Table Of Contents Page, PNAS Volume 123, Number 13
This Week in PNAS
Opinion
Retrospective
Cuban-born Pedro A. Sanchez (1940-2026) became the face of tropical soil science at
Cornell University and the North Carolina State University. His combination of process-based
understanding of soils, emphasis on farmer choices and conducive policy ...
Commentaries
Perspectives
Resolving the biological and geological events that led to the origin of eukaryotes
is an ongoing challenge in biology. A major step in the evolution of complex cellular
life was the merger between an ancestral host cell and a bacterium (that became the
...
Foundation models—large AI systems pretrained on broad, heterogeneous data—are transforming
scientific discovery. These models (e.g., GPT, GenCast, AlphaFold) excel at learning
generalizable representations and adapting to new tasks with limited data. Yet,...
Letters
This article has a reply:
Reply to Sacco: Complete spaces as outcomes of evolutionary optimization
View the original article:Payoff equivalence and complete strategy spaces of direct reciprocity
This article has a reply:
View the original article:
Berry Batesian mimicry enables bird dispersal of asexual bulbils in a yam
Brief Reports
In early 2025, the NIH unexpectedly terminated 2,291 active research grants, withdrawing
$2.45 billion and disrupting thousands of projects. While the economic magnitude of
these cuts is known, less is understood about how they differed across researchers’...
Why do girls outperform boys in education? One contributing factor might be that girls
read more than boys, which fosters competencies relevant in education. Moreover, boys
might rely more heavily on schools to support and encourage reading, meaning that
...
Physical Sciences
Applied Mathematics
The replicator and the Generalized Lotka–Volterra equations are closely related, foundational
models in evolutionary game theory and community ecology, respectively. The concept
of evolutionary stability and its relationship with dynamic stability has ...
Empirical research on sensory processing often focuses on group averages to uncover
how sensory input translates into behavior. While this population-level approach has
revealed important general principles of genetic and environmental control of behavior,...
Infectious disease spread is a multiscale process composed of within-host (biological)
and between-host (social) drivers and disentangling them from each other is a central
challenge in epidemiology. Here, we introduce VIBES, a multiscale modeling ...
Microbial communities play essential roles in shaping ecosystem functions and predictive
modeling frameworks are crucial for understanding, controlling, and harnessing their
properties. Competition and cross-feeding of metabolites drives microbiome ...
Applied Physical Sciences
Predicting and controlling the propagation of nonlinear responses in materials is
critical to a range of fields, from the manipulation of single electrons in quantum
optics to the understanding of crack propagation and failure of quasi-brittle materials.
...
Many organisms leverage an interplay between shape and activity to generate motion
and adapt to their environment. Embedding such mechanical feedback into synthetic
micrometer-sized robots could eliminate the need for sensors, software, and actuators.
...
Astronomy
Mesoscale structures in turbulent media can often be described as fractional dimensional
across a wide range of scales. The goal of this paper is to determine the structure’s
dimension from a projected image. Our method exploits the laws of scaling of ...
Biophysics and Computational Biology
Influenza continues to be a major threat to global health and a substantial economic
burden. Innovative strategies are needed to tackle the growing resistance to established
influenza therapeutics and to develop new therapeutics with novel mechanisms of ...
The architecture of early olfactory processing is a striking example of convergent
evolution. Typically, a panel of broadly tuned receptors is selectively expressed
in sensory neurons (each neuron expressing only one receptor), and each glomerulus
...
Chemistry
Recent advances in prebiotic chemistry suggest that hydrogen cyanide (HCN) serves
as a fundamental precursor for nearly all essential biomolecules and protometabolic
processes for life’s emergence. Although prevailing models of endogenous cyanide ...
Electrocatalysts in combination with photoelectrodes can provide higher activity and/or
lower overpotential for a broad range of photoelectrochemical processes. Although
cocatalyst nanoparticles (NPs) on semiconductor surfaces have been extensively ...
