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The gH-associated tropism and entry (GATE) complex consists of glycoprotein H, UL116 and UL141. This complex is abundant on human cytomegalovirus virions and enables entry into human endothelial cells.

The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.

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.

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.

CAR T cell manufacturing faces significant challenges that impact cell quality and in vivo efficacy. This necessitates reliable cellular characterization methods. Here the authors present a real-time, label-free, microfluidic method that profiles cellular biophysical properties and correlates them to activation state and CAR T potency, facilitating the rapid phenotypic cell assessment during production.

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.

Here, in a representative cohort of 7,095 Finnish adults, the authors reveal that gut antibiotic resistance is shaped not only by antibiotic use but also by the microbiome, diet, lifestyle, household income—and is linked to higher long-term mortality.

Authors report MagNet, a plasma extracellular vesicle (EV) enrichment strategy using magnetic beads. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of mass spectrometry of unfractionated plasma.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

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.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Hepatitis B virus (HBV) infection is associated with hepatitis and hepatocellular carcinoma (HCC). Here, the authors show that HBV promotes HCC formation only in response to environmental carcinogens, involving increased IL-33 signaling and regulatory T 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.

Sensitive diagnostics are needed to detect carcinogenic human liver fluke infections. Sadaow et al. here use an immunomics approach to develop field-deployable tests for diagnosing liver fluke infection and its associated liver cancer.

The choroid plexus is a crucial but understudied brain tissue. Here, the authors use stem cells and tissue samples to trace its origins and lineage during pregnancy and to create new models for its support of the developing human brain.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Long non-coding RNAs (lncRNA) are known immune regulators, yet a systemic understanding of their regulatory crosstalk is still elusive. Here the authors establish a platform integrating RNA-binding proteome analyses and protein interactomes to map the lncRNA target network in human primary macrophages to build a searchable atlas of lncRNA.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Around 20% of synonymous sites are conserved in placental mammal genomes, but the evolutionary forces determining this is unclear. This study show that a combination of GC-biased gene conversion, functional constraint, and mutation rate variation has likely shaped synonymous site evolution.

A new algorithm combined with ultrasound imaging allows for the quantification of kidney quality before transplantation, potentially helping to alleviate global demand for kidney transplantation.

Targeting CD8⁺ T cell exhaustion is a strategy to enhance immune checkpoint inhibition and to fight cancer. Here the authors show a NRF2-dependent role for the prostaglandin I₂ receptor PTGIR in controlling T cell exhaustion.

ERK signaling involves complex spatiotemporal dynamics, making it difficult to quantify in many systems. In this study, live-cell activity measurements are combined with multiplexed immunofluorescence in a quantitative framework, allowing ERK dynamics to be quantified within fixed-cell samples.

Dysregulated R-loops can compromise genome stability, leading to pathological consequences. Li et al. demonstrate that R-loop-induced poly(ADP-ribose) polymerase 1 activation orchestrates exonuclease 3′–5′ ___domain-containing 2-mediated R-loop resolution, thereby safeguarding genomic integrity.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

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.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Human enhancers contain a high density of sequence features that are required for their normal in vivo function.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Cheek swabs are widely used in pediatric epigenetic studies, but changes in their cellular composition with age are unclear. Here the authors show that buccal epithelial cells decline with age until adolescence, then stabilize, while variability increases with age, impacting the precision of tools like the PedBE clock in pediatric epigenetics.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

This study presents CSNN, a tool leveraging network homophily and training-free graph neural networks with labels as features to predict drug-target-interactions (DTIs). The model is then experimentally validated on a new dataset of 3773 DTIs from a yeast-based screen on 7 human GPCRs.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

The temporal regulation of intracellular insulin signaling is not well studied. Here the authors conducted a time-resolved analysis of the global insulin-regulated phosphoproteome in human muscle cells, revealing synchronized signaling pathways for propagating information to insulin effector sites.

Aging affects multiple organs and tracking these changes could improve our understanding of disease risk. Here, the authors show that metabolomics-based organ-specific aging clocks can predict future risk of cardiometabolic disease and mortality.

The authors consider the future climate resilience and genomic adaptive capacity of the globally important crop sorghum using 1,937 global accessions. They identify the best potential parents and geographies for crop improvements, and underscore the need for better accessibility of plant resources.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

In this study, three individuals with tetraplegia designed vivid, reliable and object-appropriate sensations with a variety of tactile characteristics using self-selected stimulus parameters that stimulated their somatosensory cortex upon digital object contact

Using 1,854 routinely collected clinical samples from early in pregnancy, with validation in an external cohort, low-coverage cfDNA sequence data identified distinctive features among those who developed preeclampsia.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

Beck et al. conducted single-cell and spatial profiling of embryonal tumors with multilayered rosettes, finding that malignant cellular hierarchies are driven by developmental programs and specific members of the chromosome 19 microRNA cluster.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.