Table Of Contents Page, PNAS Volume 122, Number 20
This Week in PNAS
QnAs
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Retrospective
Floyd E. Bloom, M.D. was a prominent leader and spokesperson for the neuroscience
and broader scientific communities; sadly, Floyd passed away on January 8, 2025. His
scientific contributions were focused on multidisciplinary characterizations of ...
Commentaries
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Perspective
Geological observations informed by climate dynamics imply that the oceans were 99.9%
covered by light-blocking ice shelves during two discrete, self-reversing Snowball
Earth epochs spanning a combined 60 to 70 Myr of the Cryogenian Period (720 to 635
Ma)...
Letters
Brief Reports
Substance use disorders disrupt the dopaminergic system of the human brain, which
plays a central role in movement and reward processing, altering perception, and cognition.
The pleasurable urge to move to music, known as groove, relies on dopamine for ...
Squash is a widely popular racket sport, practiced by millions of people worldwide,
played inside a walled court. When played well, players can last for several minutes
before the ball bounces twice on the floor. There is, however, an unanswerable shot.
...
Humans differ in their levels of aversive (“dark”) personality traits such as egoism
or psychopathy. Building upon theories suggesting that socioecological factors coshape
the development of personality traits, it can be predicted that prior aversive ...
In 2022, the US Supreme Court overturned the constitutional protection of abortion
rights established in Roe v. Wade. In doing so, Dobbs v. Jackson Women’s Health Organization moved status quo on abortion policy more into line with the Republican Party’s ...
Physical Sciences
Applied Mathematics
Nonlinear dynamical systems are ubiquitous in nature and they are hard to forecast.
Not only they may be sensitive to small perturbations in their initial conditions,
but they are often composed of processes acting at multiple scales. Classical approaches
...
Buckling in compression is the archetype of elastic instability: when compressed along
its longest dimension, a thin structure such as a playing card will buckle out-of-plane
accommodating the imposed compression without a significant change of length. ...
Applied Physical Sciences
Evaporation of sessile multicomponent droplets is ubiquitous in many common processes,
such as printing, cooling, and coating. The evaporation rate is not evenly distributed
across the surface of the droplet. As a result, there are regions with high ...
The ability to coherently manipulate phonons through light permits cooling and heating
microscale quantum systems for various critical fields in metrology, information processing,
and sensing. However, these physical systems often are hard to isolate and ...
Using pulsed-power magnetic field sources to compress gallium to gigapascal pressures
on nanosecond timescales, we report here experiments on shockless dynamic compression
of a liquid metal. Time-resolved velocimetry data reveal signatures of rapid ...
In the insect realm, liquids become traps due to capillary and viscous forces dominant
at their scale. Yet, aphids handle the highly viscous honeydew droplets they secrete
by coating them with hydrophobic wax powder which maintains an air layer between ...
Critical to their survival, natural organisms have developed exoskeletons that can
withstand and inflict damage over their lifetime. The Bouligand structure of the exoskeleton
plays a key role in toughness and damage resistance under external impacts. ...
Biophysics and Computational Biology
Caveolin is a monotopic integral membrane protein, widely expressed in metazoans and
responsible for constructing enigmatic membrane invaginations known as caveolae. Recently,
the high-resolution structure of a purified human caveolin assembly, the CAV1-...
Photosystem II (PSII) is a protein–pigment complex that utilizes sunlight to catalyze
water oxidation and plastoquinone reduction, initiating the electron transfer (ET)
cascade in oxygenic photosynthesis. The D1 and D2 proteins are the most important
...
Collagen has been evolutionarily selected as the preferred building block of extracellular
structures. Despite inherent thermodynamic instability of individual proteins at body
temperature, collagen manages to assemble into higher-order structures that ...
Ewing sarcoma (EwS) is an aggressive cancer of bone and soft tissue that predominantly
affects children and young adults. A chromosomal translocation joins the low-complexity
domain (LCD) of the RNA-binding protein EWS (EWSLCD) with the DNA-binding domain ...
