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Cystine levels in pancreatic ductal adenocarcinoma (PDAC) tumour microenvironment are deficient, despite its crucial role for cancer cell maintenance. Here, the authors show that adaptation to cystine limitation stress promotes PDAC growth through induces metabolic reprogramming to promote PDAC tumor growth, while conferring a vulnerability in lipid metabolism targetable by lomitapide.

Delamination and cracking hinder the durability of air electrodes in ceramic cells. Here, the authors introduce oxide wedging at particle interfaces to enhance mechanical robustness and thermal compatibility, significantly improving electrode longevity.

Spontaneous scrolling in two-dimensional polar van der Waals materials, driven by intrinsic out-of-plane electric polarization, enables the scalable production of nanoscrolls and their heterostructures.

Global change is driving a global biodiversity crisis. Here, using a global meta-analysis, the authors find no overall change in plant β-diversity, though effects vary by region, ecosystem, global change factor, and biodiversity dimension.

An analogue memory built from a two-dimensional material with antimony contacts enables very high, energy-efficient in-memory searches and k-nearest-neighbour classification, offering a scalable, low-power hardware platform for real-time edge artificial intelligence applications.

This study elucidates the underlying cell death mechanism of NECSO (Necrosis by sodium overload). TRPM4-mediated sodium influx activates mitochondrial sodium–calcium exchange, which impairs mitochondrial energy production. This energy deficit inactivates the Na/K-ATPase, ultimately leading to cellular swelling and lysis.

Mutation of conserved prolines enhances correct pairing of light and heavy chains for bispecific IgG-like antibody production.

A blocking assay based on the recombinant receptor-binding domain of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 receptor provides an alternative to conventional antibody neutralization assays requiring live virus.

Cells decode temporal patterns into gene expression states through amplitude and frequency modulation. Now it is shown that frequency modulation increases information entropy compared with amplitude modulation alone.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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

Azides are common moieties in chemical synthesis. Here the authors present a methodology to synthesize alkyl azides in one step from simple alcohols under mild conditions.

Solution-processed small-molecule solar cells with almost 100% internal quantum efficiency and a power conversion efficiency of 9% are reported. The cells make use of a donor molecule called DRCN7T and use PC71BM as an acceptor.

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.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

X. Du, W. Li, G. Li, C. Guo et al. report that dietary galactose regulates the cellular crosstalk between hepatocytes and CD8⁺ T cells via IGFBP-1 production and IGF-1 signalling, thereby modulating T cell exhaustion and antitumour immunity.

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.

Bone and blood lineage cells communicate each other to maintain skeletal homeostasis. Here authors show that osteolineage RIPK4 couples osteogenesis and myelopoiesis via MFN2 to regulate mitochondrial dynamics.

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.

Comprenhensive analysis of human antibody responses to SARS-CoV-2 variants and animal sarbecoviruses finds that Omicron escapes neutralization more readily than distantly related animal sarbecoviruses.

Responses to SARS-CoV-2 vaccines in different populations are important to define efficacy. Here the authors show using a cohort in Singapore that two doses of mRNA vaccine is less effective in recipients over 60 years of age and that a further dose of vaccine can improve these antibody levels.

Neural mechanisms underlying sex-dependent conditioned pain hypersensitivity are not fully understood. Here authors found that a neural circuit from the medial preoptic area to the ventrolateral periaqueductal gray mediates context-dependent pain hypersensitivity in male, but not female, mice, which requires activation of testosterone signaling.

This study explores a precise and efficient chromosome editing technology that enables the scarless deletion, replacement and inversion of large DNA fragments, up to the megabase scale, in plants and holds considerable promise for crop improvement.

Epitaxial growth of the two-dimensionally thin material flakes with effective layer number and shape calls for precise control over temperature and carrier gas. Here, authors report controlled epitaxial growth of the second layer vertically for MoS2, WS2, MoWS and MoWSSe compounds by reverse hydrogen gas flow chemical vapor epitaxy.

Here, the authors provide detailed analyses of viral RNA structure in virions and in infected cells for four dengue virus serotypes and four Zika virus strains, and identify conserved structures that are important for virus replication.

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.

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.

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.

In this work, the authors discovered that Panax species, the valuable medicinal plants, have evolved a two-component chemical defence system comprising a chloroplast-localized β-glucosidase and 20(S)-protopanaxadiol ginsenosides.

Here, Yang et al. apply different RNA sequencing approaches to characterize the secondary structure of SARS-CoV-2 viral RNAs, report on long-range interactions along the viral genome, and uncover the virus-host RNA interactome in cells.

A bat origin for SARS-CoV-2 has been proposed. Here, by sampling wild Rhinolophus acuminatus bats from Thailand, the authors identified a SARS-CoV-2-related coronavirus (SC2r-CoV), designated as RacCS203, with 91.5% genome similarity to SARS-CoV-2, and show that sera obtained from bats and Malayan pangolin neutralize SARS-CoV-2.

The authors reveal a complex polarization network in twisted bilayer h-BN, featuring edge polarization topology and sliding ferroelectricity, driven by the interplay of ferroelectric and piezoelectric effects.

The mechanism of action of artemisinin, an antimalarial drug, is not well understood. Here, the authors use a labelled artemisinin analogue to show that the drug is mainly activated by haem and then binds covalently to over 120 proteins in the malaria parasite, affecting many of its cellular processes.