Table Of Contents Page, PNAS Volume 122, Number 52
This Week in PNAS
News Feature
Commentaries
Physical Sciences
Applied Physical Sciences
In the water cycle, erosion begins with the entrainment of soil by raindrops. The
discrete, discontinuous, and three-phase nature of raindrop erosion—at the boundary
of fluid and granular mechanics—makes this problem particularly challenging, compared
to ...
Biophysics and Computational Biology
Dormant bacterial spores germinate to become vegetative cells upon germinant exposure.
Despite many germinants being energy sources, bioenergetic processes have been overlooked
as germination can proceed, albeit slowly, without exogenous energy sources. ...
Channelrhodopsins are light-gated ion channels that are used in modern neurosciences
for the precise control of cellular ion fluxes by light. With a peak absorption at
585 nm, Chrimson is the most red-shifted cation-conducting ChR. It is frequently ...
Understanding the mechanisms that dictate the localization of cytoskeletal filaments
is crucial for elucidating cell shape regulation in prokaryotes. The actin homolog
MreB plays a pivotal role in maintaining the shape of many rod-shaped bacteria such
as ...
α-Synuclein is an intrinsically disordered neuronal protein that forms an amphipathic
helix when it peripherally binds to lipid membranes. This membrane interaction is
integral to the protein’s function but is also associated with its dysfunction. ...
Recent studies have identified diverse hollow biomolecular condensates, characterized
by biomolecule-depleted interiors surrounded by biomolecule-rich shells. Although
several formation mechanisms have been proposed, a general thermodynamic driving force
...
Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical
benefit, binds selectively to aggregated Aβ via the N-terminal region. Yet, the molecular
details of how the antibody engages Aβ1-42 fibrils remain unresolved. Using magic-...
Predicting cellular responses to genetic perturbations is critical for advancing our
understanding of gene regulation. While single-cell CRISPR perturbation assays such
as Perturb-seq provide direct measurements of gene function, the scale of these ...
Glycine receptors (GlyR) and γ-aminobutyric acid type A receptors (GABAAR) are ligand-gated chloride channels that mediate inhibitory neurotransmission throughout
the central nervous system. The receptors colocalize widely at inhibitory synapses
in the ...
Computer Sciences
Symbolic regression (SR) has regained research prominence as deep learning advancements
accelerate the search for analytical models from observational data. However, the
vast search space often hinders existing algorithms to yield complex analytical ...
Earth, Atmospheric, and Planetary Sciences
This study reports a tropical cyclone (TC) series reconstructed from documentary records
that have been digitized in the REACHES database for the period of 1368–1911. The
series has been validated through comparison with early instrumental data from 1884
...
The Mesoproterozoic eon [1.8 to 0.8 billion years ago (Ga)] is a crucial but enigmatic
period in Earth’s history. Many facets of this interval remain unresolved, especially
how atmospheric evolution influenced and responded to changes in climate and ...
Engineering
Continuous biomarker monitoring and on-demand therapy are essential for chronic disease
management, with diabetes being a key example. Although continuous glucose monitoring
(CGM) and insulin pumps are moving toward a closed-loop system, it remains ...
Humanoid robots with advanced sensory capabilities are increasingly demanded for empathetic,
close-contact interactions with humans. Electronic skin (E-skin) is a key enabling
technology for such tactile perception. However, current E-skins are limited to ...
Physics
Photoelectron circular dichroism (PECD) is a method whereby randomly oriented chiral
molecules are irradiated by circularly polarized light (CPL), photoionizing electrons,
which are measured in a momentum-resolved manner. This scheme permits chiral light–...
Metallic delafossite oxides are of exceptional interest due to their ultraclean metallic
transport. In the case of PdCrO2, this arises in a triangular-lattice antiferromagnet, creating a unique opportunity
to study frustrated magnetism in a very clean ...
Social Sciences
Economic Sciences
Organisms in nature and humans in socioeconomic systems alike face tradeoffs between
selfish consumption of resources and investment in the welfare of their offspring.
Previous work across the disciplines of biology and economics has sought to elucidate
...
Environmental Sciences
Two-thirds of the journey to achieving the Sustainable Development Goals (SDGs) has
passed. However, insights into country-specific progress covering pre- and post-SDG
and the prospects remain limited. Here, we compare the progress of 117 SDG indicators
...
