Table Of Contents Page, PNAS Volume 118, Number 51

PNAS December 21, 2021

This Week in PNAS

Opinion

QnAs

Commentaries

Perspectives

Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially ...
The term “core microbiome” has become widely used in microbial ecology over the last decade. Broadly, the core microbiome refers to any set of microbial taxa, or the genomic and functional attributes associated with those taxa, that are characteristic of ...

Letters

Beyond Cases and Deaths: The Benefits of Auxiliary Data Streams In Tracking the COVID-19 Pandemic

Introduction

Research Articles

Short-term forecasts of traditional streams from public health reporting (such as cases, hospitalizations, and deaths) are a key input to public health decision-making during a pandemic. Since early 2020, our research group has worked with data partners ...
The US COVID-19 Trends and Impact Survey (CTIS) is a large, cross-sectional, internet-based survey that has operated continuously since April 6, 2020. By inviting a random sample of Facebook active users each day, CTIS collects information about COVID-19 ...
Simultaneously tracking the global impact of COVID-19 is challenging because of regional variation in resources and reporting. Leveraging self-reported survey outcomes via an existing international social media network has the potential to provide ...

Physical Sciences

Applied Mathematics

Ecological systems can undergo sudden, catastrophic changes known as critical transitions. Anticipating these critical transitions remains challenging in systems with many species because the associated early warning signals can be weakly present or even ...

Applied Physical Sciences

In the past decade, a great effort has been devoted to develop new biosensor platforms for the detection of a wide range of analytes. Among the various approaches, magneto-DNA assay platforms have received extended interest for high sensitive and specific ...

Biophysics and Computational Biology

The presence of a single cluster of nonoptimal codons was found to decrease a transcript’s half-life through the interaction of the ribosome-associated quality control machinery with stalled ribosomes in Saccharomyces cerevisiae. The impact of multiple ...
Recent studies have revealed that extensive heterogeneity of biological systems arises through various routes ranging from intracellular chromosome segregation to spatiotemporally varying biochemical stimulations. However, the contribution of physical ...
When host cells are in low abundance, temperate bacteriophages opt for dormant (lysogenic) infection. Phage lambda implements this strategy by increasing the frequency of lysogeny at higher multiplicity of infection (MOI). However, it remains unclear how ...
Imaging of proteins at the single-molecule level can reveal conformational variability, which is essential for the understanding of biomolecules. To this end, a biologically relevant state of the sample must be retained during both sample preparation and ...
Gene coexpression networks yield critical insights into biological processes, and single-cell RNA sequencing provides an opportunity to target inquiries at the cellular level. However, due to the sparsity and heterogeneity of transcript counts, it is ...

Chemistry

Photosynthetic reaction centers (RCs) from Rhodobacter sphaeroides were engineered to vary the electronic properties of a key tyrosine (M210) close to an essential electron transfer component via its replacement with site-specific, genetically encoded ...
Lithium peroxide is the crucial storage material in lithium–air batteries. Understanding the redox properties of this salt is paramount toward improving the performance of this class of batteries. Lithium peroxide, upon exposure to p–benzoquinone (p–C6H4O2)...
Abiotic CO2 reduction on transition metal minerals has been proposed to account for the synthesis of organic compounds in alkaline hydrothermal systems, but this reaction lacks experimental support, as only short-chain hydrocarbons (<C5) have been ...

Computer Sciences

Earth, Atmospheric, and Planetary Sciences

Anthropogenic activities have led to widespread contamination with mercury (Hg), a potent neurotoxin that bioaccumulates through food webs. Recent models estimated that, presently, 200 to 600 t of Hg is sequestered annually in deep-sea sediments, ...
Halogens are important tracers of various planetary formation and evolution processes, and an accurate understanding of their abundances in the Earth’s silicate reservoirs can help us reconstruct the history of interactions among mantle, atmosphere, and ...
Fluids are known to trigger a broad range of slip events, from slow, creeping transients to dynamic earthquake ruptures. Yet, the detailed mechanics underlying these processes and the conditions leading to different rupture behaviors are not well ...
Reconstructing the history of biological productivity and atmospheric oxygen partial pressure (pO2) is a fundamental goal of geobiology. Recently, the mass-independent fractionation of oxygen isotopes (O-MIF) has been used as a tool for estimating pO2 and ...

