging and multiplexed in situ hybridization were combined to investigate how trigeminal neurons encode heat and mechanical stimuli, revealing distinct cellular mechanisms for continuing pain, heat hypersensitivity and tactile allodynia during inflammation.

The cuneiform nucleus regulates locomotor activity. Here the authors show that this nucleus has a more context-dependent role than previously thought, whereby GABAergic projections from the zona incerta act to promote exploratory behaviour in mice.

Imaging the visible light emitted from accelerated electron bunches reveals important information about the three-dimensional charge structure of the bunches, which strongly influences the performance of free-electron lasers.

Magic state distillation is achieved with logical qubits on a neutral-atom quantum computer using a dynamically reconfigurable architecture for parallel quantum operations.

Corral-Lopez et al. use guppies as a model system for the evolution of collective motion. They show that guppies artificially selected for schooling remain highly coordinated across predation contexts and show key changes in brain morphology that likely increase the efficiency of sensory information relay.

Microscale fluctuations originating from the mirror instability can effectively keep sub-teraelectronvolt cosmic rays confined to galaxy clusters and explain recent observations.

A-SOiD is a computational platform for behavioral annotation whose training includes elements of supervised and unsupervised learning. The approach is demonstrated on mouse, macaque and human datasets.

Here, the authors characterize the spectroscopic and transport properties of heterojunctions composed of quasi-metallic and semiconducting graphene nanoribbons (GNRs) with different widths, showing a predominant quantum tunnelling mechanism. The GNR heterojunctions can also be used to realize adsorbate sensors with high sensitivity.

How does the brain balance specialization and integration? Using high-resolution MRI and a post-mortem atlas, this study reveals how local and global cortical organization are linked, shaping functional diversity across brain areas.

Theoretical estimations of solvation free energy by continuum solvation models are generally not accurate. Here the authors report a polarizable force field fitted entirely to first-principles calculations for the estimation of free energy of solvation of arbitrary molecules.

Longitudinal data in electronic health records could be used to improve definitions of patient clusters and therefore inform precision medicine interventions. Here, the authors introduce VaDeSC-EHR, a machine learning model that uses patient longitudinal trajectories and time-to-event data to define clusters.

A quantum simulation of a (2 + 1)-dimensional lattice gauge theory is carried out on a quantum computer working with neutral atoms trapped by optical tweezers in a Kagome geometry.

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.

Interaction between Cooper pairs and other collective excitations may reveal important information about the pairing mechanism. Here, the authors observe a universal jump in the phase of the driven Higgs oscillations in cuprate thin films, indicating the presence of a coupled collective mode, as well as a nonvanishing Higgs-like response at high temperatures, suggesting a potential nonzero pairing amplitude above Tc.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

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.

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.

Malik, Guo et al. show that Ntrk2/Trkb-mediated neurotrophic signalling regulates dopamine levels by controlling glutathione–ascorbate metabolism, thus impacting striatal dopaminergic circuits and motor function

The critical floating phase can bridge crystalline orders and the disordered phase. Here, the authors experimentally observe the quantum floating phase in neutral atom qubit arrays, revealing domain walls and incommensurate quasi long-range order, and analyse its emergence via Fourier spectroscopy.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are still unclear. Here the authors show that a SCFA, pentanoate, suppresses autoimmune inflammation in mouse models of colitis and multiple sclerosis via epigenetic modulation of immune cell metabolic and functional pathways.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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 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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

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.

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

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.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.