Table Of Contents Page, PNAS Volume 123, Number 23
This Week in PNAS
Editorial
Opinion
Commentaries
Letters
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When alternative becomes essential: The role of mitochondrial glycerol-3-phosphate dehydrogenase
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The 2023 Canadian fire season was record-breaking in terms of burned area and carbon
emissions. Here, we present estimates of the regional climate-cooling effect from
postfire surface albedo changes, which have historically partially offset the warming
...
Achieving coherent control of ionic transport in solids, analogous to electron waveguides,
remains a fundamental challenge, as ionic motion is typically limited by slow, stochastic
hopping. Here, we demonstrate that a two-dimensional electrochemical cell (...
Physical Sciences
Applied Mathematics
Every research university has a distribution of faculty research activity that is
fueled by the external support from government, industry, and philanthropy. The large
decreases in federal support proposed in 2025 by the Administration would dramatically
...
Biophysics and Computational Biology
Turing patterns are a cornerstone of biological self-organization, yet their emergence
typically requires finely tuned parameters occupying narrow regions of high-dimensional
space. This poses a fundamental challenge: how can evolving biological systems ...
Precise monitoring of cardiac electrophysiology in vitro is crucial to understanding
heart function and cardiac disease. However, high-throughput, contact-free methods
for directly measuring excitation–contraction coupling remain limited. Here, we ...
To improve crop yield and resilience, it is essential to identify the steps limiting
assimilation rate in plant leaves. The combined effect of multiple traits can be
resolved by mechanistic models of the underlying diffusion, biochemistry, and geometry.
...
Stretches of double-stranded DNA sharing the same sequence can recognize each other
in cells. This phenomenon, known as homologous recognition, is essential for DNA recombination
and repair. Yet, its mechanism remains debated, with purely physical ...
T cell receptor (TCR) restriction by highly polymorphic major histocompatibility complex
(MHC) proteins is a foundation of cellular immunity. Although the effects of MHC polymorphisms
on peptide binding and selection are well established, how ...
Plant primary cell walls are dynamic supramolecular assemblies composed of layered
cellulose, hemicellulose, and pectin, progressively built through synthesis and secretion.
However, the specific architectural features and structural components sufficient
...
Chemistry
Biological strategies for manipulating light have revealed new concepts in light scattering,
inspiring the design of sustainable photonic materials. While iridescent optical systems
have been extensively studied, many applications require noniridescent ...
Proteins that bind to a target protein of interest, termed “binders”, are essential
components of biological research reagents and therapeutics. Target proteins present
multiple binding surfaces with varying interaction potential. “Hot spots”, or high-...
Early-stage drug discovery involves a complex set of processes that typically requires
iterative exploration of a vast chemical-biological search space. Over the past few
decades, these processes have been facilitated using automated experimentation in
...
General anesthetics are widely used to induce reversible unconsciousness, yet their
molecular mechanisms remain incompletely understood. Despite their low binding affinities
and broad protein-binding promiscuity, general anesthetics still interact with ...
Earth, Atmospheric, and Planetary Sciences
Making predictions of global change relevant to individual communities is a critical
challenge, especially where local impacts diverge from global predictions. While sea
level is rising globally, in Greenland, sea level is predicted to fall over the ...
Environmental Sciences
Geopolitical tensions and the disruption of major energy imports have sharply elevated
energy prices across the European Union (EU), creating a persistent energy supply
gap and posing long-term challenges for energy security. Here, we introduce a ...
Physics
The chiral spin liquid is a canonical state of quantum spins combining topological
and symmetry-breaking order, and possible experimental realizations have attracted
growing interest. We examine the physics at interfaces between chiral spin liquid
domains ...
We introduce a physics-informed training-data generation strategy that efficiently
captures the complete interlayer interactions in multilayer moiré systems, enabling
a machine-learning force field transferable across layer numbers and stacking ...
Dynamical heterogeneity, in which transitory local fluctuations occur in the conformation
and dynamics of constituent particles, is widely hypothesized to be essential to the
evolution of supercooled liquids into the structural glass state. Yet its ...
Statistics
We prove that kernel covariance embeddings lead to information-theoretically perfect
separation of distinct continuous probability distributions. In statistical terms,
we establish that testing for the equality of two nonatomic (Borel) probability ...
Sustainability Science
Making predictions of global change relevant to individual communities is a critical
challenge, especially where local impacts diverge from global predictions. While sea
level is rising globally, in Greenland, sea level is predicted to fall over the ...
Geopolitical tensions and the disruption of major energy imports have sharply elevated
energy prices across the European Union (EU), creating a persistent energy supply
gap and posing long-term challenges for energy security. Here, we introduce a ...
