Table Of Contents Page, PNAS Volume 121, Number 46
Special Feature
RNAs and Their Intracellular Processing During Oxidative Stress
From tumorigenesis to advanced metastatic stages, tumor cells encounter stress, ranging
from limited nutrient and oxygen supply within the tumor microenvironment to extrinsic
and intrinsic oxidative stress. Thus, tumor cells seize regulatory pathways to ...
Similar to DNA and histone, RNA can also be methylated. In its most common form, a
N6-methyladenosine (m6A) chemical modification is introduced into nascent messenger ribonucleic acid (mRNA)
by a specialized methyltransferase complex and removed by the ...
Over two decades ago, increased levels of RNA oxidation were reported in postmortem
patients with ALS, Alzheimer’s, Parkinson’s, and other neurodegenerative diseases.
Interestingly, not all cell types and transcripts were equally oxidized. Furthermore,
it ...
Stress-induced modification of Escherichia coli tRNA generates 5-methylcytidine in the variable loop
There has been recent interest in trying to understand the connection between transfer
RNA (tRNA) posttranscriptional modifications and changes in-cellular environmental
conditions. Here, we report on the identification of the modified nucleoside 5-...
Fe–S clusters are essential cofactors involved in many reactions across all domains
of life. Their biogenesis in Escherichia coli and other enterobacteria involves two machineries: Isc and Suf. Under conditions
where cells operate with the Suf system, ...
In the last decade, several novel functions of the mammalian Apurinic/Apyrimidinic
Endodeoxyribonuclease 1 (APE1) have been discovered, going far beyond its canonical
function as DNA repair enzyme and unveiling its potential roles in cancer development.
...
Post-transcriptional modification of RNA regulates gene expression at multiple levels.
ALKBH8 is a tRNA-modifying enzyme that methylates wobble uridines in a subset of tRNAs
to modulate translation. Through methylation of tRNA-selenocysteine, ALKBH8 ...
RNA oxidation, predominantly through the accumulation of 8-oxo-7,8-dihydroguanosine
(8-oxo-rG), represents an important biomarker for cellular oxidative stress. Polynucleotide
phosphorylase (PNPase) is a 3′-5′ exoribonuclease that has been shown to ...
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Brief Report
From infancy, children show heightened interest in events that are impossible or improbable,
relative to likely events. Do young children represent impossible and improbable events
as points on a continuum of possibility, or do they instead treat them as ...
Physical Sciences
Applied Mathematics
Neural manifolds summarize the intrinsic structure of the information encoded by a
population of neurons. Advances in experimental techniques have made simultaneous
recordings from multiple brain regions increasingly commonplace, raising the possibility
...
It has been widely recognized that technologies evolve with recombinant inventions.
However, it remains unknown whether technologies developed using different approaches
would exhibit different features during evolution. In particular, would technologies
...
Applied Physical Sciences
Fluxes of energy generate active forces in living matter, yet also active fluctuations.
As a canonical example, collections of molecular motors exhibit spontaneous oscillations
with frequency jitter caused by nonequilibrium phase fluctuations. We ...
In this work, the phenomenon of strain induced by a mismatch in thermal expansion
coefficients between a thin film and its substrate is harnessed in a new context,
replacing the canonical planar support with a three-dimensional (3-D), nanoconfining
...
High-resolution full waveform seismic tomography of the Earth’s mantle beneath the
south and central Atlantic Ocean brings into focus a series of asthenospheric low
shear velocity channels, or “fingers” on both sides of the southern and central mid-...
Biophysics and Computational Biology
Many prokaryotic and eukaryotic cells metabolize glucose to organism-specific by-products
instead of fully oxidizing it to carbon dioxide and water—a phenomenon referred to
as the Warburg Effect. The benefit to a cell is not fully understood, given that ...
Cells adapt to environments and tune gene expression by controlling the concentrations
of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes,
experiments and theory increasingly attest that these networks can and do ...
All life forms depend on the conversion of energy into biomass used in growth and
reproduction. For unicellular heterotrophs, the energetic cost associated with building
a cell scales slightly sublinearly with cell weight. However, observations on ...
Chemistry
Burkholderia thailandensis has emerged as a nonpathogenic surrogate for Burkholderia pseudomallei, the causative agent of melioidosis, and an important Gram-negative model bacterium
for studying the biosynthesis and regulation of secondary metabolism. We ...
