Table Of Contents Page, PNAS Volume 111, Number 29

PNAS July 22, 2014

This Week in PNAS

Letters (Online Only)

Science and Culture

QnAs

Commentaries

PNAS Plus Significance Statements

Physical Sciences

Applied Mathematics

Human activities increasingly take place in online environments, providing novel opportunities for relating individual behaviors to population-level outcomes. In this paper, we introduce a simple generative model for the collective behavior of millions of ...
As polio eradication inches closer, the absence of poliovirus circulation in most of the world and imperfect vaccination coverage are resulting in immunity gaps and polio outbreaks affecting adults. Furthermore, imperfect, waning intestinal immunity among ...

Applied Physical Sciences

We demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein. As an example, we show the specific binding of the common ...
Swarming is a conspicuous behavioral trait observed in bird flocks, fish shoals, insect swarms, and mammal herds. It is thought to improve collective awareness and offer protection from predators. Many current models involve the hypothesis that ...
Oxygen, one of the most common and important elements in nature, has an exceedingly well-explored phase diagram under pressure, up to and beyond 100 GPa. At low temperatures, the low-pressure antiferromagnetic phases below 8 GPa where O2 molecules have ...
In the field of spintronics, the archetype solid-state two-terminal device is the spin valve, where the resistance is controlled by the magnetization configuration. We show here how this concept of spin-dependent switch can be extended to magnetic ...

Chemistry

We present measurements of rate constants for thermal-induced reactions of the 11-cis retinyl chromophore in vertebrate visual pigment rhodopsin, a process that produces noise and limits the sensitivity of vision in dim light. At temperatures of 52.0–64.6 ...
Chemoresistance of cisplatin therapy is related to extensive repair of cisplatin-modified DNA in the nucleus by the nucleotide excision repair (NER). Delivering cisplatin to the mitochondria to attack mitochondrial genome lacking NER machinery can lead to ...
Overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC) oncogene is one of the most commonly implicated causes of human tumorigenesis. MYC is known to regulate many aspects of cellular biology including glucose and glutamine ...
Neon hydrate was synthesized and studied by in situ neutron diffraction at 480 MPa and temperatures ranging from 260 to 70 K. For the first time to our knowledge, we demonstrate that neon atoms can be enclathrated in water molecules to form ice II-...
Using 3D infrared (IR) exchange spectroscopy, the ultrafast hydrogen-bond forming and breaking (i.e., complexation) kinetics of phenol to benzene in a benzene/CCl4 mixture is investigated. By introducing a third time point at which the hydrogen-bonding ...
Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the ...

Computer Sciences

Even the most seasoned students of evolution, starting with Darwin himself, have occasionally expressed amazement that the mechanism of natural selection has produced the whole of Life as we see it around us. There is a computational way to articulate the ...

Earth, Atmospheric, and Planetary Sciences

Deciphering the origin of seismic velocity heterogeneities in the mantle is crucial to understanding internal structures and processes at work in the Earth. The spin crossover in iron in ferropericlase (Fp), the second most abundant phase in the lower ...
Tonga was unique in the prehistoric Pacific for developing a maritime state that integrated the archipelago under a centralized authority and for undertaking long-distance economic and political exchanges in the second millennium A.D. To establish the ...
Pelagornithidae is an extinct clade of birds characterized by bizarre tooth-like bony projections of the jaws. Here, the flight capabilities of pelagornithids are explored based on data from a species with the largest reported wingspan among birds. ...

Engineering

Encapsulation of islets of Langerhans may represent a way to transplant islets in the absence of immunosuppression. Traditional methods for encapsulation lead to diffusional limitations imposed by the size of the capsules (600–1,000 μm in diameter), which ...
The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias ...

Environmental Sciences

Secondary organic aerosol (SOA) formed from the atmospheric oxidation of nonmethane organic gases (NMOG) is a major contributor to atmospheric aerosol mass. Emissions and smog chamber experiments were performed to investigate SOA formation from gasoline ...

Physics

Four-dimensional multiple-cathode ultrafast electron microscopy is developed to enable the capture of multiple images at ultrashort time intervals for a single microscopic dynamic process. The dynamic process is initiated in the specimen by one ...
Quantum electromagnetic fluctuations induce forces between neutral particles, known as the van der Waals and Casimir interactions. These fundamental forces, mediated by virtual photons from the vacuum, play an important role in basic physics and chemistry ...

