Table Of Contents Page, PNAS Volume 122, Number 34
This Week in PNAS
Inner Workings
Commentaries
Perspective
For centuries, scientists have been puzzled by the mystery of life’s biomolecular
homochirality—the single-handedness of biological compounds. Sugars and nucleic acids
are right-handed, while amino acids are left-handed in biological systems. Likewise,
...
Letters
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Reply to Michał Bogdziewicz et al.: Research on the summer solstice needs falsifiable predictions
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In locations that do not currently experience vector-borne disease (VBD) outbreaks
but may be at risk under climate change, modeling future climate suitability for transmission
is important for outbreak preparedness. Uncertainty in the future climate ...
Sympatric speciation is considered rare, but oceanic Howea palms, crater lake cichlids, and parasitic indigobirds provide compelling evidence
that it occurs. Still, the frequency of sympatric speciation and its relationship
to morphological divergence in ...
Physical Sciences
Applied Mathematics
It is crucial for both animal evolution and engineering to optimize the relative size
of structures. Animal wings are no exception, every structural design having its limits
in terms of achievable size and performance. For instance, many microinsects have
...
Foundation models in biology—particularly protein language models (PLMs)—have enabled
ground-breaking predictions in protein structure, function, and beyond. However, the
“black-box” nature of these representations limits transparency and explainability,
...
Applied Physical Sciences
Water droplets, acting as natural bioreactors and optical whispering-gallery-mode
(WGM) resonators, hold the potential for laser-assisted analysis. However, water/aqueous
droplet lasers can only survive in air with a limited lifespan (<100 s) due to rapid
...
Astronomy
Suppression effects of giant radio lobes from supermassive black holes on gas accretion
onto galaxies in the surrounding regions are quantified using cosmological magneto-hydrodynamic
simulations. With an appropriate amount of radio jet energy injected ...
Biophysics and Computational Biology
Cell and tissue movement in development, cancer invasion, and immune response relies
on chemical or mechanical guidance cues. In many systems, this behavior is locally
directed by self-generated signaling gradients rather than long-range, prepatterned
...
Vertebrate locomotion is due to the interplay of neural oscillators and sensory feedback
loops in the spinal cord that interact with the body and the environment. Here, we
study these circuits with a focus on undulatory locomotion as produced by elongated
...
The rapid expansion of protein sequence and structure databases has resulted in a
significant number of proteins with ambiguous or unknown function. While advances
in machine learning techniques hold great potential to fill this annotation gap, current
...
Chemistry
The gut microbiota plays a pivotal role in maintaining human health with dysbiosis
linked to a variety of diseases. Metagenome sequencing and robust statistical analysis
have linked specific strains, including the gut bacterium Campylobacter concisus, to ...
An understanding of the CO2 + H2O hydration reaction is crucial for modeling the effects of ocean acidification, for
enabling novel carbon storage solutions, and as a model process in the geosciences.
While the mechanism of this reaction has been ...
The valorization of CO2 to chemicals beyond C1-2 products is receiving significant interest; however, the direct electrosynthesis
of Cn molecules (n > 4) remains a challenge. Here, we present a two-step abiotic–biotic
system for upgrading CO2 into the ...
Understanding how electric fields influence water dissociation at heterogeneous interfaces
is crucial for controlling interfacial chemical reactions and advancing next-generation
energy technologies. Herein, ab initio–based machine learning simulations ...
Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization
and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism
underlying the selectivity remains unknown. Here, we elucidated the catalytic ...
Computer Sciences
Large-scale scientific datasets today contain tens of thousands of random variables
across millions of samples (for example, the RNA expression levels of 20,000 protein-coding
genes across 30 million single cells). Being able to quantify dependencies ...
Multiple case-controlled studies have shown that analyzing fragmentation patterns
in plasma cell-free DNA (cfDNA) can distinguish individuals with cancer from healthy
controls. However, there have been few studies that investigate various types of cfDNA
...
Earth, Atmospheric, and Planetary Sciences
The Mediterranean basin reconnected to the Atlantic Ocean ~5.33 Myr ago, following
its partial desiccation during the preceding Messinian salinity crisis (5.97 to 5.33
Myr). While the extent of terminal Messinian drawdown and abruptness of reconnection
...
