Table Of Contents Page, PNAS Volume 123, Number 16
This Week in PNAS
Inner Workings
Retrospective
Gail Roberta Martin, Professor Emerita of Anatomy at the University of California,
San Francisco, and one of the founding figures of modern stem cell and developmental
biology, passed away on February 9, 2026. A memorial service celebrating her life
was ...
Profile
Helen M. Piwnica-Worms has devoted her career to uncovering how cancer cells evade
control and resist treatment. From pioneering work on cell cycle checkpoints to revealing
drug resistance mechanisms in breast cancer, her research spans the continuum from
...
Commentaries
Perspective
Viral discovery efforts have uncovered millions of zoonotic viruses across multiple
continents, listed on the World Health Organization’s pandemic risk register. Over
two-thirds of these zoonotic viruses pose significant risks, are poised to infect
humans,...
Letters
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Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion
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High rates of polygyny do not lock large proportions of men out of the marriage market
This article has a reply:Reply to Deng: Polygyny’s marriage squeeze has little power to explain violence
Brief Report
We investigate associations between community water fluoridation (CWF), adolescent
IQ, and cognition across the life course using representative data from the US state
of Wisconsin. Exposure is inferred from historical records on community water ...
Physical Sciences
Applied Mathematics
Modeling real-world spatiotemporal data is exceptionally difficult due to inherent
high dimensionality, measurement noise, partial observations, and often expensive
data collection procedures. In this paper, we present Sparse Identification of Nonlinear
...
Under starvation, Myxococcus xanthus bacteria initiate a multicellular developmental program in which cells move to form
fruiting bodies and differentiate into distinct cell types. Many genes affecting this
process have been identified, and it is assumed ...
Applied Physical Sciences
The long-standing classification of ions as water “structure-makers” or “structure-breakers”
is fundamentally reevaluated through advanced Molecular Dynamics simulations employing
the accurate Madrid-2019 force field. We quantitatively study the local ...
Excessive administration of glucocorticoids leads to arterial involvement and induces
osteonecrosis. Conventional biomaterial-based strategies aimed at direct vascularization
have shown limited therapeutic efficacy, primarily due to pronounced ...
Biophysics and Computational Biology
Understanding how viral proteins adapt under immune pressure while preserving viability
is crucial for anticipating antibody-resistant variants. We present a probabilistic
framework that predicts viral escape trajectories and shows that immune evasion is
...
The error catastrophe refers to the proliferation of nonfunctional molecules in conditions
where molecular replication has low accuracy, which is likely to correspond to conditions
present at the Origin of Life. This error catastrophe can be avoided ...
Riboswitches are structural elements in the 5’ untranslated region of mRNAs that adopt
different conformations under different conditions. Transitions between these different
states are involved in controlling gene expression and occur on relatively slow ...
As a single cell grows and multiplies, at what stage does it constitute a swarm? Here,
we provide an answer for Bacillus subtilis. We place single planktonic cells onto agar and monitor the biological and physical
phases as they transition into an active, ...
A universal polymer signature in Hi-C resolves cohesin loop density and supports monomeric extrusion
The genome is folded by molecular motors, yet how many motors are required to generate
a single chromatin loop has remained unknown. In vertebrates, cohesin extrudes loops
along interphase chromosomes, but the linear density of these loops—and therefore
...
Chemistry
The long-standing classification of ions as water “structure-makers” or “structure-breakers”
is fundamentally reevaluated through advanced Molecular Dynamics simulations employing
the accurate Madrid-2019 force field. We quantitatively study the local ...
The desolvation and recombination of protons and hydroxides in the bulk is one of
the fastest reactions known to mankind. The very existence of an increased activation
barrier at heterogenous interfaces reflects a key component of interfacial chemistry.
...
Monitoring molecular activities within single live cells is vital for understanding
cellular differentiation, senescence, heterogeneity, and disease progression. However,
conventional single-cell analyses often rely on micromanipulation or extraction ...
