Table Of Contents Page, PNAS Volume 121, Number 44
This Week in PNAS
Inner Workings
Commentaries
Letters
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Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFβ1 and IL-27
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Reply to Masters: Recombinant coronavirus balances biosafety and benefit
Brief Reports
Body fossils set limits on feasible reconstructions of functional capacity and behavior
in theropod dinosaurs, but do not document in-life behaviors. In contrast, trace fossils
such as footprints preserve in-life behaviors that can potentially test and ...
The growth rate of the atmospheric abundance of methane (CH4) reached a record high of 15.4 ppb yr−1 between 2020 and 2022, but the mechanisms driving the accelerated CH4 growth have so far been unclear. In this work, we use measurements of the 13C:12C ...
Bacteria have evolved many defenses against invading viruses (phage). Despite the
many bacterial defenses and phage counterdefenses, in most environments, bacteria
and phage coexist, with neither driving the other to extinction. How is coexistence
...
Physical Sciences
Applied Physical Sciences
Thermal nonreciprocity plays a vital role in chip heat dissipation, energy-saving
design, and high-temperature hyperthermia, typically realized through the use of advanced
metamaterials with nonlinear, advective, spatiotemporal, or gradient properties. ...
Active matters, characterized by multi-mode motions, have been emerging for both engineering
and biological applications. Generally, active objects rely on the symmetry-broken
structures, compositions, or interfacial activities through a physical or ...
Biophysics and Computational Biology
Interactions mediated by intrinsically disordered protein regions (IDRs) pose formidable
challenges in structural characterization. IDRs are highly versatile, capable of adopting
diverse structures and engagement modes. Motivated by recent strides in ...
As their statistical power grows, genome-wide association studies (GWAS) have identified
an increasing number of loci underlying quantitative traits of interest. These loci
are scattered throughout the genome and are individually responsible only for ...
The biological function of membranes is closely related to their softness, which is
often studied through the membranes’ thermally driven fluctuations. Typically, the
analysis assumes that the relaxation rate of a pure bending deformation is determined
by ...
The collective patterns that emerge in schooling fish are often analyzed using models
of self-propelled particles in unbounded domains. However, while schooling fish in
both field and laboratory settings interact with domain boundaries, these effects
are ...
Intrinsically disordered regions (IDRs) play a pivotal role in organellar remodeling.
They transduce signals across membranes, scaffold signaling complexes, and mediate
vesicular traffic. Their functions are regulated by constraining conformational ...
Multivesicular endosomes (MVEs) sequester membrane proteins destined for degradation
within intralumenal vesicles (ILVs), a process mediated by the membrane-remodeling
action of Endosomal Sorting Complex Required for Transport (ESCRT) proteins. In ...
The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the
human spleen involves sequential processes of prefiltration, filtration, and postfiltration.
While prior work has elucidated the mechanisms underlying the first two ...
Chemistry
Intracellular protein delivery has the potential to revolutionize cell-biological
research and medicinal therapy, with broad applications in bioimaging, disease treatment,
and genome editing. Herein, we demonstrate successful delivery of a functional ...
Lithium (Li) metal has been recognized as a promising anode to advance the energy
density of current Li-based batteries. However, the growth of the solid–electrolyte
interphase (SEI) layer and dendritic Li microstructure pose significant challenges
for ...
It is broadly recognized that intramolecular electric fields, produced by the protein
scaffold and acting on the active site, facilitate enzymatic catalysis. This field
effect can be described by several theoretical models, each of which is intuitive
to ...
Earth, Atmospheric, and Planetary Sciences
Pleistocene Ice Ages display abrupt Dansgaard–Oeschger (DO) climate oscillations that
provide prime examples of Earth System tipping points—abrupt transition that may result
in irreversible change. Greenland ice cores provide key records of DO climate ...
Methane (CH4) is a potent greenhouse gas but also an important carbon and energy substrate for
some lake food webs. Understanding how CH4 incorporates into food webs is, therefore, crucial for unraveling CH4 cycling and its impacts on climate and ...
Subduction zones play a pivotal role in the mechanics of plate tectonics by providing
the driving force through slab pull and weak megathrusts that facilitate the relative
motion between tectonic plates. The initiation of subduction zones is intricately
...
Large meteorite impacts must have strongly affected the habitability of the early
Earth. Rocks of the Archean Eon record at least 16 major impact events, involving
bolides larger than 10 km in diameter. These impacts probably had severe, albeit temporary,
...
Engineering
Transforming atmospheric water vapor into liquid form can be a way to supply water
to arid regions for uses such as drinking water, thermal management, and hydrogen
generation. Many current methods rely on solid sorbents that cycle between capture
and ...