Oxygen is crucial for mitochondrial energy production in neurons and is efficiently
stored and transported within the hydrophobic core of phospholipid bilayers. Using
a diffusive model derived from molecular dynamics simulations, we demonstrate that
...
The bacterial transcriptional regulator RfaH comprises structurally and functionally
distinct N- (NTD) and C- (CTD) terminal domains. The latter switches from a helical
hairpin packed against the NTD to a five-stranded β-roll upon displacement by RNA
...
Animal behavior can be decomposed into a sequence of discrete activity bouts over
time. Analyzing the statistical structure of such behavioral sequences can provide
insights into the drivers of behavioral decisions. Laboratory studies, predominantly
in ...
Myosin is the primary motor protein in skeletal muscle, responsible for adenosine
triphosphate (ATP) hydrolysis that drives muscle contraction. In addition to force
production, resting myosin consumes ATP in futile cycles at two rates, the slower
one ...
Chemistry
A kinetic model coupling prebiotically plausible synthesis of enantioenriched proteinogenic
amino acids with catalytic peptide ligation leads to an autocatalytic network that
may exhibit symmetry breaking and chiral amplification, providing a feasible ...
Computer Sciences
Large language models (LLMs) show emergent patterns that mimic human cognition. We
explore whether they also mirror other, less deliberative human psychological processes.
Drawing upon classical theories of cognitive consistency, two preregistered studies
...
Earth, Atmospheric, and Planetary Sciences
The global energy budget is fundamental for understanding climate change. It states
that the top-of-atmosphere imbalance between radiative forcing (which drives climate
change) and radiative response (which resists the forcing) equals energy storage in
...
Desert surfaces are typically nonuniform, with individual sand dunes generally surrounded
by gravel or nonerodible beds. Similarly, beaches vary in composition and moisture
that enhances cohesion between the grains. These bed heterogeneities affect the ...
The Great Oxidation Event (GOE) represents a major shift in Earth’s surficial redox
balance. Delineating the driver(s) and tempo of the GOE and its impact on microbial
evolution and biogeochemistry can be aided by characterizing the cycling of redox-...
The interaction between interplanetary shocks or planetary bow shock and upstream
magnetohydrodynamics (MHD) waves (hereafter referred to as wave–shock interactions)
is of fundamental importance to plasma physics. Linear waves and shocks, which are
...
Engineering
Delivering biomedicines to specific sites of disease using remote-controlled devices
is a long-standing vision in biomedical research. However, most existing externally
triggered delivery systems are based on complex micromachines that are controlled
with ...
Distribution networks, with large-scale integration of distributed renewable resources,
particularly rooftop solar photovoltaic systems, represent the most extensive yet
vulnerable components of modern electric power systems during climate extremes such
...
Material-to-system tailored multilayer-cyclic strategy toward practical atmospheric water harvesting
Solar-driven atmospheric water harvesting (AWH) presents a sustainable approach for
freshwater production with sunlight as the sole energy input. To address challenges
posed by diurnal moisture variations and diffusive sunlight, we present a system-wide
...
Environmental Sciences
Breast milk is crucial for infant health, offering essential nutrients and immune
protection. However, despite increasing exposure risks from nanoparticles (NPs), their
potential infiltration into human breast milk remains poorly understood. This study
...
Mathematics
We show that, in the space of all totally real fields equipped with the constructible
topology, the set of fields that admit a universal quadratic form, or have the Northcott
property, is meager. The main tool is a theorem on the number of square classes ...
Physics
We employ a family of ancilla qubit variational wave functions [Y.-H. Zhang and S.
Sachdev, Phys. Rev. Res. 2, 023172 (2020)] to describe the polaronic correlations in the pseudogap metal phase
of a hole-doped 2D Fermi–Hubbard model. Comparison to ...
Statistics
The distribution of personal names provides unique, yet often overlooked, insight
into modern and historical societies. This study employs diversity statistics—commonly
used in ecology—to analyze onomastic data from Iron Age II archaeological excavations
...
Sustainability Science
Distribution networks, with large-scale integration of distributed renewable resources,
particularly rooftop solar photovoltaic systems, represent the most extensive yet
vulnerable components of modern electric power systems during climate extremes such
...
