Table Of Contents Page, PNAS Volume 122, Number 32
This Week in PNAS
Inner Workings
Profile
Chris Greene grew up with an early interest in science. During his undergraduate studies
at the University of Nebraska in Lincoln, he realized he wanted to focus on theoretical
atomic, molecular, and optical (AMO) physics. With help from influential ...
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Commentaries
Perspective
What will it take to eliminate hunger in a world that is increasingly serious about
climate change mitigation? For the past two decades, climate activism and mitigation
efforts have largely focused on energy, industry, and transportation as the main ...
Letter
Brief Report
Adeno-associated viruses (AAVs) are nonpathogenic DNA viruses with potent gene delivery
capabilities, making them essential tools in gene therapy and biomedical research.
Despite their therapeutic importance, key aspects of AAV natural biology remain ...
Physical Sciences
Applied Mathematics
We introduce a mathematical model of the cancer–immunity cycle and use it to test
several hypotheses regarding the combination, timing, and optimization associated
with chemotherapy and immunotherapy dosing schedules in the context of competition
and time-...
Applied Physical Sciences
Diffusion in physical, chemical, and biological systems often occurs under transient
conditions and involves coupling across multiple physical fields, challenging conventional
control methods limited to steady-state, single-field settings. Here, we ...
The Kosterlitz–Thouless and the Hexatic phase transitions are celebrated examples
of dipole (vortex, dislocation) induced transitions in condensed matter physics. For
very clear reasons, these important “topological” transitions are restricted to 2-...
The link between characteristic coherent structures and their statistical properties
in turbulent flows remains largely unclear and is thus a central bottleneck for a
better understanding of turbulent flows. Here, we demonstrate this link for the ...
Biophysics and Computational Biology
Conjugation accelerates bacterial evolution by enabling bacteria to acquire genes
horizontally from their neighbors. Plasmid donors must physically encounter and connect
with recipients to allow plasmid transfer, and different environments are ...
DNA loop extrusion by cohesin has emerged as a critical pathway for chromosome organization.
In vitro single-molecule experiments indicate that loop extrusion requires the assembly
of a heteropentameric complex consisting of the SMC1/SMC3 heterodimer, ...
Chemistry
Identifying reaction intermediates is a critical component of elucidating the mechanisms
of chemical reactions. Spectroscopic techniques are instrumental in this identification
process. The capacity of AI to establish the correlations between spectra and ...
Nitroaromatic compounds are pollutants emitted from biomass burning and fossil fuel
combustion. They are a major component of brown carbon aerosols, affecting radiative
forcing in the lower atmosphere. Among these species, 2,4-dinitrophenol (DNP) is toxic
...
The molecular origins of water’s anomalous properties have long been a subject of
scientific inquiry. The liquid–liquid phase transition hypothesis, which posits the
existence of distinct low-density and high-density liquid states separated by a first-...
Chirality-induced spin selectivity (CISS) results in spin polarization of electrons
transmitted through chiral molecules and materials. Since CISS results in spin polarization
even at room temperature, it affords the possibility of using it to develop ...
Precise control of the physicochemical properties of metal–organic materials has been
a challenge in the fields of materials science and engineering and can be achieved
through the construction of morphology/size-dependent supramolecular functional model
...
Apoptosis is a critical outcome of stress-induced processes, with the endoplasmic
reticulum (ER) playing a central role in apoptotic protein processing and stress signal
transduction. Profiling the ER proteome during stress to cell death offers valuable
...
X-succinate synthases (XSSs) are glycyl radical enzymes (GREs) that catalyze the addition
of hydrocarbons to fumarate via radical chemistry, thereby activating them for microbial
metabolism. To date, the only structurally characterized XSS is ...
Fluorescent proteins (FPs) are noninvasive genetically encodable probes that have
revolutionized bioimaging and health fields with vivid images and an ever-growing
repertoire from jellyfish to sea anemones and corals. Inside the protein matrix, ...