Fast, nondestructive three-dimensional (3D) imaging of live suspension cells remains
challenging without substrate treatment or fixation, precluding scalable single-cell
morphometry with minimal alterations. While optical sectioning techniques achieve
3D ...
Environmental Sciences
At the northern high latitudes, rapid warming, associated changes in the hydrological
cycle, and rising atmospheric CO2 concentrations, [CO2], are observed at present. Under rapid environmental changes, it is important to
understand the current and future ...
Climate warming enables easier access and operation in the Arctic, fostering industrial
and urban development. However, there is no comprehensive pan-Arctic overview of industrial
and urban development, which is crucial for the planning of sustainable ...
Epidemiological studies show a strong correlation between air pollution and fetal
growth restriction (FGR), but existing results are controversial due to inherent limitations,
such as causality of specific pollutants, developmental origin, and maternal–...
Metapopulation models have been instrumental in quantifying the ecological impact
of landscape structure on the survival of a focal species. However, extensions to
multiple species with arbitrary dispersal networks often rely on phenomenological
...
Mathematics
We consider certain convolution sums that are the subject of a conjecture by Chester,
Green, Pufu, Wang, and Wen in string theory. We prove a generalized form of their
conjecture, explicitly evaluating absolutely convergent sums
Physics
Quantum mechanics imposes limits on the statistics of certain observables. Perhaps
the most famous example is the uncertainty principle. Similar trade-offs also exist
for the simultaneous violation of multiple Bell inequalities. In the simplest case
of ...
We use electrostatic force microscopy to spatially resolve random telegraph noise
at the Si/SiO2 interface. Our measurements demonstrate that two-state fluctuations are localized
at interfacial traps, with bias-dependent rates and amplitudes. These two-...
Social Sciences
Anthropology
The relationship between sociopolitical organization and violence remains an enduring
question in anthropological research. Less studied is the articulation of gender with
violence in societies of different sociopolitical organization. We investigate the
...
Psychological and Cognitive Sciences
Reducing hostility in social media interactions is a key public concern. Most extant
research emphasizes how online contextual factors breed hostility. Here, we take a
different perspective and focus on the offline roots of hostility, that is, offline
...
Current research on memory indicates that learning is most effective when it involves
spaced retrieval practice of study materials. Here, we investigated whether the benefits
of both retrieval practice and spacing can be further boosted when variability ...
Nuanced portrayals of stigmatized groups in media have been shown to reduce prejudice.
In an online experiment (N = 749), we tested whether a feature film depicting incarcerated
peoples’ experiences in the criminal justice system can increase a) empathic ...
Sustainability Science
Climate warming enables easier access and operation in the Arctic, fostering industrial
and urban development. However, there is no comprehensive pan-Arctic overview of industrial
and urban development, which is crucial for the planning of sustainable ...
Ecological change in the Brazilian Amazon is closely linked to human mobility and
health. Mining, agriculture, logging, and other activities alter highly diverse ecological
and demographic contexts and subsequent exposure to diseases such as malaria. ...
Biological Sciences
Applied Biological Sciences
Fast, nondestructive three-dimensional (3D) imaging of live suspension cells remains
challenging without substrate treatment or fixation, precluding scalable single-cell
morphometry with minimal alterations. While optical sectioning techniques achieve
3D ...
The ability to remotely control the activity of chimeric antigen receptors (CARs)
with small molecules can improve the safety and efficacy of gene-modified T cells.
Split ON- or OFF-switch CARs involve the dissociation of tumor–antigen binding from
T cell ...
Many types of viruses infect insects and other arthropods. In contrast, little is
known about how arthropods sense viruses, although several innate immune pathways
including Toll have antiviral functions. Large DNA viruses in the family Baculoviridae are ...
Biochemistry
An RNA ligase ribozyme that catalyzes the joining of RNA molecules of the opposite
chiral handedness was optimized for the ability to synthesize its own enantiomer from
two component fragments. The mirror-image D- and L-ligases operate in concert to ...
Guanine-rich DNA forms G-quadruplexes (G4s) that play a critical role in essential
cellular processes. Previous studies have mostly focused on intramolecular G4s composed
of four consecutive guanine tracts (G-tracts) from a single strand. However, this
...
Aerobic glycolysis and immune evasion are two key hallmarks of cancer. However, how
these two features are mechanistically linked to promote tumor growth is not well
understood. Here, we show that the glycolytic enzyme enolase-1 (ENO1) is dynamically
...
