Table Of Contents Page, PNAS Volume 122, Number 37
Lasker Awards 2025
Simple reductionist systems can serve as powerful catalysts for unlocking complex
innovations in science and art. The evolution from simplicity to complexity is illustrated
by the career journeys of the scientist Earl W. Sutherland, who discovered cyclic
...
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Up to 10 to 20% of the proteome contains regions with much lower amino acid diversity
than would be expected by chance. This year’s Lasker Basic Science Award is given
to Steven McKnight and Dirk Görlich for their pioneering work on such low-complexity
...
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The 2025 Lasker~DeBakey Clinical Medical Research Award has been given to Michael
Welsh, Jesús (Tito) González, and Paul Negulescu for their key roles in developing
a novel treatment for cystic fibrosis (CF)—a three-drug combination that saves the
lives ...
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Scientists can contribute to society in numerous ways. Some scientists discover new
biological principles and found entirely new fields. Some scientists are inspiring
mentors and create the next generation of inclusive lab leaders. Some scientists are
...
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This Week in PNAS
Opinion
Commentary
Perspective
Antarctic krill (Euphausia superba) is the central prey species in the Southern Ocean food web, supporting the largest
and fastest-growing fishery in the region, managed by the Commission for the Conservation
of Antarctic Marine Living Resources (CCAMLR). ...
Letter
Brief Report
Animals can improve their decision-making abilities by integrating information from
multiple senses, which is especially beneficial when living in fluctuating environments.
However, understanding how wild predators may use multimodal sensing when hunting
...
Physical Sciences
Applied Mathematics
Inferring dynamical models from data continues to be a significant challenge in computational
biology, especially given the stochastic nature of many biological processes. We explore
a common scenario in omics, where statistically independent cross-...
Applied Physical Sciences
We present a geometric design rule for size-controlled clustering of self-propelled
particles. We show that active particles that tend to rotate under an external force
have an intrinsic, signed parameter with units of curvature which we call curvity,
...
Many essential cellular processes, including cell division and the establishment of
cell polarity during embryogenesis, are regulated by pattern-forming proteins. These
proteins often need to bind to a substrate, such as the cell membrane, onto which
they ...
Programmable self-assembly has recently enabled the creation of complex structures
through precise control of the interparticle interactions and the particle geometries.
Targeting ever more structurally complex, dynamic, and functional assemblies ...
Many soft, tough materials have emerged in recent years, paving the way for advances
in wearable electronics, soft robotics, and flexible displays. However, understanding
the interfacial fracture behavior of these materials remains a significant challenge,...
Turbulent convection governs heat transport in both natural and industrial settings,
yet optimizing it under extreme conditions remains a significant challenge. Traditional
control strategies, such as predefined temperature modulation, struggle to achieve
...
The sliding motion of aqueous droplets on hydrophobic surfaces leads to charge separation
at the trailing edge, with implications from triple-line friction to hydrovoltaic
energy generation. Charges deposited on the solid surface have been attributed to
...
Despite periods of permanent darkness and extensive ice coverage in polar environments,
photosynthetic ice diatoms display a remarkable capability of living inside the ice
matrix. How these organisms navigate such hostile conditions with limited light and
...
Biophysics and Computational Biology
During wound healing, tumor growth, and organ formation, epithelial cells migrate
and cluster in layered tissue environments. Although cellular mechanosensing of adhered
extracellular matrices is now well recognized, it is unclear how deeply cells sense
...
The self-organization of cortical microtubule (MT) arrays within plant cells is an
emergent phenomenon with important consequences for the synthesis of the cell wall,
cell shape, and subsequently the structure of plants. Mathematical modeling and ...
We analyzed the patterns of transmission in the 2022 clade IIb mpox epidemic as it
unfolded in the European population of men who have sex with men (MSM). We developed
an agent-based model that simulates sexual pair formation, incorporating both brief
and ...
Chemistry
Multivalent binding and the resulting dynamical clustering of receptors and ligands
are known to be key features in biological interactions. For optimizing biomaterials
capable of similar dynamical features, it is essential to understand the first step
of ...
