Table Of Contents Page, PNAS Volume 122, Number 50
This Week in PNAS
Opinion
Commentaries
Perspective
In the United States, people of color are disproportionately and unjustly exposed
to air pollution. Historically, environmental policy has emphasized aggregate emission
reductions, yet major emission reduction scenarios do not sufficiently mitigate ...
Letters
Contrasting outcomes of inherited NOD2 loss-of-function variants on immunotherapy response in cancer
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Physical Sciences
Applied Mathematics
Single-cell RNA-sequencing captures a temporal slice, or a snapshot, of a cell differentiation
process. A major bioinformatical challenge is the inference of differentiation trajectories
from a single snapshot, and methods that account for outlier cells ...
In recent years, there has been growing interest in jointly analyzing a foreground
dataset, representing an experimental group, and a background dataset, representing
a control group. The goal of such contrastive investigations is to identify salient
...
Applied Physical Sciences
Acoustic levitation provides a unique method for manipulating small particles as it
completely evades effects from gravity, container walls, or physical handling. These
advantages make it a tantalizing platform for studying complex phenomena in many-...
Biophysics and Computational Biology
Biological systems can display diverse patterns of self-organization, even when built
on conserved networks of interaction between molecular species. In these cases, reaction–diffusion
equations provide a valuable tool to learn how new dynamics could ...
Epigenetic landscapes were proposed by Waddington as the central concept to describe
cell fate dynamics in a locally low-dimensional space. In modern landscape models,
attractors represent cell types, and stochastic jumps and bifurcations drive cellular
...
Bacteriophage T7 RNA polymerase (T7 RNAP) is commonly used for large-scale RNA synthesis
in science and industry. Although T7 RNAP exhibits high processivity, its usage faces
two major challenges: During initiation, the enzyme frequently aborts ...
Chemistry
Water microdroplets offer a chemical environment that can dramatically accelerate
reaction rates compared to bulk-phase solutions and even drive chemical transformations
not found in bulk solutions. While mass spectrometry has proven indispensable for
...
Computer Sciences
Brain-inspired spiking neural networks (SNNs) have garnered significant research attention
in algorithm design and perception applications. However, their potential in the decision-making
domain, particularly in model-based reinforcement learning, remains ...
Large language models (LLMs) have shown remarkable capabilities in algorithm design,
but their effectiveness in solving data science challenges in real-world settings
remains poorly understood. We conducted a classroom experiment in which graduate ...
Earth, Atmospheric, and Planetary Sciences
The Amazon is a key climate system component, hotspot of biodiversity and many other
ecosystem functions. However, progressive rainforest degradation, driven by anthropogenic
climate change and land-use change, is increasing the risk of a large-scale ...
The thermal structure of the Earth beneath Greenland reflects the tectonic history
of the region and impacts ice sheet evolution due to surface heat flow and the influence
of temperature on Earth rheology, and thus glacial isostatic adjustment. We present
...
This study presents a high-resolution, multiproxy (carbon and oxygen isotopes, trace
elements, and strontium isotopes) speleothem record from the Kurdistan Region of Iraq
extending from the end of the Last Glacial Maximum (LGM) to the Early Holocene (18.0
...
Methane (CH4) is the second most important greenhouse gas and has been rising following a brief
period of stabilization from 1999 to 2006. Determining the cause of this rise is critical
for reducing emissions and predicting future climate sensitivity. The ...
The ocean carbon cycle is directly impacted by storms in the atmosphere. Tropical
cyclones (TCs), particularly, are known to drive intense air–sea CO2 fluxes and to trigger phytoplankton blooms. However, the current generation of Earth
system models (ESM) ...
Cloud optical properties and precipitation, which are crucial to weather and climate,
are strongly influenced by cloud microphysical properties that are still poorly understood.
Here, we develop a high-resolution time-correlated single-photon-counting ...
Engineering
Charge transport in porous electrodes is foundational for modern energy storage technologies
like supercapacitors, fuel cells, and batteries. Supercapacitors in particular rely
solely on storing energy in charged pores. Here, we simulate the charging of a ...
Noninvasive electrophysiological source imaging (ESI) is a valuable tool for localizing
and imaging brain activity, with significant potential to aid presurgical planning
in focal drug-resistant epilepsy (fDRE) patients. Scalp electroencephalography (EEG)
...
Mathematics
Given a link in the three-sphere, its Lagrangian conormal can be transplanted to the
“resolved conifold,” which is a certain noncompact Calabi–Yau threefold. Here we show
that, as predicted by Ooguri and Vafa using string theoretic arguments, the count
of ...
