Table Of Contents Page, PNAS Volume 122, Number 22
This Week in PNAS
Inner Workings
Retrospective
Lynn Landmesser, whose studies transformed our view of how neurons find the proper
partners on which to form synapses, died at the age of 80 in November 2024. Using
elegant electrophysiological methods, she showed that specificity is apparent from
the ...
Commentaries
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Perspectives
A growing body of research suggests that the recent generation of large language model
(LLMs) excel, and in many cases outpace humans, at writing persuasively and empathetically,
at inferring user traits from text, and at mimicking human-like conversation ...
The process of domestication is commonly perceived as a human achievement, and domestic
species are typically assumed to be those under human control. Domestic species have
emerged from a greater diversity of interactions than this perspective allows, and
...
Letters
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Utilizing Martian samples for future planetary exploration—Characterizing hazards and resources
This article has a reply:Physical Sciences
Applied Physical Sciences
We investigate mechanisms for the observed nonlinear growth in the number of polymer
vesicles generated during a photo-Reversible Addition-Fragmentation Chain Transfer-based
polymerization-induced self-assembly (PISA) reaction. Our experimental results ...
The maximum spreading of an impacting liquid drop is a key metric for characterizing
the fundamental fluid process of drop impact. While extensively studied for Newtonian
liquids, how far a non-Newtonian drop can spread upon impacting a solid substrate
...
The next generation of force fields for molecular dynamics will be developed using
a wealth of data. Training systematically with experimental data remains a challenge,
however, especially for machine-learning potentials. Differentiable molecular ...
The synthesis of new polyhydrides with high superconducting Tc is challenging owing to the high pressures and temperatures required. In this study,
we used machine-learning potential molecular dynamics simulations to investigate the
initial stage of ...
Biophysics and Computational Biology
Spleen tyrosine kinase (Syk) mediates early signaling events in immunity by coupling
membrane receptors to immune responses. Syk comprises a tandem SH2 (tSH2) regulatory
module—two SH2 domains connected by a structured linker—and a kinase domain. The ...
The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis,
a complex process involving hundreds of proteins and RNAs. The proper execution of
ribosome biogenesis likely depends on the material properties of the nucleolus. ...
The nucleolus is a multicomponent structure made of RNA and proteins that serves as
the site of ribosome biogenesis within the nucleus. It has been extensively studied
as a prototype of a biomolecular condensate whose assembly is driven by phase ...
The eukaryotic leading-strand DNA polymerase ε (Polε) is a dual-function enzyme with
a proofreading 3′-5′ exonuclease (exo) site located 40 Å from the DNA synthesizing pol site. Errors in Polε proofreading can cause various mutations, including C-to-G ...
T cells display the remarkable ability to detect single foreign peptides displayed
on target cells, while ignoring highly abundant self-peptides. This selectivity has
been explained by kinetic proofreading in the T cell receptor (TCR) signaling pathway,
...
Chemistry
Pigmentation plays a vital role in the survival of organisms, supporting functions
such as camouflage, communication, and mate attraction. In vertebrates, these functions
are mediated by specialized pigment cells known as chromatophores of which, uric ...
Coherent superposition of electronic states, created by ionizing a molecule, can initiate
ultrafast dynamics of the electron density. Correlation between nuclear and electron
motions, however, typically dissipates the electronic coherence in only a few ...
Tessellation, as an ancient and fascinating mathematical pursuit, has not only captivated
mathematicians but also has attracted chemists’ increasing attention at the molecular
level in recent years. Exploring tessellation at the molecular scale is pivotal ...
Earth, Atmospheric, and Planetary Sciences
The extent of moderately volatile elements (MVE) depletion and its effects on the
Moon’s evolutionary history remain contentious, partly due to unintentionally biased
sampling by the Apollo missions from the Procellarum KREEP Terrane. In this study,
we ...
Partial melting of metasedimentary rocks is generally accepted as the source of peraluminous
Himalayan leucogranites—they are commonly considered as pure “S-type” (sedimentary
source) granites. Here, a uniquely comprehensive geochronological and ...
Natural ice plays salient roles in making the Earth habitable and sustainable. Previously
overlooked, its role in chemical processes is now of emerging interest, particularly
due to the freeze concentration effect, which can substantially promote chemical ...
