Proceedings of the National Academy of Sciences
Articles in this Issue
Insulin and leucokinin pathways coordinate adaptive salt appetite in <i>Drosophila</i>
Salt intake must be tightly regulated: Too little compromises physiological function, while too much is harmful. Animals therefore display an adaptive salt appetite, dynamically switching between attr...
Nonoxidative pentose phosphate pathway regulates CD8 <sup>+</sup> T cell immunity by maintaining NADPH homeostasis
NADPH is essential for cellular biosynthesis and redox balance in CD8 + T cells. Here, we demonstrate that the nonoxidative pentose phosphate pathway (non-oxPPP...
Clemastine fumarate promotes myelin repair in a nonhuman primate model of demyelination characterized by absent spontaneous remyelination
Promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery in white matter diseases such as multiple sclerosis. Clemastine fumarate among sev...
Stress and resilience in northern European marine ecosystems
Marine ecosystems are facing multiple pressures from human activities, such as fishing and nutrient inputs from farming and agriculture, compounded by the global effects of climate change. As a result...
Robust input disentanglement through dendritic calcium–mediated action potentials
In daily life, living beings encounter a continuous stream of mixed information, which has to be disentangled by the brain to form proper representations. Using computational modeling, we demonstrate...
A Meier–Gorlin syndrome mutation impairs the loading of the MCM2–7 complex during DNA replication initiation
Chromatin loading of the hexameric replicative helicase MCM2–7 complex requires coordinated interactions with the origin recognition complex (ORC), CDC6, and CDT1. MCM2–7 not bound to DNA forms a sing...
Decadal extreme drought reduces alpine subsoil carbon stocks
Grassland soil organic carbon (SOC) stocks are increasingly vulnerable to intensified drought. Yet, how long-term, especially extreme, drought affects these C reserves across soil profiles remains unr...
Operator-level quantum acceleration of non-logconcave sampling
Sampling from probability distributions of the form σ ∝...
DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes
Retinal pigment epithelium (RPE) cell damage is a critical factor of age-related macular degeneration (AMD), the leading cause of blindness among the aged population. This study focuses on the AMD sus...
Correction for Nasca et al., Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity
The Crohn’s disease–related RNF123 prevents NLRP3 inflammasome assembly by catalyzing unanchored K63-linked ubiquitination on NEK7
The NLRP3 inflammasome is crucial for host defense against pathogen invasion and is implicated in various inflammatory disorders. The pathogenic association and the involved mechanism between the NLRP...
Pheromone receptors for japonilure in <i>Anomala corpulenta</i> and <i>Popillia japonica</i>
Using gas chromatography-electroantennographic detection (GC-EAD), gas chromatography-mass spectrometry (GC-MS), and chiral capillary GC with synthetic stereoisomers, followed by laboratory and field...
Human lncRNA <i>RMRP</i> interacts with DEAD-box helicases and modulates mitochondrial function
The human long noncoding RNA (lncRNA) RMRP , initially identified as part of the RNase MRP complex, is linked to various human diseases. However, its structural...
Aging-associated differences in mammary tumor–initiating populations and immune evasion pathways in breast cancer
Aging is a major risk factor for breast cancer, yet how it shapes tumor development, molecular phenotype, and immune evasion remains incompletely understood. Deciphering how aging influences cancer ev...
Lipoprotein diffusion in dense yolk plasma is governed by softness, hydrodynamics, and caging: Insights from MHz-XPCS
Low-density lipoproteins (LDLs) are central to nutrient transport in egg yolk and have emerged as natural nanocarriers for drug delivery. Their biological function critically depends on mobility withi...
Temperature and sex ratios at birth
Human sex ratios at birth (SRBs) shape population composition and are closely linked to maternal health and gender discrimination. In the context of environmental change, SRBs may theoretically be ske...
Reversible acetylation of Hpo regulates the Hippo pathway
The Hippo pathway, which is highly conserved from Drosophila to mammals, plays a crucial role in regulating organ size and tissue homeostasis. Dysregulation of...
Mfsd2a is important for maintaining epidermal homeostasis
The skin epidermis is a multilayered lipid rich organ completely reliant on exogenous delivery and uptake of the essential fatty linoleate for the synthesis of acylceramides required for barrier funct...
Hallucination, monofacts, and miscalibration: An empirical investigation
Hallucinated facts in large language models have recently been shown to obey a statistical lower bound determined by the monofact rate (related to the classical Good-Turing missing mass estimator) min...
Plastid 2-oxoglutarate-dependent dioxygenases mediate stereoselective C14β-hydroxylation in cardenolide biosynthesis
Cardenolides, widely distributed across multiple plant families, have long been utilized in traditional and modern medicine for treating heart failure and various cancers. Despite progress in understa...
Selective control of ligand binding through a distal mutation that alters the protein native ensemble
Unraveling the molecular mechanisms underlying long-range mutational effects on function is a challenging prospect. In this study, we delineate the consequences of a mutation located at a site distal...
A hybrid compass mechanism combining radical pairs and magnetite crystals
That night-migratory songbirds have a magnetic compass sense is undisputed. The nature of the sensor, however, is far from certain. The two leading hypotheses are organic radical pairs in cryptochrome...
Km-scale coupled simulation and model–observation SST trend discrepancy
The spatial pattern of sea surface temperature (SST) change in the tropical Pacific plays a central role in shaping global climate through its influence on atmospheric circulation, rainfall, and extre...
TROP2-targeted NIR-II fluorescence imaging for visualizing surgical margins and metastatic sentinel lymph nodes in breast cancers
In early breast cancer surgery (EBC), free margins significantly decrease local recurrence in breast-conserving surgery (BCS), while metastatic status of sentinel lymph node (SLN) impacts axillary man...
Valuing wildfire smoke–related mortality benefits from climate mitigation
Human-induced climate change has increased wildfire risks, associated air pollution, and health damages in North America. Despite its large potential for damage, climate-induced wildfire smoke is rare...