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Synovial sarcoma (SyS) is a cancer driven by a fusion oncoprotein, SS18::SSX, but the mechanism underlying the oncoprotein-mediated tumorigenesis remains unclear. Here, the authors employ transgenic mouse models and multi-omics to show how SS18:SSX modifies the activity and recruitment of BAF-family chromatin remodeling complexes to drive SyS tumorigenesis.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

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.

Optogenetic manipulation of spindle dynamics reveals that microtubule shortening at kinetochores limits spindle elongation rather than moving chromosomes, revealing local chromosome–spindle interactions.

The earliest appearance of mega-body size in sharks is pushed back by 15 million years with the discovery of new fossils from Northern Australia. Using a comprehensive dataset of living sharks to estimate sizes of extinct taxa, results demonstrate that mega-body size is an ancient trait.

DNA methylation is associated with breast cancer risk. Here the authors measure DNA methylation in the blood of individuals from 25 Australian families with multiple cases of breast cancer but not known mutations associated with breast cancer risk to identify possible heritable methylation markers.

A vagal reflex to blood volume changes in the heart involves PIEZO2 and helps to stabilize blood pressure in an upright posture and after blood loss.

Covalent histone modifications have been linked to many DNA processes. The repertoire of modifications is still growing, and histone H3K64 trimethylation is now shown to be localized to pericentric chromatin and its levels dynamically altered during developmental reprogramming in both embryos and primordial germ cells.

A large-scale mouse study reveals that while existing epigenomic data detect many developmental enhancers, a substantial fraction is missed - highlighting the need for expanded resources to fully annotate enhancers genome-wide.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Cancer stem cells (CSCs) are thought to be the main drivers for disease progression and treatment resistance in liver cancer. This study identifies the LGR5+ compartment as an important CSC population, representing a viable therapeutic target for combating liver cancer.

Neoadjuvant immunotherapy can induce promising response rates in patients with localised deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) solid tumours but whether this translates to long term survival benefits is less clear. Here, the authors report long-term survival outcomes and ctDNA analysis of a phase II trial investigating neoadjuvant pembrolizumab in patients with dMMR/MSI-H solid tumours.

The cellular origin of soft-tissue cancers, such as synovial sarcoma (SyS), is unknown. Here, expression of the oncoprotein, SS18::SSX, in fibroblasts was sufficient to produce human-like SyS tumours, thereby identifying a cell of origin for SyS.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

A subpopulation of adaptive immune cells patrols the brain and cerebrospinal fluid in people who have Alzheimer’s disease. This discovery should broaden our understanding of how the immune system can influence neurodegeneration.

Single particle cryo-electron microscopy of membrane proteins is limited by their small size and difficulty to orient. Here the authors generate recombinant antibodies against the 12 kDa fusion partner BRIL domain from apocytochrome b562 to use them as plug and play fiducial marks for structure determination of BRIL fused membrane proteins.

When hominins dispersed into Eurasia is unclear. Here, the authors present multiple cut-marked bones from Grăunceanu, Romania dated to at least 1.95 million years ago and suggest hominins would have lived in a temperate and seasonal environment.

Superlubric arrays of double-bilayer graphene enable elastically coupled switching between Bernal and rhombohedral graphene polytypes under shear forces below 1 nN with an estimated energy cost of less than 1 fJ per switching event.

Inhibition of the histone methyltransferase NSD2 and the androgen receptor in preclinical models can reverse lineage plasticity to suppress tumour growth and promote cell death in multiple subtypes of castration-resistant prostate cancer.

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.

Centromeres ensure chromosome segregation. Analyzed sister species with distinct centromere types show that kinetochore mutations, histone modifications, and centromeric DNA amplification underlie the process of mono- to holocentromere evolution.

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.

Macrophages are critical for granuloma formation, but the cell-intrinsic mechanisms remain unknown. Weichhart and colleagues demonstrate that chronic mTOR activity leads to macrophage-dependent granuloma formation, which may have relevance to sarcoidosis.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

In mdx mouse fetuses, the lack of dystrophin markedly impairs secondary myogenesis due to reduced muscle stem cell polarity. AAK1 deletion restores polarity and rescues secondary myogenesis, revealing fetal onset in Duchenne muscular dystrophy.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

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.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Metabolomics, metagenomics, proteins and genetics were combined with clinical data to define a metabolic signature of obesity.

Nshanian et al. investigate the differential effects of the short-chain fatty acids propionate and butyrate on chromatin remodelling and gain insight into the mechanisms that drive selective histone acylation.

A comprehensive benchmarking of 19 histopathology foundation models finds that a vision-language foundation model outperforms vision-only models.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

Floquet engineering is often limited by weak light–matter coupling and heating. Now it is shown that exciton-driven fields in monolayer semiconductors produce stronger, longer-lived Floquet effects and reveal hybridization linked to excitonic phases.

DNA data storage is an alternative to silicon-based data storage, but it demands advanced encryption and readout techniques. Here, the authors present an enhanced DNA origami cryptography protocol for data storage, using DNA-PAINT super-resolution imaging and unsupervised clustering to retrieve information in DNA cryptography.

Cadherin-based junctions connect cells to support tissue architecture. Here, the authors show that the condensation of core component β-catenin organizes cadherin complexes into clusters to promote formation of new adhesions.

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

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Mapping of spatial metabolic gradients in the mouse liver and intestine identifies fructose-induced focal derangements in liver metabolism.

Reagents that recognize specific chemical modifications while ignoring the surrounding protein offer valuable proteomic insights.

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.

A new mechanism is identified for correct placement of the division machinery in Streptococcus pneumoniae that relies on the novel factor MapZ to form ring structures at the cell equator; these structures move apart as the cell elongates, acting as permanent markers of division sites.

The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.