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Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

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.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

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.

Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

This study of magic-angle twisted trilayer graphene moiré superconductors using scanning tunnelling microscopy and spectroscopy identifies two energy gaps that develop from many-body resonance in this highly tunable class of materials.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

Exercise has considerable health benefit, including modulation of the immune system. Here the authors compare the molecular make-up of peripheral blood immune cells at resting state and upon a single bout of two different aerobic exercise modes by proteomics and show that although both exercise modes trigger similar changes, the effect is more pronounced after high intensity interval training.

Distinct neuron subtypes compartmentalize specific functions by differentially localizing and translating specific RNAs. This work identifies dynamic subtype- and stage-specific growth cone molecular machinery during neocortical circuit development.

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.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Experimental realizations of discrete time crystals have mainly involved 1D models with Ising-like couplings. Here, the authors realize a 2D discrete time crystal with anisotropic Heisenberg coupling on a quantum simulator based on superconducting qubits, uncovering a rich phase diagram.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

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.

A classical device generates states with no relative superposition. Here, authors introduce models to simulate sets of quantum states by stochastically combining classical devices. They present an avenue to understand to what extent quantum states defy generic models based on classical devices.

This study finds that native tree extinctions and alien naturalizations are pushing forests towards fast-growing, resource-demanding species. This global shift could affect carbon storage and ecosystem stability, highlighting the need to protect slow-growing trees.

Systematic screening of transcription factors reveals conserved mechanisms governing cortical radial glia lineage progression across primates and provides a framework for functional dissection of gene regulatory networks in human cortical neurogenesis.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

This study examines long-term changes in species richness across tropical forests in the Andes and Amazon. Hotter, drier and more seasonal forests in the eastern and southern Amazon are losing species, while Northern Andean forests are accumulating species, acting as a refuge for climate-displaced species.

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.

A cellular neural network that incorporates transistors and multilevel non-volatile memristor synapses can be used for efficient image and video processing.

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.

While the photoreceptor outer segments in the bird outer retina have access to oxygen, the inner retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

The use of antimicrobial agents can exacerbate the proliferation of antimicrobial resistance genes, which can put public health at risk; evaluating this risk requires proper monitoring. An extensive investigation of Australian wastewater reveals a distinct correlation between the type of antimicrobial used and the socioeconomic status of the population.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

Genetic variants of TREX1, a negative regulator of type I interferon responses, have been linked previously to non-monogenic systemic lupus erythematosus (SLE). Here the authors analyze UK Biobank multi-omics data to show that, while a derived oligoprotein interferon signature associates with increased SLE risk, TREX1 variants do not.

This study finds stem-like endothelial cells in the optic nerve that supply and repair retinal blood vessels after injury, revealing a hierarchical repair system that may enable new treatments for blinding vascular eye diseases.

Neri et al. develop elegant tools to understand how the sympathetic nervous system regulates intrascapular brown adipose tissue (iBAT) function. Using these tools, they find that sympathetic nerves targeting the iBAT parenchyma control local blood flow and heat production, while those innervating the iBAT vasculature regulate systemic glucose metabolism.

Comparative genomics and high-resolution mass spectrometry reveal the biosynthetic gene clusters, and vast chemical diversity of natural products that they encode, in Photorhabdus and Xenorhabdus, bacteria that interact with hosts as symbionts and entomopathogens.

Nuclear envelope (NE) rupture triggers cancer genome instability and inflammation, but mechanisms of NE repair are unclear. Here, the authors map the NE repairome and identify LRRC59 and KPNB1 as a key regulatory axis to restrain NE repair activity.

Here natural language processing tools are used to systematically analyse 124 national food system pathway documents submitted by countries between 2021 and 2023, following the 2021 United Nations Food Systems Summit. Besides drawing out key themes, the authors reveal key issues that remain unaddressed.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.