Social Sciences

Anthropology

Tonga was unique in the prehistoric Pacific for developing a maritime state that integrated the archipelago under a centralized authority and for undertaking long-distance economic and political exchanges in the second millennium A.D. To establish the ...
There is considerable controversy over whether pre-Columbian (pre-A.D. 1492) Amazonia was largely “pristine” and sparsely populated by slash-and-burn agriculturists, or instead a densely populated, domesticated landscape, heavily altered by extensive ...

Economic Sciences

Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during ...

Social Sciences

Human activities increasingly take place in online environments, providing novel opportunities for relating individual behaviors to population-level outcomes. In this paper, we introduce a simple generative model for the collective behavior of millions of ...

Biological Sciences

Anthropology

One of the morphological features that has been identified as uniquely derived for the western Eurasian Neandertals concerns the relative sizes and positions of their semicircular canals. In particular, they exhibit a relatively small anterior canal, a ...

Applied Biological Sciences

Encapsulation of islets of Langerhans may represent a way to transplant islets in the absence of immunosuppression. Traditional methods for encapsulation lead to diffusional limitations imposed by the size of the capsules (600–1,000 μm in diameter), which ...

Biochemistry

The Ras/MAPK signaling cascade regulates various biological functions, including cell growth and proliferation. As such, this pathway is frequently deregulated in several types of cancer, including most cases of melanoma. RSK (p90 ribosomal S6 kinase) is ...
DEAD-box proteins are nonprocessive RNA helicases and can function as RNA chaperones, but the mechanisms of their chaperone activity remain incompletely understood. The Neurospora crassa DEAD-box protein CYT-19 is a mitochondrial RNA chaperone that ...
Replication-dependent histone mRNAs end with a conserved stem loop that is recognized by stem-loop–binding protein (SLBP). The minimal RNA-processing domain of SLBP is phosphorylated at an internal threonine, and Drosophila SLBP (dSLBP) also is ...
WOPR-domain proteins are found throughout the fungal kingdom where they function as master regulators of cell morphology and pathogenesis. Genetic and biochemical experiments previously demonstrated that these proteins bind to specific DNA sequences and ...
View related content:

Profile of Alexander D. Johnson

Methanogenic archaea lack cysteinyl-tRNA synthetase; they synthesize Cys-tRNA and cysteine in a tRNA-dependent manner. Two enzymes are required: Phosphoseryl-tRNA synthetase (SepRS) forms phosphoseryl-tRNACys (Sep-tRNACys), which is converted to Cys-tRNA...
Local levels of active thyroid hormone (3,3′,5-triiodothyronine) are controlled by the action of activating and inactivating iodothyronine deiodinase enzymes. Deiodinases are selenocysteine-dependent membrane proteins catalyzing the reductive elimination ...
Extracellular fatty acid incorporation into the phospholipids of Staphylococcus aureus occurs via fatty acid phosphorylation. We show that fatty acid kinase (Fak) is composed of two dissociable protein subunits encoded by separate genes. FakA provides the ...
The activity of proteins delivered into host cells by the Dot/Icm injection apparatus allows Legionella pneumophila to establish a niche called the Legionella-containing vacuole (LCV), which is permissive for intracellular bacterial propagation. Among ...
γ-Secretase is an intramembrane-cleaving protease responsible for the generation of amyloid-β (Aβ) peptides. Recently, a series of compounds called γ-secretase modulators (GSMs) has been shown to decrease the levels of long toxic Aβ species (i.e., Aβ42), ...

Biophysics and Computational Biology

Myosin is a molecular motor responsible for biological motions such as muscle contraction and intracellular cargo transport, for which it hydrolyzes adenosine 5'-triphosphate (ATP). Early steps of the mechanism by which myosin catalyzes ATP hydrolysis ...
We demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein. As an example, we show the specific binding of the common ...
We present measurements of rate constants for thermal-induced reactions of the 11-cis retinyl chromophore in vertebrate visual pigment rhodopsin, a process that produces noise and limits the sensitivity of vision in dim light. At temperatures of 52.0–64.6 ...
Ligand binding modulates the energy landscape of proteins, thus altering their folding and allosteric conformational dynamics. To investigate such interplay, calmodulin has been a model protein. Despite much attention, fully resolved mechanisms of ...
Guide trees are used to decide the order of sequence alignment in the progressive multiple sequence alignment heuristic. These guide trees are often the limiting factor in making large alignments, and considerable effort has been expended over the years ...
Folding of globular proteins can be envisioned as the contraction of a random coil unfolded state toward the native state on an energy surface rough with local minima trapping frustrated species. These substructures impede productive folding and can serve ...

