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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.

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.

Neural mechanisms underlying active avoidance are not fully understood. Here authors show that avoidance actions are positively reinforced by learned safety signals. With training, control shifts from goal-directed to habitual behavior via distinct dorsal striatal circuits, like reward-based learning.

Negative regulation of the cGAS-STING pathway is crucial to limit damaging inflammation. Here, by combining in vitro experiments and myeloid cell-specific conditional knockout mice, the authors identify the autophagy receptor TAX1BP1 as a negative regulator of STING by targeting it for degradation through Golgiphagy and ESCRT-mediated microautophagy.

The physiology and behavioral function of proprioceptors that detect joint limits are not fully understood. In this study, the authors used calcium imaging, optogenetics, behavioral genetics, and the connectome to demonstrate that hair plate proprioceptors on the fly leg detect joint limits and engage circuits to drive the leg away from those limits.

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..

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.

Using recent TMTH-sulfoximine (THS)-based biorthogonal chemistry in live cells, Smits et al. identify micro- and nanodomains in cell-cell and cell-matrix contacts of heterogenous glycocalyx density in invading melanoma cells.

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.

Mapping of neurogenesis in human hippocampi across ages and different cognitive abilities using multiomic single-cell sequencing reveals distinct signatures between cognitive preservation and decline.

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.

Johnson et al. link ARIA, a complication of anti-amyloid therapy, to clonal expansion of cytotoxic CD8 + T cells with glycolytic reprogramming and vascular trafficking potential, with implications for biomarker development and risk mitigation.

The authors realize two- and three-site Kitaev chains in semiconducting quantum dots coupled via superconductors and tune them to the sweet spot where zero-energy Majorana modes appear at the chain ends. To assess Majorana localization, they couple the system to an additional quantum dot.

The Mouse Cancer Cell line Atlas (MCCA) provides major advances towards a mechanistic understanding of cancer genomes.

Anderson et al. demonstrate that the glucokinase activator AZD1656 reduces inflammation and reverses cardiac dysfunction and metabolic remodeling in mice with diabetic cardiomyopathy.

Ribosomes drive protein synthesis, but their dynamics are hard to visualize. Here, authors introduce RiboBright, a fluorescent probe that illuminates ribosomes in live and fixed cells, revealing cell-type-specific content, organization, and movement.

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusion.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

The APOE-ε4/ε4 genotype is the strongest genetic risk factor for sporadic Alzheimer’s disease. Here, Brutman et al. identify a deletion common in people of African ancestry that reduces the relative risk conferred by the APOE-ε4/ε4 genotype.

In the context of ongoing A(H5N1) outbreak events, in this study, the authors use a ferret transmission model to show that genotype B3.13 viruses are shed into the air at higher levels than other A(H5N1) strains, highlighting the need for continued surveillance and aerobiological analyses.

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.

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.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

A genetic study in over 300,000 males reveals that Y chromosome loss affects type 2 diabetes risk differently in East Asians and Europeans. Multi-omics data suggest that this may be due to impaired glucose metabolism in Y-deficient pancreatic β cells.

The cell states and lineage connections underlying the progression from Barrett’s esophagus to esophageal adenocarcinoma remain unresolved. Here, the authors use single-cell lineage tracing and transcriptomics to analyse patient samples from the gastroesophageal junction and identify cellular relationships in the progression of Barrett’s esophagus to cancer.

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.

This study uncovers hidden atomic order in high-entropy ceramics and shows it can be engineered to dramatically boost resistance to radiation damage, opening a new pathway for design of ceramics for extreme environments.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

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.

This trial found spinal cord stimulation was well tolerated in people with gait-impaired Parkinson’s disease. It suggests that longer use improved lower-body motor symptoms while reducing thalamic hypermetabolism and cholinergic overactivity.

Conventional carbon synthesis is energy intensive. Here, the authors introduce an energy-autonomous pathway using polyaniline-HClO₄ composites. This rapid reaction yields carbon nanosheets with tunable active sites for electrocatalysis.

METALoci, a new three-dimensional genome computational tool, reveals a major rewiring of regulatory interactions during sex determination. By combining this method with transgenic models, the authors identify a noncoding regulatory region at the Fgf9 locus and reveal that Meis genes are key regulators of sexual differentiation.

The vacuum process is scalable and solvent free, yet all-vacuum-deposited perovskite solar cells still trail solution-processed counterparts. Facet-directed co-evaporation yields (100)-oriented mixed-halide wide-bandgap films for efficient, stable single-junction cells and perovskite–silicon tandem cells.

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.

Zhai et al. report newly designed self-assembled molecules exhibiting strong and ordered anchoring on the perovskite surface to reduce defects and modulate the dipole-induced energy-level, enabling certified efficiencies of 26.23% in a normal device structure, which are also applicable to inverted perovskite solar cells.

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.

Proteins can affect traits through their interactions with one another. Here, the authors propose the COWAS method to identify pairs of interacting genes or proteins whose genetically regulated co-expression is associated with complex traits.

Huang, Rigau and colleagues observe major changes in how DNA is organized in early germ cells before they start developing into sperm or eggs. These results show that germline removes structural ‘memory’ of DNA folding to start fresh for the next generation.

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.

Biocatalysis of the chemotherapy drug, doxorubicin, relies on the cytochrome P450 DoxA, which is inefficient. Here, the authors ameliorated the biosynthetic limitations by identifying DoxA redox partners and DnrV, which prevents product inhibition, helping improve microbial production.

Previous studies of Teneurins identified an uncharacterized family of Teneurin-like proteins in bacteria. Here, the authors show these proteins are widespread across both Gram groups but limited to certain species, where they form barrel-like structures that encapsulate a toxin and are co-expressed with potent immunity genes.

This study quantifies the environmental impact associated with photovoltaics manufacturing and demonstrates significant CO₂ emissions savings, depending on solar cell technology and the composition of the electricity mix in the region of manufacture.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

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.

Most GWAS have focused on common variants or rare protein coding variants. Here, the authors interrogate the contribution of rare non-coding variants for anthropometric traits, identifying new genes associated with increased BMI and height.

This study demonstrates a sub-THz free-space link, achieving 120 Gbit/s across 5 m enabled by compact plasmonic components with >300 GHz bandwidth, paving the way for next-generation scalable wireless networks at high carrier frequencies.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.