Table Of Contents Page, PNAS Volume 123, Number 21
This Week in PNAS
Core Concepts
Commentaries
Letters
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Brief Reports
Delayed age-related cortical thinning has been proposed as a biomarker of attention-related
psychopathology and attention-deficit/hyperactivity disorder (ADHD), but these findings
have not been adequately replicated in large, longitudinal samples with ...
Religious institutions’ engagement in prohibited electoral advocacy is a growing concern
for democratic governance. In the United States, such mobilization has been especially
visible within the evangelical movement. We examine this phenomenon using a ...
Most Americans claim to support freedom of speech, including President Donald Trump
who has portrayed himself as an ardent defender of this constitutional right. However,
in the wake of Charlie Kirk’s assassination, Trump and members of his administration
...
Physical Sciences
Applied Mathematics
Seasonal influenza epidemics exhibit complex transmission dynamics influenced by time-varying
extrinsic factors such as social behavior and seasonal effects. Estimating changes
in transmission rates is critical to enable accurate forecasting of the ...
Applied Physical Sciences
Branching patterns can emerge when one fluid is injected into a more viscous one within
a quasi-two-dimensional cavity. While these patterns have dazzled physicists for decades,
modern engineering efforts have focused on suppressing, rather than ...
Biophysics and Computational Biology
Developmental patterning is remarkably robust to intrinsic and extrinsic variation.
Morphogen gradients are a key mechanism driving patterning, and themselves often scale
with the size of developing tissues and exhibit robustness to other perturbations.
...
In suspensions of swimming bacteria, individual cells interact via long-range hydrodynamic
forces and self-organize into collective states that drive large-scale chaotic flows,
commonly referred to as “bacterial turbulence.” Despite extensive experimental ...
Epithelial cortinoids, fluid-filled shells formed from induced pluripotent stem cells
(iPSCs), must accommodate large deformations during growth and morphogenesis. Using
inflation–deflation assays and high-resolution imaging, we find that these fluid-...
Complex life would be impossible without cooperation at all levels of biological organization.
However, Darwinian selection is commonly believed to favor selfish behavior, making
societies of cooperators vulnerable to cheaters. A quintessential model of ...
Chemistry
The tumor glycocalyx forms a protective shield that masks checkpoint proteins and
compromises the efficacy of immunotherapies. While the bacterial protease StcE can
degrade this barrier by cleaving O-glycosylated mucin domains, its therapeutic potential
...
Cancer cell dormancy is a key contributor to therapy resistance and disease relapse.
The glucocorticoid receptor (GR), a major mediator of stress hormone signaling, has
emerged as a central regulator of dormancy in non-lymphoid solid tumors, particularly
...
Innate immunity mediated by myeloid cells defends against infection and injury, but
when chronically activated, it drives tissue damage and neurodegeneration. Molecular
imaging with positron emission tomography (PET) enables noninvasive, real-time ...
Computer Sciences
The Turing test has been widely discussed as a test of machine intelligence, but it
also provides a measure of how humans distinguish other humans from machines. We evaluated
4 systems (ELIZA, GPT-4o, LLaMa-3.1-405B, and GPT-4.5) in two randomized, ...
Earth, Atmospheric, and Planetary Sciences
Interest in the economic potential for hydrogen for decarbonization and the green
energy transition is a recent phenomenon. Major questions remain concerning the concentrations,
volumes, and sustainability of potential reservoirs, as projections to date ...
The Trinity nuclear test of July 16, 1945, generated extreme transient conditions
that produced trinitite, a silicate glass containing rare metallic phases. Here we
report the discovery and structural and chemical characterization of a previously
unknown ...
Tropical cyclones (TCs) are among the most energetic phenomena in the climate system.
Given their energetic nature, TCs induce upscale effects on the climate system, although
these effects have not been extensively assessed. Understanding the influence of ...
The 2D dendritic structure of stream networks within fluvial catchments has not previously
been linked to reach-scale channel processes. Existing extensions of 2D network models
to 3D landscapes yield only pixelized landscapes, without resolving channels ...
Engineering
RNA therapeutics offer promising potential for treating heart disease; however, their
clinical application has been limited by insufficient cardiac delivery. Here, we developed
a screening platform using human induced pluripotent stem cell–derived ...
Autocatalytic CRISPR architecture offers amplification-free nucleic acid detection
by directly linking target recognition to self-reinforcing ribonucleoprotein (RNP)
generation. However, spontaneous background activation remains a key barrier, because
...
