Table Of Contents Page, PNAS Volume 122, Number 38
This Week in PNAS
Opinion
Science and Culture
Retrospective
Margaret Bryan Davis, a prominent ecologist, died on May 22, 2024. She was a Regents
Professor at the University of Minnesota and a member of the National Academy of Sciences.
Her students remember her as a creative and clear-thinking scientist who ...
Commentaries
Perspective
Climate policy faces increasingly complex challenges that span multiple human decision
scales in nature–society systems. Contemporary climate policy models, while valuable
and increasingly versatile in handling spatial and temporal scales, struggle to ...
Letters
This article has a reply:
Reply to Quillien: Intuitive preferences and interpretive humility in intentionality judgments
View the original article:
This article has a reply:
Reply to Possenriede et al.: LDLR as a targetable HlyA receptor in Escherichia coli pyelonephritis
View the original article:LDL receptor–mediated endocytosis of Escherichia coli α-hemolysin mediates renal epithelial toxicity
Brief Report
Social media platforms have become vital channels for businesses to reach consumers
through advertising. But in the United States, the digital advertising market in which
these platforms operate is dominated by a few major players, raising concerns for
...
Physical Sciences
Applied Physical Sciences
Tissue deformations during morphogenesis can be active, driven by internal processes,
or passive, resulting from stresses applied at their boundaries. Here, we introduce
the Drosophila hindgut primordium as a model for studying boundary-driven tissue ...
Liquid crystal elastomers (LCEs) are anisotropic, viscoelastic materials integrating
polymer networks and liquid crystals. While their mechanical responses have been extensively
studied, their fracture behavior remains largely unexplored. Specifically, ...
Elastic turbulence (ET) and elastoinertial turbulence (EIT) of viscoelastic fluids
are unique flow states with features distinct from the inertial turbulence of Newtonian
fluids. Whether these two states are connected or entirely decoupled remains ...
Topological defects, such as disclination lines in nematic liquid crystals, are fundamental
to many physical systems and applications. In this work, we study the behavior of
nematic disclinations in thin parallel-plate geometries with strong patterned ...
Unlike gas molecules at equilibrium, the spatial organization of self-propelled particles
can be very sensitive to what happens at the boundaries of their container. Understanding
the link between boundary phenomena and bulk stationary distributions could ...
Understanding mesoscale structural dynamics of precipitation-strengthened alloys is
essential for optimizing the mechanical performances of these alloys. Herein, we establish
a multimodal coherent X-ray diffraction imaging framework for spatiotemporal ...
Influenza A virus (IAV) entry into host cells begins with interactions between the
viral envelope proteins hemagglutinin (HA)/neuraminidase (NA) and sialic acid moieties
on the cell plasma membrane. These interactions drive IAV’s lateral diffusion along
...
Biophysics and Computational Biology
Cyclic dimeric-GMP (c-di-GMP) is a ubiquitous bacterial second messenger that regulates
a variety of cellular processes, including motility, biofilm formation, secretion,
cell cycle progression, and development, and also contributes to the virulence of
...
G protein–coupled receptors (GPCRs) comprise a large class of membrane proteins that
mediate cellular responses to a wide range of external signals and as such constitute
major drug targets. While oligomerization has been shown to play a well-established
...
Chemistry
Solid-state electrolytes (SSEs) are being extensively researched as replacements for
liquid electrolytes in future batteries. Despite significant advancements, there are
still challenges in using SSEs, particularly in extreme conditions. This study ...
Multireference methods such as multiconfiguration pair-density functional theory accurately
capture electronic correlation in systems with strong multiconfigurational character,
but their cost precludes direct use in molecular dynamics. Combining these ...
This study presents a comparative cradle-to-gate environmental and economic evaluation
of nine synthetic routes for Molnupiravir (EIDD-2801), a broad-spectrum antiviral
drug. Integrating Life Cycle Assessment (LCA) with Life Cycle Costing (LCC), we ...
Computer Sciences
Social networks scaffold the diffusion of information on social media. Much attention
has been given to the spread of true vs. false content on online social platforms,
including the structural differences between their diffusion patterns. However, much
...
