Table Of Contents Page, PNAS Volume 123, Number 2
This Week in PNAS
Editorial
News Feature
Commentaries
Perspective
The Kunming-Montreal Biodiversity Targets present the most ambitious and serious conservation
agenda ever developed—the overarching goal of preserving 30% of the planet by 2030.
An organizational framework is now in place to deliver stable, predictive, ...
Letters
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Brief Report
Cognitive aging research has long observed that older adults’ autobiographical memories
and future thoughts, as assessed in laboratory contexts, lack spatiotemporal detail
compared to young adults. Does this pattern also hold in everyday contexts? Across
...
Physical Sciences
Applied Mathematics
Ecological systems can experience sudden and often irreversible regime shifts, also
known as critical transitions, with major consequences such as desertification, locust
outbreaks, and coral reef collapse. Anticipating these shifts is a central challenge,...
Understanding the geographic spread of emerging respiratory viruses is critical for
pandemic preparedness, yet the early spatiotemporal dynamics of the 2009 H1N1 pandemic
influenza and severe acute respiratory syndrome coronavirus 2 in the United States
...
Applied Physical Sciences
Immune cell populations are dysregulated in COVID-19 for currently unknown reasons:
Plasmacytoid dendritic cell (pDC) populations are reduced, thus hampering antiviral
responses. CD8+ T cell populations are reduced, the level of which has emerged as an ...
Organic single crystals endowed with intrinsic anisotropy hold great promise for the
realization of miniaturized, polarization-sensitive photodetectors. However, conventional
dip-coating approaches struggle to produce wafer-scale single-crystalline films, ...
Sequence-selective dynamic bonds (SSDBs) are ubiquitous in nature and man-made systems
as diverse as DNA, proteins, and synthetic sequence-defined oligomers. The specific
and dynamic nature of this class of bonds enables encoded linkers to program the ...
Biophysics and Computational Biology
The use of oxygen and nitrate as terminal electron acceptors provides organisms with
a huge amount of available energy but necessitates methods to detoxify reactive intermediates.
The mechanisms of NO and O2 detoxification in many organisms involve ...
Chemistry
Gene delivery has emerged as a groundbreaking technique for altering gene expression,
offering new possibilities in treating a vast array of diseases. We report a layer-by-layer
elastin-like polypeptide nucleic acid nanoparticle (LENN) system for mRNA ...
We present an alternative approach to conventional small-molecule and antisense strategies
for selectively targeting expanded CUG-RNA repeats associated with Myotonic Dystrophy
type 1. Our alternatively designed nucleic acid ligands uniquely integrate ...
For valuable ammonia synthesis and green nitrogen recycling, electrocatalytic nitrate
reduction reaction (NO3RR) presents a sustainable alternative to the conventional Haber–Bosch process. The
NO3RR involves intricate, multi-step proton-coupled electron ...
Aqueous salt solutions occur in many aspects of chemistry, biology, and geology. Increasing
the concentration of most aqueous salt solutions increases the viscosities. In contrast,
adding CsCl to water initially decreases the viscosity, but at moderate ...
Cell-specific regulation of endogenous G protein–coupled receptors (GPCRs) is crucial
for understanding their roles in physiological processes. We present chemogenetic
tools using shield-1-dependent irreversible protein switches to regulate peptide ...
Computer Sciences
The human brain excels at complex tasks with remarkable efficiency, adaptability,
and resilience, making it a powerful source of inspiration for AI. Here, we present
a neural dynamics model inspired by the primate dorsal visual pathway, a circuit crucial
...
Earth, Atmospheric, and Planetary Sciences
The rise of atmospheric oxygen during the Great Oxidation Event (GOE) (ca. 2.5 to
2.1 billion years ago) permanently transformed Earth’s biogeochemical cycles. The
chemistry of contemporaneous marine carbonates provides a window into operation of
the ...
A ~fivefold decrease in the atmospheric concentration of CO2 took place during the Cenozoic. This has often been viewed within the context of
silicate weathering changes, although the specific contributions of the potential
drivers remain poorly ...
