Table Of Contents Page, PNAS Volume 122, Number 51
This Week in PNAS
Opinion
Retrospective
David John “Davo” Mangelsdorf passed away on August 3, 2025, in Dallas, Texas at age
67 from an unexpected postsurgical complication. Davo made transformative contributions
to nuclear receptor and metabolic biology. He discovered the retinoid X receptor (...
Commentaries
Perspective
This perspective addresses two of humanity’s greatest challenges: feeding a growing
population and conserving biodiversity. We begin by examining the legacy of Nikolai
Vavilov, who pioneered the improvement of crops such as wheat and beans by hybridizing
...
Letters
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Reply to Kohl: Moving beyond the 19th-century view of domestication
View the original article:Brief Reports
The COVID-19 pandemic provided a natural experiment to test the impacts of human activity
on urban-dwelling wildlife. Urban dark-eyed juncos differ in bill shape and size in
Los Angeles in comparison to local wildlands. We measured juncos that hatched ...
We investigate why work from home (WFH) rates vary so widely across countries using
the Global Survey of Working Arrangements (G-SWA). Conducted in late 2024 and early
2025, G-SWA is the only harmonized international survey of remote work, covering 14,427
...
We all likely agree that tactile experience contributes to the emergence of the feeling
of ownership over one’s own body. Is the opposite true? We answered this question
by testing whether and how the sense of body ownership gates our tactile experience.
...
Atmospheric micro(nano)plastics (MNPs), including polyethylene terephthalate (PET),
enter plants via leaves, accumulating in tissues. Foliar PET nanoplastic exposure
alters Nicotiana benthamiana nicotine biosynthesis, favoring the more potent (S)-isomer ...
Physical Sciences
Applied Mathematics
Complex adaptive networks exhibit remarkable resilience, driven by the dynamic interplay
of structure (interactions) and function (state). While static-network analyses offer
valuable insights, understanding how structure and function coevolve under ...
Evolutionary games provide a flexible mathematical framework for many problems in
biology and social evolution. Prisoners’ dilemma, and in particular, the important
special case of donation games, represents social dilemmas where cooperation is mutually
...
Applied Physical Sciences
Classical fluctuation theorems for work have been obtained theoretically, and verified
experimentally, within a nonautonomous framework in which work is performed on a system
of interest, , by the external manipulation of a work parameter, such as a ...
A previous modification removed a nonphysical divergence of the elastic displacement
field of an edge dislocation. The traditional elastic equations are correct to linear
elastic order. However, there is a disregistry of the displacement field at ± ...
Strong coupling photonics, in which coupling strengths significantly exceed decay
factors, holds great promise for applications in energy conversion and information
processing. However, the effective and scalable design of strongly coupled polaritonic
...
Biophysics and Computational Biology
Mutualistic interactions are widespread in nature, from plant communities and microbiomes
to human organizations. Along with competition for resources, cooperative interactions
shape biodiversity and contribute to the robustness of complex ecosystems. We ...
Directional sensing enables eukaryotic cells to detect spatial gradients of extracellular
ligands, allowing them to orient and migrate within complex environments. Prevalent
models explain this computation through a circuit where signaling species with ...
Computer Sciences
As large language models (LLMs) gradually demonstrate their potential to boost productivity
and become integral tools for problem-solving in daily life worldwide, understanding
the linguistic inequalities they introduce is becoming increasingly important. ...
The widespread adoption of electric vehicles (EVs) in recent years has necessitated
the development of effective charging infrastructures. However, charging infrastructure
expansion is a multifaceted problem that requires careful consideration of the ...
Earth, Atmospheric, and Planetary Sciences
Many regions of the world have seen an increase in highly destructive wildfires, driven
by well-documented increases in burned area and growth of housing in the wildland–urban
interface (WUI), which exposes more homes to fire. However, it is unclear ...
Models for prebiotic syntheses often have many steps, each separately validated by
laboratory experiments. The challenge then asks whether these steps work together
in natural geological environments, absent human intervention. Here, we analyze a
six-step ...