Statistics
NMR-based metabolic biomarkers provide comprehensive insights into human metabolism;
however, extracting biologically meaningful patterns from such high-dimensional data
remains a significant challenge. In this study, we propose a manifold-fitting-based
...
The rise of foundation models marks a paradigm shift in machine learning: instead
of training specialized models from scratch, foundation models are trained on massive
datasets before being adjusted or fine-tuned to make predictions on smaller datasets.
...
Social Sciences
Economic Sciences
The rise of foundation models marks a paradigm shift in machine learning: instead
of training specialized models from scratch, foundation models are trained on massive
datasets before being adjusted or fine-tuned to make predictions on smaller datasets.
...
Biological Sciences
Agricultural Sciences
Rhomboid-mediated cleavage of the immune receptor XA21 protects grain set and male fertility in rice
To maintain growth and to successfully reproduce, organisms must protect key functions
in specific tissues, particularly when countering pathogen invasion using internal
defensive proteins that may disrupt their own developmental processes. The rice ...
Applied Biological Sciences
Interleukin (IL)-23 is a validated therapeutic target in inflammatory bowel disease.
While antibodies targeting IL23 demonstrate clinical efficacy, they face challenges
such as high costs, safety risks, and the necessity of parenteral administration.
Here,...
A full spontaneous single-cell Raman spectrum captures the metabolic phenome in a
label-free and noninvasive manner. However, Raman-activated cell sorting (RACS) of
rare target cells from highly heterogeneous systems has remained largely conceptual.
Here, ...
Aberrant activation and overexpression of the epidermal growth factor receptor (EGFR)
occurs in various solid cancers and often correlates with poor outcome. The clinical
benefit from EGFR-targeted therapies is usually short-lived, with resistance being
...
Biochemistry
Spleen tyrosine kinase (Syk) mediates early signaling events in immunity by coupling
membrane receptors to immune responses. Syk comprises a tandem SH2 (tSH2) regulatory
module—two SH2 domains connected by a structured linker—and a kinase domain. The ...
The eukaryotic leading-strand DNA polymerase ε (Polε) is a dual-function enzyme with
a proofreading 3′-5′ exonuclease (exo) site located 40 Å from the DNA synthesizing pol site. Errors in Polε proofreading can cause various mutations, including C-to-G ...
FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced
forms of lipophilic quinone antioxidants, such as coenzyme Q10 and vitamin K. These
quinone antioxidants function as radical scavenging agents that prevent the propagation
...
A fully functional Dicer helicase, present in the modern arthropod, uses energy from
ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA
cleavage required for efficient antiviral defense. However, modern Dicer orthologs
...
The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates
critical physiological and pathological processes, ranging from sleep regulation to
inflammatory responses and cardiovascular function. Despite its therapeutic significance,...
Biophysics and Computational Biology
Microtubules are dynamic cytoskeletal polymers that add and lose tubulin dimers at
their ends. Microtubule growth, shortening, and transitions between them are linked
to GTP hydrolysis. Recent evidence suggests that flexible tubulin protofilaments at
...
Mitochondrial damage determines cell fate, leading to mitochondrial autophagy or cellular
apoptosis in health and disease. The molecular mechanisms and role of the acto-myosin
cytoskeleton regulating mitochondrial clearance and membrane remodeling are ...
Voltage-gated calcium (Ca) channels are pivotal in cellular signaling due to their selective calcium ion permeation
upon membrane depolarization. While previous studies have established the highly selective
permeability of Ca channels, the detailed ...
Cell Biology
The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis,
a complex process involving hundreds of proteins and RNAs. The proper execution of
ribosome biogenesis likely depends on the material properties of the nucleolus. ...
The nucleolus is a multicomponent structure made of RNA and proteins that serves as
the site of ribosome biogenesis within the nucleus. It has been extensively studied
as a prototype of a biomolecular condensate whose assembly is driven by phase ...
Pigmentation plays a vital role in the survival of organisms, supporting functions
such as camouflage, communication, and mate attraction. In vertebrates, these functions
are mediated by specialized pigment cells known as chromatophores of which, uric ...
