Table Of Contents Page, PNAS Volume 123, Number 10
This Week in PNAS
News Feature
Retrospective
The death of Sir John Bertrand Gurdon in October 2025 marks the passing of one of
the most influential biologists of the modern era. A developmental biologist, Sir
Gurdon’s best-known experiments were performed with frog eggs and nuclear transfer,
leading ...
Profile
The 2024 Nobel Prize in Chemistry recognized revolutionary computational success in
predicting protein structures from amino acid sequences and for designing amino acid
sequences that fold into desired protein structures. The ultimate accomplishment ...
Commentaries
Perspectives
Achieving the goals of the Kunming–Montreal Global Biodiversity Framework (GBF) requires
monitoring systems that can transform heterogeneous observations into consistent,
decision-relevant knowledge. Yet current biodiversity data are fragmented, uneven
in ...
Biodiversity is declining in many parts of the world. Biological diversity measurement
and monitoring are fundamental to the assessment of the causes and consequences of
environmental changes, identification of key areas for the protection of biodiversity
...
Letters
View the original article:
Strategies reimagined: SDG-driven solutions for combating global desertification
This article has a reply:
This article has a reply:
Reply to Pernet et al.: Mesocosm experiment reveals the carbon removal mechanisms in oyster farming
View the original article:Oyster farming acts as a marine carbon dioxide removal (mCDR) hotspot for climate change mitigation
Physical Sciences
Applied Mathematics
From soft tissues to seismic damping systems, mechanical compliance is widely exploited
by natural and engineered systems for dissipating energy and averting catastrophic
failure. While this principle is well understood under quasi-static conditions, the
...
Applied Physical Sciences
Despite their ubiquity in Nature, spikes or stingers rarely exhibit sharp tips. Instead,
a closer inspection of their roughly conical tips reveals a striking similarity in
their profiles: They adhere to a power-law,
The mechanosensory lateral line system, found in all fishes, detects water movement
and pressure fields and mediates crucial behaviors in aquatic environments. Neuromast
sensory organs, the functional units of the system, exhibit diversity in shape and
...
Lithium-ion battery formation is a pivotal step that dictates performance, longevity,
and manufacturing safety. At the core of this process is the formation and evolution
of the solid electrolyte interphase (SEI), whose nanoscale thickness, high ...
Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids.
Hybrid polymer–lipid vesicles incorporate both polymers and lipids, offering promising
properties for developing pharmaceuticals, biosensors, and artificial cells. The ...
Multiple polymer networks, such as double-network elastomers comprising a sacrificial
and a matrix network, exhibit exceptional mechanical resilience, commonly attributed
to the formation of an extended damage zone before a crack can grow. However, the
...
This study presents a biocompatible, ultrasound-responsive platform for remotely activating
mechanochemical reactions within live plant tissue. Fluorogenic Mechanophore-embedded
silica NanoParticles (FMNPs) that are thermally stable were engineered to ...
Biophysics and Computational Biology
In most organisms, ATP synthesis is powered by the proton motive force (pmf) and catalyzed
by ATP synthase. While the chemiosmotic theory originally proposed a “delocalized
coupling” between proton pumps and consumers, growing evidence implicates the ...
Revealing the complex mechanisms of protein folding, including the transient intermediate
states that govern the process, is a fundamental goal in computational biophysics.
While molecular dynamics (MD) simulations generate vast amounts of data to this ...
Chemistry
Molecular organization at the nano-bio interface governing the colloidal stability,
reactivity, immune recognition, and drug delivery performance of nanoparticles remains
difficult to predict. Quantifying the primary hydration energetics of biomolecule-...
Site 1 sodium channel blockers (S1SCBs), such as tetrodotoxin (TTX) and neosaxitoxin,
are ultrapotent local anesthetics with low tissue toxicity. Their duration of action
is relatively brief, but increasing the dose can lead to systemic toxicity. Here,
we ...
Graphene supported on Si(111) (short Gr/Si) is one of the very few examples of a metal-free
carbon catalyst that catalyzes gas–surface reactions. Kinetics measurements indicate
dissociation of SO2 and H2S but molecular adsorption of N2O. In addition, ...
