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A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

The genomewide meta-analysis of lumbar spinal stenosis LSS identifies 73 previously unreported loci in addition to 15 known loci and highlights spinal degeneration as a key pathogenic mechanism. Overall, the findings expand knowledge of the genetic background of LSS.

CRISPR screening shows that claudin-4 is a receptor for the pro-carcinogenic B. fragilis toxin on colonic epithelial cells, and that this interaction promotes cleavage of E-cadherin, leading to epithelial barrier disruption and inflammation.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Proton-exchange membrane water electrolysers rely on iridium to catalyse their anodic reaction, and while ruthenium is a less costly alternative due to its similar activity, it is not as stable. Now, a hierarchical machine-learning catalyst discovery workflow, termed mixed acceleration, is put forward to predict catalyst synthesis, activity and stability, and identify promising RuO_x-based water oxidation catalysts.

Oxidative catalytic depolymerization of polystyrene (PS) can produce benzoic acid, but the annual consumption of benzoic acid is ~40 times lower than PS, so benzoic acid should be converted to higher-volume chemicals for the process to be viable. Here, the authors report a hybrid chemical and biological process that uses PS as feedstock for production of adipic acid, a high-volume co-monomer for nylon 6,6, via benzoic acid.

Divergent white matter metabolic patterns reveal a mechanistic basis for cognitive resilience and enhance prediction of future cognitive decline beyond established aging and dementia biomarkers.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

The deactivation of CO₂ reduction electrocatalyst in microbial media remains a key barrier for hybrid bio-electrochemical systems. Here, the authors present a bioadaptive nickel single atom catalyst that resists organic poisoning to enable high-rate CO-mediated isopropanol production from CO₂.

Metastasis-initiating cells can reawaken from a dormant state that initially allowed them to survive, triggering metastatic outgrowth. Here, authors show that loss of Brd7 promotes an immunosuppressive tumor microenvironment that drives breast cancer metastatic reawakening from dormancy in the lung.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Arginine methylation by PRMTs is dysregulated in cancer. Here, the authors use functional genomics screens and identify PRMT1 as a vulnerability in pancreatic ductal adenocarcinoma, and further show that PRMT1 regulates RNA metabolism and coordinates expression of genes in cell cycle progression, maintaining genomic stability and tumour growth.

An inverse design strategy is reported for the organization of nanoscale matter using DNA-programmable bonds and the fabrication of hierarchically ordered 3D assemblies.

Here, the authors systematically interrogate the impact of acute stress on the sexually-dimorphic ventral subiculum circuitry and identify sex-specific synaptic and behavioral adaptations. Critically, these sex-specific adaptations are driven by distinct signaling pathways.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

The presence of all canonical nucleobases in samples from Bennu has previously provided evidence that some of life’s ingredients were synthesized abiotically in the parent body of this asteroid and/or its precedent components. Here, the authors extend research on the distribution of nucleobases and other N-heterocycles in Bennu by using a larger sample and an updated analytical protocol, reporting the concentrations of a diverse suite of N-heterocycles including nucleobases and their precursors extracted from a homogenized Bennu sample.

Pancreatic cancer progression is driven by a switch from HNF4G-driven transcriptional activity in primary disease to FOXA1-mediated transcription in the metastatic setting.

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 this Expert Recommendation, Bowtell and colleagues outline progress made over the last decade in the research and treatment of high-grade serous carcinoma as well as current challenges and research priorities for the coming years to reduce incidence and improve patient outcomes.

T-cell acute lymphoblastic leukemia is a highly aggressive disease with varying recurrence rates. Here, the authors build a single cell transcriptomic atlas of childhood T-cell acute lymphoblastic leukaemia (T-ALL). They identified a distinctive cancer cell state that correlates with high risk, treatment refractory T-ALL.

Spatial transcriptomics and single-cell profiling identify previously uncharacterized cell types of human terminal and respiratory bronchioles, and show that cell differentiation and lineage trajectories are distinct from those in the mouse lung.

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.

This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Mammary gland resident macrophages are known to be crucial components of the mammary stem cell niche. Here, the authors show that CXCR4⁺ macrophages form a niche that regulates the tumor-initiating activity of breast cancer cells and induces early immune evasion through the recruitment of regulatory T cells.

In budding yeast, many inducible genes translocate to the nuclear periphery when activated. Sequence motifs have now been identified in promoters, which target genes to the nuclear periphery and contribute to gene activation

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

The Devonian fossil Tiktaalik roseae represents a transitional form between fishes and tetrapods. This paper presents a detailed examination of the braincase of this creature. Although primitive in many respects, some features nod to the tetrapod state.

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

Mammalian oocytes and embryos undergo major epigenetic changes. Here, genome-wide mapping of the histone variant H2A.Z across mouse oogenesis and early embryogenesis reveals distinct maternal, embryonic and persistent enrichment patterns, linking histone variant dynamics to epigenetic inheritance, repeats and developmental reprogramming.

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.

Targeted protein degradation of cell-surface glycoproteins suppresses cancer in mice.

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.

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.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

Comparison of paired primary and recurrent glioblastomas at the single-cell transcriptomic level describes molecular and cellular trajectories associated with tumor recurrence, highlighting extensive heterogeneity and microenvironmental co-evolution.

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.

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.

Integrated single-cell transcriptomic and genetic characterization of 121 adult glioblastomas identifies heterogeneity at cell type, cell state and baseline expression program levels associated with specific mutations that form three stereotypical ecosystems.