Proceedings of the National Academy of Sciences
Articles in this Issue
Large infinities and definable sets
Large cardinal axioms extend the standard set of axioms for mathematics by asserting that very large infinite sets exist. A prominent line of current research in mathematical logic is identifying ever...
The rhythm of aging: Stability and drift in the individual rate of senescence
Human aging is marked by a steady rise in the risk of dying with age–a process demographers call senescence. Over the past century, life expectancy has risen dramatically, but is this because we are a...
An acetyltransferase family required for biosynthesis of diverse marine carotenoids
Chromalveolate algae such as diatoms, haptophytes, and dinoflagellates are main contributors to oceanic primary production, sustaining marine ecosystems and global carbon cycles while synthesizing a s...
B cells enable autoreactive T cells to avoid suppression
Clinical trials and experimental observations have shown that B cells are essential for development of T cell–mediated organ-specific autoimmunity, although their exact contribution is not clear. As a...
Light-activated cAMP signaling controls sodium-driven motility in <i>Vibrio cholerae</i>
Light is one of the most pervasive physical cues in aquatic environments, yet its impact on nonphototrophic pathogens remains largely unexplored. Here, we show that a strain of cholera bacterium...
Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation
Zygotic genome activation (ZGA) marks the first transcriptional milestone and establishes embryonic totipotency. Although pioneer factors have been reported to initiate this process, how chromatin is...
Structure-guided design of 7-azaindole DNMT1 inhibitors active against hypomethylating agent–resistant acute myeloid leukemia
Pharmacological reversal of abnormal promoter DNA hypermethylation at tumor suppressor genes (TSGs) is a key therapeutic paradigm for cancer management. However, the clinical efficacy of currently app...
Probing rock rupture with naturally occurring nuclide signals
Rocks release subtle geochemical warning signals before breaking. These signals, coming from naturally occurring nuclides (e.g., radon, helium, argon, and thoron), have often been reported before eart...
MDFIC2 is a sensory neuron–specific PIEZO channel auxiliary subunit
PIEZO channels are critical for sensory mechanotransduction. While MyoD-family inhibitor proteins were identified as PIEZO1 auxiliary subunits, their broader regulatory roles, particularly in sensory...
Variability in alluvial river width driven by intermittent bank collapse
Alluvial rivers have long been described by hydraulic geometry theory, which links equilibrium channel dimensions to flow discharge. Yet natural rivers are inherently dynamic, with planforms evolving...
Metabolite mimicry identifies butyrate analogs with select protective functions in the intestinal mucosa
Microbial-derived short-chain fatty acids regulate a variety of pathways in the healthy colonic mucosa. In particular, butyrate serves as the primary energy source for colonocytes and regulates gene t...
Diffusive spreading across dynamic mitochondrial network architectures
In eukaryotic cells, mitochondria form networks that range from highly fused interconnected structures to fragmented populations of individual organelles that undergo transient interactions. These str...
Resolving competing evolutionary histories in joint ancestral state reconstruction
Ancestral state reconstruction (ASR) is a foundational tool in comparative biology, offering insights into the evolutionary history of lineages. With each new evolutionary model, our ability to estima...
mtHsp70 chaperone converts mitochondrial proteostasis stress into impaired protein import
Heat shock proteins 70 (Hsp70) represent a ubiquitous and conserved family of molecular chaperones involved in a variety of cellular processes. The conformational cycles of several Hsp70 chaperones, d...
Lysosome-related organelles orchestrate guanine crystal formation in pigment cells
Iridosomes, the guanine crystal-forming organelles of pigment-producing iridophores, are among the most versatile, visually striking yet mechanistically uncharacterized organelles in vertebrate biolog...
Dopamine D1 and D2 receptors differentially control strength and dynamics of abstract decision codes in the primate prefrontal cortex
Dopamine critically modulates prefrontal circuits underlying cognitive control, but how D1-type (D1R) and D2-type (D2R) receptors influence abstract decision coding is unclear. We recorded single-neur...
Spatial multiomics profiling reveals ZFP36-mediated immunometabolic reprogramming in bladder cancer
Bladder cancer remains a significant therapeutic challenge due to its marked heterogeneity and capacity for immune evasion. Here, we employ spatial metabolomics and spatial transcriptomics to systemat...
Chromosome-specific drift under stabilizing selection generates polygenic barriers to sex chromosome turnover
While sex chromosome systems show frequent evolutionary transitions in some clades, in many others they show long-term stability. Previous explanations of this stasis rely on evolutionary dynamics pec...
Negative design enables cell-free expression and folding of designed transmembrane β-barrels
De novo design of membrane proteins (MPs) is a rapidly growing field with transformative potential for synthetic biology. Yet, progress has lagged behind that of soluble proteins, largely due to limit...
Demystifying invasivorism as a management strategy
SARS-CoV-2 and MERS-CoV disrupt host protein synthesis via nsp1 with differential effects on the integrated stress response
Coronaviruses pose a serious threat to public health, driving the need for antiviral therapeutics and vaccines. Therefore, it is paramount to understand how this family of viruses evades cellular anti...
Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists
The chemokine system, comprising a network of chemokines and their receptors, orchestrates leukocyte migration and plays a central role in immune surveillance and inflammation. Targeting this system h...
From female to female: Communication via chemosignals
In many species, chemosensory cues convey important information about reproductive status, but their role in shaping social interactions among women is less understood. Here, we combined functional ne...
Estimating returns to education using the genetic lottery
Does more schooling cause higher lifetime earnings? Social scientists have long sought to determine the economic returns to schooling given its importance to individual life chances and public policy....
A scalable embryonic stem cell–based platform for efficient generation of mitochondrial DNA mutant mice
Mitochondria are central to energy metabolism and cellular signaling, and mutations in mitochondrial DNA (mtDNA) can disrupt these processes and contribute to human disease. However, progress in defin...