Proceedings of the National Academy of Sciences

Nonequilibrium colloidal transport mechanisms such as diffusiophoresis and Marangoni transport enable rapid and targeted delivery of colloids by exploiting in-situ or externally imposed chemical gradients, particularly in systems like dead-end pores where pressure-driven flow is ineffective. However, the duration of such transport is limited by how long the driving gradient persists. Here, we pre…

DNA double-strand breaks, including those arising from DNA interstrand crosslinks, are highly cytotoxic forms of DNA damage. Their precise repair by homologous recombination (HR) is essential for maintaining genomic stability. During HR, timely disassembly of the core machinery, RAD51 nucleoprotein filaments, is critical. The FIGNL1–FIRRM (also known as C1orf112) AAA+ ATPase has recently been ide…

Epstein–Barr virus (EBV) colonizes secondary lymphoid tissues to establish persistent infection and is strongly associated with malignancy and autoimmunity. Our understanding of EBV infection biology is hindered by a lack of models that capture infected B cell activity in the lymphoid tissue microenvironment. We therefore developed an EBV human tonsil organoid model to evaluate key B cell states …

With the persistent threats from severe respiratory diseases and airborne pollutants, billions of people worldwide lack timely access to essential diagnostic services, particularly in low-resource regions where laboratory infrastructure is scarce. Conventional pump-suction airborne samplers face challenges including cost, power dependency, and unavoidable analyte loss in complex systems. Here, we…

Diffuse midline gliomas (DMGs) are highly aggressive, WHO grade 4 glial tumors that arise in midline central nervous system structures and are defined by K27M mutations in histone H3 genes. These K27M mutations shape intratumoral myeloid cell composition in DMG. In H3.1K27M DMGs, genetic ablation of monocyte recruitment reshapes the tumor microenvironment (TME) by reducing monocyte-derived macrop…

Vacuoles store up to 90% of cellular phosphorus in plants, serving as a critical buffer against cytosolic fluctuations during environmental nutrient stress. Despite this central role, the molecular mechanisms governing vacuolar inorganic phosphate (Pi) release through vacuolar Pi efflux transporters (VPEs) remain unclear. Through integrative structural biology, we elucidate how the rice transport…

Cellular processes often exhibit irreversible state transitions even after external signals responsible for a transition are withdrawn. Long-standing questions remain: Where does such irreversibility originate from and can it be reversed? Although positive-feedback circuits among cellular components are known to relate to irreversibility, which circuits hold the dynamical origin of such irreversi…

Out-of-frame translation events, arising from ribosomal frameshifting or noncanonical initiation, are an unavoidable feature of translation. Their consequences depend on the distribution of stop codons in alternative reading frames, which determines the permissiveness of those frames: whether out-of-frame translation terminates quickly or generates extended products. Using quantitative dual-fluor…

Many computational methods in ab initio quantum chemistry are formulated in terms of high-order tensor contractions, whose cost determines the size of system that can be studied. We introduce stochastic tensor contraction to perform such operations with greatly reduced cost, and present its application to the gold-standard quantum chemistry method, coupled cluster theory with up to perturbative t…

Common knowledge—what everyone knows that everyone knows, ad infinitum—is theoretically required for coordination. But a finite mind cannot represent infinitely embedded propositions, and even a few are cognitively taxing. We propose that people perceive common knowledge by combining a capacity-limited ability for recursive mentalizing with an intuitive sense of public salience: When an event is …

Many fibrils of amyloid proteins are characterized by a dense core structure that largely excludes water. However, an increasing number of amyloid fibril structures are observed to contain water channels. Although water in membrane protein channels and pores has been studied, the structure and dynamics of water in amyloid protein fibril nanochannels is largely unexplored. In this computational st…

Expanded genetic alphabets based on synthetic nucleotides offer a powerful strategy to increase the chemical diversity and functional potential of nucleic acids. Hydrophobic unnatural base pairs (UBPs) represent a unique class of UBPs that operate without canonical hydrogen bonding and shapes, which are distinct from natural base pairs. However, the molecular mechanisms governing hydrophobic UBP …

It has been hypothesized that divergence in animal decision processes can be attributed to differences in information processing mechanisms. However, the required comparative tests of this idea are hindered by ecological, perceptual, or motivational divergence among species that confound a direct analysis of decision processes. To overcome these limitations, we study two closely related, sympatri…

Phenotypic variability is a hallmark of human disease. It results from a combination of genetic modifiers, environment, and stochastic effects, but their contributions are hard to disentangle. Here, we establish the specification of terminal cells in the Drosophila tracheal system as a model for phenotypic variability and phenotypic emergence in Mendelian disorders. By perturbing Fibroblast growt…

IL4I1, a human L-amino acid oxidase (LAAO), has drawn considerable interest for its role in catabolism with implications for cancer biology and immune modulation. The function and activity of this enzyme in humans contrast with the cytotoxic effects exerted by LAAOs from snake venoms. The inherent instability of IL4I1 has hindered detailed biochemical characterization and its exploration as a dru…

Chromosomal rearrangements are hypothesized to facilitate speciation by suppressing recombination in locally adapted genomic regions, yet how they shape evolutionary rates during rapid divergence remains poorly understood. Here, we investigate the genomic architecture of two sister Carex (Cyperaceae) species on Réunion Island, which rapidly diverged (∼0.5 Mya) to occupy contrasting tropical-monta…

A critical analytical task in sc-CRISPR screening is identifying downstream genes influenced by perturbed target genes. Existing methods for this task primarily rely on traditional association-based analyses, which not only fall short in establishing causal relationships between genes but also suffer from high false positive rates and limited statistical power. To overcome these limitations, we i…

One-year-old infants rapidly form and generalize categories from idiosyncratic experiences of very few exemplars of those categories. Here we provide evidence on the statistics of infants’ daily-life visual experiences for 8 object categories. Using a corpus of infant head-camera images recorded at mealtimes (87 mealtimes,14 infants), we measure the frequency of the unique instances of each categ…

This paper examines whether officers with high prior alleged misconduct are more likely to make convictionless arrests (arrests that result in no or dismissed charges or where the defendant is found not guilty). Using the Chicago Police Department’s rotational duty calendar to obtain plausibly exogenous variation in the set of officers assigned to work on a particular day, we find that high-misco…

Capturing molecular machines in action is essential for understanding protein complex architecture, cellular regulation, and gene function. Here, we present a large-scale structural proteomics resource for Arabidopsis thaliana generated using an optimized cross-linking mass spectrometry workflow. Using the trifunctional cross-linker PhoX, whose phosphonic acid moiety enables immobilized metal aff…