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Hepatitis C virus remains a health burden due to the lack of an effective vaccine, hindered by difficulties in replicating the native E1E2 antigen structure. Here, the authors engineer a stabilized E1E2 heterodimer using cryo-EM-guided modifications, enhancing immunogenicity and paving the way for future HCV vaccine development.

Here, the authors report that the protein language model ESM-2 is broadly useful for variant effect prediction, including unobserved changes, and can be applied to understand novel viral pathogens with the potential to be applied to any protein sequence, pathogen or otherwise.

Spectroscopic observations of the ultra-hot Jupiter WASP-189b reveal both volatile (H₂O, CO, OH) and refractory (Fe, Mg, Si) gas in its atmosphere. Here, the authors show that the abundance ratio of refractory species reflects that of the host star.

Most patients with B-cell leukemia respond to chimeric antigen receptor T cell (CAR T) therapy, yet many relapse due to loss of CAR T function. Here, the authors show that the metabolism of CAR T from short- and long-term responders is different, which may explain why CAR T lose functionality.

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.

PAN2-PAN3 complexes trim poly(A) tails of mRNAs. Here, the authors show that PAN2 associates with translation initiation factors and that germline-specific deletion of Pan2 in mice causes male infertility and compromises stability of key components of the translational machinery.

Brief ultrasound to human frontal eye fields, but not motor cortex, rapidly biases eye movement contralaterally in a perceptual choice task. The size of this effect scales with individual baseline FEF inhibitory tone.

Here the authors identify nicotine-derived inhibitors of the SARS-CoV−2 main protease that outperform Paxlovid in cells and mice, remain effective against resistant variants, and show broad activity against multiple human coronaviruses.

ASXL1 is often mutated in myeloid cancers. Here, the authors describe the molecular and structural mechanism by which ASXL1 associates with the transcriptional coactivator BRD4, helping to explain their high correlation in cancers.

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.

Dynamos can generate magnetic fields, which are present across various scales in space plasmas. Here, the authors show evidence for a turbulent dynamo in the terrestrial magnetosheath, indicating that Earth’s magnetosheath may be used as a natural laboratory for testing dynamo theories and simulations.

Cyclisation of R27 plasmid TrhA pilin occurs via a Gly1–Asp69 bond. Here, authors show Gly1/Lys and Asp69/Lys substitutions impose positive pilus charge, abolishing conjugation into wild-type recipients, rescued in phosphatidylethanolamine-deficient recipients, highlighting phospholipid importance in both donors and recipients.

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.

Neuropathic pain is commonly treated with opioids due to limited alternatives. Here, authors determine cryo-EM structures of the neuronal glycine transporter GlyT2 and develop a reversible inhibitor that provides analgesia in vivo without side effects.

In this study, the authors develop a stoichiometric-thermodynamic model linking seismic decarbonation to Mw 5.9–6.5 earthquakes. They demonstrate that seismic CO₂ pressurization can sustain dynamic slip and enhance the destructive potential of earthquakes.

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.

Loss of KRIT1 or CCM2 drives harmful KLF4 overexpression in brain vessels. Here, authors show a single KRIT1 must recruit two CCM2 proteins via dual PTB-NPxF interactions to suppress KLF4, revealing a previously unknown PTB clustering mechanism.

Large biospecimen banks are limited by a lack of fast, flexible, database-like retrieval. Here, authors encode metadata as DNA barcodes on silica-encapsulated samples and demonstrate numerical range, categorical, and Boolean queries, enabling rapid, precise recall from pooled DNA/RNA archives.

Exhaustion is a functional state that hampers anti-cancer and antiviral CD8 T cell activity, and is preceded by a stem-like state, maintained by the transcription factor TCF1. Here authors develop mouse models that allow a precise understanding of the developmental trajectory between the stem-cell-like and exhausted states of CD8 T cells and find that while constitutive overexpression of TCF1 expands the stem-like T cell pool, TCF1 expression specifically in already exhausted cells is unable to promote dedifferentiation.

The existence of multi-centennial natural variability in the North Atlantic is demonstrated over the last millennia by compiling proxy data. This variability mode will potentially amplify northern Europe warming by up to 30% over 2000-2035.

2D covalent organic frameworks usually possess a polycrystalline nature as well as lower porosity and surface area than 3D counterparts, limiting their gas storage application. Here, the authors report the formation of single-crystal 2D covalent organic frameworks isomers with atom-resolution structures for methane storage.

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.