Proton exchange membrane fuel cells (PEMFCs) hold great promise for clean energy conversion,
yet their performance is limited by insufficient mass transport bottlenecks within
the catalyst layer. Addressing this fundamental issue demands innovative ...
Transition metal-catalyzed cross-coupling of two similar electrophiles (XEC) to construct
C(sp2)–C(sp2) bonds is a powerful emerging synthetic methodology. However, efficient and selective
XEC to create heterocoupled C*(sp2)–C(sp2) linkages from equimolar ...
Water’s anomalous thermodynamic behavior arises from the presence of intricate hydrogen-bond
networks that are highly sensitive to many-body interactions, challenging molecular
modeling for decades. The ongoing machine learning revolution has opened the ...
Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals,
including the strains of current concern. Current treatments, such as Zanamivir and
Oseltamivir, are limited by noncovalent binding and emerging resistance. We ...
Earth, Atmospheric, and Planetary Sciences
The capacity of some plants to access water and nutrients at depths greater than one
meter is a critical functional trait that confers resistance to drought and impacts
both belowground and shallow soil processes. Here, we report water and strontium ...
Between 2023 and 2024, Amazonian rainforests experienced two consecutive, record-breaking
droughts—each more intense than any previously observed—yet their impacts remain largely
unquantified. Using newly developed monthly radar satellite observations (...
Engineering
Artificial muscles offer unique advantages for robotics, but their inability to adapt
to diverse scenarios significantly limits their widespread application. We present
the helical anisotropically reinforced polymer actuator (HARP)—a versatile class of
...
Transplantation-free neuron regeneration remains attractive yet unsolved for reversing
Parkinson’s disease (PD). Here, we present enzyme-driven mesoporous gold nanomotors
(Apyrase@Au) that leverage endogenous biochemical energy for spatiotemporally ...
Ultrasound offers a noninvasive, clinically relevant means to achieve precise spatiotemporal
control of cargo release from ultrasound-responsive drug delivery systems within deep
tissues. This approach enables targeted delivery of therapeutic agents, ...
Traditional solar energy harvesters are single-mode—typically designed to convert
available sunlight either into heat or electricity. However, neither energy form is
continuously useful, and an optimal variant should instead be capable of autonomously
...
Natural rubber outperforms synthetic rubbers because of its long chains and strain-induced
crystallization (SIC). However, these advantages are largely lost when the natural
rubber chains are masticated during processing, and silica particles are added ...
The mammalian cerebral cortex projects to the striatum in a precise, hierarchical
topography, forming parallel loops that underlie sensorimotor, associative, and limbic
processing. Despite the striatum’s lack of clear anatomical boundaries, these ...
Physics
The dynamics of Lagrangian particles in turbulence play a crucial role in mixing,
transport, and dispersion in complex flows. Their trajectories exhibit highly nontrivial
statistical behavior, motivating the development of surrogate models that can ...
Nanophotonics relies on precise nanoscale structuring, yet conventional fabrication
techniques remain complex and costly. Layered van der Waals (vdW) materials, with
their intrinsic anisotropy and high refractive indices, offer a promising route toward
...
Sustainability Science
Global anthropogenic phosphorus (P) cycle changes require active management with differentiated
sustainability strategies across countries. This study developed a universal framework
that integrates the comprehensive P flow process with sustainability ...
Social Sciences
Demography
Migration decisions are embedded in social and family trajectories that escape traditional
data sources, which tend to observe individuals in isolation. Genealogical microdata
now make it possible to trace these dynamics over long time horizons. This ...
Economic Sciences
Abandoning detrimental social norms is complex due to the strong pressure to conform.
We examine how leaders can guide norm change in heterogeneous societies where individual
preferences evolve at different rates. Inspired by the model and experimental ...
Psychological and Cognitive Sciences
Language influences our thinking and affects many aspects of cognition, from how we
perceive the world to how we interact socially. Thus, objectively characterizing linguistic
background is crucial for research in many areas, including second language ...