The Southern Ocean plays an important role in the global carbon cycle by absorbing
atmospheric CO2, aiding climate change mitigation. Antarctic coastal polynyas (ACPs) are key CO2 uptake areas, yet whether this CO2 is effectively sequestered as organic ...
Engineering
Capturing high-rate spatiotemporal deformation of materials in three dimensions (3D)
remains a significant challenge with current X-ray imaging techniques. We present
a methodology that combines advances in neural rendering techniques with volume ...
The concept of microfluidics has shown considerable promise for advancing chemistry,
diagnostics, and biology. However, there have been no guaranteed routes of microfluidics
that can achieve widespread adoption in mainstream chemistry and biomedical ...
Electrochemical ammonia synthesis at ambient conditions via calcium-mediated nitrogen
fixation holds considerable promise but is impeded by fundamental gaps such as poor
gas–liquid interface stability, sluggish hydrogen oxidation reaction (HOR) kinetics,
...
Environmental Sciences
Convection (thunderstorm) develops rapidly within hours and is highly destructive,
posing a significant challenge for nowcasting and resulting in substantial losses
to infrastructure and society. After the emergence of AI-based methods, convection
...
Electrochemical recovery of heavy metals from acid mine drainage (AMD) offers a sustainable
solution to global AMD contamination, yet remains challenged by thermodynamic and
kinetic barriers in reducing redox-active metals with negative standard reduction
...
Physics
The interplay between magnetism and flat-band (FB) instability is a central theme
in quantum materials research. A striking example is the emergence of magnetic order
in a nominally nonmagnetic compound when a flat band is tuned near the Fermi energy
(). ...
Like human decision-making under real-world constraints, artificial neural networks
may balance free exploration in parameter space with task-relevant adaptation. In
this study, we identify consistent signatures of criticality during neural network
...
Motivated by the experimental discovery of the fractional quantum anomalous Hall effect,
we develop a theory of doping-induced transitions out of the lattice Jain state in the presence of quenched disorder. We show that disorder strongly
affects the ...
Statistics
Centrifugation of biological matter in density gradient solutions is a standard method
for separating cell types or components. It is also used to separate red blood cells
(RBCs) by age, as they lose water and become denser over their lifespan. When the
...
Sustainability Science
The widespread adoption of electric vehicles (EVs) in recent years has necessitated
the development of effective charging infrastructures. However, charging infrastructure
expansion is a multifaceted problem that requires careful consideration of the ...
Understanding the mortality effects of the most extreme heat events is central to
climate change risk analysis and adaptation decision-making. Accurate representation
of these impacts requires accounting for the effects of prolonged sequences of hot
days ...
Cement-based products sequester CO2 in the atmosphere throughout their life cycle. The extent of sequestration highly
depends on the context. We implement a bottom–up model of different cement end-use
applications (buildings, pavements, bridges, pipelines,...
Social Sciences
Anthropology
Evidence for tattooing in ancient Nubia is long-standing, although no systematic studies
have compared application techniques, motifs, and the demography of tattooed individuals.
We surveyed 1,048 Meroitic to medieval (c. 350 BCE–1400 CE) human remains ...
Environmental Sciences
Many regions of the world have seen an increase in highly destructive wildfires, driven
by well-documented increases in burned area and growth of housing in the wildland–urban
interface (WUI), which exposes more homes to fire. However, it is unclear ...
Understanding the mortality effects of the most extreme heat events is central to
climate change risk analysis and adaptation decision-making. Accurate representation
of these impacts requires accounting for the effects of prolonged sequences of hot
days ...
Psychological and Cognitive Sciences
In sign languages, linguistic information is transmitted through the simultaneous
movement of several bodily articulators. This study investigates cortical tracking
of sign language and whether experience and knowledge of sign language can modulate
the ...
Children’s cognitive abilities vary across short and long timescales, from circadian
fluctuations to year-by-year developmental changes. “Summer slide” refers to seasonal
variation in academic performance, characterized by decreased performance following
...