Social Sciences
Anthropology
The distribution of personal names provides unique, yet often overlooked, insight
into modern and historical societies. This study employs diversity statistics—commonly
used in ecology—to analyze onomastic data from Iron Age II archaeological excavations
...
This study presents the results of geochemical compositional analysis through portable
X-ray fluorescence of 788 artifacts from the Templo Mayor in Mexico City. The results
reveal that the Mexica (Aztecs) preferred green obsidian from Sierra de Pachuca. ...
Evidence across a broad range of disciplines has demonstrated how individuals’ social
environments can impact their health, lifespan, reproduction, and ultimately their
evolutionary fitness. Past research has primarily focused on either traits specific
to ...
Over the past few decades, studies have provided strong evidence that the robust links
between the social environment, health, and survival found in humans also extend to
nonhuman social animals. A number of these studies emphasize the early life origins
...
Environmental Sciences
The adoption of information and communication technology (ICT) by rural–urban migrants
is reshaping job-search mobility, significantly shaping city-level workforce geographical
diversity. This study provides compelling evidence of ICT’s impact by ...
Political Sciences
After many elections, the accuracy of the vote count is assessed by retabulating a
small percentage of ballots. These audits form one of the richest bodies of evidence
regarding electoral legitimacy, which is particularly important in democracies where
...
Psychological and Cognitive Sciences
Large language models (LLMs) show emergent patterns that mimic human cognition. We
explore whether they also mirror other, less deliberative human psychological processes.
Drawing upon classical theories of cognitive consistency, two preregistered studies
...
Previous studies on fear extinction have primarily focused on repeated exposure to
fear-inducing context without negative consequences. However, it is also possible
that an individual can reduce fear responses by predicting that they can transition
to a ...
Mitigating climate change requires urgent action at individual, collective, and institutional
levels. However, individuals may fail to act because they perceive climate change
as a threat that is distant or not personally relevant, or believe their ...
Social Sciences
While most people believe that women (vs. men) experience more discriminatory treatment
at work, especially in male-dominated professions, relatively few women report experiencing
such treatment themselves. These low levels of reporting may arise either ...
Sustainability Science
Efforts to anticipate and adapt to future climate can benefit from historical experiences.
We examine agroclimatic conditions over the past 50 y for five major crops around
the world. Most regions experienced rapid warming relative to interannual ...
Biological Sciences
Agricultural Sciences
Efforts to anticipate and adapt to future climate can benefit from historical experiences.
We examine agroclimatic conditions over the past 50 y for five major crops around
the world. Most regions experienced rapid warming relative to interannual ...
Delivering biomedicines to specific sites of disease using remote-controlled devices
is a long-standing vision in biomedical research. However, most existing externally
triggered delivery systems are based on complex micromachines that are controlled
with ...
Vetiver (Vetiveria zizanioides) is highly attractive to the rice stem borer (Chilo suppressalis, RSB) and is widely utilized as a trap plant for RSB control in East Asia. However,
the underlying mechanism driving this high level of attractiveness remains ...
Applied Biological Sciences
The gut microbiota influences systemic immunity and the function of distal tissues,
including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota
in the foreign body response and fibrosis is largely unexplored. To investigate ...
Aberrant expression of lysine-specific demethylase 1 (LSD1) has been implicated in
various cancers, including acute myeloid leukemia (AML). Recent studies have revealed
both catalytic and noncatalytic oncogenic functions of LSD1, which cannot be ...
Biochemistry
Collagen has been evolutionarily selected as the preferred building block of extracellular
structures. Despite inherent thermodynamic instability of individual proteins at body
temperature, collagen manages to assemble into higher-order structures that ...
Only two nonvisual arrestins recognize many hundreds of different, intracellularly
phosphorylated G protein-coupled receptors (GPCRs). Due to the highly dynamic nature
of GPCR•arrestin complexes, the critical determinants of GPCR–arrestin recognition
have ...
Found from bacteria to humans, small heat shock proteins (sHSPs) are the least understood
protein chaperones. HSPB5 (or αB-crystallin) is among the most widely expressed of
the 10 human sHSPs, including in muscle, brain, and eye lens where it is ...