Phosphoprotein phosphatases (PPPs) are the key serine/threonine phosphatases that
regulate all essential signaling cascades. In particular, Protein Phosphatase 1 (PP1)
dephosphorylates ~80% of all ser/thr phosphorylation sites. Here, we developed a ...
DNA repair processes modulate genotoxicity, mutagenesis, and adaption. Nucleotide
excision repair removes bulky DNA damage, and in Escherichia coli, basal excision repair, carried out by UvrA, B, C, and D, with DNA PolI and DNA ligase,
occurs genome-wide. ...
Biophysics and Computational Biology
Interactions mediated by intrinsically disordered protein regions (IDRs) pose formidable
challenges in structural characterization. IDRs are highly versatile, capable of adopting
diverse structures and engagement modes. Motivated by recent strides in ...
It is broadly recognized that intramolecular electric fields, produced by the protein
scaffold and acting on the active site, facilitate enzymatic catalysis. This field
effect can be described by several theoretical models, each of which is intuitive
to ...
The collective patterns that emerge in schooling fish are often analyzed using models
of self-propelled particles in unbounded domains. However, while schooling fish in
both field and laboratory settings interact with domain boundaries, these effects
are ...
Intrinsically disordered regions (IDRs) play a pivotal role in organellar remodeling.
They transduce signals across membranes, scaffold signaling complexes, and mediate
vesicular traffic. Their functions are regulated by constraining conformational ...
Cys-loop receptors are a large superfamily of pentameric ligand-gated ion channels
with various physiological roles, especially in neurotransmission in the central nervous
system. Among them, zinc-activated channel (ZAC) is a Zn2+-activated ion channel ...
Cell Biology
Intracellular protein delivery has the potential to revolutionize cell-biological
research and medicinal therapy, with broad applications in bioimaging, disease treatment,
and genome editing. Herein, we demonstrate successful delivery of a functional ...
Multivesicular endosomes (MVEs) sequester membrane proteins destined for degradation
within intralumenal vesicles (ILVs), a process mediated by the membrane-remodeling
action of Endosomal Sorting Complex Required for Transport (ESCRT) proteins. In ...
The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the
human spleen involves sequential processes of prefiltration, filtration, and postfiltration.
While prior work has elucidated the mechanisms underlying the first two ...
The dysfunction of the ubiquitin–proteasome system (UPS) facilitates the malignant
progression of hepatocellular carcinoma (HCC). While targeting the UPS for HCC therapy
has been proposed, identifying effective targets has been challenging. In this study,
...
Defective glucose-stimulated insulin secretion (GSIS) and β-cell senescence are hallmarks
in diabetes. The mitochondrial enzyme pyruvate carboxylase (PC) has been shown to
promote GSIS and β-cell proliferation in the clonal β-cell lines, yet its ...
The eIF4F translation initiation complex plays a critical role in melanoma resistance
to clinical BRAF and MEK inhibitors. In this study, we uncover a function of eIF4F
in the negative regulation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma
(...
Chimeric antigen receptor T cell therapies have achieved great success in eradicating
some liquid tumors, whereas the preclinical results in treating solid tumors have
proven less decisive. One of the principal challenges in solid tumor treatment is
the ...
The maintenance of lipid asymmetry on the plasma membrane is regulated by flippases,
such as ATP8A2, ATP11A, and ATP11C, which translocate phosphatidylserine and phosphatidylethanolamine
from the outer leaflet to the inner leaflet. We previously ...
T cell receptor (TCR) engagement causes a global cellular response that entrains signaling
pathways, cell cycle regulation, and cell death. The molecular regulation of mRNA
translation in these processes is poorly understood. Using a whole-genome CRISPR ...
Ecology
Ethanol, a natural by-product of sugar fermentation, can be found in various fruits
and nectar. Although many animals routinely consume ethanol in low concentrations
as part of their natural diets, its inherent toxicity can cause severe damage. Even
...
The loss of wild plant populations is often assumed to lead to coextinctions, particularly
among specialized insects. Despite global declines in both terrestrial insects and
plants, the relationship between these trends remains elusive. Here, we address ...
Although the impacts of invasive plants on soil ecosystems are widespread, the role
and impacts of invader root traits in structuring microbial communities remain poorly
understood. Here, we present a macroecological study investigating how plant invaders
...
Environmental Sciences
At the northern high latitudes, rapid warming, associated changes in the hydrological
cycle, and rising atmospheric CO2 concentrations, [CO2], are observed at present. Under rapid environmental changes, it is important to
understand the current and future ...
Evolution
The dominance of beneficial mutations is a key evolutionary parameter affecting the
rate and genetic basis of adaptation, yet it is notoriously difficult to estimate.
A leading method to infer it is to compare the relative rates of adaptive substitution
...