Social Sciences
As large language models (LLMs) gradually demonstrate their potential to boost productivity
and become integral tools for problem-solving in daily life worldwide, understanding
the linguistic inequalities they introduce is becoming increasingly important. ...
Complex adaptive networks exhibit remarkable resilience, driven by the dynamic interplay
of structure (interactions) and function (state). While static-network analyses offer
valuable insights, understanding how structure and function coevolve under ...
A collaborative group can often outperform a single individual in complex problem
solving, even when information is limited. This phenomenon, called collective intelligence,
can be achieved by engineering a central planner who assigns subtasks distributed
...
Sustainability Science
The climate is already changing. The present study shows that these changes have already
affected the U.S. economy. It develops a formal framework that accounts for how climate
change has affected each county’s economy by altering current and past weather,...
Many coral reefs have fish stocks that are depleted below the level at which sustainable
production is maximized. Lower production means that millions of people are losing
out on potential food, income, and livelihoods. Rebuilding these stocks to maximize
...
Wildfire smoke, once rare, is a hazard that populations across the globe are increasingly
exposed to repeatedly. Evidence of acute health effects of wildfire particulate matter
(PM2.5) is growing, but less is known about long-term effects related to ...
Biological Sciences
Agricultural Sciences
Many coral reefs have fish stocks that are depleted below the level at which sustainable
production is maximized. Lower production means that millions of people are losing
out on potential food, income, and livelihoods. Rebuilding these stocks to maximize
...
Anthropology
Oxytocin, a hormone linked to reproduction and health, may mediate life-history trade-offs
across the human life course. Yet, how oxytocin naturally varies with age remains
poorly understood. Here, working with the Tsimane, forager-horticulturalists of ...
Applied Biological Sciences
Surgery remains the mainstay treatment for many kinds of solid tumors, while tumor
recurrence frequently occurs. Adjuvant therapy can reduce the risk of recurrence and
improve the prognosis of surgery. Chimeric antigen receptor (CAR)-T cell therapy can
be ...
Biochemistry
Cytosine methylation is a key epigenetic modification that regulates transcription
factor (TF) binding and gene expression. While most current understanding of methylation-sensitive
TF binding derives from studies focused exclusively on fully methylated ...
H/ACA small nucleolar ribonucleoproteins (H/ACA snoRNPs) facilitate essential cellular
processes such as RNA modification, folding, and stability. Here, we present multiple
cryo-EM structures of endogenous insect H/ACA snoRNPs containing two protomers ...
The somatostatin receptor subtype 5 (SSTR5) is a critical pharmacological target involved
in neuroendocrine signaling, metabolic regulation, and tumorigenesis. Despite its
therapeutic potential, the structural mechanisms underlying SSTR5 inhibition by ...
Small-molecule sensing in plants is dominated by chemical-induced dimerization modules.
In the abscisic acid (ABA) system, allosteric receptors recruit phosphatase effectors
and achieve nM in vivo responses from µM receptor–ligand interactions. This ...
Although most studies of the RNAs within extracellular vesicles (EVs) have focused
on messenger RNA (mRNA) and microRNAs (miRNAs), recent analyses have revealed that
transfer RNAs (tRNAs) and other noncoding RNAs (ncRNAs) are far more abundant. However,
...
Biophysics and Computational Biology
Centrifugation of biological matter in density gradient solutions is a standard method
for separating cell types or components. It is also used to separate red blood cells
(RBCs) by age, as they lose water and become denser over their lifespan. When the
...
Directional sensing enables eukaryotic cells to detect spatial gradients of extracellular
ligands, allowing them to orient and migrate within complex environments. Prevalent
models explain this computation through a circuit where signaling species with ...
Multicellular organisms utilize epithelial folding to achieve remarkable three-dimensional
forms. During embryonic development, stereotypical epithelial folds emerge from underlying
active cellular and molecular processes including cell shape change and ...
The signal peptide peptidase (SPP) remains the only intramembrane protease family
that is yet to be structurally characterized. Here, we report the cryoelectron microscopy
(cryo-EM) structures of human SPPL2a in two functional states: ligand-free and ...