Social Sciences
Economic Sciences
Every research university has a distribution of faculty research activity that is
fueled by the external support from government, industry, and philanthropy. The large
decreases in federal support proposed in 2025 by the Administration would dramatically
...
How do contractual restrictions on worker voice affect information flows about employers?
We develop a framework in which the legal risk from violating a nondisclosure agreement
(NDA) reduces the willingness of workers to share negative information, ...
Environmental Sciences
Avoiding human fatalities during wildfires is a key public policy objective. Outward
road access, or the number of egress routes, is widely assumed to influence wildfire
fatalities, yet few studies have quantified if or when this factor becomes critical.
...
Political Sciences
We conducted an international AI negotiation competition in which participants designed
and refined prompts for AI negotiation agents. We then facilitated over 180,000 negotiations
between these agents across multiple scenarios with diverse ...
Psychological and Cognitive Sciences
In the 1970s, physicist Richard Feynman turned lunch with a friend into a math problem—how
to optimize dish selection over multiple meals—but his handwritten notes remained
a mystery for decades. Here we present the fully deciphered problem and solution,
...
Bilingualism has been associated with enhanced executive functions (EFs), particularly
attentional control, and may confer protection against cognitive decline in older
age. At the same time, the COVID-19 pandemic has emerged as a factor negatively ...
Sustainability Science
Avoiding human fatalities during wildfires is a key public policy objective. Outward
road access, or the number of egress routes, is widely assumed to influence wildfire
fatalities, yet few studies have quantified if or when this factor becomes critical.
...
Childhood stunting is associated with increased mortality, higher risk of chronic
disease, impaired cognitive development, lower educational attainment, reduced economic
opportunities, and intergenerational transmission of stunting. These risks are likely
...
Biological Sciences
Agricultural Sciences
Genome editing has emerged as a powerful tool for genome manipulation and trait improvement
in crops. However, most commonly used approaches rely on tissue culture and transgenic
materials, which are time-consuming, labor-intensive, and often strongly ...
Applied Biological Sciences
Biological strategies for manipulating light have revealed new concepts in light scattering,
inspiring the design of sustainable photonic materials. While iridescent optical systems
have been extensively studied, many applications require noniridescent ...
Nonpharmaceutical interventions (NPIs) are essential for controlling infectious diseases
during prevaccine periods, yet their success hinges on sustained population behavioral
responses to restrictions. This study investigates how mobility responses to ...
Plastic pollution poses an escalating global threat, demanding biological strategies
capable of transforming waste into valuable products. Polyethylene terephthalate (PET)
can be hydrolyzed into its monomers, including terephthalate, but microbial ...
Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest cancer survival rates.
Recent studies using RAS inhibitors have opened the door to more efficacious therapies
although their beneficial effect is still limited mainly due to the rapid ...
Biochemistry
Proteins that bind to a target protein of interest, termed “binders”, are essential
components of biological research reagents and therapeutics. Target proteins present
multiple binding surfaces with varying interaction potential. “Hot spots”, or high-...
c-Myc, an important oncoprotein, is highly regulated via posttranslational modifications.
Herein, we report c-Myc crotonylation, an acylation stemming from the short-chain
fatty acid crotonate. By biochemical analyses and high-resolution mass spectrometry
...
The cellular response to transition metal scarcity is multifaceted and complex. Members
of the Cluster of Orthologous Groups 0523 (COG0523) superfamily are proposed to chaperone
a bound metal to activate an apoenzyme client and are thus candidate ...
Melanization is a central insect immune response to wounding and microbial invasion.
It is mediated by a system of serine proteases and their homologs, mostly members
of the CLIP subfamily, and leads to prophenoloxidase (proPO) activation and PO-mediated
...
Biophysics and Computational Biology
Myotrem is an untreatable, early-onset, congenital myopathy characterized by hypotonia,
muscle weakness, skeletal deformities, dysmorphia, respiratory insufficiency, and
myogenic tremor (V. Shashi et al., Hum Mutat, 2019 and J. Stavusis et al., Ann. ...
Ebola virus (EBOV) and Marburg virus (MARV) are highly lethal filoviruses that cause
severe hemorrhagic fever in humans. A recently identified bat-borne filovirus, Měnglà
virus (MLAV), uses the same NPC1 receptor as EBOV and MARV, raising concerns about
...
Cell Biology
Proper proinsulin folding in the endoplasmic reticulum (ER) is prerequisite to producing
bioactive insulin, and proinsulin misfolding causing β cell ER stress accompanies
pancreatic β cell dysfunction in type 2 diabetes (T2D). How (and which) ER ...
Chondrodysplasia is a genetic disorder characterized by impaired cartilage development
and bone growth. Dysregulation of the endoplasmic reticulum (ER) stress is associated
with chondrodysplasia. Here, we demonstrate a critical role for the ER stress ...
