Table Of Contents Page, PNAS Volume 123, Number 18
This Week in PNAS
Commentaries
Perspective
Ketamine has been shown to reduce depression and suicidality in individuals resistant
to treatment by other drugs. Exactly how ketamine works is not known. Here, I propose
a new hypothesis that involves synaptic and circuit plasticity and may lead to ...
Letters
Physical Sciences
Applied Mathematics
Understanding flight evolution requires quantifiable metrics. The complex flight dynamics
and the vast morphological space insects have explored make it extremely challenging
to define and understand what combinations of traits lead to these successful ...
Applied Physical Sciences
Emerging wearable health monitoring technologies require conformable and stretchable
devices. Polymer semiconductors composed of π-conjugated polymer aggregates in an
elastomeric matrix are remarkable in their ability to provide both high stretchability
...
Neural networks have promise as surrogate partial differential equation (PDE) solvers,
but it remains a challenge to use these concepts to solve problems with high accuracy
and scalability. In this work, we show that neural network surrogates can combine
...
Quantum key distribution (QKD) is a promising technology for information-theoretic
secure communications. The practicality of QKD systems is critical for large-scale
network deployment, requiring both high key generation rate and miniaturized modules
for ...
Atomic force microscopy–based infrared (AFM-IR) microscopy has emerged as a powerful
tool for nanoscale chemical imaging, combining the topographical precision of AFM
with the molecular specificity of IR spectroscopy. However, its performance is still
...
Rare-earth oxide-phosphates (historically termed oxyphosphates) occupy the compositional
space between RE2O3 and REPO4 and form during REPO4 melting and high-temperature degradation of REPO4-based environmental barrier coatings. For several reported ...
In surgical oncology, precise intraoperative delineation of malignant tumors for complete
yet non-excessive resection has been challenging. Near-infrared II (NIR-II, 1,000
to 3,000 nm) imaging enables deep-tissue, high-contrast visualization, but clinical
...
Chemistry
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 synthesis of hierarchical heteronanocrystals by ...
Earth, Atmospheric, and Planetary Sciences
The Nile River played a central role in ancient civilizations of Northeast Africa,
yet its response to Holocene climate change and its impact on societies along its
course remain poorly understood. Here we show how climatic and environmental changes
over ...
Continental margins are sources of iron (Fe), a critical oceanic micronutrient limiting
productivity over nearly a third of the ocean. Paradoxically, they are also sinks
of Fe and other particle-reactive elements that are sequestered in margin sediments.
...
Unambiguous body fossils of annelids (ringed worms) first appear in the Cambrian Period
but are so far known exclusively as flattened specimens preserved in Burgess Shale-type
Lagerstätten. Here, we report phosphatized microfossils, interpreted as ...
The evolution of El Niño–Southern Oscillation (ENSO) under past and future climate
change and its influence on marine ecosystems is highly debated. To examine links
between tropical climate variability, high-latitude feedbacks, and deep-sea ecosystems,
we ...
Engineering
Chronic neural interfaces are essential for advancing brain–computer interfaces, neuroprosthetics,
and neuromodulation technologies. However, a long-standing trade-off between performance
and longevity persists due to the scarcity of materials that ...
Charged water drops are more widespread than commonly acknowledged. For example, raindrops
typically carry charges of order
Environmental Sciences
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 Arabidopsis thaliana perceives 2’-aminoacetophenone (2’-AA), a volatile QS ...
Mathematics
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 factors of random integers, and various parameters of random ...
Physics
Ultra-low-crosslinked (ULC) microgels are among the softest colloidal particles nowadays
routinely synthesized experimentally. Despite a growing literature of experimental
results, their microscopic behavior under crowded conditions is yet to be revealed.
...
The coexistence of ferroelectric and antiferromagnetic order in BiFeO3 makes it promising for next-generation magnetoelectric devices. But, single-phase
multiferroics with robust room-temperature polarization and magnetization are rare.
Here, enhanced, ...
The cuprate pseudogap phase displays Fermi arc spectral weight in photoemission and
scanning tunneling microscopy, while recent magnetotransport observations yield evidence
for the existence of hole pockets of fractional area p/8, where p is the doping ...
Sustainability Science
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 the first global map to explicitly differentiate the ...
Social Sciences
Anthropology
The Nile River played a central role in ancient civilizations of Northeast Africa,
yet its response to Holocene climate change and its impact on societies along its
course remain poorly understood. Here we show how climatic and environmental changes
over ...
The Kura–Araxes culture emerged in the South Caucasus in the mid-4th millennium BCE
as an expression of small-scale, household-based communities. It subsequently expanded
across the highlands, becoming the most widespread cultural tradition of the early
...