Earth, Atmospheric, and Planetary Sciences
The evolution of continents is shaped by the growth and destruction of long-lived
cratons, which serve as their stable cores. Processes for craton destruction are controversial
because most invoked mechanisms occur frequently throughout Earth history, ...
Changes in oceanic circulation and carbon storage have been implicated as important
drivers of atmospheric pCO2 variability during the last glacial cycle (0 to 150 ka), though consensus on the
mechanisms responsible remains elusive due to sparse marine ...
The Nankai Trough is a major subduction zone in southern Japan capable of generating
the next M7 or larger earthquake off Kii Peninsula. In addition to earthquakes characterized
by sharp P and S arrivals, there are numerous slow earthquakes without clear ...
Engineering
Topological states of matter, first discovered in quantum systems, have opened new
avenues for wave manipulation beyond the quantum realm. In elastic media, realizing
these topological effects requires identifying lattices that support the corresponding
...
In materials, the ability to retain the memory of applied stresses or strains opens
up new opportunities for enhancing their performance adaptively via training. In dense
suspensions, a stress-adaptive response is enabled by non-Newtonian rheology; ...
Lubricated contacts in soft materials are important in various engineering systems
and natural settings. Three major lubrication regimes are boundary (BL), mixed (ML),
and elastohydrodynamic (EHL) lubrication, where the contact region is dry, partially
...
Mathematics
We revisit and elucidate the -genus, Hirzebruch’s -genus, and Witten’s -genus, cobordism invariants of special classes of manifolds. After slight modification,
involving Hecke’s trick, we find that the -genus and -genus arise directly from Jacobi’s theta ...
Physics
During drying, particle-laden sessile droplets will leave so-called coffee-stain rings
behind. This phenomenon is well known and well understood (Deegan et al., Nature 389, 827–829 (1997). Here, we show that when particle-laden droplets confined in a slit
...
The question of whether or not passive subwavelength cavities can alter the properties
of quantum materials is currently attracting a great deal of attention. In this article,
we show that the Fermi liquid parameters of a two-dimensional metal are ...
We explore the impact of excluded volume interactions on the local assembly of linear
physical networks, where nodes are spheres and links are rigid cylinders with varying
length. To focus on the effect of elongated links, we introduce a minimal 3D model
...
Social Sciences
Anthropology
Identifying the influence of low-density Indigenous populations in paleofire records
has been methodologically challenging. In the Southwest United States, well-replicated
fire histories suggest that abundant lightning and suitable climate conditions ...
Political Sciences
One longstanding explanation for bias and excessive force in policing is selection—the
assertion that those who select to work in law enforcement are more likely to hold
far-right, intolerant, and antiegalitarian, views than the public. While intuitive
...
Psychological and Cognitive Sciences
Authorities, from parents of toddlers to leaders of formal institutions, use punishment
to communicate disapproval and enforce social norms. Ideally, from whether and how
severely a transgression is punished, targets and observers infer shared social ...
As memories age, their immediate retrievability decreases albeit, due to ongoing memory
consolidation, their future rate of forgetting weakens. Here, we show in two experiments
(N = 1.216 participants) that mentally traveling back in time to older ...
Whether and to what degree culture modifies cognition has been an area of research
often limited by possibilities to gather relevant data across societies. In this project,
we leverage webcam-based eye-tracking to study cultural variations of cognitive ...
People and cultures differ in the extent to which they view the world as a zero-sum
environment (where one person’s gain is another’s loss) or a positive-sum environment
(where certain actions can benefit everyone). These beliefs shape individuals’ ...
Social Sciences
Science is characterized by collaboration and cooperation, but also by uncertainty,
competition, and inequality. While there has always been some concern that these pressures
may compel some to defect from the scientific research ethos—i.e., fail to make ...
Understanding refugees’ destination choices is key to designing appropriate policies,
but little is known about this beyond correlational patterns and the effects of isolated
policy changes. To derive causal evidence on how destination country ...
Biological Sciences
Applied Biological Sciences
Precise control over the dosage of Cas9-based technologies is essential because off-target
effects, mosaicism, chromosomal aberrations, immunogenicity, and genotoxicity can
arise with prolonged Cas9 activity. Type II anti-CRISPR proteins (Acrs) inhibit ...