Glucagon-like peptide-1 receptor agonists, including long-acting semaglutide, are
transformative anti-obesity therapies. However, emerging evidence indicates that weight
loss may come at the expense of skeletal muscle mass, a tissue essential for mobility,...
Developmental Biology
Turing patterns are a cornerstone of biological self-organization, yet their emergence
typically requires finely tuned parameters occupying narrow regions of high-dimensional
space. This poses a fundamental challenge: how can evolving biological systems ...
The developing limb is a classical model system for studying genetic aspects of pattern
formation and mechanisms underlying tissue differentiation. The transition from early
to differentiated cell fates during limb bud development requires the precise ...
Ecology
Anthropogenic activities severely impair biodiversity and ecosystem functionality.
A prime example is the loss of frugivores and their corresponding seed dispersal services
due to defaunation (the decline of animal populations), ultimately affecting the ...
Trade-offs between lifespan and reproduction are a central theme in evolution and
ecology, often attributed to physiological constraints on the allocation of limiting
resources. However, recent work suggests such trade-offs may depend on macro- and
...
Evolution
Host–pathogen interactions are often characterized by spatial and temporal fluctuations
in host density. Such variability may promote the evolution of phenotypic plasticity
in pathogen virulence. However, it remains unclear how pathogens can reliably ...
The late Ediacaran marks a pivotal interval in early animal evolution, when benthic
organisms began engaging with increasingly heterogeneous and dynamic seafloor environments.
These shifts signal the emergence of more sophisticated locomotory and sensory ...
Microbial competition drives rapid adaptation, often forcing organisms to specialize
in new ecological niches. Adaptations that improve competitive ability can reduce
performance in other environments creating trade-offs. Whether such trade-offs persist
...
Understanding how sequence context influences the likelihood of mutation at a given
genomic locus is critical for deciphering evolutionary processes. It is well established
that the immediately adjacent bases influence mutation rates, but the role of more
...
Immunology and Inflammation
T cell receptor (TCR) restriction by highly polymorphic major histocompatibility complex
(MHC) proteins is a foundation of cellular immunity. Although the effects of MHC polymorphisms
on peptide binding and selection are well established, how ...
Blood cells are common and unique to animals, enabling them to address critical challenges
of defense and transport. Thus, their evolution represents a defining innovation in
metazoan multicellular life. However, their evolutionary trajectory about how ...
Severe respiratory infections such as COVID-19 are characterized by excessive inflammation
leading to the development of pneumonia and acute respiratory distress syndrome. Bioactive
lipid mediators (LMs) derived from ω6 and ω3 polyunsaturated fatty acids ...
Despite revolutionizing oncology, PD-1/PD-L1-directed immune-checkpoint blockade (ICB)
is limited by primary or acquired resistance that is routinely countered—without mechanistic
clarity—by empiric rechallenge. Here, we identify substrate-based protein ...
Medical Sciences
APOBEC2 is a well-conserved member of the AID/APOBEC family of cytidine deaminases.
Most members of the family catalyze the conversion of cytosine to uracil either in
DNA or RNA, thereby acting as DNA mutators and/or RNA editors. APOBEC2 is the only
...
High-risk human papillomaviruses (HPVs) promote malignant progression through sustained
expression of the viral oncoprotein E6, which drives degradation of the tumor suppressor
p53 and creates an oncogenic dependency in HPV-positive cancers. Here, we ...
In peripheral tissues, lipoprotein lipase (LPL) is secreted by parenchymal cells (adipocytes,
myocytes) into the interstitial spaces, where it is captured by GPIHBP1 (a glycosylphosphatidylinositol-anchored
protein of capillary endothelial cells) and ...
Microbiology
In soil ecosystems, aerobic bacteria survive oxygen deprivation (hypoxia) by entering
nonreplicative persistent states. In contrast to the well-studied metabolism of obligate
and facultative anaerobes, little is known about how obligately aerobic bacteria ...
Dominant carbapenem-resistant Klebsiella pneumoniae (CRKP) clones have markedly intensified the burden of invasive infections while severely
restricting treatment options. Although genomic determinants of these high-risk lineages
are well characterized, ...
Bacteriophages (phages) are well known to be one of the major driving forces in bacterial
evolution. This also applies to virulent microorganisms, such as the major human pathogen
Vibrio cholerae, whose pathogenic potential and epidemic proliferation ...
Interferon regulator factor 3 (IRF3) inhibition is a shared strategy of many virally
encoded proteins to effectively block the induction of interferon signaling. Although
rotavirus nonstructural protein 1 (NSP1) is known to target IRF3 for proteasomal ...
Bacteria deploy diverse antiphage defense systems, including small bioactive molecules
providing protection at the multicellular level. DNA-intercalating anthracyclines,
such as daunorubicin, exhibit broad antiphage activity, but the underlying mechanism
...