Aqueous sodium-ion batteries (ASIBs) are gaining attention for their inherent safety
and the use of abundant sodium resources. Bismuth (Bi) anode, with its high theoretical
capacity and low cost, enhances the performance and competitiveness of ASIBs in ...
We applied micro-computed tomography, high-resolution cryo-scanning electron microscopy
(SEM) combined with cathodoluminescence, and cryo-focused ion beam Milling-SEM to
perform three-dimensional imaging of human atherosclerotic tissues with tens of ...
Computer Sciences
We propose a theoretical framework and a cost-effective automated method for the interpretation
of prosodic messages (e.g., chunking of information, emphasis, conversation action,
emotion). At the core of the proposal is a hierarchy of layered prosodic ...
Engineering
The biophysical properties of single cells are crucial for understanding cellular
function and behavior in biology and medicine. However, precise manipulation of cells
in 3-D microfluidic environments remains challenging, particularly for heterogeneous
...
Engineering functional exosomes represents a cutting-edge approach in biomedicine,
holding the promise to transform targeted therapy. However, challenges such as achieving
consistent modification and scalability have limited their wider adoption. Herein,
...
Low-cost yet high-performance structural materials have been invariantly sought for
modern engineering applications. However, due to the localized stress concentration
induced by a high Peierls-Nabarro stress and limited dislocation mobility, increasing
...
Environmental Sciences
Aquatic microorganisms typically inhabit a heterogeneous resource landscape, composed
of localized and transient patches. To effectively exploit these resources, they have
evolved a wide range of feeding strategies that combine chemotactic motility with
...
The streams of Alaska’s Brooks Range lie within a vast (~14M ha) tract of protected
wilderness and have long supported both resident and anadromous fish. However, dozens
of historically clear streams have recently turned orange and turbid. Thawing ...
Physics
The iron-based high-
We analyze the spin-glass transition in a field in finite dimension
Statistics
Diversified economies are critical for cities to sustain their growth and development,
but they are also costly because diversification often requires expanding a city’s
capability base. We analyze how cities manage this trade-off by measuring the ...
Sustainability Science
We model the effect of plug-in electric vehicle (EV) adoption on U.S. power system
generator capacity investment, operations, and emissions through 2050 by estimating
power systems outcomes under a range of EV adoption trajectory scenarios. Our EV ...
Social Sciences
Economic Sciences
We model the effect of plug-in electric vehicle (EV) adoption on U.S. power system
generator capacity investment, operations, and emissions through 2050 by estimating
power systems outcomes under a range of EV adoption trajectory scenarios. Our EV ...
Diversified economies are critical for cities to sustain their growth and development,
but they are also costly because diversification often requires expanding a city’s
capability base. We analyze how cities manage this trade-off by measuring the ...
Environmental Sciences
Climate change is expected to pose significant threats to public health, particularly
vector-borne diseases. Despite dramatic recent increases in dengue that many anecdotally
connect with climate change, the effect of anthropogenic climate change on ...
Psychological and Cognitive Sciences
We propose a theoretical framework and a cost-effective automated method for the interpretation
of prosodic messages (e.g., chunking of information, emphasis, conversation action,
emotion). At the core of the proposal is a hierarchy of layered prosodic ...
Behaviorally informed “nudges” are widely used in government outreach but are often
seen as too modest to address poverty at scale. In four field experiments over 2 y
(n = 542,804 low-income households), we test whether more proactive communication, ...
Social Sciences
Typically, people perform actions in a valenced—positive or negative—way, depending
on their attitudes or desires. These forms of action are named vitality forms (VFs).
While it is well established that action goals are mediated by a parieto-frontal ...
The transmission of communicable diseases in human populations is known to be modulated
by behavioral patterns. However, detailed characterizations of how population-level
behaviors change over time during multiple disease outbreaks and spatial ...