Engineering

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer ...
Mechanical properties are fundamental to structural materials, where dislocations play a decisive role in describing their mechanical behavior. Although the high-yield stresses of multiprincipal element alloys (MPEAs) have received extensive attention in ...

Environmental Sciences

Decades of air pollution regulation have yielded enormous benefits in the United States, but vehicle emissions remain a climate and public health issue. Studies have quantified the vehicle-related fine particulate matter (PM2.5)-attributable mortality but ...

Physics

In cuprate superconductors, due to strong electronic correlations, there are multiple intertwined orders which either coexist or compete with superconductivity. Among them, the antiferromagnetic (AF) order is the most prominent one. In the region where ...
Magnetoelastic dilatometry of the piezomagnetic antiferromagnet UO2 was performed via the fiber Bragg grating method in magnetic fields up to 150 T generated by a single-turn coil setup. We show that in microsecond timescales, pulsed-magnetic fields ...
Diamond is the hardest known material in nature and features a wide spectrum of industrial and scientific applications. The key to diamond's outstanding properties is its elasticity, which is associated with its exceptional hardness, shear strength, and ...

Statistics

We investigated historical redlining, a government-sanctioned discriminatory policy, in relation to cardiovascular health (CVH) and whether associations were modified by present-day neighborhood physical and social environments. Data included 4,779 ...
Fast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity ...
Short-term forecasts of traditional streams from public health reporting (such as cases, hospitalizations, and deaths) are a key input to public health decision-making during a pandemic. Since early 2020, our research group has worked with data partners ...

Social Sciences

Psychological and Cognitive Sciences

The surge of post-truth political argumentation suggests that we are living in a special historical period when it comes to the balance between emotion and reasoning. To explore if this is indeed the case, we analyze language in millions of books covering ...

Social Sciences

We investigated historical redlining, a government-sanctioned discriminatory policy, in relation to cardiovascular health (CVH) and whether associations were modified by present-day neighborhood physical and social environments. Data included 4,779 ...
Peer review is an integral component of contemporary science. While peer review focuses attention on promising and interesting science, it also encourages scientists to pursue some questions at the expense of others. Here, we use ideas from forecasting ...
The US COVID-19 Trends and Impact Survey (CTIS) is a large, cross-sectional, internet-based survey that has operated continuously since April 6, 2020. By inviting a random sample of Facebook active users each day, CTIS collects information about COVID-19 ...
Simultaneously tracking the global impact of COVID-19 is challenging because of regional variation in resources and reporting. Leveraging self-reported survey outcomes via an existing international social media network has the potential to provide ...

Sustainability Science

Decades of air pollution regulation have yielded enormous benefits in the United States, but vehicle emissions remain a climate and public health issue. Studies have quantified the vehicle-related fine particulate matter (PM2.5)-attributable mortality but ...

Biological Sciences

Applied Biological Sciences

Benzylisoquinoline alkaloids (BIAs) are a diverse class of medicinal plant natural products. Nearly 500 dimeric bisbenzylisoquinoline alkaloids (bisBIAs), produced by the coupling of two BIA monomers, have been characterized and display a range of ...

Biochemistry

RNA-dependent RNA polymerases play essential roles in RNA-mediated gene silencing in eukaryotes. In Arabidopsis, RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) physically interacts with DNA-dependent NUCLEAR RNA POLYMERASE IV (Pol IV) and their activities are ...
Human phagocytes have key functions in the resolution of inflammation. Here, we assessed the role of the proposed 4S,5S-epoxy-resolvin intermediate in the biosynthesis of both resolvin D3 and resolvin D4. We found that human neutrophils converted this ...

Biophysics and Computational Biology

Recent studies have revealed that extensive heterogeneity of biological systems arises through various routes ranging from intracellular chromosome segregation to spatiotemporally varying biochemical stimulations. However, the contribution of physical ...
The presence of a single cluster of nonoptimal codons was found to decrease a transcript’s half-life through the interaction of the ribosome-associated quality control machinery with stalled ribosomes in Saccharomyces cerevisiae. The impact of multiple ...
Photosynthetic reaction centers (RCs) from Rhodobacter sphaeroides were engineered to vary the electronic properties of a key tyrosine (M210) close to an essential electron transfer component via its replacement with site-specific, genetically encoded ...
G protein-coupled receptors (GPCRs) are the largest family of human proteins. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and effectors, activate downstream pathways that often modulate hallmark ...
Cells contain membraneless compartments that assemble due to liquid–liquid phase separation, including biomolecular condensates with complex morphologies. For instance, certain condensates are surrounded by a film of distinct composition, such as Ape1 ...
Over the past five decades, tremendous effort has been devoted to computational methods for predicting properties of ligands—i.e., molecules that bind macromolecular targets. Such methods, which are critical to rational drug design, fall into two ...
Simultaneously tracking the global impact of COVID-19 is challenging because of regional variation in resources and reporting. Leveraging self-reported survey outcomes via an existing international social media network has the potential to provide ...