Organic semiconductors offering efficient mixed ionic-electronic charge transport
are key components of organic electrochemical transistors (OECTs) needed for future
bioelectronics and other technologies. However, hydrophobic semiconductors typically
have ...
Water and its ability to modulate the protonation states of biomolecules govern the
physical chemistry of life, dictating their metabolic functions. However, how amino
acid protonation alters protein hydration and solubility is an open question since
...
Earth, Atmospheric, and Planetary Sciences
Large volcanic eruptions and intense wildfires perturb Earth’s atmospheric temperature.
Understanding the climate response to such natural forcings is essential for obtaining
reliable estimates of its response to anthropogenic greenhouse gas emissions. ...
Mobile-lid tectonics is a first-order feature characterizing the modern Earth, yet
its origins remain enigmatic due to a scarcity of ancient terrestrial materials. Detrital
zircons provide the most complete archive of Earth’s early crust and preserve the
...
Dunes are widely distributed on Earth and other extraterrestrial bodies, yet relatively
little is known about what controls their maximum size. Earth’s megadunes (>100 m
tall) have traditionally been attributed to constraints including atmospheric ...
Land surface relative humidity (RH) is a key variable in the coupled land–atmosphere
system that profoundly influences terrestrial hydroclimate and ecosystems. Yet historical
changes in land RH are not well understood due to limited observations, biased ...
Persistent knowledge gaps in precipitation microphysics, particularly the nonlinear
coupling between microphysical process hierarchies and raindrop size distribution
(DSD) variability, keep introducing systemic uncertainties into precipitation retrievals
...
The Grounding Line (GL)—the transition from ice grounded on the continent and ice
afloat in the ocean—is a sensitive indicator of glacier stability and mass balance.
Using differential synthetic aperture radar interferometry from ERS-1/2, Sentinel-1,
...
Engineering
Mechanoresponsive cell proliferation is a feature of growing tumors, despite the suppression
of many other regulatory checkpoints in cancer, but the underlying cell-scale mechanisms
driving this behavior have not yet been established. In this study, we ...
Altermagnetism refers to a wide class of magnetic orders featuring magnetic sublattices
with opposite spins related by rotational symmetries, resulting in nontrivial spin
splitting and magnetic multipoles. However, the direct observation of the ...
Legged machines are becoming increasingly agile and adaptive, but they have so far
lacked the morphological diversity of legged animals, which have been rearranged and
reshaped to fill millions of niches. Unlike their biological counterparts, legged
...
Physics
We present the finite-difference parquet method that greatly improves the applicability
and accuracy of two-particle correlation approaches to interacting electron systems.
This method incorporates the nonperturbative local physics from a reference ...
High temperature superconductivity (HTSC) typically occurs as a “dome” over a narrow
range of doping in its phase diagram. The reaction of YBa2Cu3O7 with Ag2O2 at ≥800 °C and 6 GPa inserts oxygen atoms between the Cu1 sites to form tetragonal
YBa2Cu3O8 ...
Liquid crystal mesophases of achiral molecules are normally achiral, yet in a few
materials they spontaneously segregate and form right- and left-handed chiral domains.
One mechanism that drives chiral segregation is molecular shape fluctuations between
...
Social Sciences
Anthropology
Rapid decay of organic artifacts obscures our view of ancient tropical settlements.
We present a study of architecture and artifact assemblages from an ancient settlement
excavated at the Birds of Paradise (BOP) fields, the largest lidar and field-...
Psychological and Cognitive Sciences
The present study examined the accuracy of conscious representations that emerge from
implicit statistical learning (ISL), a fundamental cognitive process through which
we extract regularities in the environment. While ISL has several characteristics
of ...
Can Large Language Models (LLMs) accurately estimate various societies’ moral values?
Here, we query the perceptions of LLMs regarding the moral norms of the “average”
person from 48 nations and compare them to a large-scale (
Symbols may represent the first form of human visual communication, yet little is
known about the cognitive and neural mechanisms supporting memory for these pervasive
graphics. By investigating memory for everyday symbols, we can understand how abstract
...
