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This study reveals that adhesion G-protein-coupled receptors (GPCRs) promote extracellular vesicle (EV) formation and EVs spread GPCRs into neighboring cells to activate G-protein signaling, providing a novel mechanism for cell–cell communication.

Industrial hydrogen production often uses carbon-based sources, necessitating complex purification processes to separate hydrogen from impurities. Here the authors present a reversible catalytic cycle that converts crude hydrogen into pure hydrogen, bypassing the need for pressure swing adsorption or membrane systems.

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.

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

Electrosynthesis of higher carbon products (C₄₊) in a high selectivity has not been achieved by the direct reduction of CO₂ or CO. Here, the authors use a cascade electrocatalysis–thermocatalysis approach to produce butane from CO with an overall selectivity of 43%.

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.

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.

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.

SAP05, a secreted effector of the obligate parasitic bacteria phytoplasma, bridges host SPL and GATA transcription factors (TFs) to the 26 S proteasome subunit RPN10 for ubiquitination-independent degradation. Here, the authors report the details on how SAP05 interacts with SPL5, GATA18 and RPN10.

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.

Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability and function in prostate 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 quantitative fluorescence-activated cell sorting method for generating fully human conformational antibodies against amyloid aggregates associated with neurodegenerative disorders—without the need for immunization—has now been developed. Engineered antibodies obtained using this approach show properties rivaling those of clinical-stage antibodies specific for tau and α-synuclein amyloid aggregates.

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.

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.

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.

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.

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 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.

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.

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.

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.

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 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.

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.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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.

Lei et al. show that cold preservation of heart transplants triggers mineralocorticoid receptor clustering in cardiomyocyte nuclei, and blocking this improves heart transplant function.

Magnetic phases that are stabilized by quantum fluctuations in low dimensions are rare. A thickness-dependent crossover from three-dimensional antiferromagnetism to a two-dimensional vestigial nematic state that is driven by fluctuations has now been observed.

BicA is a bicarbonate transporter involved in cyanobacterial photosynthesis. The structure of BicA from Synechocystis suggests a mechanism for all SLC26/4-family transporters and can aid bioengineering of BicA to boost CO₂ assimilation.

Directional solidification of a simple AgCl-KCl lamellar eutectic material is modified by the presence of a pillar template, leading to disordered, trefoil, quatrefoil, cinquefoil and hexafoil mesostructures.

The genetic link between placenta function and congenital heart defects has been established, though the cellular mechanisms underlying this connection is less clear. Here they show that PIBF1 regulates syncytiotrophoblast fusion and that loss of PIBF1 also negatively impacts heart development, providing a potential link between the development of these two organs.

Diverse plant species synthesize salicylic acid from phenylalanine through a pathway that includes a conserved triple-enzyme module that converts benzoyl-CoA to salicylic acid.

Many neurotransmitters act on receptors coupled to GTP-binding G proteins. Here authors report the structure and activity of a mutant that locks the nucleotide-free and receptor-bound state of the G protein, leading to a rare neurological disorder.

Moroidins are plant ribosomally-synthesized and posttranslationally-modified peptides with anticancer activity. Here, the authors generate a searchable database of publicly available plant RNAseq data and identify a moroidin analog with higher cytotoxic activity.

By isolating one-dimensional tellurium nanowires in boron nitride nanotubes, the electronic properties of the atomic chains can be measured and the structures used to create field-effect transistors.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Halo-structured nuclei are examples of many-body open quantum system. Here the authors use a complete kinematics measurement and find an elastic breakup of proton halo nucleus ⁸B.

The E1A binding protein p300 and its close paralogue CREB-binding protein are transcriptional coactivators with intrinsic histone acetyltransferase activity. Here, the authors show that the TAZ2 domain of p300 has a HAT autoinhibitory function that is relieved upon binding of transcription factors.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Hou, Chen et al. show that aged bone marrow macrophages propagate senescence to multiple tissues in vivo, through extracellular vesicles containing PPARα-targeted microRNAs. They demonstrate the therapeutic potential of intervening in this process using the PPARα agonist fenofibrate.

Flexible and fatigue-resistant optical fibers made from hydrogel allow optogenetic manipulations in the periphery in freely behaving mice.

The orphan nuclear receptor SHP is a transcriptional corepressor in the liver. Jo and colleagues show that it also acts to negatively regulate Toll-like receptor signaling at multiple levels.

Hypoxia induces ·NO-dependent hydrogen sulfide (H₂S) biogenesis by inhibiting the transsulfuration pathway. H₂S oxidation promotes endothelial cell proliferation to support neovascularization in tissue injury and tumor xenograft models.

The multiple sclerosis brain shows massive demyelination. Now, Sha Mi and colleagues show that upregulation of DR6 in multiple sclerosis brain is responsible for inhibiting remyelination and brain repair by oligodendrocytes.

The histone methyltransferase ASH1L plays a role in various diseases, including cancer, and has been validated as a therapeutic target; however, no inhibitors of ASH1L have been reported. Here the authors present small molecule inhibitors of ASH1L and demonstrate their on-target activity in leukemia cells and a mouse model of leukemia.