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Preview: Proceedings of the National Academy of Sciences recent issues

Proceedings of the National Academy of Sciences recent issues



Proceedings of the National Academy of Sciences RSS feed -- recent issues



 



In This Issue [This Week in PNAS]

2017-04-25T09:21:09-07:00

El Niño and cholera in Africa Cholera incidence rates between El Niño and non-El Niño years throughout Africa. Cholera outbreaks have long been linked to climatic factors, particularly the El Niño Southern Oscillation, but little evidence supports such a link in Africa. Using datasets comprising more than 17,000 annual observations...



Controversy in statistical analysis of functional magnetic resonance imaging data [Biological Sciences]

2017-04-25T09:21:10-07:00

To test the validity of statistical methods for fMRI data analysis, Eklund et al. (1) used, for the first time, large-scale experimental data rather than simulated data. Using resting-state fMRI measurements to represent a null hypothesis of no task-induced activation, the authors compare familywise error rates for voxel-based and cluster-based...



fMRI clustering and false-positive rates [Biological Sciences]

2017-04-25T09:21:10-07:00

Recently, Eklund et al. (1) analyzed clustering methods in standard fMRI packages: AFNI (which we maintain), FSL, and SPM. They claim that (i) false-positive rates (FPRs) in traditional approaches are greatly inflated, questioning the validity of “countless published fMRI studies”; (ii) nonparametric methods produce valid, but slightly conservative, FPRs; (iii)...



Reevaluating “cluster failure” in fMRI using nonparametric control of the false discovery rate [Biological Sciences]

2017-04-25T09:21:10-07:00

In a substantial contribution to the fMRI field, Eklund et al. (1) use nonparametric methods to demonstrate that random field theory (RFT)-based familywise error (FWE) correction for cluster inference does not control errors appropriately, and this discrepancy is more pronounced for lenient cluster-defining thresholds (CDT). Moreover, they point to violations...



Reply to Brown and Behrmann, Cox, et al., and Kessler et al.: Data and code sharing is the way forward for fMRI [Biological Sciences]

2017-04-25T09:21:10-07:00

We are glad that our paper (1) has generated intense discussions in the fMRI field (2–4), on how to analyze fMRI data, and how to correct for multiple comparisons. The goal of the paper was not to disparage any specific fMRI software, but to point out that parametric statistical methods...



Ralph J. Cicerone: His scientific legacy and a long friendship [Retrospectives]

2017-04-25T09:21:09-07:00

The discovery of the Antarctic ozone hole and anthropogenic climate change has thrust the atmospheric sciences into the forefront of scientific disciplines, and such findings routinely appear on the front pages of the media and on the desks of world leaders. Two events can be cited as examples of the...



Are there many different routes to becoming a global biodiversity hotspot? [Evolution]

2017-04-25T09:21:09-07:00

A major question in evolution and ecology is why biodiversity is so unevenly distributed across the planet. The most obvious and salient diversity pattern is the order-of-magnitude greater species richness in the tropics compared with the temperate zones. Superimposed on this latitudinal diversity gradient is a much more complex and...



Bringing disorder and dynamics in protein allostery into focus [Biophysics and Computational Biology]

2017-04-25T09:21:09-07:00

The intricacies of protein-mediated signaling continue to be revealed in exquisite detail. It therefore seems fitting to return to the fundamental and almost magical feature of protein molecules that makes it all possible: allostery, or action at a distance. This long-held concept arose and was refined during the explosive expansion...



Shining a light on the dark world of plant root-microbe interactions [Plant Biology]

2017-04-25T09:21:09-07:00

Interactions between bacteria and roots are critical to the terrestrial ecosystem. The zone of soil immediately surrounding roots is known as the rhizosphere and the surface of the root the rhizoplane (1, 2). This region is of paramount importance to the growth and productivity of plants because it is the...



Achiral symmetry breaking and positive Gaussian modulus lead to scalloped colloidal membranes [Applied Physical Sciences]

2017-04-25T09:21:10-07:00

In the presence of a nonadsorbing polymer, monodisperse rod-like particles assemble into colloidal membranes, which are one-rod-length–thick liquid-like monolayers of aligned rods. Unlike 3D edgeless bilayer vesicles, colloidal monolayer membranes form open structures with an exposed edge, thus presenting an opportunity to study elasticity of fluid sheets. Membranes assembled from...



Automated glycan assembly using the Glyconeer 2.1 synthesizer [Chemistry]

2017-04-25T09:21:10-07:00

Reliable and rapid access to defined biopolymers by automated DNA and peptide synthesis has fundamentally altered biological research and medical practice. Similarly, the procurement of defined glycans is key to establishing structure–activity relationships and thereby progress in the glycosciences. Here, we describe the rapid assembly of oligosaccharides using the commercially...



Pseudomagnetic fields for sound at the nanoscale [Physics]

2017-04-25T09:21:10-07:00

There is a growing effort in creating chiral transport of sound waves. However, most approaches so far have been confined to the macroscopic scale. Here, we propose an approach suitable to the nanoscale that is based on pseudomagnetic fields. These pseudomagnetic fields for sound waves are the analogue of what...