Cell Biology
Previous studies of the tight junction protein occludin (OCLN) suggest that multiple
phosphorylation sites on the carboxy-terminal domain contribute a regulatory role
in vascular barrier properties. However, gene deletion studies failed to identify
a ...
The activation of the vesicular trafficking system, including endosomal recycling
and extracellular vesicle (EV) release, represents an adaptive mechanism in cancer
cells to counteract cellular stress or necroptotic death signals, which hampers cancer
...
Tumor cells heavily depend on proteasome-mediated protein turnover, making the proteasome
an attractive therapeutic target. Clinically, proteasome inhibitors are effective
against hematologic cancers but show limited success with solid tumors, and the ...
Developmental Biology
Motile cilia are eukaryotic organelles with essential chemo- and mechanosensing functions
across evolution, from single cell organisms to humans. Motile cilia of the mammalian
nervous, respiratory, and reproductive systems are characterized by unique ...
Assembly of cells into epithelial layers marks the early steps of tissue organization
and embryonic development in most animals. Although several conserved proteins are
known to be essential for epithelialization in bilaterians, it is unclear whether
...
Androgens drive the morphogenesis and differentiation of the Wolffian duct (WD) into
the epididymis, an essential organ for male reproduction, by binding to the androgen
receptor (AR). However, it remains unclear whether other transcriptional programs
...
Ecology
Mutualistic interactions are widespread in nature, from plant communities and microbiomes
to human organizations. Along with competition for resources, cooperative interactions
shape biodiversity and contribute to the robustness of complex ecosystems. We ...
A fundamental challenge in developing data-driven approaches to ecological systems
for tasks such as state estimation and prediction is the paucity of the observational
or measurement data. For example, modern machine-learning techniques such as deep
...
Interannually highly variable and synchronized production of large seed crops by perennial
plants, called masting, drives resource pulses and famines with cascading effects
on food webs. While the spatial scale of masting synchrony is well documented, it
...
Herbivorous insects have evolved many fascinating adaptations to overcome the chemical
defenses of their host plants. This study employed targeted and untargeted metabolomics,
coupled with isotope labeling, to shed light on the metabolism of salicinoids—...
Environmental Sciences
Wildfire smoke, once rare, is a hazard that populations across the globe are increasingly
exposed to repeatedly. Evidence of acute health effects of wildfire particulate matter
(PM2.5) is growing, but less is known about long-term effects related to ...
Evolution
Evolutionary games provide a flexible mathematical framework for many problems in
biology and social evolution. Prisoners’ dilemma, and in particular, the important
special case of donation games, represents social dilemmas where cooperation is mutually
...
A collaborative group can often outperform a single individual in complex problem
solving, even when information is limited. This phenomenon, called collective intelligence,
can be achieved by engineering a central planner who assigns subtasks distributed
...
The middle ear of mammals is a major functional innovation, distinctive in that it
is detached from the mandible and has a tympanic membrane supported by a ring-like
ectotympanic. These novelties of the middle ear have enabled modern mammals to develop
...
The magnitude and shape of phenotypic variation depends on properties of the genotype-to-phenotype
(GP) map, which itself can evolve over time. The evolution of GP maps is particularly
interesting in variable environments, as GP maps can evolve to bias ...
Hypermutable hotspot enables the rapid evolution of self/non-self recognition genes in Dictyostelium
Cells require highly polymorphic receptors to perform accurate self/non-self recognition.
In the amoeba Dictyostelium discoideum, polymorphic TgrB1 and TgrC1 proteins are used to bind sister cells and exclude cheaters,
but it remains unknown how cells ...
Genetics
DNA end resection to generate 3′ single-stranded DNA (ssDNA) overhangs is the first
step in homology-directed mechanisms of double-strand break (DSB) repair. While end
resection has been extensively studied in the repair of endonuclease-induced DSBs,
...
Immunology and Inflammation
Autoantibodies contribute to many autoimmune diseases, yet there is no approved therapy
to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis
(EAE), could serve to develop such a therapy, provided we can better ...
