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Preview: Proceedings of the National Academy of Sciences current issue

Proceedings of the National Academy of Sciences current issue



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In This Issue [This Week in PNAS]

2017-02-21T12:11:34-08:00

Brain circuit for body temperature control Neural pathway for body temperature control. Image courtesy of Wei Shen and Blue-Rider Art Studio (ShanghaiTech University, Shanghai, China). Animals maintain optimal core body temperatures under changing ambient conditions by adjusting energy expenditure, heat generation, and physical activity. Studies have implicated temperature-sensitive neurons in...



Are human heads getting larger? [Biological Sciences]

2017-02-21T12:11:35-08:00

I am responding to the intriguing PNAS article by Mitteroecker et al. (1), “Cliff-edge model of obstetric selection in humans.” My understanding is that the authors believe that Caesarean section births will allow fetuses with larger heads to survive, thus allowing our species to evolve larger heads. This is an...



Reply to Grossman: The role of natural selection for the increase of Caesarean section rates [Biological Sciences]

2017-02-21T12:11:35-08:00

Recently, we presented the “cliff-edge model” (1) to explain why natural selection has not reduced the high rates of fetopelvic disproportion (FPD) in childbirth. This evolutionary model predicts that birth-relevant anatomical dimensions have changed in response to the regular use of Caesarean sections (C-sections). Grossman’s (2) interesting comment on our...



Ahmed Zewail: A force for Egyptian science [Retrospectives]

2017-02-21T12:11:34-08:00

Undoubtedly, Dr. Ahmed Zewail, who passed away on August 2, 2016, had a strong, positive impact on science in the Middle East and in the West. I knew Zewail as one of his mentors and close friends. Zewail wanted to come from Egypt (Alexandria University) to get his PhD in...



Profile of David Heeger [Profile]

2017-02-21T12:11:34-08:00

“Interdisciplinary” has become a buzzword in science in recent years. According to David Heeger, a professor of psychology and neural science at New York University (NYU), “You don’t do interdisciplinary science by putting a physicist and a biologist in the same office. Nor do you make interdisciplinary science happen by...



Profile of Lily and Yuh Nung Jan, winners of the 2017 Vilcek Prize in Biomedical Science [Profile]

2017-02-21T12:11:34-08:00

The 2017 Vilcek Prize in Biomedical Science has been awarded to Lily Y. Jan and Yuh Nung Jan, professors in the department of physiology at the University of California, San Francisco (UCSF), and Howard Hughes Medical Institute Investigators. The Jans are being recognized for demonstrating how ion channels contribute to...



Losing pieces without disintegrating: Contractile protein loss during muscle atrophy [Cell Biology]

2017-02-21T12:11:34-08:00

Skeletal muscle is a plastic tissue that can increase in size (hypertrophy) in response to exercise or decrease in size (atrophy) with inactivity (1). Muscle atrophy occurs systemically in physiological conditions, such as fasting or aging, and in a variety of pathological conditions, including cancer cachexia, cardiac failure, renal failure,...



Myosin-driven transport network in plants is functionally robust and distinctive [Cell Biology]

2017-02-21T12:11:34-08:00

Transport of Myosin Cargoes in Animal and Yeast Cells Directional transport of intracellular cargoes by cytoskeleton-based motors is one of the signature features of eukaryotic cells. It was proposed that the last common ancestor of eukaryotes possessed several prototype motor proteins, including evolutionarily related kinesins and myosins (1, 2). Among...



Getting to the bottom of global fishery catches [Ecology]

2017-02-21T12:11:34-08:00

When one tugs at a single thing in nature, he finds it attached to the rest of the world. John Muir, The Yosemite Ecosystems are complex, interconnected systems fueled by primary production, from vegetation on land and phytoplankton in the sea. In the oceans, this energy moves from prey to...



Targeting tail-anchored proteins into plant organelles [Plant Biology]

2017-02-21T12:11:34-08:00

The extensive evolution of intracellular compartmentalization requires highly selective mechanisms for protein targeting to distinct membrane systems. One of the fundamental processes in protein targeting is the insertion of proteins into biological membranes. The efficient and accurate insertion of membrane proteins is an important step for their proper function in...



Deconstructing mammalian thermoregulation [Neuroscience]

2017-02-21T12:11:34-08:00

Several recent ground-breaking papers address the deconstruction of neural circuits that regulate mammalian thermoregulation (1–3), including “A hypothalamic circuit that controls body temperature,” by Zhao et al. (3) from Wei Shen’s new laboratory at ShanghaiTech University, recently published in PNAS. In this study, Zhao et al. define neural circuit mechanisms...



Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis [Applied Biological Sciences]

2017-02-21T12:11:35-08:00

Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability....



Estrogen receptor {alpha} wields treatment-specific enhancers between morphologically similar endometrial tumors [Applied Biological Sciences]

2017-02-21T12:11:35-08:00

The DNA-binding sites of estrogen receptor α (ERα) show great plasticity under the control of hormones and endocrine therapy. Tamoxifen is a widely applied therapy in breast cancer that affects ERα interactions with coregulators and shifts the DNA-binding signature of ERα upon prolonged exposure in breast cancer. Although tamoxifen inhibits...



Kinetics, subcellular localization, and contribution to parasite virulence of a Trypanosoma cruzi hybrid type A heme peroxidase (TcAPx-CcP) [Biochemistry]

2017-02-21T12:11:35-08:00

The Trypanosoma cruzi ascorbate peroxidase is, by sequence analysis, a hybrid type A member of class I heme peroxidases [TcAPx-cytochrome c peroxidase (CcP)], suggesting both ascorbate (Asc) and cytochrome c (Cc) peroxidase activity. Here, we show that the enzyme reacts fast with H2O2 (k = 2.9 × 107 M−1⋅s−1) and...



Reaction dynamics analysis of a reconstituted Escherichia coli protein translation system by computational modeling [Biophysics and Computational Biology]

2017-02-21T12:11:35-08:00

To elucidate the dynamic features of a biologically relevant large-scale reaction network, we constructed a computational model of minimal protein synthesis consisting of 241 components and 968 reactions that synthesize the Met-Gly-Gly (MGG) peptide based on an Escherichia coli-based reconstituted in vitro protein synthesis system. We performed a simulation using...



Cdon deficiency causes cardiac remodeling through hyperactivation of WNT/{beta}-catenin signaling [Cell Biology]

2017-02-21T12:11:35-08:00

On pathological stress, Wnt signaling is reactivated and induces genes associated with cardiac remodeling and fibrosis. We have previously shown that a cell surface receptor Cdon (cell-adhesion associated, oncogene regulated) suppresses Wnt signaling to promote neuronal differentiation however its role in heart is unknown. Here, we demonstrate a critical role...



Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments [Cell Biology]

2017-02-21T12:11:35-08:00

Cardiac myosin binding protein C (cMyBP-C) has a key regulatory role in cardiac contraction, but the mechanism by which changes in phosphorylation of cMyBP-C accelerate cross-bridge kinetics remains unknown. In this study, we isolated thick filaments from the hearts of mice in which the three serine residues (Ser273, Ser282, and...



Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry [Cell Biology]

2017-02-21T12:11:35-08:00

S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing...



Myofibril breakdown during atrophy is a delayed response requiring the transcription factor PAX4 and desmin depolymerization [Cell Biology]

2017-02-21T12:11:35-08:00

A hallmark of muscle atrophy is the excessive degradation of myofibrillar proteins primarily by the ubiquitin proteasome system. In mice, during the rapid muscle atrophy induced by fasting, the desmin cytoskeleton and the attached Z-band–bound thin filaments are degraded after ubiquitination by the ubiquitin ligase tripartite motif-containing protein 32 (Trim32)....



Myosin-driven transport network in plants [Cell Biology]

2017-02-21T12:11:35-08:00

We investigate the myosin XI-driven transport network in Arabidopsis using protein–protein interaction, subcellular localization, gene knockout, and bioinformatics analyses. The two major groups of nodes in this network are myosins XI and their membrane-anchored receptors (MyoB) that, together, drive endomembrane trafficking and cytoplasmic streaming in the plant cells. The network...



Targeting IRE1 with small molecules counteracts progression of atherosclerosis [Cell Biology]

2017-02-21T12:11:35-08:00

Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory...



An amidase is required for proper intercellular communication in the filamentous cyanobacterium Anabaena sp. PCC 7120 [Cell Biology]

2017-02-21T12:11:35-08:00

Channels that cross cell walls and connect the cytoplasm of neighboring cells in multicellular cyanobacteria are pivotal for intercellular communication. We find that the product of the gene all1140 of the filamentous cyanobacterium Anabaena sp. PCC 7120 is required for proper channel formation. All1140 encodes an amidase that hydrolyses purified...



RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo [Cell Biology]

2017-02-21T12:11:35-08:00

Fibroblasts are a main player in the tumor-inhibitory microenvironment. Upon tumor initiation and progression, fibroblasts can lose their tumor-inhibitory capacity and promote tumor growth. The molecular mechanisms that underlie this switch have not been defined completely. Previously, we identified four proteins overexpressed in cancer-associated fibroblasts and linked to Rho GTPase...



Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation [Developmental Biology]

2017-02-21T12:11:35-08:00

GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline...



Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia [Developmental Biology]

2017-02-21T12:11:35-08:00

Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the...



Reconciling fisheries catch and ocean productivity [Ecology]

2017-02-21T12:11:35-08:00

Photosynthesis fuels marine food webs, yet differences in fish catch across globally distributed marine ecosystems far exceed differences in net primary production (NPP). We consider the hypothesis that ecosystem-level variations in pelagic and benthic energy flows from phytoplankton to fish, trophic transfer efficiencies, and fishing effort can quantitatively reconcile this...



Selection maintains signaling function of a highly diverged intrinsically disordered region [Evolution]

2017-02-21T12:11:35-08:00

Intrinsically disordered regions (IDRs) are characterized by their lack of stable secondary or tertiary structure and comprise a large part of the eukaryotic proteome. Although these regions play a variety of signaling and regulatory roles, they appear to be rapidly evolving at the primary sequence level. To understand the functional...



Dynamics of genome size evolution in birds and mammals [Evolution]

2017-02-21T12:11:35-08:00

Genome size in mammals and birds shows remarkably little interspecific variation compared with other taxa. However, genome sequencing has revealed that many mammal and bird lineages have experienced differential rates of transposable element (TE) accumulation, which would be predicted to cause substantial variation in genome size between species. Thus, we...



Low escape-rate genome safeguards with minimal molecular perturbation of Saccharomyces cerevisiae [Genetics]

2017-02-21T12:11:35-08:00

As the use of synthetic biology both in industry and in academia grows, there is an increasing need to ensure biocontainment. There is growing interest in engineering bacterial- and yeast-based safeguard (SG) strains. First-generation SGs were based on metabolic auxotrophy; however, the risk of cross-feeding and the cost of growth-controlling...



TGF-{beta} inhibitor Smad7 regulates dendritic cell-induced autoimmunity [Immunology and Inflammation]

2017-02-21T12:11:35-08:00

TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the...



Dnmt3a restrains mast cell inflammatory responses [Immunology and Inflammation]

2017-02-21T12:11:35-08:00

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation...



SGK3 sustains ER{alpha} signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis [Medical Sciences]

2017-02-21T12:11:35-08:00

Many estrogen receptor alpha (ERα)-positive breast cancers initially respond to aromatase inhibitors (AIs), but eventually acquire resistance. Here, we report that serum- and glucocorticoid-inducible kinase 3 (SGK3), a kinase transcriptionally regulated by ERα in breast cancer, sustains ERα signaling and drives acquired AI resistance. SGK3 is up-regulated and essential for...



Gene activation of SMN by selective disruption of lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy [Medical Sciences]

2017-02-21T12:11:35-08:00

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by progressive motor neuron loss and caused by mutations in SMN1 (Survival Motor Neuron 1). The disease severity inversely correlates with the copy number of SMN2, a duplicated gene that is nearly identical to SMN1. We have delineated a mechanism of...



Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract [Microbiology]

2017-02-21T12:11:35-08:00

Bacterial pathogens coordinate virulence using two-component regulatory systems (TCS). The Bordetella virulence gene (BvgAS) phosphorelay-type TCS controls expression of all known protein virulence factor-encoding genes and is considered the “master virulence regulator” in Bordetella pertussis, the causal agent of pertussis, and related organisms, including the broad host range pathogen Bordetella...



ACSS2-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection [Microbiology]

2017-02-21T12:11:35-08:00

Recent studies have shown that human cytomegalovirus (HCMV) can induce a robust increase in lipid synthesis which is critical for the success of infection. In mammalian cells the central precursor for lipid biosynthesis, cytosolic acetyl CoA (Ac-CoA), is produced by ATP-citrate lyase (ACLY) from mitochondria-derived citrate or by acetyl-CoA synthetase...



Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis [Plant Biology]

2017-02-21T12:11:35-08:00

Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. However, the proteins and sites subject to this posttranslational modification are largely unknown. Here, we report a large-scale proteomic identification of O-GlcNAc–modified proteins and sites in the model plant Arabidopsis thaliana. Using lectin weak affinity chromatography to...



Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance [Plant Biology]

2017-02-21T12:11:35-08:00

Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the...



PPR-SMR protein SOT1 has RNA endonuclease activity [Plant Biology]

2017-02-21T12:11:35-08:00

Numerous attempts have been made to identify and engineer sequence-specific RNA endonucleases, as these would allow for efficient RNA manipulation. However, no natural RNA endonuclease that recognizes RNA in a sequence-specific manner has been described to date. Here, we report that SUPPRESSOR OF THYLAKOID FORMATION 1 (SOT1), an Arabidopsis pentatricopeptide...



Human and rat gut microbiome composition is maintained following sleep restriction [Psychological and Cognitive Sciences]

2017-02-21T12:11:35-08:00

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized...



Female sociality and sexual conflict shape offspring survival in a Neotropical primate [Anthropology]

2017-02-21T12:11:35-08:00

Most mammals live in social groups in which members form differentiated social relationships. Individuals may vary in their degree of sociality, and this variation can be associated with differential fitness. In some species, for example, female sociality has a positive effect on infant survival. However, investigations of such cases are...



Modular assembly of thick multifunctional cardiac patches [Applied Biological Sciences]

2017-02-21T12:11:35-08:00

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac...



Pure circular polarization electroluminescence at room temperature with spin-polarized light-emitting diodes [Applied Physical Sciences]

2017-02-21T12:11:35-08:00

We report the room-temperature electroluminescence (EL) with nearly pure circular polarization (CP) from GaAs-based spin-polarized light-emitting diodes (spin-LEDs). External magnetic fields are not used during device operation. There are two small schemes in the tested spin-LEDs: first, the stripe-laser-like structure that helps intensify the EL light at the cleaved side...



H3K4me3 induces allosteric conformational changes in the DNA-binding and catalytic regions of the V(D)J recombinase [Biochemistry]

2017-02-21T12:11:35-08:00

V(D)J recombination is initiated by the recombination-activating gene (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain...



Biosynthesis of cabbage phytoalexins from indole glucosinolate [Biochemistry]

2017-02-21T12:11:35-08:00

Brassica crop species are prolific producers of indole–sulfur phytoalexins that are thought to have an important role in plant disease resistance. These molecules are conspicuously absent in the model plant Arabidopsis thaliana, and little is known about the enzymatic steps that assemble the key precursor brassinin. Here, we report the...



Functional importance of stripping in NF{kappa}B signaling revealed by a stripping-impaired I{kappa}B{alpha} mutant [Biophysics and Computational Biology]

2017-02-21T12:11:35-08:00

Stress-response transcription factors such as NFκB turn on hundreds of genes and must have a mechanism for rapid cessation of transcriptional activation. We recently showed that the inhibitor of NFκB signaling, IκBα, dramatically accelerates the dissociation of NFκB from transcription sites, a process we have called “stripping.” To test the...



Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection [Biophysics and Computational Biology]

2017-02-21T12:11:35-08:00

With the introduction of direct-acting antivirals (DAAs), treatment against hepatitis C virus (HCV) has significantly improved. To manage and control this worldwide infectious disease better, the “best” multidrug treatment is demanded based on scientific evidence. However, there is no method available that systematically quantifies and compares the antiviral efficacy and...



Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T [Cell Biology]

2017-02-21T12:11:35-08:00

Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we...



Full atomistic reaction mechanism with kinetics for CO reduction on Cu(100) from ab initio molecular dynamics free-energy calculations at 298 K [Chemistry]

2017-02-21T12:11:35-08:00

A critical step toward the rational design of new catalysts that achieve selective and efficient reduction of CO2 to specific hydrocarbons and oxygenates is to determine the detailed reaction mechanism including kinetics and product selectivity as a function of pH and applied potential for known systems. To accomplish this, we...



Probing equilibrium of molecular and deprotonated water on TiO2(110) [Chemistry]

2017-02-21T12:11:35-08:00

Understanding adsorbed water and its dissociation to surface hydroxyls on oxide surfaces is key to unraveling many physical and chemical processes, yet the barrier for its deprotonation has never been measured. In this study, we present direct evidence for water dissociation equilibrium on rutile-TiO2(110) by combining supersonic molecular beam, scanning...



Hippo signaling promotes JNK-dependent cell migration [Developmental Biology]

2017-02-21T12:11:35-08:00

Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion...



Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia [Developmental Biology]

2017-02-21T12:11:35-08:00

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas...



Redox chemistry changes in the Panthalassic Ocean linked to the end-Permian mass extinction and delayed Early Triassic biotic recovery [Earth, Atmospheric, and Planetary Sciences]

2017-02-21T12:11:35-08:00

The end-Permian mass extinction represents the most severe biotic crisis for the last 540 million years, and the marine ecosystem recovery from this extinction was protracted, spanning the entirety of the Early Triassic and possibly longer. Numerous studies from the low-latitude Paleotethys and high-latitude Boreal oceans have examined the possible...



Timing and tempo of the Great Oxidation Event [Earth, Atmospheric, and Planetary Sciences]

2017-02-21T12:11:35-08:00

The first significant buildup in atmospheric oxygen, the Great Oxidation Event (GOE), began in the early Paleoproterozoic in association with global glaciations and continued until the end of the Lomagundi carbon isotope excursion ca. 2,060 Ma. The exact timing of and relationships among these events are debated because of poor...



Northward extent of East Asian monsoon covaries with intensity on orbital and millennial timescales [Earth, Atmospheric, and Planetary Sciences]

2017-02-21T12:11:35-08:00

The magnitude, rate, and extent of past and future East Asian monsoon (EAM) rainfall fluctuations remain unresolved. Here, late Pleistocene–Holocene EAM rainfall intensity is reconstructed using a well-dated northeastern China closed-basin lake area record located at the modern northwestern fringe of the EAM. The EAM intensity and northern extent alternated...



Role of eruption season in reconciling model and proxy responses to tropical volcanism [Earth, Atmospheric, and Planetary Sciences]

2017-02-21T12:11:35-08:00

The response of the El Niño/Southern Oscillation (ENSO) to tropical volcanic eruptions has important worldwide implications, but remains poorly constrained. Paleoclimate records suggest an “El Niño-like” warming 1 year following major eruptions [Adams JB, Mann ME, Ammann CM (2003) Nature 426:274–278] and “La Niña-like” cooling within the eruption year [Li...



K isotopes as a tracer of seafloor hydrothermal alteration [Earth, Atmospheric, and Planetary Sciences]

2017-02-21T12:11:35-08:00

At ocean spreading ridges, circulation of seawater through rock at elevated temperatures alters the chemical and isotopic composition of oceanic crust. Samples obtained from drilling into ocean floor and from ophiolites have demonstrated that certain isotope systems, such as 18O/16O and 87Sr/86Sr, are systematically modified in hydrothermally altered oceanic crust....



Ghrelin affects stopover decisions and food intake in a long-distance migrant [Ecology]

2017-02-21T12:11:35-08:00

Billions of birds migrate long distances to either reach breeding areas or to spend the winter at more benign places. On migration, most passerines frequently stop over to rest and replenish their fuel reserves. To date, we know little regarding how they decide that they are ready to continue their...



Architected cellular ceramics with tailored stiffness via direct foam writing [Engineering]

2017-02-21T12:11:35-08:00

Hierarchical cellular structures are ubiquitous in nature because of their low-density, high-specific properties, and multifunctionality. Inspired by these systems, we created lightweight ceramic architectures composed of closed-cell porous struts patterned in the form of hexagonal and triangular honeycombs by direct foam writing. The foam ink contains bubbles stabilized by attractive...



Role of vascular normalization in benefit from metronomic chemotherapy [Engineering]

2017-02-21T12:11:35-08:00

Metronomic dosing of chemotherapy—defined as frequent administration at lower doses—has been shown to be more efficacious than maximum tolerated dose treatment in preclinical studies, and is currently being tested in the clinic. Although multiple mechanisms of benefit from metronomic chemotherapy have been proposed, how these mechanisms are related to one...



Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics [Engineering]

2017-02-21T12:11:35-08:00

Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do...



Interaction between top-down and bottom-up control in marine food webs [Environmental Sciences]

2017-02-21T12:11:35-08:00

Climate change and resource exploitation have been shown to modify the importance of bottom-up and top-down forces in ecosystems. However, the resulting pattern of trophic control in complex food webs is an emergent property of the system and thus unintuitive. We develop a statistical nondeterministic model, capable of modeling complex...



Cross-cultural regularities in the cognitive architecture of pride [Evolution]

2017-02-21T12:11:35-08:00

Pride occurs in every known culture, appears early in development, is reliably triggered by achievements and formidability, and causes a characteristic display that is recognized everywhere. Here, we evaluate the theory that pride evolved to guide decisions relevant to pursuing actions that enhance valuation and respect for a person in...