The cryo-EM structure of YjeQ bound to the 30S subunit suggests a fidelity checkpoint function for this protein in ribosome assembly [Biochemistry]

2017-04-25T09:21:10-07:00

Recent work suggests that bacterial YjeQ (RsgA) participates in the late stages of assembly of the 30S subunit and aids the assembly of the decoding center but also binds the mature 30S subunit with high affinity. To determine the function and mechanisms of YjeQ in the context of the mature...



Ubiquitinated proteins promote the association of proteasomes with the deubiquitinating enzyme Usp14 and the ubiquitin ligase Ube3c [Biochemistry]

2017-04-25T09:21:10-07:00

In mammalian cells, the 26S proteasomes vary in composition. In addition to the standard 28 subunits in the 20S core particle and 19 subunits in each 19S regulatory particle, a small fraction (about 10–20% in our preparations) also contains the deubiquitinating enzyme Usp14/Ubp6, which regulates proteasome activity, and the ubiquitin...



Altering the allosteric pathway in IGPS suppresses millisecond motions and catalytic activity [Biophysics and Computational Biology]

2017-04-25T09:21:10-07:00

Imidazole glycerol phosphate synthase (IGPS) is a V-type allosteric enzyme, meaning that its catalytic rate is critically dependent on activation by its allosteric ligand, N′-[(5′-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR). The allosteric mechanism of IGPS is reliant on millisecond conformational motions for efficient catalysis. We engineered four mutants of IGPS designed to disrupt...



SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner [Cell Biology]

2017-04-25T09:21:10-07:00

Many DNA repair proteins have additional functions other than their roles in DNA repair. In addition to catalyzing PCNA polyubiquitylation in response to the stalling of DNA replication, SHPRH has the additional function of facilitating rRNA transcription by localizing to the ribosomal DNA (rDNA) promoter in the nucleoli. SHPRH was...



PIK3CA mutant tumors depend on oxoglutarate dehydrogenase [Cell Biology]

2017-04-25T09:21:10-07:00

Oncogenic PIK3CA mutations are found in a significant fraction of human cancers, but therapeutic inhibition of PI3K has only shown limited success in clinical trials. To understand how mutant PIK3CA contributes to cancer cell proliferation, we used genome scale loss-of-function screening in a large number of genomically annotated cancer cell...



Uplift-driven diversification in the Hengduan Mountains, a temperate biodiversity hotspot [Evolution]

2017-04-25T09:21:10-07:00

A common hypothesis for the rich biodiversity found in mountains is uplift-driven diversification—that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We tested this hypothesis in the context of the Qinghai–Tibetan Plateau (QTP) and adjoining mountain ranges, using the phylogenetic and geographic histories of multiple groups of...



Parallel adaptive evolution of geographically distant herring populations on both sides of the North Atlantic Ocean [Genetics]

2017-04-25T09:21:10-07:00

Atlantic herring is an excellent species for studying the genetic basis of adaptation in geographically distant populations because of its characteristically large population sizes and low genetic drift. In this study we compared whole-genome resequencing data of Atlantic herring populations from both sides of the Atlantic Ocean. An important finding...



Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M [Immunology and Inflammation]

2017-04-25T09:21:10-07:00

Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase...



Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity [Immunology and Inflammation]

2017-04-25T09:21:10-07:00

A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) Flicr (Foxp3 long intergenic noncoding RNA) is a negative regulator that tunes Foxp3 expression, resulting in...



Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling [Immunology and Inflammation]

2017-04-25T09:21:10-07:00

It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the “master” protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1–dependent formation of K63-Ub chains, TAK1...



Plasma fibronectin stabilizes Borrelia burgdorferi-endothelial interactions under vascular shear stress by a catch-bond mechanism [Microbiology]

2017-04-25T09:21:10-07:00

Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with...



SAGA complex mediates the transcriptional up-regulation of antiviral RNA silencing [Microbiology]

2017-04-25T09:21:10-07:00

Pathogen recognition and transcriptional activation of defense-related genes are crucial steps in cellular defense responses. RNA silencing (RNAi) functions as an antiviral defense in eukaryotic organisms. Several RNAi-related genes are known to be transcriptionally up-regulated upon virus infection in some host organisms, but little is known about their induction mechanism....



Identification of a cono-RFamide from the venom of Conus textile that targets ASIC3 and enhances muscle pain [Neuroscience]

2017-04-25T09:21:10-07:00

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels that are expressed throughout the nervous system. ASICs have been implicated in several neuronal disorders, like ischemic stroke, neuronal inflammation, and pathological pain. Several toxins from venomous animals have been identified that target ASICs with high specificity and potency. These toxins are...



Context-dependent spatially periodic activity in the human entorhinal cortex [Neuroscience]

2017-04-25T09:21:10-07:00

The spatially periodic activity of grid cells in the entorhinal cortex (EC) of the rodent, primate, and human provides a coordinate system that, together with the hippocampus, informs an individual of its location relative to the environment and encodes the memory of that location. Among the most defining features of...



Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity [Neuroscience]

2017-04-25T09:21:10-07:00

Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus...



Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus [Neuroscience]

2017-04-25T09:21:11-07:00

Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrow-derived mesenchymal...



Dual optical control and mechanistic insights into photoswitchable group II and III metabotropic glutamate receptors [Physiology]

2017-04-25T09:21:11-07:00

G protein-coupled receptor (GPCR) signaling occurs in complex spatiotemporal patterns that are difficult to probe using standard pharmacological and genetic approaches. A powerful approach for dissecting GPCRs is to use light-controlled pharmacological agents that are tethered covalently and specifically to genetically engineered receptors. However, deficits in our understanding of the...



PIF4-controlled auxin pathway contributes to hybrid vigor in Arabidopsis thaliana [Plant Biology]

2017-04-25T09:21:11-07:00

F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are...



Malate-dependent Fe accumulation is a critical checkpoint in the root developmental response to low phosphate [Plant Biology]

2017-04-25T09:21:11-07:00

Low phosphate (Pi) availability constrains plant development and seed production in both natural and agricultural ecosystems. When Pi is scarce, modifications of root system architecture (RSA) enhance the soil exploration ability of the plant and lead to an increase in Pi uptake. In Arabidopsis, an iron-dependent mechanism reprograms primary root...



Variations in crowding, saccadic precision, and spatial localization reveal the shared topology of spatial vision [Psychological and Cognitive Sciences]

2017-04-25T09:21:11-07:00

Visual sensitivity varies across the visual field in several characteristic ways. For example, sensitivity declines sharply in peripheral (vs. foveal) vision and is typically worse in the upper (vs. lower) visual field. These variations can affect processes ranging from acuity and crowding (the deleterious effect of clutter on object recognition)...



A close-up look at the spliceosome, at last [Biochemistry]

2017-04-25T09:21:09-07:00

Major developments in cryo-electron microscopy in the past three or four years have led to the solution of a number of spliceosome structures at high resolution, e.g., the fully assembled but not yet active spliceosome (Bact), the spliceosome just after the first step of splicing (C), and the spliceosome activated...



Enhanced hyperuniformity from random reorganization [Applied Physical Sciences]

2017-04-25T09:21:09-07:00

Diffusion relaxes density fluctuations toward a uniform random state whose variance in regions of volume v=ℓd scales as σρ2≡⟨ρ2(ℓ)⟩−⟨ρ⟩2∼ℓ−d. Systems whose fluctuations decay faster, σρ2∼ℓ−λ with d<λ≤d+1, are called hyperuniform. The larger λ, the more uniform, with systems like crystals achieving the maximum value: λ=d+1. Although finite temperature equilibrium dynamics...



Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids [Biochemistry]

2017-04-25T09:21:09-07:00

Arachidonic acid (ARA) is metabolized by cyclooxygenase (COX) and cytochrome P450 to produce proangiogenic metabolites. Specifically, epoxyeicosatrienoic acids (EETs) produced from the P450 pathway are angiogenic, inducing cancer tumor growth. A previous study showed that inhibiting soluble epoxide hydrolase (sEH) increased EET concentration and mildly promoted tumor growth. However, inhibiting...



Structural basis of Tie2 activation and Tie2/Tie1 heterodimerization [Biochemistry]

2017-04-25T09:21:09-07:00

The endothelial cell (EC)-specific receptor tyrosine kinases Tie1 and Tie2 are necessary for the remodeling and maturation of blood and lymphatic vessels. Angiopoietin-1 (Ang1) growth factor is a Tie2 agonist, whereas Ang2 functions as a context-dependent agonist/antagonist. The orphan receptor Tie1 modulates Tie2 activation, which is induced by association of...



Dimerization of Tie2 mediated by its membrane-proximal FNIII domains [Biochemistry]

2017-04-25T09:21:09-07:00

Tie1 and Tie2, members of the tyrosine kinase family with immunoglobulin and EGF homology domains, are receptor tyrosine kinases found primarily in endothelial cells with key roles in development and maintenance of the vasculature and in angiogenesis. They are attractive targets for therapeutic intervention in tumor angiogenesis, inflammation, and sepsis....



Proteolytic control of the mitochondrial calcium uniporter complex [Biochemistry]

2017-04-25T09:21:09-07:00

The mitochondrial calcium uniporter is a Ca2+-activated Ca2+ channel complex mediating mitochondrial Ca2+ uptake, a process crucial for Ca2+ signaling, bioenergetics, and cell death. The uniporter is composed of the pore-forming MCU protein, the gatekeeping MICU1 and MICU2 subunits, and EMRE, a single-pass membrane protein that links MCU and MICU1...



Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance [Biochemistry]

2017-04-25T09:21:09-07:00

The metazoan Integrator complex (INT) has important functions in the 3′-end processing of noncoding RNAs, including the uridine-rich small nuclear RNA (UsnRNA) and enhancer RNA (eRNA), and in the transcription of coding genes by RNA polymerase II. The INT contains at least 14 subunits, but its molecular mechanism of action...