Cell Biology

The kinesin family members (KIFs) KIF2A and KIF2C depolymerize microtubules, unlike the majority of other kinesins, which transport cargo along microtubules. KIF2A regulates the localization of lysosomes in the cytoplasm, which assists in activation of ...
Metformin, a first-line diabetes drug linked to cancer prevention in retrospective clinical analyses, inhibits cellular transformation and selectively kills breast cancer stem cells (CSCs). Although a few metabolic effects of metformin and the related ...
Mitochondria maintain tight regulation of inner mitochondrial membrane (IMM) permeability to sustain ATP production. Stressful events cause cellular calcium (Ca2+) dysregulation followed by rapid loss of IMM potential known as permeability transition (PT),...
The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 ...
The hematopoietic system declines with age. Myeloid-biased differentiation and increased incidence of myeloid malignancies feature aging of hematopoietic stem cells (HSCs), but the mechanisms involved remain uncertain. Here, we report that 4-mo-old mice ...

Developmental Biology

We present the use of recently developed live imaging methods to examine the dynamic regulation of even-skipped (eve) stripe 2 expression in the precellular Drosophila embryo. Nascent transcripts were visualized via MS2 RNA stem loops. The eve stripe 2 ...

Ecology

Swarming is a conspicuous behavioral trait observed in bird flocks, fish shoals, insect swarms, and mammal herds. It is thought to improve collective awareness and offer protection from predators. Many current models involve the hypothesis that ...
There is considerable controversy over whether pre-Columbian (pre-A.D. 1492) Amazonia was largely “pristine” and sparsely populated by slash-and-burn agriculturists, or instead a densely populated, domesticated landscape, heavily altered by extensive ...
As polio eradication inches closer, the absence of poliovirus circulation in most of the world and imperfect vaccination coverage are resulting in immunity gaps and polio outbreaks affecting adults. Furthermore, imperfect, waning intestinal immunity among ...
Invasive species cost the global economy billions of dollars each year, but ecologists have struggled to predict the risk of an introduced species naturalizing and invading. Although carefully designed experiments are needed to fully elucidate what makes ...

Environmental Sciences

Responses by flowering plants to climate change are complex and only beginning to be understood. Through analyses of 10,295 herbarium specimens of Himalayan Rhododendron collected by plant hunters and botanists since 1884, we were able to separate these ...

Evolution

Time-calibrated species phylogenies are critical for addressing a wide range of questions in evolutionary biology, such as those that elucidate historical biogeography or uncover patterns of coevolution and diversification. Because molecular sequence data ...
Even the most seasoned students of evolution, starting with Darwin himself, have occasionally expressed amazement that the mechanism of natural selection has produced the whole of Life as we see it around us. There is a computational way to articulate the ...
Pelagornithidae is an extinct clade of birds characterized by bizarre tooth-like bony projections of the jaws. Here, the flight capabilities of pelagornithids are explored based on data from a species with the largest reported wingspan among birds. ...
Repeat sequences, especially mobile elements, make up large portions of most eukaryotic genomes and provide enormous, albeit commonly underappreciated, evolutionary potential. We analyzed repeatomes of Drosophila melanogaster that have been diverging in ...
To assess the role of human disturbances in species’ extinction requires an understanding of the species population history before human impact. The passenger pigeon was once the most abundant bird in the world, with a population size estimated at 3–5 ...

Genetics

The type II clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system has emerged recently as a powerful method to manipulate the genomes of various organisms. Here, we report a toolbox for high-efficiency genome ...
Cytosine methylation at CG sites (mCG) plays critical roles in development, epigenetic inheritance, and genome stability in mammals and plants. In the dicot model plant Arabidopsis thaliana, methyltransferase 1 (MET1), a principal CG methylase, functions ...
Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, ...
A majority of mitochondrial DNA (mtDNA) mutations reported to be implicated in diseases are heteroplasmic, a status with coexisting mtDNA variants in a single cell. Quantifying the prevalence of mitochondrial heteroplasmy and its pathogenic effect in ...

Immunology and Inflammation

The adaptive immune system provides critical defense against pathogenic bacteria. Commensal bacteria have begun to receive much attention in recent years, especially in the gut where there is growing evidence of complex interactions with the adaptive ...
Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We now have developed this molecular strategy to render cytotoxic T cells ...
Cross-talk between sterol regulatory pathways and inflammatory pathways has been demonstrated to significantly impact the development of both atherosclerosis and infectious disease. The oxysterol 25-hydroxycholesterol (25HC) plays multiple roles in lipid ...
The costimulatory B7-1 (CD80)/B7-2 (CD86) molecules, along with T-cell receptor stimulation, together facilitate T-cell activation. This explains why in vivo B7 costimulation neutralization efficiently silences a variety of human autoimmune disorders. ...

