Proceedings of the National Academy of Sciences
Articles in this Issue
Reducing PTSD symptoms through unconscious intervention
Intrusive traumatic memories are a hallmark symptom of posttraumatic stress disorder (PTSD). Conventional therapies typically require explicit and emotionally distressing reexposure to trauma cues, of...
SonoPIN enables precise, noninvasive, and efficient intracellular delivery of PROTACs
Proteolysis-targeting chimeras (PROTACs) have emerged as a promising molecular approach for degrading undruggable proteins and for overcoming drug resistance in cancer therapy. However, their clinical...
Stretch and flow at the gliovascular interface: High-fidelity modeling of astrocyte endfeet
Astrocyte endfeet form a near-continuous sheath around the brain’s vasculature, defining the perivascular spaces (PVS) that are crucial for brain fluid flow and solute transport. Yet, their precise ph...
Nonreciprocal buckling makes active filaments polyfunctional
Active filaments are a workhorse for propulsion and actuation across biology, soft robotics, and mechanical metamaterials. However, artificial active rods suffer from limited robustness and adaptivity...
Narrative “twist” shifts within-individual neural representations of dissociable story features
Given the same input, understanding of that input can differ depending on context. How does the brain represent the latent mental frameworks that support different interpretations of the same sensory...
Reversibility and β-sheet formation are decoupled in tau condensate aging
Neurofibrillary tangles (NFTs) formed from the protein tau disrupt neuronal function in Alzheimer’s disease and are strongly associated with cognitive decline. Early events in tau aggregation are incr...
Methylation-associated mutagenesis underlies variation in the mutation spectrum across eukaryotes
Mutation spectra vary across genetic and environmental contexts, leading to differences between and within species. Most research on mutation spectrum has focused on trinucleotide (3-mer) mutation typ...
ODC1 restricts meningeal B cell age-associated-like phenotype and function in multiple sclerosis: A human and experimental study
Meningeal inflammation, as a clinical feature of multiple sclerosis (MS), is associated with worse clinical disease outcomes. In both relapsing and secondary progressive MS and the experimental autoim...
Non-Fickian diffusion within assemblies of the intrinsically disordered protein β-casein
The molecular mechanisms governing internal fluctuations in intrinsically disordered protein (IDP) assemblies are crucial to the stability and dynamics of both regulated and aberrant toxic cellular ag...
A global analysis of patterns of tuberculosis exposure and transmission
Tuberculosis (TB) is a major public health concern and the leading infectious cause of mortality globally. The disease exhibits strong prevalence patterns by age and sex, but the implications of these...
Anion-mediated solvation structures and intercalation chemistry of aqueous zinc-ion electrolytes
Understanding solvent/solute-borne coordination structures and their impact on electrode intercalation chemistry is crucial for the rational design of high-performance electrolytes. Nevertheless, the...
DeepDegradome: A structure-aware deep learning framework for PROTAC and ligand generation against protein targets
Targeted protein degradation is a promising strategy for drug discovery, but designing effective PROTACs remains challenging, especially for proteins without well-defined binding sites. Current method...
Host ESCRT machinery orchestrates the assembly of tomato spotted wilt virus ribonucleoproteins
The genomic RNA of negative-strand RNA viruses is encapsidated by nucleocapsid proteins and associates with RNA polymerase to form a ribonucleoprotein (RNP) complex. Lacking both a 5’ cap and a 3’ pol...
Charge-reversal proteolysis polymers enable tissue-specific STING degradation in rheumatoid arthritis
Inhibiting stimulator of interferon genes (STING) is critical for treating rheumatoid arthritis (RA), yet achieving precise suppression with high tissue specificity across protein variants remains cha...
A <i>KCNC1</i> variant linked to Rett syndrome disrupts ER to Golgi trafficking of Kv3.1 channel
Intrinsic neuronal excitability, defined by the balance between input and output signals, is crucial to neural function, and its disruption underlies various neurological diseases. Kv3.1 channels, enc...
Atomistic simulations reveal the photoactivation mechanism of a carotenoid-binding photoreceptor
The orange carotenoid protein (OCP) is a key photoreceptor in the photoprotection of cyanobacterial antenna complexes. Its peculiar activity is governed by a bound keto-carotenoid that functions both...
Online supervised learning of temporal patterns in biological neural networks under feedback control
In vitro biological neural networks (BNNs) provide well-defined model systems for constructively investigating how living cells interact with their environments to shape high-dimensional dynamics that...
Structural innovation in the evolution of plant chemical defense
Chemical defenses are fundamental in organismal biology and widely used in medicine and agriculture. Plant defense chemistry evolves in response to various selective pressures, particularly herbivory,...
Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels
The transcription factor c-Myc is a master oncoprotein that regulates over 15% of all genes. Protein phosphatase 2A (PP2A), a crucial tumor suppressor, destabilizes c-Myc protein. Classically, PP2A-me...
Generating a stratocumulus-like cloud top in a convection-cloud chamber
Stratocumulus-topped boundary layers play a crucial role in influencing daily weather and earth energy balance. Entrainment at the stratocumulus cloud top affects the cloud’s lifetime, precipitation,...
Cultural evolution accelerated human range expansion by more than two orders of magnitude
Humans occupy a geographic and ecological range wider than that of any other extant vertebrates, having rapidly expanded into nearly every habitat on the planet. This expansion was driven not only by...
Hypothalamic endoplasmic reticulum stress drives pubertal precocity due to early-onset obesity in female rodents
Early-onset obesity, especially in girls, is frequently associated with advanced puberty; a phenomenon bound to increased risk of long-term complications. Hypothalamic endoplasmic reticulum (ER) stres...
Acoustic Pancharatnam–Berry geometric phase for structured sound manipulation
Phase control is fundamental to acoustic wave manipulation. The propagation and resonant phases have been widely used to modulate acoustic waves. However, the real-space geometric phase, also known as...
Integrated framework to study genomic surveillance of selective sweeps in multivariants dynamics
Pandemics often involve complex transmission dynamics in which epidemiological surveillance is essential but not sufficient for containment, as resurgence may be driven by emerging or imported variant...
Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1
Microglia use a highly complex and dynamic network of branched processes to sense and respond to their surroundings. Despite emerging evidence that microglial motility plays important roles in brain d...