Earth, Atmospheric, and Planetary Sciences
Tropical cyclones are expected to intensify more rapidly with warming, but relatively
little work has examined whether they could expand more rapidly with warming, too.
Recent theory predicts that peak expansion rate should increase with sea surface ...
Venus and Earth are rocky planets of roughly the same size and bulk density, yet their
surface volcanic and tectonic features appear substantially different. On Venus, the
coexistence of large volcanic highlands—interpreted as the surface expression of ...
The Turkana Basin is a renowned paleoanthropological region in Kenya and Ethiopia
and is famous for discoveries of numerous hominin fossils and their associated cultural
technologies. The Plio-Pleistocene sedimentary sequences hosting these important ...
Bubble-mediated gas exchange associated with wave breaking is a critical pathway for
ocean–atmosphere exchange of low solubility gases such as oxygen. Yet, ocean and climate
models, as well as observation-based products, usually rely on wind-only air–sea ...
Winds generate waves over the oceans with a wide range of properties. The largest
wave heights and periods are important parameters in the design of marine structures.
Extreme waves also play an outsize role in air–sea fluxes and coastal dynamics, and
...
Engineering
Tailoring the nanoscale distribution of chemical species at grain boundaries is a
powerful method to dramatically influence the properties of polycrystalline materials.
However, classical approaches to the problem have tacitly assumed that only ...
Recent discovery of “extreme clustering” of inertial particles in isotropic turbulent
flow suggests a hidden mechanism of particle–particle interaction at sub-Kolmogorov
separations unexplained by hydrodynamic interaction. The near-contact radial ...
Inferring accurate and precise material models necessary for high-fidelity predictions
has been a central challenge in constitutive modeling. Both traditional regression
methods and modern machine-learning approaches require specialized data labels, which
...
Programming physical intelligence into mechanisms holds great promise for machines
that can accomplish tasks such as navigation of unstructured environments while utilizing
a minimal amount of computational resources and electronic components. In this ...
Physics
The optimal control of finite-time processes on the microscale is of significant theoretical
and practical interest, particularly for the energy-efficient operation of nanomachines.
While previous studies have primarily focused on transitions between ...
Recent advances in 2D materials featuring nonzero Berry curvature have inspired extensions
of the Wigner crystallization paradigm. This paper derives a low-energy effective
theory for such quantum crystals, including the anomalous Hall crystal (AHC) with
...
Statistics
The use of AI, or more generally data-driven algorithms, has become ubiquitous in
today’s society. Yet, in many cases and especially when stakes are high, humans still
make final decisions. The critical question, therefore, is whether AI helps humans
make ...
Social Sciences
Anthropology
In southern China and Southeast Asia (collectively, Southeastern Asia), Terminal Pleistocene
and Early to Middle Holocene (ca. 12,000 to 4,000 cal. BP) hunter-gatherer burials
feature tightly crouched or squatting postures, sometimes with indications of ...
The Casas Grandes region in northwest Chihuahua, Mexico, is ideally situated to explore
the notion of contact between the US Southwest/Northwest Mexico and Mesoamerica, as
it lies geographically in a region where cultural traditions were combined in ...
Political Sciences
Social networks scaffold the diffusion of information on social media. Much attention
has been given to the spread of true vs. false content on online social platforms,
including the structural differences between their diffusion patterns. However, much
...
Psychological and Cognitive Sciences
Scientific explanation is one of the most sophisticated forms of human reasoning.
Nevertheless, here we hypothesize that scientific explanation is susceptible to some
of the same biases that influence everyday thinking—particularly during the initial
...
Social Sciences
The use of AI, or more generally data-driven algorithms, has become ubiquitous in
today’s society. Yet, in many cases and especially when stakes are high, humans still
make final decisions. The critical question, therefore, is whether AI helps humans
make ...
Romantic (typically sexual) relationships are important to personal, physical, mental,
social, and economic well-being, and to human evolution. Yet little is known about
factors contributing to long-term lack of intimate relationships. We investigated
...
Biological Sciences
Agricultural Sciences
Crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) have revolutionized pest management, but their benefits have been reduced by
evolution of practical resistance in at least 31 cases. To delay ...