Medical Sciences

Chemoresistance of cisplatin therapy is related to extensive repair of cisplatin-modified DNA in the nucleus by the nucleotide excision repair (NER). Delivering cisplatin to the mitochondria to attack mitochondrial genome lacking NER machinery can lead to ...
Induced pluripotent stem (iPS) cells hold great promise for regenerative medicine. To overcome potential problems associated with transgene insertions, efforts have been directed over the past several years to generate transgene-free iPS cells by using ...
In mammalian cells, tumor suppressor p53 plays critical roles in the regulation of glucose metabolism, including glycolysis and oxidative phosphorylation, but whether and how p53 also regulates gluconeogenesis is less clear. Here, we report that p53 ...
The X-ray crystal structure of epitope II on the E2 protein of hepatitis C virus, in complex with nonneutralizing antibody mAb#12, has been solved at 2.90-Å resolution. The spatial arrangement of the essential components of epitope II (ie, the C-terminal ...
The host defense response critically depends on the production of leukocytes by the marrow and the controlled delivery of these cells to relevant sites of inflammation/infection. The cytokine granulocyte-colony stimulating factor (G-CSF) is commonly used ...

Microbiology

Quorum sensing (QS) using N-acyl homoserine lactones (AHLs) as signal molecules is a common strategy used by diverse Gram-negative bacteria. A widespread mechanism of AHL sensing involves binding of these molecules by cytosolic LuxR-type transcriptional ...
Since the development of infectious cDNA clones of viral RNA genomes and the means of delivery of the in vitro-synthesized RNA into cells, alphaviruses have become an attractive system for expression of heterologous genetic information. Alphaviruses ...
Long-standing questions in marine viral ecology are centered on understanding how viral assemblages change along gradients in space and time. However, investigating these fundamental ecological questions has been challenging due to incomplete ...

Neuroscience

In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. ...
Celsr3 and Fzd3, members of “core planar cell polarity” (PCP) genes, were shown previously to control forebrain axon guidance and wiring by acting in axons and/or guidepost cells. Here, we show that Celsr2 acts redundantly with Celsr3, and that their ...
Targeted mutation of the Frizzled3 (Fz3) gene in mice has been shown to disrupt the growth and guidance of a subset of peripheral and central axons. Here we used conditional deletion of Fz3 to explore the forebrain territories in which Fz3 action is ...
Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during ...
There is enduring interest in why some of us have clearer memories than others, given the substantial individual variation that exists in retrieval ability and the precision with which we can differentiate past experiences. Here we report novel evidence ...
Postnatal neurogenesis in mammals is confined to restricted brain regions, including the subventricular zone (SVZ). In rodents, the SVZ is a lifelong source of new neurons fated to migrate to the olfactory bulb (OB), where the majority become GABAergic ...
It has been hypothesized that α-synuclein (αS) misfolding may begin in peripheral nerves and spread to the central nervous system (CNS), leading to Parkinson disease and related disorders. Although recent data suggest that αS pathology can spread within ...
Segregating streams of sounds from sources in complex acoustic scenes is crucial for perception in real world situations. We analyzed an objective psychophysical measure of stream segregation obtained while simultaneously recording forebrain neurons in ...

Pharmacology

Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the ...
The nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously ...
ML297 was recently identified as a potent and selective small molecule agonist of G-protein–gated inwardly rectifying K+ (GIRK/Kir3) channels. Here, we show ML297 selectively activates recombinant neuronal GIRK channels containing the GIRK1 subunit in a ...

Physiology

Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics ...

Plant Biology

Plants, as sessile organisms, must coordinate various physiological processes to adapt to ever-changing surrounding environments. Stomata, the epidermal pores facilitating gas and water exchange, play important roles in optimizing photosynthetic ...

Population Biology

Outbreaks of highly pathogenic strains of avian influenza viruses (AIVs) cause considerable economic losses to the poultry industry and also pose a threat to human life. The possibility that one of these strains will evolve to become transmissible between ...

Systems Biology

The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias ...

Corrections

View the cover image for PNAS Vol.111; No.29

Advertisement

Submit to PNAS

Submit to the Proceedings of the National Academy of Sciences (PNAS) and have your research discovered by millions of researchers in the biological, physical, and social sciences.

Submit your manuscript