Environmental Sciences
In recent years, the Earth has likely experienced an accelerated warming trend, raising
growing interest in the possible contributing factors. From 2013 to 2023, global anthropogenic
air pollutant emissions declined significantly and brought enormous ...
Mathematics
We resolve a $1,000 Erdős prize problem, complete with formal verification generated
by a large language model. In over a dozen papers, beginning in 1976 and spanning
two decades, Paul Erdős repeatedly posed one of his “favorite” conjectures: every
finite ...
A paper torus, also called an origami torus, is a torus in three-dimensional space
that is made from finitely many triangles which fit together in such a way that the
sum of the angles around each vertex is 2π. This article announces the result that there ...
This paper establishes the simplicity of the Hodge bundle, a theorem in the branch
of modern mathematics known as algebraic geometry. Notably, the essential mathematical
content was autonomously generated by Aletheia, a custom AI agent powered by Gemini
...
Physics
Autonomous physical learning systems modify their internal parameters and solve computational
tasks without relying on external computation. Compared to traditional computers,
they enjoy distributed and energy-efficient learning due to their physical ...
The ordering of rod-like particles in soft, deformable containers emerges from the
interplay of anisotropic interactions, geometric confinement, and boundary compliance.
This competition couples internal particle organization to container morphology, ...
Topologically protected solitonic structures have garnered significant attention in
condensed matter physics due to their unique stability and potential applications
in next-generation technologies such as high-density data storage and spintronics.
Vortex ...
Observation of chiral bound states in the continuum in self-biased magneto-optical photonic crystals
Chiral bound states in the continuum (BICs) are confined photonic modes with infinite
quality factors and chiral response, offering significant potential for chiral optics.
Although a novel type of spin-orbital-locking chiral BIC was recently predicted in
...
Nuclear quantum effects are essential for correctly describing hydrogen-rich materials
at high pressures. Superconducting hydrides and ice are prime examples of such systems,
requiring the inclusion of lattice anharmonicity and nuclear quantum effects to ...
Sustainability Science
In recent years, the Earth has likely experienced an accelerated warming trend, raising
growing interest in the possible contributing factors. From 2013 to 2023, global anthropogenic
air pollutant emissions declined significantly and brought enormous ...
Social Sciences
Economic Sciences
Rapid growth of wind energy plays a key role in global efforts to reduce carbon emissions,
yet public concerns persist about its potential health effects, particularly through
noise exposure. While some studies and media reports suggest that wind turbines ...
Immigrants play a critical role in the US childcare workforce, yet little is known
about how immigration enforcement shapes employment in this essential sector. We study
how the sharp escalation in community-based Immigration and Customs Enforcement (ICE)
...
Psychological and Cognitive Sciences
The Turing test has been widely discussed as a test of machine intelligence, but it
also provides a measure of how humans distinguish other humans from machines. We evaluated
4 systems (ELIZA, GPT-4o, LLaMa-3.1-405B, and GPT-4.5) in two randomized, ...
Are large language models (LLMs) susceptible to the same persuasive appeals as humans?
We tested whether classic persuasion principles (authority, commitment, liking, reciprocity,
scarcity, social proof, and unity) could induce three widely used LLMs (GPT-...
The decisional reference point, the central mechanism underlying behavioral economics,
conditions our evaluations of all reinforcers. Whether a given event is experienced
as positive or negative depends on this reference point. A pathological elevation
of ...
Social Sciences
Beauty standards shape self-perception and health through social comparison and objectification,
while exposure to idealized imagery exacerbates body-image concerns. Media and fashion
are central arbiters of these ideals, yet long-term, quantitative, ...
Understanding the origins of volunteerism and free-riding is crucial in collective
action situations where a sufficient number of cooperators is necessary to achieve
shared benefits, such as in vaccination campaigns and social change movements. Despite
...
Sustainability Science
As one of the main causes of habitat loss, agricultural cropland expansion is a major
threat to biodiversity. We analyze past and anticipated future trends in population,
per capita crop demand, and crop yield to estimate agricultural cropland ...
Understanding what and who shapes urban growth and how it unfolds in the Global South
is critical to ensure theories and predictive models of urban expansion and, consequently,
global environmental change, are salient to contemporary contexts. Much of the ...