Social Sciences
Recent discussion of voting in US elections claims a strong movement of White working-class
voters away from voting for Democrats, with much discussion focusing only on elections
between 2012 and the present. We examine longer-term trends from 1980 to ...
Biological Sciences
Agricultural Sciences
D-amino acids are key components of the bacterial cell wall and play important roles
in neural communication and inflammatory responses in animals. However, knowledge
about D-amino acid metabolism and physiological functions in plants is limited. Here,
we ...
Nitrous oxide (N2O) is a potent and persistent greenhouse gas, with rising atmospheric concentrations
driven in part by inefficient use of synthetic nitrogen (N) fertilizers in agriculture.
Predicting soil N2O emissions is challenging due to high spatial ...
Biochemistry
Molecular organization at the nano-bio interface governing the colloidal stability,
reactivity, immune recognition, and drug delivery performance of nanoparticles remains
difficult to predict. Quantifying the primary hydration energetics of biomolecule-...
In most organisms, ATP synthesis is powered by the proton motive force (pmf) and catalyzed
by ATP synthase. While the chemiosmotic theory originally proposed a “delocalized
coupling” between proton pumps and consumers, growing evidence implicates the ...
Water and its ability to modulate the protonation states of biomolecules govern the
physical chemistry of life, dictating their metabolic functions. However, how amino
acid protonation alters protein hydration and solubility is an open question since
...
The prevailing view frames microglia and macrophages as guardians against amyloid
beta (Aβ) accumulation in Alzheimer’s disease (AD). Here, we overturn this paradigm
by demonstrating that human phagocytic cells, including differentiated THP-1 macrophages
...
Glycosylation, a key and prevalent modification in brain proteins and lipids, is essential
for brain development and function. O-GalNAc glycosylation, initiated by the family
of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts, GALNTs), is the ...
Starting from human colon cancer cells showing aberrant WNT/β-catenin/TCF signaling,
hyperactivated MYC, and silenced BASP1, we generated stable cell lines overexpressing BASP1, either ectopically, or by reactivating the dormant BASP1 promoter using a ...
FicD regulates Unfolded Protein Response (UPR) through reversible AMPylation and deAMPylation
of BiP, an HSP70 chaperone and master regulator of the UPR. FicD activity is regulated
by endoplasmic reticulum-stress, catalyzing BiP AMPylation under low ...
Biophysics and Computational Biology
Despite their ubiquity in Nature, spikes or stingers rarely exhibit sharp tips. Instead,
a closer inspection of their roughly conical tips reveals a striking similarity in
their profiles: They adhere to a power-law,
The mechanosensory lateral line system, found in all fishes, detects water movement
and pressure fields and mediates crucial behaviors in aquatic environments. Neuromast
sensory organs, the functional units of the system, exhibit diversity in shape and
...
Mechanoresponsive cell proliferation is a feature of growing tumors, despite the suppression
of many other regulatory checkpoints in cancer, but the underlying cell-scale mechanisms
driving this behavior have not yet been established. In this study, we ...
Revealing the complex mechanisms of protein folding, including the transient intermediate
states that govern the process, is a fundamental goal in computational biophysics.
While molecular dynamics (MD) simulations generate vast amounts of data to this ...
The human adenosine A2A receptor (A2AR) is a prototypical member of the class A family of G Protein–Coupled Receptors (GPCRs),
which are engaged by over one-third of FDA-approved drugs. Here, we used 19F NMR to simultaneously evaluate functional states ...
Predicting small molecule binding sites on proteins remains a key challenge in structure-based
drug discovery. While AlphaFold3 has transformed protein structure prediction, accurate
identification of functional sites such as ligand binding pockets ...
In many enzymes, movement of domains from open to closed state forms the environment
required for catalysis. We have studied ligand-induced domain motion in 82 enzymes
by generating ensembles of AlphaFold 3 (AF3) models both with and without the presence
...
Cell Biology
Long-term recurrence in breast cancer is driven by reactivation of dormant disseminated
tumor cells (DTCs) and remains a major clinical challenge, particularly in estrogen
receptor–positive (ER+) tumors. This process is underpinned by regulation of the ...
Self-association by small GTPases on membrane is critical for their signaling output
and cellular function. However, a mechanistic understanding of how membrane components
regulate this process remains incompletely understood. Here, we show that ...
