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The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

This study analyses whole-genome sequencing data of cancer samples from 10,983 patients and explores relationships among mutational signatures, various biomarkers and clinical outcomes.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Highly pathogenic avian influenza H5N1 viruses are of global concern. This study shows that a low-dose H5N1 clade 2.3.4.4b Alum/CpG-adjuvanted vaccine elicits broad, durable antibody and T cell responses and protects female mice against lethal homologous and heterologous H5N1 challenges.

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

Icosahedral viruses package their genomes into a proteinaceous capsid to near crystalline density. Here, the authors report cryo-EM-based insights into the post-packaging genome positioning, virion assembly and maturation mechanisms in the tailed bacteriophage T4.

How is specific ribosomal RNA expression precisely controlled in the malaria parasite? Dr. Couble et al. show that a switch between distinct energy-generating pathways during parasite development directly impacts the accessibility to rDNA chromatin.

Neuroimmune interactions are important in amyotrophic lateral sclerosis (ALS). Here the authors characterize the role of NK cells in mouse models of ALS, and in patient tissue.

The meningeal compartment communicates with the brain to modulate homeostatic functions. Here, the authors demonstrate that natural killer (NK) cells and innate lymphoid cells (ILC) 1 shape synaptic neuronal transmission and affect mouse behavior.

Despite high morbidity and mortality, there are currently no approved vaccines for protection against Middle East respiratory syndrome (MERS) coronavirus. Here the authors develop a ferritin nanoparticle-based MERS-CoV vaccine that elicits high levels of neutralizing antibodies in mice, non-human primates, and alpacas and prevents infection in an alpaca challenge model.

Yashinskie, Zhu and colleagues show that p53 activation triggers increased synthesis and accumulation of phospholipids, with enhanced activation of autophagy and lysosomal catabolism programmes and increased reliance on lipid headgroup recycling.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Drugs that rescue function of episodic ataxia 1 (EA1) mutant potassium channels are lacking. Here, Manville et al identify and describe the molecular basis for Native American botanical ataxia remedies that directly rescue EA1 mutant channels.

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

The phase 2/3 DEVOTE trial demonstrated that high-dose nusinersen significantly improved motor function and was safe in patients with spinal muscular atrophy, compared with a matched sham control.

Vestibular schwannomas that are caused by genetic mutations in the NF2 gene are hard to treat and lead to hearing loss. Here authors show in a mouse model that faithfully represents the human condition that combination therapy with anti-PD-1 and anti-VEGF inhibits tumor growth via normalizing the tumor vasculature and enhances T and NK cell antitumor cytotoxicity via upregulation of NKG2D.

In this study, Dahmane et al use a method called cryo-electron tomography to uncover new details of how tick-borne flaviviruses transform cells into virus factories.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

Here authors report Syngap1 loss or reduction in mice does not affect cortical progenitors, unlike in human organoids. This suggests some species-specific differences but still supports synaptic dysfunction as the most probable cause of SYNGAP1-related disorders.

Dynein–dynactin–cargo adaptor complexes typically function with two dynein motors. Rao et al. show that, under mechanical load, these complexes can recruit a third dynein via a second adaptor, increasing force generation.

A resource of human RNA-protein associations is produced using a sequencing-based method.

Paul and colleagues report the development and characterization of an antibody–drug conjugate targeting TRBC2 for the treatment of T cell malignancies.

DNA damage threatens genome stability, but its dynamics in living systems remain difficult to track. Here, the authors engineer MCPH1-based protein probes that specifically recognize γH2AX, enabling real-time visualization and mapping of DNA damage across diverse cellular and organismal contexts.

Allelic losses occurring in cancer cells have been suggested as potential targets for therapy. Here, the authors show how recurring loss of heterozygosity of a drug metabolic gene in colorectal cancers can be exploited using a low molecular weight compound.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

This study applies generalized linear mixed models (GLMM) and advanced transcriptome wide association study (TWAS) methods to improve the discovery of colorectal cancer risk transcription factors and genes, including potential druggable targets.

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.

Dysregulated protein levels can cause disease. The authors present a scalable platform capable of identifying small molecules that alter disease-linked target protein levels, and report >40 that increase SynGAP protein abundance, with SR1815 restoring neuronal function in Syngap1 deficient neurons.

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

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.

The sequential recruitment of a thalamocortical transcriptional cascade enables memory maintenance over long timescales.

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuropathy.

The evolutionary dynamics of aneuploidy in solid tumors are challenging to study. Here the authors introduce a method, ALFA-K, which estimates karyotype fitness and predicts emergent karyotypes before experimental detection, and test its performance on synthetic and empirical data.

The Greenland shark, the longest-living vertebrate, inhabits the dim, frigid depths of the Arctic Ocean. Despite its extreme lifespan, this study finds that its vision remains intact and well-adapted for life in dim light, revealing remarkable preservation of sensory function across centuries.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

The order in which driver mutations of colorectal cancer occur in intestinal epithelium can determine whether clones are positively or negatively selected and can shape subsequent tumour development.

Mechanical confinement of cancer cells at the tumour–microenvironment interface induces phenotype switching through chromatin remodelling by HMGB2, leading to a more invasive and drug-resistant state in melanoma.

Specificity in interactions with otherwise common glycan structures is likely achieved through glycan context. Here, the authors show that such glycan context is generated through tunable glycan arrangements that are translated into function by galectins.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

An RNA-binding protein on leukemia cells provides an effective target in mouse models.

Structural analyses of antibody-virus complexes offer critical insights into immune recognition mechanisms. In this report, we present how a patient-derived IgG recognizes a quaternary epitope on EEEV particles through strictly bivalent interactions.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

SmartEM is a ‘smart’ pipeline for electron microscopy-based data acquisition for connectomics. In order to efficiently image large datasets, the approach involves imaging at short pixel dwell times and identifying problematic regions that are then imaged with longer dwell times and therefore higher quality.

SARS-CoV-2 spike protein mediates viral entry into host cells. Shi et al. report a cryoEM structure of a proteolytically processed spike, possibly representing a functional intermediate state, with important implications for intervention strategies.

A molecular glue induces CRBN homodimerization and degradation through degron mimicry, revealing a distinct glue mechanism and offering a tool to study CRBN biology.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.