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The DNA-dependent protease SPRTN cleaves toxic DNA-protein crosslinks (DPCs). Here, the authors show that SPRTN is activated by DPC-ubiquitylation through an allosteric ubiquitin binding interface. This regulatory mechanism enables precise control of SPRTN activity during DNA repair.

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

Membrane budding plays pivotal roles in cellular processes, but a fully artificial system mimicking natural budding processes remains elusive. Here, the authors report a DNA origami-based membrane budding system that recapitulates key aspects of clathrin-mediated endocytosis without relying on components of cellular budding machineries.

In this work, we focused on Wadsley–Roth phase TiNb₂O₇ with an octahedral network as a negative electrode material for lithium-ion batteries and investigated the effect of the network structure, which is considered to form Li⁺ conduction pathways, on the electrode properties. To this end, we prepared samples with different charge/discharge properties and generated atomic configurations that simultaneously reproduce both total scattering and Bragg profile data. Topological analyses based on persistent homology demonstrated that the network disorder significantly degrades the electrode properties.

Transcription factors shape cell identity, but mapping their genomic targets remains challenging. Here the authors present DynaTag, a modified CUT&Tag method for profiling TF occupancy in bulk and single cells, and apply it to assess changes in TF activity in SCLC tumours following chemotherapy.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

Engineering structurally and functionally complex synthetic cells remains a key challenge. Here DNA condensate synthetic cells combine phase separation and DNA nanostructures to reveal how switchable artificial cytoskeletons assemble in viscoelastic confinements. These cytoskeletons improve the mechanical properties of synthetic cells and enable stable mechano-interfaces with mammalian cells.

Myeloperoxidase, a highly expressed neutrophil protein, disassembles nucleosomes, facilitating neutrophil extracellular trap (NET) formation, and binds stably to NETs extracellularly.

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.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Polymer electrolytes are promising candidates as separators in lithium metal batteries. Here, authors reveal the existence of local lithium-based crystallites inside the polymer electrolyte in a lithium symmetric cell. A combination of unique operando wide-angle X-ray scattering with a nano-sized beam and complementary spectroscopic techniques identifies these crystallites as lithium carbonate, lithium hydroxide, and even metallic lithium. It is shown that these crystallites lower the ionic conductivity and the transference number.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.

By combining left- and right-handed DNA-PAINT probes, Unterauer et al. achieve simple, robust, and highly multiplexed super-resolution. They show 13-plex neuronal maps, revealing nanoscale organization of cytoskeleton, organelles, and synapses.

RNA base editing represents an exciting modality in precision genetic medicine. Here the authors develop short, metabolically stable RNA oligonucleotides (RESTORE 2.0) that enable precise and efficient RNA base editing, demonstrating successful in-vivo correction of a disease-causing human mutation.

The involvement of cell death pathways in the early stage of pancreatic ductal adenocarcinoma (PDAC) development, especially KRAS-dependent acinar-to-ductal metaplasia (ADM), remains to be investigated. Here, the authors find that TAK1 mediates cell survival during ADM transdifferentiation through suppression of apoptosis and necroptosis, which could be targeted for prevention and treatment of PDAC.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Genomic and biochemical analyses of prokaryotic sulfur metabolism identify diverse microorganisms with the capacity to oxidize sulfide using iron(iii).

Gut microbiota contribute to the pathogenesis of ulcerative colitis (UC), but the molecular mechanisms are still unclear. Here the authors show that colonic fluid from patients with UC is enriched for bacteria extracellular vesicles (BEV) coated with host IgA, and that these IgA-coated BEV may activate CD89⁺ immune cells to aggravate inflammation and colitis in mouse models.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

Conventional Dendritic cells (cDCs) continually migrate from peripheral tissues in homeostasis. Here, the authors analyse the homeostatic turnover of cDC subsets in the intestine from tissue entry to migration to the draining lymph nodes, noting a dynamic life cycle with changes in transcriptome and proliferation rates.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

Niobium tungsten oxides block structures, consisting of ReO3-type blocks of specific sizes, are promising fast-charging negative electrode materials. Here, the authors propose a partially disordered Nb12WO33 structure that enhances the Li-ion storage performance.

