Search

A single-crystalline aluminum nitride seed layer improves crystal alignment in scandium-doped aluminum nitride films, and subsequent removal eliminates polarity mismatch, enabling high-performance film bulk acoustic resonators and wideband filters.

Nav1.7 is a threshold current generator. Here, authors show that Thr1398 underlies the low voltage dependence of hNav1.7, determines its function as a threshold channel. This low-voltage dependence may be exploited to develop Nav1.7 selective inhibitors for pain therapy.

Toxicity of antibody drug conjugates (ADCs) is often caused by off-target shedding of therapeutic payloads due to linker instability. Here, the authors demonstrate that site-specific ligase-dependent conjugation of therapeutic payloads to engineered trastuzumab via a ring-opening linker improves stability compared to conventional HER2- targeting ADCs.

Here they identify a functional Thyroid Hormone protein precursor in ascidian, named ScTG-like, and detected the follicle-like structure for TH synthesis. These findings suggest TG-like proteins are conserved in bilaterians, providing insight into the evolution of TH synthesis.

Femtosecond X-ray solution scattering reveals how solvent environments direct the outcome of ultrafast roaming reactions in bromoform, determining whether transient hot isomers undergo rapid solvolysis or rearrange into long-lived isomeric products.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Marine cloud brightening over the Pacific offsets global warming from aerosol reductions but creates uneven regional cooling and precipitation shifts, revealing complex trade-offs for geoengineering strategies, based on climate model simulations with targeted sea salt injections.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

The Margin Unit of Jezero crater contains olivine with a forsterite content similar to the olivine cumulates in the crater floor, according to an approach which uses X-ray data from the Perseverance rover to analyse monocrystalline olivine composition

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Over the past 40 years, 42% of tropical and subtropical ecosystems have experienced an increase in plant reliance on past precipitation, consistent with greening during the late growing season in drylands and drying during the wet-to-dry period in non-drylands.

Genome assemblies of 100 cultivated and seven semi-wild Gossypium hirsutum accessions provide insights into the evolutionary history of upland cotton and the genetic basis of fiber trait variation.

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.

Arginine addiction induced by argininosuccinate synthase (ASSN1) deficiency has been exploited to treat ASS1-deficient cancers. Here, the authors show an alternative therapeutic approach where ASS1 activity is increased by the pesticide spinosyn A and is shown to inhibit breast cancer cell proliferation.

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.

A genus-wide super-pangenome across 16 tomato species generated by integrating 20 telomere-to-telomere genome assemblies and 27 published genomes identifies structural variants associated with salinity or disease resistance for molecular breeding.

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.

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.

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

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Materials that combine high mechanical strength with stable and reversible switching states are highly desirable for advanced technology applications. Here, the authors reported hydrogen-bond nanoconfined self-destructive polymers that have reversible solid-fluid switching capability at 25 °C and maintain good mechanical properties.

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.

Mechanisms confer to the enhanced cold tolerance in japonica rice have not been fully elucidated. Here, the authors report a homeodomain-leucine zipper (HD-Zip) I transcription factor encode gene CTB5 is responsible for japonica rice cold tolerance by interacting with genes in gibberellin and abscisic acid pathways.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

This study utilized a longitudinal cohort of adolescents to identify distinct brain signatures linked to ADHD symptom trajectories, revealing that specific cortical and subcortical changes correlate with symptom persistence, remission and emergence, enhancing predictive capabilities for ADHD outcomes.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

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.

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.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

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.

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.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

The authors develop textile electronic substrates with tailored stiffness and interfacial affinities by selective and controllable laser-matter interaction, addressing the mechanical mismatch between hybrid electronics and elastic textiles.

Kinetic resolution allows to obtain enantioenriched compounds from racemic mixtures. Here, the authors report a synergistic magnesium catalyst promoting kinetic resolution of an intramolecular vinylogous Michael reaction to access [6.6.5]-tricyclic chiral skeletons.

Disease heterogeneity complicates precision medicine, which focuses on single conditions and ignores shared mechanisms. Here the authors introduce ‘pan-disease’ analysis using a deep learning model on multi-organ data, identifying 11 AI-derived biomarkers that reveal new therapeutic targets and pathways, enhancing patient stratification for disease risk monitoring and drug discovery.