Proceedings of the National Academy of Sciences
Articles in this Issue
Loss of FoxO in skeletal muscle leads to disrupted muscle metabolism and exacerbates starvation-induced hepatic steatosis
Up to a third of the global population is afflicted by metabolic dysfunction-associated steatotic liver disease with excessive triglyceride accumulation in the liver. Prolonged fasting rapidly causes...
Selective reuse of prior ensemble data improves the latest air temperature forecast over North America
Accurate subseasonal to seasonal (S2S) weather forecasts are critical for managing risks to society, yet improving forecast skill remains challenging. Ensemble forecasting mitigates atmospheric chaos...
Nanocondensate bioadhesive delivery via metal–halogenated catechol coordination in tunicate rhizoid holdfasts
The root-like holdfast of the tunicate Halocynthia roretzi provides strong underwater adhesion. However, the biological processing and biochemical composition u...
China’s demographic dividend has moved from age-based labor supply to skill-based productivity
Accelerated global population aging challenges conventional economic growth paths. Yet, the mechanisms underlying the transition from the age-based demographic dividend, derived from a favorable age s...
Reconstruction of human metabolic models with large language models
Genome-scale metabolic models (GEMs) have become essential tools for understanding human metabolism. Here, we introduce Human2, a consensus human GEM with enhanced precision and biological relevance,...
Offspring chemical control of adult reproductive transitions in a social insect
Parental care enhances offspring survival and growth but often entails a trade-off in which caregivers temporarily suppress their own reproduction to invest in existing young. In vertebrates, these pa...
Alternative microexon splicing code for a four-amino acid peptide of PTPRD governs behavioral development
Microexons of 3 to 27 nucleotides selectively regulated in the vertebrate nervous system have attracted attention as new elements for modifying the function of neuronal proteins. Protein tyrosine phos...
STAG2 loss amplifies EWS-FLI1-driven microsatellite enhancer activity promoting Ewing sarcoma aggressiveness
Ewing sarcoma is driven by chromosomal translocations that fuse a FET RNA-binding protein to an ETS transcription factor, most commonly generating the EWS-FLI1 fusion oncoprotein. EWS-FLI1 engages GGA...
Nocturnal hydration prepares desert cyanobacteria for dawn-light harvesting by inducing phycoerythrin synthesis
As crucial ecosystem engineers in global drylands, desert cyanobacteria regulate biogeochemical cycling and contribute to the stabilization of arid soils. These extremophiles frequently exploit noctur...
Simulation-based inference captures non-Markovian effects as exemplified in protein production kinetics through cell division
Inferring protein production kinetics in dividing cells is complicated by protein inheritance from the mother cell. For instance, fluorescence measurements commonly used to assess gene activation may...
Selective depletion of virus-specific CD8 T cells from the liver after PD-1 therapy with Fc-intact antibody during chronic infection
Anti-programmed cell death 1 (PD-1) antibody therapy is now widely used in various cancers. However, the role of the antibody Fc region in PD-1 directed immunotherapy is not well understood. Preclinic...
Hypoxia inducible factors regulate pneumovirus replication by enhancing innate immune sensing
The immune mechanisms responsible for protection and pathogenesis in pneumoviral infection are not well defined. We demonstrated that pharmacological activation of the hypoxic inducible factor (HIF) s...
RIPK1 ubiquitination regulates its kinase-independent function in development and inflammation
Receptor-interacting protein kinase 1 (RIPK1) is a key regulator of cell death and inflammation, with its activation modulated by diverse posttranslational modifications. While ubiquitination of RIPK1...
Transient ion-mediated interactions regulate subunit rotation in a eukaryotic ribosome
While it is well known that ion binding can stabilize RNA structure, little is known about how transient/probabilistic ionic interactions facilitate biologically relevant conformational rearrangements...
Elucidation of the aragonite nanofiber formation mechanism of LICP contained in the hinge ligament of <i>Pinctada fucata</i>
The hinge ligament of bivalves exhibits remarkable flexibility and compressive strength due to its composite structure of aragonite nanofibers embedded in an organic matrix. While these nanofibers are...
Targeted degradation of c-Myc through the midnolin–proteasome pathway
Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy; however, most TPD technologies employ either the ubiquitin–proteasome system or the lysosomal degradation system. He...
Aging alters DNA structure–induced genetic instability in mice
Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the devel...
Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability
Astrocytes and tanycytes play essential roles in hypothalamic metabolic sensing, yet how glial–glial communication translates metabolic cues into neuronal activity remains poorly understood. We previo...
A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation
The Arg/N-degron pathway of Saccharomyces cerevisiae is mediated by two interacting E3 ubiquitin ligases, Ubr1 and U...
Chemputer and chemputation—A universal chemical compound synthesis machine
Chemputation treats chemical synthesis as the execution of reaction code on programmable hardware. We show that a Chemputer, equipped with an extensible set of reagents, catalysts, and process conditi...
Multimetric analysis uncovers time-dependent climate forcings from China’s 2.3-fold cropland reactive nitrogen emissions
China is the largest emitter of cropland gaseous reactive nitrogen (Ngr, including NH 3 , N 2 O, and NOx), which greatly...
Whole-genome combinatorial gene fusions generate novel genes for advanced microbial trait development
Translational fusion of two separate genes into a compound sequence encoding a fusion protein is a key evolutionary mechanism which underpins the emergence of new protein activities, families, and arc...
Pathogen hijacks focal adhesion signaling by a T3SS effector CteX
Infections by Gram-negative pathogens like Salmonella and Shigella...
A secreted citrus protease cleaves an outer membrane protein of the Huanglongbing pathogen
Plants secrete a variety of proteases as a defense response during infection by microbial pathogens. However, the relationship between their catalytic activities and antimicrobial functions remains la...
Sender–receiver subdivisions of the default mode network in perceptual and memory-guided cognition
Everyday cognition depends on the brain’s capacity to shift between sensing the external world and constructing it from memory. To achieve this, large-scale cortical systems must flexibly integrate in...