Cell Biology

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer ...
KRAS is mutated in 90% of human pancreatic ductal adenocarcinomas (PDACs). To function, KRAS must localize to the plasma membrane (PM) via a C-terminal membrane anchor that specifically engages phosphatidylserine (PtdSer). This anchor-binding specificity ...
Local blood flow control within the central nervous system (CNS) is critical to proper function and is dependent on coordination between neurons, glia, and blood vessels. Macroglia, such as astrocytes and Müller cells, contribute to this neurovascular ...
N6-methyladenosine (m6A) deposition on messenger RNA (mRNA) controls embryonic stem cell (ESC) fate by regulating the mRNA stabilities of pluripotency and lineage transcription factors (TFs) [P. J. Batista et al., Cell Stem Cell 15, 707–719 (2014); Y. ...
Microtubules are dynamic cytoskeletal polymers that spontaneously switch between phases of growth and shrinkage. The probability of transitioning from growth to shrinkage, termed catastrophe, increases with microtubule age, but the underlying mechanisms ...
The ability to interrogate total RNA content of single cells would enable better mapping of the transcriptional logic behind emerging cell types and states. However, current single-cell RNA-sequencing (RNA-seq) methods are unable to simultaneously monitor ...
The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of three-dimensional (3D) organoids from adult thyroid tissue representing murine and human thyroid follicular cells (TFCs). ...

Developmental Biology

The axial skeleton of tetrapods is organized into distinct anteroposterior regions of the vertebral column (cervical, trunk, sacral, and caudal), and transitions between these regions are determined by colinear anterior expression boundaries of Hox5/6, -9,...

Ecology

Ecological systems can undergo sudden, catastrophic changes known as critical transitions. Anticipating these critical transitions remains challenging in systems with many species because the associated early warning signals can be weakly present or even ...

Evolution

How genome instability is harnessed for fitness gain despite its potential deleterious effects is largely elusive. An ideal system to address this important open question is provided by the protozoan pathogen Leishmania, which exploits frequent variations ...
Although males are a ubiquitous feature of animals, they have been lost repeatedly in diverse lineages. The tendency for obligate asexuality to evolve is thought to be reduced in animals whose males play a critical role beyond the contribution of gametes, ...
Invasion rates have increased in the past 100 y irrespective of international conventions. What characterizes a successful invasion event? And how does genetic diversity translate into invasion success? Employing a whole-genome perspective using one of ...
Two classes of major histocompatibility complex (MHC) molecules, MHC class I and class II, play important roles in our immune system, presenting antigens to functionally distinct T lymphocyte populations. However, the origin of this essential MHC class ...

Genetics

Fisheries induce one of the strongest anthropogenic selective pressures on natural populations, but the genetic effects of fishing remain unclear. Crucially, we lack knowledge of how capture-associated selection and its interaction with reductions in ...
Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant ...
Complete genome sequencing has identified millions of DNA changes that differ between humans and chimpanzees. Although a subset of these changes likely underlies important phenotypic differences between humans and chimpanzees, it is currently difficult to ...

Immunology and Inflammation

In mammals, cyclic dinucleotides (CDNs) bind and activate STING to initiate an antiviral type I interferon response. CDNs and STING originated in bacteria and are present in most animals. By contrast, interferons are believed to have emerged in ...
Epigenetic changes have been consistently detected in different cell types in multiple sclerosis (MS). However, their contribution to MS pathogenesis remains poorly understood partly because of sample heterogeneity and limited coverage of array-based ...
Here, we show that Porphyromonas gingivalis (Pg), an endogenous oral pathogen, dampens all aspects of interferon (IFN) signaling in a manner that is strikingly similar to IFN suppression employed by multiple viral pathogens. Pg suppressed IFN production ...

