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Break-induced replication (BIR) repairs broken DNA but can also destabilize genomes. The authors identify 33 new genes controlling BIR completion, showing that spindle assembly and spindle positioning checkpoints coordinate repair, and that nuclear pore proteins regulate BIR at multiple steps.

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

Here, Zerio et al. use cryo-electron microscopy to show how the helicase domain of DNA polymerase θ aligns broken DNA strands by matching short sequences, a process linked to cancer. These findings may guide future therapies targeting error-prone DNA repair.

Integration of data representing 35,120 brain scans from diverse global studies enables construction of reference charts that define normative microstructural and macrostructural properties across the human lifespan for research and clinical diagnosis.

Tissue-specific fibroblast lipid cues are shown to significantly influence the invasion rate of squamous cell carcinomas (SCCs), with oral and lung fibroblasts promoting aggressive cancer behaviour through distinct lipid metabolic pathways, while dermal fibroblasts, being lipid poor, limit cutaneous SCC invasion.

DNA double strand breaks are repaired by nonhomologous end-joining (NHEJ) or homologous recombination (HR) pathways. Here, Pai et al.discover that post-translational modification of lysine 36 of histone H3 plays a key role in determining double strand repair pathway choice.

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.

Intensive control using village malaria posts and mass drug administration reduces parasite effective population size and increases genetic drift, driving founder effects and rapid shifts in resistance allele frequency.

This study shows that transcranial ultrasound stimulation can suppress a pathological biomarker in the brain network responsible for symptoms of Parkinson’s disease. This discovery could pave the way for future ultrasound-based deep brain stimulation.

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.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

The role of the cerebral cortex in cognitive and behavioral tasks is not fully understood.In this study, widefield imaging in freely moving mice navigating an 8-maze reveals global patterns of cortical activity. These cortical states represent multiple aspects of spatial decision making. Anterior and posterior state propagation is common and occurs throughout the maze, consistent with sensorimotor transformation and top-down control, respectively.

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.

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.

Atopic dermatitis is an immune disease driven by cytokines including IL-4/IL-13. This study shows that a topical ITK/TRK inhibitor blocks an array of T cell cytokines, inhibits NGF-induced basophil activation, and reduces inflammation in human skin explants and dermatitis models, indicating therapeutic potential.

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.

Long‑range chromosome encounters in cells are hard to quantify. Here, the authors induce artificial contacts in yeast and show that intra‑chromosomal interactions form faster than inter‑chromosomal ones in G1 yeast, driven by condensin‑mediated loop extrusion.

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.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

Dysregulation of H3K4 methylation is associated with neurodevelopmental disorders. Here, the authors perturb H3K4 methylation in the MGE and hypothalamus, resulting in altered gene expression and cell fate as well as changes in behavior that mimic NDD symptoms.

DNA recognition and cleavage control in type II topoisomerases are poorly understood processes. Here, the authors determine cleaved and uncleaved structures of supercoiled DNA-bound topoisomerase VI that reveal how the enzyme activates its cleavage state and prefers to act at deformable substrates.

Topologically protected states of matter are receiving widespread attention owing to their unusual electronic properties. Using numerical simulations, this study predicts that tin telluride is a physical realization of a new class of materials termed topological crystalline insulators.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

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.

The authors demonstrate high-fidelity multi-tone electronic control of trapped-ion qudits up to d=8 levels, enabling efficient SU(d) operations and showcasing advantage by implementing Grover’s search algorithm using encoding in a single qudit, rather than in multiple qubits.

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.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

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.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.

Periodic marine oxygen oscillations occurred throughout the middle Ediacaran Gaskiers Glaciation, probably stemming from increased organic carbon burial destabilizing ocean redox systems, according to geochemical constraints and modelling.

Latitudinal ecosystem boundaries in the global upper ocean may be driven by many factors. Here the authors investigate pole-to-pole eukaryotic phytoplankton metatranscriptomes, gene co-expression networks, and beta diversity, finding that geographic patterns are best explained by temperature gradients.

This study provides evidence of a cascading positive tipping point towards electric vehicles, which has occurred or lies within the next few years in lead markets of the EU and China, and potentially the US, and it could spill out into peripheral vehicle marketss across the rest of the world.

Topological crystalline insulators are characterized by metallic states originating from crystal symmetries. A transistor device that takes advantage of the quantum properties of the topological crystalline insulating materials SnTe and Pb_1−xSn_xSe(Te) is now proposed.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Despite being essential to organic chemistry, the curly arrow notation of reaction mechanisms has been treated with suspicion due to its unclear connection with quantum mechanics. Here, the authors show that analysis of wavefunction 'tiles' along a reaction coordinate reveals the electron motion depicted by curly arrows.

The oxidative prowess of cytochrome P450s has been suggested to stem from the electron-donating axial ligand. Now, a selenocysteine-ligated P450 compound I has been trapped and characterized providing an avenue to examine this hypothesis. Measurements reveal that the selenolate-ligated compound I cleaves C–H bonds more rapidly than the wild-type equivalent.

Structural variants are an underexplored source of genetic diversity. Here, the authors use phased pangenome graphs to improve detection of these variants in dairy cattle and link these variants to traits of economic importance.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Metabolic and proteomic profiles derived from fossilized skeletal remains of animals enable inferences regarding physiological health and disease as well as diet to provide reconstructions of ancient soil, vegetation and palaeoclimate characteristics.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Does aromaticity have a size limit? Evidence is presented for global aromaticity in porphyrin nanorings with circuits of up to 162 π-electrons. The conformation of the nanoring can be altered by changing the template, which in turn controls the aromaticity. Whenever a ring current is observed, its direction is correctly predicted by Hückel’s rule.