Excess amounts of saturated fatty acids (FAs) are toxic to organisms, a condition
termed lipotoxicity, which is often accompanied by pleiotropic cellular and tissue
dysfunction. Here, we show that pentadecanoic acid (C15:0) exerts toxicity on the
fission ...
Two endogenous Dictyostelium discoideum chemorepellents use different mechanisms to induce repulsion
The directed movement of eukaryotic cells is critical for processes such as development
and immune responses. While much is known about chemoattraction, much less is known
about chemorepulsion. The eukaryotic amoeba Dictyostelium discoideum secretes a 60 ...
Ferroptosis is a cell death mechanism distinguished by its dependence on iron-mediated
lipid oxidation. Cancer cells highly resistant to conventional therapies often demonstrate
lipid metabolic and redox vulnerabilities that sensitize them to cell death ...
Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus,
pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput
studies showed interconnection between ATP8B1 and ...
DNA double-strand breaks (DSBs) are harmful lesions and major sources of genomic instability.
Studies have suggested that DSBs induce local transcriptional silencing that consequently
promotes genomic stability. Several factors have been proposed to ...
Maintenance of pH within membranous organelles is crucial for cellular processes such
as posttranslational modifications, ligand–receptor interactions, and proteostasis.
The precise mechanisms that determine the luminal pH of each organelle are not fully
...
Clathrin-mediated endocytosis (CME) begins with the assembly of clathrin onto the
plasma membrane. These structures grow and stabilize to form clathrin-coated pits
(CCPs), which invaginate and accumulate cargo. Finally, through membrane fission,
CCPs ...
Developmental Biology
Melanocyte development involves key pathways that are often recapitulated during melanoma
initiation, highlighting the importance of understanding these regulatory processes.
Our study identifies mgat4b, a glycosyl transferase involved in selective N-...
Evolution
The ecological upheavals produced by the Cretaceous–Paleogene mass extinction event
(K-Pg, −66 Ma) have been mostly studied at large scale with emphasis on clades’ diversity
dynamics. How this event affected the structure of paleocommunities is ...
The tight link between brain and skull formation is a fundamental aspect of vertebrate
evolution and embryogenesis. Their developmental synchronization is essential for
structural and functional integration. The brain and skull shape coevolution is ...
Evolution is often uneven in its pace and outcomes, with long periods of stasis interrupted
by abrupt increases in morphological and ecological disparity. With thousands of gene
histories, phylogenomics can uncover the genomic signatures of these broad ...
Life history traits influence marine species dispersal and habitat colonization. Medusozoans
(jellyfish and siphonophores) exhibit diverse life cycles, evolved from an ancestral
cycle alternating between a benthic polyp and a pelagic medusa. Despite their ...
Genetics
In eukaryotic genomes, DNA is packaged into nucleosomes to form chromatin. The incorporation
of canonical or variant histones into nucleosomes confers different properties and
influences chromatin structure to regulate cellular processes, including ...
Gastric cancer ranks as the fifth most common human cancer worldwide and has a poor
survival rate and limited treatment options. Despite the high prevalence and mortality
rate, the genetic etiology is largely unknown. In dogs, a clinically and ...
Many human phenotypic traits vary between the sexes, including adult height for which
males are, on average, 13 cm taller than females. The biological mechanisms for this
sexual dimorphism are not entirely understood. One hypothesis to explain the sexual
...
Immunology and Inflammation
T cells display the remarkable ability to detect single foreign peptides displayed
on target cells, while ignoring highly abundant self-peptides. This selectivity has
been explained by kinetic proofreading in the T cell receptor (TCR) signaling pathway,
...
Upon injury, epithelial-derived IL-18 is released and induces an inflammatory response
in underlying IL18R1+ lamina propria cells. Notably, Il18r1 is also predicted to be expressed and functional in intestinal epithelial cells (IECs),
since epithelial ...
Bispecific T cell engagers (TcEs) link T cell receptors to tumor-associated antigens
on cancer cells, forming cytotoxic immunological synapses (IS). Close membrane-to-membrane
contact (≤13 nm) has been proposed as a key mechanism of TcE function. To ...
