Table Of Contents Page, PNAS Volume 115, Number 12

PNAS March 20, 2018

This Week in PNAS

Letters (Online Only)

Opinion

Commentaries

PNAS Plus Significance Statements

Perspective

Aging is the most significant risk factor associated with chronic disease in humans. The accumulation of genetic damage throughout life leads to a variety of biological aberrations, including disrupted protein homeostasis, metabolic dysfunction, and ...

Physical Sciences

Applied Physical Sciences

Ferromagnetic insulators are required for many new magnetic devices, such as dissipationless quantum-spintronic devices, magnetic tunneling junctions, etc. Ferromagnetic insulators with a high Curie temperature and a high-symmetry structure are critical ...
The control and manipulation of thermal fields is a key scientific and technological challenge, usually addressed with nanophotonic structures with a carefully designed geometry. Here, we theoretically investigate a different strategy based on epsilon-...
Buckling, first introduced by Euler in 1744 [Euler L (1744) Opera Omnia I 24:231], a sudden mechanical sideways deflection of a structural member under compressive stress, represents a bifurcation in the solution to the equations of static equilibrium. ...

Biophysics and Computational Biology

We present a method enabling the noninvasive study of minute cellular changes in response to stimuli, based on the acquisition of multiple parameters through label-free microscopy. The retrieved parameters are related to different attributes of the cell. ...
Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains ...
Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein−lipid assemblies. Despite this inherent complexity, the identification of specific protein−lipid interactions and the ...
Succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria. The biogenesis of flavinylated SdhA, the catalytic subunit of SQR, is assisted by a ...
During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data ...

Chemistry

An in-depth knowledge of the interaction of water with amorphous silica is critical to fundamental studies of interfacial hydration water, as well as to industrial processes such as catalysis, nanofabrication, and chromatography. Silica has a tunable ...
Crystals that show mechanical response against various stimuli are of great interest. These stimuli induce polymorphic transitions, isomerizations, or chemical reactions in the crystal and the strain generated between the daughter and parent domains is ...
Atomically dispersed catalysts refer to substrate-supported heterogeneous catalysts featuring one or a few active metal atoms that are separated from one another. They represent an important class of materials ranging from single-atom catalysts (SACs) and ...
Protein–protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein–protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled ...

Computer Sciences

Earth, Atmospheric, and Planetary Sciences

A deep lower-mantle (DLM) water reservoir depends on availability of hydrous minerals which can store and transport water into the DLM without dehydration. Recent discoveries found hydrous phases AlOOH (Z = 2) with a CaCl2-type structure and FeOOH (Z = 4) ...
Cities are concentrated areas of CO2 emissions and have become the foci of policies for mitigation actions. However, atmospheric measurement networks suitable for evaluating urban emissions over time are scarce. Here we present a unique long-term (decadal)...
Oceanic Anoxic Event 2 (OAE 2), occurring ∼94 million years ago, was one of the most extreme carbon cycle and climatic perturbations of the Phanerozoic Eon. It was typified by a rapid rise in atmospheric CO2, global warming, and marine anoxia, leading to ...
Marine stratocumulus clouds cover nearly one-quarter of the ocean surface and thus play an extremely important role in determining the global radiative balance. The semipermanent marine stratocumulus deck over the southeastern Atlantic Ocean is of ...
Idealized simulations of tropical moist convection have revealed that clouds can spontaneously clump together in a process called self-aggregation. This results in a state where a moist cloudy region with intense deep convection is surrounded by extremely ...

Engineering

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi)...
Microbial production of value-added chemicals from biomass is a sustainable alternative to chemical synthesis. To improve product titer, yield, and selectivity, the pathways engineered into microbes must be optimized. One strategy for optimization is ...

Physics

The nasal cavity is a vital component of the respiratory system that heats and humidifies inhaled air in all vertebrates. Despite this common function, the shapes of nasal cavities vary widely across animals. To understand this variability, we here ...

Sustainability Science

Food production is a major driver of global environmental change and the overshoot of planetary sustainability boundaries. Greater affluence in developing nations and human population growth are also increasing demand for all foods, and for animal ...

Social Sciences

Economic Sciences

Between 1776 and 1920, the US Congress designed more than 200 distinct securities and stated the maximum amount of each that the Treasury could sell. Between 1917 and 1939, Congress gradually delegated all decisions about designing US debt instruments to ...

Environmental Sciences

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection ...
Vacant and blighted urban land is a widespread and potentially risky environmental condition encountered by millions of people on a daily basis. About 15% of the land in US cities is deemed vacant or abandoned, an area roughly the size of Switzerland. In ...