A record-breaking melt season affected the Arctic glaciers of Svalbard in summer 2024
by a substantial margin. Across the entire archipelago, glacier melting corresponded
to an anomaly of up to four SD and exceeded any previous observation. The pan-...
Environmental Sciences
River flow connectivity, the continuity of fluvial discharge in space and time, provides
a crucial lifeline for most biotic communities on Earth. Yet there is still limited
understanding of the impacts of climate change and human water withdrawal on river
...
Statistics
AI is now a cornerstone of modern dataset analysis. In many real world applications,
practitioners are concerned with controlling specific kinds of errors, rather than
minimizing the overall number of errors. For example, biomedical screening assays
may ...
Sustainability Science
River flow connectivity, the continuity of fluvial discharge in space and time, provides
a crucial lifeline for most biotic communities on Earth. Yet there is still limited
understanding of the impacts of climate change and human water withdrawal on river
...
Social Sciences
Environmental Sciences
Interest in bringing Traditional Ecological Knowledge (TEK) and Western Science together
to enhance climate and landscape resilience is growing rapidly, particularly for engagement
with pyrogenic communities around the world. For these systems, Indigenous ...
Psychological and Cognitive Sciences
Humans can implicitly learn about multistep sequential relationships between events
in the environment from their statistical co-occurrence. Theoretical work has suggested
that neural replay is a candidate mechanism that aids such learning. Here, we used
...
Prediction errors drive learning by signaling mismatches between expectations and
reality, but the neural systems supporting these computations remain debated. The
hippocampus is implicated in mismatch detection, yet it is not known whether it signals
...
The remarkable human capacity for bilingual and multilingual acquisition raises fundamental
questions about how the brain develops efficient systems for processing multiple languages.
In this study, we used neural network models trained on natural speech ...
Third-party punishment is theorized by some scholars to be essential to the evolution
of large-scale cooperation, but empirically, it often fails to bring about its desired
effects. Here, we suggest that third-party punishment destabilizes cooperation ...
Educational research highlights strong developmental links between numerical and spatial
cognition in humans, often shaped by cultural tools like the number line. However,
emerging evidence suggests that these number–space connections may reflect our ...
How are actions represented in the motor system? Although the sensorimotor system
is broadly organized somatotopically, higher-level sensorimotor areas encode action-type
information for reaching and grasping actions—regardless of the acting body part.
...
Intonation units (IUs) are a hypothesized universal building block of human speech
[W. Chafe, Discourse, Consciousness and Time: The Flow and Displacement of Conscious Experience
in Speaking and Writing (1994); N. P. Himmelmann et al., Phonology 35, 207–...
Social Sciences
Recent scholarship has highlighted the rise of “diversity projects” across various
educational and business contexts, but few studies have explored the meaning of diversity
in biomedical research. In this paper, we employ a computationally driven matching
...
Biological Sciences
Applied Biological Sciences
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited
treatment options due to its desmoplastic and immunosuppressive tumor microenvironment
(TME), which impedes drug delivery and limits T cell infiltration. Immune checkpoint
...
The KRAS oncogene has been associated with many types of cancer, including pancreatic, lung,
and colorectal. For decades, its gene products were thought to be undruggable. However,
during the last decade, a large battery of KRAS inhibitors selective ...
Biochemistry
Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization
and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism
underlying the selectivity remains unknown. Here, we elucidated the catalytic ...
Disulfide bonds stabilize many bioactive peptides, but their susceptibility to reduction
under physiological conditions limits broad applicability in biotechnology. PapB is
a promiscuous radical S-adenosyl-L-methionine enzyme that is involved in the ...
In cardiac muscle, myosin molecules exist in multiple structural states as they transit
through their ATPase cycle, including an off-cycle resting or OFF-state with their
catalytic heads in a folded structure known as the interacting-heads motif (IHM).
...
Biophysics and Computational Biology
It is crucial for both animal evolution and engineering to optimize the relative size
of structures. Animal wings are no exception, every structural design having its limits
in terms of achievable size and performance. For instance, many microinsects have
...
Vertebrate locomotion is due to the interplay of neural oscillators and sensory feedback
loops in the spinal cord that interact with the body and the environment. Here, we
study these circuits with a focus on undulatory locomotion as produced by elongated
...
