Proceedings of the National Academy of Sciences
Articles in this Issue
Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology
Myasthenia gravis (MG) is an autoimmune disorder caused mainly by autoantibodies against the acetylcholine receptor (AChR), leading to muscle weakness. While treatments targeting AChR autoantibodies b...
Joint disruption of <i>Ret</i> and <i>Ednrb</i> transcription shifts cell fate trajectories in the enteric nervous system in Hirschsprung disease
Despite extensive genetic heterogeneity, 72% of pathogenic alleles for Hirschsprung disease (HSCR) arise from coding and regulatory variants in genes of the RET...
HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma
The role of HIF2α, encoded by EPAS1 , in neuroblastoma remains controversial. Here, we demonstrate that induction of high levels of HIF2α in MYCN-amplified neur...
Beyond adoption: The persistence of conservation and climate-smart agricultural practices in the United States
Achieving sustainability goals requires that humans change their behavior not just once but persistently. Yet despite decades of research on the adoption of conservation and climate-smart agricultural...
Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway–dependent Rho/ROCK signaling
Certain TP53 mutations can confer neomorphic gain of function (GOF) activities to the p53 protein that affect cancer progression. Yet the concept of mutant p53...
Capillary self-thinning of threads of polyelectrolyte solutions with axial electric fields
A theory of solutions of charged polyelectrolyte (PE) macromolecules, treating them as electric dipoles, is proposed. In a thin thread of PE solution sustained between two disks—whether wettable or no...
Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19
Neutrophils are central mediators of the hyperinflammatory response in severe SARS-CoV-2 infection. We report elevated cytosolic levels of proliferating cell nuclear antigen (PCNA) in neutrophils from...
From retinotopic to ordinal coding: Dissecting the cortical stages of visual word recognition
Fluent reading requires the brain to precisely encode the positions of letters within words, distinguishing for instance FORM and FROM...
Proteolytically activated antibacterial toxins inhibit the growth of diverse gram-positive bacteria
Many species of bacteria produce small-molecule antibiotics that enter and kill a wide range of competitor microbes. However, diffusible antibacterial proteins (ABPs) that share this broad-spectrum ac...
Physical activity is directly associated with total energy expenditure without evidence of constraint or compensation
The prevailing linear model of physical activity (PA) and total energy expenditure (TEE) has been challenged by models that predict an upper limit of TEE linked to a compensatory reduction elsewhere i...
Neuronal plasticity at puberty in mouse hypothalamic <i>Kiss1</i> neurons that control fertility
Puberty is a critical transition period to achieve reproductive capacity in all mammalian species. At puberty, hypothalamic Kiss1 neurons release kisspeptin, st...
Adipose cullin 3 mediates the antiobesity effect of pan neddylation inhibitors
Cullin Ring E3 Ligases (CRLs) belong to the largest family of multisubunit ubiquitin E3 ligases. A cullin serves as the scaffold protein that recruits E3 ligases and substrate receptors in a CRL compl...
Single-cell sequencing uncovers sensory neuron–mediated CGRP signaling as a driver of sarcoma progression
Bone pain is a presenting feature of bone cancers such as osteosarcoma (OS), relayed by skeletal-innervating peripheral afferent neurons. Potential functions of tumor-associated sensory neurons in bon...
Foot placement control underlies stable locomotion across species
Animals navigate their environment stably without inefficient course corrections despite unavoidable errors. In humans, this stability is achieved by modulating the placement of the foot on each step...
Disrupted developmental signaling induces novel transcriptional states
Signaling pathways induce stereotyped transcriptional changes as stem cells progress into mature cell types during embryogenesis. Signaling perturbations are necessary to discover which genes are resp...
HEIP1 orchestrates pro-crossover protein activity during mammalian meiosis
Meiotic crossovers (COs) are needed to produce genetically balanced gametes. In mammals, CO formation is mediated by a conserved set of pro-CO proteins via mechanisms that remain unclear. Here, we cha...
Impact of baleen whales on ocean primary production across space and time
Primary production in the ocean is a fundamental process that supports marine food webs and global carbon sequestration. This process depends on nutrients that are often limited in surface waters. Wha...
The moving mantle beneath Hawaii: A new look at an old bend
Evolutionary histories of functional mutations during the domestication and spread of <i>japonica</i> rice in Asia
Rice ( Oryza sativa ) was first domesticated beginning ~9,000 y ago in China as the japonica variety group/subspecies. U...
Museum genomics suggests long-term population decline in a putatively extinct bumble bee
Pollinator declines globally threaten ecosystem stability and agricultural productivity. Reconstructing pollinator historic demographies provides an evolutionary perspective to understand contemporary...
Viscoelastic structural damping enables broadband low-frequency sound absorption
Low-frequency sound absorption has traditionally relied on air-resonant structures, such as Helmholtz resonators, which are made of stiff materials that undergo negligible deformation. In these system...
A yellow warbler is for the climate as a canary is for the coal mine
A national randomized controlled trial of the impact of public Montessori preschool at the end of kindergarten
Although seminal studies from the early 1960s suggested quality preschool can have lasting positive effects, agreement is lacking on the efficacy of different preschool models. The Montessori model is...