Structure of a DNA glycosylase that unhooks interstrand cross-links [Biochemistry]

2017-04-25T09:21:09-07:00

DNA glycosylases are important editing enzymes that protect genomic stability by excising chemically modified nucleobases that alter normal DNA metabolism. These enzymes have been known only to initiate base excision repair of small adducts by extrusion from the DNA helix. However, recent reports have described both vertebrate and microbial DNA...



In situ structural studies of tripeptidyl peptidase II (TPPII) reveal spatial association with proteasomes [Biophysics and Computational Biology]

2017-04-25T09:21:10-07:00

Tripeptidyl peptidase II (TPPII) is a eukaryotic protease acting downstream of the 26S proteasome; it removes tripeptides from the degradation products released by the proteasome. Structural studies in vitro have revealed the basic architecture of TPPII, a two-stranded linear polymer that assembles to form a spindle-shaped complex of ∼6 MDa....



Balance of microtubule stiffness and cortical tension determines the size of blood cells with marginal band across species [Biophysics and Computational Biology]

2017-04-25T09:21:10-07:00

The fast bloodstream of animals is associated with large shear stresses. To withstand these conditions, blood cells have evolved a special morphology and a specific internal architecture to maintain their integrity over several weeks. For instance, nonmammalian red blood cells, mammalian erythroblasts, and platelets have a peripheral ring of microtubules,...



Entropy redistribution controls allostery in a metalloregulatory protein [Biophysics and Computational Biology]

2017-04-25T09:21:10-07:00

Allosteric communication between two ligand-binding sites in a protein is a central aspect of biological regulation that remains mechanistically unclear. Here we show that perturbations in equilibrium picosecond–nanosecond motions impact zinc (Zn)-induced allosteric inhibition of DNA binding by the Zn efflux repressor CzrA (chromosomal zinc-regulated repressor). DNA binding leads to...



CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel [Biophysics and Computational Biology]

2017-04-25T09:21:10-07:00

Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxyl-terminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has...



Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma [Cell Biology]

2017-04-25T09:21:09-07:00

KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been associated with altered glucose and glutamine metabolism. Here, we show that KRAS activates lipogenesis, and this activation results in distinct proteomic and lipid signatures. By gene expression analysis, KRAS is shown to be associated with a lipogenesis gene signature and...



Formation of nucleobases in a Miller-Urey reducing atmosphere [Chemistry]

2017-04-25T09:21:09-07:00

The Miller–Urey experiments pioneered modern research on the molecular origins of life, but their actual relevance in this field was later questioned because the gas mixture used in their research is considered too reducing with respect to the most accepted hypotheses for the conditions on primordial Earth. In particular, the...



Pressure dependence of viscosity in supercooled water and a unified approach for thermodynamic and dynamic anomalies of water [Chemistry]

2017-04-25T09:21:09-07:00

The anomalous decrease of the viscosity of water with applied pressure has been known for over a century. It occurs concurrently with major structural changes: The second coordination shell around a molecule collapses onto the first shell. Viscosity is thus a macroscopic witness of the progressive breaking of the tetrahedral...



Aggregation landscapes of Huntingtin exon 1 protein fragments and the critical repeat length for the onset of Huntington’s disease [Chemistry]

2017-04-25T09:21:10-07:00

Huntington’s disease (HD) is a neurodegenerative disease caused by an abnormal expansion in the polyglutamine (polyQ) track of the Huntingtin (HTT) protein. The severity of the disease depends on the polyQ repeat length, arising only in patients with proteins having 36 repeats or more. Previous studies have shown that the...



Quantifying the driving factors for language shift in a bilingual region [Computer Sciences]

2017-04-25T09:21:09-07:00

Many of the world’s around 6,000 languages are in danger of disappearing as people give up use of a minority language in favor of the majority language in a process called language shift. Language shift can be monitored on a large scale through the use of mathematical models by way...



Tectonic controls on the long-term carbon isotope mass balance [Earth, Atmospheric, and Planetary Sciences]

2017-04-25T09:21:09-07:00

The long-term, steady-state marine carbon isotope record reflects changes to the proportional burial rate of organic carbon relative to total carbon on a global scale. For this reason, times of high δ13C are conventionally interpreted to be oxygenation events caused by excess organic burial. Here we show that the carbon...



Subduction zone forearc serpentinites as incubators for deep microbial life [Earth, Atmospheric, and Planetary Sciences]

2017-04-25T09:21:09-07:00

Serpentinization-fueled systems in the cool, hydrated forearc mantle of subduction zones may provide an environment that supports deep chemolithoautotrophic life. Here, we examine serpentinite clasts expelled from mud volcanoes above the Izu–Bonin–Mariana subduction zone forearc (Pacific Ocean) that contain complex organic matter and nanosized Ni–Fe alloys. Using time-of-flight secondary ion...