Engineering
Nature’s structural composites, such as bone and wood, achieve mechanical performance
through hierarchical multimaterial design. Though, their real vantage lies in the
exceptional ability to repeatedly heal after damage. Synthetic fiber-reinforced polymer
...
High-precision in vivo therapeutic technologies that establish three-dimensional (3D),
multimodal neural interfaces with targeted biotissues offer significant clinical potential
for the timely treatments of localized peripheral nerve injury (PNI). Current ...
While transcranial neuroimaging of individual capillary function holds transformative
potential for diagnostics, it has proven difficult to achieve. Superresolution ultrasound,
while capable of achieving micron-scale resolution, relies on the accumulation ...
Physics
Molecules in dense environments, such as biological cells, are subjected to forces
that fluctuate both in time and in space. While spatial fluctuations are captured
by Lifson-Jackson-Zwanzig’s model of “diffusion in a rough potential,” and temporal
...
Social Sciences
Anthropology
Culture has been a central concept in the social sciences for well over a century.
Yet, a theory of culture with an associated measurement model providing the means
to systematically study its effects has proven elusive. Developments in cognitive
culture ...
Psychological and Cognitive Sciences
Early adversity is associated with brain changes that negatively impact development,
social-emotional functioning, and academic achievement. The multifaceted nature of
adversity complicates efforts to isolate specific factors that affect brain development
...
How do shared narratives emerge in decentralized online networks? Prior research using
simplified group coordination tasks (e.g., face-naming) shows network structure shapes
group consensus, but the underlying cognitive mechanisms remain unclear. Here, we
...
Gender stereotypes, defined as widely shared beliefs about the typical attributes
of women and men, have far-reaching consequences for both stereotyped groups. This
preregistered research examined cross-cultural variation in gender stereotypes based
on ...
Biological Sciences
Applied Biological Sciences
Tissue engineering strategies predominantly consist of the autologous generation of
living substitutes capable of restoring damaged body parts. Persisting challenges
with patient-specific approaches include inconsistent performance, high costs, and
...
Biochemistry
CatSper serves as the primary Ca2+ entry pathway in the principal piece of sperm flagellum and is crucial for sperm
motility and fertility. Sperm lacking functional CatSper channels fail to undergo
hyperactivation during fertilization, leading to complete ...
Biopsy-resolved cryo-EM structures of amyloid fibrils provide molecular insights into AL amyloidosis
Systemic light chain amyloidosis (AL) is characterized by amyloid fibril deposition
in multiple organs, often severely affecting cardiac function. In this study, we extracted
amyloid fibrils directly from abdominal fat and cardiac tissue biopsies obtained ...
Protein misfolding in the brain is a key pathological hallmark of neurodegenerative
diseases. Optical imaging of misfolded proteins in disease models is essential for
elucidating etiology and early diagnosis. However, developing specific optical imaging
...
J-domain protein (JDP) chaperones function widely in proteostasis. Notably, eukaryotic
class B JDPs of the cytosol/nucleus prevent assembly or drive disassembly of amyloid
aggregates known to cause neurodegenerative diseases, yet their evolutionary origin
...
Biophysics and Computational Biology
Molecules in dense environments, such as biological cells, are subjected to forces
that fluctuate both in time and in space. While spatial fluctuations are captured
by Lifson-Jackson-Zwanzig’s model of “diffusion in a rough potential,” and temporal
...
The use of oxygen and nitrate as terminal electron acceptors provides organisms with
a huge amount of available energy but necessitates methods to detoxify reactive intermediates.
The mechanisms of NO and O2 detoxification in many organisms involve ...
VcINDY, the sodium-dependent dicarboxylate transporter from Vibrio cholerae, is responsible for C4-carboxylate uptake into cells. The molecular mechanism of how VcINDY physically moves
substrates across the membrane, and does so in an energetically ...
Adenosine-to-inosine (A-to-I) RNA editing by ADAR enzymes shapes transcript fate and
underpins emerging RNA editing therapeutics, yet predicting which adenosines are edited
remains difficult. We introduce ADAR-GPT, a model-agnostic fine-tuning framework ...