MYC amplification contributes to poor survival and outcome in pancreatic ductal adenocarcinoma
(PDAC). Here we show that in PDAC cell lines with amplified MYC, MondoA is required
for viability, facilitating proliferation while suppressing apoptosis in ...
Binding of GLP-1 to its receptor in pancreatic beta cells triggers activation of the
cAMP pathway and phosphorylation of CREB, leading to induction of cellular target
genes containing CREB binding sites. By contrast with their acute effects on beta
cell ...
Developmental Biology
During development, cells sequentially acquire specific fates through temporally ordered
regulatory systems. To ensure the harmonious progression, each system must be activated
and subsequently inactivated at the appropriate time. In this study, we show ...
Ecology
Damage to the water supply system in plants (xylem) during water stress is a major
cause of plant mortality under drought. However, theory is lacking for the evolutionary
emergence of, and variation in, the ability of xylem to resist damage when the ...
Precipitation influences animal physiology, behavior, and ecological interactions,
therefore affecting demography. However, the nature and strength of those effects
vary widely, have been attributed to mechanisms operating over different time scales,
and ...
Biological communities are connected through dispersal, which regulates diversity
across local and regional scales. However, dispersal is difficult to measure directly,
limiting what is known about dispersal’s impact on species composition in complex
...
Understanding how changes in community composition and function are driven by environmental
change remains a fundamental challenge—to which trait-based approaches offer a mechanistic
perspective. To examine links between functional and compositional ...
Species distribution models (SDMs) are essential tools for ecologists and conservationists
because they can identify environmental determinants of species occurrences and predict
species distributions. Unfortunately, most SDM algorithms rely on point-...
Wild vegetables contribute to improving the diversity and sustainability of vegetable diets in China
Vegetables are vital to human diets, supplying essential micronutrients critical to
overall health. Despite this, it remains unclear whether current supply systems effectively
ensure equitable access to cultivated vegetables across regions or fully ...
Earth is experiencing a biodiversity crisis. Among the declining taxa are insects
and arachnids, which account for most of the world’s animal species, and are ecologically
and economically vital. Thus, understanding the factors influencing insect and ...
Environmental Sciences
Ammonia-oxidizing archaea (AOA) are among the most abundant microorganisms in the
ocean, playing a fundamental role in the marine nitrogen cycle. Although temperature
and trace metal availability each individually influence the growth and activity of
...
Evolution
Translation is carried out by the most conserved assemblies in biology. Among these
assemblies, the ribosome and RNase P are central players. These ancient ribonucleoprotein
complexes achieved structural and functional maturity by the last universal ...
Bacteria exhibit varying niche breadths, with generalists thriving in diverse environments
and specialists confined to specific habitats. Although genes for cooperative traits
have been suggested to influence niche breadth evolution, their precise role ...
Genetics
Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by inheriting
an expanded CAG repeat tract in the huntingtin gene (HTT) that further expands in somatic cells over an individual’s lifetime. Genome-wide
association studies have ...
DNA N6-methyladenine (6mA) is a newly recognized transcription-associated epigenetic mark
in eukaryotes. While its methylation pathway has been well established, the identity
of eukaryotic 6mA demethylase(s) responsible for its removal and dynamic ...
Understanding the global regulatory mechanisms that control pathogen virulence gene
expression is essential for elucidating the molecular basis of pathogenicity. N6-methyladenine
(6 mA) plays a crucial role in regulating gene expression in response to ...
Schizophrenia has been linked to severely damaging de novo mutations in synaptic junction
proteins, neurotransmitter receptors, transcription factors, and chromatin remodeling
proteins. In a patient with schizophrenia in the absence of a family history of ...
Immunology and Inflammation
The human developmental disorder 3MC syndrome (Malpuech, Michels, Mingarelli, and
Carnevale) features skeletal deformities associated with a deficiency of the pattern
recognition molecule collectin-11 (CL-11), yet the underlying molecular and cellular
...
Glucocorticoids (GCs) are potent immunosuppressive agents that compromise anticancer
immune responses, yet the molecular mediators of this effect remain incompletely understood.
