Proceedings of the National Academy of Sciences
Articles in this Issue
mRNA lipid nanoparticle cancer vaccine platform delivering multiple STING activators for enhanced antitumor activity
mRNA-based cancer vaccines offer a modular and safe platform to elicit antitumor immunity, yet their efficacy is often limited by inefficient mRNA delivery and inadequate dendritic cell (DC) activatio...
QnAs with Daniel Herschlag
Mapping the dialogue: Decoding alveolar stem–niche interactions
While cellular atlases have revealed remarkable phenotypic diversity, how cells navigate this landscape to influence tissue behavior remains poorly understood. We present an alveolosphere screening pl...
Physically intelligent capsule robots with embodied memory and logic in the gastrointestinal tract
Miniaturized medical robots offer a promising solution for minimally invasive measurements and interventions in the gastrointestinal (GI) tract. Clinical assessment of GI disorders is commonly guided...
Dopamine-driven mitochondrial reverse electron transport in immune cells mediates gut–brain ROS signaling during sleep deprivation
Sleep deprivation (SD), together with inevitable stress inherent to conventional SD protocols, can induce oxidative stress and inflammation, thereby increasing the risk of premature death. However, th...
High-resolution structure of monomorphic Aβ <sub>1-40</sub> fibrils
Amyloid-β (Aβ) fibrils primarily composed of Aβ 1-40 and Aβ 1-42 form the core of senile plaques in Alzheimer’s disease....
Structural basis of complement anaphylatoxin receptor activation by an immunostimulant lead candidate
Activation of the complement cascade is a primary innate immune response mechanism to combat pathogenic infections. Complement anaphylatoxins (i.e., C3a and C5a) exert a robust inflammatory response v...
Diffusion-induced instabilities promote cooperation in eco-evolutionary networks
Understanding how cooperation persists despite the advantage of selfish behavior remains a central challenge in evolutionary dynamics. Classical models of public goods dilemmas predict dominance of de...
Circadian screening of neutrophils identifies therapeutic targets in multiple sclerosis
Circadian rhythms are intrinsic time-keeping mechanisms that play a critical role in tuning immunity. Here, we investigated the impact of circadian rhythms on the pathogenesis of experimental autoimmu...
Why human societies adopt rigid moral rules: The efficiency–robustness trade-off
Humans are capable of remarkably flexible moral judgment. Yet societies rely on rigid rules—obligations and prohibitions that apply categorically, even when case-by-case reasoning could yield better o...
Divergent population trajectories despite similar response to temperature in a widespread aerial insectivore
Climate change is shifting when animals breed [C. Parmesan, G. Yohe, Nature 421 , 37–42 (2003) and S. J. Thackeray et al...
Cell competition overcomes host tissue resistance to unleash tumor growth in a <i>Drosophila</i> brain cancer model
Primary tumors of the central nervous system are extremely aggressive and often incurable. While tumor cells are known to interact with their microenvironment, the complexity and temporal dynamics of...
Structural insights into the nairovirus nucleoprotein endonuclease activity
Nairoviruses are emerging tick-borne pathogens for which effective antiviral therapies are currently unavailable. Although nucleoproteins (NPs) are essential for viral genome encapsulation and have be...
Human and animal morbillivirus strains causing chronic neurological infections share key genotypic and phenotypic traits
Long-term persistent measles virus (MeV) infection of the central nervous system (CNS) can result in subacute sclerosing panencephalitis (SSPE), an invariably fatal late neurological complication of m...
Endothelial Arf6 sustains electrical signaling and cerebral blood flow in mice through PIP <sub>2</sub> -dependent activation of Kir2.1 channels
Brain capillaries sense neural activity and direct blood flow to active regions—a process termed neurovascular coupling that underlies activity-dependent increases in local perfusion (functional hyper...
Mitonuclear discordance modulates mitochondrial ageing dynamics in natural <i>Drosophila</i> populations
Mitochondrial decline is a hallmark of ageing, yet the role of intergenomic compatibility in shaping ageing trajectories remains poorly understood, particularly in an ecologically relevant framework....
Dendritic morphology and synaptic nonlinearities enhance functional complexity in human cortical neurons
Humans exhibit unique cognitive abilities within the animal kingdom, but the neural mechanisms driving these advanced capabilities remain poorly understood. Human cortical neurons differ from those of...
Costunolide ameliorates autoimmune uveitis by targeting USP15 to suppress TNF-α-induced retinal endothelial inflammation
Autoimmune uveitis is a sight-threatening inflammatory disease, with the majority of entities driven by leukocyte infiltration into the retina. A critical early step in this process is the activation...
Divergent trait controls on soluble sugars and starch underlie global strategies of tree carbohydrate storage
Nonstructural carbohydrate (NSC) stores buffer tree metabolism, osmotic regulation, and defense, thereby mediating tolerance and survival under climate extremes. Yet, the functional and evolutionary d...
A ligandable PNT domain establishes ERG as a directly targetable oncogenic driver in prostate cancer
The TMPRSS2:ERG gene fusion, present in approximately 50% of prostate cancers in patients of European ancestry, drives oncogenesis through aberrant overexpressi...
Sex- and experience-dependent regulation of synaptic protein turnover
Synaptic transmission can be tuned through plasticity mechanisms that regulate synaptic strength, structure, and number. In vivo measurements demonstrate remarkable spine dynamics, with subsets of syn...
Identification of cellular intermediates unveils unique enzymes for flagellar glycan biosynthesis in <i>Clostridioides difficile</i>
Glycosylation of bacterial surface proteins, such as flagellin (FliC), is important for their function and is often involved in virulence of pathogens. Glycans can be further modified by so-called pos...
Probing anharmonic and heterogeneous carrier dynamics across sublattice melting in a minimal model superionic conductor
Despite decades of research, the microscopic origin of sublattice melting and fast ion transport in superionic conductors remains elusive. Here, we introduce a chemically neutral minimal binary model...
Covalent phytobilin adducts of GUN4 implicate a photoprotective mechanism in chlorophyll biosynthesis
In the green alga Chlamydomonas reinhardtii, loss of chlorophyll synthesis under light stress is associated with degradation of the porphyrin-binding H-subunit...
<i>Arabidopsis</i> BSL phosphatases regulate zygote polarity through a brassinosteroid-independent essential function in MAP kinase signaling
The main axis of the plant body is established in early embryogenesis. Polar growth and asymmetric division of the Arabidopsis zygote require the Mitogen-Activa...