Biological Sciences
Applied Biological Sciences
Multivalent binding and the resulting dynamical clustering of receptors and ligands
are known to be key features in biological interactions. For optimizing biomaterials
capable of similar dynamical features, it is essential to understand the first step
of ...
The biophysical properties of single cells are crucial for understanding cellular
function and behavior in biology and medicine. However, precise manipulation of cells
in 3-D microfluidic environments remains challenging, particularly for heterogeneous
...
Biochemistry
The P2X2 receptor (P2X2R) is a slowly desensitizing adenosine triphosphate (ATP)-gated
ion channel that is highly expressed in the cochlea. When mutated, the P2X2R exacerbates
age- and noise-related hearing loss, but selective modulators of the receptor ...
Rad51 catalyzes the DNA pairing reactions that take place during homologous recombination
(HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes.
Rad54 is an ATP-dependent DNA motor protein that stimulates Rad51 activity ...
Improving the Calvin–Benson–Bassham cycle enzyme Ribulose 1,5-bisphosphate carboxylase/oxygenase
(Rubisco) has the potential to increase crop productivity. However, the selectivity
of the chaperones mediating Rubisco assembly in vascular plants toward ...
Replication of cellular chromosomes requires a primase to generate short RNA primers
to initiate genomic replication. While bacterial and archaeal primase generate short
RNA primers, the eukaryotic primase, Polα-primase, contains both RNA primase and DNA
...
Biophysics and Computational Biology
We present a geometric design rule for size-controlled clustering of self-propelled
particles. We show that active particles that tend to rotate under an external force
have an intrinsic, signed parameter with units of curvature which we call curvity,
...
Inferring dynamical models from data continues to be a significant challenge in computational
biology, especially given the stochastic nature of many biological processes. We explore
a common scenario in omics, where statistically independent cross-...
Despite periods of permanent darkness and extensive ice coverage in polar environments,
photosynthetic ice diatoms display a remarkable capability of living inside the ice
matrix. How these organisms navigate such hostile conditions with limited light and
...
Cell Biology
Adrenal lipomas are benign tumors containing ectopic adipose tissue in the adrenal
gland, an organ that normally lacks both adipocytes and their progenitors. The origin
of this ectopic fat remains enigmatic, and the absence of a genetic animal model has
...
The β2-adrenergic receptor (β2AR), a prototype G protein–coupled receptor, controls cardiopulmonary function underpinning
O2 delivery. Abundance of the β2AR is canonically regulated by G protein–coupled receptor kinases and β-arrestins,
but neither ...
Developmental Biology
Chimaeras (Holocephali) are an understudied group of mostly deep-ocean cartilaginous fishes (Chondrichthyes) with unique characteristics that distinguish them from their distant relatives,
sharks, skates, and rays. Unlike sharks, chimaeras lack scales and ...
Ecology
Climate change is expected to pose significant threats to public health, particularly
vector-borne diseases. Despite dramatic recent increases in dengue that many anecdotally
connect with climate change, the effect of anthropogenic climate change on ...
Vegetation phenology, i.e., seasonal biological events such as leaf-out and leaf-fall,
regulates local climate through biophysical processes like evapotranspiration (ET)
and albedo. However, the net surface temperature impact of these processes—whether
ET ...
The size and composition of local species pools are, in part, determined by past dispersal
events. Predicting how communities respond to future disturbances, such as fluctuating
environmental conditions, requires knowledge of such histories. We assessed ...
Microscale symbioses can be critical to ecosystem functions, but the mechanisms of
these interactions in nature are often cryptic. Here, we use a combination of stable
isotope imaging and tracing to reveal carbon (C) and nitrogen (N) exchanges among
three ...
Environmental Sciences
The streams of Alaska’s Brooks Range lie within a vast (~14M ha) tract of protected
wilderness and have long supported both resident and anadromous fish. However, dozens
of historically clear streams have recently turned orange and turbid. Thawing ...
Evolution
Organisms often face multiple selective pressures simultaneously (e.g., mine tailings
with multiple heavy metal contaminants), yet we know little about when adaptation
to one stressor provides cross-tolerance or cross-intolerance to other stressors.
