WorldWideScience

Sample records for reveal distinct modes

  1. Crystal structure of the thioesterification conformation of Bacillus subtilis o-succinylbenzoyl-CoA synthetase reveals a distinct substrate-binding mode.

    Science.gov (United States)

    Chen, Yaozong; Li, Tin Lok; Lin, Xingbang; Li, Xin; Li, Xiang David; Guo, Zhihong

    2017-07-21

    o -Succinylbenzoyl-CoA (OSB-CoA) synthetase (MenE) is an essential enzyme in bacterial vitamin K biosynthesis and an important target in the development of new antibiotics. It is a member of the adenylating enzymes (ANL) family, which reconfigure their active site in two different active conformations, one for the adenylation half-reaction and the other for a thioesterification half-reaction, in a domain-alternation catalytic mechanism. Although several aspects of the adenylating mechanism in MenE have recently been uncovered, its thioesterification conformation remains elusive. Here, using a catalytically competent Bacillus subtilis mutant protein complexed with an OSB-CoA analogue, we determined MenE high-resolution structures to 1.76 and 1.90 Å resolution in a thioester-forming conformation. By comparison with the adenylation conformation, we found that MenE's C-domain rotates around the Ser-384 hinge by 139.5° during domain-alternation catalysis. The structures also revealed a thioesterification active site specifically conserved among MenE orthologues and a substrate-binding mode distinct from those of many other acyl/aryl-CoA synthetases. Of note, using site-directed mutagenesis, we identified several residues that specifically contribute to the thioesterification half-reaction without affecting the adenylation half-reaction. Moreover, we observed a substantial movement of the activated succinyl group in the thioesterification half-reaction. These findings provide new insights into the domain-alternation catalysis of a bacterial enzyme essential for vitamin K biosynthesis and of its adenylating homologues in the ANL enzyme family. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Characterization of distinct Arctic aerosol accumulation modes and their sources

    DEFF Research Database (Denmark)

    Lange, R.; Dall'Osto, M.; Skov, H.

    2018-01-01

    -August). By association to chemical composition, cloud condensation nuclei properties, and meteorological variables, three typical accumulation mode aerosol clusters were identified: Haze (32% of the time), Bimodal (14%) and Aged (6%). In brief: (1) Haze accumulation mode aerosol shows a single mode at 150 nm, peaking...

  3. Characterization of distinct Arctic aerosol accumulation modes and their sources

    Science.gov (United States)

    Lange, R.; Dall'Osto, M.; Skov, H.; Nøjgaard, J. K.; Nielsen, I. E.; Beddows, D. C. S.; Simo, R.; Harrison, R. M.; Massling, A.

    2018-06-01

    In this work we use cluster analysis of long term particle size distribution data to expand an array of different shorter term atmospheric measurements, thereby gaining insights into longer term patterns and properties of Arctic aerosol. Measurements of aerosol number size distributions (9-915 nm) were conducted at Villum Research Station (VRS), Station Nord in North Greenland during a 5 year record (2012-2016). Alongside this, measurements of aerosol composition, meteorological parameters, gaseous compounds and cloud condensation nuclei (CCN) activity were performed during different shorter occasions. K-means clustering analysis of particle number size distributions on daily basis identified several clusters. Clusters of accumulation mode aerosols (main size modes > 100 nm) accounted for 56% of the total aerosol during the sampling period (89-91% during February-April, 1-3% during June-August). By association to chemical composition, cloud condensation nuclei properties, and meteorological variables, three typical accumulation mode aerosol clusters were identified: Haze (32% of the time), Bimodal (14%) and Aged (6%). In brief: (1) Haze accumulation mode aerosol shows a single mode at 150 nm, peaking in February-April, with highest loadings of sulfate and black carbon concentrations. (2) Accumulation mode Bimodal aerosol shows two modes, at 38 nm and 150 nm, peaking in June-August, with the highest ratio of organics to sulfate concentrations. (3) Aged accumulation mode aerosol shows a single mode at 213 nm, peaking in September-October and is associated with cloudy and humid weather conditions during autumn. The three aerosol clusters were considered alongside CCN concentrations. We suggest that organic compounds, that are likely marine biogenic in nature, greatly influence the Bimodal cluster and contribute significantly to its CCN activity. This stresses the importance of better characterizing the marine ecosystem and the aerosol-mediated climate effects in the

  4. Slowest kinetic modes revealed by metabasin renormalization

    Science.gov (United States)

    Okushima, Teruaki; Niiyama, Tomoaki; Ikeda, Kensuke S.; Shimizu, Yasushi

    2018-02-01

    Understanding the slowest relaxations of complex systems, such as relaxation of glass-forming materials, diffusion in nanoclusters, and folding of biomolecules, is important for physics, chemistry, and biology. For a kinetic system, the relaxation modes are determined by diagonalizing its transition rate matrix. However, for realistic systems of interest, numerical diagonalization, as well as extracting physical understanding from the diagonalization results, is difficult due to the high dimensionality. Here, we develop an alternative and generally applicable method of extracting the long-time scale relaxation dynamics by combining the metabasin analysis of Okushima et al. [Phys. Rev. E 80, 036112 (2009), 10.1103/PhysRevE.80.036112] and a Jacobi method. We test the method on an illustrative model of a four-funnel model, for which we obtain a renormalized kinematic equation of much lower dimension sufficient for determining slow relaxation modes precisely. The method is successfully applied to the vacancy transport problem in ionic nanoparticles [Niiyama et al., Chem. Phys. Lett. 654, 52 (2016), 10.1016/j.cplett.2016.04.088], allowing a clear physical interpretation that the final relaxation consists of two successive, characteristic processes.

  5. CW EPR parameters reveal cytochrome P450 ligand binding modes.

    Science.gov (United States)

    Lockart, Molly M; Rodriguez, Carlo A; Atkins, William M; Bowman, Michael K

    2018-06-01

    Cytochrome P450 (CYP) monoxygenses utilize heme cofactors to catalyze oxidation reactions. They play a critical role in metabolism of many classes of drugs, are an attractive target for drug development, and mediate several prominent drug interactions. Many substrates and inhibitors alter the spin state of the ferric heme by displacing the heme's axial water ligand in the resting enzyme to yield a five-coordinate iron complex, or they replace the axial water to yield a nitrogen-ligated six-coordinate iron complex, which are traditionally assigned by UV-vis spectroscopy. However, crystal structures and recent pulsed electron paramagnetic resonance (EPR) studies find a few cases where molecules hydrogen bond to the axial water. The water-bridged drug-H 2 O-heme has UV-vis spectra similar to nitrogen-ligated, six-coordinate complexes, but are closer to "reverse type I" complexes described in older liteature. Here, pulsed and continuous wave (CW) EPR demonstrate that water-bridged complexes are remarkably common among a range of nitrogenous drugs or drug fragments that bind to CYP3A4 or CYP2C9. Principal component analysis reveals a distinct clustering of CW EPR spectral parameters for water-bridged complexes. CW EPR reveals heterogeneous mixtures of ligated states, including multiple directly-coordinated complexes and water-bridged complexes. These results suggest that water-bridged complexes are under-represented in CYP structural databases and can have energies similar to other ligation modes. The data indicates that water-bridged binding modes can be identified and distinguished from directly-coordinated binding by CW EPR. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    Science.gov (United States)

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  7. Distinct modes of adventitious rooting in Arabidopsis thaliana.

    Science.gov (United States)

    Correa, L da Rocha; Troleis, J; Mastroberti, A A; Mariath, J E A; Fett-Neto, A G

    2012-01-01

    The literature describes different rooting protocols for Arabidopsis thaliana as models to study adventitious rooting, and results are generally perceived as comparable. However, there is a lack of investigations focusing on the distinct features, advantages and limitations of each method in the study of adventitious rooting with both wild-type (WT) ecotypes and their respective mutants. This investigation was undertaken to evaluate the adventitious rooting process in three different experimental systems, all using A. thaliana, analysing the same rooting parameters after transient exposure to auxin (indole-3-acetic acid) and control conditions: excised leaves, de-rooted plants and etiolated seedlings. The founding tissues and sites of origin of roots differed depending on the system used, whereas all rooting patterns were of the direct type (i.e., without callus formation). None of the systems had an absolute requirement for exogenous auxin, although rooting was enhanced by this phytohormone, with the exception of de-rooted plants, which had adventitious rooting strongly inhibited by exogenous auxin. Root elongation was much favoured in isolated leaves. Auxin-overproducing mutants could not be used in the detached leaf system due to precocious senescence; in the de-rooted plant system, these mutants had a WT-like rooting response, whereas the expression of the 'rooty' phenotype was only evident in the etiolated seedling system. Adventitious rooting of etiolated WT seedlings in the presence of exogenous auxin was inhibited by exogenous flavonoids, which act as auxin transport inhibitors; surprisingly, the flavonoid-deficient mutant chs had a lower rooting response compared to WT. Although Arabidopsis is an excellent model system to study adventitious rooting, physiological and developmental responses differed significantly, underlining the importance of avoiding data generalisation on rooting responses derived from different experimental systems with this species.

  8. Mapping Phylogenetic Trees to Reveal Distinct Patterns of Evolution.

    Science.gov (United States)

    Kendall, Michelle; Colijn, Caroline

    2016-10-01

    Evolutionary relationships are frequently described by phylogenetic trees, but a central barrier in many fields is the difficulty of interpreting data containing conflicting phylogenetic signals. We present a metric-based method for comparing trees which extracts distinct alternative evolutionary relationships embedded in data. We demonstrate detection and resolution of phylogenetic uncertainty in a recent study of anole lizards, leading to alternate hypotheses about their evolutionary relationships. We use our approach to compare trees derived from different genes of Ebolavirus and find that the VP30 gene has a distinct phylogenetic signature composed of three alternatives that differ in the deep branching structure. phylogenetics, evolution, tree metrics, genetics, sequencing. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

    Directory of Open Access Journals (Sweden)

    David P Hall

    Full Text Available Acute mountain sickness (AMS is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS, we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25. These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

  10. Topic Modeling Reveals Distinct Interests within an Online Conspiracy Forum

    Directory of Open Access Journals (Sweden)

    Colin Klein

    2018-02-01

    Full Text Available Conspiracy theories play a troubling role in political discourse. Online forums provide a valuable window into everyday conspiracy theorizing, and can give a clue to the motivations and interests of those who post in such forums. Yet this online activity can be difficult to quantify and study. We describe a unique approach to studying online conspiracy theorists which used non-negative matrix factorization to create a topic model of authors' contributions to the main conspiracy forum on Reddit.com. This subreddit provides a large corpus of comments which spans many years and numerous authors. We show that within the forum, there are multiple sub-populations distinguishable by their loadings on different topics in the model. Further, we argue, these differences are interpretable as differences in background beliefs and motivations. The diversity of the distinct subgroups places constraints on theories of what generates conspiracy theorizing. We argue that traditional “monological” believers are only the tip of an iceberg of commenters. Neither simple irrationality nor common preoccupations can account for the observed diversity. Instead, we suggest, those who endorse conspiracies seem to be primarily brought together by epistemological concerns, and that these central concerns link an otherwise heterogenous group of individuals.

  11. Two distinct microbial communities revealed in the sponge Cinachyrella

    Science.gov (United States)

    Cuvelier, Marie L.; Blake, Emily; Mulheron, Rebecca; McCarthy, Peter J.; Blackwelder, Patricia; Thurber, Rebecca L. Vega; Lopez, Jose V.

    2014-01-01

    Marine sponges are vital components of benthic and coral reef ecosystems, providing shelter and nutrition for many organisms. In addition, sponges act as an essential carbon and nutrient link between the pelagic and benthic environment by filtering large quantities of seawater. Many sponge species harbor a diverse microbial community (including Archaea, Bacteria and Eukaryotes), which can constitute up to 50% of the sponge biomass. Sponges of the genus Cinachyrella are common in Caribbean and Floridian reefs and their archaeal and bacterial microbiomes were explored here using 16S rRNA gene tag pyrosequencing. Cinachyrella specimens and seawater samples were collected from the same South Florida reef at two different times of year. In total, 639 OTUs (12 archaeal and 627 bacterial) belonging to 2 archaeal and 21 bacterial phyla were detected in the sponges. Based on their microbiomes, the six sponge samples formed two distinct groups, namely sponge group 1 (SG1) with lower diversity (Shannon-Weiner index: 3.73 ± 0.22) and SG2 with higher diversity (Shannon-Weiner index: 5.95 ± 0.25). Hosts' 28S rRNA gene sequences further confirmed that the sponge specimens were composed of two taxa closely related to Cinachyrella kuekenthalli. Both sponge groups were dominated by Proteobacteria, but Alphaproteobacteria were significantly more abundant in SG1. SG2 harbored many bacterial phyla (>1% of sequences) present in low abundance or below detection limits (<0.07%) in SG1 including: Acidobacteria, Chloroflexi, Gemmatimonadetes, Nitrospirae, PAUC34f, Poribacteria, and Verrucomicrobia. Furthermore, SG1 and SG2 only had 95 OTUs in common, representing 30.5 and 22.4% of SG1 and SG2's total OTUs, respectively. These results suggest that the sponge host may exert a pivotal influence on the nature and structure of the microbial community and may only be marginally affected by external environment parameters. PMID:25408689

  12. Two distinct microbial communities revealed in the sponge Cinachyrella

    Directory of Open Access Journals (Sweden)

    Marie Laure Cuvelier

    2014-11-01

    Full Text Available Marine sponges are vital components of benthic and coral reef ecosystems, providing shelter and nutrition for many organisms. In addition, sponges act as an essential carbon and nutrient link between the pelagic and benthic environment by filtering large quantities of seawater. Many sponge species harbor a diverse microbial community (including Archaea, Bacteria and Eukaryotes, which can constitute up to 50% of the sponge biomass. Sponges of the genus Cinachyrella are common in Caribbean and Floridian reefs and their archaeal and bacterial microbiomes were explored here using 16S rDNA tag pyrosequencing. Cinachyrella specimens and seawater samples were collected from the same South Florida reef at two different times of year. In total, 639 OTUs (12 archaeal and 627 bacterial belonging to 2 archaeal and 21 bacterial phyla were detected in the sponges. Based on their microbiomes, the six sponge samples formed two distinct groups, namely sponge group 1 (SG1 with low diversity (Shannon-Weiner index: 3.73 ± 0.22 and SG2 with higher diversity (Shannon-Weiner index: 5.95 ± 0.25. Hosts’ 28S rDNA sequences further confirmed that the sponge specimens were composed of two taxa closely related to Cinachyrella kuekenthalli. Both sponge groups were dominated by Proteobacteria, but Alphaproteobacteria were significantly more abundant in SG1. SG2 harbored many bacterial phyla (>1% of sequences present in low abundance or below detection limits (<0.07% in SG1 including: Acidobacteria, Chloroflexi, Gemmatimonadetes, Nitrospirae, PAUC34f, Poribacteria and Verrucomicrobia. Furthermore, SG1 and SG2 only had 95 OTUs in common, representing 30.5% and 22.4% of SG1 and SG2’s total OTUs, respectively. These results suggest that the sponge host may exert a pivotal influence on the nature and structure of the microbial community and may only be marginally affected by external environment parameters.

  13. Distinct soil bacterial communities revealed under a diversely managed agroecosystem.

    Directory of Open Access Journals (Sweden)

    Raymon S Shange

    Full Text Available Land-use change and management practices are normally enacted to manipulate environments to improve conditions that relate to production, remediation, and accommodation. However, their effect on the soil microbial community and their subsequent influence on soil function is still difficult to quantify. Recent applications of molecular techniques to soil biology, especially the use of 16S rRNA, are helping to bridge this gap. In this study, the influence of three land-use systems within a demonstration farm were evaluated with a view to further understand how these practices may impact observed soil bacterial communities. Replicate soil samples collected from the three land-use systems (grazed pine forest, cultivated crop, and grazed pasture on a single soil type. High throughput 16S rRNA gene pyrosequencing was used to generate sequence datasets. The different land use systems showed distinction in the structure of their bacterial communities with respect to the differences detected in cluster analysis as well as diversity indices. Specific taxa, particularly Actinobacteria, Acidobacteria, and classes of Proteobacteria, showed significant shifts across the land-use strata. Families belonging to these taxa broke with notions of copio- and oligotrphy at the class level, as many of the less abundant groups of families of Actinobacteria showed a propensity for soil environments with reduced carbon/nutrient availability. Orders Actinomycetales and Solirubrobacterales showed their highest abundance in the heavily disturbed cultivated system despite the lowest soil organic carbon (SOC values across the site. Selected soil properties ([SOC], total nitrogen [TN], soil texture, phosphodiesterase [PD], alkaline phosphatase [APA], acid phosphatase [ACP] activity, and pH also differed significantly across land-use regimes, with SOM, PD, and pH showing variation consistent with shifts in community structure and composition. These results suggest that use of

  14. Vibrio cholerae classical biotype strains reveal distinct signatures in Mexico.

    Science.gov (United States)

    Alam, Munirul; Islam, M Tarequl; Rashed, Shah Manzur; Johura, Fatema-tuz; Bhuiyan, Nurul A; Delgado, Gabriela; Morales, Rosario; Mendez, Jose Luis; Navarro, Armando; Watanabe, Haruo; Hasan, Nur-A; Colwell, Rita R; Cravioto, Alejandro

    2012-07-01

    Vibrio cholerae O1 classical (CL) biotype caused the fifth and sixth pandemics, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the seventh pandemic in Asia in the 1970s by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia and although it had never been reported from Latin America, V. cholerae CL and ET biotypes, including a hybrid ET, were found associated with areas of cholera endemicity in Mexico between 1991 and 1997. In this study, CL biotype strains isolated from areas of cholera endemicity in Mexico between 1983 and 1997 were characterized in terms of major phenotypic and genetic traits and compared with CL biotype strains isolated in Bangladesh between 1962 and 1989. According to sero- and biotyping data, all V. cholerae strains tested had the major phenotypic and genotypic characteristics specific for the CL biotype. Antibiograms revealed the majority of the Bangladeshi strains to be resistant to trimethoprim-sulfamethoxazole, furazolidone, ampicillin, and gentamicin, while the Mexican strains were sensitive to all of these drugs, as well as to ciprofloxacin, erythromycin, and tetracycline. Pulsed-field gel electrophoresis (PFGE) of NotI-digested genomic DNA revealed characteristic banding patterns for all of the CL biotype strains although the Mexican strains differed from the Bangladeshi strains in 1 to 2 DNA bands. The difference was subtle but consistent, as confirmed by the subclustering patterns in the PFGE-based dendrogram, and can serve as a regional signature, suggesting the pre-1991 existence and evolution of the CL biotype strains in the Americas, independent from Asia.

  15. Distinct sets of locomotor modules control the speed and modes of human locomotion

    Science.gov (United States)

    Yokoyama, Hikaru; Ogawa, Tetsuya; Kawashima, Noritaka; Shinya, Masahiro; Nakazawa, Kimitaka

    2016-01-01

    Although recent vertebrate studies have revealed that different spinal networks are recruited in locomotor mode- and speed-dependent manners, it is unknown whether humans share similar neural mechanisms. Here, we tested whether speed- and mode-dependence in the recruitment of human locomotor networks exists or not by statistically extracting locomotor networks. From electromyographic activity during walking and running over a wide speed range, locomotor modules generating basic patterns of muscle activities were extracted using non-negative matrix factorization. The results showed that the number of modules changed depending on the modes and speeds. Different combinations of modules were extracted during walking and running, and at different speeds even during the same locomotor mode. These results strongly suggest that, in humans, different spinal locomotor networks are recruited while walking and running, and even in the same locomotor mode different networks are probably recruited at different speeds. PMID:27805015

  16. A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

    Science.gov (United States)

    Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

    2015-01-01

    Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

  17. Distinct effects of reminding mortality and physical pain on the default-mode activity and activity underlying self-reflection.