The drastic shape deformation that accompanies the structural phase transition in
thermosalient materials offers great potential for their applications as actuators
and sensors. The microscopic origin of this fascinating effect has so far remained
obscure,...
Computer Sciences
A key function of the lexicon is to express novel concepts as they emerge over time
through a process known as lexicalization. The most common lexicalization strategies
are the reuse and combination of existing words, but they have typically been studied
...
Movies are a massively popular and influential form of media, but their computational
study at scale has largely been off-limits to researchers in the United States due
to the Digital Millennium Copyright Act. In this work, we illustrate use of a new
...
Earth, Atmospheric, and Planetary Sciences
The snowball Earth hypothesis predicts that continental chemical weathering diminished
substantially during, but rebounded strongly after, the Marinoan ice age some 635
Mya. Defrosting the planet would result in a plume of fresh glacial meltwater with
a ...
View related content:
The end-Triassic extinction (ETE) on land was synchronous with the initial lavas of
the Central Atlantic Magmatic Province (CAMP) and occurred just after the brief 26
thousand year (kyr) reverse geomagnetic polarity Chron E23r that can be used for global
...
The formation of mineral-associated organic matter (MAOM) is a key phenomenon that
may explain the slow turnover rates of carbon in soil organic matter (SOM). Despite
this, important details pertaining to the structure and dynamics of MAOM remain unknown.
...
Latitudinal patterns in ocean C:N:P reflect phytoplankton acclimation and macromolecular composition
The proportions of carbon (C), nitrogen (N), and phosphorus (P) in surface ocean particulate
matter deviate greatly from the canonical Redfield Ratio (C:N:P = 106:16:1) in space
and time with significant implications for global carbon storage as this ...
Engineering
The concepts of origami and kirigami have often been presented separately. Here, we
put forth a synergistic approach—the folded kirigami—in which kirigami assemblies
are complemented by means of folding, typical of origami patterns. Besides the emerging
...
Continuously monitoring human airway conditions is crucial for timely interventions,
especially when airway stents are implanted to alleviate central airway obstruction
in lung cancer and other diseases. Mucus conditions, in particular, are important
...
Physics
Frictional slip between bodies having different elastic or geometrical properties
(bimaterial interfaces) creates a unique type of rupture, bimaterial “slip pulses.”
These slip pulses propagate along the interfaces separating elastically different
...
A key ingredient for realizing a magnetically confined tritium-deuterium plasma fusion
reactor is plasma heating by fusion-born high-energy helium ions, as a chained cycle
of “nuclear burning.” Efficient collisionless plasma heating by high-energy ...
The Stoner instability remains a cornerstone for understanding metallic ferromagnets.
This instability captures the interplay of Coulomb repulsion, Pauli exclusion, and
twofold fermionic spin degeneracy. In materials with spin–orbit coupling, this ...
The expression of a few key genes determines the body plan of the fruit fly. We show
that the spatial expression patterns for several of these genes scale precisely with
embryo size. Discrete positional markers such as the peaks in striped patterns or
the ...
A faster cruising speed increases drag and thereby the thrust (T) needed to fly, while weight and lift (L) requirement remains constant. Birds can adjust their wingbeat in multiple ways to
accommodate this change in aerodynamic force, but the relative ...
Studying the early events that occur after viral infection in humans is difficult
unless one intentionally infects volunteers in a human challenge study. Here, we use
data about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in such a
study ...
Sustainability Science
Urban heat mitigation is a pressing concern for cities. Intense urban heat poses a
threat to human health and urban sustainability. Tree planting is one of the most
widely employed nature-based heat mitigation methods worldwide. Therefore, city policy
...
Social Sciences
Demography
As the world’s climate continues to change, human populations are exposed to increasingly
severe and extreme weather conditions that can promote migration. Here, we examine
how extreme weather influences the likelihood of undocumented migration and return
...
While female education has long been recognized as a key driver of fertility decline
during the process of demographic transition and most population projection models
consider it implicitly or explicitly in their forecasts of overall fertility, there
...
Psychological and Cognitive Sciences
A key function of the lexicon is to express novel concepts as they emerge over time
through a process known as lexicalization. The most common lexicalization strategies
are the reuse and combination of existing words, but they have typically been studied
...
A striking feature of human cognition is an exceptional ability to rapidly adapt to
novel situations. It is proposed this relies on abstracting and generalizing past
experiences. While previous research has explored how humans detect and generalize
single ...