The rapid expansion of protein sequence and structure databases has resulted in a
significant number of proteins with ambiguous or unknown function. While advances
in machine learning techniques hold great potential to fill this annotation gap, current
...
Both DNA methylation and homologous recombination (HR) are extensively studied. In
bacteria, Dam methylation is the most studied DNA modification, while RecA-mediated
HR is a primary mechanism to repair DNA damages including double-stranded breaks,
single-...
Heart failure is a leading cause of death worldwide, and even with current treatments,
the 5-y transplant-free survival rate is only ~50 to 70%. As such, there is a need
to develop new treatments for patients that improve survival and quality of life.
...
The human Fic enzyme FicD plays an important role in regulating the Hsp70 homolog
BiP in the endoplasmic reticulum: FicD reversibly modulates BiP’s activity through
attaching an adenosine monophosphate to the substrate binding domain. This reduces
BiP’s ...
Cell Biology
Large-scale scientific datasets today contain tens of thousands of random variables
across millions of samples (for example, the RNA expression levels of 20,000 protein-coding
genes across 30 million single cells). Being able to quantify dependencies ...
Selected proteins containing an N-terminal cysteine (Nt-Cys) are subjected to rapid,
O2-dependent proteolysis via the Cys/Arg-branch of the N-degron pathway. Cysteine dioxygenation
is catalyzed in mammalian cells by 2-aminoethanethiol dioxygenase (ADO), ...
Understanding mechanisms that determine the response of cells to ferroptotic stress
is a timely issue that has significant ramifications for biology and pathology. We
investigated these mechanisms in the context of breast cancer where tumors are composed
...
Extrinsic apoptosis is initiated by signaling from death receptors, leading to the
assembly of RIPK1, FADD, and caspase-8 complex. Subsequently, caspase-8 forms a filamentous
structure through the oligomerization of its tandem death effector domain (tDED),...
Ecology
Climate change is shifting species distributions, leading to changes in community
composition and novel species assemblages worldwide. However, the responses of tropical
forests to climate change across large-scale environmental gradients remain largely
...
Fish population biomass fluctuates through time in ways that may be either gradual
or abrupt. While abrupt shifts in fish population productivity have been shown to
be common, they are rarely integrated into stock assessment or fishery management,
in part ...
Highly pathogenic avian influenza viruses (HPAIV) persistently threaten wild waterfowl,
domestic poultry, and public health. The East Asian–Australasian Flyway plays a crucial
role in HPAIV dynamics due to its large populations of migratory waterfowl and ...
Environmental DNA (eDNA) is increasingly used for biodiversity monitoring, but validation
of the spatial scale(s) at which eDNA reflects extant communities is scarce, particularly
in tropical forests: the terrestrial biome with the most concentrated ...
Atmospheric nitrogen (N) deposition is generally expected to stimulate plant carbon
(C) sequestration and promote tree growth, thereby mitigating atmospheric CO2 accumulation. Yet, the magnitude of N deposition contribution to forest productivity
remains ...
Environmental Sciences
Carbon sequestration through plant biomass responses to global warming plays a vital
role in mitigating climate change, but recent evidence suggests that this effect diminishes
in the long term. To investigate the effect of warming duration on plant ...
Biochar amendment reshapes microbial community dynamics in vermicomposting, but the
mechanism of how phages respond to this anthropogenic intervention and regulate the
dissemination of antibiotic resistance genes (ARGs) remains unclear. In this study,
we ...
Evolution
Rates of phenotypic evolution vary across traits, and these evolutionary patterns
themselves evolve. Understanding how development contributes to such patterns remains
a challenge because it requires large-scale measurement of phenotypic variation ...
Hybridization is a double-edged sword: While it can erode distinct evolutionary lineages,
it can also introduce genetic diversity and adaptive potential into dwindling populations.
In the Critically Endangered Balearic shearwater (Puffinus mauretanicus), ...
Indirect ecological effects occur when the impact of one species on another is mediated
by a third species or the shared environment. Although indirect effects are ubiquitous
in nature, we know remarkably little about how they may drive ecoevolutionary ...
Genetics
ZNF93 is a primate-restricted Krüppel-associated box zinc finger protein responsible
for repressing 20- to 12-My-old L1 transposable elements. Here, we reveal that ZNF93
also regulates the key cancer driver APOBEC3B—a mutagenic enzyme linked to ...
