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Ramaglia and colleagues show that aberrant formation of B cell-rich lymphoid structures in the brain meninges is associated with high CXCL13:BAFF ratios. Inhibiting the kinase BTK reduces the lymphotoxin signaling needed to sustain such structures, lowers CXCL13:BAFF ratios and reduces cortical tissue injury.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Small cell lung cancer (SCLC) cells show inherently low antioxidant defenses, making them prone to lethal oxidative stress induced by thioredoxin reductase 1 (TXNRD1) inhibitors. Here, authors demonstrate that activating NRF2 mediated tissue protection allows increased therapeutic dose of TXNRD1 inhibitors to enhances SCLC cell killing in vivo without added toxicity to healthy tissues.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Machine learning–driven optimization of drug candidates remains a central challenge in medicinal chemistry, particularly when attempting to improve potency without relying on external scoring functions. In this manuscript, the authors show that incrementally fine-tuning chemical language models along a structure-activity series enables the de novo design of PPARγ and RORγ modulators that surpass existing ligands in activity, demonstrating that CLMs can internalize SAR relationships and long-range dependencies for prospective molecular optimization.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

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.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

A new cerebrospinal fluid biomarker, AcTau174, was elevated in frontotemporal lobar degeneration with TAR DNA-binding protein (FTLD-TDP), distinguishing this pathology from FTLD-Tau, and was associated with disease severity and progression in FTLD-TDP.

The mechanisms driving reversible dedifferentiation events towards a drug-tolerant persister (DTP) state remain to be explored. Here, multi-omics, information-theoretic approaches and dynamic systems modelling highlight the role of the oxidative-stress–mediated NF-κB/RelA axis in driving the transition towards DTP across multiple cancer types.

Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

Tubulin conservation presents a challenge to understanding microtubules’ diverse functions in eukaryotes. Here, the authors characterize the structures of P. falciparum microtubules to show how evolutionary adaptation of tubulin modulates the material properties of the cytoskeleton.

Antisense oligonucleotides (ASOs) are used in research and therapy. Here, the authors show that PS-modified ASOs bind key DNA repair enzymes and form nuclear condensates that dysregulate the DNA damage response, disrupt DNA repair, and cause toxic DNA lesions, revealing mechanisms underlying ASO-induced toxicity.

Analyses of epidemiological, clinical and molecular data from a prospective cohort of 3,100 patients with esophageal carcinoma suggest intestinal metaplasia as a single precancer pathway preceding the disease.

WIN332 is an HIV-1 Env protein designed to elicit a new class of Asn332-glycan-independent antibodies (type II) to the V3-glycan site of Env. WIN332 immunization rapidly induces type-II V3-glycan antibodies with low inhibitory activity indicative of a neutralization activity in macaques.

Desmoplastic small round cell tumor (DSRCT), a very rare and understudied sarcoma, presents serious challenges for both diagnosis and treatment. Here, the authors employ multi-omics profiling on 30 refractory DSRCT patients to improve the diagnosis and identify potentially actionable targets for individualized DSRCT treatment.

The large-scale analysis of neural cell reconstructions provides a base line for morphological characteristics, and informs diffusion MRI modelling.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

Epigenetic programming of myeloid and CD4⁺ T cells promotes decay of the SIV reservoir in rhesus macaques and a similar molecular pathway is found in HIV elite controllers.

Endocrine-exocrine pancreas crosstalk is known to play a role in pancreatic ductal adenocarcinoma. Here, the authors discover that obesity induces the expression of the peptide hormone cholecystokinin (CCK) in β cells, affecting the peri-islet acinar cells and promoting islet-proximal tumor formation.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

An analysis of whole-exome sequencing data linked to longitudinal electronic health records from 44,028 British South Asians finds new gene–phenotype associations and identifies 2,991 genes with rare biallelic predicted loss-of-function genotypes.

Adsorption of trace transition-metal cations endows common Ca/Mg-carbonates and phyllosilicates with catalytic activity for electrochemical CO2 reduction under planetary conditions, potentially promoting prebiotic chemistry and the origin of life.

The authors reveal how the intrinsically disordered oncoprotein N-Myc dynamically interacts with Aurora kinase A in an inhibitable binding mode that allosterically promotes its activation, offering opportunities to restrict neuroendocrine tumor growth.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Toker et al. present an AI framework that identifies mechanisms of consciousness. The model predicts new drivers of unconsciousness and identifies subthalamic nucleus stimulation as a potential therapy for disorders of consciousness.