Cell Biology
Gene delivery has emerged as a groundbreaking technique for altering gene expression,
offering new possibilities in treating a vast array of diseases. We report a layer-by-layer
elastin-like polypeptide nucleic acid nanoparticle (LENN) system for mRNA ...
Cellular rejuvenation through transcriptional reprogramming is an exciting approach
to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq
screening, we developed a systematic approach to identify single transcription factor
(...
Diabetic peripheral neuropathy (DPN), the most common complication of diabetes, lacks
effective treatments and is characterized by early axonal degeneration mediated by
sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1). Here,
...
Skeletal muscle fibrosis, as occurs with age, in response to injury, or in the setting
of degenerative diseases, results in impairments of muscle regeneration and function.
Fibro-adipogenic progenitors (FAPs), a distinct population of muscle-resident ...
Developmental Biology
The Ciona heart cell lineage can be accurately traced back to a pair of blastomeres, the B7.5
cells, that form at the 64-cell stage. In addition to the adult heart, the B7.5 cells
also contribute to two tail muscle cells in the larva, as well as the ...
Ecology
Ecological systems can experience sudden and often irreversible regime shifts, also
known as critical transitions, with major consequences such as desertification, locust
outbreaks, and coral reef collapse. Anticipating these shifts is a central challenge,...
Seasonal dormancy in extratropical trees is a critical adaptation that synchronizes
growth with favorable climatic conditions. Traditionally, the effective chilling temperatures
(ECT) required for dormancy release have been assumed to be fixed, ranging ...
Environmental Sciences
The great phytoplanktonic shift from green to red plastid lineage dominance in the
early Mesozoic marks a primary producer revolution in marine ecosystems, facilitating
the rise of modern ecosystems and impacting global carbon cycling and energy flows.
...
Evolution
The great phytoplanktonic shift from green to red plastid lineage dominance in the
early Mesozoic marks a primary producer revolution in marine ecosystems, facilitating
the rise of modern ecosystems and impacting global carbon cycling and energy flows.
...
The theory of sex allocation is hailed as one of evolutionary biology’s great successes.
But while it has successfully predicted strategies of resource allocation to male
versus female offspring under a wide range of conditions in species with separate
...
The ecological context of developmental physiology remains largely unexplored. We
previously showed that thermal selection primarily targets early embryos in Drosophila melanogaster. Here, we used advanced introgression and pooled whole-genome ...
Phylodynamic analysis has been instrumental in elucidating epidemiological and evolutionary
dynamics of pathogens. Bayesian phylodynamics integrates out phylogenetic uncertainty,
which is typically substantial in phylodynamic datasets due to limited ...
Evolutionary transitions in mating strategy have profound consequences for genetic
variation and adaptation. In Saccharomyces cerevisiae, mating-type switching is a central feature of the life cycle that enables haploid
cells to be self-fertile and mate ...
Sex determination is fundamental to eukaryotic life, yet its molecular basis varies
widely across the tree of life. In most animal clades, sex-determining mechanisms
are highly diverse and evolve rapidly. Here, we identify an exception in aculeate
...
Lethal mutagenesis is a strategy to achieve viral extinction by drugging viral mutation
rates beyond an extinction threshold. Accurate estimation of the extinction threshold
is critical, as elevating viral mutation rates near, but not past this threshold ...
Multiple primate species, including humans, evolved brains that are exceptionally
large relative to their body sizes. These large brains coevolved with metabolic adaptations
that enhance cerebral energy supply, including increased circulating glucose ...
Genetics
Genome scale engineering has enabled codon compression of the universal genetic code
to eliminate seven codons in Escherichia coli, but to allow more radical schemes for codon compression and reassignment to be tested
at genome scale, while avoiding ...
For thousands of years, humans have domesticated animals and cultivated crops by managing
reproduction and selecting for desirable traits. In contrast, microbial domestication
has often occurred unintentionally, and the variation of life cycle as well as ...