    Science.gov (United States)

    Shi, Zhenhao; Han, Shihui

    2018-06-01

    Behavioral research suggests that reminding both mortality and negative affect influences self-related thoughts. Using functional magnetic resonance imaging (MRI), we tested the hypothesis that reminders of mortality and physical pain decrease brain activity underlying self-related thoughts. Three groups of adults underwent priming procedures during which they answered questions pertaining to mortality, physical pain, or leisure time, respectively. Before and after priming, participants performed personality trait judgments on oneself or a celebrity, identified the font of words, or passively viewed a fixation. The default-mode activity and neural activity underlying self-reflection were identified by contrasting viewing a fixation vs. font judgment and trait judgments on oneself vs. a celebrity, respectively. The analyses of the pre-priming functional MRI (fMRI) data identified the default-mode activity in the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (MPFC), and parahippocampal gyrus, and the activity underlying instructed self-reflection in both the ventral and dorsal regions of the MPFC. The analyses of the post-priming fMRI data revealed that, relative to leisure time priming, reminding mortality significantly reduced the default-mode PCC activity, and reminding physical pain significantly decreased the dorsal MPFC activity during instructed self-reflection. Our findings suggest distinct neural underpinnings of the effect of reminding morality and aversive emotion on default-mode and instructed self-reflection.

  18. Three distinct modes of intron dynamics in the evolution of eukaryotes.

    Science.gov (United States)

    Carmel, Liran; Wolf, Yuri I; Rogozin, Igor B; Koonin, Eugene V

    2007-07-01

    Several contrasting scenarios have been proposed for the origin and evolution of spliceosomal introns, a hallmark of eukaryotic genes. A comprehensive probabilistic model to obtain a definitive reconstruction of intron evolution was developed and applied to 391 sets of conserved genes from 19 eukaryotic species. It is inferred that a relatively high intron density was reached early, i.e., the last common ancestor of eukaryotes contained >2.15 introns/kilobase, and the last common ancestor of multicellular life forms harbored approximately 3.4 introns/kilobase, a greater intron density than in most of the extant fungi and in some animals. The rates of intron gain and intron loss appear to have been dropping during the last approximately 1.3 billion years, with the decline in the gain rate being much steeper. Eukaryotic lineages exhibit three distinct modes of evolution of the intron-exon structure. The primary, balanced mode, apparently, operates in all lineages. In this mode, intron gain and loss are strongly and positively correlated, in contrast to previous reports on inverse correlation between these processes. The second mode involves an elevated rate of intron loss and is prevalent in several lineages, such as fungi and insects. The third mode, characterized by elevated rate of intron gain, is seen only in deep branches of the tree, indicating that bursts of intron invasion occurred at key points in eukaryotic evolution, such as the origin of animals. Intron dynamics could depend on multiple mechanisms, and in the balanced mode, gain and loss of introns might share common mechanistic features.

  19. Performance goals in conflictual social interactions: towards the distinction between two modes of relational conflict regulation.

    Science.gov (United States)

    Sommet, Nicolas; Darnon, Céline; Mugny, Gabriel; Quiamzade, Alain; Pulfrey, Caroline; Dompnier, Benoît; Butera, Fabrizio

    2014-03-01

    Socio-cognitive conflict has been defined as a situation of confrontation with a disagreeing other. Previous research suggests that individuals can regulate conflict in a relational way, namely by focusing on social comparison between relative levels of competences. Relational conflict regulation has been described as yielding particularly negative effects on social interactions and learning, but has been understudied. The present research addresses the question of the origin of relational conflict regulation by introducing a fundamental distinction between two types of regulation, one based on the affirmation of one's own point of view and the invalidation of the other's (i.e., 'competitive' regulation), the other corresponding to the protection of self-competence via compliance (i.e., 'protective' regulation). Three studies show that these modes of relational conflict regulation result from the endorsement of distinct performance goals, respectively, performance-approach goals (trying to outperform others) and performance-avoidance goals (avoiding performing more poorly than others). Theoretical implications for the literature on both conflict regulation and achievement goals are discussed. © 2012 The British Psychological Society.

  20. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  1. Toward an implicit measure of emotions: ratings of abstract images reveal distinct emotional states.

    Science.gov (United States)

    Bartoszek, Gregory; Cervone, Daniel

    2017-11-01

    Although implicit tests of positive and negative affect exist, implicit measures of distinct emotional states are scarce. Three experiments examined whether a novel implicit emotion-assessment task, the rating of emotion expressed in abstract images, would reveal distinct emotional states. In Experiment 1, participants exposed to a sadness-inducing story inferred more sadness, and less happiness, in abstract images. In Experiment 2, an anger-provoking interaction increased anger ratings. In Experiment 3, compared to neutral images, spider images increased fear ratings in spider-fearful participants but not in controls. In each experiment, the implicit task indicated elevated levels of the target emotion and did not indicate elevated levels of non-target negative emotions; the task thus differentiated among emotional states of the same valence. Correlations also supported the convergent and discriminant validity of the implicit task. Supporting the possibility that heuristic processes underlie the ratings, group differences were stronger among those who responded relatively quickly.

  2. TALE factors use two distinct functional modes to control an essential zebrafish gene expression program.

    Science.gov (United States)

    Ladam, Franck; Stanney, William; Donaldson, Ian J; Yildiz, Ozge; Bobola, Nicoletta; Sagerström, Charles G

    2018-06-18

    TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages - a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs. © 2018, Ladam et al.

  3. Coral transcriptome and bacterial community profiles reveal distinct Yellow Band Disease states in Orbicella faveolata

    KAUST Repository

    Closek, Collin J.

    2014-06-20

    Coral diseases impact reefs globally. Although we continue to describe diseases, little is known about the etiology or progression of even the most common cases. To examine a spectrum of coral health and determine factors of disease progression we examined Orbicella faveolata exhibiting signs of Yellow Band Disease (YBD), a widespread condition in the Caribbean. We used a novel combined approach to assess three members of the coral holobiont: the coral-host, associated Symbiodinium algae, and bacteria. We profiled three conditions: (1) healthy-appearing colonies (HH), (2) healthy-appearing tissue on diseased colonies (HD), and (3) diseased lesion (DD). Restriction fragment length polymorphism analysis revealed health state-specific diversity in Symbiodinium clade associations. 16S ribosomal RNA gene microarrays (PhyloChips) and O. faveolata complimentary DNA microarrays revealed the bacterial community structure and host transcriptional response, respectively. A distinct bacterial community structure marked each health state. Diseased samples were associated with two to three times more bacterial diversity. HD samples had the highest bacterial richness, which included components associated with HH and DD, as well as additional unique families. The host transcriptome under YBD revealed a reduced cellular expression of defense- and metabolism-related processes, while the neighboring HD condition exhibited an intermediate expression profile. Although HD tissue appeared visibly healthy, the microbial communities and gene expression profiles were distinct. HD should be regarded as an additional (intermediate) state of disease, which is important for understanding the progression of YBD. © 2014 International Society for Microbial Ecology. All rights reserved.

  4. Dynamic Changes in Amygdala Psychophysiological Connectivity Reveal Distinct Neural Networks for Facial Expressions of Basic Emotions.

    Science.gov (United States)

    Diano, Matteo; Tamietto, Marco; Celeghin, Alessia; Weiskrantz, Lawrence; Tatu, Mona-Karina; Bagnis, Arianna; Duca, Sergio; Geminiani, Giuliano; Cauda, Franco; Costa, Tommaso

    2017-03-27

    The quest to characterize the neural signature distinctive of different basic emotions has recently come under renewed scrutiny. Here we investigated whether facial expressions of different basic emotions modulate the functional connectivity of the amygdala with the rest of the brain. To this end, we presented seventeen healthy participants (8 females) with facial expressions of anger, disgust, fear, happiness, sadness and emotional neutrality and analyzed amygdala's psychophysiological interaction (PPI). In fact, PPI can reveal how inter-regional amygdala communications change dynamically depending on perception of various emotional expressions to recruit different brain networks, compared to the functional interactions it entertains during perception of neutral expressions. We found that for each emotion the amygdala recruited a distinctive and spatially distributed set of structures to interact with. These changes in amygdala connectional patters characterize the dynamic signature prototypical of individual emotion processing, and seemingly represent a neural mechanism that serves to implement the distinctive influence that each emotion exerts on perceptual, cognitive, and motor responses. Besides these differences, all emotions enhanced amygdala functional integration with premotor cortices compared to neutral faces. The present findings thus concur to reconceptualise the structure-function relation between brain-emotion from the traditional one-to-one mapping toward a network-based and dynamic perspective.

  5. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

    Directory of Open Access Journals (Sweden)

    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  6. Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos.

    Science.gov (United States)

    Raisch, Tobias; Bhandari, Dipankar; Sabath, Kevin; Helms, Sigrun; Valkov, Eugene; Weichenrieder, Oliver; Izaurralde, Elisa

    2016-05-02

    Nanos proteins repress the expression of target mRNAs by recruiting effector complexes through non-conserved N-terminal regions. In vertebrates, Nanos proteins interact with the NOT1 subunit of the CCR4-NOT effector complex through a NOT1 interacting motif (NIM), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR4-NOT deadenylase complex in invertebrates. Here, we identify an effector domain (NED) that is necessary for the Drosophila melanogaster (Dm) Nanos to repress mRNA targets. The NED recruits the CCR4-NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C-terminal domains of NOT1-3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT1 and NOT3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N-terminal regions of Nanos proteins recruit CCR4-NOT to assemble analogous repressive complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  7. Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis.

    Science.gov (United States)

    Zheng, Wenning; Tan, Mui Fern; Old, Lesley A; Paterson, Ian C; Jakubovics, Nicholas S; Choo, Siew Woh

    2017-06-07

    Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virulence genes. However, we observed subtle differences in genomic islands and prophages between the species. Comparative pathogenomics analysis identified S. sanguinis strains have genes encoding IgA proteases, mitogenic factor deoxyribonucleases, nickel/cobalt uptake and cobalamin biosynthesis. On the contrary, genomic islands of S. gordonii strains contain additional copies of comCDE quorum-sensing system components involved in genetic competence. Two distinct polysaccharide locus architectures were identified, one of which was exclusively present in S. gordonii strains. The first evidence of genes encoding the CylA and CylB system by the α-haemolytic S. gordonii is presented. This study provides new insights into the genetic distinctions between S. gordonii and S. sanguinis, which yields understanding of tooth surfaces colonization and contributions to dental plaque formation, as well as their potential roles in the pathogenesis of IE.

  8. Two independent modes of chromatin organization revealed by cohesin removal.

    Science.gov (United States)

    Schwarzer, Wibke; Abdennur, Nezar; Goloborodko, Anton; Pekowska, Aleksandra; Fudenberg, Geoffrey; Loe-Mie, Yann; Fonseca, Nuno A; Huber, Wolfgang; H Haering, Christian; Mirny, Leonid; Spitz, Francois

    2017-11-02

    Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.

  9. Expression of cytokeratins in odontogenic jaw cysts: monoclonal antibodies reveal distinct variation between different cyst types.

    Science.gov (United States)

    Hormia, M; Ylipaavalniemi, P; Nagle, R B; Virtanen, I

    1987-08-01

    Immunostaining with monoclonal antibodies was used to study and compare the cytokeratin content of odontogenic cysts and normal gingival epithelium. Two monoclonal antibodies, PKK2 and KA1, stained the whole epithelium in all cyst samples. In gingiva, PKK2 gave a suprabasal staining and KA1 reacted with all epithelial cell layers. Antibodies PKK1, KM 4.62 and KS 8.12 gave a heterogeneous staining in follicular and radicular cysts. In keratocysts and in gingiva PKK1 and KM 4.62 reacted mainly with basal cells and KS 8.12 gave a suprabasal staining. Antibodies reacting with the simple epithelial cytokeratin polypeptide No. 18 (PKK3, KS 18.18) recognized in gingiva only solitary cells compatible with Merkel cells. In a case of follicular ameloblastoma a distinct staining of tumor epithelium was revealed with these antibodies. In 2 follicular cysts, but not in other cyst types, a layer of cytokeratin 18-positive cells was revealed. KA5 and KK 8.60 antibodies, reacting exclusively with keratinizing epithelia, including normal gingiva, gave no reaction in radicular cysts, keratocysts and ameloblastoma. Two of the follicular cysts, were negative for PKK3 and KS 18.18, but reacted strongly with KA5 and KK 8.60. The present results show that odontogenic jaw cysts have distinct differences in their cytokeratin content. With the exception of some follicular cysts, they lack signs of keratinizing epithelial differentiation. Only follicular cysts appear to share with some types of ameloblastoma the expression of cytokeratin polypeptide No. 18.

  10. Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission.

    Science.gov (United States)

    Xu, Wei; Morishita, Wade; Buckmaster, Paul S; Pang, Zhiping P; Malenka, Robert C; Südhof, Thomas C

    2012-03-08

    Neurons encode information by firing spikes in isolation or bursts and propagate information by spike-triggered neurotransmitter release that initiates synaptic transmission. Isolated spikes trigger neurotransmitter release unreliably but with high temporal precision. In contrast, bursts of spikes trigger neurotransmission reliably (i.e., boost transmission fidelity), but the resulting synaptic responses are temporally imprecise. However, the relative physiological importance of different spike-firing modes remains unclear. Here, we show that knockdown of synaptotagmin-1, the major Ca(2+) sensor for neurotransmitter release, abrogated neurotransmission evoked by isolated spikes but only delayed, without abolishing, neurotransmission evoked by bursts of spikes. Nevertheless, knockdown of synaptotagmin-1 in the hippocampal CA1 region did not impede acquisition of recent contextual fear memories, although it did impair the precision of such memories. In contrast, knockdown of synaptotagmin-1 in the prefrontal cortex impaired all remote fear memories. These results indicate that different brain circuits and types of memory employ distinct spike-coding schemes to encode and transmit information. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

    Science.gov (United States)

    Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

    2017-01-01

    Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88

  12. Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

    Science.gov (United States)

    Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

    2015-01-01

    Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

  13. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    International Nuclear Information System (INIS)

    Ang, Pei Woon; Soong, Richie; Loh, Marie; Liem, Natalia; Lim, Pei Li; Grieu, Fabienne; Vaithilingam, Aparna; Platell, Cameron; Yong, Wei Peng; Iacopetta, Barry

    2010-01-01

    Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate ® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

  14. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    Directory of Open Access Journals (Sweden)

    Vaithilingam Aparna

    2010-05-01

    Full Text Available Abstract Background Most previous studies of the CpG island methylator phenotype (CIMP in colorectal cancer (CRC have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. Methods DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI, methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. Results A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases, CIMP-mid (CIMP-M, 14% and CIMP-high (CIMP-H, 65%. In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P Conclusions Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

  15. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

    Energy Technology Data Exchange (ETDEWEB)

    Jager, Tjalling [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)]. E-mail: tjalling@bio.vu.nl; Crommentuijn, Trudie [Ministry of Spatial Planning, Housing and the Environment (VROM), Rijnstraat 8, P.O. Box 30945, 2500 GX, The Hague (Netherlands); Gestel, Cornelis A.M. van [Department of Animal Ecology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands); Kooijman, Sebastiaan A.L.M. [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)

    2007-01-15

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms.

  16. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

    International Nuclear Information System (INIS)

    Jager, Tjalling; Crommentuijn, Trudie; Gestel, Cornelis A.M. van; Kooijman, Sebastiaan A.L.M.

    2007-01-01

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms

  17. The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

    2016-01-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  18. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  19. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    Science.gov (United States)

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies.

  20. Two distinct modes of RecA action are required for DNA polymerase V-catalyzed translesion synthesis.

    Science.gov (United States)

    Pham, Phuong; Seitz, Erica M; Saveliev, Sergei; Shen, Xuan; Woodgate, Roger; Cox, Michael M; Goodman, Myron F

    2002-08-20

    SOS mutagenesis in Escherichia coli requires DNA polymerase V (pol V) and RecA protein to copy damaged DNA templates. Here we show that two distinct biochemical modes for RecA protein are necessary for pol V-catalyzed translesion synthesis. One RecA mode is characterized by a strong stimulation in nucleotide incorporation either directly opposite a lesion or at undamaged template sites, but by the absence of lesion bypass. A separate RecA mode is necessary for translesion synthesis. The RecA1730 mutant protein, which was identified on the basis of its inability to promote pol V (UmuD'(2)C)-dependent UV-mutagenesis, appears proficient for the first mode of RecA action but is deficient in the second mode. Data are presented suggesting that the two RecA modes are "nonfilamentous". That is, contrary to current models for SOS mutagenesis, formation of a RecA nucleoprotein filament may not be required for copying damaged DNA templates. Instead, SOS mutagenesis occurs when pol V interacts with two RecA molecules, first at a 3' primer end, upstream of a template lesion, where RecA mode 1 stimulates pol V activity, and subsequently at a site immediately downstream of the lesion, where RecA mode 2 cocatalyzes lesion bypass. We posit that in vivo assembly of a RecA nucleoprotein filament may be required principally to target pol V to a site of DNA damage and to stabilize the pol V-RecA interaction at the lesion. However, it is only a RecA molecule located at the 3' filament tip, proximal to a damaged template base, that is directly responsible for translesion synthesis.

  1. Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications.

    Directory of Open Access Journals (Sweden)

    Jose L Ortega Roldan

    Full Text Available SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination.

  2. Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes

    Energy Technology Data Exchange (ETDEWEB)

    Dahms, Sven O., E-mail: sdahms@fli-leibniz.de [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany); Mayer, Magnus C. [Freie Universität Berlin, Thielallee 63, 14195 Berlin (Germany); Miltenyi Biotec GmbH, Robert-Koch-Strasse 1, 17166 Teterow (Germany); Roeser, Dirk [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany); Multhaup, Gerd [McGill University Montreal, Montreal, Quebec H3G 1Y6 (Canada); Than, Manuel E., E-mail: sdahms@fli-leibniz.de [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany)

    2015-03-01

    Two X-ray structures of APLP1 E2 with and without a heparin dodecasaccharide are presented, revealing two distinct binding modes of the protein to heparan sulfate. The data provide a mechanistic explanation of how APP-like proteins bind to heparan sulfates and how they specifically recognize nonreducing structures of heparan sulfates. Beyond the pathology of Alzheimer’s disease, the members of the amyloid precursor protein (APP) family are essential for neuronal development and cell homeostasis in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding domain E2, which effects various (patho)physiological functions. Here, two crystal structures of the E2 domain of APLP1 are presented in the apo form and in complex with a heparin dodecasaccharide at 2.5 Å resolution. The apo structure of APLP1 E2 revealed an unfolded and hence flexible N-terminal helix αA. The (APLP1 E2){sub 2}–(heparin){sub 2} complex structure revealed two distinct binding modes, with APLP1 E2 explicitly recognizing the heparin terminus but also interacting with a continuous heparin chain. The latter only requires a certain register of the sugar moieties that fits to a positively charged surface patch and contributes to the general heparin-binding capability of APP-family proteins. Terminal binding of APLP1 E2 to heparin specifically involves a structure of the nonreducing end that is very similar to heparanase-processed HS chains. These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins.

  3. Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties

    Science.gov (United States)

    Nguyen, Leonard T.; Vogel, Hans J.

    2016-01-01

    Staphylokinase (Sak) is a plasminogen activator protein that is secreted by many Staphylococcus aureus strains. Sak also offers protection by binding and inhibiting specific antimicrobial peptides (AMPs). Here, we evaluate Sak as a more general interaction partner for AMPs. Studies with melittin, mCRAMP, tritrpticin and bovine lactoferricin indicate that the truncation of the first ten residues of Sak (SakΔN10), which occurs in vivo and uncovers important residues in a bulge region, improves its affinity for AMPs. Melittin and mCRAMP have a lower affinity for SakΔN10, and in docking studies, they bind to the N-terminal segment and bulge region of SakΔN10. By comparison, lactoferricin and tritrpticin form moderately high affinity 1:1 complexes with SakΔN10 and their cationic residues form several electrostatic interactions with the protein’s α-helix. Overall, our work identifies two distinct AMP binding surfaces on SakΔN10 whose occupation would lead to either inhibition or promotion of its plasminogen activating properties. PMID:27554435

  4. Laboratory-Cultured Strains of the Sea Anemone Exaiptasia Reveal Distinct Bacterial Communities

    KAUST Repository

    Herrera Sarrias, Marcela; Ziegler, Maren; Voolstra, Christian R.; Aranda, Manuel

    2017-01-01

    Exaiptasia is a laboratory sea anemone model system for stony corals. Two clonal strains are commonly used, referred to as H2 and CC7, that originate from two genetically distinct lineages and that differ in their Symbiodinium specificity. However, little is known about their other microbial associations. Here, we examined and compared the taxonomic composition of the bacterial assemblages of these two symbiotic Exaiptasia strains, both of which have been cultured in the laboratory long-term under identical conditions. We found distinct bacterial microbiota for each strain, indicating the presence of host-specific microbial consortia. Putative differences in the bacterial functional profiles (i.e., enrichment and depletion of various metabolic processes) based on taxonomic inference were also detected, further suggesting functional differences of the microbiomes associated with these lineages. Our study contributes to the current knowledge of the Exaiptasia holobiont by comparing the bacterial diversity of two commonly used strains as models for coral research.