People often rely on numeric metrics to make decisions and form judgments. Numbers
can be difficult to process, leading to their underutilization, but they are also
uniquely suited to making comparisons. Do people decide differently when some dimensions
...
Social Sciences
Movies are a massively popular and influential form of media, but their computational
study at scale has largely been off-limits to researchers in the United States due
to the Digital Millennium Copyright Act. In this work, we illustrate use of a new
...
The “27 Club” refers to the widespread legend that notable people, particularly musicians,
are unusually likely to die at age 27. A 2011 inquiry in The BMJ showed this is not
the case, dismissing the 27 Club as a myth. We expand on this discourse by ...
Biological Sciences
Agricultural Sciences
To address rising global food demand, the development of sustainable technologies
to increase productivity is urgently needed. This study revealed that foliar application
of zinc oxide nanoparticles (ZnO NPs; 30 to 80 nm, 0.67 mg/d per plant, 6 d) to rice
...
Anthropology
Oysters (Ostreidae) play a pivotal role in the health and productivity of marine ecosystems.
Their unique ability to filter water, provide habitat, and contribute to nutrient
cycling has remained underused in many parts of Europe following the destruction ...
Applied Biological Sciences
Spatial-transcriptomics technologies have demonstrated exceptional performance in
characterizing brain and visceral organ tissues, as well as brain and retinal organoids.
However, it has not yet been proven whether spatial transcriptomics can effectively
...
Biochemistry
Many prokaryotic and eukaryotic cells metabolize glucose to organism-specific by-products
instead of fully oxidizing it to carbon dioxide and water—a phenomenon referred to
as the Warburg Effect. The benefit to a cell is not fully understood, given that ...
The maturation and installation of the active site metal cluster (FeMo-co, Fe7S9CMo-R-homocitrate) in Mo-dependent nitrogenase requires the protein product of the nifB gene for production of the FeS cluster precursor (NifB-co, [Fe8S9C]) and the action of ...
Collagens are the foundational component of diverse tissues, including skin, bone,
cartilage, and basement membranes, and are the most abundant protein class in animals.
The fibrillar collagens are large, complex, multidomain proteins, all containing the
...
Within a cell, protein-bound methionines can be chemically or enzymatically oxidized,
and subsequently reduced by methionine sulfoxide reductases (Msrs). Methionine oxidation
can result in structural damage or be the basis of functional regulation of ...
The pathway for synthesis of proline in most forms of life produces a highly unstable
intermediate, γ-L-glutamyl 5-phosphate (GP). For nearly 70 y, channeling of this intermediate
from the active site of glutamate 5-kinase to the active site of GP ...
P450 peroxidase activities are valued for their ability to catalyze complex chemical
transformations using economical H2O2; however, they have been largely underexplored compared to their monooxygenase and
peroxygenase activities. In this study, we ...
Biophysics and Computational Biology
Fluxes of energy generate active forces in living matter, yet also active fluctuations.
As a canonical example, collections of molecular motors exhibit spontaneous oscillations
with frequency jitter caused by nonequilibrium phase fluctuations. We ...
Cells adapt to environments and tune gene expression by controlling the concentrations
of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes,
experiments and theory increasingly attest that these networks can and do ...
Cellular deconvolution via bulk RNA sequencing (RNA-seq) presents a cost-effective
and efficient alternative to experimental methods such as flow cytometry and single-cell
RNA-seq (scRNA-seq) for analyzing the complex cellular composition of tumor ...
SARS-CoV-2 carries a sizeable number of proteins that are accessory to replication
but may be essential for virus–host interactions and modulation of the host immune
response. Here, we investigated the structure and interactions of the largely unknown
...
Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating
numerous substrates, including ion channels, enzymes, and transcription factors. It
has long served as a model system for understanding the eukaryotic kinases. ...
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the anion channel mutated
in cystic fibrosis (CF) patients, is activated by the catalytic subunit of protein
kinase A (PKA-C). PKA-C activates CFTR both noncatalytically, through binding, and
...
Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies
consistent with ACTA1’s high expression in skeletal muscle. Rare de novo mutations
in ACTA1 associated with combined cardiac and skeletal myopathies have been reported,
...
Cell Biology
Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe
vision loss in the elderly in the developed world. While the introduction of therapies
targeting vascular endothelial growth factor (VEGF) has provided the first ...