During infection, foreign DNA is sensed by cyclic GMP-AMP synthase (cGAS) leading
to the production of cGAMP, STING-dependent type I interferon and proinflammatory
cytokine expression, and autophagy. To prevent a response to self-DNA, cGAS activity
is ...
Medical Sciences
NMR-based metabolic biomarkers provide comprehensive insights into human metabolism;
however, extracting biologically meaningful patterns from such high-dimensional data
remains a significant challenge. In this study, we propose a manifold-fitting-based
...
Microbiology
Necroptosis is an inflammatory programmed cell death pathway triggered by RIPK3 activation
through one of the upstream RHIM-domain-containing proteins including RIPK1, TRIF,
and ZBP1. Whether necroptosis can be activated independent of the upstream ...
The underlying factors that lead to specific strains within a species to emerge as
human pathogens remain mostly enigmatic. The diarrheal disease cholera is caused by
strains from a phylogenetically confined group within the Vibrio cholerae species, the ...
The human cytomegalovirus (HCMV) UL135 and UL138 genes play opposing roles regulating latency and reactivation in CD34+ human progenitor cells. We designed an RNA sequencing study to compare the transcriptional
profile of HCMV infection in the presence ...
Host-derived factors ingested during mosquito blood feeding are poorly understood
modulators of malaria transmission. Here, we demonstrated that host complement C3,
acquired by mosquitoes during Plasmodium infection, significantly enhanced rodent malaria ...
Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide
rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative
to antibiotics for the treatment of resistant bacterial infections. Up ...
Horizontal gene transfer by natural transformation (NT) is induced in Vibrio cholerae upon attachment to chitin surfaces in the aquatic environment. Here, we show that
free environmental DNA adsorbs to chitin surfaces under physiologically realistic
...
Neuroscience
Neuroligins (NLGNs) are important cell adhesion molecules mediating trans-synaptic
contacts between neurons. However, the high-yield biochemical isolation and visualization
of endogenous NLGNs is hampered by the lack of efficient antibodies. Thus, to ...
Longitudinal associations between birth-to-six cortical growth and childhood neurocognitive function
The human cortex undergoes immense change in the first years of life, doubling in
thickness within the first year and evidencing the greatest change within the first
5 y. While substantial research has identified the early postnatal period as a sensitive
...
Microsaccades (MSs) are commonly associated with covert spatial attention, yet their
impact on cortical processing of visual objects remains unclear. Rhesus macaques,
randomly cued to attend to a target object amid distracters, were rewarded for detecting
...
Modular arrangement of synaptic and intrinsic homeostatic plasticity within visual cortical circuits
Neocortical circuits use synaptic and intrinsic forms of homeostatic plasticity to
stabilize key features of network activity, but whether these different homeostatic
mechanisms act redundantly or can be independently recruited to stabilize different
...
Pharmacology
Imbalanced production and clearance of amyloid-β (Aβ) is a hallmark pathological feature
of Alzheimer’s disease (AD). While several monoclonal antibodies targeting Aβ have
shown reductions in amyloid burden, their impact on cognitive function remains ...
Nav1.8 voltage-gated sodium channels are strongly expressed in human primary pain-sensing
neurons (nociceptors) and a selective Nav1.8 inhibitor VX-548 (suzetrigine) has shown
efficacy for treating acute pain in clinical trials. Nociceptors also express ...
Physiology
Ethanol rapidly stimulates the liver to synthesize the hormone fibroblast growth factor
21 (FGF21), which then acts on the brain to elicit a multifaceted protective response.
We show that in mice, this induction of FGF21 occurs at the level of gene ...
Plant Biology
Greening immediately after etiolated-seedling’s emergence from the soil is critical
for plants to initiate their autotrophic life cycle through photosynthesis. The greening
process relies on a complex transcriptional network that fine-tunes the ...
Psychological and Cognitive Sciences
Mind wandering attenuates widespread sensory and motor processing, both of which are
mediated by phase coherence. However, it remains unclear i) whether mind wandering
impacts both sensory input and motor output processing by modulating ii) neural ...
Systems Biology
This study investigates the intricate interplay among neutral landscape structure,
mutation rate, recombination rate, and population dynamics in shaping evolutionary
robustness. We provide a comprehensive framework that elucidates how different ...
Corrections
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