Hearing regulates Drosophila aggression [Genetics]

2017-02-21T12:11:35-08:00

Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an...



iPSCs and fibroblast subclones from the same fibroblast population contain comparable levels of sequence variations [Genetics]

2017-02-21T12:11:35-08:00

Genome integrity of induced pluripotent stem cells (iPSCs) has been extensively studied in recent years, but it is still unclear whether iPSCs contain more genomic variations than cultured somatic cells. One important question is the origin of genomic variations detected in iPSCs–whether iPSC reprogramming induces such variations. Here, we undertook...



Failure to reproduce period-dependent song cycles in Drosophila is due to poor automated pulse-detection and low-intensity courtship [Genetics]

2017-02-21T12:11:35-08:00

Stern has criticized a body of work from several groups that have independently studied the so-called “Kyriacou and Hall” courtship song rhythms of male Drosophila melanogaster, claiming that these ultradian ∼60-s cycles in the interpulse interval (IPI) are statistical artifacts that are not modulated by mutations at the period (per)...



Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection [Immunology and Inflammation]

2017-02-21T12:11:35-08:00

A significant challenge to HIV eradication is the elimination of viral reservoirs in germinal center (GC) T follicular helper (Tfh) cells. However, GCs are considered to be immune privileged for antiviral CD8 T cells. Here, we show a population of simian immunodeficiency virus (SIV)-specific CD8 T cells express CXCR5 (C-X-C...



Conformational disruption of PI3K{delta} regulation by immunodeficiency mutations in PIK3CD and PIK3R1 [Immunology and Inflammation]

2017-02-21T12:11:35-08:00

Activated PI3K Delta Syndrome (APDS) is a primary immunodeficiency disease caused by activating mutations in either the leukocyte-restricted p110δ catalytic (PIK3CD) subunit or the ubiquitously expressed p85α regulatory (PIK3R1) subunit of class IA phosphoinositide 3-kinases (PI3Ks). There are two classes of APDS: APDS1 that arises from p110δ mutations that are...



A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes [Immunology and Inflammation]

2017-02-21T12:11:35-08:00

Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5+CD81+ pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34+ progenitors. These CD2hiCD5+CD81+ cells express classical...



High-resolution imaging and quantification of plasma membrane cholesterol by NanoSIMS [Medical Sciences]

2017-02-21T12:11:35-08:00

Cholesterol is a crucial lipid within the plasma membrane of mammalian cells. Recent biochemical studies showed that one pool of cholesterol in the plasma membrane is “accessible” to binding by a modified version of the cytolysin perfringolysin O (PFO*), whereas another pool is sequestered by sphingomyelin and cannot be bound...



Synergistic antileukemic therapies in NOTCH1-induced T-ALL [Medical Sciences]

2017-02-21T12:11:35-08:00

The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with...



Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation [Medical Sciences]

2017-02-21T12:11:35-08:00

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS that causes disability in young adults as a result of the irreversible accumulation of neurological deficits. Although there are potent disease-modifying agents for its initial relapsing-remitting phase, these therapies show limited efficacy in secondary progressive MS (SPMS). Thus,...



Systematic identification of anti-interferon function on hepatitis C virus genome reveals p7 as an immune evasion protein [Microbiology]

2017-02-21T12:11:35-08:00

Hepatitis C virus (HCV) encodes mechanisms to evade the multilayered antiviral actions of the host immune system. Great progress has been made in elucidating the strategies HCV employs to down-regulate interferon (IFN) production, impede IFN signaling transduction, and impair IFN-stimulated gene (ISG) expression. However, there is a limited understanding of...



AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses [Microbiology]

2017-02-21T12:11:35-08:00

Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus...



High-resolution imaging of cellular dopamine efflux using a fluorescent nanosensor array [Neuroscience]

2017-02-21T12:11:35-08:00

Intercellular communication via chemical signaling proceeds with both spatial and temporal components, but analytical tools, such as microfabricated electrodes, have been limited to just a few probes per cell. In this work, we use a nonphotobleaching fluorescent nanosensor array based on single-walled carbon nanotubes (SWCNTs) rendered selective to dopamine to...



Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via {alpha}-actinin and focal adhesion kinase [Neuroscience]

2017-02-21T12:11:35-08:00

Inositol hexakisphosphate kinase 1 (IP6K1), which generates 5-diphosphoinositol pentakisphosphate (5-IP7), physiologically mediates numerous functions. We report that IP6K1 deletion leads to brain malformation and abnormalities of neuronal migration. IP6K1 physiologically associates with α-actinin and localizes to focal adhesions. IP6K1 deletion disrupts α-actinin’s intracellular localization and function. The IP6K1 deleted cells...



A hypothalamic circuit that controls body temperature [Neuroscience]

2017-02-21T12:11:35-08:00

The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify...



Reelin transiently promotes N-cadherin-dependent neuronal adhesion during mouse cortical development [Neuroscience]

2017-02-21T12:11:35-08:00

Reelin is an essential glycoprotein for the establishment of the highly organized six-layered structure of neurons of the mammalian neocortex. Although the role of Reelin in the control of neuronal migration has been extensively studied at the molecular level, the mechanisms underlying Reelin-dependent neuronal layer organization are not yet fully...



Spectrin {beta}V adaptive mutations and changes in subcellular location correlate with emergence of hair cell electromotility in mammalians [Neuroscience]

2017-02-21T12:11:35-08:00

The remarkable hearing capacities of mammals arise from various evolutionary innovations. These include the cochlear outer hair cells and their singular feature, somatic electromotility, i.e., the ability of their cylindrical cell body to shorten and elongate upon cell depolarization and hyperpolarization, respectively. To shed light on the processes underlying the...



Crystal structure of the adenosine A2A receptor bound to an antagonist reveals a potential allosteric pocket [Pharmacology]

2017-02-21T12:11:35-08:00

The adenosine A2A receptor (A2AR) has long been implicated in cardiovascular disorders. As more selective A2AR ligands are being identified, its roles in other disorders, such as Parkinson’s disease, are starting to emerge, and A2AR antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure...



A statics-dynamics equivalence through the fluctuation-dissipation ratio provides a window into the spin-glass phase from nonequilibrium measurements [Physics]

2017-02-21T12:11:35-08:00

We have performed a very accurate computation of the nonequilibrium fluctuation–dissipation ratio for the 3D Edwards–Anderson Ising spin glass, by means of large-scale simulations on the special-purpose computers Janus and Janus II. This ratio (computed for finite times on very large, effectively infinite, systems) is compared with the equilibrium probability...



Quantum chaos on a critical Fermi surface [Physics]

2017-02-21T12:11:35-08:00

We compute parameters characterizing many-body quantum chaos for a critical Fermi surface without quasiparticle excitations. We examine a theory of N species of fermions at nonzero density coupled to a U(1) gauge field in two spatial dimensions and determine the Lyapunov rate and the butterfly velocity in an extended random-phase...



Long-wavelength fluctuations and the glass transition in two dimensions and three dimensions [Physics]

2017-02-21T12:11:35-08:00

Phase transitions significantly differ between 2D and 3D systems, but the influence of dimensionality on the glass transition is unresolved. We use microscopy to study colloidal systems as they approach their glass transitions at high concentrations and find differences between two dimensions and three dimensions. We find that, in two...



Mermin-Wagner fluctuations in 2D amorphous solids [Physics]

2017-02-21T12:11:35-08:00

In a recent commentary, J. M. Kosterlitz described how D. Thouless and he got motivated to investigate melting and suprafluidity in two dimensions [Kosterlitz JM (2016) J Phys Condens Matter 28:481001]. It was due to the lack of broken translational symmetry in two dimensions—doubting the existence of 2D crystals—and the...



MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases [Physiology]

2017-02-21T12:11:35-08:00

Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic factors in the regulation of vascular physiology. This study aimed to elucidate the relationship between HDACs and miRs in the hemodynamic modulation of endothelial cell (EC) dysfunction. We found that miR-10a has the lowest expression among all examined...



Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells in Arabidopsis thaliana [Plant Biology]

2017-02-21T12:11:35-08:00

The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana. DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the...



HY5, a positive regulator of light signaling, negatively controls the unfolded protein response in Arabidopsis [Plant Biology]

2017-02-21T12:11:35-08:00

Light influences essentially all aspects of plant growth and development. Integration of light signaling with different stress response results in improvement of plant survival rates in ever changing environmental conditions. Diverse environmental stresses affect the protein-folding capacity of the endoplasmic reticulum (ER), thus evoking ER stress in plants. Consequently, the...