Because shame leads to evasions, aggression, and other behaviors that victims and
third parties find undesirable, a prominent theory regards this emotion as maladaptive.
By contrast, an alternative, adaptationist theory asks whether shame might benefit
...
Evolutionary theory and historical evidence suggest humans possess distinct psychological
tendencies for defensive and offensive violence, which have insufficiently been considered
in research. In a large-scale preregistered study across 58 countries (N = ...
Biological Sciences
Anthropology
We present a genome sequenced to ~37-fold genomic coverage from an approximately 110,000-y-old
male Neandertal from Denisova Cave in the Altai Mountains and analyze it together
with previously published Neandertal genomes of high quality. We show that he ...
Applied Biological Sciences
The variable domains in Fab regions are well-established contributors to high concentration
viscosity of IgG, primarily through charge and hydrophobic interactions. In contrast,
the roles of the Fc and the number of self-interacting sites (valency) are ...
Cytokines are critical signaling molecules, but their therapeutic potential remains
unrealized due to pleiotropic effects across cell types. Current strategies to develop
conditionally active cytokines involve complex engineering and production, limiting
...
Biochemistry
Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals,
including the strains of current concern. Current treatments, such as Zanamivir and
Oseltamivir, are limited by noncovalent binding and emerging resistance. We ...
The identification of functional ligand-membrane protein interactions under native
conditions remains a major challenge in cancer biology. Using cell-systematic evolution
of ligands by exponential enrichment, we identified a high-affinity DNA aptamer, ...
Ribosomal RNA (rRNA) modifications are important for ribosome function and can influence
bacterial susceptibility to ribosome-targeting antibiotics. The universally conserved
16S rRNA nucleotide C1402, for example, is the only 2’-O-methylated nucleotide ...
The bacterial pathogen Legionella pneumophila secretes effector proteins that remodel host endomembranes to establish a replication-permissive
niche known as the Legionella-containing vacuole (LCV). Among these, SetA disrupts vesicle trafficking by ...
Inside-Out (I-O) protein display, the noncanonical surface localization of intracellular
proteins, represents an underexplored feature of tumor cell biology. Here, we map
the molecular landscape and trafficking mechanisms that control the presentation of
...
Biophysics and Computational Biology
Interactions between amyloidogenic proteins are emerging as critical drivers of neurodegenerative
diseases. Among others, in Alzheimer’s disease (AD) and severe forms of chronic traumatic
encephalopathy (CTE), codeposition of tau and amyloid-β (Aβ) leads ...
The integration of environmental cues into cellular programs is crucial for cell function.
Yet, how this integration is modulated due to cellular aging remains unclear. We propose
that the 3D chromatin organization filters these signals and investigated ...
Cell Biology
Metabolic reprogramming is a fundamental hallmark of cancer progression. However,
the oncogenic mechanisms underlying serine metabolism and its impact on chemotherapeutic
sensitivity in gastric cancer (GC) remain poorly defined. Here, through integrated
...
Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations
in the SMN1 gene. Although classically viewed as a neurogenic disease, SMA patients exhibit poor
skeletal muscle regeneration and increased fatty-fibrotic infiltration. ...
Endocytosis of the epidermal growth factor receptor (EGFR) is considered a key regulator
of the receptor signaling activity. However, the molecular mechanisms underlying EGFR
endocytosis are incompletely understood. Although ligand-induced ubiquitination ...
Through alternative splicing, the TP53 gene can generate multiple protein isoforms
with distinct biochemical properties. The p53psi isoform has been identified as a
shorter variant than full-length p53 as it lacks nuclear localization, oligomerization,
...
Clathrin-mediated endocytosis (CME) is a multistage process that involves the initiation
and stabilization of clathrin-coated pits (CCPs) that invaginate and finally detach
from the plasma membrane to form clathrin-coated vesicles (CCVs). Given that ...
