Table Of Contents Page, PNAS Volume 122, Number 47
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Perspectives
Numerous research efforts have used paleoecological data to reconstruct past biodiversity
in Europe. In these projects, researchers have identified increases in biodiversity
over the Holocene and hinted at a positive correlation with human population. ...
Social scientists not only conduct impact evaluations but also participate in the
design and implementation of the programs being evaluated. While Institutional Review
Boards (IRBs) oversee research activities, they do not assess risks posed by the ...
Letters
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Brief Reports
Marine heatwaves (MHW) are common destructive events affecting coral reefs. After
decades of degradation, the shallow reefs of the United States Virgin Islands have
been depleted of scleractinian corals, leaving abundant colonies of the hydrozoan
fire ...
Lethal coalitionary intergroup aggression is a conspicuous aspect of wild chimpanzee
behavior. Evidence indicates that such violence can lead to territorial expansion,
but whether this results in fitness benefits is unknown. Here, we show that female
...
Pain is a multifaceted experience that not only impacts individuals physiologically
but also reshapes their emotional well-being and social dynamics. The expression of
pain and postpain emotional states is profoundly influenced by social contexts. Recent
...
Do neural network models capture the cognitive demands of human reasoning? Across
seven reasoning tasks, we show that the length of the chain-of-thought generated by
large reasoning models predicts human reaction times both within tasks—tracking item-...
Saccadic eye movements rapidly shift the visual scene across the retina, raising the
question of how object correspondence is established between gaze fixations. Using
submillisecond video projection, we isolated the role of high-speed retinal motion
from ...
Physical Sciences
Applied Mathematics
This study explores how individuals perceive their social networks, with a focus on
their own positioning. Using experimental methods and network analysis, we show that
people have a limited understanding of their social standing in terms of popularity
(...
Applied Physical Sciences
The rapid advancement of synthetic biology has enabled the construction of artificial
cells that closely mimic the morphology and functionality of their natural counterparts.
However, significant limitations remain in engineering artificial cells capable ...
Axolotls can regenerate lost limbs throughout life, while they continue to grow. This
poses the question of how the size and pattern of a regenerating limb is matched to
a widely varying animal size. Two interacting signaling molecules, Sonic Hedgehog
(...
Foams and dense emulsions display complex mechanical behavior, including intermittent
rearrangement dynamics, power-law rheology, and slow recovery after perturbation.
These effects have long been considered evidence for glassy physics in these and other
...
The mechanisms by which light interacts with ice and the impact of photoinduced reactions
are central to our understanding of environmental, atmospheric, and astrophysical
processes. However, a microscopic description of the photoproducts originating from
...
Biophysics and Computational Biology
During photosynthesis, the photosystem II (PSII) enzyme catalyzes the light-driven
oxidation of water, fueling life on Earth by storing light energy and releasing O2 as a byproduct. Determining the molecular mechanism for this water oxidation reaction
has ...
Cells in tissues navigate fibrous environments fundamentally differently than they
do on flat substrates, but the establishment of cell forces in physiological fibrous
settings remains poorly understood. Although factors such as the stiffness of the
...
Membrane protein homo-oligomers named higher-order transient structures (HOTS) are
formed through cohesive self-interactions in the range of a few . The small magnitude of these interactions underlies the rapid reversibility of HOTS
on the timescale of ...
The spatial organization of chromatin is governed by epigenetic factors, including
epigenetic marks and the reader proteins that bind them. By dictating the accessibility
of genomic loci, epigenetic factors contribute to the physical regulation of gene
...
Cell migration relies on balancing focal adhesion (FA) stability—necessary for traction
generation—and turnover—essential for forward translocation. Here, we dissect how
integrin binding frequency and force-dependent bond duration jointly regulate this
...
The architectures of biological neural networks result from developmental processes
shaped by genetically encoded rules, biophysical constraints, stochasticity, and learning.
Understanding these processes is crucial for comprehending neural circuits’ ...
Chemistry
As an electron-deficient element, boron possesses fascinating three-dimensional structures
and unconventional chemical bonds. Nanoclusters of boron have also been found to exhibit
intriguing structural properties, observed to have predominantly planar ...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies,
largely due to its highly immunosuppressive tumor microenvironment (TME), which fuels
metastasis and resistance to immunotherapy. Through comprehensive analysis of single-...
