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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.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

Gel ionotronics are typically easy to prepare, but control of local ionic character is unusual. Here, the authors report the combination of elastomers with photo-ion generators for photopatterned control of conductivity in the gel materials.

Plants require the plastid encoded RNA polymerase PEP to generate viable photosynthetic apparatus. Here the authors genetically engineer an optoswitch that enables photo-induced complementation of an albino mutant restoring transcription and chloroplast biogenesis on demand.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

CRISPR/Cas9 screens have identified genetic contributions to many phenotypes. However, studying combinations of genes or regulatory elements remains challenging. Here, the authors use CRISPR/Cas12a to overcome those challenges and enable new approaches to study combinatorial genetic mechanisms.

The identification and optimization of bifunctional small-molecule protein degraders remain labor-intensive processes largely restricted to proteins with well-defined ligandable pockets. Here, the authors present a polymer-based strategy, HYbrid DegRAding Copolymer (HYDRAC): modular copolymers that densely display target-binding peptides in conjunction with peptide-based or small molecule-derived degrons in a multivalent fashion, enabling selective degradation of disease-relevant proteins.

R2SP belongs to the R2TPlike quaternary chaperone family and consists of RUVBL1/RUVBL2 AAA+ ATPases, SPAG1 and PIH1D2. Here, authors combined biochemistry, NMR, structural MS and cryo-EM to investigate its 3D organization, mode of assembly and ATPase activity.

Here, the authors show that dietary fiber availability shapes the development and survival strategies of an intestinal worm, revealing stage-dependent plasticity and tight links between diet, the gut microbiome, host metabolism, and worm persistence.

Maurice et al. examine how cytokines regulate antigen-independent activation of memory CD8⁺ T cells. They show that IL-4 signaling changes the quality of the bystander T cell response by antagonizing IL-18 sensing and subsequent IFNγ production, but increasing granzyme B expression without changing perforin, thereby limiting bystander-mediated protection.

The authors present evidence for the coexistence and coupling of ferroelectricity and superconductivity at amorphous LaAlO3/KTaO3(111) interfaces. Furthermore, flipping ferroelectric polarization reduces interfacial conductivity by more than 1000 times, and simultaneously suppresses superconductivity

Supersolid phases are quantum-entangled states of matter exhibiting the dual characteristics of superfluidity and solidity. Here, the authors map the phase diagram of K₂Co(SeO₃)₂. and identify signatures of two supersolid phases separated by a 1/3 magnetization plateau.

The transformations for aragonite precursors in coral are not fully understood but have implications in bio, biogenic and geological mineralization. Here, the authors use high-resolution mapping and observe exponential decay from the edge of four precursors to coral aragonite skeleton in Stylophora pistillata.

Mechanical response of semiconducting polymers affects their electrical properties, yet the detail remains elusive. Zhong et al. examine the multiscale structural evolution of conjugated polymer thin films during uniaxial deformation and link it to mechanical resilience and solar cell performance.

Radical protein footprinting reveals protein structure and interactions, but has not – to the best of the authors knowledge - been applied in whole blood. Here, authors demonstrate in-blood footprinting in mice, uncovering diabetes-associated protein conformational changes that were validated by orthogonal assays.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

The roles of orbitofrontal and cingulate cortex in emotional decisions remain unclear. Here the authors show distinct timing between caudal orbitofrontal and cingulate signals, that orbitofrontal stimulation increases avoidance, and that physiological responses mirror behavior.

A shift in organic carbon to total phosphorus (C_org/P_total) ratios in marine siliciclastic strata from approximately 455 million years ago suggests an earlier-than-previously-thought spread of land plants and their impact on the Earth system, based on analogy with extant C/P ratios of terrestrial and marine organic matter.

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

Gestational exposure of mice to the obesogen tributyltin alters 3-D chromatin interactions in primordial germ cells leading to stable reduction of hepatic Ide expression and predisposing male descendants to insulin dysregulation and obesity.

Melting ice and associated sea-level change will expose new land in Antarctica. Here the authors quantify this change and combine it with our understanding of known Antarctic mineral occurrences, showing that substantial mineral deposits may become accessible over the next few centuries in Antarctica.

