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The ATP-dependent chromatin assembly factor (ACF) generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. But how the enzyme moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Nucleosome movement is now shown to depend cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

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.

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.

Linear scaling relationships often hinder the optimization of heterogeneous catalysts. Now, an intermediate spillover strategy is put forward by designing bi-component catalysts, thereby decoupling elementary electron-transfer steps and circumventing linear scaling relationships.

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.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

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.

In this study, Cheng et al. show that ammonia released from glutaminolysis disrupts the SCAP–Insig association, thus activating SREBP-1 and promoting lipogenesis to support tumour growth

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.

Cell division is governed by the positioning of a cytoskeletal structure called the spindle. Two methods, one based on laser ablation and the other on fluid flow assessments, are now shown to be useful tools for studying spindle positioning.

Drug molecules operate through physical interaction with specific cellular targets, and understanding this interaction is important for mechanisms and the potential therapeutic effect of drug candidates. Here, the authors show that bioluminescence resonance energy transfer can be used to monitor the intracellular engagement of a drug with its target.

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.

The effect of fluid viscosity on fault mechanics is mainly conjectured by theoretical models. Here, the authors present experimental data from rock friction experiments, showing both static and dynamic friction coefficients to decrease with viscosity and dynamic friction to depend on the Sommerfeld number.

Gas adsorption in porous materials offers an alternative technology for efficient hydrogen isotope separation. Here, the authors report high separation efficiency through isotopologue-induced structural dynamics in a readily scalable manganese-triazole metal-organic framework.

Lewis acid additive semicarbazide hydrochloride improves the formation of α-phase FAPbI₃-based films and promotes a homogeneous vertical distribution of A-site cations through a deprotonation–reprotonation process. The upgraded device performance reaches up to 26.12% with high stability, and mini-module perovskite solar cells achieving 21.47% (area, 11.52 cm²) demonstrate great scalability.

An E(3)-equivariant deep learning interatomic potential is introduced for accelerating molecular dynamics simulations. The method obtains state-of-the-art accuracy, can faithfully describe dynamics of complex systems with remarkable sample efficiency.

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.

The overlap between different phases has hindered the understanding of how each phase affects superconductivity in FeSe. Here, Matsuura et al. achieve a complete separation of non-magnetic nematic and antiferromagnetic phases for FeSe_1-x S _x , observing a tetragonal phase in between with a strikingly enhanced T _c.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Amado et al. develop a gene therapy for sporadic ALS using motor neuron-targeting AAVs to deliver RNAi targeting ataxin-2. In a mouse model, survival, strength, and disease-related pathology are improved; and human motor neurons are strongly transduced.

DNA methylation is a critical component for repression of fetal haemoglobin in adult blood cells. Removing DNA methylation from the fetal haemoglobin promoter effectively upregulates the gene, opening avenues for the treatment of blood disorders.

An approach combining machine learning and combinatorial chemistry enables the creation and evaluation of ionizable lipid libraries for lipid nanoparticle formulation to effectively deliver messenger RNA to several cells and tissues.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

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.

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 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.

Radiometrically dated speleothems are used to constrain the timing and duration of Marine Isotope Stage 11c. Early low-to-middle latitude warming in the North Atlantic led to an exceptionally developed interglacial despite weak insolation forcing.

An optical tweezer array of individual polyatomic molecules is created, revealing the obvious state control in the tweezer array and enabling further research on polyatomic molecules with diverse spatial arrangements.

¹⁴C can be absorbed by trees as a result of the interaction of cosmic rays produced by high-energy phenomena with the Earth’s atmosphere. Here, the authors observe a rapid increase of ¹⁴C in an ancient buried tree from BC 3372 to BC 3371, and suggest that it could originate from a large solar proton event.

Loss-of-function mutations in Myosin Binding Protein C3, MYBPC3, are the most common genetic cause of hypertrophic cardiomyopathy. Here, the authors present an AAV9-based gene therapy system with an optimized expression cassette with minimal promoter and cis-regulatory elements that can ameliorate cardiac functions and prolong survival in a murine MYBPC3-deficient model.

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.

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.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a powerful tool for neuroscience, but the standard DREADD ligand, CNO, has significant drawbacks. Here the authors report two novel high-potency DREADD ligands and a novel DREADD radiotracer for imaging purposes.

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.

Multiple computational methods have been developed to understand how mutations drive tumourigenesis, but their insights are largely non-overlapping. Here, the authors introduce NetFlow3D, a framework for integrating protein structure and interaction networks to map the mechanistic effects of somatic mutations in cancer.

Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.

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.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.