Proceedings of the National Academy of Sciences
Articles in this Issue
An activity–resistance trade-off constrains enzyme evolution
The presence of self-resistance genes in antibiotic-producing organisms poses a paradox: How can resistance evolve before the antibiotic exists, and how can an antibiotic producer arise without first...
Sentinel plants enable quantitative monitoring of bioavailable nitrate in soils and microbial environments
Microbial transformations of nitrogen in soils strongly influence plant nutrition and ecosystem function, yet monitoring these processes remains challenging. Existing approaches rely largely on extrac...
The quantum ensemble variational optimization algorithm: Applications to molecular inverse design
Designing molecules with optimized properties remains a fundamental challenge due to the intricate relationship between molecular structure and properties. Traditional computational approaches that ad...
Hazard curvature makes within-host variability costly for survival
Tumors, pathogens, and immune responses are increasingly modeled as ecological and evolutionary systems inside hosts. Yet the clinically meaningful endpoint is usually not the trajectory of those inte...
Matrix effects reshape organic aerosol volatility and atmospheric persistence
The volatility of individual species is a fundamental property governing the gas-particle partitioning of organic aerosols. However, in complex organic mixtures, a compound’s apparent volatility may d...
PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization
The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of enzymes generate most of the phosphatidylinositol-4,5-bisphosphate [PI(4,5)P 2 ] lipids in eukar...
Peroxisomal ether lipid synthesis regulates cortical neurogenesis and maintains mitochondrial energy homeostasis in radial glial cells
Neurogenesis is characterized by dynamic structural changes and functional remodeling of multiple organelles, which interact to form an intricate network that precisely modulates processes including n...
Wireless, skin-attachable patch with 3D liquid metal electrodes for vagus nerve stimulation in depression
Current nonsurgical vagus nerve stimulation (VNS) approaches often suffer from broad current spread, high electrode-skin impedance, and unintended stimulation of surrounding tissues, which can reduce...
Cortical gray matter myelin cuts energy cost of spike propagation without increasing conduction velocity
Myelin is a hallmark of vertebrate nervous systems, yet its roles in central axons remain elusive. Using optical and electrical recordings from thin axons of Layer 5 pyramidal neurons in murine cortic...
Blm10 and PI31 comprise a failsafe mechanism for proteasome inhibition
Blm10 (PA200 in mammals) is an evolutionarily conserved regulator of the proteasome’s core particle (CP), a barrel-shaped complex that houses six individual protease subunits. Despite decades of study...
Electro-nuclear quantum phase transition in TmVO <sub>4</sub>
Hyperfine interactions couple nuclear and electronic degrees of freedom. The present work explores how hyperfine coupling within the Tm ions in TmVO 4 single cr...
<i>SHOOT GRAVITROPISM 9</i> links sensory timing to the initial lateral root growth angle
Plants strategically respond to gravity and actively set defined growth angles. These gravitropic set-point angles (GSAs) shape the width and depth of the root system, determining soil exploration for...
Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment
G protein–coupled receptors (GPCRs) constitute the largest superfamily of cell-surface receptors, yet the spatial constraints governing their signaling remain poorly defined. Here, we demonstrate that...
Richard D. Alba 1942–2025: Distinguished scholar of ethnicity and immigrant assimilation and cherished mentor and friend
Richard D. Alba, a path-breaking sociologist who studied immigrant assimilation and its impact on mainstream cultures, in the United States and in Western Europe, passed away on June 4, 2025, at the a...
Structural rigidity of the I–II loop couples Ca <sub>V</sub> β anchoring to Ca <sub>V</sub> 2.2 gating modes
The auxiliary β subunits of voltage-gated Ca 2+ (Ca V ) channels are fundamental regulators of channel gating and neuron...
Deciphering the mechanism of protein aggregation and effects of inhibitors using single-molecule mass photometry
Aggregation of misfolded proteins is a prominent feature of many diseases and hence an attractive drug target. However, the small oligomers that are critical early species in the aggregation cascade a...
Cell division sets a universal flow geometry in cell layers
Collective flows in epithelial tissues contain a geometric backbone of vortical interfaces whose statistics exhibit hallmarks of critical percolation and conformal invariance. Yet how fundamental cell...
Parabrachial <i>Ntsr1</i> neurons modulate food intake and anxiety through a projection to the ventromedial hypothalamus
The parabrachial nucleus (PBN) is an important hub located in the pons that relays sensory signals from peripheral regions. It is genetically diverse and contains many populations that modulate feedin...
Long-range magnetoelectricity in type-II multiferroic NiI <sub>2</sub>
Type-II multiferroics, where spin order induces ferroelectricity, exhibit strong magnetoelectric coupling. However, for the typical 2D type-II multiferroic NiI 2...
Mechanisms of von Willebrand factor activation driving no reflow in ischemic stroke
Rapid restoration of cerebral blood flow is the cornerstone of acute ischemic stroke treatment. Endovascular thrombectomy achieves substantial reperfusion in 90% of patients with large-vessel occlusio...
Why shear adhesion is not monotonically enhanced by stiffening
Interfaces between dissimilar elastic materials are ubiquitous in biological and engineered systems and often span orders of magnitude in stiffness. Yet it remains unclear whether stiffening an adhesi...
Small subunit M20 augments inhibitory phosphorylation of MYPT1 in myosin light chain phosphatase by inhibiting autodephosphorylation
Smooth muscle myosin light chain phosphatase (MLCP), composed of a catalytic subunit PP1c and large and small noncatalytic subunits (MYPT1 and M20, respectively), is a key mediator of Rho-associated c...
Correction for Sen et al., mTOR signaling governs the formation of epithelial apical projections via S6K1–RhoA and aPKC–Lgl2 axes
Classification models for KCNQ1 variants distinguish functional and trafficking effects to enhance pathogenicity interpretation
Missense variants in the potassium channel KCNQ1 underlie most cases of congenital long QT syndrome (LQTS), one of the most common genetic arrhythmias. Variants affect protein stability, trafficking,...
Fluid polarity shifts initiate and amplify preferential flow in clay-rich media
Preferential flow governs fluid and solute transport across scales from micropores to regional watersheds, yet it is commonly attributed to static pore-structure heterogeneity. Here, we show that flui...