Biological Sciences
Agricultural Sciences
Odorant-binding proteins (OBPs) are crucial mediators in the peripheral olfactory
perception of insects, functioning as a link between the external environment and
odor receptors. Recent research has revealed their noncanonical role as salivary proteins
...
Applied Biological Sciences
Cancer cell dormancy is a key contributor to therapy resistance and disease relapse.
The glucocorticoid receptor (GR), a major mediator of stress hormone signaling, has
emerged as a central regulator of dormancy in non-lymphoid solid tumors, particularly
...
RNA therapeutics offer promising potential for treating heart disease; however, their
clinical application has been limited by insufficient cardiac delivery. Here, we developed
a screening platform using human induced pluripotent stem cell–derived ...
Autocatalytic CRISPR architecture offers amplification-free nucleic acid detection
by directly linking target recognition to self-reinforcing ribonucleoprotein (RNP)
generation. However, spontaneous background activation remains a key barrier, because
...
Mutations that arise in the shoot apical meristems can become fixed, but typically
only in one of the meristem layers. Therefore, in long-lived, clonally propagated
species, polymorphic genomes coexist in the form of periclinal chimeras. Given their
...
Biochemistry
Pif1-family helicases are essential for proper nuclear and mitochondrial genome maintenance,
yet the regulation of their activities remains incompletely understood. Here, we use
single-molecule manipulation and visualization techniques to dissect the real-...
Disulfide bonds act as reversible switches that regulate cellular function in nearly
all organisms. Their behavior is set by the midpoint potential (Em), yet Em is known for only a small number of sites, mostly in purified proteins studied away
from their ...
Localized protein translation occurs in numerous subcellular compartments and regulates
diverse biological processes by rapidly changing protein compositions in response
to subcellular needs. Existing assays for subcellular local translation either ...
Cells continuously produce and degrade molecules, essential for maintaining homeostasis.
The study of these dynamics has gained momentum since the development of pulse–chase
methods, utilizing fluorescent or isotopic labeling to assess properties such as ...
Copper homeostasis in bacteria requires tightly regulated import systems to balance
copper’s essential redox functions with its inherent cytotoxicity; yet, the mechanisms
of cytoplasmic copper uptake remain poorly understood. In particular, the widespread
...
Biophysics and Computational Biology
Epithelial cortinoids, fluid-filled shells formed from induced pluripotent stem cells
(iPSCs), must accommodate large deformations during growth and morphogenesis. Using
inflation–deflation assays and high-resolution imaging, we find that these fluid-...
Noncovalent interaction between proteins and carbohydrates (sugars, glycans) is the
basis for biological functions from metabolic regulation to intercellular recognition.
It is a grand challenge to identify the protein–carbohydrate interactomes in ...
Language models trained on biological sequences are advancing inference tasks from
the scale of single proteins to that of genomic neighborhoods. Here, we introduce
ProteomeLM, a transformer-based language model that uniquely operates on entire proteomes
...
Bleb-based cell migration involves rapid plasma membrane expansion driven by intracellular
pressure. How the membrane reorganizes its curvature and protein composition during
this process remains unclear. Here, we identify a distinct inward membrane ...
Apoptosis-inducing factor (AIF) is a flavoprotein located in the mitochondrial intermembrane
space, and it is believed to trigger caspase-independent cell death after its release
from the mitochondria into the nucleus. Here, the proapoptotic activity of ...
Intrinsically disordered regions (IDRs) represent at least one-third of the human
proteome and defy the established structure–function paradigm. Because IDRs often
have limited positional sequence conservation, the functional classification of IDRs
using ...
Developmental Biology
Developmental patterning is remarkably robust to intrinsic and extrinsic variation.
Morphogen gradients are a key mechanism driving patterning, and themselves often scale
with the size of developing tissues and exhibit robustness to other perturbations.
...
The uterine microenvironment is critical for establishing pregnancy and sustaining
embryonic development. Embryo attachment induces profound endometrial transformation,
including stromal differentiation and vascularization, termed decidualization. This
...
While genetic mutations can promote hyperplastic growth, they do not always result
in oncogenic outcomes. We and others have previously identified the transcription
factors Nerfin-1 and Lola as inhibitors of dedifferentiation. Here, we investigate
how the ...
Ecology
Darwin’s Naturalization Conundrum holds that both functional similarity and distinctiveness
can facilitate biological invasions: invaders similar to natives may succeed through
preadaptation to local abiotic conditions, whereas functionally distinct ...
