Multiomics profiling of healthy individuals reveals differences across molecular layers and key pathways related to immune, metabolic, and microbiome-linked processes across ethnicities, while geographic relocation reshapes these networks and influences aging trajectories.

An optogenetic model of accelerated intermittent theta burst stimulation reveals cell type-specific plasticity mechanisms and a key role for a fronto-insular circuit in driving the antidepressant effects of this treatment in humans.

Cancers evade RAS-targeting molecular glues through distinct alterations that converge on disrupting synthetic complex formation, exposing strategies for improved drug design and rational combination therapy.

Opposing oncogenic and tumor-suppressive forces establish a progenitor-like state that builds a self-reinforcing niche to drive benign-to-malignant transition in pancreatic cancer models. Disruption of p53 activity or KRAS inhibits malignancy by collapsing the niche.

Gallego-del-Sol et al. show that arbitrium-coding phages can sense non-cognate peptide signals from other phages to regulate lysis-lysogeny decisions. This crosstalk affects lysis-lysogeny outcomes of phage infections, mixed lysogenic communities, and polylysogens. Our results demonstrate that crosstalk is an important mechanism that drives phage interactions in microbial communities.

Synergizing with senescence-inducing therapies, uPAR CAR T cells eradicate primary and metastatic solid tumors with minimal myelodepletion by targeting both tumor cells and the stroma in preclinical models.

A pan-neurodegeneration atlas built from multilayer, deep proteomics of 2,279 brain samples across 6 major diseases integrates whole proteome, detergent-insoluble proteome, and posttranslational modifications to enable intra- and inter-disease comparisons to reveal disease-specific subtypes and dysregulated pathways, while identifying shared changes such as GPNMB upregulation and NPTX2 downregulation.

A platform called MIST enables quantification and genotyping of infectious influenza in expelled respiratory particles, revealing diverse, individual-specific viral loads and aerosolized variants that correlate with saliva and nasopharyngeal viral loads and symptoms. Overall, the findings indicate heterogeneity in transmission potential.

A comprehensive multi-omic analysis of healthy humans reveals two major axes of immunological variation characterized by interferon responses, one of which is coordinated with the microbiome and its metabolites and is stable over time within individuals.

The E3-ome defines the human repertoire of ubiquitin E3 ligases, creating a unified resource that maps their diversity across the ubiquitin and ubiquitin-like systems. By consolidating fragmented knowledge, this framework provides a foundation for studying ubiquitin signaling and accelerating discovery.

A multi-omic single-cell atlas of the aging mouse brain reveals cell-type-specific transposon methylation changes, strengthening of 3D genome boundaries, and regionally heterogeneous aging signatures. These findings offer a resource to understand the molecular mechanisms of brain aging and guide future research on neurodegeneration.

Nuclear speckles are key subnuclear structures that regulate gene expression in GC-rich regions. This work shows that the evolution and expansion of core speckle proteins were crucial for the increased GC content seen in amniote genomes.

MicrobeAtlas (www.microbeatlas.org) is an integrated, reference-based resource for truly planet-wide microbiomics, analyzing hundreds of thousands of microbial lineages across diverse environments, conditions, and technologies.

Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome.

Human-specific transcriptomic and regulatory features are present in the cerebellum, with ZP2 playing a key role in synapse regulation. ZP2 expression is induced by pontine mossy fibers, leading to decreased synaptic proteins and neuronal activity, which provides insights into the evolutionary development of the human cerebellum.

Optovolution leverages optogenetics and the yeast cell cycle to impose rapid, tunable selection, enabling the continuous evolution of light-responsive regulators, logic gates, and other complex protein behaviors that were previously difficult to evolve.

Integration of electrophysiology with single-cell transcriptomics defines the molecular signature of human dermal sleeping nociceptors and reveals oncostatin M as a selective modulator of these neurons in humans, providing a therapeutic entry point for neuropathic pain.