Polyproline motifs induce ribosome stalling during translation. Here, Ignatov et al. identify RNA-binding proteins in the pathogenic bacterium Streptococcus pyogenes, and show that one of these proteins, YebC, acts as a translation factor enhancing translation of proteins with polyproline motifs.

As the military alliance created to counter the Soviet Union expands, it is prioritizing studies on how climate change affects security, cyberattacks and election interference.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Reliable measuring the voltage dynamics of individual neurons in the intact brain is significantly challenging. Here authors developed an all-optical method combining two-photon voltage imaging and optogenetics to measure and induce synaptic plasticity in vivo, revealing LTP of inhibition in cerebellar circuits and providing a blueprint to link synaptic changes to learning.

A cell surface reporter that binds to a fluorine-18-labelled radioligand enables the monitoring of CAR T cells and gene therapy vectors in preclinical models using PET imaging.

Gross et al. show that Atg13 and Atg17 are dispensable for pexophagy during phosphate starvation in yeast. Instead, the metabolite sensor Pho81 binds the Atg1 kinase complex via Atg11 to promote Atg11 phosphorylation by Atg1 and pexophagy.

Iridoids are terpenoid metabolites found in thousands of plants. Using single-cell transcriptomics, the authors discovered an unexpected enzyme that has been neofunctionalized to catalyse the cyclization required to form the iridoid scaffold.

An optical sieve—an array of optically resonant voids in gallium arsenide—enables sorting, detecting and counting nanoplastics as small as a few hundreds of nanometres at concentrations as low as 150 μg ml⁻¹ in lake water samples.

Augmin is essential for microtubule nucleation during cell division. This study reveals how the conserved calponin homology domain of the augmin subunit HAUS6 binds to microtubules to orient augmin for microtubule branching.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

The durability of Fe-N-C single-atom-catalysts for oxygen reduction in acidic medium remains elusive. Here, the authors report how a low amount of platinum stabilizes the FeN4 sites via a long-range electronic effect.

Tutas et al. show an unconventional role for autophagy in the regulation of glycolytic flux in cerebellar Purkinje cells by maintaining the levels of the glucose transporter GLUT2.

The Candida albicans toxin, candidalysin, is embedded in an unusual conserved precursor peptide sequence (Ece1). The precursor is not required to block premature pore-forming toxicity, but rather to prevent candidalysin auto-aggregation.

Zangari et al. show that d-cysteine targets NFS1, thus affecting Fe–S cluster biogenesis and impairing tumour growth.

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.

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.

Withanolides are plant steroids with potent bioactivities found in many medicinal plants including Withania somnifera, but their biosynthetic pathway is largely unknown. Here, the authors report the genome assembly of W. somnifera and reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.

The function of DNMT1 (DNA methyltransferase 1) in these subsets of immature, migrating cortical inhibitory interneurons is not fully understood. This study shows that DNMT1 regulates cortical development by orchestrating the migration of postmitotic SST+ interneurons and their signaling to cortical progenitors, with implications for proper cortical architecture and function.

The catalytic mechanism of [Fe]-hydrogenases is not well understood. Now a signal-enhanced nuclear magnetic resonance method based on parahydrogen is introduced to study [Fe]-hydrogenase under turnover conditions in situ, revealing intermediates of the catalytic cycle.

The enzymatic breakdown of the lipid sphingomyelin is associated with various infectious diseases. Here, the authors introduce trifunctional sphingomyelin derivatives for the visualisation of sphingomyelin distribution and sphingomyelinase activity in infection processes.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Gebhardt and colleagues developed a computational method using a naïve Bayes classifier to identify optimal protein labelling sites. Their analysis of 100+ proteins revealed four predictive parameters, leading to a Python package and a web-tool for protein structure analysis and labelling score calculations.