Proceedings of the National Academy of Sciences
Articles in this Issue
A binary trait model reveals the fitness effects of HIV-1 escape from T cell responses
Natural selection often acts on multiple traits simultaneously. For example, the virus HIV-1 faces pressure to evade host immunity while also preserving replicative fitness. While past work has studie...
Cell-based glycoengineering for production of homogeneous and specific glycoform-enriched antibodies with improved effector functions
Glycosylation of humanized antibody at Fc-Asn297 significantly affects the Fc-mediated killing of target cells through effector functions, especially antibody-dependent cellular cytotoxicity (ADCC), a...
Stepwise activation of SARM1 for cell death and axon degeneration revealed by a biosynthetic NMN mimic
Axon degeneration, driven by the NAD + hydrolyzing enzyme SARM1, is an early pathological hallmark of numerous neurodegenerative diseases. SARM1 exists in an in...
pH-dependent dissociation from CTLA-4 in early endosomes improves both safety and antitumor activity of anti-CTLA-4 antibodies
Anti-CTLA-4 Abs (ACAs) are a breakthrough for cancer therapy, but their potential is limited by immunotherapy-related adverse events (irAE). We previously reported that ACAs with acidic pH-sensitive b...
ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep
Metabolism plays a key role in the maintenance of sleep/wake states. Brain lactate fluctuations are a biomarker of sleep/wake transitions, where increased interstitial fluid (ISF) lactate levels are a...
Fungal-derived methyldeoxaphomins target <i>Plasmodium falciparum</i> segregation through the inhibition of PfActin1
Herein we report the finding and structure determination of a natural product based on the methyldeoxaphomin scaffold family from the fungus Trichocladium asperum...
PCSK9 potentiates innate immune response to RNA viruses by preventing AIP4-mediated polyubiquitination and degradation of VISA/MAVS
Upon viral infection, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) detect viral RNA to initiate antiviral innate immune response, which is mediated by the mitochondrial adaptor protein...
Fluoride-based hydrogen bond chemistry in a layered double hydroxide cathode toward high-performance aqueous NH <sub>4</sub> <sup>+</sup> storage
In aqueous ammonium-ion storage, hydrogen bonds play a pivotal role in the reversible insertion/extraction of NH 4 + within transition metal...
Global diversity and energy of animals shaping the Earth’s surface
The collective influence of animals on the processes shaping the Earth’s surface remains largely unknown, with most studies limited to individual species and well-known exemplars. To establish the glo...
Illuminating an invisible state of the HIV-1 capsid protein CTD dimer using <sup>19</sup> F NMR and weighted ensemble simulations
The HIV-1 capsid protein (CA) assembles into a conical shell during viral maturation, encasing and protecting the viral RNA genome. The C-terminal domain (CTD) of the two-domain capsid protein dimeriz...
Fungal effector disables cathepsin-driven Toll immunity in insects
Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR
G protein–coupled receptors (GPCRs) modulate various physiological functions by rewiring cellular gene expression in response to extracellular signals. Control of gene expression by GPCRs has been stu...
Viral circular RNA–encoded protein, ceVP28, divulges an antiviral response in invertebrates
Invertebrates mostly use innate immunity to counteract pathogenic infections. In this study, shrimp was used as a model organism to explore the functions of circular RNAs (circRNAs) derived from white...
Independent effects of the human circadian system and sleep/eating cycles on caloric intake in adolescents vary by weight status
Late-day eating is linked to increased obesity risk; however, whether the endogenous circadian system independently influences caloric intake and if this control differs among individuals based on wei...
Modeling energy requirements for oxygen production on the Moon
Spacecraft using combustion engines require substantial amounts of oxygen for their propellant. The Moon could be a source of oxygen for rocket propellant, since the material composing the lunar surfa...
Simple genetic mechanisms toward more intricate molecular complexes
PSKH1 kinase activity is differentially modulated via allosteric binding of Ca <sup>2+</sup> sensor proteins
Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regu...
Control of flow behavior in complex fluids using automatic differentiation
Inverse design of complex flows is notoriously challenging because of the high cost of high dimensional optimization. Usually, optimization problems are either restricted to few control parameters, or...
A circRNA–mRNA pairing mechanism regulates tumor growth and endocrine therapy resistance in ER-positive breast cancer
The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and drug resistance remain incompletely understood. Elevated expression of CCND1 is linked to enhanced invasiv...
Risks of habitat loss from seaweed cultivation within seagrass
Measuring population heterogeneity requires heterogeneous populations
High spatial resolution charge sensing of quantum Hall states
Charge distribution offers a unique fingerprint of important properties of electronic systems, including dielectric response, charge ordering, and charge fractionalization. We develop an architecture...
Do LLMs write like humans? Variation in grammatical and rhetorical styles
Large language models (LLMs) are capable of writing grammatical text that follows instructions, answers questions, and solves problems. As they have advanced, it has become difficult to distinguish th...
Gene duplication captures morph-specific promoter usage in the evolution of aphid wing dimorphisms
Understanding how morphology evolves requires identifying the types of mutations that contribute to changes in development. We integrated comparative genomics and transcriptomics to reconstruct the ev...
GABAergic synapses between auditory efferent neurons and type II spiral ganglion afferent neurons in the mouse cochlea
Cochlear outer hair cells (OHCs) are electromotile and implicated in amplification of responses to sound that enhance sound sensitivity and frequency tuning. They send afferent information through glu...