Experimental dispersal reveals characteristic scales of biodiversity in a natural landscape [Ecology]

2017-04-25T09:21:10-07:00

Ecological theory posits that dispersal among habitat patches links local communities and is a key “regional” process that maintains biological diversity. However, manipulations required to experimentally test regional processes are infeasible for most systems, and thus more work is needed to detect the scales at which regional processes manifest and...



Role of surface and subsurface processes in scaling N2O emissions along riverine networks [Environmental Sciences]

2017-04-25T09:21:09-07:00

Riverine environments, such as streams and rivers, have been reported as sources of the potent greenhouse gas nitrous oxide (N2O) to the atmosphere mainly via microbially mediated denitrification. Our limited understanding of the relative roles of the near-surface streambed sediment (hyporheic zone), benthic, and water column zones in controlling N2O...



Salting our freshwater lakes [Environmental Sciences]

2017-04-25T09:21:10-07:00

The highest densities of lakes on Earth are in north temperate ecosystems, where increasing urbanization and associated chloride runoff can salinize freshwaters and threaten lake water quality and the many ecosystem services lakes provide. However, the extent to which lake salinity may be changing at broad spatial scales remains unknown,...



Mechanosensation is evolutionarily tuned to locomotor mechanics [Evolution]

2017-04-25T09:21:10-07:00

The biomechanics of animal limbs has evolved to meet the functional demands for movement associated with different behaviors and environments. Effective movement relies not only on limb mechanics but also on appropriate mechanosensory feedback. By comparing sensory ability and mechanics within a phylogenetic framework, we show that peripheral mechanosensation has...



Determining the factors driving selective effects of new nonsynonymous mutations [Evolution]

2017-04-25T09:21:10-07:00

The distribution of fitness effects (DFE) of new mutations plays a fundamental role in evolutionary genetics. However, the extent to which the DFE differs across species has yet to be systematically investigated. Furthermore, the biological mechanisms determining the DFE in natural populations remain unclear. Here, we show that theoretical models...



Mutation in sorghum LOW GERMINATION STIMULANT 1 alters strigolactones and causes Striga resistance [Genetics]

2017-04-25T09:21:10-07:00

Striga is a major biotic constraint to sorghum production in semiarid tropical Africa and Asia. Genetic resistance to this parasitic weed is the most economically feasible control measure. Mutant alleles at the LGS1 (LOW GERMINATION STIMULANT 1) locus drastically reduce Striga germination stimulant activity. We provide evidence that the responsible...



Antigenicity-defined conformations of an extremely neutralization-resistant HIV-1 envelope spike [Immunology and Inflammation]

2017-04-25T09:21:10-07:00

The extraordinary genetic diversity of the HIV-1 envelope spike [Env; trimeric (gp160)3, cleaved to (gp120/gp41)3] poses challenges for vaccine development. Envs of different clinical isolates exhibit different sensitivities to antibody-mediated neutralization. Envs of difficult-to-neutralize viruses are thought to be more stable and conformationally homogeneous trimers than those of easy-to-neutralize viruses,...



Endotoxin-induced autocrine ATP signaling inhibits neutrophil chemotaxis through enhancing myosin light chain phosphorylation [Immunology and Inflammation]

2017-04-25T09:21:10-07:00

Although the neutrophil recruitment cascade during inflammation has been well described, the molecular players that halt neutrophil chemotaxis remain unclear. In this study, we found that lipopolysaccharide (LPS) was a potent stop signal for chemotactic neutrophil migration. Treatment with an antagonist of the ATP receptor (P2X1) in primary human neutrophils...



Formation of neurodegenerative aggresome and death-inducing signaling complex in maternal diabetes-induced neural tube defects [Medical Sciences]

2017-04-25T09:21:10-07:00

Diabetes mellitus in early pregnancy increases the risk in infants of birth defects, such as neural tube defects (NTDs), known as diabetic embryopathy. NTDs are associated with hyperglycemia-induced protein misfolding and Caspase-8–induced programmed cell death. The present study shows that misfolded proteins are ubiquitinylated, suggesting that ubiquitin-proteasomal degradation is impaired....



Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis [Microbiology]

2017-04-25T09:21:10-07:00

Persistence, manifested as drug tolerance, represents a significant obstacle to global tuberculosis control. The bactericidal drugs isoniazid and rifampicin kill greater than 99% of exponentially growing Mycobacterium tuberculosis (Mtb) cells, but the remaining cells are persisters, cells with decreased metabolic rate, refractory to killing by these drugs, and able to...



Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes [Microbiology]

2017-04-25T09:21:10-07:00

Explosive growth in the study of microbial epigenetics has revealed a diversity of chemical structures and biological functions of DNA modifications in restriction–modification (R-M) and basic genetic processes. Here, we describe the discovery of shared consensus sequences for two seemingly unrelated DNA modification systems, 6mA methylation and phosphorothioation (PT), in...



Enterococcus faecalis bacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence of Candida albicans [Microbiology]

2017-04-25T09:21:10-07:00

Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species also are among the most important and problematic, opportunistic nosocomial pathogens. Surprisingly, these two species antagonize each other’s virulence in both nematode infection and in vitro...



