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The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

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.

IκBζ is a rather unknown transcriptional co-factor of NF-κB. Here, the authors show that constitutive IκBζ expression in a subgroup of patients with melanoma drives immunotherapy resistance and enhanced tumor growth.

A single dose of the anti-sporozoite monoclonal antibody CIS43LS can achieve durable, sterile protection against Plasmodium falciparum infection.

Snakes are capable of non-planar gaits, such as sidewinding. Now observations of juvenile anacondas reveal another non-planar gait resembling an S shape. Calculations show how topological dynamics of active filaments enable such movements.

Hepatocellular carcinomas (HCC) present spatial intratumour heterogeneity (sITH). Here, the authors perform a genomic and phylogenetic analysis of spatially-sampled HCC tumour sections, observe block-shaped sITH, and find ongoing natural selection where ancestral and derived clones spatially compete in the same tumor.

Song et al. developed a computational tool to profile binding pairs between tumor-derived antigens and antibodies from high-throughput B cell receptor sequencing data, predicting response to immune-checkpoint inhibitor therapy and risk of adverse events.

When senescent cells accumulate during adulthood they negatively influence lifespan and promote age-dependent changes in several organs; clearance of these cells delayed tumorigenesis in mice and attenuated age-related deterioration of several organs without overt side effects, suggesting that the therapeutic removal of senescent cells may be able to extend healthy lifespan.

Tacrolimus is a critical immunosuppressant for liver transplant recipients, but its dosing is challenging due to individual variability. Here, the authors show that a phenotypic personalized medicine approach improves tacrolimus dosing precision, reducing large deviations from target levels and shortening hospital stays in a Phase 2 randomized trial.

The authors combine fossil occurrence data, phylogenies and climatic niche modelling to explore the palaeobiogeography of early pterosaurs and their non-flying close relatives, the lagerpetids.

Stable microRNAs (miRNAs) can undergo turnover via target-directed miRNA degradation (TDMD). Here, the authors show that TDMD triggers in non-coding regions degrade miRNAs more effectively than those in coding regions, where translation interferes with this process.

Clarke et al. identify chromatin factor ZNF280A, which is recruited to damaged chromatin where it promotes long-range DNA-end resection. Loss of ZNF280A is linked to genome instability in patients with 22q11.2 distal deletion syndrome.

Polymersomes with surface-integrated nanoparticles have potential in a range of applications, but are challenging to prepare. Here, the authors report a method for the preparation of such polymersomes by a hierarchical phase separation approach.

The authors describe a sensory circuit involving the medial septum (MS), where MS glutamatergic neurons integrate food odours to prime satiety and regulate nutrient intake.

By combining modelling and simulated data with empirical data from 76 grassland sites across 6 continents, the authors show that the relative abundance of dominant species predicts species richness, while their absolute abundance predicts community biomass.

A product-oriented strategy that leverages the reactivities of different functional groups in real-life plastic mixtures can be used to obtain valuable products, opening a path for managing end-of-life plastic mixtures.

Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

A genomic study of 125 individuals from the Carpathian Basin (4800–3900 BCE) reveals different kinship systems in nearby Copper Age communities, and highlights both genetic continuity and contrasting patterns of social organization.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Ecological assemblages may be spatially organized by both context dependency and general processes. Here the authors find general patterns in the organization of regional biodiversity in biogeographical regions.

The identification of two cryptic species of the fungal pathogen that causes white-nose disease in bats highlights the need to integrate studies of genetic variability in pathogens into disease surveillance, management and prevention strategies.

The antiviral protein SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of the immune regulator RESIST.

Liu et al. developed a platform to identify transcription factors (TFs) that turn stem cells into desired cell types. They discovered six key TFs that produce microglia efficiently, enhancing cell differentiation methods.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

Individuals with symptoms of anxiety and depression exhibit persistent underconfidence. Here, the authors show that distortions in learning from local metacognition can explain how underconfidence is maintained in the face of intact performance.