DNA recognition and cleavage control in type II topoisomerases are poorly understood processes. Here, the authors determine cleaved and uncleaved structures of supercoiled DNA-bound topoisomerase VI that reveal how the enzyme activates its cleavage state and prefers to act at deformable substrates.

This work describes three people living with HIV-1 who maintain long-term immune-mediated control of HIV-1 after pausing antiretroviral therapy. Autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4⁺ and CD8⁺ T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. This serves as a model of ART-free control of HIV-1 and informs new HIV-1 cure strategies.

In one-shot perceptual learning, what we see can be dramatically altered by a single past experience. Using psychophysics, fMRI, iEEG, and DNNs, the authors identify neural and computational mechanisms underlying this remarkable ability in humans.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Saturation genome editing of RNU4-2 identifies the functional and clinical impact of variants across the entire gene and delineates variants that cause a new recessive neurodevelopmental disorder distinct from ReNU syndrome.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Coulomb explosion imaging provides real space/time resolution of molecular processes. Here the authors develop a generative model to reconstruct molecular geometries from ion momentum measurements which extends the system size accessible with this technique.

Mitochondrial ROS are thought to be involved in NLRP3 inflammasome activation, but how this occurs is unclear. Here, the authors show that cofilin-1 negatively regulates NLRP3 activity by binding it at baseline, but cofilin-1 oxidation by ROS results in dissociation from the complex, thereby releasing NLRP3 activity.

Quantum coin flipping is an essential cryptographic building block for distrustful scenarios. Here, the authors implement this protocol using polarisation-encoded single-photon states and show a quantum advantage compared to both classical realizations and implementations using faint laser pulses.

RAS-driven cancers depend on SHOC2–PP1C. Here, the authors reveal that KRAS forms a low-affinity SHOC2–PP1C complex with fewer contacts than MRAS and show that dual inhibition of KRAS- and MRAS-dependent assemblies strengthens SHOC2 suppression and may overcome resistance.

Simultaneous profiling of adenylated and non-adenylated RNAs reveals regulatory programs across diverse cell types.

C-COMPASS is an open-source software designed to predict the spatial cellular distribution of proteins and lipids from cellular organelle profiling using a neural network-based regression model.

Here authors show Trisomy 21 alters fetal brain development by increasing activity of the RNA-editing enzyme ADARB1, leading to premature RNA editing of key genes involved in early synaptic signaling.

The authors find that distinct radial glia subtypes generate and support midbrain dopaminergic neurons, revealing specialized function and lineage relationships among the diverse cell types that shape dopamine neuron development.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

Particle processing plays a critical role in advancing solid state batteries. Here, authors show how solvent-free mechanofusion enables mixed conducting matrix coatings on cathode particles and relate coating quality to macroscopic mixing stresses for scalable solid state battery manufacturing.

Using active and passive genomic surveillance, researchers observed the rapid spread of high pathogenicity avian influenza H5N1 D1.1 viruses in wild birds during the 2024 migratory season, which coincided with detection in humans, but did not identify mammalian adaptive markers in viruses from wild birds.

Synapse dysfunction contributes to cognitive decline with age. Here, the authors show that aging-related changes in microglia and the extracellular matrix are associated with synapse abundance, extracellular matrix buildup, and cognitive deficits in aging mice.

Regulatory DNA screens often lack nucleotide-level resolution. Here, authors present an end-to-end CRISPR base-editing and sequencing framework that maps regulatory variants at single-nucleotide resolution, revealing enhancer mutations that alter CD19 expression and enable CAR-T therapy resistance.

The origin and composition of stromal fibroblasts in the fibrotic CNS scar are unclear. Here, the authors demonstrate that pericytes and perivascular fibroblasts contribute to fibrotic scarring following spinal cord injury in mice in a region-dependent manner.

For individuals with APOL1 high-risk genotypes, which are enriched in individuals of African ancestry, a nine-protein proteomic risk score enables early prediction of kidney disease progression and may, thereby, enable early intervention.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

SingleBrain integrates publicly available single-nucleus RNA sequencing and genotype data from 983 individuals of European ancestry, mapping eQTLs across major brain cell types and subtypes and providing insights into the genetic regulation of brain disorders.

Researchers applied high resolution inversions of satellite methane observations to estimate methane emissions from 161 countries, finding that global anthropogenic emissions are 15% larger than Paris Agreement reporting.