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Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Authors show that Antarctic glaciers deliver high particle loads to the ocean, rich in iron that is potential food for marine algae. Microscopy techniques reveal this iron interacts with carbon. Ocean tracers show this glacial iron reaches far offshore.

Individual variation in fMRI-derived brain networks is reproduced in a model using only the smoothness (autocorrelation) of the fMRI time series. Smoothness has implication for aging and can be causally manipulated by psychedelic serotonergic drugs.

In the canonical model of auditory processing, thalamocortical inputs to the primary auditory cortex initiate a hierarchical transmission to higher-order cortices. Here, authors reveal alternative auditory pathways that bypass the primary auditory cortex and directly activate higher-order cortex within <10 ms in mice, enabling parallel and distributed processing of fast sensory information across cortical areas.

The dynamics and molecular mechanisms of T cell therapies are probed in cancer organoids.

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.

In Alzheimer’s disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. Here the authors show that, at the myelin–axon interface, axon–glial signaling, paranodal architecture and amyloid-β aggregation are altered in AD, implicating myelin–axon disruption in disease progression.

KEAP1 mutations are frequently observed in NSCLC and lead to drug resistance. Here, the authors show that KEAP1 mutations in lung cancer cells leads to FSP1 upregulation through NRF2, resulting in ferroptosis resistance and radioresistance.

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.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

The authors report TEQUILA-seq, a versatile, easy-to-implement, and low-cost method for targeted long-read RNA sequencing. TEQUILA-seq uncovers transcript isoforms and RNA mechanisms associated with human health and disease.

Nitroxoline is a bacteriostatic quinoline antibiotic, known to form complexes with metals, with few clinical applications. Here, Cacace et al. show that the compound displays a broad activity spectrum, with species-specific bactericidal activity, and acts as a metallophore inducing copper and zinc intoxication in bacterial cells.

Adrenocortical carcinoma (ACC) has limited treatment options and few tumor-specific targets. Here the authors report that the Notch ligand DLK1 is highly expressed in ACC acting as a regulator of tumor cell plasticity and chemoresistance, and that DLK1 can be targeted with an antibody drug conjugate.

The cellular differentiation states of paediatric rhabdomyosarcoma (RMS) remain to be explored. Here, single-cell RNA sequencing analysis of RMS tumours reveals an immunosuppressive microenvironment and distinct transcriptional programs predictive of patient outcomes.

Here, Cilleros-Portet et al. present a large placental methylation database as a tool to explore the genetic burden that acts in prenatal stages, giving insight into neuropsychiatric disorders, and with especial emphasis on schizophrenia.

Griffin et al. present a versatile method for scalable and low-cost sequencing for the construction of epigenetic clocks. They assay 2,892 human or mouse samples, benchmark their method and assess diverse interventions.

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.

The human immune system naturally edits cancers of high-quality neoantigens.

The development of neuroblastoma (NB) is regulated by multiple core transcription factors. Here, SOX11 is identified as a potential epigenetic master regulator upstream of the core regulatory circuitry in adrenergic high-risk neuroblastoma.

Recombinases generated by phage-assisted evolution enhance the efficiency of the prime-editing-assisted targeted integration of large genes in mammalian cells.

The neural circuits in the hindbrain that link satiety and aversion are shown to be separate, raising the possibility of developing obesity drugs without the common side effects of nausea and vomiting.

ER tubules grow and fuse to give the ER its characteristic shape. English and Voeltz show that the small GTPase Rab10 is crucial for ER tubule growth and fusion. Rab10 localizes to the leading edge of new ER tubules with enzymes that promote phospholipid synthesis, suggesting that ER tubule growth, fusion and phospholipid synthesis might be coupled.

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.

The antibody response to infection and vaccination is an essential component of the anti-infective immune response. Here the authors present a de novo protein sequencing method for antibody discovery from polyclonal IgG from human plasma and characterise the antibody response to the Moderna Spikevax COVID-19 vaccine.

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.

Five genome-wide approaches are integrated to give a comprehensive picture of jasmonic acid signalling networks in Arabidopsis. New genes, validated by mutant analysis, and important connections with other pathways are revealed.

Aponte et al. show that cortical direction selectivity to frequency modulated sounds is shaped by asymmetric signal amplification within recurrent circuits. Optogenetics and network modelling demonstrate that this asymmetry arises due to broad spatial topography of SOM cell mediated inhibition.

The authors identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that increases with age and promotes cognitive decline. Targeting FTL1 in the brain improved cognition in old mice.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

scHLApers is an analysis pipeline that quantifies single-cell expression of HLA genes using a personalized genomic reference. Mapping of HLA expression quantitative trait loci at single-cell resolution identifies dynamic effects across cell states.

Martinez et al. identified the protein interactome of the tau seed responsible for propagation. The authors found how the presynaptic protein Bassoon interacts with the tau seed enhancing its stability and subsequently tau toxicity and spreading.

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 multi-modal analysis of pre-metastatic liver biopsies from patients with localized pancreatic cancer with a minimum of 3 years of follow-up shows that immunological, proliferative and metabolomic features distinguish patients who develop metastases from disease-free survivors and can be used to predict outcomes.

SMARCA4/2 loss in ovarian and lung cancers is associated with chemotherapy resistance. Here, the authors show that SMARCA4/2 deficiency in cancer cells reduces the expression of the ER-Ca²⁺ channel IP3R3 and subsequently calcium transfer to the mitochondria, which inhibits apoptotic cell death.

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.

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.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

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.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

The failure of metabolic tissues to respond to insulin is an early marker of type 2 diabetes. Here, the authors show, using global phosphoproteomics, that insulin resistance is caused by a marked rewiring of both canonical and non-canonical insulin signalling, and includes dysregulated GSK3 activity.

Fibroblastic reticular cells (FRCs) provide structural support and soluble factors necessary for proper lymph node organization and function. Turley and colleagues use scRNA-seq to identify a unique Gremlin1-expressing FRC subset that is found in T cell zones. Grem1⁺ FRCs support the survival of resident cDCs and are necessary to promote T cell immunity.

Tracking analyses of tens of thousands of individual chromatophores in freely behaving cephalopods enable studies of behaviour and development at cellular resolution.

Activity in anterior deep cerebellar nuclei reduces food consumption in mice without reducing metabolic rate, potentially identifying a therapeutic target for disorders involving excessive eating.

An integrated genomic analysis of 456 human pancreatic ductal adenocarcinomas identifies four subtypes defined by transcriptional expression profiles and show that these are associated with distinct histopathological characteristics and differential prognosis.

The genomes of 102 primary pancreatic neuroendocrine tumours have been sequenced, revealing mutations in genes with functions such as chromatin remodelling, DNA damage repair, mTOR activation and telomere maintenance, and a greater-than-expected contribution from germ line mutations.