Earth, Atmospheric, and Planetary Sciences
Throughout Earth’s history, organic molecules from both abiogenic and biogenic sources
have been buried in sedimentary rocks. Most of these organic molecules have been significantly
altered by geologic processes through deep time. Nonetheless, the nature ...
Aerosol–cloud interactions remain one of the largest uncertainties in the anthropogenic
forcing of the climate; a significant contribution to this is due to the aerosol effect
on the development of cloud fraction and liquid water path in stratocumulus ...
Engineering
The creatine kinase (CK) is a key enzyme involved in brain bioenergetics, playing
an important role in brain function and the pathogenesis of neurological and psychiatric
diseases and cancers. However, imaging its activity noninvasively in the human brain
...
Rapid, nonequilibrium heating drives mesoscale structural evolution in heterogeneous
composite materials under extreme thermal conditions, critically influencing performance
in aerospace propulsion and advanced structural applications. However, existing ...
Elucidating the fundamental microscopic mechanisms governing plastic deformation is
crucial for the rational design of functional materials with tailored mechanical properties.
Recent advances in Mg3Bi2-based thermoelectric materials have revealed ...
Environmental Sciences
Fluorescence in phytoplankton and other autotrophic organisms originates within the
cell chloroplasts, where a fraction of the absorbed solar radiation is reemitted at
longer wavelengths by photopigments. While traditionally employed as an indicator
of ...
Physics
Spatiotemporal correlation of magnetic field fluctuations is investigated using the
Magnetospheric Multiscale mission in the terrestrial magnetosheath. The first observation
of the turbulence propagator in space emerges through analysis of more than a ...
Social Sciences
Anthropology
Paleolithic representations of human–animal interaction are rare, with only a few
painted or engraved examples recorded in Upper Paleolithic contexts, mostly from Europe.
Such scenes, depicting real or imagined interactions, are of major importance for
...
Political Sciences
The advancement of large language models poses a severe, potentially existential threat
to online survey research, a fundamental tool for data collection across the sciences.
This work demonstrates that the foundational assumption of survey research—that ...
Psychological and Cognitive Sciences
Many domains in life require people to wait to access better outcomes, such as waiting
in line to access prized tickets for a show, waiting to obtain a job offer from a
selective firm, or being waitlisted for a prestigious university. Although waiting
...
Social Sciences
This study explores how individuals perceive their social networks, with a focus on
their own positioning. Using experimental methods and network analysis, we show that
people have a limited understanding of their social standing in terms of popularity
(...
We advance the understanding of so-called “cancel culture” at the university by presenting
the results of three survey experiments among university students. Designed in an
“adversarial collaboration” among researchers with competing perspectives, these ...
Biological Sciences
Applied Biological Sciences
The rapid advancement of synthetic biology has enabled the construction of artificial
cells that closely mimic the morphology and functionality of their natural counterparts.
However, significant limitations remain in engineering artificial cells capable ...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies,
largely due to its highly immunosuppressive tumor microenvironment (TME), which fuels
metastasis and resistance to immunotherapy. Through comprehensive analysis of single-...
Metabolically versatile Pseudomonas species can assimilate various glycolytic and gluconeogenic substrates. Simultaneous
assimilation is known to segregate carbons from each substrate type into different
metabolic pathways. However, the mechanisms of this ...
Biochemistry
Throughout Earth’s history, organic molecules from both abiogenic and biogenic sources
have been buried in sedimentary rocks. Most of these organic molecules have been significantly
altered by geologic processes through deep time. Nonetheless, the nature ...
Mitochondrial DNA (mtDNA) is crucial for cellular energy production, metabolism, and
signaling. Its dysfunction is implicated in various diseases, including mitochondrial
disorders, neurodegeneration, and diabetes. mtDNA is susceptible to damage by ...
Sphingosine-1-phosphate (S1P) is one of the most extensively studied bioactive lipids
that transduces signals via the S1P receptor (S1PR) family (S1PR1-5), a class of G-protein-coupled
receptors (GPCRs), to regulate immune cell migration, vascular ...
DNA replication requires precise coordination between DNA unwinding and DNA synthesis.
In all domains of life, protein–protein interactions at the replisome maintain proximity
between the enzymes that catalyze these two activities. Surprisingly, in ...