Genetics
As their statistical power grows, genome-wide association studies (GWAS) have identified
an increasing number of loci underlying quantitative traits of interest. These loci
are scattered throughout the genome and are individually responsible only for ...
Epidemiologic associations estimated from observational data are often confounded
by genetics due to pervasive pleiotropy among complex traits. Many studies either
neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS)
in ...
Immunology and Inflammation
Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance
and immune escape, and they are a crucial source of tumor recurrence and metastasis.
However, the underlying mechanisms remain unrevealed. We demonstrate that enriched
...
The intestinal lumen is rich in gut microbial metabolites that serve as signaling
molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites
and can act as key mediators that translate gut luminal signals into host immune ...
Antibody responses induced by current vaccines for influenza and SARS-CoV-2 often
lack robust cross-reactivity. As hubs where diverse immune cells converge and interact,
the alterations in the immune microenvironment within lymph nodes (LNs) are ...
To withstand complex microbial challenges, the mammalian gut largely depends on the
secretion of diverse antimicrobial proteins. Type III interferons (IFNλs) are ordinarily
considered inducible antiviral cytokines involved in intestinal immunity. Unlike ...
Complement activation through antibody–antigen complexes is crucial in various pathophysiological
processes and utilized in immunotherapies to eliminate infectious agents, regulatory
immune cells, or cancer cells. The tertiary structures of the four IgG ...
Both genetic and environmental factors contribute to multiple sclerosis (MS) risk.
Infection with the Epstein–Barr virus (EBV) is the strongest environmental risk factor,
and HLA-DR15 is the strongest genetic risk factor for MS. We employed computational
...
Atherosclerosis results from lipid-driven inflammation of the arterial wall that fails
to resolve. Imbalances in macrophage accumulation and function, including diminished
migratory capacity and defective efferocytosis, fuel maladaptive inflammation and
...
Microbiology
Syncytin-1, a human fusogenic protein of retroviral origin, is crucial for placental
syncytiotrophoblast formation. To mediate cell-to-cell fusion, Syncytin-1 requires
specific interaction with its cognate receptor. Two trimeric transmembrane proteins,
...
The Type VI Secretion System (T6SS) is a sophisticated mechanism utilized by gram-negative
bacteria to deliver toxic effector proteins into target cells, influencing microbial
community dynamics and host interactions. In this study, we investigated the ...
Bacteria power rotation of an extracellular flagellar filament for swimming motility.
Thousands of flagellin subunits compose the flagellar filament, which extends several
microns from the bacterial surface. It is unclear whether bacteria actively control
...
EfpA, the first major facilitator superfamily (MFS) protein identified in Mycobacterium tuberculosis (Mtb), is an essential efflux pump implicated in resistance to multiple drugs. EfpA-inhibitors
have been developed to kill drug-tolerant Mtb. However, the ...
Neuroscience
Meta-learning enables us to learn how to learn the same or similar tasks more efficiently.
Decision-making literature theorizes that a prefrontal network, including the orbitofrontal
and anterior cingulate cortices, underlies meta-learning of decision ...
Sleep is an essential behavior that supports lifelong brain health and cognition.
Neuronal synapses are a major target for restorative sleep function and a locus of
dysfunction in response to sleep deprivation (SD). Synapse density is highly dynamic
...
Physiology
Sexual reproduction requires the choreographed interaction of female cells and molecules
with sperm and seminal fluid. In internally fertilizing animals, these interactions
are managed by specialized tissues within the female reproductive tract (FRT), ...
Plant Biology
Abscission is the programmed separation of plant organs. It is widespread in the plant
kingdom with important functions in development and environmental response. In Arabidopsis,
abscission of floral organs (sepals, petals, and stamens) is controlled by ...
Psychological and Cognitive Sciences
The hippocampus is functionally specialized along its longitudinal axis with intricate
interactions with cortical systems, which is crucial for understanding development
and cognition. Using a well-established connectopic mapping technique on two large
...
Corrections
Cover image: Pictured is an illustration of a pre-avian theropod flapping its wings to run across a lakeshore. T. Alexander Dececchi et al. examined a fossil trackway in South Korea that contained foot tracks from a theropod from the Lower Cretaceous Period. The speed needed to produce the ratio of stride length to footprint length observed in the foot tracks using hindlimb propulsion alone far exceeds the speeds of quickfooted modern animals such as roadrunners, ostriches, and cheetahs. Hence, the authors suggest, wing flap-assisted ground locomotion might account for the observed tracks at reduced speeds. See the article by Dececchi et al. e2413810121. Image credit: Julius T. Csotonyi (artist).
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