Proceedings of the National Academy of Sciences
Articles in this Issue
Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime
Epstein–Barr virus (EBV) lytic infection contributes to oncogenesis and autoimmunity and depends on subversion of host DNA damage responses (DDR). We used high-content screening (HCS) to systematicall...
The politicization of academic collaborations threatens to harm international science
Fluorescence-lifetime optical electrophysiology in contracting cardiomyocytes
Precise monitoring of cardiac electrophysiology in vitro is crucial to understanding heart function and cardiac disease. However, high-throughput, contact-free methods for directly measuring excitatio...
Targeting XIAP-coordinated PKC signaling resensitizes PD-1-refractory tumors for rechallenge
Despite revolutionizing oncology, PD-1/PD-L1-directed immune-checkpoint blockade (ICB) is limited by primary or acquired resistance that is routinely countered—without mechanistic clarity—by empiric r...
Simultaneous transformations of view and place coding across reference frames in the macaque brain
Vision enables primates to remotely map their environment using eye movements rather than physical locomotion. While view-related spatial coding is prevalent in the primate hippocampus, its origin and...
Polyphosphate synthesis is essential for phosphate and ATP homeostasis during nutrient upshift
Inorganic polyphosphate (polyP) is a ubiquitous molecule found across all domains of life. Although implicated in diverse cellular processes, including phosphate storage, stress responses, and pathoge...
A conserved mechanism for stabilization of viral innate immune antagonists via interaction with Elongin BC
Interferon regulator factor 3 (IRF3) inhibition is a shared strategy of many virally encoded proteins to effectively block the induction of interferon signaling. Although rotavirus nonstructural prote...
Extended sequence context shapes mutational bias in <i>Escherichia coli</i>
Understanding how sequence context influences the likelihood of mutation at a given genomic locus is critical for deciphering evolutionary processes. It is well established that the immediately adjace...
DNA-intercalating antiphage molecules trigger abortive infection through mutual destruction and synergize with bacterial immunity
Bacteria deploy diverse antiphage defense systems, including small bioactive molecules providing protection at the multicellular level. DNA-intercalating anthracyclines, such as daunorubicin, exhibit...
Host methylglyoxal activates the <i>Listeria</i> virulence program, allowing bacteria to evade inflammatory phagocytes by cell-to-cell spread
Methylglyoxal is a reactive aldehyde produced by macrophages as part of their antimicrobial innate immune arsenal. Our prior work showed that Listeria...
Social cues drive the evolution of plastic pathogen virulence in spatially and temporally variable environments
Host–pathogen interactions are often characterized by spatial and temporal fluctuations in host density. Such variability may promote the evolution of phenotypic plasticity in pathogen virulence. Howe...
Aerobic soil bacteria adapt to hypoxia by hybridizing fermentation with carbon storage
In soil ecosystems, aerobic bacteria survive oxygen deprivation (hypoxia) by entering nonreplicative persistent states. In contrast to the well-studied metabolism of obligate and facultative anaerobes...
Terephthalate, a plastic monomer, triggers phosphate metabolism rewiring in yeast
Plastic pollution poses an escalating global threat, demanding biological strategies capable of transforming waste into valuable products. Polyethylene terephthalate (PET) can be hydrolyzed into its m...
Layerwise stratification and band reordering in twisted multilayer MoTe <sub>2</sub>
We introduce a physics-informed training-data generation strategy that efficiently captures the complete interlayer interactions in multilayer moiré systems, enabling a machine-learning force field tr...
Mating-dependent lifespan cost of sterol depletion in male <i>Drosophila melanogaster</i>
Trade-offs between lifespan and reproduction are a central theme in evolution and ecology, often attributed to physiological constraints on the allocation of limiting resources. However, recent work s...
A 3’UTR-derived small RNA modulates the life cycle of the cholera toxin–encoding filamentous phage, CTXϕ
Bacteriophages (phages) are well known to be one of the major driving forces in bacterial evolution. This also applies to virulent microorganisms, such as the major human pathogen...
Positive allosteric modulator selective for adult muscle nicotinic acetylcholine receptor
The muscle nicotinic acetylcholine receptor (AChR) is the key mediator of neuromuscular signal transmission and is essential for all voluntary movement in our body. In this study, we present DC-98-LC7...
Mean field game model of the impact of reductions in support on faculty research activity
Every research university has a distribution of faculty research activity that is fueled by the external support from government, industry, and philanthropy. The large decreases in federal support pro...
TadA-mediated A-to-I mRNA editing rewires redox metabolism to promote dominance of epidemic <i> <i>Klebsiella pneumoniae</i> </i> clones
Dominant carbapenem-resistant Klebsiella pneumoniae (CRKP) clones have markedly intensified the burden of invasive i...
15-PGDH inhibition promotes muscle repair and strength recovery during GLP-1 receptor agonist–induced weight loss
Glucagon-like peptide-1 receptor agonists, including long-acting semaglutide, are transformative anti-obesity therapies. However, emerging evidence indicates that weight loss may come at the expense o...
Self-activation by a C-terminal domain arginine finger regulates GTP hydrolysis in bacterial zinc metallochaperones
The cellular response to transition metal scarcity is multifaceted and complex. Members of the Cluster of Orthologous Groups 0523 (COG0523) superfamily are proposed to chaperone a bound metal to activ...
Subsarcomeric regulation of thin and thick filaments in skeletal muscle myofibrils
Muscle contraction relies on the coordinated activation of myosin motors from a folded-OFF state on the thick filament surface and their actin tracks on the thin filaments in response to calcium. Thic...
Quantum coherent Chladni-like resonance: Programming ions as matter waves for subpicosecond conduction
Achieving coherent control of ionic transport in solids, analogous to electron waveguides, remains a fundamental challenge, as ionic motion is typically limited by slow, stochastic hopping. Here, we d...
Early-stage drug discovery in a new-generation ultrahigh-throughput mass spectrometry platform
Early-stage drug discovery involves a complex set of processes that typically requires iterative exploration of a vast chemical-biological search space. Over the past few decades, these processes have...
Persistent trade-offs balance competition and colonization across centuries
Microbial competition drives rapid adaptation, often forcing organisms to specialize in new ecological niches. Adaptations that improve competitive ability can reduce performance in other environments...