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McGavern and colleagues identified a CD8⁺ T cell population that expresses GZMK in ʽtau-richʼ brains, where it may play a protective role against neurodegeneration.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

The pupil is known to assist retinal adaptation to light level changes. Here, the authors find a mechanism for how the pupillary light reflex drives monocular and binocular retinal activity in mice and shapes conscious visual perception in humans.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Using infant fMRI, the authors show that, by 2 months of age, representations in high-level visual cortex encode visual categories that align with deep neural networks, and lateral object-selective regions are later to develop.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

Genes encoding key epigenetic regulators, including Lysine Demethylase 6A (KDM6A), are frequently mutated in bladder cancer. Here, the authors show that loss of KDM6A promotes formation of extrachromosomal circular DNA (eccDNA), genomic instability, and metabolic reprogramming, driving resistance to cisplatin chemotherapy while simultaneously enhancing sensitivity to immune checkpoint inhibitors.

Stem cell repair of injured monkey spinal cords restores hand function in 53% of trials.

Enhancer-gene selectivity establishes gene expression networks during development. Here, the authors link Evf2 enhancer-gene guidance and seizure gene regulation, Evf2 RNA binding sites and chromosomal RNP recruitment domains, and homeodomain motif recognition to support multilayered mechanisms.

Yang et al. show that moments of failed attention we experience after sleep deprivation reflect brief ‘sleep-like’ episodes in the brain, corresponding to a brain- and body-wide event with altered brain activity, pupil size and brain fluid movement.

Single-particle tracking experiments in intact cells reveal dynamic co- and post-translational interactions of the TRiC–PFD chaperonin complex with client proteins during in vivo protein folding.

Previous structural studies of T cell recognition of SARS-CoV-2 have been confined to spike epitopes. Here the authors assess T cell recognition of SARS-CoV-2 nucleocapsid epitopes, which are more conserved than spike epitopes, providing structural insights into recognition of two epitopes.

Long-term study reveals how intra-morph plumage color variation in a polymorphic bird shapes morph-specific evolutionary responses to environmental change, highlighting complex selection dynamics acting within genetically discrete color morphs.

Achieving efficient violet, yellow, and red emission in a single robust, scalable host is challenging. The authors achieve this by constructing Gd³⁺-mediated cluster traps in alkaline-earth fluorochlorides to reduce energy loss during electron migration.

Ye et al. define the structure and mechanisms of a bacterial pathway that performs ubiquitination-like protein conjugation, revealing new insights into the evolution and biological roles of ubiquitination pathways across kingdoms.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

GM4951 is a GTPase in hepatic lipid metabolism. Here, the authors determine the atomic structure of GM4951, which forms a tail-to-tail dimer essential for lipid droplet localization. MASLD-linked mutations destabilize the protein and alter the dynamics of switch loops of the GTPase domain.

An optimized 3D culture system enabled a stem cell-derived monkey blastoid to develop to day 25, recapitulating key events of primate late gastrula and demonstrating notable similarity to natural embryos.

This study shows that adherent cells maintain membrane tension gradients even without moving. Using a fluorescent probe, the authors reveal that actin and adhesion forces shape these gradients, providing a new view of cell mechanics.

Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.

Omnivores like bears can switch between plant and animal diets, potentially helping them respond to changing conditions. By combining modern and fossil data, this study shows that bears shift toward carnivory in harsher climates and toward herbivory in more productive environments.

Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

In Alzheimer’s disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. Here the authors show that, at the myelin–axon interface, axon–glial signaling, paranodal architecture and amyloid-β aggregation are altered in AD, implicating myelin–axon disruption in disease progression.

In this work, authors present a nanoinducer (bacNID), which enables targeted bacterial protein degradation via ClpXP, leading to the effective treatment of bacterial infection (Staphylococcus aureus and Salmonella typhimurium) without inducing resistance.

Smith et al. present M-PACT, a deep neural network leveraging low-input cell-free DNA methylation profiles to achieve robust classification of pediatric brain tumors and enable cellular deconvolution and sensitive copy-number variation detection.

Liquid biopsy methods have mainly been focused on the use of peripheral blood, and comparison between body fluids has been limited. Here, the authors utilize samples from a rapid tissue donation program to compare body fluid sites in their representativeness of the metastatic disease in patients with breast cancer.

Asexual-to-sexual switching underpins malaria transmission. Prajapati et al. identify an AP2-G loss-of function mutation and use it as a genetic tool to show that GDV1 is essential for initial ap2-g activation and sexual commitment initiation.

In Cys-loop receptors, the capping of neurotransmitter binding-site loop C has often been proposed to mechanically couple binding to gating. Here, the authors test this idea experimentally and conclude that, instead, the functional impact of this marked rearrangement must be restricted to local changes at the level of the orthosteric sites.

A statistical method to quantify crystallographic textures in aluminum alloys under additive manufacturing conditions is introduced. Experiments and simulations reveal interfacial energy anisotropy dominates texture selection and grain competition.

This Perspective discusses current evidence on clonal hematopoiesis dynamics in humans and compares mathematical models used to predict CH progression, highlighting their implications for the clinical management of individuals with precursor states.

Mucosal influenza vaccines promise enhanced protection but lack defined immune correlates of protection. Here, the authors conduct a phase I trial of an intranasal recombinant influenza A/H5 vaccine with a nanoemulsion adjuvant, demonstrating successful mucosal priming and broad cross-clade immune responses, advancing the development of intranasal influenza vaccines.

CRISPR-Cas12a diagnostics are limited by strict PAM requirements. Here, authors show that higher temperatures activate numerous noncanonical PAMs, enabling a versatile one-pot platform that improves sensitivity, specificity, and rapid on-site pathogen detection.

Niche conservatism is a key assumption when planning non-native species management, but it is not always met. This study suggests that regional differences in niche conservatism are primarily transient and thus a matter of time.

Gollo et al. introduce random ‘mutations’ to the human connectome to study the trade-off between complexity vs. parsimony. The cortical hubs that are most fragile to these perturbations show the strongest loss of gray matter volume in schizophrenia.

Herpesvirales utilize a unique nuclear egress route for capsid export. Here the authors show that herpesviruses exploit a cellular membrane protein, once thought to transport chloride, to facilitate membrane fusion and egress from the nucleus.

The North American southwest was dustier during interglacial climates, in contrast with global trends. Long-term regional dust emissions depend on the erosion of hillslope and tributary sediments into alluvial, river, and playa dust sources downstream.

Research in the tropics is unevenly distributed across regions and biomes. Here, the authors find that moist broadleaf forests account for 73% of all tropical citations but cover 29% of the land area, while drier, climate-vulnerable areas with fewer trees remain under-sampled and under-cited.

Multi-template PCR enables parallel DNA amplification but suffers from sequence-specific biases. Here, the authors develop a 1D-CNN model predicting amplification efficiency directly from the DNA sequence and discover adapter-mediated self-priming as a key cause of uneven amplification during PCR.

Spontaneous neural activity has been experimentally linked to learning ability. Here, the authors derive theoretical formulae showing that higher variance along task-relevant directions accelerates learning speed, providing a framework consistent with empirical findings.