Gating in voltage-dependent ion channels is regulated by the transmembrane voltage.
This form of regulation is enabled by voltage-sensing domains (VSDs) that respond
to transmembrane voltage differences by changing their conformation and exerting force
on ...
Prostaglandin E2 (PGE2) mediates diverse physiological processes through four G protein–coupled receptor
subtypes (EP1–EP4). While structures of EP2, EP3, and EP4 have been determined, the
structural basis for PGE2 recognition and activation of the EP1 ...
MEX-5 regulates the formation and dissolution of P granules in Caenorhabditis elegans embryos, yet the thermodynamic basis of its activity remains unclear. Here, using
a time-resolved in vitro reconstitution system, we show that MEX-5 dissolves ...
Schnyder corneal dystrophy (SCD) is a rare autosomal dominant condition characterized
by the opacification of the cornea owing to the abnormal deposition of cholesterol.
SCD-associated mutations have been identified in the gene encoding UbiA ...
Biophysics and Computational Biology
Caveolin is a monotopic integral membrane protein, widely expressed in metazoans and
responsible for constructing enigmatic membrane invaginations known as caveolae. Recently,
the high-resolution structure of a purified human caveolin assembly, the CAV1-...
Ewing sarcoma (EwS) is an aggressive cancer of bone and soft tissue that predominantly
affects children and young adults. A chromosomal translocation joins the low-complexity
domain (LCD) of the RNA-binding protein EWS (EWSLCD) with the DNA-binding domain ...
Oxygen is crucial for mitochondrial energy production in neurons and is efficiently
stored and transported within the hydrophobic core of phospholipid bilayers. Using
a diffusive model derived from molecular dynamics simulations, we demonstrate that
...
The bacterial transcriptional regulator RfaH comprises structurally and functionally
distinct N- (NTD) and C- (CTD) terminal domains. The latter switches from a helical
hairpin packed against the NTD to a five-stranded β-roll upon displacement by RNA
...
The northern white rhinoceros (NWR; Ceratotherium simum cottoni) is functionally extinct, with only two nonreproductive females alive. Efforts to
rescue the NWR from its inevitable demise have inspired the exploration of unconventional
conservation ...
Intermolecular interactions underlie all cellular functions, yet visualizing these
interactions at the single-molecule level remains challenging. Single-molecule localization
microscopy (SMLM) offers a potential solution. Given a nanoscale map of two ...
Intensely contracting fast skeletal muscle rapidly loses the ability to generate force,
due in part to the accumulation of phosphate (Pi) inhibiting myosin’s force-generating capacity, in a process that is strain dependent.
Crucial aspects of the ...
Voltage-gated Nav1.5 channels are central to the generation and propagation of cardiac action potentials.
Aberrations in their function are associated with a wide spectrum of cardiac diseases
including arrhythmias and heart failure. Despite decades of ...
Cell Biology
New immunosenescence targets for preventing senescence-associated pathological cardiac
hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically
aged human and mouse samples, the IL-17A level increased with physiological aging,
...
Homologous proteins share similar sequences, enabling them to work together in cells
to support normal physiological functions. Phosphatidylserine synthases 1 and 2 (PSS1
and PSS2) are homologous enzymes that catalyze the synthesis of phosphatidylserine
(...
In human acute myeloid leukemia (AML), mutations of isocitrate dehydrogenase-1 (IDH1) often co-occur with NPM1 mutations, and less frequently with FLT3 mutations. To investigate whether the effects of IDH1 mutation differ according to the specific co-...
Developmental Biology
Intercalated cells (ICs) in the mammalian kidney regulate circulatory pH through IC
subtype–restricted actions of bicarbonate transporters: pH is elevated by Slc4a1 restricted
to type A-ICs (A-ICs) and depressed by Slc26a4 in type B-IC (B-ICs). NonA-nonB-...
While paradigms for patterning of cell fates in development are well established,
paradigms for patterning morphogenesis, particularly when organ shape is influenced
by the extracellular matrix (ECM), are not. Morphogenesis of the Drosophila egg chamber (...
