Table Of Contents Page, PNAS Volume 123, Number 24
This Week in PNAS
Core Concepts
Retrospective
Madhav Gadgil was an evolutionary ecologist and champion of governmental and intergovernmental
policies for biodiversity conservation, human coexistence with nature, and indigenous
rights to land, natural resources, and self-governance. He made ...
Commentaries
Letters
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Reply to Xiao and Imada: Prosociality across group boundaries is possible without partner choice
View the original article:The co-occurrence of ingroup and outgroup prosociality across 121 societies
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Reply to González González et al.: The contribution of bacteria to kidney stone formation
View the original article:Intercalated bacterial biofilms are intrinsic internal components of calcium-based kidney stones
Brief Reports
α-synuclein (α-syn) aggregation is a hallmark of synucleinopathies, a class of neurodegenerative
disorders such as Parkinson’s disease (PD). Several lines of evidence indicate the
involvement of mitochondria in the disease pathology. Despite extensive ...
Dietary guidelines form the foundation of federal food policy, informing programs
such as the Supplemental Nutrition Assistance Program (SNAP), government food procurement,
school meals, and military and hospital food services. The most recent guidelines,
...
Ultrathin films of widely different materials exhibit a dramatic enhancement of projectile
penetration resistance under high–velocity impact. Despite extensive simulations and
experiments, a unifying physical explanation has remained elusive. Here we show ...
Atmospheric ammonia emissions are harmful to ecosystems and human health. These emissions
have traditionally been monitored using thermal infrared spectrometers, though such
techniques are limited by thermal contrast requirements, the coarse spatial ...
Paternal epigenetic inheritance remains mechanistically unresolved. Recent studies
propose that environmental exposures induce mitochondrial DNA (mtDNA)-dependent transcription
in sperm during epididymal transit, altering small RNA content and offspring ...
In Italy, evergreen holm oaks (Quercus ilex) and deciduous sessile oaks (Quercus petraea) experienced a synchronized establishment pulse starting at the beginning of 1400s
CE, consistent with a release from anthropogenic pressure following demographic ...
View related content:
Forests shaped by historical human tragedies: Insights from Europe’s oldest angiosperms
Physical Sciences
Applied Mathematics
We present a framework for efficient extraction of the viscosity solutions of nonlinear
Hamilton–Jacobi equations with convex Hamiltonians. These viscosity solutions play
a central role in areas such as front propagation, mean-field games, optimal control,...
Applied Physical Sciences
Biomineralized structures produced by living organisms are widely recognized for their
exceptional mechanical performance, yet their potential optical roles are relatively
less explored. Here, we demonstrate that within the calcitic ossicle-based skeleton
...
The coalescence time of bubbles in a liquid depends on the nature of the liquid, which
determines both its surface thermodynamics and the molecular interactions between
the gas/liquid interfaces, and on the geometry, prescribed by the curvature of the
...
Biophysics and Computational Biology
Predicting the substrate reactivity strength for a given biocatalyst remains a central
challenge in computational biocatalysis. Here, we present Subdate, a modular workflow
that combines descriptor-guided organization of substrate analogs with ab initio ...
Protein phosphorylation is dynamically regulated by the opposing activities of phosphowriter
enzymes (kinases) and phosphoeraser enzymes (phosphatases and phospholyases). While
significant progress has been made toward defining the sequence preferences of ...
Chemistry
Immune checkpoint blockade has revolutionized oncology, yet low response rates and
acquired resistance—often driven by inadequate Programmed death-ligand 1 (PD-L1) suppression—remain
significant barriers. While degradation-based proteolysis-targeting ...
High-valent metal-oxo species, such as cobalt(IV)-oxo (CoIV=O) complexes, represent promising candidates for catalytic olefin epoxidation via
oxygen atom transfer (OAT) under mild conditions. However, their utility is often
limited by radical-mediated ...
Before the invention of encoded protein translation, early stages of life likely relied
on catalytic RNAs (ribozymes). To test how such a system could have functioned, researchers
have developed ribozymes that could have provided central functions. The ...
Earth, Atmospheric, and Planetary Sciences
Rapid agricultural expansion has driven forest loss worldwide. Deforestation reduces
evaporation, potentially decreasing precipitation and crop yields far beyond agricultural
frontiers. Here, we quantified the teleconnection impacts of Amazon ...
