Proceedings of the National Academy of Sciences
Articles in this Issue
Life’s homochirality: Across a prebiotic network
For centuries, scientists have been puzzled by the mystery of life’s biomolecular homochirality—the single-handedness of biological compounds. Sugars and nucleic acids are right-handed, while amino ac...
Nitric oxide promotes cysteine N-degron proteolysis through control of oxygen availability
Selected proteins containing an N-terminal cysteine (Nt-Cys) are subjected to rapid, O 2 -dependent proteolysis via the Cys/Arg-branch of the N-degron pathway....
Unraveling the neuroimmune mechanisms in cancer-induced bone pain: New horizons for therapeutic intervention of the two-phase paradigm
Cancer-induced bone pain (CIBP) is a severely painful condition that profoundly impacts patients’ quality of life. However, the neuroimmune mechanisms underlying CIBP remain largely elusive. Substance...
Loss of sialic acid side-chain <i>O</i> -acetylation exacerbates colitis
Sialic acids (Sias) are a diverse family of nine-carbon backbone monosaccharides occupying terminal positions on cell surface and secreted glycans and are abundant at mucosal surfaces. Sias can be mod...
A universal of speech timing: Intonation units form low-frequency rhythms
Intonation units (IUs) are a hypothesized universal building block of human speech [W. Chafe, Discourse, Consciousness and Time: The Flow and Displacement of Conscious Experience i...
GATA3 promotes ferroptosis resistance by repressing integrin β1 signaling
Understanding mechanisms that determine the response of cells to ferroptotic stress is a timely issue that has significant ramifications for biology and pathology. We investigated these mechanisms in...
ER-resident CCDC134 safeguards TLR4 maturation by maintaining gp96 stability
Toll-like receptor 4 (TLR4), a pattern-recognition receptor located on the plasma membrane, senses extracellular danger signals to initiate inflammatory immune responses. It is initially synthesized i...
Synergistic action of specialized metabolites from divergent biosynthesis in the human oral microbiome
Despite extensive efforts, our understanding of the virulence factors contributing to oral biofilm formation—a hallmark of dental caries—remains incomplete. We present evidence that the specialized me...
Sparse autoencoders uncover biologically interpretable features in protein language model representations
Foundation models in biology—particularly protein language models (PLMs)—have enabled ground-breaking predictions in protein structure, function, and beyond. However, the “black-box” nature of these r...
Melanocyte-dependent macrophage redistribution enhances skin immunity upon acute stress
It is well established that stress generally suppresses immunity. However, under certain conditions, acute stress has been shown to stimulate the immune system, particularly those at barrier surfaces...
Aspartic acid residues in BBE-like enzymes from <i>Morus alba</i> promote a function shift from oxidative cyclization to dehydrogenation
Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism underlying the selectivity...
The rise of diversity terminology in biomedical research
Recent scholarship has highlighted the rise of “diversity projects” across various educational and business contexts, but few studies have explored the meaning of diversity in biomedical research. In...
Asymmetric development and function of paired sperm-storage organs in <i>Drosophila melanogaster</i>
Paired structures often have similar forms and functions, but the processes underlying their formation can differ. They may originate from a common source or from parallel sources, or arise from disti...
Altricial brains and the evolution of infant vocal learning
Vocal development in human infants is strongly influenced by interactions with caregivers who reinforce more speech-like sounds. This trajectory of vocal development in humans is radically different f...
Systemic <i>Kras</i> ablation disrupts myeloid cell homeostasis in adult mice
The KRAS oncogene has been associated with many types of cancer, including pancreatic, lung, and colorectal. For decades, its gene products were thought to be u...
Multisensory feedback makes swimming circuits robust against spinal transection and enables terrestrial crawling in elongate fish
Vertebrate locomotion is due to the interplay of neural oscillators and sensory feedback loops in the spinal cord that interact with the body and the environment. Here, we study these circuits with a...
The likelihood of sympatric speciation and morphological divergence in plants
Sympatric speciation is considered rare, but oceanic Howea palms, crater lake cichlids, and parasitic indigobirds provide compelling evidence that it occurs. St...
Svalbard’s 2024 record summer: An early view of Arctic glacier meltdown?
A record-breaking melt season affected the Arctic glaciers of Svalbard in summer 2024 by a substantial margin. Across the entire archipelago, glacier melting corresponded to an anomaly of up to four S...
The nature of ant caste allometry
Reply to Michał Bogdziewicz et al.: Research on the summer solstice needs falsifiable predictions
Into the belly of the brainstem: The neurons of the “extended” enteric nervous system
Identifying fish populations prone to abrupt shifts via dynamical footprint analysis
Fish population biomass fluctuates through time in ways that may be either gradual or abrupt. While abrupt shifts in fish population productivity have been shown to be common, they are rarely integrat...
Transient oxygenation of the Mediterranean after the Zanclean megaflood
The Mediterranean basin reconnected to the Atlantic Ocean ~5.33 Myr ago, following its partial desiccation during the preceding Messinian salinity crisis (5.97 to 5.33 Myr). While the extent of termin...
Germline variants in <i>UHRF1</i> are associated with multilocus imprinting disturbance in humans and mice
The investigation of congenital imprinting disorders (CIDs) provides opportunities to elucidate the molecular mechanisms and role of genomic imprinting in development and human disease. Beckwith–Wiede...
Indigenous fire stewardship shaped North American Great Lakes forests
Interest in bringing Traditional Ecological Knowledge (TEK) and Western Science together to enhance climate and landscape resilience is growing rapidly, particularly for engagement with pyrogenic comm...