Evolution
Complex life would be impossible without cooperation at all levels of biological organization.
However, Darwinian selection is commonly believed to favor selfish behavior, making
societies of cooperators vulnerable to cheaters. A quintessential model of ...
Understanding the origins of volunteerism and free-riding is crucial in collective
action situations where a sufficient number of cooperators is necessary to achieve
shared benefits, such as in vaccination campaigns and social change movements. Despite
...
Heterotopy—the spatial relocation of developmental processes—is a key mechanism driving
morphological innovation, yet its underlying regulatory basis remains poorly understood.
In chordates, the left–right (L–R) organizer shifted from the anterior domain ...
Speciation with gene flow poses a central paradox: how do genome-wide barriers to
gene exchange accumulate as recombination continually breaks down associations among
selected loci? Although theory predicts that together recombination, selection, and
...
Gossypium hirsutum is the leading fiber crop globally, but its origin as a domesticated plant and patterns
of diversity in the wild remain to be elucidated. Here, we use extensive sampling
of wild populations and comparative genome sequence data to ...
Genetics
Individuals respond differently to environmental cues because of inherent variations
in genome sequences. This study demonstrates that natural variation in small RNA (sRNA)
within embryos epigenetically shapes adaptive neural circuits underlying diverse ...
The Greenland shark (Somniosus microcephalus) is known for its slow metabolism and deep-sea habitat. It is thought to be the longest-lived
vertebrate on Earth, with an estimated lifespan of 392 ± 120 y. Despite its remarkable
longevity and unusual ...
Mapping the molecular identities and functions of cells within their spatial context
is key to understanding the complex interplay within and between tissue neighborhoods.
A wide range of methods have recently enabled spatial profiling of cellular ...
How generalist pathogens infect phylogenetically diverse hosts remains a central question
in plant-pathogen biology. In particular, the extent to which broad host range is
enabled by genetic variation vs. transcriptional plasticity is unclear. To ...
Immunology and Inflammation
Innate immunity mediated by myeloid cells defends against infection and injury, but
when chronically activated, it drives tissue damage and neurodegeneration. Molecular
imaging with positron emission tomography (PET) enables noninvasive, real-time ...
Metastasis is facilitated by epithelial-to-mesenchymal transition (EMT), a process
in which epithelial cancer cells, including breast cancer cells, acquire mesenchymal-like
phenotypes. Production of reactive oxygen species (ROS) by NADPH oxidase 2 (NOX2)
...
Resistance to immune checkpoint blockade (ICB) often arises from immunologically cold
tumors enriched in suppressive myeloid cells. Previous studies have implicated NOD2
signaling in antitumor immunity and in modulation of ICB responses, but approaches
to ...
Fibroblasts are key potentiators of chronic disease pathophysiology. Despite their
established roles in promoting pathological inflammation and tissue remodeling, activated
myofibroblasts are generally characterized as a single, homogeneous cell ...
Medical Sciences
The tumor glycocalyx forms a protective shield that masks checkpoint proteins and
compromises the efficacy of immunotherapies. While the bacterial protease StcE can
degrade this barrier by cleaving O-glycosylated mucin domains, its therapeutic potential
...
Mycobacterium tuberculosis is the leading global cause of infectious disease deaths. A growing proportion of
tuberculosis cases in high-income countries occur among foreign-born individuals,
due to infections acquired before migration. We developed a ...
Invasive pulmonary mucormycosis (IPM) is a severe opportunistic mold infection whose
outcome is predominantly host driven. Preclinical proof-of-concept studies and clinical
case reports in salvage therapy settings suggested a benefit of immune checkpoint
...
Multiple myeloma (MM) develops with the acquisition of genetic abnormalities in plasmacytes
and changes in microenvironment cells (MECs). Despite the progress in understanding
MM disease mechanism through omics studies, the genomic/transcriptomic ...
Microbiology
Several orthoebolaviruses have been established, including Orthoebolavirus zairense [for Ebola virus (EBOV)], Orthoebolavirus sudanense [for Sudan virus (SUDV)], and Orthoebolavirus bundibugyoense [for Bundibugyo virus (BDBV)]. Orthoebolaviruses are ...
Type VI secretion systems (T6SSs) are widely distributed among Gram-negative bacteria,
where they mostly act to promote bacterial warfare. Bacteria from the Francisella genus possess T6SSs that phylogenetically diverge from all other T6SSs and constitute
...