Computer Sciences
Though women comprise a growing share of the scientific workforce, the gender innovation
gap in patenting between men and women inventors persists, potentially limiting innovation
output and equity. We study millions of scientific and technological ...
Earth, Atmospheric, and Planetary Sciences
Cities around the world have united to form coalitions, like the C40 network, in pursuit
of ambitious climate goals. These efforts often include reducing methane emissions.
However, sources and magnitudes of urban methane emissions are not well known, and
...
The deformation regime that accommodates tectonic motion at plate boundaries changes
as pressures and temperatures increase with depth, transitioning from the shallow
frictional sliding of seismic ruptures to deep, viscous flow. We use recurring swarms
of ...
The thermodynamic properties of molten iron under Earth’s outer core conditions are
fundamental to understanding the core’s structure, composition, and dynamics. However,
experimental constraints under such extreme conditions remain scarce. Shock ...
Environmental Sciences
Monitored seabird populations have declined by up to 70% worldwide since the 1950s.
Yet, data on long-term seabird population dynamics prior to the anthropogenic era
are largely unknown. This limits our ability to understand future population trajectories,...
Physics
For nearly a century, introduction of nanoparticles to elastomers has yielded extraordinarily
tough nanocomposites that are critical to technologies from actuators to tires. The
mechanisms by which this reinforcement occurs have nevertheless remained a ...
The origin of life remains a scientific mystery, particularly the emergence of protocells.
One hypothesis proposes that protocells arose as droplets formed via liquid–liquid
phase separation of polymers. The work on this hypothesis leaves open how ...
Social Sciences
Demography
Latinos, a diverse group comprised primarily of immigrants and their descendants,
are a large and growing part of the US population. Using our research from the past
twenty years, we explore health outcomes and patterns among Latinos, many of which
are ...
Economic Sciences
Climate change will increase the frequency and severity of extreme heat, which is
a leading cause of weather-related mortality. We combine causal estimates of how temperature
forecast accuracy affects mortality in the United States with expert projections ...
Psychological and Cognitive Sciences
Humans routinely solve social problems by navigating densely interconnected networks—gossiping
strategically, brokering across cliques, and coordinating with allies. Yet, the neural
representations supporting such complex navigation remain undocumented, ...
Information selection plays a crucial role in how individuals navigate online content.
While confirmation bias has been implicated in this phenomenon, its interaction with
reinforcement learning dynamics and internal confidence signals remains poorly ...
Social Sciences
Though women comprise a growing share of the scientific workforce, the gender innovation
gap in patenting between men and women inventors persists, potentially limiting innovation
output and equity. We study millions of scientific and technological ...
Sustainability Science
Climate change will increase the frequency and severity of extreme heat, which is
a leading cause of weather-related mortality. We combine causal estimates of how temperature
forecast accuracy affects mortality in the United States with expert projections ...
Biological Sciences
Agricultural Sciences
Pathogens frequently employ vector-manipulation strategies to enhance their transmission
efficiency. Exosomes are increasingly recognized as mediators of interspecific communication
between pathogens and their vectors. However, the mechanisms by which ...
Anthropology
Estrogens influence many aspects of human physiology and health, including fertility,
growth, metabolic function, and susceptibility to disease. Up to 65% of circulating
estrogens are excreted into the gut via bile, but only 10-15% are eliminated in feces,...
Applied Biological Sciences
mRNA-based vaccines have demonstrated tremendous success during the era of COVID-19,
but its therapeutic potential for treating cancer, especially poorly immunogenic solid
tumors, remains largely underachieved. Herein, we report a class of self-...
Biochemistry
Oxidative stress induces damage to DNA, RNA, and nucleotide pools. Unlike well-studied
DNA damage, the formation of RNA damage and the impact of an oxidized ribonucleotide
pool on transcription fidelity are poorly understood. Here, we investigate the ...
Cardiotoxicity is a dose-limiting complication of doxorubicin (DOX) chemotherapy,
yet the molecular mechanisms governing the transition from acute stress to terminal
heart failure remain incompletely defined. Here, we identify Protein Phosphatase 1
...