  5. Laboratory-Cultured Strains of the Sea Anemone Exaiptasia Reveal Distinct Bacterial Communities

    KAUST Repository

    Herrera Sarrias, Marcela

    2017-05-02

    Exaiptasia is a laboratory sea anemone model system for stony corals. Two clonal strains are commonly used, referred to as H2 and CC7, that originate from two genetically distinct lineages and that differ in their Symbiodinium specificity. However, little is known about their other microbial associations. Here, we examined and compared the taxonomic composition of the bacterial assemblages of these two symbiotic Exaiptasia strains, both of which have been cultured in the laboratory long-term under identical conditions. We found distinct bacterial microbiota for each strain, indicating the presence of host-specific microbial consortia. Putative differences in the bacterial functional profiles (i.e., enrichment and depletion of various metabolic processes) based on taxonomic inference were also detected, further suggesting functional differences of the microbiomes associated with these lineages. Our study contributes to the current knowledge of the Exaiptasia holobiont by comparing the bacterial diversity of two commonly used strains as models for coral research.

  6. NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma

    OpenAIRE

    Rocha, CM; Barros, AS; Goodfellow, BJ; Carreira, IM; Gomes, AA; Sousa, V; Bernardo, J; Carvalho, L; Gil, AM; Duarte, IF

    2015-01-01

    Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissue...

  7. Genomic analyses of breast cancer progression reveal distinct routes of metastasis emergence

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Brasch-Andersen, Charlotte

    2017-01-01

    receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound...... clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis....

  8. Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.

    Science.gov (United States)

    Montefusco, David J; Chen, Lujia; Matmati, Nabil; Lu, Songjian; Newcomb, Benjamin; Cooper, Gregory F; Hannun, Yusuf A; Lu, Xinghua

    2013-10-29

    Ceramide, the central molecule of sphingolipid metabolism, is an important bioactive molecule that participates in various cellular regulatory events and that has been implicated in disease. Deciphering ceramide signaling is challenging because multiple ceramide species exist, and many of them may have distinct functions. We applied systems biology and molecular approaches to perturb ceramide metabolism in the yeast Saccharomyces cerevisiae and inferred causal relationships between ceramide species and their potential targets by combining lipidomic, genomic, and transcriptomic analyses. We found that during heat stress, distinct metabolic mechanisms controlled the abundance of different groups of ceramide species and provided experimental support for the importance of the dihydroceramidase Ydc1 in mediating the decrease in dihydroceramides during heat stress. Additionally, distinct groups of ceramide species, with different N-acyl chains and hydroxylations, regulated different sets of functionally related genes, indicating that the structural complexity of these lipids produces functional diversity. The transcriptional modules that we identified provide a resource to begin to dissect the specific functions of ceramides.

  9. Viromes of one year old infants reveal the impact of birth mode on microbiome diversity.

    LENUS (Irish Health Repository)

    McCann, Angela

    2018-05-01

    Establishing a diverse gut microbiota after birth is being increasingly recognised as important for preventing illnesses later in life. It is well established that bacterial diversity rapidly increases post-partum; however, few studies have examined the infant gut virome\\/phageome during this developmental period. We performed a metagenomic analysis of 20 infant faecal viromes at one year of age to determine whether spontaneous vaginal delivery (SVD) or caesarean section (CS) influenced viral composition. We find that birth mode results in distinctly different viral communities, with SVD infants having greater viral and bacteriophage diversity. We demonstrate that CrAssphage is acquired early in life, both in this cohort and two others, although no difference in birth mode is detected. A previous study has shown that bacterial OTU\\'s (operational taxonomic units) identified in the same infants could not discriminate between birth mode at 12 months of age. Therefore, our results indicate that vertical transmission of viral communities from mother to child may play a role in shaping the early life microbiome, and that birth mode should be considered when studying the early life gut virome.

  10. Viromes of one year old infants reveal the impact of birth mode on microbiome diversity

    Directory of Open Access Journals (Sweden)

    Angela McCann

    2018-05-01

    Full Text Available Establishing a diverse gut microbiota after birth is being increasingly recognised as important for preventing illnesses later in life. It is well established that bacterial diversity rapidly increases post-partum; however, few studies have examined the infant gut virome/phageome during this developmental period. We performed a metagenomic analysis of 20 infant faecal viromes at one year of age to determine whether spontaneous vaginal delivery (SVD or caesarean section (CS influenced viral composition. We find that birth mode results in distinctly different viral communities, with SVD infants having greater viral and bacteriophage diversity. We demonstrate that CrAssphage is acquired early in life, both in this cohort and two others, although no difference in birth mode is detected. A previous study has shown that bacterial OTU’s (operational taxonomic units identified in the same infants could not discriminate between birth mode at 12 months of age. Therefore, our results indicate that vertical transmission of viral communities from mother to child may play a role in shaping the early life microbiome, and that birth mode should be considered when studying the early life gut virome.

  11. Microstructure of atmospheric particles revealed by TXM and a new mode of influenza virus transmission

    Energy Technology Data Exchange (ETDEWEB)

    Bao, L.M., E-mail: baoliangman@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhang, G.L., E-mail: zhangguilin@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Lei, Q.T.; Li, Y.; Li, X.L. [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Hwu, Y.K. [Institute of Physics, Academia Sinica, Taipei 11529, Taiwan (China); Yi, J.M. [Advanced Photon Source, Argonne National Laboratory, Argonne 60439 (United States)

    2015-09-15

    For control of influenza, firstly it is important to find the real virus transmission media. Atmospheric aerosol particles are presumably one of the media. In this study, three typical atmospheric inhaled particles in Shanghai were studied by the synchrotron based transmission X-ray microscopes (TXM). Three dimensional microstructure of the particles reveals that there are many pores contained in, particularly the coal combustion fly particles which may be possible virus carrier. The particles can transport over long distance and cause long-range infections due to its light weight. We suggest a mode which is droplet combining with aerosol mode. By this mode the transmission of global and pandemic influenzas and infection between inland avian far from population and poultry or human living in cities along coast may be explained.

  12. Reconstructing dynamic mental models of facial expressions in prosopagnosia reveals distinct representations for identity and expression.

    Science.gov (United States)

    Richoz, Anne-Raphaëlle; Jack, Rachael E; Garrod, Oliver G B; Schyns, Philippe G; Caldara, Roberto

    2015-04-01

    The human face transmits a wealth of signals that readily provide crucial information for social interactions, such as facial identity and emotional expression. Yet, a fundamental question remains unresolved: does the face information for identity and emotional expression categorization tap into common or distinct representational systems? To address this question we tested PS, a pure case of acquired prosopagnosia with bilateral occipitotemporal lesions anatomically sparing the regions that are assumed to contribute to facial expression (de)coding (i.e., the amygdala, the insula and the posterior superior temporal sulcus--pSTS). We previously demonstrated that PS does not use information from the eye region to identify faces, but relies on the suboptimal mouth region. PS's abnormal information use for identity, coupled with her neural dissociation, provides a unique opportunity to probe the existence of a dichotomy in the face representational system. To reconstruct the mental models of the six basic facial expressions of emotion in PS and age-matched healthy observers, we used a novel reverse correlation technique tracking information use on dynamic faces. PS was comparable to controls, using all facial features to (de)code facial expressions with the exception of fear. PS's normal (de)coding of dynamic facial expressions suggests that the face system relies either on distinct representational systems for identity and expression, or dissociable cortical pathways to access them. Interestingly, PS showed a selective impairment for categorizing many static facial expressions, which could be accounted for by her lesion in the right inferior occipital gyrus. PS's advantage for dynamic facial expressions might instead relate to a functionally distinct and sufficient cortical pathway directly connecting the early visual cortex to the spared pSTS. Altogether, our data provide critical insights on the healthy and impaired face systems, question evidence of deficits

  13. An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes.

    Directory of Open Access Journals (Sweden)

    Katrin Kremer

    2013-03-01

    Full Text Available The basic organisation of the endomembrane system is conserved in all eukaryotes and comparative genome analyses provides compelling evidence that the endomembrane system of the last common eukaryotic ancestor (LCEA is complex with many genes required for regulated traffic being present. Although apicomplexan parasites, causative agents of severe human and animal diseases, appear to have only a basic set of trafficking factors such as Rab-GTPases, they evolved unique secretory organelles (micronemes, rhoptries and dense granules that are sequentially secreted during invasion of the host cell. In order to define the secretory pathway of apicomplexans, we performed an overexpression screen of Rabs in Toxoplasma gondii and identified Rab5A and Rab5C as important regulators of traffic to micronemes and rhoptries. Intriguingly, we found that not all microneme proteins traffic depends on functional Rab5A and Rab5C, indicating the existence of redundant microneme targeting pathways. Using two-colour super-resolution stimulated emission depletion (STED we verified distinct localisations of independent microneme proteins and demonstrate that micronemal organelles are organised in distinct subsets or subcompartments. Our results suggest that apicomplexan parasites modify classical regulators of the endocytic system to carryout essential parasite-specific roles in the biogenesis of their unique secretory organelles.

  14. Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

    Science.gov (United States)

    Johnston, Josiah; Iser, Wendy B; Chow, David K; Goldberg, Ilya G; Wolkow, Catherine A

    2008-07-30

    Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

  15. The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

    Science.gov (United States)

    Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

    2014-10-07

    Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Revealing spatio-spectral electroencephalographic dynamics of musical mode and tempo perception by independent component analysis.

    Science.gov (United States)

    Lin, Yuan-Pin; Duann, Jeng-Ren; Feng, Wenfeng; Chen, Jyh-Horng; Jung, Tzyy-Ping

    2014-02-28

    Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Empirical results showed that music with major mode augmented delta-band activity over the right sensorimotor cortex, suppressed theta activity over the superior parietal cortex, and moderately suppressed beta activity over the medial frontal cortex, compared to minor-mode music, whereas fast-tempo music engaged significant alpha suppression over the right sensorimotor cortex. The resultant EEG brain sources were comparable with previous studies obtained by other neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In conjunction with advanced dry and mobile EEG technology, the EEG results might facilitate the translation from laboratory-oriented research to real-life applications for music therapy, training and entertainment in naturalistic environments.

  17. Identifying Two Groups of Entitled Individuals: Cluster Analysis Reveals Emotional Stability and Self-Esteem Distinction.

    Science.gov (United States)

    Crowe, Michael L; LoPilato, Alexander C; Campbell, W Keith; Miller, Joshua D

    2016-12-01

    The present study hypothesized that there exist two distinct groups of entitled individuals: grandiose-entitled, and vulnerable-entitled. Self-report scores of entitlement were collected for 916 individuals using an online platform. Model-based cluster analyses were conducted on the individuals with scores one standard deviation above mean (n = 159) using the five-factor model dimensions as clustering variables. The results support the existence of two groups of entitled individuals categorized as emotionally stable and emotionally vulnerable. The emotionally stable cluster reported emotional stability, high self-esteem, more positive affect, and antisocial behavior. The emotionally vulnerable cluster reported low self-esteem and high levels of neuroticism, disinhibition, conventionality, psychopathy, negative affect, childhood abuse, intrusive parenting, and attachment difficulties. Compared to the control group, both clusters reported being more antagonistic, extraverted, Machiavellian, and narcissistic. These results suggest important differences are missed when simply examining the linear relationships between entitlement and various aspects of its nomological network.

  18. Complete sequence analysis reveals two distinct poleroviruses infecting cucurbits in China.

    Science.gov (United States)

    Xiang, Hai-ying; Shang, Qiao-xia; Han, Cheng-gui; Li, Da-wei; Yu, Jia-lin

    2008-01-01

    The complete RNA genomes of a Chinese isolate of cucurbit aphid-borne yellows virus (CABYV-CHN) and a new polerovirus tentatively referred to as melon aphid-borne yellows virus (MABYV) were determined. The entire genome of CABYV-CHN shared 89.0% nucleotide sequence identity with the French CABYV isolate. In contrast, nucleotide sequence identities between MABYV and CABYV and other poleroviruses were in the range of 50.7-74.2%, with amino acid sequence identities ranging from 24.8 to 82.9% for individual gene products. We propose that CABYV-CHN is a strain of CABYV and that MABYV is a member of a tentative distinct species within the genus Polerovirus.

  19. Distinctive anatomical and physiological features of migraine aura revealed by 18 years of recording

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Baca, Serapio Michael; Vanvalkenburgh, Paul

    2013-01-01

    insight into basic aura mechanisms. An individual made detailed drawings of his visual percept of migraine aura in real time during more than 1000 attacks of migraine aura without headache over 18 years. Drawings were made in a consistent fashion documenting the shape and location of the aura wavefront...... originated centrally (within 10° eccentricity), but there were also other distinct sites of initiation in the visual field. Auras beginning centrally preferentially propagated first through lower nasal field (69-77% of all auras) before travelling to upper and temporal fields, on both sides. Some auras...... propagated from peripheral to central regions of the visual field-these typically followed the reverse path of those travelling in the opposite direction. The mean velocity of the perceived visual phenomenon did not differ between attacks starting peripherally and centrally. The estimated speed...

  20. Physical versus psychological social stress in male rats reveals distinct cardiovascular, inflammatory and behavioral consequences

    Science.gov (United States)

    Padi, Akhila R.; Moffitt, Casey M.; Wilson, L. Britt; Wood, Christopher S.; Wood, Susan K.

    2017-01-01

    Repeated exposure to social stress can precipitate the development of psychosocial disorders including depression and comorbid cardiovascular disease. While a major component of social stress often encompasses physical interactions, purely psychological stressors (i.e. witnessing a traumatic event) also fall under the scope of social stress. The current study determined whether the acute stress response and susceptibility to stress-related consequences differed based on whether the stressor consisted of physical versus purely psychological social stress. Using a modified resident-intruder paradigm, male rats were either directly exposed to repeated social defeat stress (intruder) or witnessed a male rat being defeated. Cardiovascular parameters, behavioral anhedonia, and inflammatory cytokines in plasma and the stress-sensitive locus coeruleus were compared between intruder, witness, and control rats. Surprisingly intruders and witnesses exhibited nearly identical increases in mean arterial pressure and heart rate during acute and repeated stress exposures, yet only intruders exhibited stress-induced arrhythmias. Furthermore, re-exposure to the stress environment in the absence of the resident produced robust pressor and tachycardic responses in both stress conditions indicating the robust and enduring nature of social stress. In contrast, the long-term consequences of these stressors were distinct. Intruders were characterized by enhanced inflammatory sensitivity in plasma, while witnesses were characterized by the emergence of depressive-like anhedonia, transient increases in systolic blood pressure and plasma levels of tissue inhibitor of metalloproteinase. The current study highlights that while the acute cardiovascular responses to stress were identical between intruders and witnesses, these stressors produced distinct differences in the enduring consequences to stress, suggesting that witness stress may be more likely to produce long-term cardiovascular

  1. Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

    Directory of Open Access Journals (Sweden)

    Josiah Johnston

    2008-07-01

    Full Text Available Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

  2. Phylogenetic variation of Aggregatibacter actinomycetemcomitans serotype e reveals an aberrant distinct evolutionary stable lineage

    NARCIS (Netherlands)

    van der Reijden, Wil A.; Brunner, Jorg; Bosch-Tijhof, Carolien J.; van Trappen, Stefanie; Rijnsburger, Martine C.; de Graaff, Marcel P. W.; van Winkelhoff, Arie J.; Cleenwerck, Ilse; de Vos, Paul

    2010-01-01

    The periodontal pathogen Aggregatibacter actinomycetemcomitans that comprises six serotypes (a-f), is often identified by PCR-based techniques targeting the 16S rRNA gene. In this study, 16S rRNA gene sequence analysis revealed an aberrant cluster of 19 strains within serotype e, denoted as serotype

  3. Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis

    OpenAIRE

    Zheng, Wenning; Tan, Mui Fern; Old, Lesley A.; Paterson, Ian C.; Jakubovics, Nicholas S.; Choo, Siew Woh

    2017-01-01

    Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virule...

  4. Internal Transcribed Spacer 1 (ITS1 based sequence typing reveals phylogenetically distinct Ascaris population

    Directory of Open Access Journals (Sweden)

    Koushik Das

    2015-01-01

    Full Text Available Taxonomic differentiation among morphologically identical Ascaris species is a debatable scientific issue in the context of Ascariasis epidemiology. To explain the disease epidemiology and also the taxonomic position of different Ascaris species, genome information of infecting strains from endemic areas throughout the world is certainly crucial. Ascaris population from human has been genetically characterized based on the widely used genetic marker, internal transcribed spacer1 (ITS1. Along with previously reported and prevalent genotype G1, 8 new sequence variants of ITS1 have been identified. Genotype G1 was significantly present among female patients aged between 10 to 15 years. Intragenic linkage disequilibrium (LD analysis at target locus within our study population has identified an incomplete LD value with potential recombination events. A separate cluster of Indian isolates with high bootstrap value indicate their distinct phylogenetic position in comparison to the global Ascaris population. Genetic shuffling through recombination could be a possible reason for high population diversity and frequent emergence of new sequence variants, identified in present and other previous studies. This study explores the genetic organization of Indian Ascaris population for the first time which certainly includes some fundamental information on the molecular epidemiology of Ascariasis.

  5. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  6. Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer.

    Science.gov (United States)

    Kim, Jung H; Dhanasekaran, Saravana M; Prensner, John R; Cao, Xuhong; Robinson, Daniel; Kalyana-Sundaram, Shanker; Huang, Christina; Shankar, Sunita; Jing, Xiaojun; Iyer, Matthew; Hu, Ming; Sam, Lee; Grasso, Catherine; Maher, Christopher A; Palanisamy, Nallasivam; Mehra, Rohit; Kominsky, Hal D; Siddiqui, Javed; Yu, Jindan; Qin, Zhaohui S; Chinnaiyan, Arul M

    2011-07-01

    Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in select prostate tissues and cell lines using MethylPlex-next-generation sequencing (M-NGS). Hidden Markov model-based next-generation sequence analysis identified ∼68,000 methylated regions per sample. While global CpG island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation significantly increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively (P-value prostate tissues, 2481 differentially methylated regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer-specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization, and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and we confirmed this observation using pyrosequencing on a tissue panel. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.

  7. Molecular phylogenetics of the genus Costularia (Schoeneae, Cyperaceae) reveals multiple distinct evolutionary lineages.