Anthropology
The Casas Grandes region in northwest Chihuahua, Mexico, is ideally situated to explore
the notion of contact between the US Southwest/Northwest Mexico and Mesoamerica, as
it lies geographically in a region where cultural traditions were combined in ...
Applied Biological Sciences
With the advent and widespread use of messenger RNA (mRNA) vaccines against severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), RNA vaccines have emerged as
an exciting class of vaccine offering low cost, rapid development, and high modularity
...
Seasonal changes in time policy, such as switching between Standard Time (SDT) and
Daylight Saving Time (DST), have been adopted by many countries, including the United
States. While transitioning between SDT and DST has notable acute negative population
...
Fluorescence imaging enables visualization of the specific molecules of interest with
high contrast, and the use of multiple fluorophores in a single tissue sample allows
visualization of complex relationships between biological molecules, cell types, and
...
Biochemistry
The RAF kinases (ARAF, BRAF, and CRAF) are essential components of the RAS-ERK signaling
pathway, which controls vital cellular processes and is frequently dysregulated in
human disease. Notably, mutations that alter BRAF function are prominent drivers of
...
To survive in highly competitive environments, bacteria use specialized secretion
systems to deliver antibacterial toxins into neighboring cells, thereby inhibiting
their growth. In many Gram-positive bacteria, the export of such toxins requires a
...
The noncoding small nuclear RNAs (snRNAs) associate with a large set of proteins to
form small nuclear ribonucleoprotein particles (snRNPs). While the function of snRNAs
is well characterized, the regulation of their transcription remains poorly ...
R-loops are an important class of non-B DNA structures that form co-transcriptionally.
Using in vitro transcription and unbiased quantitative sequencing readouts, we show
that the addition of single-strand DNA binding proteins co-transcriptionally can ...
Prohibitin 1 (PHB1) and Prohibitin 2 (PHB2), two conserved prohibitin members, are
primarily localized to the mitochondrial inner membrane (MIM) to form a nanoscale
macromolecular prohibitin complex. This prohibitin complex can facilitate the spatial
...
One-carbon metabolism influences gene expression by providing methyl units for DNA,
RNA, and histone methylation. Robust methylation requires rapid hydrolysis of the
methylation by-product S-adenosylhomocysteine (SAH) by S-adenosylhomocysteinase (Ahcy). ...
Pancreatic cancer remains one of the most lethal malignancies with limited therapeutic
options. Among the alternative targets explored for pancreatic cancer, the glycolipid
stage-specific embryonic antigen-4 (SSEA4) has been extensively studied. We have ...
Palytoxin (PTX), a potent marine toxin, has long been known to transform Na+,K+-ATPase (NKA), an indispensable ion pump, into a nonselective cation channel. It has
been postulated that PTX takes control of the two gates on either side of a channel-like
...
Biophysics and Computational Biology
G protein–coupled receptors (GPCRs) comprise a large class of membrane proteins that
mediate cellular responses to a wide range of external signals and as such constitute
major drug targets. While oligomerization has been shown to play a well-established
...
Francis Crick’s global parameterization of coiled coil geometry has been widely useful
for guiding design of new protein structures and functions. However, design guided
by similar global parameterization of beta barrel structures has been less successful,...
In the host–pathogen arms race, herpesviruses and poxviruses encode proteins that
sabotage the transporter associated with antigen processing (TAP), thereby suppressing
MHC-I antigen presentation and enabling lifelong infection. Of the five known viral
...
In biological membranes, proteins face a fundamentally different environment than
in water. To avoid untenable lipid contacts with polar backbone atoms, they use the
continuous hydrogen bonding achieved by α-helices or β-barrels to traverse membranes.
...
Deep mutational scanning (DMS) assays provide a powerful method to generate large-scale
datasets essential for advancing AI-driven predictions in biology. The tripartite
β-lactamase assay (TPBLA), in which a protein of interest is inserted between two
...
Cell Biology
Despite the many studies on the ubiquitin–proteasome system, our understanding of
the proteasome itself is limited. The balance and regulation of 26S and 30S proteasomes
are not yet known. Here, we show that among the proteasome base assembly chaperones,
...