Top-down projections from the orbitofrontal cortex carry predictive signals that grow with sound experience and suppress the auditory cortex via inhibitory circuits, revealing a predictive mechanism for sensory habituation.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

The severity of climate change impacts calls for low-carbon thermal management solutions. This work presents a chameleon-inspired electronic skin for adaptive electrochromic thermal regulation with minimal energy input and scalability potential.

Neural mechanisms underlying high visual acuity are not fully understood. Here the authors show that high resolution visual information is transmitted from the retina to the brain by neurons in the parvocellular geniculate pathway in macaques, where signals are now shown to most often originate from single cone photoreceptors, establishing the neural mechanism that limits resolution acuity prior to cortical processing.

DNA methylation heterogeneity and dynamics hinder distinguishing early pathological changes from normal variation. Here, the authors identify stable sites whose disruption is linked to blood cancers, aging, and cardiovascular risk.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

Continuously trapped atoms provide advantage for atom interferometry, yet current schemes are limited by dephasing. Here, the authors develop a Floquet-engineered atom interferometry platform for quantum force sensing purposes, unveiling regimes where the interferometric phase is insensitive to noise.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

Targeted ablation of prostaglandin E₂ (PGE₂) signalling in CAR T cells enhances their activity in PGE₂-rich solid tumours, with demonstrations of efficacy in vitro, in mouse xenografts and in patient-derived organotypic tumour spheroids.

Chlorine electrosynthesis from seawater is limited by poor selectivity and stability under industrial-scale conditions. Here atomic-step-enriched ultrafine high-entropy alloy nanowires enable highly efficient chlorine evolution at 10 kA m⁻² for over 5,500 h through dynamic Pt–O active sites, reducing electricity consumption and feedstock costs for next-generation chlor-alkali processes.

Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Continuous monoculture of banana can result in proliferation of parasitic nematodes. Here the authors show that in the long term, soil can become suppressive to disease and this is associated with enrichment of free-living nematodes and Bacillus bacteria.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

This study shows that strain-stabilized interfacial polarization in metallic RuO₂/TiO₂ heterostructures modulates the work function by over 1 eV and the metallicity, establishing a new route to control the electronic properties of functional metals.

Rapid immune activation requires tight control of mRNA stability in CD8⁺ T cells. Here, the authors show that a compositive RNA motif – m⁶A sites positioned next to AU-rich elements - marks mRNAs for rapid decay during activation, revealing a coordinated mechanism that shapes T-cell immunity.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Expression of agouti signalling protein in neurons in the medial preoptic area is increased by group housing and negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant mice.

Skin-targeted siRNA therapies require optimized delivery to achieve therapeutic efficacy. Here, authors show that increasing conjugate hydrophobicity enhances siRNA skin retention and gene silencing in porcine and human models while limiting systemic tissue exposure.

Here, the authors show that early-life high-fat/high-sugar diet induces sex-specific alterations in adult feeding behavior, hypothalamic transcriptome and blood metabolome, with Bifidobacterium longum and prebiotic FOS + GOS administration restoring these effects via distinct mechanisms, highlighting their therapeutic potential.

Here researchers reveal a microexon in the Ank3 gene encoding Ankyrin G allows cortical interneurons to fine-tune calcium signaling and firing, revealing the contribution of alternative splicing to the functional diversity among different types of neurons.

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.

Lazarevic et al. reveal a shared loss of a TBX5-dependent atrial gene network in cardiomyocytes and a disease-specific network gain in activated fibroblasts across atrial fibrillation and heart failure models.

Here, the authors show that myoferlin is a crucial host factor that helps move viral genetic cargo to the cell surface, boosting influenza, RSV and Sendai virus spread, highlighting a common weak spot for future antivirals.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

Phylodynamic modelling shows how the changing antibiotic landscape and genetic determinants of resistance shape real-world gonococcal dynamics. Experiments validated that determinants with identical resistance phenotype differed in impact on fitness.

Expression quantitative trait loci (eQTL) analysis in patients with inflammatory bowel disease identify potential target genes for IBD GWAS loci not readily detected in individuals without disease highlighting the importance disease-focused studies.

Many viral vaccine antigen candidates are transmembrane glycoproteins, and their development requires methods which allow their biophysical characterization. Here authors present an optimized nanodisc assembly platform which provides reproducible, scalable, and accurate replication of the vaccine candidates for detailed analysis.