Table Of Contents Page, PNAS Volume 123, Number 26
This Week in PNAS
Opinion
Retrospective
Antonio García-Bellido was a pioneer of developmental biology in Spain who had the
rare ability to see beyond the trees and grasp not just the forest, but entire landscapes.
Intellectually and personally, he was indefatigable, uncompromising, and wholly ...
Profile
John P. Smol has spent more than four decades demonstrating how lake sediment cores
can reveal environmental changes spanning decades to centuries. His pioneering work
established paleolimnology as a credible scientific discipline, first, by documenting
...
View related content:
New climate regime restructures the ecology of Canada’s Northern Great Lakes
Commentaries
Perspectives
Natural hallucinogenic compounds have arisen independently across plants, fungi, and
animals, evolving into a diverse chemical arsenal that includes phenethylamines, indolealkylamines,
and terpenoid scaffolds. Beyond clinical and cultural frameworks, ...
By immersing participants in consistent virtual environments, VR enhances study realism,
reduces confounding variables, and improves procedural control, offering a promising
solution for scientists interested in studying behavior “in the wild.” The ...
Letters
This article has a reply:
Reply to Hojný et al.: Fusion-driven vs. fusion-negative high-grade endometrial stromal sarcoma
View the original article:Integrated mutational landscape analysis of endometrial stromal sarcoma
Physical Sciences
Applied Mathematics
Every year, over 700,000 people, particularly children under five, die from vector-borne
diseases worldwide. Effectively controlling endemics and preventing new outbreaks
requires an integrated approach that can lead to the elimination of both vectors and
...
How can social animals divide labor to forage effectively without a leader? Effective
foraging requires balancing individual exploration costs against collective information
gains, but without central coordination. This balance must emerge from the ...
Biophysics and Computational Biology
Evolutionary adaptation is often visualized as a population’s stochastic climb toward
the top of a fitness landscape. While there exist approaches to design or synthetically
evolve proteins into desired structures, there is a lack of methodology for ...
Cell migration through spatially confined microenvironments occurs in many biological
processes such as embryonic development, immune surveillance, and cancer metastasis.
A major bottleneck during such migration is the nucleus, which acts not only as a
...
The process by which neocortical neurons and circuits amplify their response to an
unexpected change in stimulus, typically referred to as deviance detection (DD), has
traditionally been thought to be the product of specialized cell types and/or routing
...
Chemistry
The DNA damage response (DDR) is critical for pancreatic ductal adenocarcinoma (PDAC)
development and therapeutic responses, including to genotoxic agents. While epigenetic
modulators have been shown to contribute to the DDR, how chromatin regulation ...
Elucidating the dynamic interactions between nanocarriers and cellular machinery is
critical for advancing targeted nanomedicine. However, the optical microscopy imaging
techniques can only provide a generalized view of nanomedicine localization. ...
Lysine with a characteristic amino group on its side chain is one of the most abundant
amino acids in protein structures, making libraries of lysine-based noncanonical amino
acids (ncAAs) a valuable resource for expanding the functional and structural ...
Nanoscale geometries can profoundly alter chemical reactivity, yet platforms that
isolate and control this regime remain limited primarily to microdroplets. Here, we
introduce a simple, surfactant-free method to generate a floating oil nanofilm by
...
Earth, Atmospheric, and Planetary Sciences
The thermostatic mechanisms of Earth’s persistent habitability remain unresolved.
High-resolution Cenozoic C isotope records, P accumulation, and coarse-fraction I/Ca
allow recalculation and assessment of controls on the global proportion of total carbon
...
The various slip behaviors of the subduction megathrust fault, including deadly megathrust
earthquakes, are depth-dependent. Yet, we do not know what causes this depth dependence,
in part due to variability between subduction zone thermal structures and ...
Engineering
Desert environments pose severe water scarcity challenges, leading to unique adaptations
among native fauna. Notably, many species of desert horned lizards utilize a dermal
drinking method, employing integumental microchannels to draw water from raindrops
...