    Science.gov (United States)

    Larridon, Isabel; Bauters, Kenneth; Semmouri, Ilias; Viljoen, Jan-Adriaan; Prychid, Christina J; Muasya, A Muthama; Bruhl, Jeremy J; Wilson, Karen L; Senterre, Bruno; Goetghebeur, Paul

    2018-04-19

    We investigated the monophyly of Costularia (25 species), a genus of tribe Schoeneae (Cyperaceae) that illustrates a remarkable distribution pattern from southeastern Africa, over Madagascar, the Mascarenes and Seychelles, to Malesia and New Caledonia. A further species, Tetraria borneensis, has been suggested to belong to Costularia. Relationships and divergence times were inferred using an existing four marker phylogeny of Cyperaceae tribe Schoeneae expanded with newly generated sequence data mainly for Costularia s.l. species. Phylogenetic reconstruction was executed using Bayesian inference and maximum likelihood approaches. Divergence times were estimated using a relaxed molecular clock model, calibrated with fossil data. Based on our results, Tetraria borneensis is not related to the species of Costularia. Costularia s.l. is composed of four distinct evolutionary lineages. Two lineages, one including the type species, are part of the Oreobolus clade, i.e. a much reduced genus Costularia restricted to southeastern Africa, Madagascar, the Mascarenes and Seychelles, and a small endemic genus from New Caledonia for which a new genus Chamaedendron is erected based on Costularia subgenus Chamaedendron. The other two lineages are part of the Tricostularia clade, i.e. a separate single-species lineage from the Seychelles for which a new genus (Xyroschoenus) is described, and Costularia subgenus Lophoschoenus. For the latter, more research is needed to test whether they are congeneric with the species placed in the reticulate-sheathed Tetraria clade. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias

    Science.gov (United States)

    Calin, George Adrian; Liu, Chang-Gong; Sevignani, Cinzia; Ferracin, Manuela; Felli, Nadia; Dumitru, Calin Dan; Shimizu, Masayoshi; Cimmino, Amelia; Zupo, Simona; Dono, Mariella; Dell'Aquila, Marie L.; Alder, Hansjuerg; Rassenti, Laura; Kipps, Thomas J.; Bullrich, Florencia; Negrini, Massimo; Croce, Carlo M.

    2004-01-01

    Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673–676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253–258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia. PMID:15284443

  9. Mass Spectrometry-Based Quantitative Metabolomics Revealed a Distinct Lipid Profile in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yun Yen

    2013-04-01

    Full Text Available Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2 successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.

  10. A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

    Science.gov (United States)

    Ferrando, A; Manunza, A; Jordana, J; Capote, J; Pons, A; Pais, J; Delgado, T; Atoche, P; Cabrera, B; Martínez, A; Landi, V; Delgado, J V; Argüello, A; Vidal, O; Lalueza-Fox, C; Ramírez, O; Amills, M

    2015-08-01

    In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. © 2015 Stichting International Foundation for Animal Genetics.

  11. Motor learning in childhood reveals distinct mechanisms for memory retention and re-learning.

    Science.gov (United States)

    Musselman, Kristin E; Roemmich, Ryan T; Garrett, Ben; Bastian, Amy J

    2016-05-01

    Adults can easily learn and access multiple versions of the same motor skill adapted for different conditions (e.g., walking in water, sand, snow). Following even a single session of adaptation, adults exhibit clear day-to-day retention and faster re-learning of the adapted pattern. Here, we studied the retention and re-learning of an adapted walking pattern in children aged 6-17 yr. We found that all children, regardless of age, showed adult-like patterns of retention of the adapted walking pattern. In contrast, children under 12 yr of age did not re-learn faster on the next day after washout had occurred-they behaved as if they had never adapted their walking before. Re-learning could be improved in younger children when the adaptation time on day 1 was increased to allow more practice at the plateau of the adapted pattern, but never to adult-like levels. These results show that the ability to store a separate, adapted version of the same general motor pattern does not fully develop until adolescence, and furthermore, that the mechanisms underlying the retention and rapid re-learning of adapted motor patterns are distinct. © 2016 Musselman et al.; Published by Cold Spring Harbor Laboratory Press.

  12. Gene expression profiling reveals distinct molecular signatures associated with the rupture of intracranial aneurysm.

    Science.gov (United States)

    Nakaoka, Hirofumi; Tajima, Atsushi; Yoneyama, Taku; Hosomichi, Kazuyoshi; Kasuya, Hidetoshi; Mizutani, Tohru; Inoue, Ituro

    2014-08-01

    The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10 superficial temporal arteries with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns, using clustering methods. The clustering analysis identified 4 groups: superficial temporal arteries and unruptured IAs were aggregated into their own clusters, whereas RIAs segregated into 2 distinct subgroups (early and late RIAs). Comparing gene expression levels between early RIAs and unruptured IAs, we identified 430 upregulated and 617 downregulated genes in early RIAs. The upregulated genes were associated with inflammatory and immune responses and phagocytosis including S100/calgranulin genes (S100A8, S100A9, and S100A12). The downregulated genes suggest mechanical weakness of aneurysm walls. The expressions of Krüppel-like family of transcription factors (KLF2, KLF12, and KLF15), which were anti-inflammatory regulators, and CDKN2A, which was located on chromosome 9p21 that was the most consistently replicated locus in genome-wide association studies of IA, were also downregulated. We demonstrate that gene expression patterns of RIAs were different according to the age of patients. The results suggest that macrophage-mediated inflammation is a key biological pathway for IA rupture. The identified genes can be good candidates for molecular markers of rupture-prone IAs and therapeutic targets. © 2014 American Heart Association, Inc.

  13. Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems

    Science.gov (United States)

    Hook, Vivian; Bandeira, Nuno

    2015-12-01

    Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human

  14. Comparative genome analyses reveal distinct structure in the saltwater crocodile MHC.

    Directory of Open Access Journals (Sweden)

    Weerachai Jaratlerdsiri

    Full Text Available The major histocompatibility complex (MHC is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.

  15. Quantitative proteomics and dynamic imaging of the nucleolus reveal distinct responses to UV and ionizing radiation.

    Science.gov (United States)

    Moore, Henna M; Bai, Baoyan; Boisvert, François-Michel; Latonen, Leena; Rantanen, Ville; Simpson, Jeremy C; Pepperkok, Rainer; Lamond, Angus I; Laiho, Marikki

    2011-10-01

    The nucleolus is a nuclear organelle that coordinates rRNA transcription and ribosome subunit biogenesis. Recent proteomic analyses have shown that the nucleolus contains proteins involved in cell cycle control, DNA processing and DNA damage response and repair, in addition to the many proteins connected with ribosome subunit production. Here we study the dynamics of nucleolar protein responses in cells exposed to stress and DNA damage caused by ionizing and ultraviolet (UV) radiation in diploid human fibroblasts. We show using a combination of imaging and quantitative proteomics methods that nucleolar substructure and the nucleolar proteome undergo selective reorganization in response to UV damage. The proteomic responses to UV include alterations of functional protein complexes such as the SSU processome and exosome, and paraspeckle proteins, involving both decreases and increases in steady state protein ratios, respectively. Several nonhomologous end-joining proteins (NHEJ), such as Ku70/80, display similar fast responses to UV. In contrast, nucleolar proteomic responses to IR are both temporally and spatially distinct from those caused by UV, and more limited in terms of magnitude. With the exception of the NHEJ and paraspeckle proteins, where IR induces rapid and transient changes within 15 min of the damage, IR does not alter the ratios of most other functional nucleolar protein complexes. The rapid transient decrease of NHEJ proteins in the nucleolus indicates that it may reflect a response to DNA damage. Our results underline that the nucleolus is a specific stress response organelle that responds to different damage and stress agents in a unique, damage-specific manner.

  16. The Crystal Structure of Streptococcus pyogenes Uridine Phosphorylase Reveals a Distinct Subfamily of Nucleoside Phosphorylases

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Timothy H.; Christoffersen, S.; Allan, Paula W.; Parker, William B.; Piskur, Jure; Serra, I.; Terreni, M.; Ealick, Steven E. (Cornell); (Pavia); (Lund); (Southern Research)

    2011-09-20

    Uridine phosphorylase (UP), a key enzyme in the pyrimidine salvage pathway, catalyzes the reversible phosphorolysis of uridine or 2'-deoxyuridine to uracil and ribose 1-phosphate or 2'-deoxyribose 1-phosphate. This enzyme belongs to the nucleoside phosphorylase I superfamily whose members show diverse specificity for nucleoside substrates. Phylogenetic analysis shows Streptococcus pyogenes uridine phosphorylase (SpUP) is found in a distinct branch of the pyrimidine subfamily of nucleoside phosphorylases. To further characterize SpUP, we determined the crystal structure in complex with the products, ribose 1-phosphate and uracil, at 1.8 {angstrom} resolution. Like Escherichia coli UP (EcUP), the biological unit of SpUP is a hexamer with an ?/? monomeric fold. A novel feature of the active site is the presence of His169, which structurally aligns with Arg168 of the EcUP structure. A second active site residue, Lys162, is not present in previously determined UP structures and interacts with O2 of uracil. Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is {approx}7-fold more efficient than SpUP. Biochemical studies of SpUP mutants showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that the negative charge in the transition state resides mostly on uracil O2. This is in contrast to EcUP for which transition state stabilization occurs mostly at O4.

  17. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors

    International Nuclear Information System (INIS)

    Amatruda, James F; Frazier, A Lindsay; Poynter, Jenny N; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh

    2013-01-01

    Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

  18. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W; Grubert, Fabian; Candille, Sophie I; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L; Tang, Hua; Ricci, Emiliano; Snyder, Michael P

    2015-11-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy--many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. © 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Comparative Plasmodium gene overexpression reveals distinct perturbation of sporozoite transmission by profilin.

    Science.gov (United States)

    Sato, Yuko; Hliscs, Marion; Dunst, Josefine; Goosmann, Christian; Brinkmann, Volker; Montagna, Georgina N; Matuschewski, Kai

    2016-07-15

    Plasmodium relies on actin-based motility to migrate from the site of infection and invade target cells. Using a substrate-dependent gliding locomotion, sporozoites are able to move at fast speed (1-3 μm/s). This motility relies on a minimal set of actin regulatory proteins and occurs in the absence of detectable filamentous actin (F-actin). Here we report an overexpression strategy to investigate whether perturbations of F-actin steady-state levels affect gliding locomotion and host invasion. We selected two vital Plasmodium berghei G-actin-binding proteins, C-CAP and profilin, in combination with three stage-specific promoters and mapped the phenotypes afforded by overexpression in all three extracellular motile stages. We show that in merozoites and ookinetes, additional expression does not impair life cycle progression. In marked contrast, overexpression of C-CAP and profilin in sporozoites impairs circular gliding motility and salivary gland invasion. The propensity for productive motility correlates with actin accumulation at the parasite tip, as revealed by combinations of an actin-stabilizing drug and transgenic parasites. Strong expression of profilin, but not C-CAP, resulted in complete life cycle arrest. Comparative overexpression is an alternative experimental genetic strategy to study essential genes and reveals effects of regulatory imbalances that are not uncovered from deletion-mutant phenotyping. © 2016 Sato et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  20. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

    Science.gov (United States)

    Yamagishi, Yuya; Tessier-Lavigne, Marc

    2015-01-01

    Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled

  1. Coevolved Mutations Reveal Distinct Architectures for Two Core Proteins in the Bacterial Flagellar Motor.

    Directory of Open Access Journals (Sweden)

    Alessandro Pandini

    Full Text Available Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM domains (amino-terminal (FliGN, middle (FliGM and FliGC as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6. FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM

  2. Comprehensive RNA Polymerase II Interactomes Reveal Distinct and Varied Roles for Each Phospho-CTD Residue

    Directory of Open Access Journals (Sweden)

    Kevin M. Harlen

    2016-06-01

    Full Text Available Transcription controls splicing and other gene regulatory processes, yet mechanisms remain obscure due to our fragmented knowledge of the molecular connections between the dynamically phosphorylated RNA polymerase II (Pol II C-terminal domain (CTD and regulatory factors. By systematically isolating phosphorylation states of the CTD heptapeptide repeat (Y1S2P3T4S5P6S7, we identify hundreds of protein factors that are differentially enriched, revealing unappreciated connections between the Pol II CTD and co-transcriptional processes. These data uncover a role for threonine-4 in 3′ end processing through control of the transition between cleavage and termination. Furthermore, serine-5 phosphorylation seeds spliceosomal assembly immediately downstream of 3′ splice sites through a direct interaction with spliceosomal subcomplex U1. Strikingly, threonine-4 phosphorylation also impacts splicing by serving as a mark of co-transcriptional spliceosome release and ensuring efficient post-transcriptional splicing genome-wide. Thus, comprehensive Pol II interactomes identify the complex and functional connections between transcription machinery and other gene regulatory complexes.

  3. Distinct Feedforward and Feedback Effects of Microstimulation in Visual Cortex Reveal Neural Mechanisms of Texture Segregation.

    Science.gov (United States)

    Klink, P Christiaan; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Roelfsema, Pieter R

    2017-07-05

    The visual cortex is hierarchically organized, with low-level areas coding for simple features and higher areas for complex ones. Feedforward and feedback connections propagate information between areas in opposite directions, but their functional roles are only partially understood. We used electrical microstimulation to perturb the propagation of neuronal activity between areas V1 and V4 in monkeys performing a texture-segregation task. In both areas, microstimulation locally caused a brief phase of excitation, followed by inhibition. Both these effects propagated faithfully in the feedforward direction from V1 to V4. Stimulation of V4, however, caused little V1 excitation, but it did yield a delayed suppression during the late phase of visually driven activity. This suppression was pronounced for the V1 figure representation and weaker for background representations. Our results reveal functional differences between feedforward and feedback processing in texture segregation and suggest a specific modulating role for feedback connections in perceptual organization. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

    Directory of Open Access Journals (Sweden)

    Eng Alvin KH

    2008-10-01

    Full Text Available Abstract Background Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. Methods Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides was used for validation. Results By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p Conclusion This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

  5. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  6. Phosphoproteomic dynamics of chickpea (Cicer arietinum L.) reveals shared and distinct components of dehydration response.

    Science.gov (United States)

    Subba, Pratigya; Barua, Pragya; Kumar, Rajiv; Datta, Asis; Soni, Kamlesh Kumar; Chakraborty, Subhra; Chakraborty, Niranjan

    2013-11-01

    Reversible protein phosphorylation is a ubiquitous regulatory mechanism that plays critical roles in transducing stress signals to bring about coordinated intracellular responses. To gain better understanding of dehydration response in plants, we have developed a differential phosphoproteome in a food legume, chickpea (Cicer arietinum L.). Three-week-old chickpea seedlings were subjected to progressive dehydration by withdrawing water, and the changes in the phosphorylation status of a large repertoire of proteins were monitored. The proteins were resolved by 2-DE and stained with phosphospecific fluorescent Pro-Q Diamond dye. Mass spectrometric analysis led to the identification of 91 putative phosphoproteins, presumably involved in a variety of functions including cell defense and rescue, photosynthesis and photorespiration, molecular chaperones, and ion transport, among others. Multiple sites of phosphorylation were predicted on several key elements, which include both the regulatory as well as the functional proteins. A critical survey of the phosphorylome revealed a DREPP (developmentally regulated plasma membrane protein) plasma membrane polypeptide family protein, henceforth designated CaDREPP1. The transcripts of CaDREPP1 were found to be differentially regulated under dehydration stress, further corroborating the proteomic results. This work provides new insights into the possible phosphorylation events triggered by the conditions of progressive water-deficit in plants.

  7. Next generation sequencing reveals distinct fecal pollution signatures in aquatic sediments across gradients of anthropogenic influence

    Directory of Open Access Journals (Sweden)

    Gian Marco Luna

    2016-11-01

    Full Text Available Aquatic sediments are the repository of a variety of anthropogenic pollutants, including bacteria of fecal origin, that reach the aquatic environment from a variety of sources. Although fecal bacteria can survive for long periods of time in aquatic sediments, the microbiological quality of sediments is almost entirely neglected when performing quality assessments of aquatic ecosystems. Here we investigated the relative abundance, patterns and diversity of fecal bacterial populations in two coastal areas in the Northern Adriatic Sea (Italy: the Po river prodelta (PRP, an estuarine area receiving significant contaminant discharge from one of the largest European rivers and the Lagoon of Venice (LV, a transitional environment impacted by a multitude of anthropogenic stressors. From both areas, several indicators of fecal and sewage contamination were determined in the sediments using Next Generation Sequencing (NGS of 16S rDNA amplicons. At both areas, fecal contamination was high, with fecal bacteria accounting for up to 3.96% and 1.12% of the sediment bacterial assemblages in PRP and LV, respectively. The magnitude of the fecal signature was highest in the PRP site, highlighting the major role of the Po river in spreading microbial contaminants into the adjacent coastal area. In the LV site, fecal pollution was highest in the urban area, and almost disappeared when moving to the open sea. Our analysis revealed a large number of fecal Operational Taxonomic Units (OTU, 960 and 181 in PRP and LV, respectively and showed a different fecal signature in the two areas, suggesting a diverse contribution of human and non-human sources of contamination. These results highlight the potential of NGS techniques to gain insights into the origin and fate of different fecal bacteria populations in aquatic sediments.

  8. Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder.

    Science.gov (United States)

    Balsters, Joshua H; Mantini, Dante; Wenderoth, Nicole

    2018-04-15

    Autism Spectrum Disorder (ASD) has been associated with abnormal synaptic development causing a breakdown in functional connectivity. However, when measured at the macro scale using resting state fMRI, these alterations are subtle and often difficult to detect due to the large heterogeneity of the pathology. Recently, we outlined a novel approach for generating robust biomarkers of resting state functional magnetic resonance imaging (RS-fMRI) using connectivity based parcellation of gross morphological structures to improve single-subject reproducibility and generate more robust connectivity fingerprints. Here we apply this novel approach to investigating the organization and connectivity strength of the cortico-striatal system in a large sample of ASD individuals and typically developed (TD) controls (N=130 per group). Our results showed differences in the parcellation of the striatum in ASD. Specifically, the putamen was found to be one single structure in ASD, whereas this was split into anterior and posterior segments in an age, IQ, and head movement matched TD group. An analysis of the connectivity fingerprints revealed that the group differences in clustering were driven by differential connectivity between striatum and the supplementary motor area, posterior cingulate cortex, and posterior insula. Our approach for analysing RS-fMRI in clinical populations has provided clear evidence that cortico-striatal circuits are organized differently in ASD. Based on previous task-based segmentations of the striatum, we believe that the anterior putamen cluster present in TD, but not in ASD, likely contributes to social and language processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparticle signatures in joint diseases.

    Directory of Open Access Journals (Sweden)

    Bence György

    Full Text Available INTRODUCTION: Microvesicles (MVs, earlier referred to as microparticles, represent a major type of extracellular vesicles currently considered as novel biomarkers in various clinical settings such as autoimmune disorders. However, the analysis of MVs in body fluids has not been fully standardized yet, and there are numerous pitfalls that hinder the correct assessment of these structures. METHODS: In this study, we analyzed synovial fluid (SF samples of patients with osteoarthritis (OA, rheumatoid arthritis (RA and juvenile idiopathic arthritis (JIA. To assess factors that may confound MV detection in joint diseases, we used electron microscopy (EM, Nanoparticle Tracking Analysis (NTA and mass spectrometry (MS. For flow cytometry, a method commonly used for phenotyping and enumeration of MVs, we combined recent advances in the field, and used a novel approach of differential detergent lysis for the exclusion of MV-mimicking non-vesicular signals. RESULTS: EM and NTA showed that substantial amounts of particles other than MVs were present in SF samples. Beyond known MV-associated proteins, MS analysis also revealed abundant plasma- and immune complex-related proteins in MV preparations. Applying improved flow cytometric analysis, we demonstrate for the first time that CD3(+ and CD8(+ T-cell derived SF MVs are highly elevated in patients with RA compared to OA patients (p=0.027 and p=0.009, respectively, after Bonferroni corrections. In JIA, we identified reduced numbers of B cell-derived MVs (p=0.009, after Bonferroni correction. CONCLUSIONS: Our results suggest that improved flow cytometric assessment of MVs facilitates the detection of previously unrecognized disease-associated vesicular signatures.