Biophysics and Computational Biology
A universal polymer signature in Hi-C resolves cohesin loop density and supports monomeric extrusion
The genome is folded by molecular motors, yet how many motors are required to generate
a single chromatin loop has remained unknown. In vertebrates, cohesin extrudes loops
along interphase chromosomes, but the linear density of these loops—and therefore
...
Monitoring molecular activities within single live cells is vital for understanding
cellular differentiation, senescence, heterogeneity, and disease progression. However,
conventional single-cell analyses often rely on micromanipulation or extraction ...
The origin of life remains a scientific mystery, particularly the emergence of protocells.
One hypothesis proposes that protocells arose as droplets formed via liquid–liquid
phase separation of polymers. The work on this hypothesis leaves open how ...
The bioenergetic complexes of energy-transducing membranes generate a proton current
that powers the synthesis of adenosine triphosphate. Yet, since the early days of
the chemiosmotic theory, it has remained elusive and much debated whether the proton
...
NMR spectroscopy is a powerful tool for studies of protein dynamics over timescales
extending more than twelve orders of magnitude, with motion queried at many of the
backbone and sidechain positions in the molecule of interest. NMR experiments can,
in ...
Cell Biology
Excessive administration of glucocorticoids leads to arterial involvement and induces
osteonecrosis. Conventional biomaterial-based strategies aimed at direct vascularization
have shown limited therapeutic efficacy, primarily due to pronounced ...
The most frequent causative genes in podocytopathies are NPHS1 and NPHS2 that encode the main slit diaphragm components nephrin and podocin, respectively.
The significance of the nephrin–podocin interaction has remained elusive. The NPHS2 R229Q variant is ...
Cutaneous squamous cell carcinoma (cSCC), the second most common skin cancer, remains
a major health burden worldwide. The WW domain–containing oxidoreductase (WWOX) is
frequently altered in cancer; however, its role in epidermal biology and skin ...
Whole-genome duplication (WGD) of diploid cells triggers various cell fates, such
as cell death, cell cycle arrest, and proliferation with chromosome instability, contributing
to broad bioprocesses, including differentiation, tumorigenesis, or aging. ...
Cellular senescence, a state of permanent cell cycle arrest, contributes to tissue
dysfunction and aging through the accumulation of apoptosis-resistant senescent cells.
Although the transcription factor FOXO4 is known to enhance senescent cell survival,
...
Developmental Biology
N6-methyladenosine (m6A) RNA modification regulates diverse biological process. The m6A writers and downstream readers collaboratively undertake m6A-mediated RNA metabolism, yet the functional specificity among different writers
and readers remains poorly ...
How nervous systems balance the generation of robust neuron types with gene expression
plasticity mechanisms and how these processes impact cell-type evolution are unknown.
Here, we use Caenorhabditis species to study neuron-type robustness, plasticity, ...
Myocardial infarction results in irreversible cardiomyocyte loss and fibrotic remodeling
in adult mammals, whereas some vertebrates retain the ability to regenerate cardiac
tissue. Comparative studies suggest that immune responses critically influence ...
Ecology
Tree crown damage from disturbance events strongly influences forest demography, yet
its effect on stem growth remains poorly quantified, with both positive and negative
impacts reported. Hurricanes provide a powerful natural experiment to examine these
...
Evolution
Understanding how viral proteins adapt under immune pressure while preserving viability
is crucial for anticipating antibody-resistant variants. We present a probabilistic
framework that predicts viral escape trajectories and shows that immune evasion is
...
The error catastrophe refers to the proliferation of nonfunctional molecules in conditions
where molecular replication has low accuracy, which is likely to correspond to conditions
present at the Origin of Life. This error catastrophe can be avoided ...
Speciation and extinction events are concentrated unevenly through space and time,
shaping the global distribution of extant biodiversity. Habitats modulate these dynamics
over short timescales by determining the ecological landscape and providing ...