Developmental Biology
Caste differentiation involves many functional traits that diverge during larval growth
and metamorphosis to produce adults irreversibly adapted to reproductive division
of labor. Investigating developmental differentiation is important for general ...
One of the first organizing processes during animal development is the assembly of
embryonic cells into epithelia. Common features unite epithelialization across select
bilaterians, however, we know less about the molecular and cellular mechanisms that
...
Mammalian tail length is controlled by several genetic determinants, among which are
Hox13 genes, whose function is to terminate the body axis. Accordingly, the precise timing
in the transcriptional activation of these genes may impact upon body length. ...
Ecology
Urban heat mitigation is a pressing concern for cities. Intense urban heat poses a
threat to human health and urban sustainability. Tree planting is one of the most
widely employed nature-based heat mitigation methods worldwide. Therefore, city policy
...
Many seabirds congregate in large colonies for breeding, a time when they are central
place foragers. An influential idea in seabird ecology posits that competition during
breeding results in an area of reduced prey availability around colonies, a ...
Enhancing terrestrial carbon (C) stock through ecological restoration, one of the
prominent approaches for natural climate solutions, is conventionally considered to
be achieved through an ecological pathway, i.e., increased plant C uptake. By conducting
...
Environmental Sciences
Latitudinal patterns in ocean C:N:P reflect phytoplankton acclimation and macromolecular composition
The proportions of carbon (C), nitrogen (N), and phosphorus (P) in surface ocean particulate
matter deviate greatly from the canonical Redfield Ratio (C:N:P = 106:16:1) in space
and time with significant implications for global carbon storage as this ...
Pastures, on which ruminant livestock graze, occupy one third of the earth’s surface.
Removing livestock from pastures can support climate change mitigation through carbon
sequestration in regrowing vegetation and recovering soils, particularly in ...
Evolution
All life forms depend on the conversion of energy into biomass used in growth and
reproduction. For unicellular heterotrophs, the energetic cost associated with building
a cell scales slightly sublinearly with cell weight. However, observations on ...
A faster cruising speed increases drag and thereby the thrust (T) needed to fly, while weight and lift (L) requirement remains constant. Birds can adjust their wingbeat in multiple ways to
accommodate this change in aerodynamic force, but the relative ...
A newborn F-box gene blocks gene flow by selectively degrading phosphoglucomutase in species hybrids
The establishment of reproductive barriers such as postzygotic hybrid incompatibility (HI) remains the key to speciation. Gene duplication followed by differential
functionalization has long been proposed as a major model underlying HI, but little
...
Genetics
Dinoflagellate chromosomes are extraordinary, as their organization is independent
of architectural nucleosomes unlike typical eukaryotes and shows a cholesteric liquid
crystal state. 5-hydroxymethyluridine (5hmU) is present at unusually high levels and
...
Immunology and Inflammation
Host–pathogen interactions are shaped by the metabolic status of both the host and
pathogen. The host must regulate metabolism to fuel the immune response, while the
pathogen must extract metabolic resources from the host to enable its own survival.
In ...
Medical Sciences
Studying the early events that occur after viral infection in humans is difficult
unless one intentionally infects volunteers in a human challenge study. Here, we use
data about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in such a
study ...
Microbiology
Burkholderia thailandensis has emerged as a nonpathogenic surrogate for Burkholderia pseudomallei, the causative agent of melioidosis, and an important Gram-negative model bacterium
for studying the biosynthesis and regulation of secondary metabolism. We ...
Members of the Bacteroidota compose a large portion of the human gut microbiota, contributing
to overall gut health via the degradation of various polysaccharides. This process
is facilitated by lipoproteins, globular proteins anchored to the cell surface ...
Microtubule-dependent endosomal transport is crucial for polar growth, ensuring the
precise distribution of cellular cargos such as proteins and mRNAs. However, the molecular
mechanism linking mRNAs to the endosomal surface remains poorly understood. Here,...
The proton-motive force (PMF), consisting of a pH gradient and a membrane potential
(ΔΨ) underpins many processes essential to bacterial growth and/or survival. Yet bacteria
often enter a bioenergetically diminished state characterized by a low PMF. ...
In Toxoplasma gondii, the conoid comprises a cone with spiraling tubulin fibers, preconoidal rings, and
intraconoidal microtubules. This dynamic organelle undergoes extension and retraction
through the apical polar ring (APR) during egress, gliding, and ...