While the public health burden of SARS-CoV-2 infection has lessened due to natural
and vaccine-acquired immunity, emergence of less virulent variants, and antiviral
medications, COVID-19 continues to take a significant toll. There are thousands of
new ...
Immune cells naturally secrete extracellular antigen-presenting vesicles (APVs) displaying
peptide:MHC complexes to facilitate the initiation, expansion, maintenance, or silencing
of immune responses. Previous work has sought to manufacture and purify ...
Clinical responses to CD19-directed CAR T cell therapy in B cell malignancies are
strongly associated with robust CAR T cell expansion in the peripheral blood. In contrast,
CAR T cells targeting solid tumors do not encounter cognate antigen in the ...
Preventing autoantibody secretion by rendering self-reactive B cells functionally
silent through clonal anergy has long posed the question of why fill the circulating
B cell repertoire with cells that cannot secrete antibody? Here we address this question
...
Medical Sciences
Physical exercise affects multiple physiological processes, including those regulated
by hormones, such as energy balance, stress responses, and pain perception. The prohormone
precursor proopiomelanocortin (POMC) gives rise to β-endorphin, ...
Microbiology
Entry of Rift Valley fever virus (RVFV) into host cells is mediated by the viral glycoproteins
Gn and Gc. Structural details and assembly mechanism of Gn and Gc on the surface of
RVFV remain unclear. Here, we stabilized the GnGc with the neutralizing ...
Neuroscience
Women are underrepresented in biomedical research, limiting understanding of their
disproportionate rates of stress-related disorders. Although men experience more trauma,
women are twice as likely to develop posttraumatic stress disorder (PTSD). We ...
Vasoactive intestinal peptide (VIP) cells have emerged as a crucial component of the
inhibitory network, facilitating interregional communication, particularly in the
context of associative memory. To expand our current understanding of the role of
this ...
The neurobiological origins of social behaviors are poorly understood. Previous studies
have linked the function of a single Krüppel-associated box zinc finger protein (KZFP),
ZFP189, in the mouse prefrontal cortex (PFC), with the regulation of ...
The tactile system empowers us to act on and interact with the changes of the external
environment. In rodents, tactile sensation, a fundamental sense, is largely mediated
via the vibrissae and the barrel cortex. However, it remains unclear how tactile ...
The vertebrate nervous system is traditionally parceled topographically into central
and peripheral divisions. The peripheral nervous system (PNS) in turn is commonly
viewed functionally as a set of nerves and ganglia transmitting input and output signals
...
Plant Biology
Cis-regulatory sequences, such as enhancers, play a crucial role in morphological evolution,
but how their diversification leads to evolution of novel expression patterns that
underpin diversity is still poorly understood. Recent work suggests that the ...
Intercalary meristems (IcMs), specialized developmental zones that drive rapid stem
elongation in monocots, exhibit distinct spatiotemporal dynamics; however, their genetic
basis remains poorly understood due to their transient activity and cellular ...
Psychological and Cognitive Sciences
Cochlear implants (CIs) have transformed hearing restoration for individuals with
severe or profound hearing loss, yet outcomes vary widely and remain difficult to
predict. This study introduces an approach by examining the temporal dynamics of brain
...
The ability to represent locations across multiple dimensions of space is a core function
of cognitive maps. While the influence of boundary-dependent environmental geometry
on spatial representations has been extensively studied in 2D spaces, less is ...
Corrections
Cover image: Pictured is a young moso bamboo (Phyllostachys edulis) shoot in the China Bamboo Expo Park, Huzhou, China. Ning Qin et al. combined single-nucleus RNA sequencing and spatial transcriptomics to characterize the development of intercalary meristems, which are specialized structures that drive rapid stem elongation, in moso bamboo. The authors identified three developmental stages from proliferation to elongation, distinct populations of intercalary meristem cells, and key regulatory networks. The results could inform the enhancement of crop productivity and the development of sustainable biomaterial resources. See the article by Qin et al. e2511701122. Image credit: Ning Qin.
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