APC/CCdh1-Rock2 pathway controls dendritic integrity and memory [Neuroscience]

2017-04-25T09:21:10-07:00

Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer’s disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and...



Selective entrainment of gamma subbands by different slow network oscillations [Neuroscience]

2017-04-25T09:21:10-07:00

Theta oscillations (4–12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30–160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as...



Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice [Neuroscience]

2017-04-25T09:21:10-07:00

Damage to the lateral hypothalamus (LH) causes profound physical inactivity in mammals. Several molecularly distinct types of LH neurons have been identified, including orexin cells and glutamic acid decarboxylase 65 (GAD65) cells, but their interplay in orchestrating physical activity is not fully understood. Here, using optogenetic circuit analysis and cell...



Size-selective opening of the blood-brain barrier by targeting endothelial sphingosine 1-phosphate receptor 1 [Pharmacology]

2017-04-25T09:21:10-07:00

The vasculature of the central nervous system (CNS) forms a selective barrier termed the blood–brain barrier (BBB). Disruption of the BBB may contribute to various CNS diseases. Conversely, the intact BBB restricts efficient penetration of CNS-targeted drugs. Here, we report the BBB-regulatory role of endothelial sphingosine 1–phosphate (S1P) receptor-1, a...



Universal modal radiation laws for all thermal emitters [Physics]

2017-04-25T09:21:09-07:00

We derive four laws relating the absorptivity and emissivity of thermal emitters. Unlike the original Kirchhoff radiation law derivations, these derivations include diffraction, and so are valid also for small objects, and can also cover nonreciprocal objects. The proofs exploit two recent approaches. First, we express all fields in terms...



Spontaneous emergence of catalytic cycles with colloidal spheres [Physics]

2017-04-25T09:21:09-07:00

Colloidal particles endowed with specific time-dependent interactions are a promising route for realizing artificial materials that have the properties of living ones. Previous work has demonstrated how this system can give rise to self-replication. Here, we introduce the process of colloidal catalysis, in which clusters of particles catalyze the creation...



The carbonic anhydrase CAH1 is an essential component of the carbon-concentrating mechanism in Nannochloropsis oceanica [Plant Biology]

2017-04-25T09:21:10-07:00

Aquatic photosynthetic organisms cope with low environmental CO2 concentrations through the action of carbon-concentrating mechanisms (CCMs). Known eukaryotic CCMs consist of inorganic carbon transporters and carbonic anhydrases (and other supporting components) that culminate in elevated [CO2] inside a chloroplastic Rubisco-containing structure called a pyrenoid. We set out to determine the...



Ploidy-dependent changes in the epigenome of symbiotic cells correlate with specific patterns of gene expression [Plant Biology]

2017-04-25T09:21:10-07:00

The formation of symbiotic nodule cells in Medicago truncatula is driven by successive endoreduplication cycles and transcriptional reprogramming in different temporal waves including the activation of more than 600 cysteine-rich NCR genes expressed only in nodules. We show here that the transcriptional waves correlate with growing ploidy levels and have...



Live imaging of root-bacteria interactions in a microfluidics setup [Plant Biology]

2017-04-25T09:21:10-07:00

Plant roots play a dominant role in shaping the rhizosphere, the environment in which interaction with diverse microorganisms occurs. Tracking the dynamics of root–microbe interactions at high spatial resolution is currently limited because of methodological intricacy. Here, we describe a microfluidics-based approach enabling direct imaging of root–bacteria interactions in real...



News Feature: Is video game addiction really an addiction? [Psychological and Cognitive Sciences]

2017-04-25T09:21:09-07:00

Adding video gaming to the list of recognized behavioral addictions could help millions in need. It could also pathologize a normal behavior and create a new stigma. Science fiction is replete with notions of losing oneself inside a digitally generated alternate reality. But for millions around the world, that dystopic...



Eight-minute self-regulation intervention raises educational attainment at scale in individualist but not collectivist cultures [Psychological and Cognitive Sciences]

2017-04-25T09:21:09-07:00

Academic credentials open up a wealth of opportunities. However, many people drop out of educational programs, such as community college and online courses. Prior research found that a brief self-regulation strategy can improve self-discipline and academic outcomes. Could this strategy support learners at large scale? Mental contrasting with implementation intentions...



Life skills, wealth, health, and wellbeing in later life [Psychological and Cognitive Sciences]

2017-04-25T09:21:09-07:00

Life skills play a key role in promoting educational and occupational success in early life, but their relevance at older ages is uncertain. Here we measured five life skills—conscientiousness, emotional stability, determination, control, and optimism—in 8,119 men and women aged 52 and older (mean 66.7 y). We show that the...



Increasing honesty in humans with noninvasive brain stimulation [Psychological and Cognitive Sciences]

2017-04-25T09:21:09-07:00

Honesty plays a key role in social and economic interactions and is crucial for societal functioning. However, breaches of honesty are pervasive and cause significant societal and economic problems that can affect entire nations. Despite its importance, remarkably little is known about the neurobiological mechanisms supporting honest behavior. We demonstrate...