Whole-genome sequencing of bacterial pathogens is used by public health agencies to
link cases of food poisoning caused by the same source of contamination. The vast
majority of these appear to be sporadic cases associated with small contamination
...
Quorum sensing (QS) is a cell-to-cell communication process that enables bacteria
to coordinate group behaviors. In Vibrio cholerae colonies, a program of spatial-temporal cell death is among the QS-controlled traits.
Cell death occurs in two phases, ...
Neuroscience
Neural manifolds summarize the intrinsic structure of the information encoded by a
population of neurons. Advances in experimental techniques have made simultaneous
recordings from multiple brain regions increasingly commonplace, raising the possibility
...
The visual system needs to identify perceptually relevant borders to segment complex
natural scenes. The primary visual cortex (V1) is thought to extract local borders,
and higher visual areas are thought to identify the perceptually relevant borders
...
The role of nonneuronal cells in the resolution of cerebral ischemia remains to be
fully understood. To decode key molecular and cellular processes that occur after
ischemia, we performed spatial and single-cell transcriptomic profiling of the male
mouse ...
Stroke causes pronounced and widespread slowing of neural activity. Despite decades
of work exploring these abnormal neural dynamics and their associated functional impairments,
their causes remain largely unclear. To close this gap in understanding, we ...
Active dendritic integrative mechanisms such as regenerative dendritic spikes enrich
the information processing abilities of neurons and fundamentally contribute to behaviorally
relevant computations. Dendritic Ca2+ spikes are generally thought to produce ...
Pharmacology
The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression
was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress
(CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular ...
Physiology
Double transgenic neonatal porcine islets as an alternative source for beta cell replacement therapy
To be clinically efficient, beta cell replacement therapies such as pig islet xenotransplantation
must ensure sufficient insulin secretion from grafted islets. While protection from
host immune reaction is essential for islet engraftment and their ...
Transient Receptor Potential Melastatin 2 (TRPM2) cation channels contribute to immunocyte
activation, insulin secretion, and central thermoregulation. TRPM2 opens upon binding
cytosolic Ca2+ and ADP ribose (ADPR). We present here the 2.5 Å cryo-...
The choroid is the thin, vasculature-filled layer of the eye situated between the
sclera and the retina, where it serves the metabolic needs of the light-sensing photoreceptors
in the retina. Illumination of the interior surface of the back of the eye (...
Plant Biology
Establishment of root nodule symbiosis is initiated by the perception of bacterial
Nod factor ligands by the plant LysM receptor kinases NFR1 and NFR5. Receptor signaling
initiating the symbiotic pathway depends on the kinase activity of NFR1, while the
...
Over the course of evolution, land plant mitochondrial genomes have lost many transfer
RNA (tRNA) genes and the import of nucleus-encoded tRNAs is essential for mitochondrial
protein synthesis. By contrast, plastidial genomes of photosynthetic land plants ...
To maintain CO2 fixation in the Calvin–Benson–Bassham cycle, multistep regulation of the chloroplast
ATP synthase (CF1Fo) is crucial to balance the ATP output of photosynthesis with protection of the apparatus.
A well-studied mechanism is thiol modulation;...
Psychological and Cognitive Sciences
A striking feature of human cognition is an exceptional ability to rapidly adapt to
novel situations. It is proposed this relies on abstracting and generalizing past
experiences. While previous research has explored how humans detect and generalize
single ...
Sustainability Science
Pastures, on which ruminant livestock graze, occupy one third of the earth’s surface.
Removing livestock from pastures can support climate change mitigation through carbon
sequestration in regrowing vegetation and recovering soils, particularly in ...
Corrections
SI Correction
Editorial Expression of Concern
Cover image: Pictured is RNA containing 8-oxo-rG (green), which is a biomarker of oxidative stress, in complex with an 8-oxo-rG reader enzyme. A collection of articles in the RNAs and Their Intracellular Processing During Oxidative Stress Special Feature highlights how RNA helps organisms, ranging from microbes to humans, withstand stress induced by environmental conditions and diseases including drug-resistant chronic infections, cancers, and neurodegenerative disorders. Together, the articles explore how oxidative stress modifies RNAs, how such modifications influence gene expression, and the role of small-RNAs and micro-RNAs in regulating stress responses. See the Introduction to the Special Feature, e2420445121. Image credit: Wantae Kim (University of Texas at Austin, Austin, TX).
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