Opinion: Gender diversity leads to better science [Psychological and Cognitive Sciences]

2017-02-21T12:11:34-08:00

Pick up any recent policy paper on women’s participation in science and you will find assurances that gender diversity enhances knowledge outcomes. Universities and science-policy stakeholders, including the European Commission and the US National Institutes of Health, readily subscribe to this argument (1–3). But is there, in fact, a gender-diversity...



Theory of cortical function [Psychological and Cognitive Sciences]

2017-02-21T12:11:34-08:00

Most models of sensory processing in the brain have a feedforward architecture in which each stage comprises simple linear filtering operations and nonlinearities. Models of this form have been used to explain a wide range of neurophysiological and psychophysical data, and many recent successes in artificial intelligence (with deep convolutional...



Distributed representation of context by intrinsic subnetworks in prefrontal cortex [Psychological and Cognitive Sciences]

2017-02-21T12:11:35-08:00

Human prefrontal cortex supports goal-directed behavior by representing abstract information about task context. The organizational basis of these context representations, and of representations underlying other higher-order processes, is unknown. Here, we use multivariate decoding and analyses of spontaneous correlations to show that context representations are distributed across subnetworks within prefrontal...



Spatially resolved air-water emissions tradeoffs improve regulatory impact analyses for electricity generation [Sustainability Science]

2017-02-21T12:11:35-08:00

Coal-fired power plants (CFPPs) generate air, water, and solids emissions that impose substantial human health, environmental, and climate change (HEC) damages. This work demonstrates the importance of accounting for cross-media emissions tradeoffs, plant and regional emissions factors, and spatially variation in the marginal damages of air emissions when performing regulatory...



Global socioeconomic material stocks rise 23-fold over the 20th century and require half of annual resource use [Sustainability Science]

2017-02-21T12:11:35-08:00

Human-made material stocks accumulating in buildings, infrastructure, and machinery play a crucial but underappreciated role in shaping the use of material and energy resources. Building, maintaining, and in particular operating in-use stocks of materials require raw materials and energy. Material stocks create long-term path-dependencies because of their longevity. Fostering a...



Impact of pre-Columbian “geoglyph” builders on Amazonian forests [Sustainability Science]

2017-02-21T12:11:35-08:00

Over 450 pre-Columbian (pre-AD 1492) geometric ditched enclosures (“geoglyphs”) occupy ∼13,000 km2 of Acre state, Brazil, representing a key discovery of Amazonian archaeology. These huge earthworks were concealed for centuries under terra firme (upland interfluvial) rainforest, directly challenging the “pristine” status of this ecosystem and its perceived vulnerability to human...



Climate change is projected to have severe impacts on the frequency and intensity of peak electricity demand across the United States [Sustainability Science]

2017-02-21T12:11:35-08:00

It has been suggested that climate change impacts on the electric sector will account for the majority of global economic damages by the end of the current century and beyond [Rose S, et al. (2014) Understanding the Social Cost of Carbon: A Technical Assessment]. The empirical literature has shown significant...



Correction for Slovic et al., Iconic photographs and the ebb and flow of empathic response to humanitarian disasters [Correction]

2017-02-21T12:11:35-08:00

PSYCHOLOGICAL AND COGNITIVE SCIENCES Correction for “Iconic photographs and the ebb and flow of empathic response to humanitarian disasters,” by Paul Slovic, Daniel Västfjäll, Arvid Erlandsson, and Robin Gregory, which appeared in issue 4, January 24, 2017, of Proc Natl Acad Sci USA (114:640–644; first published January 10, 2017; 10.1073/pnas.1613977114)....



Correction for Holm et al., Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase [Correction]

2017-02-21T12:11:35-08:00

BIOCHEMISTRY Correction for “Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase,” by Rikke Holm, Jaanki Khandelwal, Anja P. Einholm, Jens P. Andersen, Pablo Artigas, and Bente Vilsen, which appeared in issue 2, January 10, 2017, of Proc Natl Acad Sci...



Correction to Supporting Information for Andreu-Fernandez et al., Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes [SI Correction]

2017-02-21T12:11:35-08:00

BIOCHEMISTRY Correction to Supporting Information for “Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes,” by Vicente Andreu-Fernández, Mónica Sancho, Ainhoa Genovés, Estefanía Lucendo, Franziska Todt, Joachim Lauterwasser, Kathrin Funk, Günther Jahreis, Enrique Pérez-Payá, Ismael Mingarro, Frank Edlich, and Mar Orzáez, which appeared in issue 2, January 10,...