DNA secondary G-quadruplex (G4) structures can impair and even obstruct DNA replication.
Defects in processing G4 structures are associated with replication stress, a common
property of both B cell cancers and hyperproliferative premalignant cells. Genome
...
Immunology and Inflammation
It is well established that stress generally suppresses immunity. However, under certain
conditions, acute stress has been shown to stimulate the immune system, particularly
those at barrier surfaces like the skin. The cellular and molecular mechanisms ...
Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor
microenvironment that promote breast cancer brain metastasis (BCBM). Here, we identify
TANK-binding kinase (TBK1) as a critical signaling molecule enriched and activated
in ...
Plasmodium falciparum pathology is driven by the accumulation of parasite-infected erythrocytes in blood
capillaries. This sequestration process is mediated by the parasite’s P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins, which bind ...
Toll-like receptor 4 (TLR4), a pattern-recognition receptor located on the plasma
membrane, senses extracellular danger signals to initiate inflammatory immune responses.
It is initially synthesized in the endoplasmic reticulum (ER), undergoes N-linked
...
Medical Sciences
Multiple case-controlled studies have shown that analyzing fragmentation patterns
in plasma cell-free DNA (cfDNA) can distinguish individuals with cancer from healthy
controls. However, there have been few studies that investigate various types of cfDNA
...
AI is now a cornerstone of modern dataset analysis. In many real world applications,
practitioners are concerned with controlling specific kinds of errors, rather than
minimizing the overall number of errors. For example, biomedical screening assays
may ...
The investigation of congenital imprinting disorders (CIDs) provides opportunities
to elucidate the molecular mechanisms and role of genomic imprinting in development
and human disease. Beckwith–Wiedemann spectrum (BWSp) is a prototypic CID resulting
from ...
Cancer-induced bone pain (CIBP) is a severely painful condition that profoundly impacts
patients’ quality of life. However, the neuroimmune mechanisms underlying CIBP remain
largely elusive. Substance P (SP), which is known to play a pivotal role in pain ...
Sialic acids (Sias) are a diverse family of nine-carbon backbone monosaccharides occupying
terminal positions on cell surface and secreted glycans and are abundant at mucosal
surfaces. Sias can be modified with O-acetyl esters on the side chain (C7 to C9) ...
Microbiology
The gut microbiota plays a pivotal role in maintaining human health with dysbiosis
linked to a variety of diseases. Metagenome sequencing and robust statistical analysis
have linked specific strains, including the gut bacterium Campylobacter concisus, to ...
Despite extensive efforts, our understanding of the virulence factors contributing
to oral biofilm formation—a hallmark of dental caries—remains incomplete. We present
evidence that the specialized metabolism of the oral microbiome is a critical yet
...
Phytophthora sojae-induced root rot poses a major threat to soybean production. While the molecular
mechanisms underlying soybean–P. sojae interactions have been extensively studied, their biochemical basis remains largely
unexplored. Previous research ...
The FliPQR complex constitutes a channel for export of the flagellar proteins involved
in axial structure assembly. It also serves as a template for the assembly of the
rod structure, which consists of FliE, FlgB, FlgC, FlgF, and FlgG. FliP, FliQ, and
...
The bacterial flagellum is a complex nanomachine essential for motility, environmental
sensing, and host colonization. While many of its core components have been well characterized,
the relevance of proteins such as FliO, which are inconsistently ...
Intracellular multivesicular bodies (MVBs) act as sites of assembly and release of
HIV type 1 (HIV-1) in macrophages and microglia. Recent work has shown that processing
of amyloid precursor protein (APP) into a C-terminal fragment (CTF), termed C99, ...
Most cytoplasmic RNA viruses have evolved mechanisms to identify their genomic RNA
(gRNA) as the sole RNA species to be packaged into assembled virions. Coronaviruses
exhibit highly selective packaging of their gRNA, in spite of the presence of a large
...
Neuroscience
The microtubule (MT) cytoskeleton is essential for neuronal morphology, neurite growth,
synapse formation and maintenance, as well as regulation of signal transduction. Most
cells express multiple isotypes of α- and β-tubulin that can coassemble into MTs.
...
Humans can implicitly learn about multistep sequential relationships between events
in the environment from their statistical co-occurrence. Theoretical work has suggested
that neural replay is a candidate mechanism that aids such learning. Here, we used
...