Economic Sciences
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 deforestation have been rolled out, but relatively ...
Since transport access determines who can reach jobs, education, healthcare, and community
life, governments increasingly use accessibility improvements to reduce deprivation
and tackle social exclusion. Yet whether better access causally reduces ...
Although wildfire smoke is a major public health concern, relatively little is known
about individual avoidance behavior. In this paper, we use smartphone-location data
to study behavioral responses to smoke during the 2018 California wildfire season,
one ...
Psychological and Cognitive Sciences
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-ALPS with aging hallmarks among 40,488 UK Biobank
(UKB) ...
Social Sciences
We study the behavior of an institution that broadcasts reputational signals to facilitate
trust in a population. Using an online marketplace as a motivating example, we develop
a theoretical model in which buyers and sellers are matched on a platform to ...
Contemporary genomic studies of complex traits, such as genome-wide association studies
and polygenic index (PGI) analyses, frequently include the principal components of
the genotype matrix (PCs) among their adjustments for population stratification. In
...
Past work has documented the importance of formal collaboration, particularly coauthorship,
in increasing research productivity and innovation. However, we know much less about
how informal collaboration relates to publication success. Informal ties ...
The 2024 National Strategy for Suicide Prevention identifies suicide as “an urgent
and growing public health crisis” driven partly by mental health and overdose rates,
the COVID-19 pandemic, and declining social connectedness. Yet, data constraints have
...
Biological Sciences
Agricultural Sciences
Maize lethal necrosis (MLN) is a severe disease caused by the combined infection of
maize chlorotic mottle virus (MCMV) and a potyvirus, most often sugarcane mosaic virus
(SCMV). This disease seriously threatens food security across sub-Saharan Africa (...
Anthropology
Linguistic structures show uneven global distributions, but it remains unknown to
what extent such distributions are driven by human population history at a global
scale. Here, we track population history through population genetics and show that,
...
Applied Biological Sciences
Integrating complementary vaccine modalities is essential for combating emerging pathogens.
Although the recent mRNA-VLP hybrids enable spontaneous virus-like particles (VLPs)
self-assembly, thereby enhancing immunogenicity, they fail to elicit robust ...
Biochemistry
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 Arabidopsis thaliana perceives 2’-aminoacetophenone (2’-AA), a volatile QS ...
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 mutations in proteins throughout the pathway. ...
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 O2-regulated genes. Prior studies suggest HIF/HRE ...
Protein trafficking between the cytoplasm and the nucleus is a fundamental process
in eukaryotic cell biology. While linear nuclear localization signals (NLSs) are well
characterized, many nuclear proteins lack a predictable NLS. Here, we identify the
ETS ...
Biophysics and Computational Biology
Understanding flight evolution requires quantifiable metrics. The complex flight dynamics
and the vast morphological space insects have explored make it extremely challenging
to define and understand what combinations of traits lead to these successful ...
Mutations within the transmembrane domains (TMDs) of single-pass transmembrane receptors
often cause aberrant, ligand-independent receptor signaling associated with diverse
malignancies, but their mechanism of action remains largely unknown. These TMD ...
It might have been believed that elucidation of the atomistic structure of PrPSc would lead to an immediate understanding of the mechanism of prion propagation. However,
PrPSc, now known to be a “simple” amyloid, can only template a previously unfolded ...
CC chemokine receptor 7 (CCR7), which orchestrates adaptive immunity, exhibits a phenomenon
known as biased agonism. CCL19 induces robust G-protein signaling and β-arrestin recruitment,
leading to transient signaling. In contrast, CCL21 preferentially ...
Multiple spillovers of porcine deltacoronavirus (PDCoV) into humans in Haiti highlight
its zoonotic potential and the need for targeted interventions. No approved vaccines
or therapeutics are available for use in humans against any DCoVs. Here, we report
...
Influenza B virus contributes to seasonal influenza epidemics and causes global morbidity
and mortality. The two antigenically distinct lineages, Victoria and Yamagata, cocirculate
within the population and are subject to ongoing antigenic drift. In this ...
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 and the kinase RIPK3 serves as regulating signals
for ...
Cell Biology
Erythroferrone (ERFE), secreted by erythroblasts, is regarded as a classical regulator
of iron metabolism through its suppression of hepcidin. Thus, as a consequence of
insufficient hepcidin suppression and reduced iron availability, global Erfe–/– mice ...
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 to cell death. ATG9A, a transmembrane protein, has ...
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-associated antigen 4 (CTLA-4) fails to perform proper
...