  10. Mistletoe lectin I in complex with galactose and lactose reveals distinct sugar-binding properties

    International Nuclear Information System (INIS)

    Mikeska, Ruth; Wacker, Roland; Arni, Raghuvir; Singh, Tej P.; Mikhailov, Albert; Gabdoulkhakov, Azat; Voelter, Wolfgang; Betzel, Christian

    2004-01-01

    The structures of mistletoe lectin I in complex with lactose and galactose reveal differences in binding by the two known sites in subdomains α1 and γ2 and suggest the presence of a third low-affinity site in subdomain β1. The structures of mistletoe lectin I (ML-I) from Viscum album complexed with lactose and galactose have been determined at 2.3 Å resolution and refined to R factors of 20.9% (R free = 23.6%) and 20.9 (R free = 24.6%), respectively. ML-I is a heterodimer and belongs to the class of ribosome-inactivating proteins of type II, which consist of two chains. The A-chain has rRNA N-glycosidase activity and irreversibly inhibits eukaryotic ribosomes. The B-chain is a lectin and preferentially binds to galactose-terminated glycolipids and glycoproteins on cell membranes. Saccharide binding is performed by two binding sites in subdomains α1 and γ2 of the ML-I B-chain separated by ∼62 Å from each other. The favoured binding of galactose in subdomain α1 is achieved via hydrogen bonds connecting the 4-hydroxyl and 3-hydroxyl groups of the sugar moiety with the side chains of Asp23B, Gln36B and Lys41B and the main chain of 26B. The aromatic ring of Trp38B on top of the preferred binding pocket supports van der Waals packing of the apolar face of galactose and stabilizes the sugar–lectin complex. In the galactose-binding site II of subdomain γ2, Tyr249B provides the hydrophobic stacking and the side chains of Asp235B, Gln238B and Asn256B are hydrogen-bonding partners for galactose. In the case of the galactose-binding site I, the 2-hydroxyl group also stabilizes the sugar–protein complex, an interaction thus far rarely detected in galactose-specific lectins. Finally, a potential third low-affinity galactose-binding site in subunit β1 was identified in the present ML-I structures, in which a glycerol molecule from the cryoprotectant buffer has bound, mimicking the sugar compound

  11. Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

    Science.gov (United States)

    Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

    2016-05-10

    Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in

  12. Genomic profiling of rice sperm cell transcripts reveals conserved and distinct elements in the flowering plant male germ lineage.

    Science.gov (United States)

    Russell, Scott D; Gou, Xiaoping; Wong, Chui E; Wang, Xinkun; Yuan, Tong; Wei, Xiaoping; Bhalla, Prem L; Singh, Mohan B

    2012-08-01

    Genomic assay of sperm cell RNA provides insight into functional control, modes of regulation, and contributions of male gametes to double fertilization. Sperm cells of rice (Oryza sativa) were isolated from field-grown, disease-free plants and RNA was processed for use with the full-genome Affymetrix microarray. Comparison with Gene Expression Omnibus (GEO) reference arrays confirmed expressionally distinct gene profiles. A total of 10,732 distinct gene sequences were detected in sperm cells, of which 1668 were not expressed in pollen or seedlings. Pathways enriched in male germ cells included ubiquitin-mediated pathways, pathways involved in chromatin modeling including histones, histone modification and nonhistone epigenetic modification, and pathways related to RNAi and gene silencing. Genome-wide expression patterns in angiosperm sperm cells indicate common and divergent themes in the male germline that appear to be largely self-regulating through highly up-regulated chromatin modification pathways. A core of highly conserved genes appear common to all sperm cells, but evidence is still emerging that another class of genes have diverged in expression between monocots and dicots since their divergence. Sperm cell transcripts present at fusion may be transmitted through plasmogamy during double fertilization to effect immediate post-fertilization expression of early embryo and (or) endosperm development. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  13. Comparative genome and transcriptome analysis reveals distinctive surface characteristics and unique physiological potentials of Pseudomonas aeruginosa ATCC 27853

    KAUST Repository

    Cao, Huiluo

    2017-06-12

    Pseudomonas aeruginosa ATCC 27853 was isolated from a hospital blood specimen in 1971 and has been widely used as a model strain to survey antibiotics susceptibilities, biofilm development, and metabolic activities of Pseudomonas spp.. Although four draft genomes of P. aeruginosa ATCC 27853 have been sequenced, the complete genome of this strain is still lacking, hindering a comprehensive understanding of its physiology and functional genome.Here we sequenced and assembled the complete genome of P. aeruginosa ATCC 27853 using the Pacific Biosciences SMRT (PacBio) technology and Illumina sequencing platform. We found that accessory genes of ATCC 27853 including prophages and genomic islands (GIs) mainly contribute to the difference between P. aeruginosa ATCC 27853 and other P. aeruginosa strains. Seven prophages were identified within the genome of P. aeruginosa ATCC 27853. Of the predicted 25 GIs, three contain genes that encode monoxoygenases, dioxygenases and hydrolases that could be involved in the metabolism of aromatic compounds. Surveying virulence-related genes revealed that a series of genes that encode the B-band O-antigen of LPS are lacking in ATCC 27853. Distinctive SNPs in genes of cellular adhesion proteins such as type IV pili and flagella biosynthesis were also observed in this strain. Colony morphology analysis confirmed an enhanced biofilm formation capability of ATCC 27853 on solid agar surface compared to Pseudomonas aeruginosa PAO1. We then performed transcriptome analysis of ATCC 27853 and PAO1 using RNA-seq and compared the expression of orthologous genes to understand the functional genome and the genomic details underlying the distinctive colony morphogenesis. These analyses revealed an increased expression of genes involved in cellular adhesion and biofilm maturation such as type IV pili, exopolysaccharide and electron transport chain components in ATCC 27853 compared with PAO1. In addition, distinctive expression profiles of the

  14. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

    Science.gov (United States)

    Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

    2007-01-01

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level.

  15. Single Particle Tracking reveals two distinct environments for CD4 receptors at the surface of living T lymphocytes

    International Nuclear Information System (INIS)

    Mascalchi, Patrice; Lamort, Anne Sophie; Salomé, Laurence; Dumas, Fabrice

    2012-01-01

    Highlights: ► We studied the diffusion of single CD4 receptors on living lymphocytes. ► This study reveals that CD4 receptors have either a random or confined diffusion. ► The dynamics of unconfined CD4 receptors was accelerated by a temperature raise. ► The dynamics of confined CD4 receptors was unchanged by a temperature raise. ► Our results suggest the existence of two different environments for CD4 receptors. -- Abstract: We investigated the lateral diffusion of the HIV receptor CD4 at the surface of T lymphocytes at 20 °C and 37 °C by Single Particle Tracking using Quantum Dots. We found that the receptors presented two major distinct behaviors that were not equally affected by temperature changes. About half of the receptors showed a random diffusion with a diffusion coefficient increasing upon raising the temperature. The other half of the receptors was permanently or transiently confined with unchanged dynamics on raising the temperature. These observations suggest that two distinct subpopulations of CD4 receptors with different environments are present at the surface of living T lymphocytes.

  16. Correlation of neural activity with behavioral kinematics reveals distinct sensory encoding and evidence accumulation processes during active tactile sensing.

    Science.gov (United States)

    Delis, Ioannis; Dmochowski, Jacek P; Sajda, Paul; Wang, Qi

    2018-03-23

    Many real-world decisions rely on active sensing, a dynamic process for directing our sensors (e.g. eyes or fingers) across a stimulus to maximize information gain. Though ecologically pervasive, limited work has focused on identifying neural correlates of the active sensing process. In tactile perception, we often make decisions about an object/surface by actively exploring its shape/texture. Here we investigate the neural correlates of active tactile decision-making by simultaneously measuring electroencephalography (EEG) and finger kinematics while subjects interrogated a haptic surface to make perceptual judgments. Since sensorimotor behavior underlies decision formation in active sensing tasks, we hypothesized that the neural correlates of decision-related processes would be detectable by relating active sensing to neural activity. Novel brain-behavior correlation analysis revealed that three distinct EEG components, localizing to right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and supplementary motor area (SMA), respectively, were coupled with active sensing as their activity significantly correlated with finger kinematics. To probe the functional role of these components, we fit their single-trial-couplings to decision-making performance using a hierarchical-drift-diffusion-model (HDDM), revealing that the LOC modulated the encoding of the tactile stimulus whereas the MFG predicted the rate of information integration towards a choice. Interestingly, the MFG disappeared from components uncovered from control subjects performing active sensing but not required to make perceptual decisions. By uncovering the neural correlates of distinct stimulus encoding and evidence accumulation processes, this study delineated, for the first time, the functional role of cortical areas in active tactile decision-making. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Distinct herpesvirus resistances and immune responses of three gynogenetic clones of gibel carp revealed by comprehensive transcriptomes.

    Science.gov (United States)

    Gao, Fan-Xiang; Wang, Yang; Zhang, Qi-Ya; Mou, Cheng-Yan; Li, Zhi; Deng, Yuan-Sheng; Zhou, Li; Gui, Jian-Fang

    2017-07-24

    Gibel carp is an important aquaculture species in China, and a herpesvirus, called as Carassius auratus herpesvirus (CaHV), has hampered the aquaculture development. Diverse gynogenetic clones of gibel carp have been identified or created, and some of them have been used as aquaculture varieties, but their resistances to herpesvirus and the underlying mechanism remain unknown. To reveal their susceptibility differences, we firstly performed herpesvirus challenge experiments in three gynogenetic clones of gibel carp, including the leading variety clone A + , candidate variety clone F and wild clone H. Three clones showed distinct resistances to CaHV. Moreover, 8772, 8679 and 10,982 differentially expressed unigenes (DEUs) were identified from comparative transcriptomes between diseased individuals and control individuals of clone A + , F and H, respectively. Comprehensive analysis of the shared DEUs in all three clones displayed common defense pathways to the herpesvirus infection, activating IFN system and suppressing complements. KEGG pathway analysis of specifically changed DEUs in respective clones revealed distinct immune responses to the herpesvirus infection. The DEU numbers identified from clone H in KEGG immune-related pathways, such as "chemokine signaling pathway", "Toll-like receptor signaling pathway" and others, were remarkably much more than those from clone A + and F. Several IFN-related genes, including Mx1, viperin, PKR and others, showed higher increases in the resistant clone H than that in the others. IFNphi3, IFI44-like and Gig2 displayed the highest expression in clone F and IRF1 uniquely increased in susceptible clone A + . In contrast to strong immune defense in resistant clone H, susceptible clone A + showed remarkable up-regulation of genes related to apoptosis or death, indicating that clone A + failed to resist virus offensive and evidently induced apoptosis or death. Our study is the first attempt to screen distinct resistances and

  18. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

    Science.gov (United States)

    Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

    2011-12-01

    Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

  19. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

    Directory of Open Access Journals (Sweden)

    Olga V Viktorovskaya

    2016-08-01

    Full Text Available There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses replication.Seventy-nine novel RNA binding proteins for dengue virus (DENV were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps

  20. Three distinct modes in a surface micro-discharge in atmospheric pressure He + N{sub 2} mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dong; Liu, Dingxin, E-mail: liudingxin@mail.xjtu.edu.cn; He, Tongtong; Li, Qiaosong; Wang, Xiaohua [State Key Laboratory of Electrical Insulation and Power Equipment, Center for Plasma Biomedicine, Xi' an Jiaotong University, Xi' an 710049 (China); Kong, Michael G. [State Key Laboratory of Electrical Insulation and Power Equipment, Center for Plasma Biomedicine, Xi' an Jiaotong University, Xi' an 710049 (China); Frank Reidy Center for Bioelectrics, Old Dominion University, Norfolk, Virginia 23508 (United States); Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, Virginia 23529 (United States)

    2015-12-15

    A surface micro-discharge in atmospheric pressure He + N{sub 2} mixtures is studied in this paper with an emphasis on the discharge modes. With the N{sub 2} admixture increasing from 0.1% to 20%, the discharge evolves from a spatially diffuse mode to a filamentary mode during positive half-cycles of the applied voltage. However during the negative half-cycles, an additional patterned mode emerges between the diffuse and the filamentary modes, which has not been reported before to exist in surface micro-discharges. In the diffuse and patterned modes, the plasmas cover almost the entirety of the mesh area during one cycle after plasma ignition in all mesh elements, and the discharge power increases linearly with the applied voltage. In contrast, plasma coverage of the mesh area is only partial in the filamentary mode and the plasma is more unstable with the discharge power increasing exponentially with the applied voltage. As the surface micro-discharge evolves through the three modes, the density of excited species changes significantly, for instance, the density of N{sub 2}{sup +}(B) drops by ∼20-fold from [N{sub 2}] = 0.2% to 20%. The N{sub 2}{sup +}(B) is predicted to be generated mainly through successive processes of Penning ionization by helium metastables and electron-impact excitation of N{sub 2}{sup +}(X), the latter is most responsible for the density decrease of N{sub 2}{sup +}(B) because much more N{sub 2}{sup +}(X) is converted to N{sub 4}{sup +}(X) as the increase of N{sub 2} fraction. Also, the electron density and electron temperature decrease with the discharge mode transition.

  1. A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

    Directory of Open Access Journals (Sweden)

    Shokat Kevan M

    2008-09-01

    Full Text Available Abstract Background Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo. Results We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance. Conclusion This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1.

  2. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    Science.gov (United States)

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation.

    Science.gov (United States)

    Stobart, Jillian L; Ferrari, Kim David; Barrett, Matthew J P; Stobart, Michael J; Looser, Zoe J; Saab, Aiman S; Weber, Bruno

    2018-01-01

    Localized, heterogeneous calcium transients occur throughout astrocytes, but the characteristics and long-term stability of these signals, particularly in response to sensory stimulation, remain unknown. Here, we used a genetically encoded calcium indicator and an activity-based image analysis scheme to monitor astrocyte calcium activity in vivo. We found that different subcellular compartments (processes, somata, and endfeet) displayed distinct signaling characteristics. Closer examination of individual signals showed that sensory stimulation elevated the number of specific types of calcium peaks within astrocyte processes and somata, in a cortical layer-dependent manner, and that the signals became more synchronous upon sensory stimulation. Although mice genetically lacking astrocytic IP3R-dependent calcium signaling (Ip3r2-/-) had fewer signal peaks, the response to sensory stimulation was sustained, suggesting other calcium pathways are also involved. Long-term imaging of astrocyte populations revealed that all compartments reliably responded to stimulation over several months, but that the location of the response within processes may vary. These previously unknown characteristics of subcellular astrocyte calcium signals provide new insights into how astrocytes may encode local neuronal circuit activity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Kober, Daniel L.; Alexander-Brett, Jennifer M.; Karch, Celeste M.; Cruchaga, Carlos; Colonna, Marco; Holtzman, Michael J.; Brett, Thomas J. (WU-MED)

    2016-12-20

    Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases. To determine how TREM2 variants contribute to these diseases, we performed structural and functional studies of wild-type and variant proteins. Our 3.1 Å TREM2 crystal structure revealed that mutations found in Nasu-Hakola disease are buried whereas Alzheimer’s disease risk variants are found on the surface, suggesting that these mutations have distinct effects on TREM2 function. Biophysical and cellular methods indicate that Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer’s risk variants impact binding to a TREM2 ligand. Additionally, the Alzheimer’s risk variants appear to epitope map a functional surface on TREM2 that is unique within the larger TREM family. These findings provide a guide to structural and functional differences among genetic variants of TREM2, indicating that therapies targeting the TREM2 pathway should be tailored to these genetic and functional differences with patient-specific medicine approaches for neurodegenerative disorders.

  5. Optogenetic Inhibition Reveals Distinct Roles for Basolateral Amygdala Activity at Discrete Time Points during Risky Decision Making.

    Science.gov (United States)

    Orsini, Caitlin A; Hernandez, Caesar M; Singhal, Sarthak; Kelly, Kyle B; Frazier, Charles J; Bizon, Jennifer L; Setlow, Barry

    2017-11-29

    Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (risky decision-making task) in which rats choose between a small, "safe" reward and a large reward accompanied by varying probabilities of footshock punishment. Male Long-Evans rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the risky decision-making task. Laser delivery during the task occurred during intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did laser delivery affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active. SIGNIFICANCE STATEMENT To date, most behavioral neuroscience research on neural mechanisms of decision making has used techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the BLA has opposite effects on choice behavior in a rat model of risky decision making, depending on the phase

  6. Modes of Escherichia coli Dps Interaction with DNA as Revealed by Atomic Force Microscopy.

    Directory of Open Access Journals (Sweden)

    Vladislav V Melekhov

    Full Text Available Multifunctional protein Dps plays an important role in iron assimilation and a crucial role in bacterial genome packaging. Its monomers form dodecameric spherical particles accumulating ~400 molecules of oxidized iron ions within the protein cavity and applying a flexible N-terminal ends of each subunit for interaction with DNA. Deposition of iron is a well-studied process by which cells remove toxic Fe2+ ions from the genetic material and store them in an easily accessible form. However, the mode of interaction with linear DNA remained mysterious and binary complexes with Dps have not been characterized so far. It is widely believed that Dps binds DNA without any sequence or structural preferences but several lines of evidence have demonstrated its ability to differentiate gene expression, which assumes certain specificity. Here we show that Dps has a different affinity for the two DNA fragments taken from the dps gene regulatory region. We found by atomic force microscopy that Dps predominantly occupies thermodynamically unstable ends of linear double-stranded DNA fragments and has high affinity to the central part of the branched DNA molecule self-assembled from three single-stranded oligonucleotides. It was proposed that Dps prefers binding to those regions in DNA that provide more contact pads for the triad of its DNA-binding bundle associated with one vertex of the protein globule. To our knowledge, this is the first study revealed the nucleoid protein with an affinity to branched DNA typical for genomic regions with direct and inverted repeats. As a ubiquitous feature of bacterial and eukaryotic genomes, such structural elements should be of particular care, but the protein system evolutionarily adapted for this function is not yet known, and we suggest Dps as a putative component of this system.

  7. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states.

    Directory of Open Access Journals (Sweden)

    Kevin A Wilkinson

    2008-04-01

    Full Text Available Replication and pathogenesis of the human immunodeficiency virus (HIV is tightly linked to the structure of its RNA genome, but genome structure in infectious virions is poorly understood. We invent high-throughput SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension technology, which uses many of the same tools as DNA sequencing, to quantify RNA backbone flexibility at single-nucleotide resolution and from which robust structural information can be immediately derived. We analyze the structure of HIV-1 genomic RNA in four biologically instructive states, including the authentic viral genome inside native particles. Remarkably, given the large number of plausible local structures, the first 10% of the HIV-1 genome exists in a single, predominant conformation in all four states. We also discover that noncoding regions functioning in a regulatory role have significantly lower (p-value < 0.0001 SHAPE reactivities, and hence more structure, than do viral coding regions that function as the template for protein synthesis. By directly monitoring protein binding inside virions, we identify the RNA recognition motif for the viral nucleocapsid protein. Seven structurally homologous binding sites occur in a well-defined domain in the genome, consistent with a role in directing specific packaging of genomic RNA into nascent virions. In addition, we identify two distinct motifs that are targets for the duplex destabilizing activity of this same protein. The nucleocapsid protein destabilizes local HIV-1 RNA structure in ways likely to facilitate initial movement both of the retroviral reverse transcriptase from its tRNA primer and of the ribosome in coding regions. Each of the three nucleocapsid interaction motifs falls in a specific genome domain, indicating that local protein interactions can be organized by the long-range architecture of an RNA. High-throughput SHAPE reveals a comprehensive view of HIV-1 RNA genome structure, and further

  8. Large-scale expression analysis reveals distinct microRNA profiles at different stages of human neurodevelopment.

    Directory of Open Access Journals (Sweden)

    Brandon Smith

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are short non-coding RNAs predicted to regulate one third of protein coding genes via mRNA targeting. In conjunction with key transcription factors, such as the repressor REST (RE1 silencing transcription factor, miRNAs play crucial roles in neurogenesis, which requires a highly orchestrated program of gene expression to ensure the appropriate development and function of diverse neural cell types. Whilst previous studies have highlighted select groups of miRNAs during neural development, there remains a need for amenable models in which miRNA expression and function can be analyzed over the duration of neurogenesis. PRINCIPAL FINDINGS: We performed large-scale expression profiling of miRNAs in human NTera2/D1 (NT2 cells during retinoic acid (RA-induced transition from progenitors to fully differentiated neural phenotypes. Our results revealed dynamic changes of miRNA patterns, resulting in distinct miRNA subsets that could be linked to specific neurodevelopmental stages. Moreover, the cell-type specific miRNA subsets were very similar in NT2-derived differentiated cells and human primary neurons and astrocytes. Further analysis identified miRNAs as putative regulators of REST, as well as candidate miRNAs targeted by REST. Finally, we confirmed the existence of two predicted miRNAs; pred-MIR191 and pred-MIR222 associated with SLAIN1 and FOXP2, respectively, and provided some evidence of their potential co-regulation. CONCLUSIONS: In the present study, we demonstrate that regulation of miRNAs occurs in precise patterns indicative of their roles in cell fate commitment, progenitor expansion and differentiation into neurons and glia. Furthermore, the similarity between our NT2 system and primary human cells suggests their roles in molecular pathways critical for human in vivo neurogenesis.