Antibodies are proteins prized for their ability to bind to extracellular antigens
with exceptionally high affinities and specificities. These features have motivated
researchers to utilize antibody–antigen binding to inhibit intracellular disease targets
...
The intelligence of the human biological system is enabled by the highly distributed
sensing receptors on soft skin that can distinguish various stimulations or environmental
cues, thus establishing the fundamental logic of sensing and physiological ...
Distributed acoustic sensing (DAS) has emerged as a powerful tool for passive whale
monitoring, enabling both the detection of vocalizations and the simultaneous tracking
of multiple individuals. However, a fundamental limitation of passive acoustic ...
Understanding how mechanical, thermodynamic, and acoustic properties emerge in fluid-saturated
nanoporous materials remains a major challenge due to the breakdown of classical continuum
assumptions at molecular length scales. Here, we present a multiscale ...
Environmental Sciences
Wetlands on the world’s most fertile black soil serve as critical yet vulnerable carbon
reservoirs, yet their stability is threatened by redox fluctuations intensified by
climate change and human activities. However, how cultivation modulates this process
...
It is generally believed that CO2 physiological forcing can partially mitigate land surface drying under global warming
by reducing stomatal conductance and evapotranspiration. Most of this type of study
focuses on the direct regulation by vegetation ...
Fire severity exerts crucial ecological controls in many forests globally. In California,
where annual forest-fire area has increased dramatically in recent decades, understanding
how burn severity is changing is essential for informing environmental ...
Mathematics
In this paper, we study solid tori in contact manifolds. Specifically, we study the
contact width of a knot type and give criteria for when it can be explicitly computed.
We also prove there are many “nonthickenable” tori in many knot types. These tori
...
Predicting the human burden of vector-borne diseases from limited surveillance data
remains a major challenge, particularly in the presence of nonlinear transmission
dynamics and delayed effects arising from vector ecology and human behavior. We develop
a ...
Physics
Ferroelectric halide perovskites provide a fertile platform for optoelectronic functions
based on the bulk photovoltaic effect, where broken inversion symmetry couples with
quantum geometry of wave functions. The most prominent manifestation is the shift
...
Social Sciences
Economic Sciences
The share of the world population living in cities with more than one million people
rose from 11% in 1975 to 24% in 2025 (our estimates). Will this trend toward greater
concentration in large cities continue or level off? We introduce two new city ...
Psychological and Cognitive Sciences
Most people believe that social media discourse is negative and divisive. Here we
show how this negativity can evolve even when users are not motivated to be negative.
We propose that social media users seek to differentiate themselves from other users,
...
Social Sciences
While gender and economic outcomes in negotiation have been studied for decades, much
less is known about gender differences in subjective outcomes, such as trust, rapport,
and willingness to negotiate again, despite their importance for long-term ...
What socioecological conditions nurture the ingenuity and collaborative interactions
underlying transformative technological innovations? We compiled a dataset on more
than 400 major technological inventions from 1690 to 1990 spanning seven categories
(...
Biological Sciences
Anthropology
What socioecological conditions nurture the ingenuity and collaborative interactions
underlying transformative technological innovations? We compiled a dataset on more
than 400 major technological inventions from 1690 to 1990 spanning seven categories
(...
Applied Biological Sciences
Every year, over 700,000 people, particularly children under five, die from vector-borne
diseases worldwide. Effectively controlling endemics and preventing new outbreaks
requires an integrated approach that can lead to the elimination of both vectors and
...
Biochemistry
Members of the nucleobase ascorbate transporter (NAT) family (SLC23) are elevator-type
transporters that are responsible for the uptake of nucleobases and ascorbate. In
fungi, NAT members are also responsible for the specific uptake of antifungal ...
The tumor suppressor p53 is pivotal in repressing tumorigenesis under physiological
conditions. Paradoxically, we find that wild-type (WT) p53 plays an oncogenic role
in relieving METTL5 depletion–caused cancer regression by sustaining mitochondrial ...