An important mechanism by which receptor tyrosine kinases (RTKs) mediate cellular
responses involves the formation of signaling complexes through direct interactions
with membrane-associated docking proteins, followed by phosphorylation of multiple
...
KRAS mutations are a hallmark of pancreatic ductal adenocarcinoma (PDAC), driving
tumor initiation and progression in the vast majority of cases, with KRASG12D being the most prevalent variant. Recent advances have led to the development of
mutation-...
Developmental Biology
The host metabolic state can potentially affect the growth trajectories of tumors
growing at local sites, which are highly variable and unpredictable among populations.
The molecular links between systemic metabolism and tumor growth outcomes remain ...
Ecology
Pursuit and evasion dynamics are a general phenomenon observed in predator–prey interactions
across terrestrial, aquatic, and aerial domains. Differences in body mass and domain
generate variation in biomechanical traits that shape these encounters, yet ...
Microbial competition for scarce resources shapes biodiversity patterns and ecosystem
function across global biomes, yet quantifying this process from genomic data has
remained elusive. Here, we introduce CaCo, a scalable metric that transforms ...
Community thermophilization—the process by which communities are increasingly dominated
by species from warmer biogeographic regions—is a widespread ecological response to
warming. However, most studies on thermophilization use observational data, making
...
Environmental Sciences
Continental margins are sources of iron (Fe), a critical oceanic micronutrient limiting
productivity over nearly a third of the ocean. Paradoxically, they are also sinks
of Fe and other particle-reactive elements that are sequestered in margin sediments.
...
The evolution of El Niño–Southern Oscillation (ENSO) under past and future climate
change and its influence on marine ecosystems is highly debated. To examine links
between tropical climate variability, high-latitude feedbacks, and deep-sea ecosystems,
we ...
Evolution
Unambiguous body fossils of annelids (ringed worms) first appear in the Cambrian Period
but are so far known exclusively as flattened specimens preserved in Burgess Shale-type
Lagerstätten. Here, we report phosphatized microfossils, interpreted as ...
We study the behavior of an institution that broadcasts reputational signals to facilitate
trust in a population. Using an online marketplace as a motivating example, we develop
a theoretical model in which buyers and sellers are matched on a platform to ...
Mutualistic symbioses are potentially vulnerable to exploitation, particularly in
hosts that acquire symbionts from the environment, where harmful exploiters inhabit.
The independent evolution and persistence of intricate partner-choice mechanisms in
many ...
Advances in molecular epidemiology and computational modeling have improved our ability
to track pathogen evolution, but accurate reconstruction of spatiotemporal transmission
remains essential for epidemic preparedness and response. Structured coalescent ...
Genetics
Contemporary genomic studies of complex traits, such as genome-wide association studies
and polygenic index (PGI) analyses, frequently include the principal components of
the genotype matrix (PCs) among their adjustments for population stratification. In
...
Immunology and Inflammation
Human leukocyte antigen (HLA) class I molecules are highly polymorphic, restricting
peptide binding to narrow sequence subsets. Designing peptides that bind multiple
HLA supertypes—termed superbinders—offers a promising strategy for broad-spectrum
T cell ...
Inflammatory injury to the intestine triggers a reprogramming of the intestinal epithelium
to a fetal-like state that drives rapid restoration of the epithelial barrier. Although
the intestinal microbiota is a key modulator of inflammation, its role in ...
Th17 cell function is highly context-dependent and can be categorized into pathogenic
and nonpathogenic Th17 cell subsets. Understanding the molecule control of pathogenic
Th17 (pTh17) cell immunity will benefit the treatment for related autoimmune ...
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 TLR1 variant associated with immune dysregulation
and ...
Medical Sciences
In surgical oncology, precise intraoperative delineation of malignant tumors for complete
yet non-excessive resection has been challenging. Near-infrared II (NIR-II, 1,000
to 3,000 nm) imaging enables deep-tissue, high-contrast visualization, but clinical
...
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-ALPS with aging hallmarks among 40,488 UK Biobank
(UKB) ...
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 located in the DNA-binding domain (DBD). Due to the low
...
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 reduced levels of the mitochondrial scaffold, Mic60, ...
Dysregulation of mitochondrial dynamics modulates malignant cell fate; however, the
substantial heterogeneity in mitochondrial dynamics among tumor cells within individual
tumor nodules and the resultant functional consequences remain inadequately ...
Despite effective lipid-lowering therapies, atherosclerosis continues to be a leading
cause of death, with considerable residual cardiovascular risk. Atherosclerotic lesions
develop preferentially at arterial regions exposed to disturbed flow (d-flow), ...