  9. Distinct genetic diversity of Oncomelania hupensis, intermediate host of Schistosoma japonicum in mainland China as revealed by ITS sequences.

    Directory of Open Access Journals (Sweden)

    Qin Ping Zhao

    Full Text Available BACKGROUND: Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, which causes schistosomiasis endemic in the Far East, and especially in mainland China. O. hupensis largely determines the parasite's geographical range. How O. hupensis's genetic diversity is distributed geographically in mainland China has never been well examined with DNA sequence data. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genetic variation among O. hupensis from different geographical origins using the combined complete internal transcribed spacer 1 (ITS1 and ITS2 regions of nuclear ribosomal DNA. 165 O. hupensis isolates were obtained in 29 localities from 7 provinces across mainland China: lake/marshland and hill regions in Anhui, Hubei, Hunan, Jiangxi and Jiangsu provinces, located along the middle and lower reaches of Yangtze River, and mountainous regions in Sichuan and Yunnan provinces. Phylogenetic and haplotype network analyses showed distinct genetic diversity and no shared haplotypes between populations from lake/marshland regions of the middle and lower reaches of the Yangtze River and populations from mountainous regions of Sichuan and Yunnan provinces. The genetic distance between these two groups is up to 0.81 based on Fst, and branch time was estimated as 2-6 Ma. As revealed in the phylogenetic tree, snails from Sichuan and Yunnan provinces were also clustered separately. Geographical separation appears to be an important factor accounting for the diversification of the two groups of O. hupensis in mainland China, and probably for the separate clades between snails from Sichuan and Yunnan provinces. In lake/marshland and hill regions along the middle and lower reaches of the Yangtze River, three clades were identified in the phylogenetic tree, but without any obvious clustering of snails from different provinces. CONCLUSIONS: O. hupensis in mainland China may have considerable genetic diversity, and a more

  10. Characterization of Trichome-Expressed BAHD Acyltransferases in Petunia axillaris Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae1[OPEN

    Science.gov (United States)

    Uebler, Joseph B.; Liu, Xiaoxiao

    2017-01-01

    Acylsugars are synthesized in the glandular trichomes of the Solanaceae family and are implicated in protection against abiotic and biotic stress. Acylsugars are composed of either sucrose or glucose esterified with varying numbers of acyl chains of differing length. In tomato (Solanum lycopersicum), acylsugar assembly requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily. Tomato ASATs catalyze the sequential esterification of acyl-coenzyme A thioesters to the R4, R3, R3ʹ, and R2 positions of sucrose, yielding a tetra-acylsucrose. Petunia spp. synthesize acylsugars that are structurally distinct from those of tomato. To explore the mechanisms underlying this chemical diversity, a Petunia axillaris transcriptome was mined for trichome preferentially expressed BAHDs. A combination of phylogenetic analyses, gene silencing, and biochemical analyses coupled with structural elucidation of metabolites revealed that acylsugar assembly is not conserved between tomato and petunia. In P. axillaris, tetra-acylsucrose assembly occurs through the action of four ASATs, which catalyze sequential addition of acyl groups to the R2, R4, R3, and R6 positions. Notably, in P. axillaris, PaxASAT1 and PaxASAT4 catalyze the acylation of the R2 and R6 positions of sucrose, respectively, and no clear orthologs exist in tomato. Similarly, petunia acylsugars lack an acyl group at the R3ʹ position, and congruently, an ortholog of SlASAT3, which catalyzes acylation at the R3ʹ position in tomato, is absent in P. axillaris. Furthermore, where putative orthologous relationships of ASATs are predicted between tomato and petunia, these are not supported by biochemical assays. Overall, these data demonstrate the considerable evolutionary plasticity of acylsugar biosynthesis. PMID:28701351

  11. Characterization of Trichome-Expressed BAHD Acyltransferases in Petunia axillaris Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae.

    Science.gov (United States)

    Nadakuduti, Satya Swathi; Uebler, Joseph B; Liu, Xiaoxiao; Jones, A Daniel; Barry, Cornelius S

    2017-09-01

    Acylsugars are synthesized in the glandular trichomes of the Solanaceae family and are implicated in protection against abiotic and biotic stress. Acylsugars are composed of either sucrose or glucose esterified with varying numbers of acyl chains of differing length. In tomato ( Solanum lycopersicum ), acylsugar assembly requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily. Tomato ASATs catalyze the sequential esterification of acyl-coenzyme A thioesters to the R4, R3, R3', and R2 positions of sucrose, yielding a tetra-acylsucrose. Petunia spp. synthesize acylsugars that are structurally distinct from those of tomato. To explore the mechanisms underlying this chemical diversity, a Petunia axillaris transcriptome was mined for trichome preferentially expressed BAHDs. A combination of phylogenetic analyses, gene silencing, and biochemical analyses coupled with structural elucidation of metabolites revealed that acylsugar assembly is not conserved between tomato and petunia. In P. axillaris , tetra-acylsucrose assembly occurs through the action of four ASATs, which catalyze sequential addition of acyl groups to the R2, R4, R3, and R6 positions. Notably, in P. axillaris , PaxASAT1 and PaxASAT4 catalyze the acylation of the R2 and R6 positions of sucrose, respectively, and no clear orthologs exist in tomato. Similarly, petunia acylsugars lack an acyl group at the R3' position, and congruently, an ortholog of SlASAT3, which catalyzes acylation at the R3' position in tomato, is absent in P. axillaris Furthermore, where putative orthologous relationships of ASATs are predicted between tomato and petunia, these are not supported by biochemical assays. Overall, these data demonstrate the considerable evolutionary plasticity of acylsugar biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

  12. Comparative transcriptome analysis reveals distinct ethylene-independent regulation of ripening in response to low temperature in kiwifruit.

    Science.gov (United States)

    Asiche, William O; Mitalo, Oscar W; Kasahara, Yuka; Tosa, Yasuaki; Mworia, Eric G; Owino, Willis O; Ushijima, Koichiro; Nakano, Ryohei; Yano, Kentaro; Kubo, Yasutaka

    2018-03-21

    Kiwifruit are classified as climacteric since exogenous ethylene (or its analogue propylene) induces rapid ripening accompanied by ethylene production under positive feedback regulation. However, most of the ripening-associated changes (Phase 1 ripening) in kiwifruit during storage and on-vine occur largely in the absence of any detectable ethylene. This ripening behavior is often attributed to basal levels of system I ethylene, although it is suggested to be modulated by low temperature. To elucidate the mechanisms regulating Phase 1 ripening in kiwifruit, a comparative transcriptome analysis using fruit continuously exposed to propylene (at 20 °C), and during storage at 5 °C and 20 °C was conducted. Propylene exposure induced kiwifruit softening, reduction of titratable acidity (TA), increase in soluble solids content (SSC) and ethylene production within 5 days. During storage, softening and reduction of TA occurred faster in fruit at 5 °C compared to 20 °C although no endogenous ethylene production was detected. Transcriptome analysis revealed 3761 ripening-related differentially expressed genes (DEGs), of which 2742 were up-regulated by propylene while 1058 were up-regulated by low temperature. Propylene exclusively up-regulated 2112 DEGs including those associated with ethylene biosynthesis and ripening such as AcACS1, AcACO2, AcPL1, AcXET1, Acβ-GAL, AcAAT, AcERF6 and AcNAC7. Similarly, low temperature exclusively up-regulated 467 DEGS including AcACO3, AcPL2, AcPMEi, AcADH, Acβ-AMY2, AcGA2ox2, AcNAC5 and AcbZIP2 among others. A considerable number of DEGs such as AcPG, AcEXP1, AcXET2, Acβ-AMY1, AcGA2ox1, AcNAC6, AcMADS1 and AcbZIP1 were up-regulated by either propylene or low temperature. Frequent 1-MCP treatments failed to inhibit the accelerated ripening and up-regulation of associated DEGs by low temperature indicating that the changes were independent of ethylene. On-vine kiwifruit ripening proceeded in the absence of any detectable

  13. Machine Learning Reveals a Non-Canonical Mode of Peptide Binding to MHC class II Molecules

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Jurtz, Vanessa Isabell; Kaever, Thomas

    2017-01-01

    binding motif with a non-canonical binding core of length different from nine. This previously undescribed mode of peptide binding to MHCII molecules gives a more complete picture of peptide presentation by MHCII and allows us to model more accurately this event. This article is protected by copyright...

  14. Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language

    NARCIS (Netherlands)

    Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

    Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of

  15. fMRI Reveals Distinct CNS Processing during Symptomatic and Recovered Complex Regional Pain Syndrome in Children

    Science.gov (United States)

    Lebel, A.; Becerra, L.; Wallin, D.; Moulton, E. A.; Morris, S.; Pendse, G.; Jasciewicz, J.; Stein, M.; Aiello-Lammens, M.; Grant, E.; Berde, C.; Borsook, D.

    2008-01-01

    Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the…

  16. Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language

    NARCIS (Netherlands)

    Borgomaneri, S.; Gazzola, V.; Avenanti, A.

    2015-01-01

    Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of

  17. Interaction vs. observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study.

    Science.gov (United States)

    Tylén, Kristian; Allen, Micah; Hunter, Bjørk K; Roepstorff, Andreas

    2012-01-01

    Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an "understanding of the other," or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye-tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g., someone offering or showing you an object) elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action). In contrast, the social-cognitive perception of someone "privately" manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants' experience, behavior, and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions.

  18. Interaction versus Observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study.

    Directory of Open Access Journals (Sweden)

    Kristian eTylen

    2012-12-01

    Full Text Available Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an ‘understanding of the other’, or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g. someone offering or showing you an object elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action. In contrast, the social-cognitive perception of someone ‘privately’ manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants’ experience, behavior and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions.

  19. Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

    Science.gov (United States)

    Seely, Jeffrey S; Kaufman, Matthew T; Ryu, Stephen I; Shenoy, Krishna V; Cunningham, John P; Churchland, Mark M

    2016-11-01

    Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were 'simplest' (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

  20. Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Seely

    2016-11-01

    Full Text Available Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1 and primary motor cortex (M1. All V1 datasets were 'simplest' (there were relatively few degrees of freedom along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

  1. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

    Science.gov (United States)

    Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

    2016-01-01

    Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

  2. Sample Entropy and Traditional Measures of Heart Rate Dynamics Reveal Different Modes of Cardiovascular Control During Low Intensity Exercise

    Directory of Open Access Journals (Sweden)

    Matthias Weippert

    2014-10-01

    Full Text Available Nonlinear parameters of heart rate variability (HRV have proven their prognostic value in clinical settings, but their physiological background is not very well established. We assessed the effects of low intensity isometric (ISO and dynamic (DYN exercise of the lower limbs on heart rate matched intensity on traditional and entropy measures of HRV. Due to changes of afferent feedback under DYN and ISO a distinct autonomic response, mirrored by HRV measures, was hypothesized. Five-minute inter-beat interval measurements of 43 healthy males (26.0 ± 3.1 years were performed during rest, DYN and ISO in a randomized order. Blood pressures and rate pressure product were higher during ISO vs. DYN (p < 0.001. HRV indicators SDNN as well as low and high frequency power were significantly higher during ISO (p < 0.001 for all measures. Compared to DYN, sample entropy (SampEn was lower during ISO (p < 0.001. Concluding, contraction mode itself is a significant modulator of the autonomic cardiovascular response to exercise. Compared to DYN, ISO evokes a stronger blood pressure response and an enhanced interplay between both autonomic branches. Non-linear HRV measures indicate a more regular behavior under ISO. Results support the view of the reciprocal antagonism being only one of many modes of autonomic heart rate control. Under different conditions; the identical “end product” heart rate might be achieved by other modes such as sympathovagal co-activation as well.

  3. Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

    Science.gov (United States)

    Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

    2017-12-06

    The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these

  4. Comparison of mitochondrial and nucleolar RNase MRP reveals identical RNA components with distinct enzymatic activities and protein components.

    Science.gov (United States)

    Lu, Qiaosheng; Wierzbicki, Sara; Krasilnikov, Andrey S; Schmitt, Mark E

    2010-03-01

    RNase MRP is a ribonucleoprotein endoribonuclease found in three cellular locations where distinct substrates are processed: the mitochondria, the nucleolus, and the cytoplasm. Cytoplasmic RNase MRP is the nucleolar enzyme that is transiently relocalized during mitosis. Nucleolar RNase MRP (NuMRP) was purified to homogeneity, and we extensively purified the mitochondrial RNase MRP (MtMRP) to a single RNA component identical to the NuMRP RNA. Although the protein components of the NuMRP were identified by mass spectrometry successfully, none of the known NuMRP proteins were found in the MtMRP preparation. Only trace amounts of the core NuMRP protein, Pop4, were detected in MtMRP by Western blot. In vitro activity of the two enzymes was compared. MtMRP cleaved only mitochondrial ORI5 substrate, while NuMRP cleaved all three substrates. However, the NuMRP enzyme cleaved the ORI5 substrate at sites different than the MtMRP enzyme. In addition, enzymatic differences in preferred ionic strength confirm these enzymes as distinct entities. Magnesium was found to be essential to both enzymes. We tested a number of reported inhibitors including puromycin, pentamidine, lithium, and pAp. Puromycin inhibition suggested that it binds directly to the MRP RNA, reaffirming the role of the RNA component in catalysis. In conclusion, our study confirms that the NuMRP and MtMRP enzymes are distinct entities with differing activities and protein components but a common RNA subunit, suggesting that the RNA must be playing a crucial role in catalytic activity.

  5. Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins.

    Science.gov (United States)

    Wang, Dan; Zhang, Lin; Hu, JunFeng; Gao, Dianshuai; Liu, Xin; Sha, Yan

    2018-04-01

    Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of α/β hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors.

  6. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Brady Tang

    2011-04-01

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  7. Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language.

    Science.gov (United States)

    Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

    2015-09-01

    Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of motor cortex engagement during emotion perception. Participants observed pictures of body expressions and categorized them as happy, fearful or neutral while receiving TMS over the left or right motor cortex at 150 and 300 ms after picture onset. In the early phase (150 ms), we observed a reduction of excitability for happy and fearful emotional bodies that was specific to the right hemisphere and correlated with participants' disposition to feel personal distress. This 'orienting' inhibitory response to emotional bodies was also paralleled by a general drop in categorization accuracy when stimulating the right but not the left motor cortex. Conversely, at 300 ms, greater excitability for negative, positive and neutral movements was found in both hemispheres. This later motor facilitation marginally correlated with participants' tendency to assume the psychological perspectives of others and reflected simulation of the movement implied in the neutral and emotional body expressions. These findings highlight the motor system's involvement during perception of emotional bodies. They suggest that fast orienting reactions to emotional cues--reflecting neural processing necessary for visual perception--occur before motor features of the observed emotional expression are simulated in the motor system and that distinct empathic dispositions influence these two neural motor phenomena. Implications for theories of embodied simulation are discussed.

  8. Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

    Science.gov (United States)

    Mastro, Kevin J.; Bouchard, Rachel S.; Holt, Hiromi A. K.

    2014-01-01

    Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)–Cre and parvalbumin (PV)–Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6–GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV–GPe neurons. In contrast, PV–GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6–GPe and PV–GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease. PMID:24501350

  9. Effect of tidal triggering on seismicity in Taiwan revealed by the empirical mode decomposition method

    Directory of Open Access Journals (Sweden)

    H.-J. Chen

    2012-07-01

    Full Text Available The effect of tidal triggering on earthquake occurrence has been controversial for many years. This study considered earthquakes that occurred near Taiwan between 1973 and 2008. Because earthquake data are nonlinear and non-stationary, we applied the empirical mode decomposition (EMD method to analyze the temporal variations in the number of daily earthquakes to investigate the effect of tidal triggering. We compared the results obtained from the non-declustered catalog with those from two kinds of declustered catalogs and discuss the aftershock effect on the EMD-based analysis. We also investigated stacking the data based on in-phase phenomena of theoretical Earth tides with statistical significance tests. Our results show that the effects of tidal triggering, particularly the lunar tidal effect, can be extracted from the raw seismicity data using the approach proposed here. Our results suggest that the lunar tidal force is likely a factor in the triggering of earthquakes.

  10. Aspects of Teaching and Learning Science: What students' diaries reveal about inquiry and traditional modes

    Science.gov (United States)

    Kawalkar, Aisha; Vijapurkar, Jyotsna

    2015-09-01

    We present an analysis of students' reflective writing (diaries) of two cohorts of Grade 8 students, one undergoing inquiry and the other traditional science teaching. Students' writing included a summary of what students had learned in class on that day and their opinions and feelings about the class. The entries were analysed qualitatively and quantitatively. This analysis of students' first-person accounts of their learning experience and their notes taken during class was useful in two ways. First, it brought out a spectrum of differences in outcomes of these two teaching modes-conceptual, affective and epistemic. Second, this analysis brought out the significance and meaning of the learning experience for students in their own words, thus adding another dimension to researchers' characterisation of the two teaching methods.

  11. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.

    Science.gov (United States)

    Hidalgo, Andrés; Peired, Anna J; Wild, Martin; Vestweber, Dietmar; Frenette, Paul S

    2007-04-01

    The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.

  12. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance

    Directory of Open Access Journals (Sweden)

    Elliott Ferris

    2018-03-01

    Full Text Available The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.

  13. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

    DEFF Research Database (Denmark)

    Bultmann-Mellin, Insa; Conradi, Anne; Maul, Alexandra C

    2015-01-01

    Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been ...

  14. Profiling of REST-dependent microRNAs reveals dynamic modes of expression

    Directory of Open Access Journals (Sweden)

    Zhengliang eGao

    2012-05-01

    Full Text Available Multipotent neural stem cells (NSCs possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggest that the interaction between cell-type specific transcription factors and microRNAs (miRNAs is important as resident neural stem/progenitor cells give rise to functionally mature neurons. Recently, we demonstrated that the transcriptional repressor REST (RE1-silencing transcription factor is essential to prevent precocious neuronal differentiation and maintain NSC self-renewal in the adult hippocampus. Here we show that REST is required for orchestrating the expression of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically relevant cell type. Using miRNA array profiling, we identified known REST-regulated miRNA genes, as well as previously uncharacterized REST-dependent miRNAs. Interestingly, REST-regulated miRNAs undergo dynamic expression changes under differentiation conditions over time, but not under proliferation conditions. These results suggest that REST functions in a context-dependent manner through its target miRNAs for mediating neuronal production.

  15. Range-wide multilocus phylogeography of the red fox reveals ancient continental divergence, minimal genomic exchange and distinct demographic histories.

    Science.gov (United States)

    Statham, Mark J; Murdoch, James; Janecka, Jan; Aubry, Keith B; Edwards, Ceiridwen J; Soulsbury, Carl D; Berry, Oliver; Wang, Zhenghuan; Harrison, David; Pearch, Malcolm; Tomsett, Louise; Chupasko, Judith; Sacks, Benjamin N

    2014-10-01

    Widely distributed taxa provide an opportunity to compare biogeographic responses to climatic fluctuations on multiple continents and to investigate speciation. We conducted the most geographically and genomically comprehensive study to date of the red fox (Vulpes vulpes), the world's most widely distributed wild terrestrial carnivore. Analyses of 697 bp of mitochondrial sequence in ~1000 individuals suggested an ancient Middle Eastern origin for all extant red foxes and a 400 kya (SD = 139 kya) origin of the primary North American (Nearctic) clade. Demographic analyses indicated a major expansion in Eurasia during the last glaciation (~50 kya), coinciding with a previously described secondary transfer of a single matriline (Holarctic) to North America. In contrast, North American matrilines (including the transferred portion of Holarctic clade) exhibited no signatures of expansion until the end of the Pleistocene (~12 kya). Analyses of 11 autosomal loci from a subset of foxes supported the colonization time frame suggested by mtDNA (and the fossil record) but, in contrast, reflected no detectable secondary transfer, resulting in the most fundamental genomic division of red foxes at the Bering Strait. Endemic continental Y-chromosome clades further supported this pattern. Thus, intercontinental genomic exchange was overall very limited, consistent with long-term reproductive isolation since the initial colonization of North America. Based on continental divergence times in other carnivoran species pairs, our findings support a model of peripatric speciation and are consistent with the previous classification of the North American red fox as a distinct species, V. fulva. © 2014 John Wiley & Sons Ltd.