Broadly neutralizing antibodies (bNAbs) show promise for HIV treatment and prevention,
but are vulnerable to resistance evolution. Comprehensively understanding in vivo
viral escape from individual bNAbs is necessary to design bNAb combinations that will
...
Many insects show complex associations with vertically transmitted endosymbionts.
Here, we describe unique cellular remodeling of the oocyte’s follicular epithelial
cells into endosymbiont-bearing tubular structures in the ensign scale insect ...
The evolution of female preferences for male display traits relies on females receiving
indirect benefits from their mate. This requires substantial genetic variation in
display traits or male quality. Nevertheless, sexual selection through mate choice
...
The multicopy 47S ribosomal RNA (rRNA) genes are among the most highly expressed genes in the human
genome, yet to-date essentially no disease-causing sequence variants have been identified.
This lack of disease association is surprising, as defects in ...
Genetics
Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration.
It is caused by mutations in ABCA4, which result in the progressive degeneration of the retinal pigment epithelium (RPE),
ultimately leading to photoreceptor loss. ...
Immunology and Inflammation
Metastatic breast cancer accounts for 7% of cancer-related deaths, with the lungs
being a common site of cancer spread. In parallel, lower respiratory tract infections,
including those caused by respiratory syncytial virus (RSV), remain a common cause
of ...
The stimulator of interferon genes (STING) is a critical mediator of innate immunity
against cytosolic DNA pathogens, requiring precise regulation to balance antiviral
defense and immune tolerance. While lipid metabolism influences immune signaling,
the ...
Medical Sciences
Intrinsic and acquired resistance to poly(ADP-ribose) polymerase (PARP) inhibitors
(PARPi) remains a major barrier in treating homologous recombination (HR) repair-deficient
tumors, including those with germline or somatic BRCA1/2 mutations. Although ...
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Down syndrome (DS) is one of the most common developmental human genetic disorders
and is due to triplication of chromosome 21 (HSA21). Although previous studies using
epigenetic suppression of HSA21 by the long noncoding RNA XIST showed a potential
for ...
Allogeneic hematopoietic cell transplantation is the only curative option for many
patients with acute myeloid leukemia (AML). In the current study, we designed and
implemented a personalized assay, called v96, incorporating up to 96 mutations in
30 AML ...
Microbiology
Species of the Mycobacterium avium complex display two main colony morphologies, smooth transparent (SmT) and smooth
opaque (SmO), where SmT is associated with human disease and antimicrobial resistance.
Previous studies have suggested that smooth ...
Emergence of epidemic viruses in new hosts threatens both human and other animal populations,
and often involves virus evolution to overcome barriers that normally prevent efficient
infection and spread in that host. After transfer the separated viruses ...
Genetic hybridization within the genus Leishmania has been demonstrated experimentally, but the extent to which this occurs naturally
among circulating populations remains enigmatic. The current consensus is that natural
populations undergo preponderant ...
Neuroscience
Humans routinely solve social problems by navigating densely interconnected networks—gossiping
strategically, brokering across cliques, and coordinating with allies. Yet, the neural
representations supporting such complex navigation remain undocumented, ...
Information selection plays a crucial role in how individuals navigate online content.
While confirmation bias has been implicated in this phenomenon, its interaction with
reinforcement learning dynamics and internal confidence signals remains poorly ...
Radial glial (RG) cells serve as both neural progenitors and structural scaffolds
for neuronal migration during cortical development. Although FABP7 has long been recognized
as a marker of RG cells, its regulatory function has remained poorly defined. ...
Animals learn and adapt to environmental changes. However, neural plasticity can also
become maladaptive, leading to neurological and psychiatric disorders. How do we use
known molecular mechanisms to harness the power of neural plasticity to prevent and
...
Cochlear hair cells are the mechanosensitive receptor cells responsible for detecting
sound information. They are characterized by their apical F-actin-filled stereocilia
that are essential for mechano-electrical transduction. Previously, we and other ...