Biophysics and Computational Biology
Desert environments pose severe water scarcity challenges, leading to unique adaptations
among native fauna. Notably, many species of desert horned lizards utilize a dermal
drinking method, employing integumental microchannels to draw water from raindrops
...
Membrane order and fluidity influence many biological processes. However, tools to
manipulate membranes under physiological conditions have been limited. In the process
of high-throughput screening for molecules that shift the phase partitioning between
...
Cell Biology
Homeoproteins (HPs) and cell-penetrating peptides (CPPs) enter cells by endocytosis
and direct membrane crossing (translocation). However, unlike endocytosis, translocation
remains globally unknown. Here, we developed an electrophysiological approach to ...
Fibrosis is the end-stage of a maladaptive process that occurs when the body’s normal
wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage
of neovascular age-related macular degeneration (nAMD), the most common cause of ...
Cell polarity is essential for the formation and function of animal tissues. Atypical
protein kinase C (aPKC), its cofactor PAR-6, and scaffold protein PAR-3 regulate cell
polarity in many different animal cell types. PAR-3 oligomerization is important to
...
The p53 tumor suppressor and the c-Myc oncogene are among the most frequently deregulated
genes in human cancers, yet the molecular cross talk between these pathways remains
poorly understood. MDM2 is a key negative regulator of p53 and a target for ...
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive
neurodegenerative disorders characterized by motor neuron degeneration, leading to
muscle weakness, atrophy, and cognitive impairments. A defining pathological hallmark
...
Fasting primes small intestinal regeneration after damage via a microbiome–metabolite–chromatin axis
Fasting enhances small intestinal regeneration after radiation, but the contribution
of the gut microbiome to this process remains uncharacterized. We identify Akkermansia muciniphila (AKK) as a key mediator of this response. AKK was enriched in fasted ...
Developmental Biology
During cardiac development, the myocardium expands in response to physiological demands
to achieve proper cardiac morphology and functional contractility, while simultaneously
integrating with the developing coronary vasculature. However, the mechanisms ...
Ca2+ signaling and its regulation are important for endothelial cell (EC) function and
signaling. Yet, the spatiotemporal organization of Ca2+ activity and its regulation across a vascular plexus is poorly understood in an in
vivo mammalian context. To ...
Ecology
How can social animals divide labor to forage effectively without a leader? Effective
foraging requires balancing individual exploration costs against collective information
gains, but without central coordination. This balance must emerge from the ...
How animals handle immense incoming sensory information and regulate sensing is difficult
to study under natural conditions. Using miniature GPS tags with microphones we monitored
the sensing of freely foraging greater horseshoe bats. Bats stayed in ...
Bivalve transmissible neoplasias (BTNs) are transmissible cancers that have arisen
in multiple bivalve species, including Eastern soft-shell clam (Mya arenaria) populations on the East Coast of North America. Two sublineages of a single clone
(termed ...
Biodiversity is declining, with cascading effects of defaunation expected across trophic
levels. Widespread population declines may drive general biotic responses to global
change and determine their fitness effects. We find that a 62% decrease in insect
...
Environmental Sciences
Fire severity exerts crucial ecological controls in many forests globally. In California,
where annual forest-fire area has increased dramatically in recent decades, understanding
how burn severity is changing is essential for informing environmental ...
Riverine nitrous oxide (N2O) emissions constitute a significant yet uncertain component of global greenhouse
gas budgets. Integrating approximately 3,600 observations across the contiguous United
States (CONUS), we present a monthly resolved, national-...
Evolution
Evolutionary adaptation is often visualized as a population’s stochastic climb toward
the top of a fitness landscape. While there exist approaches to design or synthetically
evolve proteins into desired structures, there is a lack of methodology for ...
Morphological evolution can be explosive, producing visually spectacular adaptive
radiations like Caribbean anoles, Malagasy vangas, and African Rift Lake cichlids.