Tropical cyclone–induced storm surges pose significant and growing threats to coastal
regions; however, their long-term evolution in response to changing tropical cyclone
characteristics remains poorly quantified. Here, by conducting a comprehensive ...
Environmental Sciences
Food waste contributes substantially to global CO2 emissions, yet it also offers underutilized opportunities for climate change mitigation
within and beyond the food system. Direct air capture technologies can help offset
these emissions, but most current ...
Physics
In iron-based superconductors, the dz2 orbital band typically resides far below the Fermi level and has not been considered
to participate in Cooper pairing. Here, using monolayer FeSe/SrTiO3 as a model system, we demonstrate that tip-induced tensile ...
Floquet engineering has emerged as a powerful approach for dynamically tailoring the
electronic structures of quantum materials through time-periodic light fields. The
light fields generated by ultrafast laser pulses can transiently dress Bloch electrons,
...
Bilayer graphene cavities where electrons are confined within finite graphene flakes
provide an alluring platform not only for the future nanoelectronic devices owing
to the tunable energy gap but also for investigating the quantum nature of chaos due
to ...
Social Sciences
Anthropology
Does swidden agriculture, a prototypical coupled human and natural system, exhibit
a process of adaptive self-organization in which cultural practices balance environmental
constraints through adaptive feedback? Here, we investigate whether quantitative ...
Psychological and Cognitive Sciences
Our visual landscape consists of not only people, places, and objects (e.g., “soldier,”
“stadium,” “flag”) but also the conceptual relationships that unite them (e.g., “patriotism”).
Because conceptual knowledge varies across individuals, this level of ...
Oxytocin modulates social information processing by altering excitatory-inhibitory
balance at the microcircuit level, but how such local modulation gives rise to selective
processing at the level of distributed brain systems remains unclear. Here, we ...
Sustainability Science
China’s steel sector is pivotal to national and global climate goals, yet decarbonization
is constrained by entrenched coal-based processes and regional disparities. Top–down
and bottom–up models often neglect firm-level heterogeneity and behavioral ...
Many urban indicators predominantly focus on static outcomes, failing to capture the
dynamic nature of urbanization. Here, we introduce the concept of the Urban Pulse
to characterize urbanization as a process of continual spatiotemporal change. Using
...
Biological Sciences
Applied Biological Sciences
Mesenchymal stem cells (MSCs) exhibit significant heterogeneity, which limits their
therapeutic efficacy in regenerative medicine. Here, we introduce a self-assembled
interleukin-4 (IL-4) peptide hydrogel designed to shift MSC populations toward a ...
Biochemistry
Enzymes are fundamental to life, providing the rapid reactions and specificity needed
to sustain biological processes. While we have overcome the first major challenge
in understanding enzymes—identifying their reaction mechanisms—the second major ...
Predicting the substrate reactivity strength for a given biocatalyst remains a central
challenge in computational biocatalysis. Here, we present Subdate, a modular workflow
that combines descriptor-guided organization of substrate analogs with ab initio ...
Protein phosphorylation is dynamically regulated by the opposing activities of phosphowriter
enzymes (kinases) and phosphoeraser enzymes (phosphatases and phospholyases). While
significant progress has been made toward defining the sequence preferences of ...
Before the invention of encoded protein translation, early stages of life likely relied
on catalytic RNAs (ribozymes). To test how such a system could have functioned, researchers
have developed ribozymes that could have provided central functions. The ...
Prior to the emergence of the contemporary biosphere, the first replicating systems
are thought to have progressed through an RNA-based stage. Such an evolving world
would likely have transferred heritable information during replication using RNA ...
Nucleotide analogues (NAs) have been successfully used for the treatment of various
RNA virus infections by selectively targeting the viral RNA-dependent RNA polymerase
(RdRp) for incorporation into the viral genome. However two major families of human-...
Structures recently have been reported of molecular assemblies that mediate transcription–translation
coupling in Escherichia coli. In these molecular assemblies, termed “coupled transcription–translation complexes”
or “TTC-B,” RNA polymerase (RNAP) ...
Tetrameric rod phosphodiesterase-6 (PDE6), comprised of an α/β heterodimeric catalytic
core and two inhibitory γ subunits, critically regulates cyclic GMP (cGMP) levels
in rod photoreceptors. While the rod-PDE6 catalytic core is a heterodimer, the cone
...
A multisubunit ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C)
controls progress through mitosis in eukaryotic cells. The activity of APC/C in mitosis
is subject to both positive and negative regulation by the co-activator protein ...