Marine apex predators are promising sentinels for detecting the ecological impacts
of climate variability and change. Fishermen are increasingly recognized as marine
apex predators, and there are extensive satellite-based geolocation data on fishing
...
Biological Sciences
Agricultural Sciences
The spring-loaded spontaneous seed dispersal mechanism known as dehiscence, has been
a critical plant feature for the successful colonization of land by angiosperms. Although
advantageous for seed dispersal, spontaneous dehiscence is largely an ...
Herbivory is destructive for crop production in many regions worldwide. The induced
plant response to herbivores promotes resistance; therefore, characterizing the mechanisms
underlying natural host resistance is highly important. However, the genetic ...
Applied Biological Sciences
We describe peptide mapping through Split Antibiotic Resistance Complementation (SpARC-map),
a method to identify the probable interface between two interacting proteins. Our
method is based on in vivo affinity selection inside a bacterial host and uses ...
Therapeutic biological scaffolds promote tissue repair primarily through the induction
of type 2 immunity. However, systemic immunological factors, including aging, sex,
and previous infections, can modulate this response. The gut microbiota is a well-...
Biochemistry
Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived
from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion
of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation
...
The β-barrel assembly machine (BAM) is an essential protein complex that folds and
inserts outer membrane β-barrel proteins (OMPs) into the bacterial outer membrane.
The BAM complex contains the essential BamA OMP with five soluble polypeptide transport-...
Biophysics and Computational Biology
Recent studies have identified diverse hollow biomolecular condensates, characterized
by biomolecule-depleted interiors surrounded by biomolecule-rich shells. Although
several formation mechanisms have been proposed, a general thermodynamic driving force
...
Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical
benefit, binds selectively to aggregated Aβ via the N-terminal region. Yet, the molecular
details of how the antibody engages Aβ1-42 fibrils remain unresolved. Using magic-...
Liquid–liquid phase separation (LLPS) is a fundamental principle of protein organization
in intrinsically disordered proteins (IDPs) and biomaterials, yet the residue-level
interactions that link condensation to structural ordering remain poorly defined.
...
Understanding protein structure and dynamics is crucial for basic biology and drug
design. Conventional methods often provide static conformations that inadequately
capture protein flexibility. We present PackDock, a framework that integrates deep
...
Hypertrophic cardiomyopathy (HCM) is a leading cause of cardiac failure among individuals
under 35. Many genetic mutations that cause HCM seem to enhance ventricular systolic
function, suggesting that these HCM mutations are hypercontractile. Among the ...
ATP-binding cassette transporters of the D subfamily (ABCD1-3) mediate the export
of CoA thioesters of fatty acids from the cytosol into peroxisomes for further oxidation.
ABCD3 facilitates the transport of a broad spectrum of substrates, including ...
Cell Biology
Ataxia-telangiectasia (A-T), caused by biallelic mutations in the ATM gene, leads
to multiple disease phenotypes, including cerebellar neurodegeneration, radiosensitivity,
cancer predisposition, immunodeficiency, insulin resistance, and pulmonary ...
Despite great success in certain cancers, immunotherapy made little progress in treating
immune cold tumors, largely attributed to an immune-suppressive tumor microenvironment
with elusive mechanisms. Here, we report in prostate cancer cells a positive ...
The Niemann-Pick type 1 and 2 proteins (NPC1 and NPC2) coordinate cholesterol egress
from late endosomes-lysosomes (LE/LY). Proper folding, trafficking, and localization
of both NPC proteins are essential for normal LE/LY cholesterol handling. Accordingly,...
Developmental Biology
Unlike regeneration-competent species, mammals lack epimorphic regeneration capacity,
except for the most distal part of their digits. Here, we show that E10.5 mouse embryos
can initiate regeneration of their forelimb bud (FB), but this capacity is lost ...
Gap junctions mediate rapid signal transduction between contiguous cells, which are
indispensable for multicellular organisms to coordinate cellular activities across
numerous physiological processes. However, precise control of gap junctions remains
...
Ecology
Organisms in nature and humans in socioeconomic systems alike face tradeoffs between
selfish consumption of resources and investment in the welfare of their offspring.
Previous work across the disciplines of biology and economics has sought to elucidate
...
