Proceedings of the National Academy of Sciences
Articles in this Issue
Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues
Noonan syndrome (NS) is the most common RASopathy, a developmental disorder that derives from dysregulation of the mitogen-activated protein kinase (MAPK) pathway. NS results from modestly activating...
Pseudorabies virus triggers ferritinophagy-mediated ferroptosis and neuroinflammation in viral encephalitis
Pseudorabies virus (PRV), a member of the Alphaherpesvirinae subfamily, primarily infects pigs and poses a significant threat to the swine industry. In recent y...
Asymptotic distribution of the Betti numbers of M¯0,n
Asymptotic normality is frequently observed in large combinatorial structures, rigorously established for many quantities such as cycles or inversions in random permutations, the number of prime facto...
A Trojan horse pathogen breaking through partner-choice barriers in the insect gut
Mutualistic symbioses are potentially vulnerable to exploitation, particularly in hosts that acquire symbionts from the environment, where harmful exploiters inhabit. The independent evolution and per...
DARPins as pan-reactivators of temperature-sensitive p53 cancer mutants
The tumor suppressor p53 is the most frequently mutated protein in tumors and a target for drug development. More than 2000 cancer-associated p53 missense mutations have been reported, most of them lo...
The rising threats of global wildland–human interface revealed by a scale-adaptive approach
The Wildland–Human Interface (WHI), where human infrastructure and activities meet or intermingle with wildland vegetation, represents a critical zone of human–environmental conflict. Here, we present...
Strong intrinsic multiferroism and magnetoelectric coupling in (1– <i>x</i> )BiFeO <sub>3</sub> –( <i>x</i> )BaTiO <sub>3</sub> films
The coexistence of ferroelectric and antiferromagnetic order in BiFeO 3 makes it promising for next-generation magnetoelectric devices. But, single-phase multif...
Mitochondrial double-stranded RNA fuels pancreatic cancer growth via RIG-I/TLR3 inflammation
Mitochondria activate inflammation and innate immunity to protect against infections, but the role in cancer is unknown. Here, we report that patients with pancreatic ductal adenocarcinoma (PDAC) with...
TLR1 deficiency associates with immune dysregulation and colitis
Toll-like receptor 1 (TLR1), a member of the TLR family, assumes a pivotal role in pathogen recognition and the activation of innate immunity. In this study, we have identified a homozygous truncating...
Suppression rather than activation of the integrated stress response (GCN2–ATF4) pathway extends lifespan in the fly
Stress response pathways are emerging as conserved modulators of lifespan. The prevailing hypothesis is that activation of stress-responsive pathways, including the amino acid deprivation arm of the i...
The antimetastatic effects of calorie restriction are negated by voluntary exercise in an aggressive breast cancer mouse model
The role of lifestyle interventions in treatment success has become essential for nearly every disease. Healthy dietary habits, regular exercise, and stress management are key pillars that can improve...
Perception of a bacterial quorum sensing signal activates a tripartite plant immune strategy
Bacterial quorum sensing (QS) signals an increasing threat during pathogenesis. How plants deploy timely defenses through QS perception is poorly understood. Here, we report that A...
LRBA organizes distinct vesicular trafficking systems in distal nephron segments for water and sodium conservation
Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency is a rare genetic disorder characterized by immune dysregulation. The immune checkpoint molecule cytotoxic T lymphocyte-as...
Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners
Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that coordinate cellular responses to low oxygen levels by binding a short hypoxia response element (HRE) DNA sequence near O...
Expanding the repertoire for molluscan structural colors
Unveiling the glymphatic system’s role in brain aging: A comprehensive biomarker and modifiable intervention target
The focus of this study is to investigate the role of diffusion tensor imaging along the perivascular space (DTI-ALPS) index in brain aging. To address this, we first examined the association of DTI-A...
Correction for Weed and Zeitzer, Circadian-informed modeling predicts regional variation in obesity and stroke outcomes under different permanent US time policies
ATG9A-mediated plasma membrane repair is linked to Vps13A and regulated by glycosylation
Biological membranes provide a resilient framework for cellular structure and stability. Disrupting its integrity may result in irreparable damage, altering cellular homeostasis and ultimately leading...
Male-emitted benzaldehyde acts as an olfactory antagonist, disrupting moth sex pheromone communication
Sexual competition among males drives the evolution of diverse reproductive strategies in insects, including the use of chemical signals to influence the behavior of rivals. Yet, the role of chemicall...
Structural studies of an antinecroptosis viral:human functional heteroamyloid M45:RIPK3 using SSNMR
The formation of RIP-homotypic interaction motif (RHIM)-based heteromeric amyloid assemblies between effector proteins such as receptor-interacting protein kinases 1, Z-DNA Binding Protein 1, or TRIF...
Lattice and ligand engineering for hierarchical heterogeneous nanocrystals
Precise control over the morphology, structure, and composition of nanocrystals is essential for designing advanced functional materials. Herein, we establish a general paradigm for the programmable s...
Deforestation-focused policies do not reduce degradation in the Brazilian Amazon
Forest degradation causes large declines in carbon stocks, biodiversity, and ecosystem services, despite leaving some trees standing. Over the past two decades, numerous conservation policies to halt...
Physiological super-resolution in situ recording reveals kinetic changes of sympathetic norepinephrine release in heart failure
Norepinephrine (NE) in the peripheral nervous system plays crucial roles in regulating peripheral organs in health and disease. However, the spatiotemporal dynamics of sympathetic NE release and its u...