Epstein–Barr virus (EBV) lytic infection contributes to oncogenesis and autoimmunity
and depends on subversion of host DNA damage responses (DDR). We used high-content
screening (HCS) to systematically capture single-cell morphologic profiles and ...
Inorganic polyphosphate (polyP) is a ubiquitous molecule found across all domains
of life. Although implicated in diverse cellular processes, including phosphate storage,
stress responses, and pathogenicity, loss of polyP synthesis typically causes only
...
Microorganisms employ inorganic polyphosphate (polyP) as an ancient strategy for energy
and phosphate storage, yet its physiological roles in methanogenic archaea remain
largely unexplored. Here, we report that polyP metabolism is coupled to growth and
...
Methylglyoxal is a reactive aldehyde produced by macrophages as part of their antimicrobial
innate immune arsenal. Our prior work showed that Listeria monocytogenes relies on glyoxalase A (GloA) and bacterial glutathione to detoxify methylglyoxal
and that ...
Neuroscience
The vestibular system of the inner ear provides head motion and orientation information
required for maintaining balance and spatial orientation. Each of the five vestibular
sensory organs contains type I and type II hair cells (HCs). Type I HCs are ...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting
motor neurons. Here, we have profiled motor neuron microRNAs (miRNAs) during motor
neuron degeneration in vivo to gain a better understanding of ALS pathophysiology.
...
The muscle nicotinic acetylcholine receptor (AChR) is the key mediator of neuromuscular
signal transmission and is essential for all voluntary movement in our body. In this
study, we present DC-98-LC74, a positive allosteric modulator (PAM) for the adult
...
Vision enables primates to remotely map their environment using eye movements rather
than physical locomotion. While view-related spatial coding is prevalent in the primate
hippocampus, its origin and precise relationship to standard place coding remain ...
Physiology
Precise monitoring of cardiac electrophysiology in vitro is crucial to understanding
heart function and cardiac disease. However, high-throughput, contact-free methods
for directly measuring excitation–contraction coupling remain limited. Here, we ...
Muscle contraction relies on the coordinated activation of myosin motors from a folded-OFF
state on the thick filament surface and their actin tracks on the thin filaments in
response to calcium. Thick filaments contain distinct regulatory zones defined ...
The dystrophin–glycoprotein complex (DGC) provides structural integrity to the sarcolemma,
and disruption of the DGC leads to muscular dystrophy. A core member of the DGC is
dystroglycan (DG), which binds to extracellular ligands via α-DG and ...
Plant Biology
To improve crop yield and resilience, it is essential to identify the steps limiting
assimilation rate in plant leaves. The combined effect of multiple traits can be
resolved by mechanistic models of the underlying diffusion, biochemistry, and geometry.
...
Plant primary cell walls are dynamic supramolecular assemblies composed of layered
cellulose, hemicellulose, and pectin, progressively built through synthesis and secretion.
However, the specific architectural features and structural components sufficient
...
Plastids are dynamic organelles that remodel their composition, ultrastructure, and
function according to developmental and environmental demands. The synthetic molecule
X57 induces the conversion of leaf chloroplasts into tocopherol-rich plastids lacking
...
Alternative splicing expands proteome diversity and enables phenotypic plasticity
across eukaryotes. In plants, mutations in spliceosomal components impair development
and stress responses, but the molecular mechanisms remain unclear. Here, we define
the ...
The plant hormone auxin is a central regulator of plant growth and development. The
canonical nuclear auxin signaling pathway acts through the regulation of gene transcription,
and the protein levels of core component AUXIN RESPONSE FACTORS (ARFs) are key ...
Sesame (Sesamum indicum) seeds accumulate specialized lignans, including (+)-sesamin, (+)-sesamolin, and
(+)-sesaminol triglucoside (SL-TG). Although lignan biosynthesis during seed development
is well characterized—with SiCYP92B14 recognized as a (+)-...
Population Biology
Ecological populations fluctuate for reasons that are often ascribed—separately—to
historical legacies, intrinsic nonlinear dynamics, or stochastic noise. Yet these
forces rarely act in isolation. We assembled a global database of 302 abundance time
...
Cover image: Pictured are Arabidopsis seedlings grown on a medium supplemented with the synthetic molecule X57. Pablo Perez-Colao et al. found that X57 triggers the conversion of chloroplasts into sites for the storage of vitamin E. Binding to the phosphatase enzyme SAL1, X57 causes the buildup of its precursor PAP. Increased PAP levels in turn prime chloroplasts for differentiation. Withdrawing X57 restores photosynthetic function to chloroplasts. According to the authors, the findings uncover a molecular mechanism underlying chloroplast plasticity. See the article by Perez-Colao et al. e2601698123. Image credit: Pablo Perez-Colao.
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