Here, we identify the acyl-CoA-binding protein/diazepam-binding inhibitor (...
Hemolysis is associated with the release of damage-associated molecular patterns,
including free heme and extracellular DNA (ecDNA). Using several mouse models of bleeding
anemia and hemolysis, we demonstrate a significant increase in plasma ecDNA, ...
Poly-ADP-ribose polymerase (PARP) family proteins are involved in a wide range of
cellular processes. Several PARPs are targeted by inhibitors as treatments for cancer
based on their biochemical functions; however, the physiological functions of most
...
Damage-associated molecular patterns (DAMPs) are well established as key mediators
of innate immune activation; however, their functions in modulating adaptive immunity,
particularly T cell responses, remain incompletely characterized. Here, we report
the ...
Dendritic cell (DC) migration is critical for initiating adaptive immune responses.
Previous work suggested a role for ATP-binding cassette transporter C1 (ABCC1) in
skin DC migration following cutaneous fluorescein isothiocyanate (FITC) exposure,
but the ...
Medical Sciences
Site 1 sodium channel blockers (S1SCBs), such as tetrodotoxin (TTX) and neosaxitoxin,
are ultrapotent local anesthetics with low tissue toxicity. Their duration of action
is relatively brief, but increasing the dose can lead to systemic toxicity. Here,
we ...
Circadian rhythm disruption is recognized as a feature of aging and neurodegenerative
disease, yet whether intrinsic cellular circadian properties relate to underlying
processes in humans remains unknown. We measured intrinsic circadian period and its
...
The efficacy of immune checkpoint blockade is often limited by intrinsic immunosuppressive
networks within the tumor immune microenvironment (TIME). Despite progress in cancer
treatment, current extracellular targeted protein degradation approaches often ...
Myocardial infarction (MI) affects millions of individuals worldwide, with ferroptosis
recognized as a pivotal regulated cell death pathway in this context. N6-methyladenosine
(m6A), the most prevalent mRNA modification, is essential in modulating RNA ...
Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of cancer
treatment, but they also expose most patients to a variety of treatment-related adverse
events (AEs). This study introduces a modified pharmacovigilance approach to ...
Integration of the high-risk human papillomavirus 16 (HPV16) genome into the host
chromosome, frequently driven by microhomology-mediated end joining (MMEJ), is a critical
step in the carcinogenesis of HPV-associated tumors. However, the mechanisms by ...
Microbiology
Throughout the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) has shown the capacity to infect a wide range of nonhuman hosts, including
farmed mink. In early 2020, a mink-associated variant, termed mink cluster 5 (MC5V),
...
Global analysis of protein degradation reveals instability of diverse regulators in Escherichia coli
Regulated protein degradation underlies the timely execution of essential gene expression
programs in bacteria. Here, we deployed time-resolved chemoproteomics, text mining
of the PubMed and EcoCyc knowledge bases, and machine learning classification to ...
Sialic acid is an abundant terminal glycan found on the surface of almost all mammalian
cells and is utilized by many viruses as an attachment factor and/or bona fide receptor.
Altering canonical cellular glycosylation can affect the ability of viruses to ...
Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, responsible
for approximately 20 million infections annually. Despite the availability of a vaccine
in China, no direct-acting antivirals are approved, and host factors ...
Recombinant adeno-associated viruses (rAAVs) are widely used for in vivo gene delivery.
While KIAA0319L, known as AAV receptor (AAVR), is essential for the transduction of
multiserotype AAVs, it is dispensable for AAV4-related (Clade G) AAVs. We conducted
...
The rhizosphere microbiome plays a crucial role in the resistance to soilborne plant
diseases. However, the principles needed to explain and predict which microbiota will
be effective against soilborne pathogens are still lacking due to the complexity of
...
Neuroscience
Cryopreserving the adult brain is challenging due to damage from ice formation, and
traditional freezing methods fail to maintain neural architecture and function. Vitrification
offers a promising alternative but has not been surveyed in the brain. Here, ...
Understanding how brain-wide neural circuits are genetically wired remains a fundamental
question in neuroscience. While Sperry’s chemoaffinity theory [Sperry, Proc. Natl. Acad. Sci. U.S.A. 50, 703–710 (1963)] posits that molecular gradients provide ...