Hereditary spastic paraplegia subtype SPG54 is a genetic neurological disorder caused
by mutations in the DDHD2 gene. Excessive lipid droplet accumulation is observed in
the brains of SPG54 patients and DDHD2 knockout mice, consistent with DDHD2’s ...
Protein AMPylation is a highly conserved posttranslational modification in which adenosine
monophosphate (AMP) is covalently attached to protein substrates. Our studies revealed
that the mitochondrial AMPylase, Selenoprotein O (SelO), regulates cellular ...
DNA polymerase theta (Pol θ)-mediated end joining (TMEJ) initiates DNA double-strand
break repair by using short homologies (microhomologies) between single-stranded DNA
tails. This repair process is particularly important in cancer cells defective in
...
Translation of mammalian G-rich telomeric RNA via the Repeat Associated non-AUG (AUG,
the mRNA start codon) mechanism can produce proteins consisting of long repeats of
valine–arginine (VR) or glycine–leucine (GL) dipeptides. Their role in the cell has
...
Biophysics and Computational Biology
Cells in tissues navigate fibrous environments fundamentally differently than they
do on flat substrates, but the establishment of cell forces in physiological fibrous
settings remains poorly understood. Although factors such as the stiffness of the
...
Membrane protein homo-oligomers named higher-order transient structures (HOTS) are
formed through cohesive self-interactions in the range of a few . The small magnitude of these interactions underlies the rapid reversibility of HOTS
on the timescale of ...
The spatial organization of chromatin is governed by epigenetic factors, including
epigenetic marks and the reader proteins that bind them. By dictating the accessibility
of genomic loci, epigenetic factors contribute to the physical regulation of gene
...
Cell migration relies on balancing focal adhesion (FA) stability—necessary for traction
generation—and turnover—essential for forward translocation. Here, we dissect how
integrin binding frequency and force-dependent bond duration jointly regulate this
...
Cooperative regulation of biomolecular function is critical for the ability of all
organisms to respond effectively to environmental changes. Such regulation is often
manifested in a sigmoidal dependence of enzyme activity on ligand concentration. Various
...
Cell Biology
Chirality is a conserved biological feature with critical implications in tissue morphogenesis
and embryonic development. In culture, multicellular groups exhibit spontaneous chiral
symmetry break when moving collectively on micropatterned surfaces. ...
Cancer-associated fibroblasts (CAFs) shape the tumor microenvironment of primary breast
tumors to promote tumor progression and therapy resistance. While the lung is a top
metastatic site in breast cancer, the origins of lung metastasis-associated ...
Homeostasis relies on signaling networks controlled by cell membrane receptors. Although
G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors,
their specific roles in the epidermis are not fully understood. Dual CRISPR-...
BET1, GOSR2, and STX5 variants can cause fatal inherited diseases, including epilepsies, muscular dystrophy,
and multisystemic disorders. Together with Sec22b, they form a SNARE complex that
mediates fusion of ER-derived vesicles with the ER-Golgi-...
Nonsyndromic capillary malformations (CM) are seen predominantly in skin. In Sturge–Weber
Syndrome (SWS), CMs occur in the skin, leptomeninges of the brain, and choroid of
the eye. >90% of CM are caused by a somatic mutation—GNAQ p.R183Q, the gene ...
Cilia are essential cellular antennae that rely on precise motor-driven transport
to assemble and function. Two kinesin-2 motors—kinesin-II and OSM-3 in Caenorhabditis elegans—cooperate to transport cargo along cilia, with kinesin-II operating in the ...
Actin networks in cells are dynamic and constantly turning over as actin subunits
exchange between monomer and polymer pools. Understanding these dynamics in vivo requires
a detailed understanding of pure actin behavior in vitro. The prevailing model is
...
Neural stem cells (NSCs) are valuable in the quest to conquer neurodegenerative diseases
due to their capability to reconstruct the damaged neuronal networks. However, deep
understanding of the intercellular signaling mechanism controlling the lineage and
...
Developmental Biology
Axolotls can regenerate lost limbs throughout life, while they continue to grow. This
poses the question of how the size and pattern of a regenerating limb is matched to
a widely varying animal size. Two interacting signaling molecules, Sonic Hedgehog
(...