Biochemistry
DNA loop extrusion by cohesin has emerged as a critical pathway for chromosome organization.
In vitro single-molecule experiments indicate that loop extrusion requires the assembly
of a heteropentameric complex consisting of the SMC1/SMC3 heterodimer, ...
Apoptosis is a critical outcome of stress-induced processes, with the endoplasmic
reticulum (ER) playing a central role in apoptotic protein processing and stress signal
transduction. Profiling the ER proteome during stress to cell death offers valuable
...
X-succinate synthases (XSSs) are glycyl radical enzymes (GREs) that catalyze the addition
of hydrocarbons to fumarate via radical chemistry, thereby activating them for microbial
metabolism. To date, the only structurally characterized XSS is ...
Intronic GGGGCC hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal
dementia (FTD). Despite its intronic location, this repeat avidly supports synthesis
of pathogenic ...
Splicing of terminal introns is coupled to 3′-end processing by cleavage and polyadenylation
(CPA) in mammalian genes. Whether this functional coupling is universally conserved
across eukaryotes is unclear. Here, we show using long read RNA sequencing in ...
HvAACT1 is a major aluminum (Al)-tolerance gene in barley, encoding a citrate transporter
that belongs to the multidrug and toxic compound extrusion (MATE) family. This transporter
facilitates citrate secretion from the roots, thereby detoxifying external ...
Carbon monoxide (CO) poisoning causes 50,000 to 100,000 emergency department visits
and ~1,500 deaths in the United States annually. Current treatments are limited to
supplemental and/or hyperbaric oxygen to accelerate CO elimination. Even with oxygen
...
Biophysics and Computational Biology
Fluorescent proteins (FPs) are noninvasive genetically encodable probes that have
revolutionized bioimaging and health fields with vivid images and an ever-growing
repertoire from jellyfish to sea anemones and corals. Inside the protein matrix, ...
During development, groups of cells generate shape by coordinating their mechanical
properties through an interplay of self-organization and prepatterning. Hydra displays
a striking planar pattern of actin fibers at the organism scale, and mechanics ...
The phage shock protein A (PspA), a bacterial member of the endosomal sorting complexes
required for transport (ESCRT)-III superfamily, forms rod-shaped helical assemblies
that internalize membrane tubules. The N-terminal helix α0 of PspA (and other ESCRT-...
We investigate the impact of glycoform alterations on the dynamic structure of the
human immunoglobulin G1 (IgG1) Fc region using integrated computational and experimental
approaches. Four distinct IgG1-Fc glycoforms, varying in core fucosylation and ...
Biomolecular condensates mediate diverse and essential cellular functions by compartmentalizing
biochemical pathways. Many condensates have internal subdomains with distinct compositional
identities. A major challenge lies in dissecting the multicomponent ...
The cardiac voltage-gated sodium channel Nav1.5 is resistant to tetrodotoxin (TTXr). Here, we report a cryo-electron microscopy
(cryo-EM) structure of wild-type human Nav1.5, coexpressed with the β1 auxiliary subunit and treated with high-concentration
...
Cell Biology
Natural killer (NK) cells engage target cells via the immunological synapse (IS),
where inhibitory and activating signals determine whether NK cell cytotoxicity is
suppressed or activated. We previously reported that cancer cells can rapidly remodel
their ...
DNA-points accumulation for imaging in nanoscale topography (DNA-PAINT) enables nanoscale
imaging with virtually unlimited multiplexing and molecular counting. Here, we address
challenges, such as variable imaging performance and target accessibility, ...
Efficient gene expression depends on the tightly regulated export of messenger RNA
(mRNA) through nuclear pore complexes (NPCs), which are densely modified by O-linked
N-acetylglucosamine (O-GlcNAc). Although dysregulated O-GlcNAcylation has been linked
...
