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Cytosine base editing is crucial for modeling human diseases in zebrafish. Here, the authors present zevoCDA1 and zevoCDA1-198, optimized editors that improve editing efficiency and precision, allowing zebrafish modeling for disease-related mutations which were previously limited by DNA sequence contexts.

Grasslands tend to be limited by both nutrient and water availability. Here the authors use standardized field experiments to show that the effects of nutrient addition on grassland biomass may cancel out the negative impact of drought, but the outcome depends on aridity and other local conditions.

The anti-leprosy drug clofazimine inhibits coronavirus replication in several cell models and shows potent antiviral activity against SARS-CoV-2 infection in a hamster model, particularly when used in combination with remdesivir.

The human Fallopian tube (FT) is implicated as a site of origin for pelvic serous cancers. Here the authors conduct multi-omics analysis on over 100 FTs. The results challenge the assumption that BRCA1/2 mutation carriers exhibit significant molecular alterations in normal FTs before loss of heterozygosity (LOH) occurs, and suggest that tumorigenesis in BRCA1/2 carriers requires LOH or secondary genetic events rather than haploinsufficiency alone.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

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.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

Suppressing 1/f-shaped low-frequency noise is critical but fundamentally challenging to both electrical and optical transducers. Here, the authors demonstrate a 1/f-noise-free optical sensor with integrated CMOS-compatible heterodyne interferometer and an upconversion amplifying technique, which suppresses the noise by two orders of magnitude.

Sequencing and de novo assembly of seven wild relatives of soybean yields insights relevant to crop domestication and improvement.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

A new paleosol-based CO₂ record from the Chinese Loess Plateau reveals a stepwise decline in glacial CO₂ over the past 2.6 million years and suggests that climate sensitivity remained stable across glacial–interglacial cycles.

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.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

The authors implement a collection of patient-derived xenograft tumors to test cancer drug responses.

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.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

An explainable deep-learning system prospectively predicts clinical scores for breast cancer risk from multimodal breast-ultrasound images as accurately as experienced radiologists.

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.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

The large-scale analysis of neural cell reconstructions provides a base line for morphological characteristics, and informs diffusion MRI modelling.

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.

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.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Iterative expansion microscopy enables the use of confocal microscopes to uncover nanostructures in expanded yet otherwise intact tissues at a resolution of about 20 nm, as shown with the imaging of periodic amyloid nanoclusters in brain tissue.

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.

Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.

Wafer-scale realization of a nanoscale magnetic tunnel junction hosting a single, ambient skyrmion enables its large readout, efficient switching, and compatibility with lateral manipulation, and thereby provides the backbone for all-electrical skyrmionic device architectures.

An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.

Bispecific antibodies can have advantages compared to antibody cocktails. Here, the authors engineer and characterize two different approaches for generating bispecific SARS-CoV-2 specific antibodies and find that only one design increases antigen-binding and virus neutralizing activities.

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 mechanisms of adhesion between polymers and inorganic materials are not fully understood. Here, authors demonstrate the clear evidence that the surface chemistry impacts the crosslinked structures of resins near the interfaces, resulting in different fracture behaviours and adhesive strengths.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver disease in humans.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

In a phase 2 trial, the combination of gemcitabine, cisplatin and anti-PD-1 led to a clinical complete response in 43% of patients with muscle-invasive bladder cancer, which facilitated bladder sparing and was associated with long-term bladder-intact metastasis-free survival.

Many transcription factors bind to regulatory DNA elements that are distant from gene promoters. These distal binding sites are thought to regulate transcription through long-range chromatin interactions, but, until now, the impact of chromatin interactions on transcription regulation has not been investigated in a genome-wide manner. A new strategy — chromatin interaction analysis by paired-end tag sequencing — is now described for the de novo detection of global chromatin interactions.

Tumour heterogeneity in clear cell renal cell carcinoma (ccRCC) remains to be investigated. Here, the integration of spatial omics, transcriptional and chromatin accessibility profiling at the single-nucleus level and bulk proteogenomics data reveal markers and pathways important for ccRCC.

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.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

The authors develop an RNA sequencing-based platform, PERSIST-seq, to simultaneously delineate in-cell mRNA stability, ribosome load, and in-solution stability of a diverse mRNA library to derive design principles for improved mRNA therapeutics.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

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.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

An analysis of sera samples collected between January and July of 2022 in Hong Kong shows that the effectiveness of both the BNT162b2 and CoronaVac COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 variant infection waned rapidly after the third and fourth doses.