The switch from precursor cell proliferation to onset of differentiation in adult
stem cell lineages must be carefully regulated to produce sufficient progeny to maintain
and repair tissues, yet prevent overproliferation that may enable oncogenesis. In
...
Ecology
Animal behavior can be decomposed into a sequence of discrete activity bouts over
time. Analyzing the statistical structure of such behavioral sequences can provide
insights into the drivers of behavioral decisions. Laboratory studies, predominantly
in ...
Climate change is significantly impacting the geographic range of many animal species
and their associated microorganisms, hence influencing emergence of vector-borne diseases.
Mosquito-borne viruses represent a potential major reservoir of human ...
The availability of nitrogen (N) and phosphorus (P) is essential for soil microbial
activity and growth, yet global patterns of N and P limitation in soil microbial metabolism
remain largely unknown. We modeled ecoenzyme stoichiometry data from 5,259 ...
Environmental Sciences
Breast milk is crucial for infant health, offering essential nutrients and immune
protection. However, despite increasing exposure risks from nanoparticles (NPs), their
potential infiltration into human breast milk remains poorly understood. This study
...
Evolution
Evidence across a broad range of disciplines has demonstrated how individuals’ social
environments can impact their health, lifespan, reproduction, and ultimately their
evolutionary fitness. Past research has primarily focused on either traits specific
to ...
Over the past few decades, studies have provided strong evidence that the robust links
between the social environment, health, and survival found in humans also extend to
nonhuman social animals. A number of these studies emphasize the early life origins
...
Around 34 Mya, the Eocene−Oligocene transition (EOT) marked the most dramatic global
climatic cooling of the Cenozoic. On a planetary scale, paleontological evidence suggests
that this transition was associated with major faunal turnovers, sometimes even ...
Tool use is widely reported across a broad range of the animal kingdom, yet comprehensive
empirical tests of its function and evolutionary drivers remain scarce, predominantly
focused on a few relatively intelligent vertebrate lineages. In this study, we ...
Many biological studies involve inferring the evolutionary history of a sample of
individuals from a large population and interpreting the reconstructed tree. Such
an ascertained tree typically represents only a small part of a comprehensive population
...
Gene amplification can drive adaptation by rapidly increasing the cellular dosage
of critical gene products. Segmental amplifications often encompass large genomic
regions surrounding the gene(s) under selection for higher dosage. Overexpression
of ...
Genetics
The X-linked histone demethylase, UTX (KDM6A), is a master regulator of gene enhancers, though its role in self-renewing epithelia
like the skin is not well understood. Here, we find that UTX is a key regulator of
skin differentiation via the regulation ...
Immunology and Inflammation
B cells discriminate antigens in immune synapses by capturing them from antigen-presenting
cells (APCs). This discrimination relies on the application of mechanical force to
B cell receptor (BCR)-antigen bonds, allowing B cells to selectively disrupt low-...
Mitochondria coordinate several metabolic pathways, producing metabolites that influence
the immune response in various ways. It remains unclear whether mitochondria impact
antigen presentation by the MHC-class-I-related antigen-presenting molecule, MR1,
...
IgG antibodies are the basis for many successful therapeutics. A single, N-linked
glycan is present on the Fc on all IgGs, and the composition of that glycan exerts
marked influence over effector functions of the IgG. We and others have shown terminal
...
Tumor necrosis factor receptor 2 (TNFR2) activation is a promising-therapeutic strategy
for autoimmune disorders such as multiple sclerosis (MS) and chronic neuropathic pain
(CNP). This study aimed to identify mechanisms governing the sex-specific ...
Genome-editing technologies have enabled the clinical development of allogeneic cellular
therapies, yet the optimal gene-editing modality for multiplex editing of therapeutic
T cell product manufacturing remains elusive. In this study, we conducted a ...
Medical Sciences
Anemia, characterized by low blood hemoglobin (Hgb) levels, afflicts >2 billion individuals
worldwide. Here, we report real-world data generated by a smartphone app that noninvasively
screens for anemia using only “fingernail selfies.” App data for anemia ...