Small open reading frames (smORFs) encode microproteins that play crucial roles in
various biological processes, yet their functions in adipocyte biology remain largely
unexplored. In a previous study, we identified thousands of smORFs in white and brown
...
Developmental Biology
Transcription factors and histone modification-mediated chromatin accessibility coordinately
regulate spatiotemporal expression of genes that control growth and development. It
is well documented that juvenile hormone-activated Kr-h1 antagonizes 20-...
Ecology
A quantitative understanding of local transmission dynamics is essential for designing
effective prevention strategies. In this study, we developed a computational workflow
to identify viral introductions and trace locally circulating clusters. We ...
Environmental Sciences
Identifying the influence of low-density Indigenous populations in paleofire records
has been methodologically challenging. In the Southwest United States, well-replicated
fire histories suggest that abundant lightning and suitable climate conditions ...
During the last glacial period (~118 to 11.7 ka), the Arctic has been characterized
by a major redistribution of flora and fauna as a consequence of extreme climatic
fluctuations, with associated glacial advances and retreats, sea-level changes, and
...
Evolution
Adenylosuccinate lyase (ADSL), an enzyme that is crucial for purine biosynthesis,
carries an amino acid substitution that is present in almost all humans today but
absent in Neandertals and Denisovans. This substitution reduces the stability of the
enzyme,...
One of the most influential hypotheses about primate evolution postulates that their
origin, radiation, and major dispersals were associated with exceptionally warm conditions
in tropical forests at northern latitudes (henceforth the warm tropical forest ...
Different types of genomic conflicts are possible in plants with multiovulate ovaries
that produce multiseeded fruits: between the maternal plant and its offspring, among
developing seeds, between paternal and maternal genomes over seed development, and
...
Genetics
Ribosome-associated quality control (RQC) is a pivotal biological process that governs
the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in
RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on
...
Compact programmable nucleases provide versatile genome editing tools with therapeutic
potential, particularly when delivered via adeno-associated virus (AAV) vectors. However,
their limited editing efficacy and stringent protospaceradjacent motif (PAM) ...
The accumulation of RNA Polymerase III (Pol III) transcribed short interspersed nuclear
element (SINE) retrotransposon RNA is a hallmark of various cellular stressors, including
DNA virus infection. However, the molecular mechanisms driving the induction ...
Immunology and Inflammation
Pathogenic Th17 cells play crucial roles in CNS autoimmune diseases such as multiple
sclerosis (MS), but their regulation by endogenous mechanisms remains unknown. Through
RNA-seq analysis of primary brain glial cells, we identified immune-responsive gene
...
TNF receptor-associated factor 3 (TRAF3) is a signaling adaptor protein that is ubiquitously
expressed but has highly distinct cell type–specific functions. TRAF3 plays critical
roles in restraint of B lymphocyte activation, differentiation, and ...
This study examines the expression of CD45 isoforms on human yellow fever virus vaccine
(YFV-17D) specific CD8 T cells longitudinally after vaccination. As expected, effector
CD8 T cells at day 14 express CD45RO but within 4 to 6 wk these virus-specific ...
Medical Sciences
We introduce a mathematical model of the cancer–immunity cycle and use it to test
several hypotheses regarding the combination, timing, and optimization associated
with chemotherapy and immunotherapy dosing schedules in the context of competition
and time-...
Genetic investigation in Mendelian skin disorders featuring generalized or localized
skin scaling and redness, known as the ichthyoses, has revealed novel pathways relevant
to epidermal integrity, barrier function, and desquamation. Here, we show that a ...
E3 ubiquitin ligases mediating turnover of proteins engaged in cancer progression
point to key regulatory nodes. To uncover modifiers of metastatic competency, we conducted
an in vivo genome-wide CRISPR-inactivation screen using cultured breast ...
Microbiology
Conjugation accelerates bacterial evolution by enabling bacteria to acquire genes
horizontally from their neighbors. Plasmid donors must physically encounter and connect
with recipients to allow plasmid transfer, and different environments are ...