To ...
Color polymorphism can influence the evolutionary fate of cryptic species because
it increases populations’ chances of survival in heterogenous or variable environments.
Yet, little is known about the molecular and evolutionary mechanisms underlying the
...
The origin and phylogenetic distribution of symbiotic associations between nodulating
angiosperms and nitrogen-fixing bacteria have long intrigued biologists. Recent comparative
evolutionary analyses have yielded alternative hypotheses: a multistep ...
Genetics
Following encounter with an unrepaired DNA lesion, replication is halted and can restart
downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA)
gap. To complete replication, this ssDNA gap is filled in by one of the two lesion
...
Ovulation is an intricate process that is essential for reproductive success. In Drosophila melanogaster, ovulation increases after mating. This increase is initiated by the male seminal
fluid protein ovulin and is executed by female pathways, including ...
The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on
REV1’s ability to recruit inserter TLS polymerases and the POLζ extender polymerase,
enables cancer cells to bypass DNA lesions while introducing mutations that likely
...
Genetic variation within intron 3 of the CACNA1C calcium channel gene is associated with schizophrenia and other neuropsychiatric
disorders, but analysis of the causal variants and their effect is complicated by
a nearby variable-number tandem repeat (...
Immunology and Inflammation
MS4A4A belongs to the MS4A tetraspan protein superfamily and is selectively expressed
by the monocyte–macrophage lineage. In this study, we aimed to evaluate the role of
MS4A4A+ macrophages in rheumatoid arthritis (RA) pathogenesis and response to ...
High-mobility group box protein 1 (HMGB1) is a chromatin-associated nonhistone protein
widely distributed in the nucleus of eukaryotic cells. It is transported extracellularly
as a proinflammatory mediator or late warning protein to induce immune and ...
Innate B-1 cells constitute a self-maintained layer of defense for early detection
of bacteria, clearance of apoptotic cell debris, and removal of autoantigens driving
autoimmunity. B-1 cells are originated from fetal tissues, but, as opposed to B-2
cells,...
Medical Sciences
Ocular fibrosis, a severe consequence of excessive retinal wound healing, can lead
to vision loss following retinal injury. Proliferative vitreoretinopathy (PVR), a
common form of ocular fibrosis, is a major cause of blindness, characterized by the
...
The onset of puberty is increasingly observed at earlier ages in children, especially
in girls with obesity, a trend that predisposes them to long-term metabolic and reproductive
disorders in adulthood. Bile acids have emerged as pivotal signaling ...
Proliferative retinopathy is a leading cause of irreversible blindness in humans;
however, the molecular mechanisms behind the immune cell–mediated retinal angiogenesis
remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced
...
Microscopic examination of biopsy tissues remains essential for cancer diagnosis,
despite advancements in sequencing technologies. Alterations in nuclear size or the
nuclear-to-cytoplasmic ratio are hallmark features of cancer cells and often correlate
...
Microbiology
Influenza A virus (IAV) infection causes significantly greater morbidity and mortality
in the elderly population, but the molecular mechanisms in the aging process responsible
for severe infection remain unclear. In this study, we found that increased ...
A frequent goal of phage biology is to quantify how well a phage kills a population
of host bacteria. Unfortunately, traditional methods to quantify phage success can
be time-consuming, limiting the throughput of experiments. Here, we use theory to
show ...
In eukaryotic systems, three major types of cell junctions have been well characterized.
While bacterial adhesion mechanisms also exhibit remarkable diversity, the molecular
processes that regulate the dynamic modulation of binding strength between ...
Hydrogen sulfide production is a characteristic that distinguishes Salmonella serovars from closely related species, such as Escherichia coli, but its biological significance remains obscure. Here, we show that PhsABC and AsrABC-mediated
hydrogen sulfide ...
Neuroscience
Typically, people perform actions in a valenced—positive or negative—way, depending
on their attitudes or desires. These forms of action are named vitality forms (VFs).
While it is well established that action goals are mediated by a parieto-frontal ...