  16. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance.

    Science.gov (United States)

    Ferris, Elliott; Abegglen, Lisa M; Schiffman, Joshua D; Gregg, Christopher

    2018-03-06

    The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.

    Science.gov (United States)

    Clarke, Hannah F; Horst, Nicole K; Roberts, Angela C

    2015-03-31

    Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach-avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala-anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

  18. Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.; (UTSMC)

    2010-09-21

    LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

  19. OCT2, SSX and SAGE1 reveal the phenotypic heterogeneity of spermatocytic seminoma reflecting distinct subpopulations of spermatogonia

    DEFF Research Database (Denmark)

    Lim, Jasmine; Goriely, Anne; Turner, Gareth Dh

    2011-01-01

    in the normal adult testis. We analysed the expression pattern of OCT2, SSX2-4, and SAGE1 in 36 SS cases and four intratubular SS (ISS) as well as a series of normal testis samples throughout development. We describe for the first time two different types of SS characterized by OCT2 or SSX2-4 immunoexpression......, whilst SAGE1 was exclusively present in a subset of post-pubertal germ cells, most likely B spermatogonia. The presence of OCT2 and SSX2-4 in distinct subsets of germ cells implies that these markers represent germ cells at different maturation stages. Analysis of SAGE1 and SSX2-4 in ISS showed spatial...... differences suggesting ongoing maturation of germ cells during progression of SS tumourigenesis. We conclude that the expression pattern of OCT2, SSX2-4, and SAGE1 supports the origin of SS from spermatogonia and provides new evidence for heterogeneity of this tumour, potentially linked either to the cellular...

  20. Saturation Mutagenesis of the HIV-1 Envelope CD4 Binding Loop Reveals Residues Controlling Distinct Trimer Conformations.

    Directory of Open Access Journals (Sweden)

    Maria Duenas-Decamp

    2016-11-01

    Full Text Available The conformation of HIV-1 envelope (Env glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD was investigated using a novel saturation mutagenesis approach. Single mutations identified, resulted in distinct trimer conformations affecting CD4bs exposure, the glycan shield and the TAD across diverse HIV-1 clades. Importantly, mutations that improve access to the CD4bs without exposing the immunodominant V3 loop were identified. The different trimer conformations identified will affect the specificity and breadth of nabs elicited in vivo and are important to consider in design of Env immunogens for vaccines.

  1. Integrative omic analysis reveals distinctive cold responses in leaves and roots of strawberry, Fragaria × ananassa ‘Korona’

    Directory of Open Access Journals (Sweden)

    Gage eKoehler

    2015-10-01

    Full Text Available To assess underlying metabolic processes and regulatory mechanisms during cold exposure of strawberry, integrative omic approaches were applied to Fragaria × ananassa Duch. ‘Korona’. Both root and leaf tissues were examined for responses to the cold acclimation processes. Levels of metabolites, proteins, and transcripts in tissues from plants grown at 18°C were compared to those following 1 to 10 days of cold (2°C exposure. Overall, ‘Korona’ showed a modest increase of protective metabolites such as amino acids (aspartic acid, leucine, isoleucine, and valine, pentoses, phosphorylated and non-phosphorylated hexoses, and distinct compounds of the raffinose pathway (galactinol and raffinose. By 2DE proteomics a total of 845 spots were observed in leaves; 4.6% changed significantly in response to cold.Transcript levels in leaves were determined by microarray, where dozens of cold associated transcripts were quantitatively characterized, and levels of several potential key contributors (e.g., the dehydrin COR47 and GADb to cold tolerance were confirmed by qRT-PCR. Cold responses are placed within the existing knowledge base of low temperature stress change in plants, allowing an evaluation of the uniqueness or generality of Fragaria responses in photosynthetic tissues. Overall, the cold response characteristics of ‘Korona’ are consistent with a moderately cold tolerant plant.

  2. Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma.

    Science.gov (United States)

    Sivakumar, Smruthy; Lucas, F Anthony San; McDowell, Tina L; Lang, Wenhua; Xu, Li; Fujimoto, Junya; Zhang, Jianjun; Futreal, P Andrew; Fukuoka, Junya; Yatabe, Yasushi; Dubinett, Steven M; Spira, Avrum E; Fowler, Jerry; Hawk, Ernest T; Wistuba, Ignacio I; Scheet, Paul; Kadara, Humam

    2017-11-15

    There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AAH, LUAD, and normal tissues. Somatic BRAF variants were found in AAHs from 5 of 22 (23%) patients, 4 of 5 of whom had matched LUAD with driver EGFR mutations. KRAS mutations were present in AAHs from 4 of 22 (18%) of patients. KRAS mutations in AAH were only found in ever-smokers and were exclusive to BRAF -mutant cases. Integrative analysis revealed profiles expressed in KRAS -mutant cases ( UBE2C, REL ) and BRAF -mutant cases ( MAX ) of AAH, or common to both sets of cases (suppressed AXL ). Gene sets associated with suppressed antitumor (Th1; IL12A, GZMB ) and elevated protumor ( CCR2, CTLA-4 ) immune signaling were enriched in AAH development and progression. Our results reveal potentially divergent BRAF or KRAS pathways in AAH as well as immune dysregulation in the pathogenesis of this premalignant lung lesion. Cancer Res; 77(22); 6119-30. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Whole genome comparisons of Fragaria, Prunus and Malus reveal different modes of evolution between Rosaceous subfamilies.

    Science.gov (United States)

    Jung, Sook; Cestaro, Alessandro; Troggio, Michela; Main, Dorrie; Zheng, Ping; Cho, Ilhyung; Folta, Kevin M; Sosinski, Bryon; Abbott, Albert; Celton, Jean-Marc; Arús, Pere; Shulaev, Vladimir; Verde, Ignazio; Morgante, Michele; Rokhsar, Daniel; Velasco, Riccardo; Sargent, Daniel James

    2012-04-04

    Rosaceae include numerous economically important and morphologically diverse species. Comparative mapping between the member species in Rosaceae have indicated some level of synteny. Recently the whole genome of three crop species, peach, apple and strawberry, which belong to different genera of the Rosaceae family, have been sequenced, allowing in-depth comparison of these genomes. Our analysis using the whole genome sequences of peach, apple and strawberry identified 1399 orthologous regions between the three genomes, with a mean length of around 100 kb. Each peach chromosome showed major orthology mostly to one strawberry chromosome, but to more than two apple chromosomes, suggesting that the apple genome went through more chromosomal fissions in addition to the whole genome duplication after the divergence of the three genera. However, the distribution of contiguous ancestral regions, identified using the multiple genome rearrangements and ancestors (MGRA) algorithm, suggested that the Fragaria genome went through a greater number of small scale rearrangements compared to the other genomes since they diverged from a common ancestor. Using the contiguous ancestral regions, we reconstructed a hypothetical ancestral genome for the Rosaceae 7 composed of nine chromosomes and propose the evolutionary steps from the ancestral genome to the extant Fragaria, Prunus and Malus genomes. Our analysis shows that different modes of evolution may have played major roles in different subfamilies of Rosaceae. The hypothetical ancestral genome of Rosaceae and the evolutionary steps that lead to three different lineages of Rosaceae will facilitate our understanding of plant genome evolution as well as have a practical impact on knowledge transfer among member species of Rosaceae.

  4. Whole genome comparisons of Fragaria, Prunus and Malus reveal different modes of evolution between Rosaceous subfamilies

    Directory of Open Access Journals (Sweden)

    Jung Sook

    2012-04-01

    Full Text Available Abstract Background Rosaceae include numerous economically important and morphologically diverse species. Comparative mapping between the member species in Rosaceae have indicated some level of synteny. Recently the whole genome of three crop species, peach, apple and strawberry, which belong to different genera of the Rosaceae family, have been sequenced, allowing in-depth comparison of these genomes. Results Our analysis using the whole genome sequences of peach, apple and strawberry identified 1399 orthologous regions between the three genomes, with a mean length of around 100 kb. Each peach chromosome showed major orthology mostly to one strawberry chromosome, but to more than two apple chromosomes, suggesting that the apple genome went through more chromosomal fissions in addition to the whole genome duplication after the divergence of the three genera. However, the distribution of contiguous ancestral regions, identified using the multiple genome rearrangements and ancestors (MGRA algorithm, suggested that the Fragaria genome went through a greater number of small scale rearrangements compared to the other genomes since they diverged from a common ancestor. Using the contiguous ancestral regions, we reconstructed a hypothetical ancestral genome for the Rosaceae 7 composed of nine chromosomes and propose the evolutionary steps from the ancestral genome to the extant Fragaria, Prunus and Malus genomes. Conclusion Our analysis shows that different modes of evolution may have played major roles in different subfamilies of Rosaceae. The hypothetical ancestral genome of Rosaceae and the evolutionary steps that lead to three different lineages of Rosaceae will facilitate our understanding of plant genome evolution as well as have a practical impact on knowledge transfer among member species of Rosaceae.

  5. Crystal structure of a small heat-shock protein from Xylella fastidiosa reveals a distinct high-order structure.

    Science.gov (United States)

    Fonseca, Emanuella Maria Barreto; Scorsato, Valéria; Dos Santos, Marcelo Leite; Júnior, Atilio Tomazini; Tada, Susely Ferraz Siqueira; Dos Santos, Clelton Aparecido; de Toledo, Marcelo Augusto Szymanski; de Souza, Anete Pereira; Polikarpov, Igor; Aparicio, Ricardo

    2017-04-01

    Citrus variegated chlorosis is a disease that attacks economically important citrus plantations and is caused by the plant-pathogenic bacterium Xylella fastidiosa. In this work, the structure of a small heat-shock protein from X. fastidiosa (XfsHSP17.9) is reported. The high-order structures of small heat-shock proteins from other organisms are arranged in the forms of double-disc, hollow-sphere or spherical assemblies. Unexpectedly, the structure reported here reveals a high-order architecture forming a nearly square cavity.

  6. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

    Directory of Open Access Journals (Sweden)

    Rakhshan Ihsan

    Full Text Available Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR, classification and regression tree (CART and multifactor dimensionality reduction (MDR, was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01, whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively. In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His, SULT1A1 213GG (Arg/Arg or AA (His/His and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006, whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01. MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His with testing balance accuracy (TBA of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with

  7. Siple Dome ice reveals two modes of millennial CO2 change during the last ice age

    Science.gov (United States)

    Ahn, Jinho; Brook, Edward J.

    2014-01-01

    Reconstruction of atmospheric CO2 during times of past abrupt climate change may help us better understand climate-carbon cycle feedbacks. Previous ice core studies reveal simultaneous increases in atmospheric CO2 and Antarctic temperature during times when Greenland and the northern hemisphere experienced very long, cold stadial conditions during the last ice age. Whether this relationship extends to all of the numerous stadial events in the Greenland ice core record has not been clear. Here we present a high-resolution record of atmospheric CO2 from the Siple Dome ice core, Antarctica for part of the last ice age. We find that CO2 does not significantly change during the short Greenlandic stadial events, implying that the climate system perturbation that produced the short stadials was not strong enough to substantially alter the carbon cycle. PMID:24781344

  8. Rhabdovirus matrix protein structures reveal a novel mode of self-association.

    Directory of Open Access Journals (Sweden)

    Stephen C Graham

    2008-12-01

    Full Text Available The matrix (M proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus and from Lagos bat virus (genus: Lyssavirus, revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins.

  9. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia

    Science.gov (United States)

    Kerr, Peter J.; Cattadori, Isabella M.; Fitch, Adam; Geber, Adam; Liu, June; Sim, Derek G.; Boag, Brian; Ghedin, Elodie

    2017-01-01

    The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954–1955) and between 2008–2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms. PMID:28253375

  10. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

    Directory of Open Access Journals (Sweden)

    Peter J Kerr

    2017-03-01

    Full Text Available The co-evolution of myxoma virus (MYXV and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955 and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release Lausanne strain. Inferred virulence ranged from highly virulent (grade 1 to highly attenuated (grade 5. Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.

  11. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

    Science.gov (United States)

    Kerr, Peter J; Cattadori, Isabella M; Rogers, Matthew B; Fitch, Adam; Geber, Adam; Liu, June; Sim, Derek G; Boag, Brian; Eden, John-Sebastian; Ghedin, Elodie; Read, Andrew F; Holmes, Edward C

    2017-03-01

    The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955) and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.

  12. Three distinct Holocene intervals of stalagmite deposition and nondeposition revealed in NW Madagascar, and their paleoclimate implications

    Science.gov (United States)

    Riavo Gilbertinie Voarintsoa, Ny; Railsback, Loren Bruce; Brook, George Albert; Wang, Lixin; Kathayat, Gayatri; Cheng, Hai; Li, Xianglei; Edwards, Richard Lawrence; Rakotondrazafy, Amos Fety Michel; Olga Madison Razanatseheno, Marie

    2017-12-01

    Petrographic features, mineralogy, and stable isotopes from two stalagmites, ANJB-2 and MAJ-5, respectively from Anjohibe and Anjokipoty caves, allow distinction of three intervals of the Holocene in NW Madagascar. The Malagasy early Holocene (between ca. 9.8 and 7.8 ka) and late Holocene (after ca. 1.6 ka) intervals (MEHI and MLHI, respectively) record evidence of stalagmite deposition. The Malagasy middle Holocene interval (MMHI, between ca. 7.8 and 1.6 ka) is marked by a depositional hiatus of ca. 6500 years. Deposition of these stalagmites indicates that the two caves were sufficiently supplied with water to allow stalagmite formation. This suggests that the MEHI and MLHI intervals may have been comparatively wet in NW Madagascar. In contrast, the long-term depositional hiatus during the MMHI implies it was relatively drier than the MEHI and the MLHI. The alternating wet-dry-wet conditions during the Holocene may have been linked to the long-term migrations of the Intertropical Convergence Zone (ITCZ). When the ITCZ's mean position is farther south, NW Madagascar experiences wetter conditions, such as during the MEHI and MLHI, and when it moves north, NW Madagascar climate becomes drier, such as during the MMHI. A similar wet-dry-wet succession during the Holocene has been reported in neighboring locations, such as southeastern Africa. Beyond these three subdivisions, the records also suggest wet conditions around the cold 8.2 ka event, suggesting a causal relationship. However, additional Southern Hemisphere high-resolution data will be needed to confirm this.

  13. Molecular diversity of poleroviruses infecting cucurbit crops in four countries reveals the presence of members of six distinct species.

    Science.gov (United States)

    Knierim, D; Tsai, W S; Maiss, E; Kenyon, L

    2014-06-01

    When 66 cucurbit samples with yellowing symptoms from fields in Mali, the Philippines, Thailand and Uzbekistan were screened by RT-PCR using universal polerovirus primers, 21 were identified as harboring polerovirus RNA. When these 21 samples were screened with specific primers for the known cucurbit-infecting poleroviruses, suakwa aphid-borne yellows virus and a recombinant strain of cucurbit aphid-borne yellows virus were detected for the first time in the Philippines and Thailand. However, seven polerovirus-positive samples did not react with any of the known species-specific primers. Sequencing of 1.4-kb universal polerovirus RT-PCR products revealed the presence of two poleroviruses that had not been described previously. These viruses, from Mali and Thailand, were provisionally named pepo aphid-borne yellows virus and luffa aphid-borne yellows virus, respectively.

  14. Metagenome Sequence Analysis of Filamentous Microbial Communities Obtained from Geochemically Distinct Geothermal Channels Reveals Specialization of Three Aquificales Lineages

    Directory of Open Access Journals (Sweden)

    Cristina eTakacs-vesbach

    2013-05-01

    Full Text Available The Aquificales are thermophilic microorganisms that inhabit hydrothermal systems worldwide and are considered one of the earliest lineages of the domain Bacteria. We analyzed metagenome sequence obtained from six thermal ‘filamentous streamer’ communities (~40 Mbp per site, which targeted three different groups of Aquificales found in Yellowstone National Park (YNP. Unassembled metagenome sequence and PCR-amplified 16S rRNA gene libraries revealed that acidic, sulfidic sites were dominated by Hydrogenobaculum (Aquificaceae populations, whereas the circumneutral pH (6.5 - 7.8 sites containing dissolved sulfide were dominated by Sulfurihydrogenibium spp. (Hydrogenothermaceae. Thermocrinis (Aquificaceae populations were found primarily in the circumneutral sites with undetectable sulfide, and to a lesser extent in one sulfidic system at pH 8. Phylogenetic analysis of assembled sequence containing 16S rRNA genes as well as conserved protein-encoding genes revealed that the composition and function of these communities varied across geochemical conditions. Each Aquificales lineage contained genes for CO2 fixation by the reverse TCA cycle, but only the Sulfurihydrogenibium populations perform citrate cleavage using ATP citrate lyase (Acl. The Aquificaceae populations use an alternative pathway catalyzed by two separate enzymes, citryl CoA synthetase (Ccs and citryl CoA lyase (Ccl. All three Aquificales lineages contained evidence of aerobic respiration, albeit due to completely different types of heme Cu oxidases (subunit I involved in oxygen reduction. The distribution of Aquificales populations and differences among functional genes involved in energy generation and electron transport is consistent with the hypothesis that geochemical parameters (e.g., pH, sulfide, H2, O2 have resulted in niche specialization among members of the Aquificales.

  15. Discovery of a novel bottlenose dolphin coronavirus reveals a distinct species of marine mammal coronavirus in Gammacoronavirus.

    Science.gov (United States)

    Woo, Patrick C Y; Lau, Susanna K P; Lam, Carol S F; Tsang, Alan K L; Hui, Suk-Wai; Fan, Rachel Y Y; Martelli, Paolo; Yuen, Kwok-Yung

    2014-01-01

    While gammacoronaviruses mainly comprise infectious bronchitis virus (IBV) and its closely related bird coronaviruses (CoVs), the only mammalian gammacoronavirus was discovered from a white beluga whale (beluga whale CoV [BWCoV] SW1) in 2008. In this study, we discovered a novel gammacoronavirus from fecal samples from three Indo-Pacific bottlenose dolphins (Tursiops aduncus), which we named bottlenose dolphin CoV (BdCoV) HKU22. All the three BdCoV HKU22-positive samples were collected on the same date, suggesting a cluster of infection, with viral loads of 1 × 10(3) to 1 × 10(5) copies per ml. Clearance of virus was associated with a specific antibody response against the nucleocapsid of BdCoV HKU22. Complete genome sequencing and comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 have similar genome characteristics and structures. Their genome size is about 32,000 nucleotides, the largest among all CoVs, as a result of multiple unique open reading frames (NS5a, NS5b, NS5c, NS6, NS7, NS8, NS9, and NS10) between their membrane (M) and nucleocapsid (N) protein genes. Although comparative genome analysis showed that BdCoV HKU22 and BWCoV SW1 should belong to the same species, a major difference was observed in the proteins encoded by their spike (S) genes, which showed only 74.3 to 74.7% amino acid identities. The high ratios of the number of synonymous substitutions per synonymous site (Ks) to the number of nonsynonymous substitutions per nonsynonymous site (Ka) in multiple regions of the genome, especially the S gene (Ka/Ks ratio, 2.5), indicated that BdCoV HKU22 may be evolving rapidly, supporting a recent transmission event to the bottlenose dolphins. We propose a distinct species, Cetacean coronavirus, in Gammacoronavirus, to include BdCoV HKU22 and BWCoV SW1, whereas IBV and its closely related bird CoVs represent another species, Avian coronavirus, in Gammacoronavirus.

  16. Automatic and Controlled Semantic Retrieval: TMS Reveals Distinct Contributions of Posterior Middle Temporal Gyrus and Angular Gyrus.

