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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

This research finds a strong recency bias in information gathering, attenuated in those on the OCD spectrum—a possible mechanism for indecisiveness. Behavioural and MEG data show reduced evidence updating in high-OC individuals.

Quantitative image-based cytometry and spatial analysis of proliferation reveal how multiple signalling pathways integrate over time to coordinate both cell cycle entry and exit in epithelial monolayers.

The Evaluation and Enhancement (EVEN) method optimizes automatically the quality of multichannel microscopy images affected by uneven illumination, enabling accurate visual interpretation and image analysis in challenging imaging scenarios.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

The slit diaphragm is a key component of the glomerular filter. This study reveals that the slit diaphragm of Drosophila nephrocytes exhibits a fishnet architecture, offering insights into the molecular basis of renal filtration.

Treatment strategy of solid tumors requires continuous development. Here the authors develop a Macrophage Drug Conjugate (MDC) platform by loading ferritin-drug complexes to macrophages. MDC transfers the ferritin to cancer cells via ‘TRAnsfer of Iron binding protein’ (TRAIN) process and reduces tumor volume in various mouse tumor models.

Cells actively sense external and internal signals to stay quiescent or proliferate, and this trigger relies on being in a reversible primed G1 state of partial retinoblastoma inactivation and E2F activation.

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.

Epicardial engineered heart muscle allografts from induced pluripotent stem cell-derived cardiomyocytes can safely and effectively remuscularize chronically failing hearts in rhesus macaques, leading to improved cardiac function and paving the way for human clinical trials.

This research quantifies hospital admissions in Shanghai for mental and behavioral disorders linked to humid heat, projecting a 68.2% increase by the 2090s under high greenhouse gas emissions and emphasizing the importance of mitigation strategies to reduce future morbidity burdens.

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.

ChReef is an optogenetic actuator for sustained optogenetic control of excitable cells in a variety of preclinical applications.

This study examines the outcomes of dietary shifts across intrinsic and instrumental conservation perspectives, finding that most conservation benefits already come from a partial shift to healthier, more plant-based diets, whereas greater benefits depend on more targeted conservation action.

Protein aggregates are associated with a wide variety of diseases. Here, in order to address how protein aggregation affects cellular homoeostasis, the authors describe a method to rapidly create protein aggregates in living cells and organisms with precise spatial and temporal control.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Annular dark field scanning transmission electron microscopy is able to distinguish the contrasts between light elements. Here, the authors directly image the bonding configurations of oxygen and nitrogen atoms in defective graphene, and surprisingly identify instances of unusual triple-coordinated oxygen with three carbon neighbors.

Here the authors provide a deep tissue analysis of patients with autoimmune kidney diseases, identifying a conserved spatiotemporal immune program for the development of glomerular crescents and sclerosis.

Arrays of quantum dots can exhibit a variety of quantum properties, being sensitive to their spacing. Here, the authors fine tune interdot coupling using hexagonal molecular networks in which the dots are separated by single or double haloaromatic compounds, structurally identical but for a single atom.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

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.

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.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Hayer et al. observe that collectively migrating endothelial cells extend rear VE-cadherin-rich membrane structures that are engulfed by follower cells, correlating spatially with the direction of movement.

Hydrofunctionalization of α-olefins with mineral acids usually proceeds with Markovnikov selectivity. Now, a strategy based on synergistic phase transfer and photoredox catalysis is developed to facilitate anti-Markovnikov addition of aqueous hydrochloric and nitric acid to unactivated alkenes.

Persistent DNA damage is a hallmark of senescence. Here, the authors show that senescent cells accumulate DNA damage due to transcriptional stress and are unable to repair DNA damage due to the absence of cell-cycle regulated DNA repair programs.

CHIMERYS is a spectrum-centric and data acquisition method-agnostic algorithm for the analysis of MS2 spectra. It is capable of deconvoluting any MS2 spectrum, regardless of whether it was acquired by DDA, DIA or PRM, thus unifying the analysis of bottom-up proteomics data.

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.

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.

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.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

How normal cells proliferate without CDK4 and CDK6, two cancer-driving kinases, remains unclear. Here, the authors show that without CDK4/6 activity, cells start the cell cycle with a different signaling order and commitment point, revealing unexpected flexibility in cell-cycle entry mechanisms.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Podocytopathies are kidney diseases characterized by serum protein loss into the urine, and can lead to chronic kidney disease. In this Primer, the authors describe the epidemiology of this disease group, its six subtypes, diagnosis and management approaches. They also highlight effects on quality of life and future research areas.

The authors leveraged a large multimodal sample and combined normative modeling and linked independent component analysis to study a cross-modal signature of face processing within the fusiform gyrus in autism.

Aberrant redox homeostasis links lipid metabolism and cell death programs. Here, authors reveal how cell stress reduces growth factor signaling, enriching polyunsaturated fatty acids in phospholipids and sensitizing membranes to oxidative damage.

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.

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.

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.