Physics
Multi-nucleated cells exist in all domains of life, ranging from animals, plants,
and fungi to single-celled organisms such as the slime mold Physarum polycephalum. The large cell size, in the case of Physarum reaching centimeters and more, challenges the ...
In the presence of a laminar shear flow, the diffusion of passive colloidal particles
is enhanced in the direction parallel to the flow. This classical phenomenon is known
as Taylor–Aris dispersion. Besides, microorganisms, such as active microswimmers,
...
The basal ganglia (BG) are a collection of subcortical nuclei involved in motor control,
sensorimotor integration, and procedural learning. They play a key role in the acquisition
and adaptation of movements, a process driven by dopamine-dependent ...
Statistics
Genotype–phenotype associations can be context-dependent and dynamic in nature leading
to heterogeneity of genetic effects across different parts of the phenotype distribution.
Quantile regression, an alternative to linear regression for continuous ...
Sustainability Science
The Amazon is a key climate system component, hotspot of biodiversity and many other
ecosystem functions. However, progressive rainforest degradation, driven by anthropogenic
climate change and land-use change, is increasing the risk of a large-scale ...
Social Sciences
Anthropology
Cesarean section (CS) is the most common major surgery worldwide and, by enabling
birth outside physiologic labor, is an evolutionary novelty. Labor-related mechanical
and hormonal stimuli, shaped by natural selection, facilitate neonatal adaptation
to ...
Political Sciences
Voting Advice Applications (VAAs) are interactive tools that communicate information
about elections, yet their effectiveness in enhancing political knowledge and participation
remains understudied. Moreover, traditional VAAs may disproportionately ...
Psychological and Cognitive Sciences
Successful communication requires frequent inferences. Such inferences span a multitude
of phenomena: from understanding metaphors, to detecting irony and getting jokes,
to interpreting intonation patterns. Do all these inferences draw on a single ...
Social Sciences
Each year, approximately 40,000 people die in vehicle collisions in the United States,
generating $340 billion in economic costs. To make roads safer without expanding police
contact, many cities have turned to automated traffic enforcement, cameras that ...
Sustainability Science
To address climate-driven crises, we need actionable climate knowledge to inform decision-making
and support problem solving. Although the science of actionable knowledge is rapidly
evolving, less is known about how and why actionable climate knowledge ...
There is evidence of widespread human exposure to per- and polyfluoroalkyl substances
(PFAS) but limited evidence of the human health impacts of this exposure. Using data
on New Hampshire births from 2010–2019, we show that mothers receiving water that
...
Biological Sciences
Biochemistry
UBB+1, a ubiquitin variant protein resulting from a frameshift in the ubiquitin-B gene,
is a pathological hallmark of Alzheimer disease (AD). At the cellular level, UBB+1 disrupts the ubiquitin–proteasome system while inducing autophagy. Notably, UBB+1 ...
Biophysics and Computational Biology
Single-cell RNA-sequencing captures a temporal slice, or a snapshot, of a cell differentiation
process. A major bioinformatical challenge is the inference of differentiation trajectories
from a single snapshot, and methods that account for outlier cells ...
Multi-nucleated cells exist in all domains of life, ranging from animals, plants,
and fungi to single-celled organisms such as the slime mold Physarum polycephalum. The large cell size, in the case of Physarum reaching centimeters and more, challenges the ...
In the presence of a laminar shear flow, the diffusion of passive colloidal particles
is enhanced in the direction parallel to the flow. This classical phenomenon is known
as Taylor–Aris dispersion. Besides, microorganisms, such as active microswimmers,
...
Bacteriophage T7 RNA polymerase (T7 RNAP) is commonly used for large-scale RNA synthesis
in science and industry. Although T7 RNAP exhibits high processivity, its usage faces
two major challenges: During initiation, the enzyme frequently aborts ...
P2X receptors, a family of ATP-activated ion channels, encompass subtypes P2X1–7,
which are expressed in both homo- and heterotrimeric forms across various tissues.
These receptors play crucial roles in pathophysiological processes such as synaptic
...
Cell Biology
Biological systems can display diverse patterns of self-organization, even when built
on conserved networks of interaction between molecular species. In these cases, reaction–diffusion
equations provide a valuable tool to learn how new dynamics could ...
Innate immunity provides the critical first line of defense against infection and
sterile triggers. Inflammatory cell death is a key component of the innate immune
response to clear pathogens, but excessive or aberrant cell death can induce inflammation,
...