Adaptation aftereffects reveal that tactile distance is a basic somatosensory feature [Psychological and Cognitive Sciences]

2017-04-25T09:21:10-07:00

The stage at which processing of tactile distance occurs is still debated. We addressed this issue by implementing an adaptation-aftereffect paradigm with passive touch. We demonstrated the presence of a strong aftereffect, induced by the simultaneous presentation of pairs of tactile stimuli. After adaptation to two different distances, one on...



El Nino and the shifting geography of cholera in Africa [Statistics]

2017-04-25T09:21:10-07:00

The El Niño Southern Oscillation (ENSO) and other climate patterns can have profound impacts on the occurrence of infectious diseases ranging from dengue to cholera. In Africa, El Niño conditions are associated with increased rainfall in East Africa and decreased rainfall in southern Africa, West Africa, and parts of the...



Floodplains as an Achilles’ heel of Amazonian forest resilience [Sustainability Science]

2017-04-25T09:21:10-07:00

The massive forests of central Amazonia are often considered relatively resilient against climatic variation, but this view is challenged by the wildfires invoked by recent droughts. The impact of such fires that spread from pervasive sources of ignition may reveal where forests are less likely to persist in a drier...



Correction for Pishesha et al., Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease [Correction]

2017-04-25T09:21:11-07:00

IMMUNOLOGY AND INFLAMMATION Correction for “Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease,” by Novalia Pishesha, Angelina M. Bilate, Marsha C. Wibowo, Nai-Jia Huang, Zeyang Li, Rhogerry Dhesycka, Djenet Bousbaine, Hojun Li, Heide C. Patterson, Stephanie K. Dougan, Takeshi Maruyama, Harvey F. Lodish, and Hidde L....



Correction for Padilla et al., AgRP to Kiss1 neuron signaling links nutritional state and fertility [Correction]

2017-04-25T09:21:11-07:00

PHYSIOLOGY Correction for “AgRP to Kiss1 neuron signaling links nutritional state and fertility,” by Stephanie L. Padilla, Jian Qiu, Casey C Nestor, Chunguang Zhang, Arik W. Smith, Benjamin B. Whiddon, Oline K. Rønnekleiv, Martin J. Kelly, and Richard D. Palmiter, which appeared in issue 9, February 28, 2017, of Proc...



Correction to Supporting Information for Falahati and Wieschaus, Independent active and thermodynamic processes govern the nucleolus assembly in vivo [SI Correction]

2017-04-25T09:21:11-07:00

CELL BIOLOGY, APPLIED PHYSICAL SCIENCES Correction to Supporting Information for “Independent active and thermodynamic processes govern the nucleolus assembly in vivo,” by Hanieh Falahati and Eric Wieschaus, which appeared in issue 6, February 7, 2017, of Proc Natl Acad Sci USA (114:1335–1340; first published January 23, 2017; 10.1073/pnas.1615395114). The authors...



In This Issue [This Week in PNAS]

2017-04-18T09:47:26-07:00

Quantitative literary criticism 1432 Italian manuscript of the complete works of Seneca. MS Lat 47, Houghton Library, Harvard University. By adapting, quoting, and alluding to previous works, authors create links among literary texts, a phenomenon termed intertextuality, which provides grist for literary criticism. Using machine-learning tools and computational analysis of...



An antivascular vaccine to boost self-immunity and strike the tumor [Biological Sciences]

2017-04-18T09:47:26-07:00

Vascular endothelial growth factor (VEGF) family members and their receptors have long been considered suitable anticancer targets (1) because of their role in angiogenesis. Although their full potential remains to be realized, two monoclonal antibodies have been Food and Drug Administration-approved against human cancer: bevacizumab (humanized anti-VEGFA) and ramucirumab (fully...



Reply to Marchio et al.: Antitumor immune regulation by angiostatic therapy [Biological Sciences]

2017-04-18T09:47:26-07:00

We read with great interest the letter by Marchiò et al. (1) on our recently published paper describing the rational design and testing of a vaccine directed against the major angiogenic growth factor VEGF (2). The letter raises the concern that the potential of the vaccine is limited because of...



Baseball and jet lag: Correlation does not imply causation [Biological Sciences]

2017-04-18T09:47:26-07:00

My attention was drawn to the recent article by Song at al. entitled “How jet lag impairs Major League Baseball performance” (1), not only by its slightly unusual subject but more importantly because I wondered how one could ever actually prove the effect of jet lag on baseball performance. In...



Reply to Joly: Inferring causation from comprehensive analysis of observation [Biological Sciences]

2017-04-18T09:47:26-07:00

In our paper, “How jet lag impairs Major League Baseball performance,” we describe performance reductions in teams as a function of travel across time zones and attribute these effects to jet lag (1). The letter by Joly (2) raises the issue of correlation versus causation, implying that we cannot conclude...



QnAs with Christopher Monroe [QnAs]

2017-04-18T09:47:26-07:00

Classic computing can take credit for technology ranging from mobile phones to supercomputers. But in recent years, a budding counterpart to these conventional devices has emerged: quantum computers. Whereas classic computing sometimes fails to solve complex calculations, such as factoring hundred-digit numbers, quantum computing holds the potential to easily tackle...