The adult bone marrow houses progenitors for both osteoblasts and adipocytes, but
their precise molecular identity remains to be fully elucidated. Previous studies
indicate that Lepr+Cxcl12+ bone marrow stromal cells collectively give rise to both ...
In Xenopus laevis tadpole tail regeneration, lineage-restricted tissue stem cells produce differentiated
cells that form regenerated tail tissues, but the behavioral dynamics of tissue stem
cells during tail regeneration remain largely unknown. We ...
Ecology
Fluorescence in phytoplankton and other autotrophic organisms originates within the
cell chloroplasts, where a fraction of the absorbed solar radiation is reemitted at
longer wavelengths by photopigments. While traditionally employed as an indicator
of ...
Recent evidence suggests that the ecological footprints of pre-Columbian Indigenous
peoples in Amazonia persist in modern forests. Ecological impacts resulting from European
colonization c. 1550 CE and the Amazonian Rubber Boom c. 1850 to 1920 CE are ...
Amid the biodiversity crisis, functional diversity, which is critical for ecosystem
stability and conservation planning—faces challenges due to species’ complex life
cycles. As the majority of animals, species with complex life histories may have distinct
...
Our understanding of carbon and nutrient dynamics in globally vast and socioeconomically
critical dryland ecosystems lags behind mesic systems. Litter decomposition models
consistently underestimate measured decomposition in these regions. Both models and
...
Evolution
Understanding how the cellular and molecular composition of neural circuits evolves
to generate species-specific behaviors remains a major challenge in evolutionary biology
and neuroscience. The remarkable diversity of male sexual behaviors among ...
Hurricanes can be a source of strong, episodic natural selection, especially for coastal
and island populations. In Anolis lizards, selection favors morphological traits that enhance clinging performance
under hurricane-force winds. However, we know ...
Immunology and Inflammation
Ten CD3 T cell engagers (TCEs) have received regulatory approval for the treatment
of hematologic and solid tumors. However, limited costimulatory signaling essential
for sustained T cell effector activity may limit CD3 TCE clinical efficacy and response
...
T cells rely on short peptides presented by highly polymorphic major histocompatibility
complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance,
few techniques can systematically evaluate stable peptide presentation ...
Pancreatic cancer (PC) remains one of the leading causes of cancer-related mortality
worldwide. The majority of patients are diagnosed at advanced stages, with over 50%
presenting with metastatic disease at the time of diagnosis. Although chimeric antigen
...
Interleukin-2 (IL2) is the key trophic factor for T regulatory (Treg) cells, controlling
their differentiation and homeostasis. To understand how temporally regulated responses
to IL2 unfold in Tregs, we performed fine time-course analyses, at population ...
Type 2 innate lymphoid cells (ILC2s) contribute to type 2 immunity but have also been
associated with multiple inflammatory diseases, including airway inflammation and
asthma. We report that beyond its function of degrading poly-ubiquitinylated proteins,
...
Medical Sciences
The kidney proximal tubule (PT) is a specialized polarized epithelium that functions
as a high capacity resorptive machine. PT cells are exquisitely sensitive to ischemia
due to their high metabolic rate. The small GTPase Rac1 regulates epithelial ...
RNA interference (RNAi) therapeutics represent breakthrough discoveries, but their
use in cancer remains limited due to hepatocyte-specific targeting. Cancer metastasis
is regulated by complex crosstalk between tumor cells and niche-derived factors. ...
Microbiology
Natural genetic transformation is a conserved mechanism of bacterial horizontal gene
transfer, which is directed entirely by the recipient cell and facilitates the acquisition
of new genetic traits such as antibiotic resistance. Transformation proceeds ...
During microbial infection, mammalian hosts reduce the availability of free metals
such as zinc in a process known as nutritional immunity. Pathogens counteract nutritional
immunity by expressing gene products that enhance growth in metal-limited ...
Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence
of the continuous selective pressures imposed by phage predation. Despite recent mechanistic
advances, the evolutionary origins of many antiphage immune systems remain ...
Neuroscience
The architectures of biological neural networks result from developmental processes
shaped by genetically encoded rules, biophysical constraints, stochasticity, and learning.
Understanding these processes is crucial for comprehending neural circuits’ ...
Alpha-Synuclein (αSyn) plays a central role in Parkinson’s disease (PD), and the p.A53T
mutation causes an early-onset familial form of PD with severe manifestations. While
its effects on neurons are well studied, its consequences on astrocytes and ...