Although clinical research has revealed microglia-related inflammatory and immune
responses in bipolar disorder (BD) patient brains, it remains unclear how microglia
contribute to the pathogenesis of BD. Here, we demonstrated that Serinc2 is associated
...
Learning when to initiate or withhold actions is essential for survival, requiring
the integration of past experiences with new information to adapt to changing environments.
The prelimbic cortex (PL) plays a central role in this process, with a stable PL ...
Retinal ganglion cells (RGCs) are highly compartmentalized neurons whose long axons
serve as the sole connection between the eye and the brain. In both injury and disease,
RGC degeneration occurs in a similarly compartmentalized manner, with distinct ...
Excitatory glycine receptors (eGlyRs), composed of the glycine-binding NMDA receptor
subunits GluN1 and GluN3A, have recently emerged as a novel neuronal signaling modality
that challenges the traditional view of glycine as an inhibitory neurotransmitter.
...
Major depressive disorder affects millions worldwide, yet current treatments require
prolonged administration. In contrast, ketamine produces rapid antidepressant effects
by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts
...
In vivo voltage imaging is a powerful tool for monitoring action potentials and dynamic
electrical events in heterogeneous sensory neurons enabling the deciphering of rapid
somatosensory information processing. Virus-driven expression of genetically ...
Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function
has detrimental effects on neuronal circuit health. Neuroinflammation contributes
to the onset and progression of neurodegenerative diseases, including Alzheimer’s
...
Pharmacology
Agonist-induced interaction of G protein–coupled receptors (GPCRs) with β-arrestins
(βarrs) is a critical mechanism that regulates the spatiotemporal pattern of receptor
localization and signaling. While the underlying mechanism governing GPCR–βarr ...
Physiology
All organisms are exposed to various stressors, which can sometimes lead to organismal
death, depending on their intensity. While stress-induced organismal death has been
observed in many species, the underlying mechanisms remain unclear. In this study,
...
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a voltage-gated
cation channel that plays a crucial role in regulating cellular excitability, especially
in cardiac pacemaker cells and neurons. Its dysregulation is linked to heart ...
Plant Biology
The self-organization of cortical microtubule (MT) arrays within plant cells is an
emergent phenomenon with important consequences for the synthesis of the cell wall,
cell shape, and subsequently the structure of plants. Mathematical modeling and ...
The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions
in immune and cell death responses across the Tree of Life. TIR domains encoded by
plants and prokaryotes function as enzymes to produce diverse small molecule immune
...
How or whether organisms can inherit parental adaptations to the prevailing environment
is a major topic in biology. In plants, seed traits such as size, yield, and dormancy
are all affected by the environment during reproduction, but whether developing ...
Organisms use circadian clocks to synchronize physiological processes to anticipate
the Earth’s day-night cycles and regulate responses to environmental signals to gain
competitive advantage. While divergent genetic clocks have been studied extensively
in ...
Population Biology
We analyzed the patterns of transmission in the 2022 clade IIb mpox epidemic as it
unfolded in the European population of men who have sex with men (MSM). We developed
an agent-based model that simulates sexual pair formation, incorporating both brief
and ...
Psychological and Cognitive Sciences
The transmission of communicable diseases in human populations is known to be modulated
by behavioral patterns. However, detailed characterizations of how population-level
behaviors change over time during multiple disease outbreaks and spatial ...
Corrections
Cover image: Pictured are a brown and a green African grass frog (Ptychadena nana) in the Southeastern Ethiopian Highlands. Sandra Goutte and Stéphane Boissinot explored the evolutionary and molecular mechanisms behind the simultaneous occurrence of green and brown cryptic, or camouflaging, color morphs within individual frog species. The authors found that cryptic color polymorphism in frogs can persist for millions of years and is associated with increased rates of speciation and habitat shifts. The results suggest that cryptic color polymorphism can promote dispersal into new ecological niches and enhance population persistence under changing environmental conditions. See the article by Goutte and Boissinot e2425898122. Image credit: Sandra Goutte.
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