Developmental Biology
Neural crest–derived cells offer valuable opportunities to dissect mechanisms of cell
fate specification and differentiation and the underpinnings of cell type diversification
over evolutionary time. Particularly useful for such analyses are pigment cells ...
Interorgan communication is essential for metabolic homeostasis and healthy aging,
with adipose tissue acting as a central hub that coordinates systemic metabolism,
stress responses, and longevity. Here, we show that the miRNA-processing enzyme Dicer-1
(...
Ecology
The capacity of some plants to access water and nutrients at depths greater than one
meter is a critical functional trait that confers resistance to drought and impacts
both belowground and shallow soil processes. Here, we report water and strontium ...
The replicator and the Generalized Lotka–Volterra equations are closely related, foundational
models in evolutionary game theory and community ecology, respectively. The concept
of evolutionary stability and its relationship with dynamic stability has ...
Between 2023 and 2024, Amazonian rainforests experienced two consecutive, record-breaking
droughts—each more intense than any previously observed—yet their impacts remain largely
unquantified. Using newly developed monthly radar satellite observations (...
Environmental Sciences
The study documents in detail the extent of damage to the exterior of the sunken nuclear
submarine Komsomolets and that previous remedial action carried out by Russia was
still in place. No evidence was found of any plutonium in the near environment ...
Heavy metals are increasingly recognized as major drivers of antibiotic resistance
gene (ARG) dissemination in soil ecosystems. However, the role of phages in heavy
metal–driven ARG dissemination and the underlying mechanisms remain poorly understood.
...
Evolution
Genetic diversity within species underpins evolutionary adaptation and has recently
been included as a target for protection in the United Nations’ Global Biodiversity
Framework (GBF). Yet, we lack mathematical tools to estimate past genetic diversity
...
The demographic history of Neanderthals is only partially understood. In Europe, some
degree of genetic continuity has been shown from 120 thousand years ago (ka) onward
despite the occurrence of multiple subsequent diversification events. While it has
...
Phenotypic plasticity allows organisms to adapt traits in response to environmental
changes, yet the molecular basis by which such plastic traits become genetically fixed
remains unclear. Here, we investigated gut-length plasticity in medaka fish (Oryzias ...
Genetics
Boron (B) is a crucial micronutrient, particularly in volcanic soils where its deficiency
hampers agriculture. Here, we investigate the genetic basis of leaf B accumulation
in natural populations of Arabidopsis thaliana that colonized volcanic islands in ...
Circadian clocks govern daily physiological and behavioral processes and are crucial
for health; disruptions can lead to various diseases. The circadian phase of entrainment—the
phase of the internal circadian clock in relation to external environmental ...
Immunology and Inflammation
Numerous transcriptional regulators have been associated with the differentiation
pathways that lead to recirculating vs. tissue-resident memory T cells. However, it
is unclear whether independent, coordinated expression of these regulators is required
to ...
Iron-dependent phospholipid (PL) peroxidation, which is reduced by glutathione peroxidase
4, is recognized as the hallmark of cells undergoing ferroptosis. Although studies
have attempted to elucidate the molecular mechanisms underlying ferroptosis in ...
Inflammasomes are cytosolic immune complexes that recognize pathogen-associated stimuli
to initiate a potent inflammatory response. While some inflammasomes directly recognize
pathogen-associated molecules, others, such as the NLRP1B inflammasome, respond ...
Antigen-specific immunoglobulin-G (IgG) antibodies cause or contribute to the pathogenesis
of a wide spectrum of human diseases and conditions. Multiple therapeutic approaches
have been developed, yet they are limited by variable safety and efficacy, ...
Pregnancy requires expanded maternal tolerance to semiallogeneic fetal-expressed antigens
to protect against fetal loss and other pregnancy complications. Our understanding
of how this biological imperative works remains uncertain. Here we show pregnancy
...
