Proceedings of the National Academy of Sciences
Articles in this Issue
Large increases in public R&D investment are needed to avoid declines of US agricultural productivity
Increasing agricultural productivity is a gradual process with significant time lags between research and development (R&D) investment and the resulting gains. We estimate the response of US agric...
The impact of political assassinations on turnout: Evidence from Colombia
Although a growing literature has investigated the effects of various types of civil war violence on political behavior, no study has examined the impact of assassinations targeting politicians. This...
“Kids and Girls”: Parents convey a male default in child-directed speech
Adults tend to view men (more so than women) as default people , with numerous real-world consequences for gender equity. In the United States, the tendency to...
Human stem cells with in vivo high plasticity generated by cell–cell communication
Stem cells possess inherent properties of self-renewal and differentiation, and thus hold significant promise for regenerating damaged tissues or replacing lost cells. Unless their therapeutic effects...
Pattern separation and pattern completion in early childhood
Pattern separation, or distinguishing similar experiences from one another, and pattern completion, in which components of an experience prompt retrieval or forgetting of an event pattern as a unit, a...
Enhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt
Regulation of mitochondrial Ca 2+ uptake is critical in cardiac adaptation to chronic stressors. Abnormalities in Ca 2+...
Dual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy
Pancreatic ductal adenocarcinoma (PDAC) is notoriously immune-resistant, limiting the clinical efficacy of single-agent immune modulators and thereby necessitating the exploration of multimodal immuno...
Bacterial motility depends on a critical flagellum length and energy-optimized assembly
The flagellum is the most complex macromolecular structure known in bacteria and is composed of around two dozen distinct proteins. The main building block of the long, external flagellar filament, fl...
Initiation of transthyretin aggregation at neutral pH by fluid agitation
The transthyretin (TTR) tetramer, assembled as a dimer of dimers, transports thyroxine and retinol binding protein in blood plasma and cerebrospinal fluid. Aggregation of wild type (WT) or pathogenic...
Comparing color qualia structures through a similarity task in young children versus adults
Examination of the subjective qualitative aspects of an experience, or “qualia” in short, is a fundamental and core aspect of consciousness research. How can we characterize the particular quality of...
Identification of a ligand-binding site on tubulin mediating the tubulin–RB3 interaction
For decades, microtubules—composed of αβ-tubulin dimers—have been primary targets for cancer chemotherapy. While eight binding sites on the tubulin dimer have been structurally characterized, this stu...
p53 activates circASCC3 to repress R-loops and enhance resistance to chemotherapy
The tumor suppressor p53 can trigger tumor resistance to chemotherapy by facilitating DNA damage repair and maintaining genomic integrity. Here, we report that a p53-induced circular RNA circASCC3 pro...
NBS1 facilitates preribosomal RNA biogenesis
Mutations in the NBS1 gene result in Nijmegen breakage syndrome (NBS), and the gene encodes NBS1 that forms a complex with MRE11 and RAD50 and participates in D...
Cryo-ET reveals the in situ architecture of the polar tube invasion apparatus from microsporidian parasites
Microsporidia are divergent fungal pathogens that employ a unique harpoon-like apparatus called the polar tube (PT) to invade host cells. The long PT is fired out of the microsporidian spore over the...
Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity
To ensure optimal replication and spread, viruses have evolved countermeasures to evade type 1 IFN-mediated antiviral activity. During the early viral replication cycle steps until uncoating, the HIV-...
GSDMD-mediated mitochondrial dysfunction in marginal cells: A potential driver of inflammation and stria vascularis damage in CIHL
Inflammation is among the known causes of cisplatin-induced hearing loss (CIHL), but its exact pathophysiological mechanisms remain unclear. Herein, we demonstrated that pyroptosis—a recently identifi...
Expansion and pathogenic activation of skeletal muscle–resident macrophages in <i> mdx <sup>5cv</sup> /Ccr2 <sup>−/−</sup> </i> mice
Infiltrating macrophages contribute to muscle dystrophic changes in Duchenne muscular dystrophy (DMD). In a DMD mouse model, mdx 5cv...
Epstein–Barr virus and the immune microenvironment in multiple sclerosis: Insights from high-dimensional brain tissue imaging
Epstein–Barr virus (EBV) is strongly implicated in the pathogenesis of multiple sclerosis (MS), yet its exact role in disease progression remains unclear. Using high-dimensional CO-detection by indexi...
A unified neural representation model for spatial and conceptual computations
The hippocampus and entorhinal cortex encode spaces by spatially local and hexagonal grid activity patterns (place cells and grid cells), respectively. In addition, the same brain regions also implica...
Structural mechanisms underlying the modulation of CXCR4 by diverse small-molecule antagonists
CXCR4 (CXC chemokine receptor type 4), a member of the G protein–coupled receptor superfamily, plays a role in cell migration and functions as a coreceptor for HIV entry. Molecular therapeutics target...
A mechanistic basis for genetic assimilation in natural fly populations
Genetic assimilation is a process by which a trait originally driven by the environment becomes independent of the initial cue and is expressed constitutively in a population. More than seven decades...
Learning reshapes the hippocampal representation hierarchy
A key feature of biological and artificial neural networks is the progressive refinement of their neural representations with experience. In neuroscience, this fact has inspired several recent studies...
Astrocytes in the mouse brain respond bilaterally to unilateral retinal neurodegeneration
Glaucomatous optic neuropathy, or glaucoma, is the world’s primary cause of irreversible blindness. Glaucoma is comorbid with other neurodegenerative diseases, but how it might impact the environment...
The SUbventral-Gland Regulator (SUGR-1) of nematode virulence
Pathogens must precisely tailor their gene expression to cause infection. However, a signaling cascade from host signal to effector production has remained elusive for metazoan pathogens. Here, we sho...
Neanderthal adaptive introgression shaped <i>LCT</i> enhancer region diversity without linking to lactase persistence in East Asian populations
Positive selection at the 2q21.3 enhancer region for lactase gene ( LCT ) expression in Europeans and Africans has long been attributed to selection for lactase...