Biophysics and Computational Biology
Generative AI algorithms such as the transformer and diffusion models have greatly
empowered de novo design of proteins capable of specifically interacting with designated
structural sites on another protein. Most of these design methods employ a top–down
...
Cell Biology
Cell volume, a key determinant of physiology, is maintained by cell size homeostasis.
Large deviations from typical size are often harmful, yet cell sizes have diverged
drastically during evolution. How size homeostasis evolves to support such diversity
...
Tumor initiation requires the integration of oncogenic signals with environmental
cues to enable anabolic growth. MYC is central to tumorigenesis, with its deregulation
observed in over 60% of human cancers. Oncogenic MYC profoundly rewires transcription,
...
The natural course of infantile hemangioma (IH), a benign vascular infantile tumor,
is marked by the initial rapid proliferation of dystrophic capillaries, followed by
a regression phase, which is either spontaneous or induced by the first line treatment
...
The global epidemic of myopia constitutes a growing public health concern worldwide.
Myopia development is characterized by pathological scleral remodeling through fibroblast-myofibroblast
transdifferentiation (FMT) and extracellular matrix (ECM) ...
Precise spatiotemporal regulation of parathyroid hormone (PTH) and PTH-related peptide
signaling through the parathyroid hormone receptor 1 (PTH1R) is fundamental to skeletal
development and metabolic bone remodeling, yet the intracellular mechanisms that ...
The mechanisms by which Wnt/β-catenin signaling regulates gene expression in a tissue-
and context-specific manner remain poorly understood, limiting our ability to target
the aberrant cell growth typical of many Wnt-driven cancers. Here, we focus on ...
Prions are self-templating assemblies of the host prion protein in which conformational
templating encodes heritable “strain” information. Human prion diseases, including
Creutzfeldt–Jakob disease (CJD), are rare but uniformly fatal neurodegenerative ...
Developmental Biology
Trophoblasts are multifunctional cells in the placenta and essential for normal pregnancy.
Although trophoblast dysfunction can cause pregnancy complications, the underlying
mechanisms remain unclear, and effective treatments are limited, partly because ...
Cell migration across epithelial barriers occurs in diverse developmental, immunological,
and pathological contexts. Here, we investigate the contribution of heterotypic adhesion
between migrating cells and epithelial “substrate” cells to transepithelial ...
Ecology
There is global consensus on the need to prioritize conservation efforts to prevent
biodiversity loss and defaunation. Most current conservation initiatives focus on
areas with high species diversity or many threatened species, treating species ...
The spread of invasive species poses a major threat to global biodiversity, yet predicting
successful establishment of exotic species in novel environments remains challenging.
Darwin’s naturalization conundrum is a longstanding debate over whether exotic ...
Environmental Sciences
Great Bear Lake (GBL), Great Slave Lake (GSL), and Lake Hazen in northern Canada have
recently experienced a shift in fundamental aquatic ecosystem processes associated
with accelerated Arctic warming. Multiple high-resolution, 210Pb-dated sediment ...
With diminishing availability of high-quality phosphate rock and increasing supply
uncertainties, improving phosphorus (P) recovery, recycling, and waste reduction has
become critical for sustaining agricultural production. We developed an integrated
P ...
Evolution
The domestic chicken exhibits extraordinarily high plumage diversity in sharp contrast
to the uniform plumage phenotype in its wild ancestor, the red junglefowl. The melanocortin-1 receptor (MC1R) locus is the most variable pigmentation locus in domestic ...
Many social insects respond to pathogens in ways that reduce pathogen transmission
within their social groups, with behaviors such as grooming or removing infected individuals.
This “social immunity” within a group has been compared to the immune response ...
Transfer RNAs (tRNAs) are among the few genes retained in animal mitochondrial genomes
after more than a billion years of gene loss. These ancient bacterial vestiges are
often structurally aberrant and less stable than their bacterial or cytosolic tRNA
...
Immunology and Inflammation
Systemic inflammation is accompanied by overwhelming neutrophil activation, resulting
in extensive formation of neutrophil extracellular traps (NETs). Although NETs are
beneficial for pathogen entrapment, they become detrimental; therefore, their ...