Epidermal growth factor (EGF) induces anchorage-independent growth in promotion-sensitive
(P+) mouse epidermal cell model JB6 primarily through activation of the MAPK/ERK signaling
pathway. The β-blocker carvedilol inhibits EGF-promoted JB6 transformation,...
The trypanosomatid Paratrypanosoma confusum represents a key evolutionary link between free-living bodonids and parasitic trypanosomes,
yet its cellular architecture remains poorly characterized. Here, we used cryofocused
ion beam scanning electron ...
SARM1 is a neuronal Nicotinamide adenine dinucleotide (NAD+) hydrolase that drives axonal degeneration and neuronal death by depleting NAD+, yet how NAD+ loss triggers axon loss and cell death has remained unclear. Here, we define a nonapoptotic
death ...
DNA methylation is a conserved epigenetic modification essential for maintaining genome
stability. However, how methyltransferases maintain CG methylation within compact
chromatin, including centromeres, remains unclear. In humans, CDCA7 is necessary for
...
Developmental Biology
Epigenetic landscapes were proposed by Waddington as the central concept to describe
cell fate dynamics in a locally low-dimensional space. In modern landscape models,
attractors represent cell types, and stochastic jumps and bifurcations drive cellular
...
Genetic mutations in Tapt1 cause complex skeletal dysplasia and structural brain abnormalities. Although the
pathogenesis underlying skeletal dysplasia has been explored, the functions and potential
mechanisms of transmembrane anterior–posterior ...
Environmental Sciences
Here, we present an analysis of the growth and use of the Global Biodiversity Information
Facility (GBIF) over the last 5 y. GBIF is the world’s largest data integrator for
biodiversity information and plays a central role in research across the ...
The simultaneous depletion of multiple nutrients in seawater potentially leads to
colimitation of phytoplankton growth across large oceanic extents. Single limitation
versus colimitation carries implications for mathematically predicting growth, its
...
Climate change is expected to exacerbate infectious diseases, yet the climate sensitivity
of zoonotic diseases (driven by spillover from animal reservoirs) is understudied
compared to vector-borne and water-borne infections. To address this gap, we ...
Evolution
Life-history trade-offs between reproduction and survival are well documented, yet
the biological mechanisms underlying costs remain unclear. Telomere length (TL) is
a potential biomarker for such costs, although its association with reproductive efforts
...
Olfaction is a critical sense for tetrapods, playing a key role in survival and reproduction
by aiding in food detection, predator avoidance, and social interactions. Olfactory
performance has been experimentally tested in only a few taxa, so comparative ...
Genetics
Genotype–phenotype associations can be context-dependent and dynamic in nature leading
to heterogeneity of genetic effects across different parts of the phenotype distribution.
Quantile regression, an alternative to linear regression for continuous ...
Fungal centromeres are clustered near microtubule organizing centers to help adopt
the Rabl chromosomal organization. The role of centromere clustering in driving large-scale
changes in structural and functional chromatin assembly remains unclear. Here, ...
Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy
and severely affects multiple organ systems, including the brain, heart, skeletal
muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing
...
Type 1 narcolepsy (T1N), an autoimmune disease associated with a disruption of hypocretin/orexin
neurons, has conserved genetic effects transcending cultures and ethnicities. We pooled
data from 5,339 cases from China, Europe, Korea, Japan, and the United ...
The molecular genetic diagnosis of prelingual sensorineural hearing impairment (HI)
is essential for genetic counseling and patient management. Effective diagnosis requires
a knowledge of the genetic architecture of HI, which is often lacking. We ...
Immunology and Inflammation
To initiate T cell–mediated immunity, dendritic cells (DCs) present antigens to T
cells through the establishment of an immune synapse (IS). While events behind IS
formation in T cells are well understood, the organization of IS components at the
DC ...
Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of
infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that
mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development
...
Lupus nephritis (LN), which is characterized by the accumulation of DNA-containing
immune complexes (ICs), is the leading cause of death in patients with systemic lupus
erythematosus (SLE). While growing evidence highlights the central role of CD103+ T ...
The intracellular processing route used by type I conventional dendritic cells (cDC1)
for cross-presentation of viral- or tumor-associated antigens remains controversial.
One model proposes that captured antigens exit from damaged phagolysosomes and enter
...
Microbiology
Although considered primarily extracellular, Acinetobacter baumannii can survive and replicate within macrophages in vitro. Intracellular bacteria are
often protected from the host immune system and antibiotic treatment, potentially
leading to chronic or ...
Data suggest that antagonism between bacteria is prevalent within the gut microbiome.