Information processing in the brain relies on the transmission of spikes through chemical
synapses whose efficacies often depend on their recent firing history. While effects
of such short-term plasticity on neural information processing have long been ...
The thalamus is pivotal for the development and function of neural circuits in the
cerebral cortex. However, how thalamus–cortex interactions influence human cortical
development remains unknown primarily because of the inaccessibility of the human
...
SCN2A is a high-confidence risk gene for autism spectrum disorder. Loss-of-function mutations
in Scn2a reduce dendritic excitability in neocortical pyramidal cells. However, the impact
of Scn2a haploinsufficiency on dendritic signaling in vivo, ...
Glycation, the nonenzymatic attachment of reactive dicarbonyls to proteins, lipids,
or nucleic acids, contributes to the formation of advanced glycation end-products
(AGEs). In Alzheimer’s disease (AD), amyloid-beta (Aβ) undergoes posttranslational
...
Synaptic plasticity in the central nervous system enables the encoding, storing, and
integrating new information. AMPA (alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionic
acid)-type glutamate receptors (AMPARs) are ligand-gated ion channels that ...
Pharmacology
The pituitary adenylate cyclase-activating polypeptide (PACAP) 1 receptor (PAC1R)
is a class B1 G protein–coupled receptor activated by the endogenous peptide agonists
PACAP and vasoactive intestinal peptide (VIP). Alternate splicing within the receptor
...
Physiology
The creatine kinase (CK) is a key enzyme involved in brain bioenergetics, playing
an important role in brain function and the pathogenesis of neurological and psychiatric
diseases and cancers. However, imaging its activity noninvasively in the human brain
...
Plant Biology
During photosynthesis, the photosystem II (PSII) enzyme catalyzes the light-driven
oxidation of water, fueling life on Earth by storing light energy and releasing O2 as a byproduct. Determining the molecular mechanism for this water oxidation reaction
has ...
The conventional assumption is that stomatal conductance () dominates the regulation of water and carbon dioxide fluxes between leaves and the
atmosphere. Here, a nanoreporter of water status at the mesophyll cell surface and
local xylem within intact ...
Plant stem cells have the remarkable ability to give rise to distinct tissues and
organs throughout development. Two concentric cylinders of actively dividing stem
cells are the main drivers of radial thickening during secondary growth, each producing
...
The Ca2+-independent OST1 and Ca2+-dependent protein kinases CPKs both activate the anion channel SLAC1 during ABA-induced
stomatal closure pathway. However, the mechanism by which OST1 regulates SLAC1 activation
and its relationship with CPKs remain ...
While multiple chromatin-based epigenetic pathways are well characterized, their genome-wide
coordination and hierarchical interplay remain poorly understood. We previously identified
the BAH–PHD–CPL2 complex, where AIPP3 binds H3K27me3 via its BAH domain ...
Psychological and Cognitive Sciences
Recent work suggests combining physical activity with cognitive tasks may have been
critical to human evolution and may be beneficial to human brain health today. These
combined tasks are key elements of foraging, a lifestyle employed by human ancestors
...
Sustainability Science
Recent evidence suggests that the ecological footprints of pre-Columbian Indigenous
peoples in Amazonia persist in modern forests. Ecological impacts resulting from European
colonization c. 1550 CE and the Amazonian Rubber Boom c. 1850 to 1920 CE are ...
Systems Biology
Rubisco is the main gateway through which inorganic carbon enters the biosphere, catalyzing
the vast majority of carbon fixation on Earth. This pivotal enzyme has long been observed
to be kinetically constrained. Yet, this impression is based on kinetic ...
Corrections
Cover image: Pictured is Garrisson, an adult male chimpanzee. Brian M. Wood and colleagues studied wild chimpanzees from the Ngogo community in Kibale National Park, Uganda. The chimpanzees were observed killing at least 21 members of neighboring groups between 1998 and 2008 and subsequently expanding their territory. After territorial expansion, the number of recorded births among the chimpanzees more than doubled, whereas infant mortality declined. According to the authors, the findings suggest links between intergroup violence and fitness benefits in a primate species closely related to humans. See the article by Wood et al. e2524502122. Image credit: Kevin E. Langergraber.
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