Medical Sciences
Joint effect of cancer-associated fibroblasts (CAFs) and regulatory T cells (Tregs)
can drive immunosuppression in high-grade serous ovarian cancer (HGSOC), thereby promoting
tumor metastasis and limiting the clinical benefit of PD-1/PD-L1 blockade. ...
Lung adenocarcinoma (LUAD) is the most common and deadly subtype of lung cancer, with
limited therapeutic options and poor prognosis. Ubiquitination is an important posttranslational
modification (PTM) that controls protein turnover, localization and ...
High-grade gliomas (HGGs) are aggressive brain tumors with poor prognosis, driven
in part by metabolic and epigenetic adaptations. Methionine metabolism supports HGG
growth by supplying S-adenosylmethionine for methylation reactions, yet how nutrient
...
Microbiology
CRISPR-Cas adaptive immunity systems provide defense against mobile genetic elements
and are often countered by diverse anti-CRISPR (Acr) proteins. The type IE CRISPR-Cas
of Escherichia coli K12 has been a model for structural and functional studies and ...
Diverse bacterial species utilize surface appendages called type IV pili (T4P) to
interact with their environment. These structures are dynamically extended and retracted
from the cell surface, which is critical for diverse functions. Some T4P systems ...
Mucosal-associated invariant T (MAIT) cells are among the most conserved and abundant
innate-like T cells in humans that recognize microbial-derived riboflavin precursors
and elicit potent antimicrobial responses. The foodborne pathogen Listeria ...
Campylobacter jejuni is an intestinal commensal of birds and animals and a leading cause of bacterial
diarrheal disease in humans. In hosts, C. jejuni primarily resides in the mucus layer atop the lower intestinal epithelium. Persistence
in this niche ...
The unyielding antigenic drift of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2), as well as the threat of future zoonotic sarbecovirus spillovers, has
prompted the search for broadly neutralizing antibodies (bNAbs) to inform rational
...
Only a minority of Helicobacter pylori (H. pylori)-infected individuals progress along Correa’s cascade, and classical virulence markers
do not fully explain this heterogeneity, motivating genome-wide approaches to quantify
strain-level genomic risk ...
Neuroscience
Our visual landscape consists of not only people, places, and objects (e.g., “soldier,”
“stadium,” “flag”) but also the conceptual relationships that unite them (e.g., “patriotism”).
Because conceptual knowledge varies across individuals, this level of ...
Oxytocin modulates social information processing by altering excitatory-inhibitory
balance at the microcircuit level, but how such local modulation gives rise to selective
processing at the level of distributed brain systems remains unclear. Here, we ...
Hippocampal circuits form cognitive maps that represent spatial position and integrate
contextual information, including affective cues, into episodic memory representations.
We investigated how spatial and affective information are combined in the ...
Targeting the cGAS–STING pathway mitigates Huntington disease pathogenesis in a knock-in mouse model
Cyclic GMP–AMP synthase (cGAS) and its downstream effector, stimulator of interferon
genes (STING), form a key cytosolic DNA-sensing pathway that drives innate immune
activation and proinflammatory signaling. We previously showed that cGAS is upregulated
...
Striatal-Enriched Protein Tyrosine Phosphatase (STEP) constrains synaptic potentiation
by dephosphorylating postsynaptic substrates, but its presynaptic role has remained
unclear. Here, we identify a previously unrecognized function of STEP in regulating
...
Psychedelic drugs are poised to become mainstream treatments, yet we lack a circuit-level
account of how they reshape brain activity. Emerging evidence suggests that multiple
psychedelic compounds modulate activity in the brain’s default mode network (DMN)...
Sleep need is associated with both circuit dynamics and widespread synaptic plasticity,
yet the specific synaptic changes underlying sleep homeostasis remain incompletely
understood. In Drosophila, sleep loss has been shown to trigger plasticity of the ...
Tip links connect the stereocilia of mechanosensory hair cells in the inner ear and
transmit force onto mechanotransduction (MET) channels. Tip links consist of protocadherin
15 (PCDH15) and cadherin 23, which assemble into an extracellular filament ...
Myelin is a defining feature of the vertebrate nervous system, yet the cellular and
molecular mechanisms governing its integrity remain poorly understood. Here, using
volume electron microscopy and a knock-in mouse line targeting newly formed ...
Mitochondria (Mito) engage in extensive communication with other organelles through
membrane contacts. Perturbed mitochondria–organelle interactions are indicated in
a variety of neurodegenerative diseases, but the underlying mechanisms remain poorly
...
