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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.

A mode of bidirectional microglia–neuron crosstalk through Hex–GM2–MGL2 and centred around GM2 ganglioside turnover is essential for homeostatic regulation of central nervous system membrane components.

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.

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.

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

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.

Our understanding of chromosome organization and dynamics in spherical bacteria, such as Staphylococcus aureus, remains limited. Here, the authors show that chromosome replication and cell division cycles are not synchronized in S. aureus, with cells exhibiting two segregated origins of replication at the start of the cell cycle.

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.

Ca2 + -ATPases in the plasma membrane extrude Ca2+ ions from the cytosol to the extracellular space and thus terminate Ca2 + -signals and control Ca2 + -homeostasis. Here, Constantin et al. show that these pumps operate at rates of more than 5000 cycles/s.

Candida albicans normally relies on specific pathogenicity mechanisms to cause tissue damage. This study reveals that when sensing host albumin, C. albicans, even avirulent strains, can trigger an alternative pathogenicity pathway via transcriptional and metabolic reprogramming.

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

The slit diaphragm is a key component of the glomerular filter. This study reveals that the slit diaphragm of Drosophila nephrocytes exhibits a fishnet architecture, offering insights into the molecular basis of renal filtration.

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.

Genomic integration of DNA templates is made more precise through microhomology-focused design.

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.

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.

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.

In glioblastoma (GBM), tumour microtubes (TM) connect tumour cells to a broader cellular network, with roles in tumour progression and therapy resistance. Here, the authors combine a dye uptake method in GBM xenograft models with subsequent scRNA-seq to infer a TM connectivity signature, finding CHI3L1 as a marker of connectivity.

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.

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.

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.

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.

By investigating the paradoxical retention of a photolyase gene in a light-deprived blind cavefish, the authors reveal a novel light-independent function for CPD photolyase in the repair of oxidative stress-induced DNA damage

Activation of G_s signaling at mitochondria by mitoDREADD-G_s increases mitochondrial metabolism, leading to better memory in mouse models of dementia, directly linking brain mitochondrial deficits to cognitive symptoms of neurodegenerative diseases.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

Li et al. discovered that the cytotoxic synthetic small molecule BRD1732 is directly ubiquitinated in cells. Ubiquitination of BRD1732 is E3 ligase dependent and leads to inhibition of proteasomal degradation.

The authors present a novel channel rhodopsin variant with enhanced Ca²⁺ conductance in megakaryocytes and platelets.

Current antimalarials often fail to target mature stage V gametocytes. To aid antimalarial drug discovery, the authors present a preclinical malaria transmission-blocking drug research platform, using engineered parasites, that facilitates the screening for gametocytocidal compounds in vitro and the evaluation of transmission-blocking drug activity in vivo.

Carbohydrate esterases alter polysaccharides by removing ester groups. Here, the authors resolved crystal structures of two CE20 enzymes and discovered a novel, water-mediated catalytic triad essential for activity, offering insights into enzyme function and mechanism.

Mast cells are shown to function as sensor cells linking antigen recognition in type 2 immunity to antigen-specific avoidance behaviour, preventing immune activation and inflammation.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

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.

Streptococcus pneumoniae, the causative agent of pneumococcal disease, has become increasingly resistant to fluoroquinolones. Through CRISPRi-seq, the authors identify the role of the LiaFSR operon in resensitizing S. pneumoniae to fluoroquinolones.