In many sexually reproducing animals, the oocyte fuses with only one sperm during fertilization. Here, the authors show that C. elegans MARC-3, a membrane-associated RING-CH-type ubiquitin ligase, regulates polyspermy block after fertilization and maternal membrane protein degradation during the oocyte-to-embryo transition.

During early development, cells collectively sculpt the embryo’s geometry and establish the body plan. This study uncovers modular mechanisms independently controlling embryo size and shape in avian gastrulation—a model for early human development.

A common but untested expectation is that nutrient enrichment causes biotic homogenization. However, a globally standardized nutrient addition experiment in grasslands shows proportionally similar species loss across scales and no biotic homogenization after up to 14 years of treatment.

Nodelman, Folkwein et al. define a regulatory region in Chd1 containing adjacent inhibitor and activator elements that compete for binding to the remodeler ATPase. The competition between these elements shows how remodeler regulation is integrated into the nucleosome sliding cycle.

The development of efficient actuators and the understanding of their mechanisms is crucial for improving their application. Here, the authors develop a self-standing film of an ionic covalent organic framework which undergoes a reversible photoactuation following a triple energy conversion cascade in a short time.

Gradients of cell recognition molecules wire a sensorimotor interface in Drosophila.

Multimodal results (iEEG, fMRI and MEG) of predictions from integrated information theory and global neuronal workspace theory align with some predictions of both theories on visual consciousness, but also critically challenge key tenets of both theories.

Developing high-productive and energy-saving systems in formate electrosynthesis is attractive but challenging. Here, the authors report an efficient Rh-dispersed In₂O₃ catalyst for CO₂ reduction, benefiting the ampere-level formate coproduction when pairing with anodic aldehyde oxidative dehydrogenation.

Miao et al. show that loss of neuronal Vps13d in mice leads to mitochondrial dysfunction, GSDME-mediated mitochondrial DNA release, cGAS–STING inflammatory signaling and activation of microglia, culminating in neuronal loss.

Human proteases TMPRSS2 and TMPRSS11D can be highjacked to mediate cell entry of respiratory viruses. This study examines the biochemical and structural basis of TMPRSS11D auto-activation and substrate specificity, informing peptidomimetic inhibitor development.

Hernandez-Trejo, Ciuparu, and Garcia da Silva et al. report that the piriform-to-olfactory bulb feedback in the mouse carries multimodal identity and reward contingency signals, which are re-formatted within seconds, according to behavioral context.

Group-IV color centers in diamond show promise for spin-photon interfaces, but precise positioning and activation are challenging. Here the authors combine site-controlled ion implantation with laser annealing and in-situ photoluminescence monitoring to create and tune individual tin vacancy centers in diamond.

Covalent inhibitors that selectively target bacterial enzymes are potential antibiotic drug candidates. Here, the authors apply high-throughput screening to identify selective covalent inhibitors that target serine hydrolases in Staphylococcus aureus

Directing the position, orientation, and long-range lateral order of block copolymer domains to produce technologically-useful, sublithographic patterns is a challenge. Here, the authors present a promising approach to overcome the challenge by directing assembly using spatial boundaries between planar, low-resolution regions on a surface with different composition.

Multiplexed assays of variant effect can resolve clinical variants but are incompatible with secreted proteins. Here Popp et al. develop MultiSTEP, a generalizable surface-tethering method to assess variant effects in secreted proteins at scale.

Compositionally and geometrically complex nano-objects are an important goal in medicinal, photonic and electronic materials research. Here, the authors fabricate disk-sphere and disk-cylinder nanoparticles with defined multicompartments from binary mixtures of block copolymers.

In chemical-genetic and lipidomics analyses, the clinical candidate oncology drug tegavivint induced an unconventional form of nonapoptotic cell death that required the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase.

Metabolic enzymes of the tricarboxylic acid cycle, such as 2-oxoglutarate dehydrogenase, are differentially expressed in absorptive and secretory lineages, guiding cell fate establishment and offering insights for targeted regenerative therapies.