Social Sciences

Obtaining grant funding from the National Institutes of Health (NIH) is increasingly competitive, as funding success rates have declined over the past decade. To allocate relatively scarce funds, scientific peer reviewers must differentiate the very best ...

Biological Sciences

Agricultural Sciences

Food production is a major driver of global environmental change and the overshoot of planetary sustainability boundaries. Greater affluence in developing nations and human population growth are also increasing demand for all foods, and for animal ...

Applied Biological Sciences

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi)...
Microbial production of value-added chemicals from biomass is a sustainable alternative to chemical synthesis. To improve product titer, yield, and selectivity, the pathways engineered into microbes must be optimized. One strategy for optimization is ...
Efficient lignin valorization could add more than 10-fold the value gained from burning it for energy and is critical for economic viability of future biorefineries. However, lignin-derived aromatics from biomass pretreatment are known to be potent ...

Biochemistry

Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted ...
The conjugation of amino acids to the protein N termini is universally observed in eukaryotes and prokaryotes, yet its functions remain poorly understood. In eukaryotes, the amino acid l-arginine (l-Arg) is conjugated to N-terminal Asp (Nt-Asp), Glu, Gln, ...
The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be ...
Eukaryotic gene regulation is a complex process, often coordinated by the action of tens to hundreds of proteins. Although previous biochemical studies have identified many components of the basal machinery and various ancillary factors involved in gene ...
Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein−lipid assemblies. Despite this inherent complexity, the identification of specific protein−lipid interactions and the ...
Succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria. The biogenesis of flavinylated SdhA, the catalytic subunit of SQR, is assisted by a ...
The ATP synthase in human mitochondria is a membrane-bound assembly of 29 proteins of 18 kinds. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, and imported into the matrix of the organelle, where they ...
Chemically demanding reductive conversions in biology, such as the reduction of dinitrogen to ammonia or the Birch-type reduction of aromatic compounds, depend on Fe/S-cluster–containing ATPases. These reductions are typically catalyzed by two-component ...
Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the ...
Most proteins comprise two or more domains from a limited suite of protein families. These domains are often rearranged in various combinations through gene fusion events to evolve new protein functions, including the acquisition of protein allostery ...
Enzymatic substrate selectivity is critical for the precise control of metabolic pathways. In cases where chemically related substrates are present inside cells, robust mechanisms of substrate selectivity are required. Here, we report the mechanism ...
Some codons of the genetic code can be read not only by cognate, but also by near-cognate tRNAs. This flexibility is thought to be conferred mainly by a mismatch between the third base of the codon and the first of the anticodon (the so-called “wobble” ...
We used electron cryo-tomography and subtomogram averaging to investigate the structure of complex I and its supramolecular assemblies in the inner mitochondrial membrane of mammals, fungi, and plants. Tomographic volumes containing complex I were ...
Methyl-coenzyme M reductase (MCR) is an essential enzyme found strictly in methanogenic and methanotrophic archaea. MCR catalyzes a reversible reaction involved in the production and consumption of the potent greenhouse gas methane. The α-subunit of this ...

Biophysics and Computational Biology

Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains ...
Sodium-dependent transporters couple the flow of Na+ ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and ...
Protein–protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein–protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled ...
YiiP is a dimeric antiporter from the cation diffusion facilitator family that uses the proton motive force to transport Zn2+ across bacterial membranes. Previous work defined the atomic structure of an outward-facing conformation, the location of several ...
The Saccharomyces cerevisiae respiratory supercomplex factor 1 (Rcf1) protein is located in the mitochondrial inner membrane where it is involved in formation of supercomplexes composed of respiratory complexes III and IV. We report the solution structure ...
Proteins fold to their lowest free-energy structures, and hence the most straightforward way to increase the accuracy of a partially incorrect protein structure model is to search for the lowest-energy nearby structure. This direct approach has met with ...
The small multidrug resistance (SMR) family of membrane proteins is prominent because of its rare dual topology architecture, simplicity, and small size. Its best studied member, EmrE, is an important model system in several fields related to membrane ...
Transmembrane protein 16F (TMEM16F) is a Ca2+-dependent phospholipid scramblase that translocates phospholipids bidirectionally between the leaflets of the plasma membrane. Phospholipid scrambling of TMEM16F causes exposure of phosphatidylserine in ...

Cell Biology

Aggregation of islet amyloid polypeptide (IAPP) into amyloid fibrils in islets of Langerhans is associated with type 2 diabetes, and formation of toxic IAPP species is believed to contribute to the loss of insulin-producing beta cells. The BRICHOS domain ...
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and triggers the unfolded protein response (UPR). Failure to resolve ER stress leads to apoptotic cell death via a yet unclear mechanism. Here, we show that RNF183, ...

Developmental Biology

RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway ...