The neuronal K/Cl cotransporter KCC2 regulates the transmembrane chloride gradient,
which controls the efficacy of GABAergic signaling. In mesial temporal lobe epilepsy
(mTLE) and other neurological disorders, reduced KCC2 expression or function can ...
Synaptic loss is increasingly recognized as a key pathological feature in multiple
sclerosis (MS), contributing to disease progression and cognitive dysfunction. Synaptic
vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging has ...
The mitochondrial unfolded protein response (UPRmt) is triggered by cells to alleviate proteotoxicity in response to metabolic stress.
The ability to anticipate and prime cells against mitochondrial stress, by sensing
potentially toxic changes in the ...
A single learning episode induces both labile and consolidated forms of aversive olfactory
memory in Drosophila melanogaster. Retrograde amnesia triggered by post-learning perturbations specifically impairs
the labile memory. However, synaptic mechanisms ...
Exposure therapy for anxiety disorders relies on fear extinction to reduce pathological
fear responses. Here, we show that while effective at diminishing conditioned fear,
extinction training paradoxically enhances fear generalization to safe stimuli ...
Neurons are terminally differentiated cells that adapt to maintain stable function
over years, despite encountering a wide range of environmental perturbations. In some
cases, recovery from perturbation is not shaped by prior exposure; in others, recovery
...
Phosphorylated-tau 217 (pTau217) is currently the most promising blood-based biomarker
for accurately detecting Alzheimer’s disease (AD) pathology. However, interference
from peripheral tau species in the kidneys or peripheral nerves can hinder diagnostic
...
Physiology
KCNQ2/3, a major voltage-gated potassium channel at the axon initial segment (AIS),
plays a crucial role in controlling neuronal excitability. While the functionality
of KCNQ2/3 is regulated by conformational changes from voltage sensing, the AIS ...
Plant Biology
Manganese (Mn) toxicity in acidic or waterlogged soils severely impacts crop productivity.
Although high-Mn stress triggers Ca2+ signals that regulate Mn homeostasis, the mechanism generating these signals remains
unclear. Here, we show that the cyclic ...
Transposons drive genetic diversity and evolution by altering the genomic landscape
over time. Here, we describe DELAYED ABAXIAL TRICHOMES (DAB), a Helitron/RC transposable element in Arabidopsis thaliana that has a role in vegetative phase change and ...
Psychological and Cognitive Sciences
In the first months postterm, human infants are traditionally viewed as passive to
their environment, unable to focus or sustain attention on specific objects. Here,
we asked whether 4-mo-old infants could engage their attention strongly enough in
a ...
Sustainability Science
Increasing global demands for food and energy necessitate innovative land-use solutions.
Agrivoltaics, colocating solar photovoltaics with agriculture, shows promise, but
its widespread adoption faces complex biophysical and economic trade-offs in a ...
Systems Biology
The bacterial flagellar motor drives bacterial swimming and chemotaxis by rotating
helical flagellar filaments. When Escherichia coli navigates chemical gradients, the motor switches from counterclockwise (CCW) during
forward swimming to clockwise (CW) ...
Cell growth rates exhibit cell-intrinsic cell-to-cell variability, which influences
cell fitness and size homeostasis from bacteria to cancer. It remains unclear whether
this variability arises from stochasticity in cell growth or division processes, or
...
Spatial multi-omics sequencing enables the simultaneous profiling of transcriptomics,
proteomics, and epigenomics at a spatial resolution, offering insights into complex
tissue organization and molecular regulation. However, the effective integration of
...
Corrections
Cover image: Pictured is a cathodoluminescence image of zircon crystals from Jack Hills, Australia, showing igneous cores and a metamorphic rim. Shane K. Houchin et al. examined the oxidation states and trace element signatures of the cores and rims of detrital Jack Hills zircons. The authors’ analysis suggests that Earth’s mantle achieved near-modern oxidation conditions around 4.15 billion years ago, during the Hadean Eon, and that plate tectonics likely began by at least 3.35 billion years ago, in the early Archean Eon. See the article by Houchin et al. e2525466123. Image credit: Shane K. Houchin.
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