Medical Sciences

Spina bifida (SB) is a debilitating birth defect caused by multiple gene and environment interactions. Though SB shows non-Mendelian inheritance, genetic factors contribute to an estimated 70% of cases. Nevertheless, identifying human mutations conferring ...
The current high mortality of human lung cancer stems largely from the lack of feasible, early disease detection tools. An effective test with serum metabolomics predictive models able to suggest patients harboring disease could expedite triage patient to ...
Arterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in ...

Microbiology

When host cells are in low abundance, temperate bacteriophages opt for dormant (lysogenic) infection. Phage lambda implements this strategy by increasing the frequency of lysogeny at higher multiplicity of infection (MOI). However, it remains unclear how ...
Herpes simplex virus (HSV) infection relies on immediate early proteins that initiate viral replication. Among them, ICP0 is known, for many years, to facilitate the onset of viral gene expression and reactivation from latency. However, how ICP0 itself is ...
Antimicrobial chemotherapy can fail to eradicate the pathogen, even in the absence of antimicrobial resistance. Persisting pathogens can subsequently cause relapsing diseases. In vitro studies suggest various mechanisms of antibiotic persistence, but ...

Neuroscience

Fast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity ...
Receptors for bitter, sugar, and other tastes have been identified in the fruit fly Drosophila melanogaster, while a broadly tuned receptor for the taste of acid has been elusive. Previous work showed that such a receptor was unlikely to be encoded by a ...
Brains learn tasks via experience-driven differential adjustment of their myriad individual synaptic connections, but the mechanisms that target appropriate adjustment to particular connections remain deeply enigmatic. While Hebbian synaptic plasticity, ...
Cancer survivors rank sensorimotor disability among the most distressing, long-term consequences of chemotherapy. Disorders in gait, balance, and skilled movements are commonly assigned to chemotoxic damage of peripheral sensory neurons without ...
The observation of place cells has suggested that the hippocampus plays a special role in encoding spatial information. However, place cell responses are modulated by several nonspatial variables and reported to be rather unstable. Here, we propose a ...
Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry ...
The brain supports adaptive behavior by generating predictions, learning from errors, and updating memories to incorporate new information. Prediction error, or surprise, triggers learning when reality contradicts expectations. Prior studies have shown ...
Epileptic encephalopathy (EE) is characterized by seizures that respond poorly to antiseizure drugs, psychomotor delay, and cognitive and behavioral impairments. One of the frequently mutated genes in EE is KCNQ2, which encodes the Kv7.2 subunit of ...
We uncovered a transcription factor (TF) network that regulates cortical regional patterning in radial glial stem cells. Screening the expression of hundreds of TFs in the developing mouse cortex identified 38 TFs that are expressed in gradients in the ...

Plant Biology

Chiral asymmetry is important in a wide variety of disciplines and occurs across length scales. While several natural chiral biomolecules exist only with single handedness, they can produce complex hierarchical structures with opposite chiralities. ...
Clathrin-mediated endocytosis is the major route of entry of cargos into cells and thus underpins many physiological processes. During endocytosis, an area of flat membrane is remodeled by proteins to create a spherical vesicle against intracellular ...
Thioredoxin (Trx) is a protein that mediates the reducing power transfer from the photosynthetic electron transport system to target enzymes in chloroplasts and regulates their activities. Redox regulation governed by Trx is a system that is central to ...
The alternating cell specifications of root epidermis to form hair cells or nonhair cells in Arabidopsis are determined by the expression level of GL2, which is activated by an MYB–bHLH–WD40 (WER–GL3–TTG1) transcriptional complex. The phytohormone ...

Population Biology

The US COVID-19 Trends and Impact Survey (CTIS) is a large, cross-sectional, internet-based survey that has operated continuously since April 6, 2020. By inviting a random sample of Facebook active users each day, CTIS collects information about COVID-19 ...

Psychological and Cognitive Sciences

We provide evidence that human sleep is a competitive arena in which cognitive domains vie for limited resources. Using pharmacology and effective connectivity analysis, we demonstrate that long-term memory and working memory are served by distinct ...
The question of why our conceptions of space and time are intertwined with memory in the hippocampal formation is at the forefront of much current theorizing about this brain system. In this article I argue that animals bridge spatial and temporal gaps ...
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Profile of Lynn Nadel

Systems Biology

Aerobic fermentation, also referred to as the Crabtree effect in yeast, is a well-studied phenomenon that allows many eukaryal cells to attain higher growth rates at high glucose availability. Not all yeasts exhibit the Crabtree effect, and it is not ...
The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with ...
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