The immunopathogenesis of autoimmune neurological syndromes (AINS) with antibodies
against the 65 kDa isoform of glutamic acid decarboxylase (anti-GAD65 AINS) remains
poorly understood. To elucidate underlying disease mechanisms and identify relevant
cell ...
During V(D)J recombination, antibody diversity is enhanced by nontemplated junctional
modifications that generate immensely diverse heavy chain (HC) and light chain (LC)
complementarity-determining 3 antigen-contact regions (CDR3s). We previously ...
Medical Sciences
CD47 is an innate immune checkpoint that inhibits phagocytosis by myeloid cells, contributing
to immune evasion by cancer cells. CD47-blocking antibodies have limited efficacy
in glioblastoma (GBM), and the cell-intrinsic role of CD47 is poorly ...
Microbiology
Influenza continues to be a major threat to global health and a substantial economic
burden. Innovative strategies are needed to tackle the growing resistance to established
influenza therapeutics and to develop new therapeutics with novel mechanisms of ...
Staphylococcus aureus is a human pathogen capable of forming biofilms that complicate treatment and facilitate
chronic infections. A family of S. aureus serine hydrolases are important regulators of virulence and biofilm formation. Among
these, FphE is ...
The COVID-19 pandemic, which has resulted in over seven million global fatalities,
poses a substantial threat to public health and precipitated a global economic crisis.
Emerging variants of concern (VOCs) with enhanced transmissibility and improved ...
Members of the TRIM E3 ligase family are effectors of the host innate or intrinsic
defense against various viruses; however, how specific TRIM proteins antagonize coronavirus
infection is still largely elusive. Through an RNAi screen targeting 71 human ...
Some primates are immune to infection by most African trypanosome parasites due to
apolipoprotein L-1 (APOL1), a primate-specific ion channel-forming protein. Our long-term
objective has been to reduce African trypanosomiasis in livestock by genetic ...
Small RNAs and microRNAs (miRNAs) play diverse roles in host virus interactions and
hold promise for therapeutic applications. An uncharacterized shrimp miRNA with potent
activity against white spot syndrome virus (WSSV), a major double-stranded DNA ...
The US broiler production system processes over 9.3 billion chickens annually through
a highly integrated pyramid structure where two primary breeding companies supply
genetic stock to approximately 40 major integrators operating nationwide. To provide
a ...
Neuroscience
Empirical research on sensory processing often focuses on group averages to uncover
how sensory input translates into behavior. While this population-level approach has
revealed important general principles of genetic and environmental control of behavior,...
The architecture of early olfactory processing is a striking example of convergent
evolution. Typically, a panel of broadly tuned receptors is selectively expressed
in sensory neurons (each neuron expressing only one receptor), and each glomerulus
...
The mammalian cerebral cortex projects to the striatum in a precise, hierarchical
topography, forming parallel loops that underlie sensorimotor, associative, and limbic
processing. Despite the striatum’s lack of clear anatomical boundaries, these ...
Microscale electrodes, on the order of 10 to 100 µm, are rapidly becoming critical
tools for neuroscience and brain–machine interfaces for their high channel counts
and spatial resolution, yet the mechanical details of how probes at this scale insert
into ...
Human aging is marked by progressive reorganization of large-scale functional brain
networks; these brain network changes have been linked to cognitive decline and disease
vulnerability. Conversely, while mice have served as powerful models for ...
Ependymal cells in the adult ventricular-subventricular zone are increasingly recognized
for functions extending beyond cerebrospinal fluid dynamics; however, their identity
and functional specialization remain incompletely understood. While ependymal ...
Mouse vomeronasal sensory neurons are continuously generated from stem cells and differentiate
to express either V1R or V2R G protein–coupled receptors (GPCRs), along with their
respective Gαi2 or Gαo G-protein subunits. We previously reported that Gαo-...