Ductal carcinoma in situ (DCIS) is a precursor mammary lesion characterized by abnormal
epithelial cells in mammary ducts that remain confined to the luminal space. Not all
DCIS becomes invasive, and no strategy currently exists in patients to stratify ...
Gene family expansions are critical for functional diversification, yet the contributions
of paralogs to metabolic pathways are often unclear. In Caenorhabditis, the expanded O-acyltransferase (OAC) family—enzymes that transfer acyl groups to
hydroxylated ...
Immunology and Inflammation
Immune cell populations are dysregulated in COVID-19 for currently unknown reasons:
Plasmacytoid dendritic cell (pDC) populations are reduced, thus hampering antiviral
responses. CD8+ T cell populations are reduced, the level of which has emerged as an ...
IL-33-induced signals via membrane-bound ST2 (ST2L) are critical for allergies. However,
the physiological role of endogenous soluble ST2 (sST2) remains elusive. Here, we
generated sST2-deficient mice with intact ST2L using the CRISPR/Cas9 system. Skin
...
High expression alleles of the innate cytokine, macrophage migration inhibitory factor
(MIF), are associated with the development or the severity of autoimmune inflammatory
diseases, including rheumatoid arthritis. Numerous studies support MIF’s role in ...
Nonsense-mediated decay (NMD) is an mRNA decay pathway which degrades potential harmful
transcripts that contain premature termination codons. However, NMD’s importance also
extends to the control of isoform abundance under physiological conditions. ...
Interleukin-17-producing γδT cells (γδT17 cells) play a dual role in immune regulation,
serving as both protectors in various tissues and orchestrators of inflammatory responses
in autoimmune diseases, including experimental autoimmune encephalomyelitis (...
Post-acute sequelae of COVID-19 (PASC) encompasses persistent neurological disease,
including olfactory and cognitive dysfunction. The basis for this dysfunction is poorly
understood. Here, we report neurological dysfunction for at least 120 d ...
Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships
with the resident microbiota, and provides tolerance to food antigens, safeguarding
critical nutrient absorption and barrier functions of this mucosal tissue. Despite
...
Medical Sciences
While transcranial neuroimaging of individual capillary function holds transformative
potential for diagnostics, it has proven difficult to achieve. Superresolution ultrasound,
while capable of achieving micron-scale resolution, relies on the accumulation ...
Metabolic dysfunction–associated steatotic liver disease (MASLD) is characterized
by liver steatosis with cardiometabolic risk factors like dyslipidemia. Patients may
progress from steatosis alone to complications such as fibrosis, end-stage liver disease,...
Head and neck squamous cell carcinoma (HNSCC) involves aggressive invasion at the
tumor–host interface, particularly at the leading edge. However, the mechanisms sustaining
this invasive front remain unclear. Here, we performed spatially resolved ...
Microbiology
Resource competition strongly shapes microbial community dynamics and functionality.
In polysaccharide-degrading communities, primary degraders release hydrolytic enzymes,
whereas exploiters consume released products without producing enzyme themselves.
...
Bacterial motility and biofilm formation are essential for the adaptation and survival
of Vibrio cholerae, the causative agent of cholera. In many bacterial species, the second messenger
c-di-GMP regulates these processes through PilZ domain proteins, ...
Neuroscience
Cell-specific regulation of endogenous G protein–coupled receptors (GPCRs) is crucial
for understanding their roles in physiological processes. We present chemogenetic
tools using shield-1-dependent irreversible protein switches to regulate peptide ...
The human brain excels at complex tasks with remarkable efficiency, adaptability,
and resilience, making it a powerful source of inspiration for AI. Here, we present
a neural dynamics model inspired by the primate dorsal visual pathway, a circuit crucial
...
The ability to adapt to a dynamic world relies on detecting, learning, and responding
to environmental changes. The detection of novelty serves as a critical indicator
of such changes, priming mechanisms to detect and respond to goal-relevant information.
...