Yet morphological stasis, the long-term retention of a conserved body plan, is often
...
The term “Lilliput Effect” describes a substantial decrease in the average body size
of fossil assemblages during major environmental perturbations in Earth’s history,
which is reported in many paleontological studies. The limited regional, temporal
and ...
A natural assumption in evolutionary biology is that to coevolve, species must interact
with each other and should therefore co-occur. However, many evolutionary dynamics
may be mediated by migratory or vector-borne agents, raising the possibility of ...
The ecological success of modern reef-building corals is rooted in photosymbiosis,
yet its macroevolutionary benefit remains unclear. Analyzing the Phanerozoic record
of inferred zooxanthellate (Z) and azooxanthellate (AZ) corals over geologic time
scales ...
Meiotic recombination is highly conserved across vertebrates and plays an essential
role in ensuring chromosomal segmentation and generating genomic variation. However,
species employ two strikingly different mechanisms to guide recombination. In most
...
Genetics
Sexual dimorphism in infection outcomes is widespread, yet its underlying mechanisms
remain incompletely understood. Utilizing Pseudomonas entomophila intestinal infection in Drosophila, we demonstrate that sex differences in intestinal redox processes ...
Meiosis is a hallmark of sexual reproduction. Although the core meiotic machinery
is evolutionarily conserved from unicellular yeasts to Metazoan, the key regulators
responsible for initiating meiosis vary across species and remain largely unidentified
in ...
Immunology and Inflammation
Polymorphisms of human leukocyte antigen (HLA) genes confer risks for human diseases.
Predisposing effects related to T cell receptor (TCR) recognition of peptide–HLA can
be selection of TCR repertoire and/or preferential presentation of disease-driving
...
Barrier tissues with stratified epithelia rely on Langerhans cells (LCs) to maintain
immune surveillance. While TAM signaling regulates skin LC homeostasis, its role in
mucosal LC development remains unclear. Here, we identify the TAM ligand GAS6 as a
...
Medical Sciences
The DNA damage response (DDR) is critical for pancreatic ductal adenocarcinoma (PDAC)
development and therapeutic responses, including to genotoxic agents. While epigenetic
modulators have been shown to contribute to the DDR, how chromatin regulation ...
Antibodies are proteins prized for their ability to bind to extracellular antigens
with exceptionally high affinities and specificities. These features have motivated
researchers to utilize antibody–antigen binding to inhibit intracellular disease targets
...
Genetically engineered mouse models have advanced cancer research, but they fail to
mimic some human diseases. Rats offer a powerful alternative for modeling human cancers
that are inadequately represented in mice, yet their use has been constrained by ...
Ferroptosis has emerged as a key effector mechanism in antitumor immunity, yet the
transcellular metabolic cross talk that modulates ferroptotic sensitivity in colorectal
cancer (CRC) remains incompletely understood. Here, we describe an integrative ...
Microbiology
Hepatitis B virus (HBV), a major human pathogen, replicates its DNA genome by protein-primed
reverse transcription of a pregenomic RNA (pgRNA). This process is directed by the
pgRNA-borne epsilon (ε) element, which provides the origin for minus-strand DNA ...
There is a constant tug-of-war for transition metals at the pathogen–host interface.
Vertebrate hosts modulate the availability of metals to pathogens in a process known
as nutritional immunity, but pathogens have evolved numerous countermeasures to this
...
The cell wall peptidoglycan (PG) protects virtually all bacteria from osmotic lysis
and specifies cell shape. Synthesis of this exoskeleton is carried out by enzymes
that polymerize glycan strands and transpeptidases that crosslink them into the existing
...
Upon activation, macrophages generate substantial levels of reactive nitrogen species,
which can induce alkylating damage in the DNA of intracellular Mycobacterium tuberculosis (Mtb) and thereby restrict bacterial replication. However, the molecular ...