Adaptive thermogenesis is a fundamental defense against obesity through energy dissipation,
yet the molecular mechanisms that couple energy sensing to transcriptional control
remain incompletely understood. Here, we identify Feimin as a key activator of ...
Androgen receptor (AR) signaling is central to prostate cancer progression, yet resistance
to AR-targeted therapies remains a major clinical challenge. Understanding the molecular
consequences of AR pathway inhibition is therefore essential for improving ...
Microbiology
Iron is an essential element that can be growth-limiting in microbial communities,
particularly those present within host organisms. To acquire iron, many bacteria secrete
siderophores, secondary metabolites that chelate ferric iron. These iron chelates
...
Physical interactions with bacterial colonizers at mucosal barrier surfaces can have
beneficial or detrimental effects on viral infectivity and transmission. The oropharyngeal
mucosal surface is a major portal of entry for many pathogenic respiratory ...
SUMOylation is a dynamically regulated post-translational modification involving covalent
attachment of small ubiquitin-like modifiers (SUMOs) to lysine residues of target
proteins. SUMOylation modulates multiple fundamental host cellular pathways, ...
Germline targeting vaccination strategies against highly variable pathogens such as
HIV aim to elicit broadly neutralizing antibodies (bnAbs) with particular immunogenetic
or structural features. The V2 apex of the HIV Env protein is a promising target ...
Neuroscience
Retinal ganglion cell (RGC) axons form the optic nerve (ON). Numerous age-related
ON diseases, including glaucoma, the second most common cause of worldwide blindness,
result from multiple RGC stressors. Nearly all ON astrocytes in the optic nerve head
(...
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 chemically mediated male–male competition remains underexplored ...
Kinetochore proteins, long studied for their role in cell division, are also required
for the proper postmitotic development of hippocampal and cortical neurons. Proteins
of the kinetochore complex were present in axons and dendrites of postmitotic ...
Pseudorabies virus (PRV), a member of the Alphaherpesvirinae subfamily, primarily infects pigs and poses a significant threat to the swine industry.
In recent years, emerging PRV variants have been reported to infect humans, predominantly
causing ...
Mechanotransduction within the cochlea depends on the precise architecture of hair
bundles, yet our comprehension of the mechanisms that govern the formation and maintenance
of the sound-receptive structure is still limited. Here, we identify Tmem30b, a ...
Interareal communication is crucial for coordinated brain function. Given the largely
contralateral organization of the brain, bimanual coordination likely depends on interactions
across the two cerebral hemispheres for motor planning and execution. The ...
The brain is thought to produce decisions by gradual accumulation of sensory evidence
through a hierarchically organized feedforward cascade of neuronal activities that
transforms early stimulus representations in the primary somatosensory cortex (S1)
to ...
According to glymphatic system theory, cerebrospinal fluid (CSF) perfuses the brain’s
interstitial space to support waste clearance, but the magnitude of this flow and
the outflow pathway of interstitial fluid (ISF) in humans remain uncertain. To achieve
...
The arcuate fasciculus (af) is a crucial dorsal pathway underpinning human language,
yet its weak frontal connectivity in macaques—the standard primate model—creates an
evolutionary puzzle. Here, we investigate the common marmoset, a distantly related
...
The zona incerta (ZI) plays an important role in diverse behavioral functions and
is an emerging clinical target for deep brain stimulation to treat neurological conditions.
Despite their importance, the cell type composition of the ZI and the anatomical ...
Physiology
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 underlying mechanisms remain poorly characterized due to ...
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 quality of life during treatment, as well as delay
...
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 integrated stress response (ISR; the GCN2–ATF4 pathway), ...
Plant Biology
Sympetaly (fused petals) is a key morphological innovation that has arisen multiple
times during evolution. It occurs via one of two developmental pathways: late sympetaly
(from initially separate petal primordia that later fuse) or early sympetaly (...
Sustainability Science
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 deforestation have been rolled out, but relatively ...
Corrections
Retraction
Cover image: Pictured are archaeological excavations at Jebel Barkal, a sandstone outcrop and UNESCO World Heritage site in northern Sudan. Jan Peeters et al. examined 26 sediment cores from the Nile valley to reconstruct 12,500 years of climate history. The cores revealed that the Nile followed a stable course when the ancient city of Napata flourished, between 1070 BCE and 350 CE. The river helped build fertile floodplains, supported long-term settlement, and contributed to the rise of a dynasty. See the article by Peeters et al. e2529986123. Image credit: Henrik Brahe (University of Tübingen, Tübingen, Germany).
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