Proceedings of the National Academy of Sciences
Articles in this Issue
Calsyntenin-3 suppresses inflammation via inhibition of TLR N-glycosylation and membrane localization
Excessive innate immune activation drives uncontrolled inflammation and multiple inflammatory diseases. Proper N-glycosylation of membrane-associated Toll-like receptor 4 (TLR4) is essential for its t...
An autoimmunity-associated allele of <i>PTPN22</i> enhances innate antiviral immunity to protect against acute coronavirus infection
Allelic variation can impact viral clearance and disease severity. Still, our understanding of the effect of the autoimmunity-associated allelic variant of Ptpn22...
A transcription regulator atlas identifies TOX3 as an Atoh1 coactivator in cerebellar development and tumorigenesis
Organ development and function are orchestrated by intricate transcriptional circuits. Here, we present a comprehensive atlas profiling 1,904 transcription regulators in the brain, cerebellum, heart,...
Myeloarchitecture, intra- and interhemispheric and thalamocortical connections of area 3b representing the teeth and tongue in galagos
The representations of the face and oral cavity occupy a large but understudied portion of primary somatosensory cortex (S1 or area 3b) in primates. These studies are clearly important in processing f...
Monkeypox virus protein OPG188 antagonizes cGAS–STING antiviral signaling pathway to mediate immune evasion
Innate immune evasion is critical for productive viral replication. Activation of the cGAS–STING antiviral signaling pathway and its downstream effector genes plays a pivotal role in restricting viral...
Orthogonal disentanglement of single-cell multi-omics reveals private and shared drivers of tissue development and pathogenesis
Characterizing gene expression and regulatory dynamics underlying both normal tissue function and disease progression requires an integrative analysis of single-cell multi-omics data. However, the asy...
Transiently amplified fluctuations assemble dissipative materials
Chemical reactions assemble supramolecular materials with finite lifetimes, responsiveness to stimuli, and the capacity to self-heal after perturbation. These dynamic behaviors arise from a reaction c...
Subcellular calcium dynamics and organelle perturbations in resistosome-mediated cell death
Plant nucleotide-binding domain leucine-rich repeat-containing (NLR) proteins act as intracellular immune receptors that assemble into resistosomes to execute immune responses. However, the subcellula...
A nematode-built conduit for cross kingdom biotrophic interaction
Electroacupuncture-based vagal stimulation attenuates epileptic seizures through a body–brain circuit
Vagus nerve stimulation offers a promising strategy for seizure control but remains limited by its invasive delivery. Here, we reveal electroacupuncture (EA), an ancient neuromodulatory technique root...
Structural basis for substrate specificity and MSMEG_0435-0436 binding by the mycobacterial long-chain acyl-CoA carboxylase complex
The presence of mycolic acid is a defining feature of the mycobacterial cell wall, which provides a highly impermeable barrier to many antibiotics. Biosynthesis of this fatty acid, as well as tubercul...
SEL1L–HRD1 ERAD–autophagy interplay maintains mitochondrial homeostasis in brown adipocytes
Mitochondrial integrity is central to energy homeostasis, particularly in brown adipose tissue where dynamic remodeling fuels thermogenesis. Two major proteostatic systems, the SEL1L–HRD1 endoplasmic...
Hierarchical whole-brain modeling of critical synchronization dynamics in the human brain
The brain operates at the critical transition between order and disorder which supports optimal information processing. Whole-brain computational modeling is a powerful tool for uncovering the system-...
Phosphate scarcity governs methane production in the global open ocean
The observed supersaturation of methane (CH 4 ) in open-ocean surface waters implies widespread CH 4 production within t...
Reprogrammed SimCells for antimicrobial therapy
Antimicrobial resistance (AMR) is a critical global health challenge. In this study, we developed a platform based on chromosome-free and nonreplicating simple cells (SimCells, size 1 to 2 µm) and min...
Dual-encoder contrastive learning accelerates enzyme discovery
The ability to engineer enzymes for desired reactions is a cornerstone of modern biotechnology, yet identifying suitable starting proteins remains a critical bottleneck. Although contrastive learning...
Microglial fructose metabolism is essential for glioblastoma growth
Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors in adults. Its immune microenvironment is dominated by tumor-associated macrophages, including both infiltrat...
Mutually exclusive alternative pre-mRNA splicing promotes adaptive metabolic stress signaling by JNK
The JUN NH 2 -terminal kinase (JNK) signal transduction pathway is activated during the hepatic metabolic stress response. The JNK1 and JNK2 pre-mRNAs expressed...
When does higher credit lower forest area? Amazon contexts change credit’s impacts
Economic activities have transformed over half of the Earth’s surface and the large-scale conversion of rural forests to agropastoral production is ongoing. Raising access to credit may lead producers...
ATP13A2 restrains macrophage NLRP3 inflammasome activation to repress neurodegeneration via modulating mitochondrial homeostasis
Neuro-immune crosstalk is increasingly recognized in Parkinson’s disease (PD), and ATP13A2 is well known for its neuroprotective role. However, it remains unclear whether ATP13A2...
TON1 and FASS are required to recruit myosin VIII, a cell division guidance factor
Because plant cells cannot migrate, their position is fixed with respect to their neighbors. Thus, placement of the new cell plate is critical for determining cell shape, cell identity, and tissue pat...