Autophagy is a degradative process that maintains cellular homeostasis. Autophagy
biogenesis occurs at synapses, but its impact on synaptic functions is incompletely
understood. Here we show that, in Caenorhabditis elegans, synaptic ATG-9, the only ...
The extracellular matrix plays critical roles in orchestrating cell communication
and behaviors in response to various extracellular signals. It is a complex network
composed of proteins and polysaccharides, whose individual and synergistic roles in
...
Amyloid precursor protein (APP) is widely known for its role in Alzheimer’s disease
(AD) pathogenesis through its proteolytic processing into amyloid-β peptides. However,
its physiological functions remain incompletely understood. Here, we uncover a ...
Pharmacology
Tumor hypoxia promotes dedifferentiation and metabolic reprogramming in hepatocellular
carcinoma (HCC), undermining normal liver functions. Here, we identify the E3 ubiquitin
ligase RNF126 as a hypoxia-inducible “peroxisomal fate” switch that links the ...
G protein–coupled receptors (GPCRs) enable chemical communication between cells and
are involved in nearly all essential functions. They transduce signals via heterotrimeric
G proteins and are regulated by internalization, a process which redirects them ...
Physiology
Thin-strand pericytes cover the deepest reaches of the brain’s capillary network,
and their fine processes are intimately associated with adjacent endothelial cells
(ECs). Recent work has revealed that thin-strand pericytes contribute to electrical
...
Many marine organisms generate biominerals by endocytotic uptake of seawater which
is modified within calcifying cells to produce an amorphous mineral precursor required
to form the mineralized shell or skeleton. In this process, water must be removed
...
Hematopoiesis is tightly linked to an organism’s metabolic state, yet the molecular
sensors that convert nutrient availability into hematopoietic output remain poorly
understood. Here, we identify a fructose-sensitive gustatory receptor, BmGr9, as a
cell-...
Plant Biology
DNA double-strand break (DSB) repair is required to maintain genome integrity and
organismal fitness. This process occurs within chromatin and although accurate repair
requires extensive changes in chromatin structure and composition, chromatin effectors
...
Cellulose, a primary component of plant cell walls, is synthesized by cellulose synthase
complexes (CSCs) at the plasma membrane. Targeting this process with cellulose biosynthesis
inhibitors (CBIs) has significantly advanced our understanding of plant ...
The spatial organization of essential, nonessential, and toxic metal(loid) elements
(MEs) within plant cells underpins physiological function. Yet, comprehensive subcellular
imaging of the full ME spectrum remains challenging due to trade-offs among ...
Legume nodulation is initiated when soil bacteria rhizobia infect root hairs and is
tightly regulated by host-derived mechanisms that restrict nodule numbers to balance
the benefits of symbiotic nitrogen fixation with the plant’s growth and metabolic
...
Psychological and Cognitive Sciences
Animals rely on identity signaling to navigate social relationships, assess potential
mates, and avoid costly interactions. While species- and group-level recognition signals
can provide fitness advantages by preventing inbreeding depression and ...
The firmest evidence in favor of models that posit early high-level influences of
cognition on perception comes from electroencephalography (EEG). Enhanced early, preattentive
processing of light and dark blue feature changes compared to light and dark ...
Sustainability Science
Rapid agricultural expansion has driven forest loss worldwide. Deforestation reduces
evaporation, potentially decreasing precipitation and crop yields far beyond agricultural
frontiers. Here, we quantified the teleconnection impacts of Amazon ...
Does swidden agriculture, a prototypical coupled human and natural system, exhibit
a process of adaptive self-organization in which cultural practices balance environmental
constraints through adaptive feedback? Here, we investigate whether quantitative ...
There is global consensus on the need to prioritize conservation efforts to prevent
biodiversity loss and defaunation. Most current conservation initiatives focus on
areas with high species diversity or many threatened species, treating species ...
Corrections
Cover image: Pictured are Indo-Pacific bottlenose dolphins in Shark Bay in Western Australia. Alice Bouchard et al. conducted sound playback experiments to explore how female bottlenose dolphins react to the identity signals of individual males. Reproductively available female dolphins showed a strong aversion to the identity signals of males with high rates of coercive behavior. According to the authors, the finding suggests that female dolphins track male behavior and use such social knowledge to guide mate choice. See the article by Bouchard et al. e2531602123. Image credit: Shark Bay Dolphin Research/Stephanie L. King.
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