Proceedings of the National Academy of Sciences
Articles in this Issue
Focusing a viral risk ranking tool on prediction
Preparing to rapidly respond to emerging infectious diseases is critical. SpillOver: Viral Risk Ranking is an open-source tool developed to assess the risk of n...
St3gal5-mediated sialylation of glyco-CD177 on neutrophils restricts neuroinflammation following CNS injury
Neutrophils are the most abundant circulating leukocyte population that play critical roles in neuroinflammation following central nervous system (CNS) injury. CD177, a glycoprotein on neutrophils, is...
Existential risk narratives about AI do not distract from its immediate harms
There is broad consensus that AI presents risks, but considerable disagreement about the nature of those risks. These differing viewpoints can be understood as distinct narratives, each offering a spe...
Receptor kinase pathway signal tuning through a nontranscriptional incoherent feedforward loop
Cellular signaling processes can elicit powerful responses and may need to be amplified to be efficient or dampened to prevent overstimulation. Therefore, they often involve autoregulatory feedbacks....
Pulse timing dominates binaural hearing with cochlear implants
Although cochlear implants (CIs) provide valuable auditory information to more than one million profoundly deaf patients, these devices remain inadequate in conveying fine timing cues. Early deaf pati...
RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis
Mitochondrial DNA (mtDNA) replication requires a steady supply of deoxyribonucleotides (dNTPs), synthesized de novo by ribonucleotide reductase (RNR). In nondividing cells, RNR consists of RRM1 and RR...
Cryo-EM structure of the conjugation H-pilus reveals the cyclic nature of the TrhA pilin
Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, co...
Intussusceptive angiogenesis-on-a-chip: Evidence for transluminal vascular bridging by endothelial delamination
Intussusceptive angiogenesis is an increasingly recognized vessel duplication process that generates and reshapes microvascular beds. However, the mechanism by which a vessel splits into two is poorly...
Dynamic coexistence driven by physiological transitions in microbial communities
Microbial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes in exponential growth often modify their environments so strongly...
Active control of mitochondrial network morphology by metabolism-driven redox state
Mitochondria are dynamic organelles that constantly change morphology. What controls mitochondrial morphology however remains unresolved. Using actively respiring yeast cells growing in distinct carbo...
Inhibitory control explains locomotor statistics in walking <i>Drosophila</i>
In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior, switching between long-range dispersal and local search depending on resou...
Verapamil and its metabolite norverapamil inhibit the <i>Mycobacterium tuberculosis</i> MmpS5L5 efflux pump to increase bedaquiline activity
Bedaquiline is the cornerstone of a new regimen for the treatment of drug-resistant tuberculosis. However, its clinical use is threatened by the emergence of bedaquiline-resistant strains of...
Psychological impacts of climate change on US youth
Awareness of the threats of climate change is causing distress in increasingly documented ways, with youth particularly affected. Experiences such as climate distress and eco-anxiety have implications...
Dynamics of two distinct memory interactions during water seeking in <i>Drosophila</i>
Forming and forgetting memories shape our self-awareness and help us face future challenges. Therefore, understanding how memories are formed and how different memories interact in the brain is import...
Exotic mechanical properties enabled by countersnapping instabilities
Mechanical snapping instabilities are leveraged by natural systems, metamaterials, and devices for rapid sensing, actuation, and shape changes, as well as to absorb impact. In all current forms of sna...
Semaphorin 6A phase separation sustains a histone lactylation–dependent lactate buildup in pathological angiogenesis
Ischemic retinal diseases are major causes of blindness worldwide and are characterized by pathological angiogenesis. Epigenetic alterations in response to metabolic shifts in endothelial cells (ECs)...
Profile of John Hopfield and Geoffrey Hinton: 2024 Nobel laureates in Physics
The 2024 Nobel Prize in Physics recognizes breakthroughs contributing to the emergence of a new understanding of the computations that underlie human intelligence, with profound implications for artif...
Development of DPP-4-resistant CXCL9-Fc and CXCL10-Fc chemokines for effective cancer immunotherapy
CXCR3 is a chemokine receptor for three ligands: CXCL9, CXCL10, and CXCL11. Accumulating evidence, including data presented here, suggests that the interaction between CXCL9/CXCL10 and CXCR3 not only...
Quantifying the impact of biobanks and cohort studies
Biobanks advance biomedical and clinical research by collecting and offering data and biological samples for numerous studies. However, the impact of these repositories varies greatly due to differenc...
A single mutation in an enteric virus alters tropism and sensitivity to microbiota
Many enteric viruses benefit from the microbiota. In mice, microbiota depletion reduces infection by noroviruses and picornaviruses. However, Reovirales viruses...
A hydrophobic photouncaging reaction to profile the lipid droplet interactome in tissues
Most bioorthogonal photouncaging reactions preferentially occur in polar environments to accommodate biological applications in the aqueous cellular milieu. However, they are not precisely designed to...
The POLγ Y951N patient mutation disrupts the switch between DNA synthesis and proofreading, triggering mitochondrial DNA instability
Mitochondrial DNA (mtDNA) stability, essential for cellular energy production, relies on DNA polymerase gamma (POLγ). Here, we show that the POLγ Y951N disease-causing mutation induces replication sta...
Peripheral CD4 <sup>+</sup> T cells mediate the destructive effects of maternal separation on prefrontal myelination and cognitive functions
Maternal separation (MS), a chronic stress event in early life, impairs myelination in the prefrontal cortex (PFC) and leads to PFC cognitive disorders. It remains largely unclear how such deficits ar...
The “don’t eat me” signal CD47 is associated with microglial phagocytosis defects and autism-like behaviors in 16p11.2 deletion mice
Various pathological characteristics of autism spectrum disorder (ASD) stem from abnormalities in brain resident immune cells, specifically microglia, to prune unnecessary synapses or neural connectio...