Proceedings of the National Academy of Sciences
Articles in this Issue
An accurate cellular assay to determine pathogenicity of coding and noncoding variants in Lynch syndrome genes
Lynch syndrome (LS) is a genetic predisposition to mainly colorectal and endometrial cancer due to heterozygous disruptive germline mutations in the DNA mismatch-repair (MMR) genes...
Towards CRISPR-based editing of the mitochondrial genome in yeast
Mitochondria, which evolved from symbiotic bacteria, possess their own genomes (mtDNA) and support independent transcription and translation within the organelle. Given the essential role of mtDNA in...
Predicting epistasis across proteins by structural logic
Accurately predicting the phenotypic consequences of genetic variation is a major challenge for precision medicine. The problem is exacerbated by epistatic interactions, nonadditive effects between ge...
“Excluded phenotypes” restrict genetic paths toward adaptation in declining populations
Evolutionary rescue is the process by which declining populations adapt to conditions that would otherwise cause their extinction. Considering the spectrum of mutant phenotypes that can arise within a...
Proteasomal proteolysis in p62 condensates directs tumor suppression or growth depending on their subcellular localization
p62/SQSTM1 generates liquid–liquid phase-separated condensates that participate in diverse processes, including protein quality control (PQC) and autophagy. Nuclear p62 condensates were shown to act a...
Evolution of environmental sex determination via juvenile hormone–induced gene co-option in <i>Daphnia</i>
Juvenile hormone (JH) exerts pleiotropic effects in insects, regulating not only metamorphosis and reproduction but also caste differentiation, morphogenesis, and diapause. How such diverse functions...
An activator of a two-component system controls cell separation and intrinsic drug resistance in <i> <i>Mycobacterium tuberculosis</i> </i>
Unlike commonly studied rod-shaped bacteria, mycobacteria grow from their poles, requiring precise coordination between division and initiation of new pole growth. The mechanisms that mediate this tra...
An active matter model captures spatial dynamics of actomyosin oscillations in larval epithelial cells during <i>Drosophila</i> morphogenesis
The apicomedial actomyosin network is crucial for generating mechanical forces in cells. Oscillatory behavior of this contractile network is commonly observed before or during significant morphogeneti...
A bacterial translation activator with an intrinsically disordered RNA-binding region
Bacterial RNA-binding proteins (RBPs) that control the translation of multiple transcripts act largely as negative regulators. Here, we report the identification and characterization of a positive reg...
Spatial clustering modifies competition in a diverse annual plant community
Spatial patterns are widespread in nature, and their formation has been studied extensively. However, the effects of spatial aggregation on the strength of species interactions are less well understoo...
Stochastic motility energetics reveals cooperative bacterial swarming in optical tweezers
Bacterial flagellar swarming enables dense microbial populations to migrate collectively across surfaces, often resulting in emergent, coordinated behaviors. However, probing the underlying energetics...
Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium
Cigarette smoking induces epigenetic changes that can cause degenerative heterogeneity with aging and disease. In disease such as age-related macular degeneration (AMD), the leading worldwide cause of...
Regulating ion transport and solvation chemistry in zwitterionic gel polymer electrolyte for high-performance quasi-solid-state batteries
Gel polymer electrolytes (GPEs) are promising electrolyte candidates for next-generation Li metal batteries (LMBs). However, the reverse migration of free anions causes uneven distribution of space ch...
Chemical tuning reveals a cation–π gating bridge between the voltage-sensor and pore domains in the K <sub>v</sub> 7.1 potassium channel
K v 7.1 is a cardiac voltage-gated potassium channel that underlies the delayed rectifier current (I KS ) in the heart....
Molecular structure of the ESCRT-III-based archaeal CdvAB cell division machinery
Most prokaryotes divide using filaments of the tubulin-like FtsZ protein, while some archaea employ instead ESCRT-III-like proteins and their filaments for cell division and cytokinesis. The alternati...
De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D
Gasdermin D (GSDMD) is the principal executor of pyroptosis, a form of proinflammatory programmed cell death misregulation of which is associated with numerous diseases. Despite significant interest,...
Quantifying racial disparities in media representations of gun violence at scale
Previous research has documented racial disparities in gun violence news coverage in limited and small-scale contexts. This study curates and analyzes a large-scale dataset of news articles linked to...
The intrinsic impact of mechanical stress on the maintenance of oocyte dormancy
In the mammalian ovary, most oocytes remain dormant, and their dormant status plays a central role in maintaining the reservoir population of the female germ line. The equilibrium between the dormant...
Distinct contributions of hippocampal pathways in learning regularities and exceptions revealed by functional footprints
Fundamental aspects of learning are theorized to be supported by hippocampal pathways: The monosynaptic pathway (MSP) extracts regularities, whereas the trisynaptic pathway (TSP) rapidly encodes excep...
Plant diversity influences plant volatile emission with varying effects at the species and community levels
Studies have investigated the interactions between plants through competition and resource sharing to understand the mechanisms behind the positive effects of plant diversity on productivity. Volatile...
Plastid-to-nucleus communication under hypoxia involves group VII ethylene response factors in <i>Arabidopsis thaliana</i>
Plants trigger specific changes in gene transcription to acclimate to low-oxygen concentrations. Plastid-localized STEAROYL-ACYL CARRIER PROTEIN ∆9-DESATURASE 6 (SAD6) converts C18:0- into C18:1-fatty...
Host heterogeneity and unpredictability in parasite outbreaks
Experimental tests of the effects of host heterogeneities on parasite transmission are rare; previous studies focus on a single host trait over one generation of transmission. Thus, the long-term epid...
CCR5 marks a subset of mouse hematopoietic stem cells that are myeloid primed and expand with age
Hematopoietic stem cells (HSCs) are multipotent self-renewing cells that give rise to all types of blood cells. Past research has identified that long-term hematopoietic stem cells in young mice and h...
Microvascular architecture and physiological fluctuations constrain the control of cerebral microcirculation
Brain vasculature is a multiscale network that actively regulates cerebral blood flow to maintain homeostasis. A systematic understanding of how this network enables robust and precise flow control ha...