Hepatocellular carcinoma (HCC) frequently develops resistance to CD8+ T cell–based
immunotherapy, yet the mechanisms driving this immune evasion remain poorly understood.
To identify tumor-intrinsic regulators of immunotherapy resistance and explore ...
Differentiation of smooth muscle cells (SMCs) is driven by the activation of a set
of genes controlled by serum response factor (SRF), a ubiquitous transcription factor
with limited intrinsic transcriptional activity. Myocardin (MYOCD) is a strong ...
The canonical necrosome formed by receptor-interacting protein kinase 1 (RIPK1) and
RIPK3 is a functional amyloid fibril structure critical to intracellularly drive necroptosis.
Since necroptosis leads to the release of intracellular content, the fate of ...
Developmental Biology
Tissue deformations during morphogenesis can be active, driven by internal processes,
or passive, resulting from stresses applied at their boundaries. Here, we introduce
the Drosophila hindgut primordium as a model for studying boundary-driven tissue ...
Ecology
Characterizing niche space is critical for predicting species interactions and responses
to environmental change. To enhance our understanding of dietary niche breadth, we
used DNA metabarcoding to examine how diets of a widespread, model herbivore (...
Environmental Sciences
This study presents a comparative cradle-to-gate environmental and economic evaluation
of nine synthetic routes for Molnupiravir (EIDD-2801), a broad-spectrum antiviral
drug. Integrating Life Cycle Assessment (LCA) with Life Cycle Costing (LCC), we ...
Arsenic contamination in rice poses a global challenge to food safety and agricultural
productivity, as toxic methylated arsenic species—dimethylarsinic acid (DMA) and its
highly toxic derivative, methylated monothioarsenate (DMMTA)—accumulate in rice ...
Genetics
Romantic (typically sexual) relationships are important to personal, physical, mental,
social, and economic well-being, and to human evolution. Yet little is known about
factors contributing to long-term lack of intimate relationships. We investigated
...
Immunology and Inflammation
Breast tumors harbor dynamic microenvironments, with multiple immune cell types playing
opposing roles during tumor progression and/or response to therapy. Tumor-associated
macrophages promote mammary tumorigenesis, whereas the role of mammary tissue ...
Nuclear receptors (NRs) are crucial to integrate metabolite sensing and immune responses
in the gut. NR-interacting protein 1 (NRIP1) is an important coregulator of various
NRs that has been implicated in inflammatory bowel disease risk, but mechanistic ...
Engagers are antibody-based therapies which bind immune cell receptors and a target
cell ligand. Next-gen engagers typically bind two activating receptors, but the effect
of this on immune synapse formation and signaling is unknown. Here, we coligated ...
Murine and human immune systems differ significantly, particularly within the myeloid
lineage. Humanized mice, generated by transplanting human hematopoietic stem, progenitor
cells into genetically modified mice, are invaluable to study human immune ...
Medical Sciences
Kidney fibrosis is driven by multiple factors, among which impaired fatty acid oxidation
has emerged as a critical determinant. Acyl-Coenzyme A (CoA) synthetase medium-chain
family member 3 (ACSM3), a key enzyme of medium-chain fatty acid (MCFA) ...
Thrombopoietin (TPO), predominantly produced by the liver, is the key regulator for
platelet production and the hematopoietic stem cell niche. Our earlier report demonstrated
that platelet GPIbα is required for hepatocellular TPO generation, which is the ...
Wnt signaling plays a crucial role for many developmental processes. It is also pivotal
in the generation and limited treatment outcomes of glioblastoma (GBM). Here, we identified
Wnt7b, which is markedly upregulated in GBM patients, as a determinant of ...
Microbiology
Cyclic dimeric-GMP (c-di-GMP) is a ubiquitous bacterial second messenger that regulates
a variety of cellular processes, including motility, biofilm formation, secretion,
cell cycle progression, and development, and also contributes to the virulence of
...
Influenza A virus (IAV) entry into host cells begins with interactions between the
viral envelope proteins hemagglutinin (HA)/neuraminidase (NA) and sialic acid moieties
on the cell plasma membrane. These interactions drive IAV’s lateral diffusion along
...