Prediction errors drive learning by signaling mismatches between expectations and
reality, but the neural systems supporting these computations remain debated. The
hippocampus is implicated in mismatch detection, yet it is not known whether it signals
...
How are actions represented in the motor system? Although the sensorimotor system
is broadly organized somatotopically, higher-level sensorimotor areas encode action-type
information for reaching and grasping actions—regardless of the acting body part.
...
The inferior parietal lobule supports action representations that are necessary to
grasp and use objects in a functionally appropriate manner [S. H. Johnson-Frey, Trends Cogn. Sci. 8, 71–78 (2004)]. The supramarginal gyrus (SMG) is a structure within the ...
Functional connectivity (FC), a statistical correlation of pair-wise brain signals
from resting-state (RS) functional MRI (fMRI), is a widely used concept for mapping
large-scale functional networks in both humans and animals. However, its underlying
...
Vocal development in human infants is strongly influenced by interactions with caregivers
who reinforce more speech-like sounds. This trajectory of vocal development in humans
is radically different from those of our close phylogenetic relatives, ...
Neuromodulators control mood, arousal, and behavior by inducing synaptic plasticity
via G-protein-coupled receptors. While long-term presynaptic potentiation requires
structural changes, mechanisms enabling potentiation within minutes remain unclear.
...
Synaptic transmission has long been thought to regulate neuronal wiring during postnatal
development, but this assumption remains largely untested. Selective strengthening
of a single “winner” climbing fiber (CF) afferent to each Purkinje cell (PC) and ...
Physiology
Type 1 ryanodine receptor (RyR1) is a Ca2+ release channel in the sarcoplasmic reticulum in skeletal muscle. In excitation–contraction
(E-C) coupling, RyR1 opens by depolarization of transverse tubule membrane via physical
interaction with dihydropyridine ...
Paired structures often have similar forms and functions, but the processes underlying
their formation can differ. They may originate from a common source or from parallel
sources, or arise from distinct precursors that follow separate developmental ...
Plant Biology
The D1 subunit of photosystem II (PSII) is subject to light-induced damage. In plants,
D1 photodamage activates translation of chloroplast psbA mRNA encoding D1, providing D1 for PSII repair. Three D1 assembly factors have been
implicated in the ...
Factors underlying a latitudinal gradient in the S/G lignin monomer ratio in natural poplar variants
The chemical composition of wood plays a pivotal role in the adaptability and structural
integrity of trees. However, few studies have investigated the environmental factors
that determine lignin composition and its biological significance in plants. Here,...
The hallmark of the legume lncRNA EARLY NODULIN40 (ENOD40), involved in rhizobium-induced nodulation, is the presence of a highly conserved
stretch of 24 nucleotides, designated box2, preceded by a small open-reading-frame
(sORF) coding for a peptide of ...
Population Biology
Small and fragmented populations are at high risk of local extinction, in part because
of elevated inbreeding and subsequent inbreeding depression. A major conservation
priority is to identify the mechanisms and extent of inbreeding depression in small
...
Psychological and Cognitive Sciences
Intonation units (IUs) are a hypothesized universal building block of human speech
[W. Chafe, Discourse, Consciousness and Time: The Flow and Displacement of Conscious Experience
in Speaking and Writing (1994); N. P. Himmelmann et al., Phonology 35, 207–...
Sustainability Science
Interest in bringing Traditional Ecological Knowledge (TEK) and Western Science together
to enhance climate and landscape resilience is growing rapidly, particularly for engagement
with pyrogenic communities around the world. For these systems, Indigenous ...
Corrections
Cover image: Pictured are the wings of large (Acrotrichis grandicollis) and small (Primorskiella anodonta) featherwing beetles visualized using inverted light microscopy. Dmitry Kolomenskiy et al. explored why the wings of the smallest beetles are typically bristled rather than membranous. The authors report that the wing parameters scale with size. Bristle number and spacing are optimized for aerodynamic permeability, whereas bristle diameter and length are optimized for stiffness, rendering the wings extremely lightweight. According to the authors, the study yields insights that could aid the design of small, wing-flapping vehicles. See the article by Kolomenskiy et al. e2506403122. Image credit: Sergey E. Farisenkov and Alexey A. Polilov.
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