The emergence of immune-evasive SARS-CoV-2 Omicron subvariants highlights the need
to develop a mucosal SARS-CoV-2 vaccine that can provide broad protection against
virus infection and transmission. Here, we developed an intranasal monovalent SARS-CoV-2
...
The interferon (IFN)-inducible GTPases play a crucial role in cell autonomous immunity
against intracellular pathogens. Particularly, these GTPases directly recognize the
host membrane-derived vacuole containing pathogens and subsequently destroy it. ...
The nonstructural protein 1 (NS1) of influenza A virus performs a broad variety of
proviral activities in the infected cell, primarily mediating evasion from the host
innate immune response by being the main viral interferon antagonist. However, there
are ...
Neuroscience
Memory generalization allows an organism to adapt to new conditions, but overgeneralization
of fear or traumatic experiences can be detrimental to survival and contributes to
the development of various mental disorders. However, the cellular and molecular ...
Goal-directed motor performance relies on the brain’s ability to distinguish between
actions that lead to successful and unsuccessful outcomes. The basal ganglia (BG)
and cerebellum (CBL) are integral for processing performance outcomes, yet their ...
The eyelid performs critical functions to protect the eye and preserve functional
vision. These functions are driven by contraction of the orbicularis oculi (OO), which
is a unique skeletal muscle with a circular geometry and diffuse innervation. It is
...
The visualization and manipulation of proteins in neurons is widely used to deduce
their functions. While every experimental approach has limitations, the concurrent
knock-in and knockout of two different proteins can be especially challenging. To
this ...
Obtaining predictive models of a neural system is notoriously challenging. Detailed
models suffer from excess model complexity and are difficult to fit efficiently. Simplified
models must negotiate a tradeoff between tractability, predictive power, and ...
Pharmacology
Noradrenaline is a major monoaminergic neurotransmitter involved in pain modulation
through an α2A-adrenergic receptor. Hence, α2-adrenergic agonists such as clonidine
and dexmedetomidine exhibit analgesic and opioid-sparing effects. However, their use
is ...
The degradation of cellular components through autophagy is essential for longevity
and healthy aging. However, autophagy function decreases with aging, contributing
to age-related diseases. In this study, we characterized a small-molecule activator
of ...
Plant Biology
The formation of a body axis is one of the fundamental steps in developmental patterning
in multicellular organisms. Ectopic expression of the stomatal protein BASL (BREAKING
OF ASYMMETRY IN THE STOMATAL LINEAGE) reveals a proximal–distal cell polarity ...
Cells accumulate mutations throughout development, contributing to cancer, aging,
and evolution. Quantitative data on the abundance of de novo mutations within plants
or animals are limited, as new mutations are often rare within a tissue and fall below
...
The perception of the phytohormone gibberellin (GA) by its nuclear receptor GIBBERELLIN
INSENSITIVE DWARF1 (GID1) triggers polyubiquitination and proteasomal degradation
of master growth regulators—DELLA proteins—mediated by the SCFSLY1/GID2 E3 ubiquitin ...
Population Biology
Mitonuclear discordance has been observed in several shark species. Female philopatry
has often been invoked to explain such discordance but has never been explicitly tested.
Here, we focus on the white shark, for which female philopatry has been ...
Psychological and Cognitive Sciences
Authorities, from parents of toddlers to leaders of formal institutions, use punishment
to communicate disapproval and enforce social norms. Ideally, from whether and how
severely a transgression is punished, targets and observers infer shared social ...
Testing enhances memory more than studying. Although numerous studies have demonstrated
the robustness of this classic effect, its neural and computational origin remains
debated. Predictive learning is a potential mechanism behind this phenomenon: ...
Systems Biology
Understanding the molecular mechanisms behind plant response to stress can enhance
breeding strategies and help us design crop varieties with improved stress tolerance,
yield, and quality. To investigate resource redistribution from growth- to defense-...
The famous model organism Saccharomyces cerevisiae is widely present in a variety of natural and human-associated habitats. Despite
extensive studies of this organism, the metabolic mechanisms driving its adaptation
to varying niches remain elusive. We ...
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