Proceedings of the National Academy of Sciences
Articles in this Issue
Measurement of atomic scattering factors by cryoelectron microscopy
Determination of specimen structure from cryoelectron microscopy (cryo-EM) experiments relies on an accurate model of the electrostatic potential of the specimen. For biological macromolecules, the po...
Sterol divergence across eukaryotic kingdoms determines membrane susceptibility to saponins, a class of plant defense compounds
Saponins are a class of plant-derived amphiphile defense compounds that disrupt cellular membranes, yet the basis for their selective toxicity remains unclear. Because membrane sterols diverged across...
<i>MiR-155</i> -driven loss of ICOSL and SOCS1 in EBV+ gastric cancers renders abundant cytotoxic T cells ineffective, enabling immune evasion
Poorly differentiated gastric carcinomas (PDGC) comprise 30% of gastric cancers and are associated with poor prognosis, correlating with tumor size and microvascular invasion. PDGC may be subcategoriz...
How endosomal PIKfyve inhibition prevents viral membrane fusion and entry
Enveloped viruses enter cells by membrane fusion. The viral membrane fuses with a host membrane, either at the cell surface or within endocytic compartments. For endocytic entry, fusion is typically t...
Global crop introduction drives host jumps, turning native pathogens into emerging diseases
Global crop movement has traditionally been viewed as a major driver of emerging plant diseases through the introduction of pathogens into naïve environments. Here we show that the reverse process, in...
Lunar silicon cavity
The Moon’s permanently shadowed regions (PSRs) are among the coldest places in the Solar System and are expected to become key landing sites for upcoming international space agency missions. Their pro...
Demonstrating real advantage of machine learning–enhanced Monte Carlo for combinatorial optimization
Combinatorial optimization problems are central to both practical applications and the development of optimization methods. While classical and quantum algorithms have been refined over decades, machi...
Inflammasome adaptor protein ASC is a mechanistic checkpoint in IL-1β maturation
Inflammasome activation triggers caspase-1-dependent maturation of pro-interleukin-1β (pro-IL-1β) in an apoptosis-associated speck-like protein containing a CARD (ASC)-dependent manner, yet the mechan...
Reconstructing ancient genomes from gene counts: A robust likelihood framework with sampling bias correction
Deducing the makeup of ancient genomes is a fundamental challenge in evolutionary biology. While vast genomic datasets exist that span the entire tree of life, current methods for ancestral reconstruc...
Evaluating the statistical realism of LLM-generated social science data
Large language models (LLMs) hold great promise for generating social science data, potentially expanding the methodological toolkit of quantitative social research. Prior studies have primarily focus...
D614G reshapes allosteric networks and opening mechanisms of SARS-CoV-2 spikes
The severe acute respiratory syndrome coronavirus 2 spike glycoprotein enables infection through a key conformational transition that exposes its receptor binding domain (RBD). Experimental evidence i...
Clinician behavior when skin tone affects test results
We compare care for Black vs. White patients following pulse oximetry, a widely used device for measuring blood oxygen levels which overestimates oxygen saturation in darker-skinned patients. Black pa...
Evolution of species’ range and niche in changing environments
What causes species’ niche and range margins to shift is not only a fundamental theoretical question, but also directly affects how we assess the resilience of natural populations in current and futur...
A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit
The structure of the catalytic subunit of cAMP-dependent protein kinase (PKA-C), a prototype for the protein kinase superfamily, laid the foundation for the development of targeted kinase inhibitors....
Acupuncture does not work and has no place in science-based medicine
Low-barrier hydrogen bond powers long-range radical transfer in the metal-free ribonucleotide reductase
Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotide (RNA) to deoxyribonucleotide (DNA) building blocks initiated by a long-range (>30 Å) proton-coupled electron transfer (PCE...
Trade-offs between light absorption and energy transfer in a marine light-harvesting complex 2
Purple bacteria are a diverse group of photosynthetic organisms that can capture and convert light energy with high quantum efficiency across a variety of ecological niches. They absorb light via an a...
Force patterning drives quasistratification and graded tissue-scale spatial order in auditory epithelia
During development, coordinated cell behaviors drive epithelial morphogenesis toward precise three-dimensional architectures essential for physiological function. How such coordination arises in epith...
Comparing variable selection and model averaging methods for logistic regression
Model uncertainty is a central challenge in statistical models for binary outcomes such as logistic regression, arising when it is unclear which predictors should be included in the model. Many method...
The electoral choice context and support for democratic norms
In this paper, we explore whether different choice environments affect voters’ willingness to put democracy over party and policy. Using a series of candidate choice experiments in which we manipulate...
Functional dissection of <i>SPOP</i> at the amino acid level reveals a comprehensive functional landscape of variants during tumorigenesis
Numerous proteins display pleiotropic functions in different clinical contexts. However, the molecular mechanism underlying such effects is rarely understood. Speckle-type POZ protein (...
A molecular timer couples organism-wide temporal identity to developmental checkpoints
Coordinated development requires that growth and cell-fate transitions occur in a defined temporal order across tissues, yet how multicellular organisms generate and synchronize developmental timing i...
Linkage of nucleotide and functional diversity varies across gut bacteria
Understanding the forces shaping genomic diversity within bacterial species is essential for interpreting microbiome evolution, ecology, and host associations. Here, we analyze over one hundred preval...
Incentive valence differentially engages open- and closed-loop basal ganglia circuits during movement initiation
Incentives modulate voluntary movement, yet the circuitry channeling these signals into motor output remains unclear. Classical models emphasize a closed-loop circuit (CLC) linking dorsal putamen (PUT...
Robust associations of emotional intelligence with human flourishing: A second-order meta-analysis
Emotional intelligence (EI) is an umbrella term that has been used to describe i) the ability to reason accurately about emotions and use emotions to augment thought processes, ii) a constellation of...