The rapid global spread of antimicrobial resistance via β-lactamase (bla) demands
targeted strategies that selectively eliminate resistant pathogens without exacerbating
resistance. Herein, we report BIN-3I, a photosensitizer (PS) that enables bla-...
Neisseria gonorrhoeae (Gc) pilin antigenic variation is a diversity-generating system that uses gene conversion
to produce numerous PilE protein variants, the major subunit of the Type IV pilus
(T4p). Pilin antigenic variation allows the bacteria to ...
Human coronaviruses have been primarily associated with upper respiratory tract infections,
yet cases of gastrointestinal symptoms in COVID-19 patients have highlighted their
potential to cause systemic disease. Here, we detail the infection of intestinal ...
The genomic flexibility of orthocoronaviruses, including severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), is showcased by the presence of accessory genes,
which vary in number among virus species and strains. Given this flexibility, the
viral ...
Neuroscience
The process by which neocortical neurons and circuits amplify their response to an
unexpected change in stimulus, typically referred to as deviance detection (DD), has
traditionally been thought to be the product of specialized cell types and/or routing
...
The brain’s capacity for integration arises from both its structural wiring and energetically
demanding electrochemical signaling. Yet current connectome analyses treat network
nodes as functionally homogeneous, ignoring that neural communication is ...
Sensory feedback is essential for the fine-tuning of motor actions, and speech production
is no exception. It depends on continuous self-monitoring to ensure that produced
sounds match intended targets. Delaying auditory feedback (DAF) disrupts this ...
Plant Biology
The spatiotemporal organization of proteins and lipids within membranes is crucial
for ensuring proper cellular signaling. While the segregation of proteins and lipids
into membrane nanodomains is well established, it remains unclear whether nanodomains
...
In plant development, receptor kinases are often active in disparate cell types, with
each requiring vastly different signaling outputs. The ERECTA (ER) receptor kinase
and its homologs Erecta-Like1 (ERL1) and ERL2 exemplify this pleiotropy. In ...
Meristems are the growth centers of plants and fundamental in understanding plant
development, morphogenesis, and vegetative propagation. Across all plant groups, the
phytohormone auxin controls meristem maintenance, represses the emergence of new ...
Improving multistress resilience in crops is essential for sustainable agriculture,
yet the genetic mechanisms coordinating abiotic and biotic stress responses remain
poorly understood. This study identifies CTS1 (Cold Tolerance at the Seedling stage1), ...
Asymmetric cell division underpins cellular diversity in multicellular plants. These
divisions are mechanosensitive, and preprophase band (PPB) formation hinges on cell-wall
mechanical properties in plant cells. Yet, the spatial control mechanism ...
Upland cotton (Gossypium hirsutum L.) makes up about 90% of global cotton farming. Despite its importance, the origins
and domestication history of upland cotton remain poorly understood. Here, we present
a high-density pan-genome variation map ...
Population Biology
Predicting the human burden of vector-borne diseases from limited surveillance data
remains a major challenge, particularly in the presence of nonlinear transmission
dynamics and delayed effects arising from vector ecology and human behavior. We develop
a ...
Psychological and Cognitive Sciences
Past experiences stored in long-term memory (LTM) provide a valuable resource for
making predictions that shape perception and guide goal-directed behavior. Contents
from the high-capacity LTM system guide contextual selective attention to enhance
sensory ...
Corrections
Cover image: Pictured is a desert horned viper (Cerastes cerastes) coiled defensively and rubbing its scales to produce a sound that deters predators. Akiva Topper et al. used agent-based computer simulations to explore how mimicry of deterring sounds, warning colors, or similar phenomena might evolve among species that do not overlap geographically. The results revealed how migratory predators may drive the evolution of convergent forms of mimicry in geographically separate species. The analysis suggests that coevolutionary relationships between distant species may be more plausible than previously appreciated. See the article by Topper et al. e2527304123. Image credit: Akiva Topper.
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