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Mutations in mtDNA contribute to mitochondrial disease and aging only if they rise in abundance. Here, the authors show that deleterious mutations reach high abundance by hitchhiking on genomes that have a replicative advantage.

Many diseases are caused by single-nucleotide polymorphisms. Here, the authors present CRISPR base editors that use the base excision machinery for single-base transversions.

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.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Cancer mutations in histone H3 cause genome instability, but the mechanisms remain to be elucidated. Here, the authors show in a plant model that the oncohistone H3.1K27M disrupts the TSK/TONSL-H3.1 DNA repair pathway.

The large intestine mucosa possesses a surprising plasticity to switch on small intestine genes. Here, Wei G. et al. show that a chromatin complex composed of SATB2, MTA2 and HNF4A regulates this tissue plasticity in the adult gut.

Scanning tunneling microscope (STM) is a powerful tool but local control of superconductivity with the STM tip is still lacking. Here, Geet al. show the use of an STM tip to control the local pinning in a superconductor through the heating effect, allowing to manipulate single superconducting vortex at nanoscale.

Exploratory post hoc analysis of molecular residual disease from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer shows that molecular residual disease detection predicts disease recurrence with long-term adjuvant osimertinib treatment.

Mendelian randomization (MR) is a method for inferring causal relationships between risk factors and outcomes via associated genetic variants. Here, Burgess et al. develop the contamination mixture method which yields robust MR results in the presence of invalid instrumental variables and groups variants by their effect estimates.

Co-occurring mutations in the tumor suppressor LKB1 are frequent in KRAS-mutant lung cancers. Here, the authors show that LKB1 regulates JNK-dependent stress signaling apoptotic dependencies of KRAS-mutant tumors, making LKB1-deficient cells vulnerable to MCL-1 inhibition.

A method for the site-selective C–H borylation of arenes and heteroarenes is described, in which BBr₃ acts as both a reagent and a catalyst.

This work presents a framework for estimating cell division numbers using DNA replication-associated polyguanine tract mutations, with applications for understanding tumor natural histories and origins.

The nature of unconventional charge density wave in kagome metals is currently under intense debate. Here the authors report the coexistence of the 2 × 2 × 1 charge density wave in the kagome sublattice and the Sb 5p-electron assisted 2 × 2 × 2 charge density waves in CsV₃Sb₅.

Tracking ultrafast electronic changes in molecules is challenging, especially in liquids. An X-ray spectroscopy study in pyrazine now shows electronic dynamics created at conical intersections that are rapidly suppressed when the molecule is in water.

Moiré patterns and flat bands usually occur in multilayer materials with a small interlayer twist angle, but this can cause detrimental lattice reconstruction. Now, flat bands are shown in a bilayer with large twist angle and structural rigidity.

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Enzymatic mimics, capable of catalysing cascading reactions under physiological conditions, can be formed from integrating multiple components. Here, the authors report a graphene–haemin–glucose oxidase system capable of biomimetic generation of antithrombotic species from abundant glucose and L-arginine.

The control of magnetic properties by electric fields is key to realizing spintronics devices. The surface of the antiferromagnetic magnetoelectric Cr₂O₃ is now shown to exhibit room-temperature ferromagnetism, whose direction can be switched by an electric field. This magnetization switches the exchange-bias field with magnetic multilayers grown on Cr₂O₃, promising a new route towards room-temperature spintronics devices.

Quantum simulators offer a test bed to emulate physical phenomena that are difficult to reproduce numerically. Using a multi-element superconducting quantum circuit, Chen et al.emulate weak localization for a mesoscopic system using a control sequence that lets them continuously tune the level of disorder.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

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.

AI decision support system non-homogenously influences clinical decisions in dynamic treatment regimen, as it depends on several factors including prior knowledge, preference, disease type, treatment modality, and AI’s learned behavior and inherent biases.

Whole-gene sequencing of microdissected gastric glands from individuals with and without gastric cancer reveals distinct patterns of somatic mutations and provides insights into influences on the somatic evolution of the gastric epithelium.

Weak value amplification in a compact format can lead to improved measurement capabilities in practical applications. Here the authors demonstrate weak value amplification in an integrated photonic chip with a multimode interferometer.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Amino acids availability is normally a limitation for protein synthesis and can determine cancer progression and therapy response. Here, the authors show that MYC-associated cancer has a dependency on tryptophan not because of translation regulation, but Indole 3-Pyruvate synthesis.

Clarke, Hawkinson and colleagues study the contribution of glycogen accumulation in the onset and progression of lung cancer.

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.

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

Magnetic resonance imaging (MRI) contrast agents are essential for modern medical imaging, but existing MRI contrast agents have limitations that result in poor resolution and ineffective long-term monitoring. Here, the authors report the development of a T1-MRI contrast agent based on a variant of lanmodulin, LanND-Gd, with efficient renal clearance, high relaxivity, and prolonged renal retention compared with commercially available contrast agents.

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.

While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

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.

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.

Iminium-catalysed cycloaddition is a prominent example of organocatalytic reactivity, yet a biological counterpart has not been identified. Now, the authors report biochemical, structural and computational evidence for iminium catalysis by the natural Diels–Alderase SdnG.

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.

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.

By designing superconducting materials the behavior of supercurrents can be controlled to give different emergent behavior. Ge et al. fabricate superconducting films in which currents form geometrically frustrated magnetic dipoles that can be tuned further by coupling to a vortex lattice.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

A genome-wide association study of cerebral ventricle phenotypes finds 62 unique loci and reveals a genetic overlap between ventricular and neuropsychiatric traits.