The human gut microbiome plays a central role in nutrient metabolism, yet the fate
of exogenous nucleic acids within this ecosystem remains poorly understood. Here,
we show that multiple Bacteroidales species efficiently metabolize exogenous DNA,
with ...
Across all domains of life, cobalamin-dependent methyltransferases have diversified
to perform a range of crucial functions, such as methionine synthesis and the demethylation
of various reduced nitrogen and sulfur compounds. These large modular enzymes ...
Human cytomegalovirus (HCMV) is a clinically important herpesvirus that has coevolved
for millions of years with its human host, and establishes lifelong persistent infection.
A substantial proportion of its 235 kb genome is dedicated to manipulating host ...
A “σ cycle” in which the initiation factor σ associates with RNA polymerase (RNAP)
core enzyme to permit transcription initiation and dissociates from RNAP core enzyme
to permit transcription elongation, has been proposed to occur and to be an essential
...
Pseudouridylation is a prevalent RNA modification occurring in transfer RNAs (tRNAs),
ribosomal RNAs (rRNAs), small non-coding RNAs (snoRNAs), and has been most recently
identified in mRNAs and lncRNAs. Emerging evidence suggests that this dynamic RNA
...
Neuroscience
γ-aminobutyric acid type A receptor (GABAAR) is a pentameric ligand-gated ion channel that plays a crucial role in inhibition
in the adult brain. Structural and electrophysiological studies have provided numerous
insights into the receptor’s functioning ...
Neurodegenerative diseases present one of the most significant global health challenges.
These disorders are defined by the accumulation of abnormal protein aggregates that
impair synaptic function and cause progressive neuronal degeneration. Therefore, ...
In an ever-changing environment, animals make optimal decisions to ensure their well-being.
Faced with limited food sources, they often seek foods that provide the nutrients
they require to maintain homeostasis. Under extreme circumstances (e.g., ...
Synapse pruning sculpts neural circuits throughout life. The human Leukocyte immunoglobulin-like
receptor type B2 (LilrB2)/murine Paired immunoglobulin receptor B (PirB) receptors
expressed in neurons and complement protein C4 have been separately ...
Physiology
While numerous genetic risk loci are linked to kidney disease, a unifying therapeutic
target for diverse renal pathologies remains elusive. Here, through large-cohort polymorphic
locus screening, we identify the SLC39A8 A391T variant (rs13107325) as a ...
Insulin potently decreases blood glucose; thus, tight control is required to prevent
excessive insulin release and hypoglycemia. Central to this inhibition is somatostatin
released from delta cells that are clustered with beta cells in pancreatic islets.
...
Lymphatic dysfunction is linked to disease pathogenesis in Duchenne muscular dystrophy animal models
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder characterized
by progressive muscle weakness and inflammation caused by mutations in the DMD gene.
Chronic inflammation in DMD exacerbates the complications associated with disease
...
The blood–brain barrier (BBB) is critical for maintaining cerebral homeostasis, and
its deterioration with age is an important pathogenic factor in the etiology of vascular
dementia. Extracellular matrix–integrin interactions play a central role in ...
Plant Biology
Steviol glycosides (SGs) from Stevia rebaudiana are prized as noncaloric sweeteners, with rebaudioside M (Reb M)—a next-generation
SG known for its sucrose-like sweetness and lack of off-tastes—standing out for its
superior sensory profile. However, Reb M’...
Psychological and Cognitive Sciences
Our spontaneous thoughts encompass various dimensions, such as task-relatedness (off
vs. on task), and thought orientation (internal vs. external). However, their distinction
remains unclear. Our study addresses this issue by focusing on their timescales ...
Corrections
View the original article:
Cover image: Pictured are high seas (10–12 meters) in the Southern Ocean. Fabrice Ardhuin et al. determined the heights and periods of ocean swells using satellite sea level measurements. The data revealed how large waves evolve in storms; energy from steep, short waves feeds long, high waves that radiate outward as swells from the storm. The highest waves observed were around 19.7 meters high with a period of around 20.2 seconds. According to the authors, uncovering the formation and distribution of large ocean swells can help design durable coastal structures. See the article by Ardhuin et al. e2513381122. Image credit: Benoit Stichelbaut (photographer).
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