Proceedings of the National Academy of Sciences
Articles in this Issue
Neural substrate of conditioned stimulus for associative learning in the hippocampus
Associative learning allows animals to learn the predictive relationships between events. Presentation of a conditioned stimulus (CS) preceding an unconditioned stimulus (US) within a short interval a...
Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation
Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq screening, we developed a syste...
Primate-informed neural network for visual decision-making
The human brain excels at complex tasks with remarkable efficiency, adaptability, and resilience, making it a powerful source of inspiration for AI. Here, we present a neural dynamics model inspired b...
Hyperglycemia promotes SIRT3-mediated deacetylation of SARM1 to exacerbate diabetic peripheral neuropathy in mice
Diabetic peripheral neuropathy (DPN), the most common complication of diabetes, lacks effective treatments and is characterized by early axonal degeneration mediated by sterile alpha and Toll/interleu...
M cell–dependent commensal uptake confers encephalitogenic phenotypes on γδT17 cells in Peyer’s patches
Interleukin-17-producing γδT cells (γδT17 cells) play a dual role in immune regulation, serving as both protectors in various tissues and orchestrators of inflammatory responses in autoimmune diseases...
Pathogen-inspired engineering of plant protease enhances late blight resistance
The apoplast is an important battlefield in plant–pathogen interactions. The late blight oomycete pathogen Phytophthora infestans, for instance, secretes cystat...
Nonsense-mediated decay controls a negative feedback loop in innate immune sensing
Nonsense-mediated decay (NMD) is an mRNA decay pathway which degrades potential harmful transcripts that contain premature termination codons. However, NMD’s importance also extends to the control of...
The major ion chemistry of seawater was closely coupled to the long-term carbon cycle during the Cenozoic
A ~fivefold decrease in the atmospheric concentration of CO 2 took place during the Cenozoic. This has often been viewed within the context of silicate weatheri...
Cell numbers contribute to cell fate during Ciona cardiopharyngeal mesoderm specification
The Ciona heart cell lineage can be accurately traced back to a pair of blastomeres, the B7.5 cells, that form at the 64-cell stage. In addition to the adult he...
Elucidating cooperative genetic events in DCIS progression in mutant <i>p53</i> –driven breast cancer
Ductal carcinoma in situ (DCIS) is a precursor mammary lesion characterized by abnormal epithelial cells in mammary ducts that remain confined to the luminal space. Not all DCIS becomes invasive, and...
Prevention of ubiquitination at K6 and K9 in mutant huntingtin exacerbates disease pathology in a knock-in mouse model
Huntington disease (HD) is caused by an expansion of the polyglutamine (polyQ) tract in the huntingtin protein (HTT), leading to its misfolding and aggregation. The subcellular localization of mutant...
SARS-CoV-2 peptide fragments selectively dysregulate specific immune cell populations via Gaussian curvature targeting
Immune cell populations are dysregulated in COVID-19 for currently unknown reasons: Plasmacytoid dendritic cell (pDC) populations are reduced, thus hampering antiviral responses. CD8...
Domestication drives repeated evolution of sexual–asexual life cycle trade-offs in yeast
For thousands of years, humans have domesticated animals and cultivated crops by managing reproduction and selecting for desirable traits. In contrast, microbial domestication has often occurred unint...
Targeting C1q signaling in fibro-adipogenic progenitors prevents regenerative fibrosis of aged muscle
Skeletal muscle fibrosis, as occurs with age, in response to injury, or in the setting of degenerative diseases, results in impairments of muscle regeneration and function. Fibro-adipogenic progenitor...
Pathogenic role of MIF receptor (CD74) expressing T cells in inflammatory arthritis
High expression alleles of the innate cytokine, macrophage migration inhibitory factor (MIF), are associated with the development or the severity of autoimmune inflammatory diseases, including rheumat...
Enhanced episodic specificity and socioemotional content in older adults’ everyday autobiographical thoughts
Cognitive aging research has long observed that older adults’ autobiographical memories and future thoughts, as assessed in laboratory contexts, lack spatiotemporal detail compared to young adults. Do...
Implementing the Kunming-Montreal Biodiversity Targets
The Kunming-Montreal Biodiversity Targets present the most ambitious and serious conservation agenda ever developed—the overarching goal of preserving 30% of the planet by 2030. An organizational fram...
Early life-stage thermal resilience is determined by climate-linked regulatory variation
The ecological context of developmental physiology remains largely unexplored. We previously showed that thermal selection primarily targets early embryos in...
The anticipation of imminent events is time-scale invariant
Humans predict the timing of imminent events to generate fast and precise actions, decisions, and other behaviors. Such temporal anticipation is critical over wide timescales, and especially salient o...
T-bet-expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape
Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption...
The right environment switches the enzymatic character
Adult neural stem cells mediate hippocampal synapse elimination for circuit homeostasis through MERTK
Although radial-like neural stem cells (rNSCs) give rise to functional neurons throughout life in discrete regions of the adult brain, their functions are not limited to neurogenesis. Recent studies i...
Reply to Sun: Real-world bulk density changes support high carbon sequestration potential of biochar
Effective chilling temperatures for dormancy release in extratropical forest trees increase from cold to warm regions
Seasonal dormancy in extratropical trees is a critical adaptation that synchronizes growth with favorable climatic conditions. Traditionally, the effective chilling temperatures (ECT) required for dor...
O-acyltransferase genes involved in the production of volatile sex pheromones in <i> <i>Caenorhabditis elegans</i> </i>
Gene family expansions are critical for functional diversification, yet the contributions of paralogs to metabolic pathways are often unclear. In Caenorhabditis...