Ischemic stroke is a major public health challenge, with microglia-mediated neuroinflammation
exerting both protective and detrimental effects on neuronal survival. The Triggering
receptor expressed on myeloid cells 2 (Trem2), predominantly expressed by ...
The catecholamines octopamine and tyramine undoubtedly have a major impact on the
life of an insect. A wide range of physiological processes and behaviors are regulated
by these neurotransmitters/hormones. Octopamine and tyramine act homologous to the
...
Rett syndrome is an x-linked genetic neurological disorder primarily caused by mutations
in the methyl-CpG-binding protein 2 (MECP2) gene. This progressive neurodevelopmental
condition hinders patients’ ability to breathe and eat normally. It remains ...
Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy primarily
caused by mutations in OPA1. We identified and defined a spontaneous nonhuman primate (NHP) model of ADOA using
rhesus macaques heterozygous for a missense mutation (OPA1...
Pharmacology
Development of potent nonopioid analgesics (NOAs) has attracted great attentions from
both academic and industrial worlds, aiming at replacing current opioid drugs in acute
and chronic pain management. Among the diverse proposed pathways toward nonopioid
...
Physiology
Voltage-gated proton channel Hv1/VSOP has long been regarded as a plasma membrane
protein that modulates intracellular pH and membrane potential to support immune cell
function. Here, we reveal an unexpected intracellular pool of Hv1 on endosomal ...
Aromatic essential oils (EOs) exhibit anxiolytic properties, yet their neural and
molecular mechanisms remain to be understood. Here, we found that citronellal, an
EO derived from lemongrass, alleviates stress-related anxiety by modulating vagal
tone. We ...
The naked mole-rat (NMR) is a subterranean rodent known for its unique thermal biology,
exceptional longevity, and resistance to cancer and hypoxia. However, its thermal
biology remains controversial, with various reports describing NMRs as poikilotherms,
...
Plant Biology
In plants, the CO2-fixing enzyme Rubisco is hexadecameric, with each mature holoenzyme containing eight
small subunits (SSus). Many plants express multiple SSus and vary their expression
in response to environmental cues. Previous work indicates that this ...
Drought limits crop productivity, and effective mitigation requires a mechanistic
understanding of how abscisic acid (ABA) perception translates hormone levels into
physiological responses. In seed plants, ABA is sensed by PYR/PYL/RCAR (PYR/PYL) receptors,...
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the most abundant protein
on Earth, catalyzes the fixation of CO2 in photosynthesis. In terrestrial plants, Rubisco assembles as a hexadecameric complex
(L8S8), comprising eight large subunits (...
Population Biology
Monitored seabird populations have declined by up to 70% worldwide since the 1950s.
Yet, data on long-term seabird population dynamics prior to the anthropogenic era
are largely unknown. This limits our ability to understand future population trajectories,...
Ancient environmental genome reveals a migratory brown bear individual in Early Holocene Scandinavia
After the last ice age, species migrated into a newly deglaciated Scandinavia. Brown
bear recolonization is thought to have occurred from two directions—from the south
and the northeast—resulting in a nonoverlapping distribution of two distinct ...
Systems Biology
Under starvation, Myxococcus xanthus bacteria initiate a multicellular developmental program in which cells move to form
fruiting bodies and differentiate into distinct cell types. Many genes affecting this
process have been identified, and it is assumed ...
Corrections
View the original article:
Cover image: Pictured is the developing oocyte of an ensign scale insect (Insignorthezia insignis). Ojaswini et al. report that epithelial cells near the posterior pole of the oocyte undergo remodeling during development, producing tubular structures to accommodate a bacterial endosymbiont. The structures allow the endosymbiont to pass on to the next generation of insects. Depletion of the endosymbiont during embryonic development caused high insect mortality. The findings uncover a critical role for the endosymbiont in the insects’ embryonic development as well as a mechanism of intergenerational symbiont transfer. See the article by Ojaswini et al. e2532091123. Image credit: Ojaswini.
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