Epilepsy is a common neurological disorder that is widely believed to be associated
with an imbalance between neuronal excitation and inhibition (E/I). DIRAS2, a Ras-related
GTPase, has not been well understood regarding its role and function within the ...
Neurophysiological mechanisms underlying psychological resilience—the ability to overcome
adversity—have been extensively studied in animals. However, compared to that in animals,
human resilience is unique in that it is underpinned by higher-order ...
Shifts in ecological niches are often driven by evolutionary changes in the olfactory
system, yet the underlying mechanisms remain poorly understood. To investigate this,
we used Drosophila suzukii, an invasive fruit pest, as a model. Unlike most ...
Pharmacology
Tyrosine kinases (TKs) are frequently mutated or overexpressed in cancer, and TK inhibitors
(TKIs) are an important therapeutic modality against TK-driven cancers, but many patients
show an underwhelming response to TKIs prescribed on the basis of tumor ...
Physiology
Neurons experience brief, intense periods of energy demand when they are excited,
but how they rapidly coordinate energy expenditure with production is incompletely
understood. Part of the difficulty has been measuring the levels of molecules involved
in ...
Drug chemoresistance remains a major reason of treatment failure in cancer patients.
In head and neck squamous cell carcinoma (HNSCC), the seventh most common cancer worldwide,
cisplatin chemotherapy remains the gold standard for advanced tumors but often ...
The m5C orchestrator NSUN7 drives SPARC/HMGB1 axis–mediated inflammation to exacerbate kidney injury
Growing evidence indicates that kidney inflammation is a major contributor to the
pathogenesis of various renal diseases, including acute kidney injury (AKI). Although
RNA modifications have been implicated in regulating kidney inflammation, their precise
...
Ion channels are the second most common clinical drug target besides G protein–coupled
receptors. Aneurysmal diseases pose a significant threat to human life. Novel drug
targets for its treatment remain to be explored. We investigated the role of an ion
...
Plant Biology
Phycobilisomes (PBSs) are supramolecular pigment–protein complexes composed of phycobiliproteins
and linker proteins, serving as the major light-harvesting complexes that capture
and transfer light energy to photosystem II (PSII) and photosystem I (PSI) ...
Hollow stems have independently evolved multiple times across the plant kingdom and
play crucial roles in plant development and various environmental adaptations. However,
the mechanisms underlying stem hollowness remain poorly understood. Water spinach
(...
Plants monitor their environment for microbial invaders using pattern-recognition
receptors that detect microbe-associated molecular patterns (MAMPs). Flagellin, the
main component of bacterial flagellum, contains the flg22 epitope recognized by the
plant ...
Population Biology
Infectious disease spread is a multiscale process composed of within-host (biological)
and between-host (social) drivers and disentangling them from each other is a central
challenge in epidemiology. Here, we introduce VIBES, a multiscale modeling ...
Psychological and Cognitive Sciences
When at rest, the mind becomes preoccupied with self-generated thoughts, commonly
known as mind-wandering. While the social, autobiographical, and temporal features
of these thoughts have been extensively studied, little is known about how frequently
the ...
Systems Biology
Microbial communities play essential roles in shaping ecosystem functions and predictive
modeling frameworks are crucial for understanding, controlling, and harnessing their
properties. Competition and cross-feeding of metabolites drives microbiome ...
Corrections
Retraction
Cover image: Pictured are microfluidic brain-on-chip devices. Maxime Poinsot et al. used a biologically grounded brain-on-chip platform to explore the development and organization of long-range projections from the mammalian cerebral cortex to the striatum. The authors found that hyperexcitability in the cortex can disrupt the self-assembly of striatal projections, resulting in neural circuit dysfunction. This brain-on-chip platform could provide insight into neurodevelopmental and psychiatric disorders characterized by connectivity defects, such as autism spectrum disorder, schizophrenia, epilepsy, and obsessive-compulsive disorder. See the article by Poinsot et al. e2513459123. Image credit: Maxime Cazorla.
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