Table Of Contents Page, PNAS Volume 121, Number 46

PNAS November 12, 2024
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 ...
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 ...

This Week in PNAS

Inner Workings

QnAs

Profile

Commentaries

Letters

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 ...
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Profile of Shuhai Xiao

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. ...
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

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 ...
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

Physiology

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 ...

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