Marine apex predators are promising sentinels for detecting the ecological impacts
of climate variability and change. Fishermen are increasingly recognized as marine
apex predators, and there are extensive satellite-based geolocation data on fishing
...
The epidemiological dynamics of Mycoplasma pneumoniae is characterized by poorly understood complex multiannual cycles. The origins of
these cycles have long been debated, and multiple explanations of varying complexity
have been suggested. Using Bayesian ...
Climate change and biodiversity loss threaten terrestrial productivity. Mitigating
productivity loss from interactions between these global change drivers requires a
mechanistic understanding of the forces generating productivity benefits from species
...
Wild foods are critical to the food security of billions of people worldwide, yet
the ecological mechanisms that promote wild food system stability remain poorly understood.
Within complex food webs, ecological theory predicts that nonhuman consumers can ...
Environmental Sciences
Roads act as conduits for human incursions and hence underlie many of humanity’s impacts
on nature, including deforestation, wildfires, and natural-resource overexploitation.
Unfortunately, existing roadmaps often drastically underestimate the true extent ...
Vaccination against livestock diseases is an effective method to prevent and control
the spread of pathogens and reduce antimicrobial consumption and livestock production
losses. Systematic data on global vaccination coverage could unlock opportunities
to ...
Genetics
Predicting cellular responses to genetic perturbations is critical for advancing our
understanding of gene regulation. While single-cell CRISPR perturbation assays such
as Perturb-seq provide direct measurements of gene function, the scale of these ...
Multidrug efflux pumps are dynamic molecular machines that drive antibiotic resistance
by harnessing ion gradients to export chemically diverse substrates. Despite their
clinical importance, the molecular principles underlying multidrug promiscuity and
...
Eukaryotic DNA mismatch repair (MMR) involves several excision pathways, including
those mediated by exonuclease 1 (Exo1) and by the flap endonuclease Rad27 (human FEN1)
coupled with DNA polymerase δ. Simultaneous inactivation of both excision mechanisms
...
Immunology and Inflammation
The ability to synthesize essential molecules is sometimes lost in evolution. A classic
example is ascorbate (vitamin C), which is synthesized in most animals by L-gulonolactone
oxidase (GULO), an enzyme lost multiple independent times in animal ...
Dysregulated NAMPT signaling underlines the immune-suppressive microenvironment in venous leg ulcers
Venous leg ulcers (VLUs) are the most common form of lower extremity ulceration, with
a rising prevalence among the elderly. Despite their clinical significance, the molecular
mechanisms underlying VLU remain poorly defined. In this study, we constructed ...
The interaction between the immune system and the somatosensory system plays a fundamental
role in the regulation of diverse biological processes. Chronic itch is a common yet
hard-to-treat symptom of many inflammatory skin conditions. One hallmark of ...
Medical Sciences
Merkel cell polyomavirus (MCV) T antigen functions as an oncoprotein that drives the
transformation of Merkel cell carcinoma (MCC) cells by activating transcription factors
involved in cell proliferation. The viral T antigen promoter requires the activity
...
Rabies, caused by the neurotropic lyssavirus rabies virus (RABV), is nearly 100% fatal after symptom onset. A fundamental challenge
for rabies therapy is that the blood–brain barrier (BBB) prevents peripherally administered
neutralizing antibodies from ...
Microbiology
Dormant bacterial spores germinate to become vegetative cells upon germinant exposure.
Despite many germinants being energy sources, bioenergetic processes have been overlooked
as germination can proceed, albeit slowly, without exogenous energy sources. ...
Gram-negative bacteria build a multilayered cell envelope in which the peptidoglycan
layer is sandwiched between an inner membrane of glycerophospholipids and an asymmetric
outer membrane composed of glycerophospholipids and lipopolysaccharide (LPS). ...
Anelloviridae is a family of single-stranded DNA viruses that are thought to be nonpathogenic and
commensal. Despite their ubiquitous presence in human populations, little is known
about the anellovirus mechanism of replication in host cells. We ...
Zika virus (ZIKV), a flavivirus, causes a range of clinical complications including
microcephaly in human fetuses. Currently, there is no treatment or vaccine. Different
maturation states (mature and immature forms) of flavivirus particles have been ...