Predicting invasion winners and losers under climate change [Ecology]

2017-04-18T09:47:26-07:00

Invasive plant species are human-introduced, nonnative, and damaging. They can restructure natural habitats, change community composition, disrupt food webs, and degrade ecosystem services. Global climatic changes are often thought to exacerbate invasions (1), but no consensus exists over the generality of this phenomenon (2). As a consequence, anticipating areas of...



Anterior temporal lobe and the representation of knowledge about people [Neuroscience]

2017-04-18T09:47:26-07:00

Patients with semantic dementia (SD), a neurodegenerative disease affecting the anterior temporal lobes (ATL) (1), present with striking cognitive deficits: they can have difficulties naming objects and familiar people from both pictures and descriptions (2, 3). Furthermore, SD patients make semantic errors (e.g., naming “horse” a picture of a zebra),...



Neuronal androgen receptor: Molecular gateway to polycystic ovary syndrome? [Physiology]

2017-04-18T09:47:26-07:00

Polycystic ovary syndrome (PCOS) afflicts ∼15% of women in their reproductive years (1). PCOS women exhibit high circulating levels of testosterone (T), intermittent or absent menstrual cycles, and polycystic ovaries on ultrasound, or at least two of these three diagnostic criteria (2). Hyperandrogenism is at the core of PCOS, its...



Neural pathways for cognitive command and control of hand movements [Neuroscience]

2017-04-18T09:47:26-07:00

A piece of fruit—a raisin—swings on a stick in front of a monkey (Fig. 1). He likes raisins; he wants this one. He stretches out his arm, opens his hand with the fingers spread wide apart, and tries to capture it; he misses (bursts B and D). He tries again,...



Nanoparticle amount, and not size, determines chain alignment and nonlinear hardening in polymer nanocomposites [Applied Physical Sciences]

2017-04-18T09:47:26-07:00

Polymer nanocomposites—materials in which a polymer matrix is blended with nanoparticles (or fillers)—strengthen under sufficiently large strains. Such strain hardening is critical to their function, especially for materials that bear large cyclic loads such as car tires or bearing sealants. Although the reinforcement (i.e., the increase in the linear elasticity)...



Structure-metabolism relationships in human-AOX: Chemical insights from a large database of aza-aromatic and amide compounds [Chemistry]

2017-04-18T09:47:26-07:00

Aldehyde oxidase (AOX) is a metabolic enzyme catalyzing the oxidation of aldehyde and aza-aromatic compounds and the hydrolysis of amides, moieties frequently shared by the majority of drugs. Despite its key role in human metabolism, to date only fragmentary information about the chemical features responsible for AOX susceptibility are reported...



Delivering strong 1H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange [Chemistry]

2017-04-18T09:47:26-07:00

Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost parahydrogen-based approach signal amplification by reversible exchange with studies...



Quantitative criticism of literary relationships [Computer Sciences]

2017-04-18T09:47:26-07:00

Authors often convey meaning by referring to or imitating prior works of literature, a process that creates complex networks of literary relationships (“intertextuality”) and contributes to cultural evolution. In this paper, we use techniques from stylometry and machine learning to address subjective literary critical questions about Latin literature, a corpus...



Structure of aryl O-demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism [Biochemistry]

2017-04-18T09:47:26-07:00

Some strains of soil and marine bacteria have evolved intricate metabolic pathways for using environmentally derived aromatics as a carbon source. Many of these metabolic pathways go through intermediates such as vanillate, 3-O-methylgallate, and syringate. Demethylation of these compounds is essential for downstream aryl modification, ring opening, and subsequent assimilation...



Mass spectrometric identification of intermediates in the O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion in FNR [Biochemistry]

2017-04-18T09:47:26-07:00

The iron-sulfur cluster containing protein Fumarate and Nitrate Reduction (FNR) is the master regulator for the switch between anaerobic and aerobic respiration in Escherichia coli and many other bacteria. The [4Fe-4S] cluster functions as the sensory module, undergoing reaction with O2 that leads to conversion to a [2Fe-2S] form with...



Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface [Biochemistry]

2017-04-18T09:47:26-07:00

ERp44 retrieves some endoplasmic reticulum (ER)-resident enzymes and immature oligomers of secretory proteins from the Golgi. Association of ERp44 with its clients is regulated by pH-dependent mechanisms, but the molecular details are not fully understood. Here we report high-resolution crystal structures of human ERp44 at neutral and weakly acidic pH....



Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione [Biochemistry]

2017-04-18T09:47:26-07:00

The mammalian gene Nit1 (nitrilase-like protein 1) encodes a protein that is highly conserved in eukaryotes and is thought to act as a tumor suppressor. Despite being ∼35% sequence identical to ω-amidase (Nit2), the Nit1 protein does not hydrolyze efficiently α-ketoglutaramate (a known physiological substrate of Nit2), and its actual...