Heterogenous transcription start site (TSS) usage dictates the 5′ leader structure
and function of unspliced HIV-1 RNAs (usRNA). We and others have previously reported
that expression and Rev/CRM1-mediated nuclear export of HIV-1 usRNA in macrophages
...
The assembly of β-barrel proteins into the outer membrane (OM) of Gram-negative bacteria
is catalyzed by the β-barrel assembly machine (Bam) complex, which consists of two
essential proteins, the BamA β-barrel and the lipoprotein BamD, and three ...
Despite implementation of pneumococcal conjugated vaccines (PCVs) against Streptococcus pneumoniae infections, these diseases are still major contributors to global mortality and morbidity,
highlighting the need for a novel immunization strategy. ...
Neuroscience
The decisional reference point, the central mechanism underlying behavioral economics,
conditions our evaluations of all reinforcers. Whether a given event is experienced
as positive or negative depends on this reference point. A pathological elevation
of ...
The ability to induce endothelial cell (EC) damage in the mouse brain with high spatial
precision is invaluable for mechanistic studies of brain capillary injury and repair.
Here, we introduce an optical method, termed Endothelial Cell guided obliteration
...
General anesthesia is often compared to sleep but may more closely resemble a medically
induced coma. While all three states involve a loss of awareness, the extent of their
neural similarity remains unclear. Electrophysiological markers, such as delta ...
Autoantibodies against leucine-rich glioma inactivated 1 protein (LGI1) lead to limbic
encephalitis, a rare neurological autoimmune disorder characterized by faciobrachial
dystonic seizures and memory deficits. While animal models provide precious ...
Fibroblasts are a heterogeneous group of mesenchymal cells essential for tissue homeostasis
maintenance and pathological responses. However, the mechanistic contributions of
fibroblast plasticity to somatosensory dysfunction, particularly pathological ...
Gut microbiota across animals have been shown to influence host cognition and behavior.
However, it remains unclear whether these cognitive effects are driven by specific
bacterial species or arise from community-level interactions. Here, we leveraged the
...
Pharmacology
Many small-molecule antitumor drugs are administered far less frequently than would
be predicted from their plasma half-lives, in part because their efficacy is driven
by prolonged retention within tumors. Drug retention can be caused by nonspecific
...
Plant Biology
How generalist pathogens infect phylogenetically diverse hosts remains a central question
in plant-pathogen biology. In particular, the extent to which broad host range is
enabled by genetic variation vs. transcriptional plasticity is unclear. To ...
Brassinosteroids (BRs) are plant steroid hormones sensed by the membrane receptor
kinase BRI1. Activation of BRI1 leads to the dephosphorylation of BZR1/BES1 transcription
factors. Overexpression of the Kelch phosphatase BRI1 SUPPRESSOR 1 (BSU1) rescued
...
The Cape Verde Island (Cvi)-0 ecotype, a relict lineage of Arabidopsis thaliana, is characterized by exceptionally low CG methylation levels genome-wide. Numerous
population-level and molecular studies have highlighted links between this epigenomic
...
Population Biology
Seasonal influenza epidemics exhibit complex transmission dynamics influenced by time-varying
extrinsic factors such as social behavior and seasonal effects. Estimating changes
in transmission rates is critical to enable accurate forecasting of the ...
Sustainability Science
As one of the main causes of habitat loss, agricultural cropland expansion is a major
threat to biodiversity. We analyze past and anticipated future trends in population,
per capita crop demand, and crop yield to estimate agricultural cropland ...
Corrections
Cover image: Pictured are engineered cell membrane nanovesicles degrading the protective glycocalyx layer on a tumor cell. Xiaorui Geng et al. engineered nanovesicles that codisplay mucin-degrading enzymes and checkpoint nanoantibodies to selectively disrupt the glycocalyx of tumor cells, expose the tumors to the nanoantibodies, and enhance the antitumor immune response. The nanovesicle platform significantly suppressed tumor growth and metastasis in mouse models of colorectal and breast cancer. The enhanced tumor targeting, prolonged circulation, and biosafety of this approach could lead to improved cancer immunotherapies. See the article by Geng et al. e2529792123. Image credit: Chen Yan and Yixi Wang (Shenzhen Bay Laboratory, Shenzhen, China).
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