Such antagonism could have profound consequences on the fitness of species; however,
the susceptibility determinants to even the most pervasive antagonistic factors in
...
Biofilms are critical for the environmental persistence, survival, and infectivity
of Vibrio cholerae, the causative agent of cholera. Here, we find that GluP, a glutamate-specific TRAP-TAXI
protein, is an uncharacterized matrix component that plays a ...
All cells use lipid membranes to maintain cellular integrity and function, though
Archaea utilize lipids composed of glycerol-1-phosphate (G1P), while Bacteria and
Eukaryotes use glycerol-3-phosphate (G3P). Given that Archaea contribute significantly
to ...
Fluoride has long been known to possess antimicrobial properties. For many bacteria,
the toxic effects of fluoride are reversible. However, fluoride has also been shown
to trigger lysis and cell death in many other diverse bacterial species, including
...
Human enterovirus A71 (EV-A71) is a major cause of hand, foot and mouth disease. Cellular
factors critical for EV-A71 infection remain enigmatic. Here, we performed CRISPR/Cas9
screens and identified sphingolipid transporter 1 (SPNS1) as an essential ...
Neuroscience
The brain is a metabolically vulnerable organ as neurons have both high resting metabolic
rates and the need for local rapid conversion of carbon sources to ATP during activity.
Midbrain dopamine neurons are thought to be particularly vulnerable to ...
Brain-inspired spiking neural networks (SNNs) have garnered significant research attention
in algorithm design and perception applications. However, their potential in the decision-making
domain, particularly in model-based reinforcement learning, remains ...
Noninvasive electrophysiological source imaging (ESI) is a valuable tool for localizing
and imaging brain activity, with significant potential to aid presurgical planning
in focal drug-resistant epilepsy (fDRE) patients. Scalp electroencephalography (EEG)
...
The basal ganglia (BG) are a collection of subcortical nuclei involved in motor control,
sensorimotor integration, and procedural learning. They play a key role in the acquisition
and adaptation of movements, a process driven by dopamine-dependent ...
Neuropathic pain associated with central sensitization is common in diabetic patients,
but the underlying mechanisms remain unclear. Here, a proteomics screen identified
a previously uncharacterized protein, galectin-related protein (LGALSL), which was
...
microRNAs (miRNAs) are key regulators of multiple biological functions. Although intensively
studied, inactivating miRNAs in vivo is particularly challenging, especially in the
brain. Here, we designed cell-specific tools aiming at downregulating defined ...
Despite tremendous progress in promoting endogenous axon regeneration and engineering
relay pathways by cell transplantation, the obtained functional recovery is still
limited. We reason that these regenerated connections might not be able to integrate
...
Social information processing involves coordinated neural activity across distributed
brain circuits, with the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC)
playing pivotal roles. However, whether these regions employ distinct coding ...
Hierarchically nested structures are fundamental to human cognition, enabling complex
behaviors across domains including language, planning, and mathematics. However, the
neural mechanisms that enable the flexible construction of these hierarchical ...
Circadian rhythms in mammals arise from the spatiotemporal synchronization of ~20,000
neuronal clocks in the suprachiasmatic nucleus (SCN). Although anatomical, molecular,
and genetic approaches have revealed diverse SCN cell types, how network-level ...
Physiology
Store-operated Ca2+ entry is a key signaling pathway controlled by the interaction of the ER Ca2+ sensor STIM1 with the Orai1 Ca2+ channel following ER Ca2+ depletion. To avoid generating pathological effects, STIM1 must remain mostly inactive
under ...
Plant Biology
Isoflavonoids, predominantly found in legumes, are specialized metabolites with antioxidant
properties that benefit both plant resilience and human health. Using metabolic genome-wide
association studies (mGWAS), we identified the cytochrome P450 gene (...
Population Biology
Climate-driven ocean warming is profoundly reshaping marine ecosystems, with cascading
effects on biodiversity and trophic interactions. For migratory marine predators such
as seabirds, demographic responses to warming depend on when and where populations
...
Corrections
Cover image: Pictured is a composite of time-lapse images of electrically stabilized and acoustically levitated particles. Sue Shi et al. balanced attractive acoustic forces with repulsive electrostatic forces to assemble complex motifs of particles. The authors created configurations in which the particles were separated by multiple particle lengths, configurations in which the particles were in contact, and hybrid configurations. The approach could enable the design, engineering, and manipulation of microparticle systems, such as micromachines. See the article by Shi et al. e2516865122. Image credit: Sue Shi.
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