Ecology

Nonpolio enteroviruses are diverse and common viruses that can circulate year-round but tend to peak in summer. Although most infections are asymptomatic, they can result in a wide range of neurological and other diseases. Many serotypes circulate every ...
Corals are major contributors to a range of key ecosystem functions on tropical reefs, including calcification, photosynthesis, nutrient cycling, and the provision of habitat structure. The abundance of corals is declining at multiple scales, and the ...

Environmental Sciences

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection ...

Evolution

Efforts are underway to construct several recoded genomes anticipated to exhibit multivirus resistance, enhanced nonstandard amino acid (nsAA) incorporation, and capability for synthetic biocontainment. Although our laboratory pioneered the first ...
Many microbes engage in social interactions. Some of these have come to play an important role in the study of cooperation and conflict, largely because, unlike most animals, they can be genetically manipulated and experimentally evolved. However, whereas ...
The bacterial pathogen Streptococcus pneumoniae is a major public health concern, being responsible for more than 1.5 million deaths annually through pneumonia, meningitis, and septicemia. Available vaccines target only a subset of serotypes, so ...

Genetics

As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and ...
The centromere DNA locus on a eukaryotic chromosome facilitates faithful chromosome segregation. Despite performing such a conserved function, centromere DNA sequence as well as the organization of sequence elements is rapidly evolving in all forms of ...
Neural circuits utilize a coordinated cellular machinery to form and eliminate synaptic connections, with the neuronal cytoskeleton playing a prominent role. During larval development of Caenorhabditis elegans, synapses of motor neurons are ...

Immunology and Inflammation

We present a method enabling the noninvasive study of minute cellular changes in response to stimuli, based on the acquisition of multiple parameters through label-free microscopy. The retrieved parameters are related to different attributes of the cell. ...
The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B ...
Induced B7-H1 expression in the tumor microenvironment initiates adaptive resistance, which impairs immune functions and leads to tumor escape from immune destruction. Antibody blockade of the B7-H1/PD-1 interaction overcomes adaptive resistance, leading ...

Medical Sciences

Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable ...
The pH (low) insertion peptides (pHLIPs) target acidity at the surfaces of cancer cells and show utility in a wide range of applications, including tumor imaging and intracellular delivery of therapeutic agents. Here we report pHLIP constructs that ...
Aberrant activation of endothelin-1 receptors (ET-1R) elicits pleiotropic effects relevant for tumor progression. The network activated by this receptor might be finely, spatially, and temporarily orchestrated by β-arrestin1 (β-arr1)–driven interactome. ...

Microbiology

Treatment of bacterial infections is becoming a serious clinical challenge due to the global dissemination of multidrug antibiotic resistance, necessitating the search for alternative treatments to disarm the virulence mechanisms underlying these ...
Penicillin-binding proteins (PBPs) are synthases required to build the essential peptidoglycan (PG) cell wall surrounding most bacterial cells. The mechanisms regulating the activity of these enzymes to control PG synthesis remain surprisingly poorly ...

Neuroscience

Sweet-insensitive Drosophila mutants are unable to readily identify sugar. In presence of wild-type (WT) flies, however, these mutant flies demonstrated a marked increase in their preference for nutritive sugar. Real-time recordings of starved WT flies ...
Mutations in the BEST1 gene cause detachment of the retina and degeneration of photoreceptor (PR) cells due to a primary channelopathy in the neighboring retinal pigment epithelium (RPE) cells. The pathophysiology of the interaction between RPE and PR ...
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Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly ...
Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by ...
During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data ...
Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural ...

Physiology

The nasal cavity is a vital component of the respiratory system that heats and humidifies inhaled air in all vertebrates. Despite this common function, the shapes of nasal cavities vary widely across animals. To understand this variability, we here ...

Plant Biology

Tip-growing cells elongate in a highly polarized manner via focused secretion of flexible cell-wall material. Calcium has been implicated as a vital factor in regulating the deposition of cell-wall material. However, deciphering the molecular and ...
Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, ...
Monoterpenoid indole alkaloids (MIAs) possess a diversity of alkaloid skeletons whose biosynthesis is poorly understood. A bioinformatic search of candidate genes, combined with their virus-induced gene silencing, targeted MIA profiling and in vitro/in ...

Psychological and Cognitive Sciences

To coordinate movements with events in a dynamic environment the brain has to anticipate when those events occur. A classic example is the estimation of time to contact (TTC), that is, when an object reaches a target. It is thought that TTC is estimated ...
Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost–benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking “virtual ...

Sustainability Science

Vacant and blighted urban land is a widespread and potentially risky environmental condition encountered by millions of people on a daily basis. About 15% of the land in US cities is deemed vacant or abandoned, an area roughly the size of Switzerland. In ...

Systems Biology

Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, ...

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