Scheduled surgeries elicit stress in many patients. Levels of preoperative stress,
anxiety, and female gender are known risk factors for increased and prolonged postoperative
pain. The mechanisms by which psychological stress increases postoperative pain, ...
Microbiology
Mycobacterial cell envelopes are rich in unusual lipids and glycans that play key
roles during infection and vaccination. The most abundant envelope glycolipid is trehalose
dimycolate (TDM). TDM compromises the host response to mycobacterial species via ...
Enhancement of the cyclization of membrane lipids GDGTs (glycerol dialkyl glycerol
tetraethers) is a critical strategy for archaea to adapt to various environmental
stresses. However, the physiological function of membrane lipid cyclization remains
...
Staphylococcus aureus (S. aureus) is a frequent culprit in implant-associated infections and employs many virulence
factors to escape killing by the host immune system. The specific immune evasion strategies
used by small aggregates of S. aureus on a ...
Respiratory viruses represent a major global health burden. Although these viruses
have different life cycles, they may depend on common host genetic factors, which
could be targeted by broad-spectrum host-directed therapies. We used genome-wide CRISPR
...
Yellow fever virus (YFV) replicates its RNA genome in membranous vesicles derived
from the invagination of endoplasmic reticulum membranes, designated as replication
organelles (ROs). Nonstructural protein 4B (NS4B) of flaviviruses play essential roles
in ...
Neuroscience
Previous studies on fear extinction have primarily focused on repeated exposure to
fear-inducing context without negative consequences. However, it is also possible
that an individual can reduce fear responses by predicting that they can transition
to a ...
In healthy awake individuals, the neural processing of bodily signals is not only
essential for survival but can also influence perception and compete with external
stimulus processing. Yet, the mechanism underlying this bidirectional processing of
bodily ...
Genetically encoded calcium indicators (GECIs) have revolutionized the study of cellular
calcium signaling, offering powerful tools for real-time optical monitoring of calcium
dynamics. Although contemporary GECIs can be targeted to various organelles, ...
Motor imagery is frequently utilized to improve the performance of specific target
movements in sports and rehabilitation. In this study, we show that motor imagery
can facilitate learning of not only the imagined target movements but also sequentially
...
The impact of neural activity on aging and longevity remains poorly understood, with
limited understanding of the specific neuron groups and molecular mechanisms that
regulate lifespan. In this study, we uncover a correlation between human longevity
and ...
Pharmacology
Methylthioadenosine phosphorylase (MTAP) gene deletions are frequent in human cancers. Loss of MTAP leads to significantly increased cellular levels of methylthioadenosine (MTA), a
cellular metabolite and specific inhibitor of the cell-essential enzyme ...
Physiology
Myosin is the primary motor protein in skeletal muscle, responsible for adenosine
triphosphate (ATP) hydrolysis that drives muscle contraction. In addition to force
production, resting myosin consumes ATP in futile cycles at two rates, the slower
one ...
Mitochondrial energy metabolism is vital for muscle function and is tightly controlled
at the transcriptional level, both in the basal state and during adaptive muscle remodeling.
The importance of the transcription factors estrogen-related receptors (...
Plant Biology
COP1 is a conserved ubiquitin ligase found in plants and animals. In plants, COP1
acts together with SPA proteins to suppress light signaling in darkness by promoting
the degradation of transcription factors involved in photomorphogenesis. Substrates
of ...
Thylakoid-free cyanobacteria are thought to preserve ancestral traits of early-evolving
organisms capable of oxygenic photosynthesis. However, and until recently, photosynthesis
studies in thylakoid-free cyanobacteria were only possible in the model ...
Anther dehiscence is the process that facilitates pollen release from mature anthers
in flowering plants. Despite its crucial importance to reproduction, the underlying
developmental mechanism and its integration with environmental cues remain poorly
...
Root system integrates multiple environmental cues, chiefly gravity and soil humidity,
to anchor plants in soil and forage for water. While the mechanism of auxin-mediated
root gravitropism is comparably well-understood, the root’s capability to grow ...
Corrections
Retraction
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