De novo Calcineurin (CN) variants cause DEE91, with E282K being the most common. E282K alters CN’s acidic substrate binding pocket to basic, thus shifting substrate preference and dephosphorylation signaling, subsequently impacting neurodevelopment.

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.

Most studies assessing food self-sufficiency look at calories and neglect nutrient gaps. Comparing food demand and potential food production under land and water constraints, this study quantifies 9 key nutrient gaps for each of African’s 54 countries.

The authors demonstrate that targeted protein degradation of the dengue virus capsid suppresses infection through capsid-dependent pathways rather than classical inhibition, revealing a new antiviral strategy effective against resistant viral variants.

High spatial resolution is essential for resolving cellular and subcellular organization in tissues. Here, authors present Seq-Scope-X, which integrates tissue expansion with Seq-Scope to achieve an order-of-magnitude improvement in resolution of spatial transcriptomics and proteomics.

Extracellular electron transfer (EET) in bacteria requires the spatiotemporal coordination of many proteins. Here, authors show that the inner-membrane protein CymA reorganizes spatially into condensates and drives the colocalization of partner proteins to enable EET in Shewanella.

Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

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.

Multiple myeloma involves alterations to T cell function, but mechanisms underlying disease evolution remain unclear. Here the authors find that, unlike solid cancers, multiple myeloma lacks exhausted T cells and is instead characterized by antigen-driven terminal memory T cell differentiation, which may be driven by tumour-intrinsic features including tumour burden and antigen-presentation gene expression.

Here, the authors propose the Antarctic Ecosystem Value Index, an Earth systems model-based measure of marine ecological value. The index identifies potential present and future high-value locations, which often fall within coastal polynyas.

Mass spectrometry (MS)-based proteomics is increasingly central to systems biology. Here, the authors present a high-throughput, multi-organ workflow that profiles 11,472 proteins in 507 mouse samples, enabling rapid, system-level evaluation of drug efficacy and toxicity.

Precise and efficient CRISPR genome editing requires specialized delivery systems. Here, the authors develop Coomassie lipidoids that deliver purified adenine base editors into retinal tissues, making it possible to achieve robust genome editing with a defined, non-viral nanomedicine.

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.

Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

The study shows that incorporating information on pre-existing moisture conditions into the atmospheric river scale improves early-warning identification of flood-generating events.

In this study, the authors designed potent Enterovirus D68 capsid inhibitors that block viral binding and show that the lead compounds reduce virus levels, prevent paralysis and improve survival in EV-D68-challenged mice, even when treatment starts days after infection.

Amundsen Sea records show warm Circumpolar Deep Water drove major West Antarctic Ice Sheet retreat from 18,000–10,000 years ago. Subsequent cooling stabilized the grounding line, indicating ocean heat—not atmospheric warming—controlled long-term WAIS change.

Fast excitatory neurotransmission is mediated by AMPA receptors. Here, the authors discover that the GluA4 AMPA receptor subunit has distinct structural properties and conformational plasticity that tune its activation to glutamate.

Butenolides are important features of many bioactive compounds but known butenolide biosynthetic pathways are complex and challenging to harness. In this study, the authors report that avenolide, a 4-alkylbutenolide that regulates avermectin production in Streptomyces avermitilis, is assembled from a fatty acyl thioester by a multifunctional flavoenzyme and an iterative cytochrome P450.

Attention fluctuates over time and across contexts—how is this reflected in the brain? Fitting a dynamical systems model to fMRI data, Song and colleagues show that the geometry of neural dynamics along the attractor landscape reflects changes in attention.

Therapy to allergy often targets a specific allergen without addressing cross-reactivity. Here the authors develop a consensus, cross-reactive allergen, use mRNA-lipid nanoparticle immunization to induce specific, neutralizing IgG responses, but find no therapeutic effects in mouse allergy models, hinting the need for further optimization prior to translation.

Repurposing existing drugs to target new disease-associated genes is a promising strategy, but identifying these targets can be challenging. Here, the authors develop GenT, an approach that uses GWAS data to identify disease-associated druggable genes.

This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

This paper presents an active pixel power control (APPC) to minimize crosstalk in all-optical neural interrogation. Tested in vivo, APPC suppresses optogenetic artifacts while preserving Ca2+ imaging quality, enabling precise neural circuit analysis.

This manuscript from Choquette and colleagues finds that sclerostin gene expression is up-regulated in bone by β3-adrenergic signaling via an adipose to bone relay and acts as an endocrine factor to inhibit adipose tissue beiging in mice.