Neuroscience
Channelrhodopsins are light-gated ion channels that are used in modern neurosciences
for the precise control of cellular ion fluxes by light. With a peak absorption at
585 nm, Chrimson is the most red-shifted cation-conducting ChR. It is frequently ...
Glycine receptors (GlyR) and γ-aminobutyric acid type A receptors (GABAAR) are ligand-gated chloride channels that mediate inhibitory neurotransmission throughout
the central nervous system. The receptors colocalize widely at inhibitory synapses
in the ...
Some patients with moderate to severe traumatic brain injury (TBI) make a full recovery,
while others remain severely disabled. Accurate prognostication is important, because
withdrawal of life-sustaining therapy based on perceived poor prognosis is the ...
Neuromodulatory systems play an essential role in regulating brain states and functions.
The canonical view is that the release of monoamines including norepinephrine (NE)
and serotonin (5-HT) is high during wakefulness and attenuated during sleep, ...
Primate societies rely on the production and interpretation of social signals, in
particular those displayed by the face. Facial movements are controlled, according
to the dominant neuropsychological schema, by two separate circuits, one originating
in ...
Retinal ganglion cells (RGCs) transmit visual information from the eye to the brain.
In mice, several RGC types show nonuniform spatial distributions, potentially mediating
specific visual functions. However, the full extent of RGC specialization remains
...
Brain capillaries are sensors of neural activity. When a brain region is active, capillary
endothelial cells (ECs) sense neuron-derived mediators and elicit a local increase
in blood flow (functional hyperemia) to support the rise in metabolic needs. This
...
With approximately 4% of the world’s population using cannabis, there is a need to
better understand its physiological effects. Cannabis consumption acutely promotes
food intake (“the munchies”) via delta-9-tetrahydrocannabinol-mediated activation
of ...
The substantia nigra pars reticulata (SNr) is a primary output for basal ganglia signaling.
It plays an important role in the control of movement, integrating inputs from upstream
structures in the basal ganglia, before sending organized projections to a ...
Working memory (WM) is distributed across multiple cortical areas, suggesting that
behaviors relying on WM arise from interactions between these regions. In a recent
study, we found that during delayed comparison tasks, the first stimulus is not ...
Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen
sulfide production, is dysregulated in aging and neurodegenerative diseases including
Alzheimer’s disease and Huntington’s disease, both marked by cognitive decline in
...
Plant Biology
Root gravitropism is essential for plant adaptation to the environment. The cytoskeleton
is known to play a critical role in gravitropism, but the underlying mechanisms remain
unclear. In this study, we demonstrate that the Arabidopsis kinesins KCH3 and ...
Cereal crops (e.g., rice, wheat, maize, and barley) constituted the major component
of global human diet and fundamentally changed human society since the dawn of agriculture
around 12,000 y ago. Originated and domesticated in different continents and ...
Brassinosteroids (BRs) are key hormones that promote plant growth and development.
While reversible phosphorylation of the BR receptor BRASSINOSTEROID-INSENSITIVE 1
(BRI1) is critical for BR signaling, much remains to be learned about the ...
Psychological and Cognitive Sciences
Does being awake necessarily mean being conscious of something? This study investigates
the phenomenon of mind blanking (MB), characterized by an “emptiness of mind,” comparing
it with mind wandering (MW) and on-task (ON) states. Using a sustained ...
Cognitive flexibility relies on the continuous accumulation and integration of sensory
evidence to guide adaptive behavior. In natural environments, behaviorally relevant
information unfolds sequentially over time and is constantly evaluated against prior
...
Sustainability Science
Roads act as conduits for human incursions and hence underlie many of humanity’s impacts
on nature, including deforestation, wildfires, and natural-resource overexploitation.
Unfortunately, existing roadmaps often drastically underestimate the true extent ...
Correction
Cover image: Pictured are fluid inclusions in 1.4-billion-year-old halite crystals, which preserve ancient air. Justin Park et al. analyzed the gases trapped in the crystals to help constrain the atmospheric oxygen and CO2 levels during the Mesoproterozoic era, a geological period often considered uneventful. The measured levels suggest that the Mesoproterozoic climate was moderate, with sufficient oxygen for early animal respiration. The findings may reflect an episode during which the breakup of a supercontinent spurred nutrient delivery, algal productivity, and oxygen production. See the article by Park et al. e2513030122. Image credit: Justin Park.
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