Based mainly on rodents studies, forty-hertz (40-Hz) physical stimulation has been
regarded as a potential noninvasive treatment for Alzheimer’s disease (AD). Considering
the brain differences between rodents and humans, the effects of 40-Hz physical ...
Prenatal brain activity has long lasting effects on subsequent neurodevelopment. It
is unclear if early brain activity is dominated by cell intrinsic, synaptic, or nonsynaptic
mechanisms. We address this question by analyzing Caenorhabditis elegans embryo ...
Parkinson’s disease (PD) is a progressive neurodegenerative disease that casts a significant
shadow over global health and the identification of therapeutic targets for PD will
empower more effective clinical treatment. The gene encoding the ...
The human cerebellar cortex, despite containing the majority of the brain’s neurons,
remains poorly characterized in vivo due to its extreme folding and thin laminar architecture.
Here, we present a high-resolution imaging framework based on parallel-...
Ischemic white matter damage is a significant pathological feature of chronic cerebral
hypoperfusion, leading to cognitive impairments. However, the underlying molecular
mechanisms remain poorly understood. In this study, we identify a causal association
...
Associative learning allows animals to learn the predictive relationships between
events. Presentation of a conditioned stimulus (CS) preceding an unconditioned stimulus
(US) within a short interval associates these events. However, little is known about
...
Although radial-like neural stem cells (rNSCs) give rise to functional neurons throughout
life in discrete regions of the adult brain, their functions are not limited to neurogenesis.
Recent studies indicate that the processes of rNSCs approach and/or ...
Aging is associated with the decline of many bodily functions including motor coordination.
Aging-related impairment in motor coordination can result in falls, which reduce independence,
health span, and quality of life in the elderly. To study the neural ...
Huntington disease (HD) is caused by an expansion of the polyglutamine (polyQ) tract
in the huntingtin protein (HTT), leading to its misfolding and aggregation. The subcellular
localization of mutant HTT (mHTT) aggregates critically influences their ...
Epigenetic mechanisms, including histone acetylation, regulate learning and memory
and underlie Alzheimer’s disease and related dementia (ADRD). Acetyl-CoA synthetase
2 (ACSS2), an enzyme generating acetyl-CoA, locally regulates histone acetylation
and ...
Physiology
Sphingosine 1-phosphate (S1P) is a bioactive lipid that circulates in plasma bound
to high-density lipoproteins (HDL) and albumin. Circulating S1P levels correlate positively
with systolic blood pressure (BP) in hypertension and negatively with severity ...
Plant Biology
The apoplast is an important battlefield in plant–pathogen interactions. The late
blight oomycete pathogen Phytophthora infestans, for instance, secretes cystatin-like protease inhibitors EpiC1 and EpiC2B to suppress
C14, a papain-like immune protease ...
Population Biology
Understanding the geographic spread of emerging respiratory viruses is critical for
pandemic preparedness, yet the early spatiotemporal dynamics of the 2009 H1N1 pandemic
influenza and severe acute respiratory syndrome coronavirus 2 in the United States
...
The exorbitant cost of prescription pharmaceuticals is a critical and long-standing
concern facing the United States (US). To curb rising drug costs, international reference
pricing, aligning drug prices with those in other high-income countries, has ...
Psychological and Cognitive Sciences
Humans predict the timing of imminent events to generate fast and precise actions,
decisions, and other behaviors. Such temporal anticipation is critical over wide timescales,
and especially salient over the range from hundreds of milliseconds to a few ...
Corrections
Retraction
Cover image: Pictured is the European hornet (Vespa crabro). Chuanxin Yu et al. compared genomes across multiple species in the order Hymenoptera and identified a sex-determining locus that has been conserved for more than 150 million years. The conserved locus is a stark contrast to the highly variable molecular sex-determining mechanisms across the rest of the insect class. Despite its deep conservation, the sequence of the locus differs across species, offering insights into the evolution of sex-determining mechanisms. See the article by Yu et al. e2522417123. Image credit: Nicolas J. Vereecken (Université Libre de Bruxelles, Brussels, Belgium).
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