    Science.gov (United States)

    Davey, James; Cornelissen, Piers L; Thompson, Hannah E; Sonkusare, Saurabh; Hallam, Glyn; Smallwood, Jonathan; Jefferies, Elizabeth

    2015-11-18

    Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the "default mode network" and "frontoparietal control system," respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label "Alsatian" not "animal"). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval. We demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to

  17. Deep sequencing reveals exceptional diversity and modes of transmission for bacterial sponge symbionts.

    Science.gov (United States)

    Webster, Nicole S; Taylor, Michael W; Behnam, Faris; Lücker, Sebastian; Rattei, Thomas; Whalan, Stephen; Horn, Matthias; Wagner, Michael

    2010-08-01

    Marine sponges contain complex bacterial communities of considerable ecological and biotechnological importance, with many of these organisms postulated to be specific to sponge hosts. Testing this hypothesis in light of the recent discovery of the rare microbial biosphere, we investigated three Australian sponges by massively parallel 16S rRNA gene tag pyrosequencing. Here we show bacterial diversity that is unparalleled in an invertebrate host, with more than 250,000 sponge-derived sequence tags being assigned to 23 bacterial phyla and revealing up to 2996 operational taxonomic units (95% sequence similarity) per sponge species. Of the 33 previously described 'sponge-specific' clusters that were detected in this study, 48% were found exclusively in adults and larvae - implying vertical transmission of these groups. The remaining taxa, including 'Poribacteria', were also found at very low abundance among the 135,000 tags retrieved from surrounding seawater. Thus, members of the rare seawater biosphere may serve as seed organisms for widely occurring symbiont populations in sponges and their host association might have evolved much more recently than previously thought. © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

  18. Morphological and Molecular Data Reveal Three Distinct Populations of Indian Wild Rice Oryza rufipogon Griff. Species Complex.

    Science.gov (United States)

    Singh, Balwant; Singh, Nisha; Mishra, Shefali; Tripathi, Kabita; Singh, Bikram P; Rai, Vandna; Singh, Ashok K; Singh, Nagendra K

    2018-01-01

    Wild relatives of crops possess adaptive mutations for agronomically important traits, which could play significant role in crop improvement for sustainable agriculture. However, global climate change and human activities pose serious threats to the natural habitats leading to erosion of genetic diversity of wild rice populations. The purpose of this study was to explore and characterize India's huge untapped wild rice diversity in Oryza rufipogon Griff. species complex from a wide range of ecological niches. We made strategic expeditions around diversity hot spots in 64 districts of nine different agro-climatic zones of the country and collected 418 wild rice accessions. Significant variation was observed among the accessions for 46 morphological descriptors, allowing classification into O. nivara, O. rufipogon , and O. sativa f. spontanea morpho-taxonomic groups. Genome-specific pSINE1 markers confirmed all the accessions having AA genome, which were further classified using ecotype-specific pSINE1 markers into annual, perennial, intermediate, and an unknown type. Principal component analysis revealed continuous variation for the morphological traits in each ecotype group. Genetic diversity analysis based on multi-allelic SSR markers clustered these accessions into three major groups and analysis of molecular variance for nine agro-climatic zones showed that 68% of the genetic variation was inherent amongst individuals while only 11% of the variation separated the zones, though there was significant correlation between genetic and spatial distances of the accessions. Model based population structure analysis using genome wide bi-allelic SNP markers revealed three sub-populations designated 'Pro-Indica,' 'Pro-Aus,' and 'Mid-Gangetic,' which showed poor correspondence with the morpho - taxonomic classification or pSINE1 ecotypes. There was Pan-India distribution of the 'Pro-Indica' and 'Pro-Aus' sub-populations across agro-climatic zones, indicating a more

  19. Morphological and Molecular Data Reveal Three Distinct Populations of Indian Wild Rice Oryza rufipogon Griff. Species Complex

    Science.gov (United States)

    Singh, Balwant; Singh, Nisha; Mishra, Shefali; Tripathi, Kabita; Singh, Bikram P.; Rai, Vandna; Singh, Ashok K.; Singh, Nagendra K.

    2018-01-01

    Wild relatives of crops possess adaptive mutations for agronomically important traits, which could play significant role in crop improvement for sustainable agriculture. However, global climate change and human activities pose serious threats to the natural habitats leading to erosion of genetic diversity of wild rice populations. The purpose of this study was to explore and characterize India’s huge untapped wild rice diversity in Oryza rufipogon Griff. species complex from a wide range of ecological niches. We made strategic expeditions around diversity hot spots in 64 districts of nine different agro-climatic zones of the country and collected 418 wild rice accessions. Significant variation was observed among the accessions for 46 morphological descriptors, allowing classification into O. nivara, O. rufipogon, and O. sativa f. spontanea morpho-taxonomic groups. Genome-specific pSINE1 markers confirmed all the accessions having AA genome, which were further classified using ecotype-specific pSINE1 markers into annual, perennial, intermediate, and an unknown type. Principal component analysis revealed continuous variation for the morphological traits in each ecotype group. Genetic diversity analysis based on multi-allelic SSR markers clustered these accessions into three major groups and analysis of molecular variance for nine agro-climatic zones showed that 68% of the genetic variation was inherent amongst individuals while only 11% of the variation separated the zones, though there was significant correlation between genetic and spatial distances of the accessions. Model based population structure analysis using genome wide bi-allelic SNP markers revealed three sub-populations designated ‘Pro-Indica,’ ‘Pro-Aus,’ and ‘Mid-Gangetic,’ which showed poor correspondence with the morpho-taxonomic classification or pSINE1 ecotypes. There was Pan-India distribution of the ‘Pro-Indica’ and ‘Pro-Aus’ sub-populations across agro-climatic zones

  20. Lipidomic profiling reveals distinct differences in plasma lipid composition in healthy, prediabetic, and type 2 diabetic individuals

    Science.gov (United States)

    Zhong, Huanzi; Fang, Chao; Fan, Yanqun; Lu, Yan; Wen, Bo; Ren, Huahui; Hou, Guixue; Yang, Fangming; Xie, Hailiang; Jie, Zhuye; Peng, Ye; Ye, Zhiqiang; Wu, Jiegen; Zi, Jin; Zhao, Guoqing; Chen, Jiayu; Bao, Xiao; Hu, Yihe; Gao, Yan; Zhang, Jun; Yang, Huanming; Wang, Jian; Madsen, Lise; Kristiansen, Karsten

    2017-01-01

    Abstract The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development. PMID:28505362

  1. Azadirachtin(A) distinctively modulates subdomain 2 of actin - novel mechanism to induce depolymerization revealed by molecular dynamics study.

    Science.gov (United States)

    Pravin Kumar, R; Roopa, L; Sudheer Mohammed, M M; Kulkarni, Naveen

    2016-12-01

    Azadirachtin(A) (AZA), a potential insecticide from neem, binds to actin and induces depolymerization in Drosophila. AZA binds to the pocket same as that of Latrunculin A (LAT), but LAT inhibits actin polymerization by stiffening the actin structure and affects the ADP-ATP exchange. The mechanism by which AZA induces actin depolymerization is not clearly understood. Therefore, different computational experiments were conducted to delineate the precise mechanism of AZA-induced actin depolymerization. Molecular dynamics studies showed that AZA strongly interacted with subdomain 2 and destabilized the interactions between subdomain 2 of one actin and subdomains 1 and 4 of the adjacent actin, causing the separation of actin subunits. The separation was observed between subdomain 3 of subunit n and subdomain 4 of subunit n + 2. However, the specific triggering point for the separation of the subunits was the destabilization of direct interactions between subdomain 2 of subunit n (Arg39, Val45, Gly46 and Arg62) and subdomain 4 of subunit n + 2 (Asp286, Ile287, Asp288, Ile289, Asp244 and Lys291). These results reveal a unique mechanism of an actin filament modulator that induces depolymerization. This mechanism of AZA can be used to design similar molecules against mammalian actins for cancer therapy.

  2. Molecular characterization of HCV in a Swedish county over 8 years (2002–2009 reveals distinct transmission patterns

    Directory of Open Access Journals (Sweden)

    Josefine Ederth

    2016-02-01

    Full Text Available Background: Hepatitis C virus (HCV is a major public health concern and data on its molecular epidemiology in Sweden is scarce. We carried out an 8-year population-based study of newly diagnosed HCV cases in one of Sweden's centrally situated counties, Södermanland (D-county. The aim was to characterize the HCV strains circulating, analyze their genetic relatedness to detect networks, and in combination with demographic data learn more about transmission. Methods: Molecular analyses of serum samples from 91% (N=557 of all newly notified cases in D-county, 2002–2009, were performed. Phylogenetic analysis (NS5B gene, 300 bp was linked to demographic data from the national surveillance database, SmiNet, to characterize D-county transmission clusters. The linear-by-linear association test (LBL was used to analyze trends over time. Results: The most prevalent subtypes were 1a (38% and 3a (34%. Subtype 1a was most prevalent among cases transmitted via sexual contact, via contaminated blood, or blood products, while subtype 3a was most prevalent among people who inject drugs (PWIDs. Phylogenetic analysis revealed that the subtype 3a sequences formed more and larger transmission clusters (50% of the sequences clustered, while the 1a sequences formed smaller clusters (19% of the sequences clustered, possibly suggesting different epidemics. Conclusion: We found different transmission patterns in D-county which may, from a public health perspective, have implications for how to control virus infections by targeted interventions.

  3. Use of a molecular genetic platform technology to produce human Wnt proteins reveals distinct local and distal signaling abilities.

    Directory of Open Access Journals (Sweden)

    Jennifer L Green

    Full Text Available Functional and mechanistic studies of Wnt signaling have been severely hindered by the inaccessibility of bioactive proteins. To overcome this long-standing barrier, we engineered and characterized a panel of Chinese hamster ovary (CHO cell lines with inducible transgenes encoding tagged and un-tagged human WNT1, WNT3A, WNT5A, WNT7A, WNT11, WNT16 or the soluble Wnt antagonist Fzd8CRD, all integrated into an identical genomic locus. Using a quantitative real-time bioluminescence assay, we show that cells expressing WNT1, 3A and 7A stimulate Wnt/beta-catenin reporter activity, while the other WNT expressing cell lines interfere with this activation. Additionally, in contrast to WNT3A, WNT1 only exhibits activity when cell-associated, and thus only signals to neighboring cells. The reporter assay also revealed a rapid decline of Wnt activity at 37°C, indicating that Wnt activity is highly labile. These engineered cell lines will reduce the cost of making and purifying Wnt proteins and serve as a continuous, reliable and regulatable source of Wnts to research laboratories around the world.

  4. Genome-wide transcriptional profiling reveals two distinct outcomes in central Nervous system infections of rabies virus

    Directory of Open Access Journals (Sweden)

    Daiting eZhang

    2016-05-01

    Full Text Available Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq to compare the brain transcriptomes of normal mice versus HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV infection can effectively prevent the CVS-11 to invade central nervous system (CNS, but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4+ T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the postexposure treatment window

  5. Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

    Directory of Open Access Journals (Sweden)

    Miriam Matamales

    Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

  6. Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

    Science.gov (United States)

    Cauli, Alberto; Mathieu, Alessandro; Tedeschi, Valentina; Caristi, Silvana; Sorrentino, Rosa; Böckmann, Rainer A.; Fiorillo, Maria Teresa

    2012-01-01

    The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype. PMID:22403718

  7. Multistationary and oscillatory modes of free radicals generation by the mitochondrial respiratory chain revealed by a bifurcation analysis.

    Directory of Open Access Journals (Sweden)

    Vitaly A Selivanov

    Full Text Available The mitochondrial electron transport chain transforms energy satisfying cellular demand and generates reactive oxygen species (ROS that act as metabolic signals or destructive factors. Therefore, knowledge of the possible modes and bifurcations of electron transport that affect ROS signaling provides insight into the interrelationship of mitochondrial respiration with cellular metabolism. Here, a bifurcation analysis of a sequence of the electron transport chain models of increasing complexity was used to analyze the contribution of individual components to the modes of respiratory chain behavior. Our algorithm constructed models as large systems of ordinary differential equations describing the time evolution of the distribution of redox states of the respiratory complexes. The most complete model of the respiratory chain and linked metabolic reactions predicted that condensed mitochondria produce more ROS at low succinate concentration and less ROS at high succinate levels than swelled mitochondria. This prediction was validated by measuring ROS production under various swelling conditions. A numerical bifurcation analysis revealed qualitatively different types of multistationary behavior and sustained oscillations in the parameter space near a region that was previously found to describe the behavior of isolated mitochondria. The oscillations in transmembrane potential and ROS generation, observed in living cells were reproduced in the model that includes interaction of respiratory complexes with the reactions of TCA cycle. Whereas multistationarity is an internal characteristic of the respiratory chain, the functional link of respiration with central metabolism creates oscillations, which can be understood as a means of auto-regulation of cell metabolism.

  8. Revealing silent vibration modes of nanomaterials by detecting anti-Stokes hyper-Raman scattering with femtosecond laser pulses.

    Science.gov (United States)

    Zeng, Jianhua; Chen, Lei; Dai, Qiaofeng; Lan, Sheng; Tie, Shaolong

    2016-01-21

    We proposed a scheme in which normal Raman scattering is coupled with hyper-Raman scattering for generating a strong anti-Stokes hyper-Raman scattering in nanomaterials by using femtosecond laser pulses. The proposal was experimentally demonstrated by using a single-layer MoS2 on a SiO2/Si substrate, a 17 nm-thick MoS2 on an Au/SiO2 substrate and a 9 nm-thick MoS2 on a SiO2-SnO2/Ag/SiO2 substrate which were confirmed to be highly efficient for second harmonic generation. A strong anti-Stokes hyper-Raman scattering was also observed in other nanomaterials possessing large second-order susceptibilities, such as silicon quantum dots self-assembled into "coffee" rings and tubular Cu-doped ZnO nanorods. In all the cases, many Raman inactive vibration modes were clearly revealed in the anti-Stokes hyper-Raman scattering. Apart from the strong anti-Stokes hyper-Raman scattering, Stokes hyper-Raman scattering with small Raman shifts was detected during the ablation process of thick MoS2 layers. It was also observed by slightly defocusing the excitation light. The detection of anti-Stokes hyper-Raman scattering may serve as a new technique for studying the Raman inactive vibration modes in nanomaterials.

  9. Revealing climate modes in steric sea levels: lessons learned from satellite geodesy, objective analyses and ocean reanalyses

    Science.gov (United States)

    Pfeffer, J.; Tregoning, P.; Purcell, A. P.

    2017-12-01

    Due to increased greenhouse gases emissions, the oceans are accumulating heat. In response to the ocean circulation and atmospheric forcing, the heat is irregularly redistributed within the oceans, causing sea level to rise at variable rates in space and time. These rates of steric expansion are extremely difficult to assess because of the sparsity of in-situ hydrographic observations available within the course of the 20th century. We compare here three methods to reconstruct the steric sea levels over the past 13, 25 and 58 years based on satellite geodesy, objective analyses and ocean reanalyses. The interannual to decadal variability of each dataset is explored with a model merging six climate indices representative of the natural variability of the ocean and climate system. Consistent regional patterns are identified for the Pacific Decadal Oscillation (PDO) and El Niño Southern Oscillation (ENSO) in all datasets at all timescales. Despite the short time coverage (13 years), the combination of satellite geodetic data (altimetry and GRACE) also reveals significant steric responses to the North Pacific Gyre Oscillation (NPGO), Indian Dipole (IOD) and Indian ocean basinwide (IOBM) mode. The richer information content in the ocean reanalyses allows us to recover the regional fingerprints of the PDO, ENSO, NPGO, IOD and IOBM, but also of the Atlantic Multidecadal Oscillation (AMO) acting over longer time scales (40 to 60 years). Therefore, ocean reanalyses, coupled with climate mode analyses, constitute innovative and promising tools to investigate the mechanisms triggering the variability of sea level rise over the past decades.

  10. Revealing Extremely Low Energy Amplitude Modes in the Charge-Density-Wave Compound LaAgSb_{2}.

    Science.gov (United States)

    Chen, R Y; Zhang, S J; Zhang, M Y; Dong, T; Wang, N L

    2017-03-10

    Using infrared spectroscopy and ultrafast pump probe measurement, we have studied the two charge-density-wave (CDW) instabilities in the layered compound LaAgSb_{2}. The development of CDW energy gaps was clearly observed by optical spectroscopy, which removed most of the free carrier spectral weight. More interestingly, our time-resolved measurements revealed two coherent oscillations that softened by approaching the two phase transition temperatures, respectively. We addressed that these two oscillations come from the amplitude modes of CDW collective excitations, the surprisingly low energies (0.12 THz and 0.34 THz for the higher and lower temperature ones, respectively) of which are associated with the extremely small nesting wave vectors. Additionally, the amplitude and relaxation time of photoinduced reflectivity of LaAgSb_{2} single crystals stayed unchanged across the CDW phase transitions, which is quite rare and deserves further investigation.

  11. Multi-mode interference revealed by two photon absorption in silicon rich SiO2 waveguides

    International Nuclear Information System (INIS)

    Manna, S.; Ramiro-Manzano, F.; Mancinelli, M.; Turri, F.; Pavesi, L.; Ghulinyan, M.; Pucker, G.

    2015-01-01

    Photoluminescence (PL) from Si nanocrystals (NCs) excited by two-photon absorption (TPA) has been observed in Si nanocrystal-based waveguides fabricated by plasma enhanced chemical vapor deposition. The TPA excited photoluminescence emission resembles the one-photon excited photoluminescence arising from inter-band transitions in the quantum confined Si nanocrystals. By measuring the non-linear transmission of waveguides, a large TPA coefficient of β up to 10 −8  cm/W has been measured at 1550 nm. These values of β depend on the Si NCs size and are two orders of magnitude larger than the bulk silicon value. Here, we propose to use the TPA excited visible PL emission as a tool to map the spatial intensity profile of the 1550 nm propagating optical modes in multimode waveguides. In this way, multimode interference has been revealed experimentally and confirmed through a finite element simulation

  12. Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits

    Science.gov (United States)

    Marcelletti, Simone; Scortichini, Marco

    2015-01-01

    The European hazelnut (Corylus avellana) is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches. PMID:26147218

  13. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    DEFF Research Database (Denmark)

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.

    2015-01-01

    organic matter on the bacterial communities. The copy number of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below -10ºC. Multivariate statistical analysis of the bacterial diversity data (DNA......The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78º......N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable...

  14. Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

    Directory of Open Access Journals (Sweden)

    Norio Takata

    Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

  15. Revealing the distinct habitat ranges and hybrid zone of genetic sub-populations within Pseudo-nitzschia pungens (Bacillariophyceae) in the West Pacific area.

    Science.gov (United States)

    Kim, Jin Ho; Wang, Pengbin; Park, Bum Soo; Kim, Joo-Hwan; Patidar, Shailesh Kumar; Han, Myung-Soo

    2018-03-01

    Genetic sub-populations (clades) of cosmopolitan marine diatom Pseudo-nitzschia pungens might have distinct habitats, and their hybrid zone is suspected in higher latitude area of the West Pacific area, however, it is still unrevealed because of technical difficulties and lack of evidences in natural environments. The aim of this study is to investigate the habitat characteristics of each clade of P. pungens on geographical distribution with the habitat temperature ranges of each clade and to reveal their hybrid zone in the West Pacific area. We employed the 137 number of nucleotide sequences of P. pungens and its sampling data (spatial and temporal scale) originated from the West Pacific area, and used field application of qPCR assay for intra-specific level of P. pungens. Only two genotypes, clade I and III, were identified in the West Pacific area. Clade I was distributed from 39 to 32.3°N, and clade III were from 1.4 to 34.4°N. The estimated habitat temperature for the clade I and clade III ranges were 8.1-26.9 °C and 24.2-31.2 °C, respectively. The latitudinal distributions and temperature ranges of each clade were significantly different. The qPCR assay employed, and results suggested that the hybrid zone for clade I and III has been observed in the southern Korean coasts, and clade III might be introduced from the Southern Pacific area. The cell abundances of clade III were strongly related with the higher seawater temperature and warm current force. This study has defined distinct habitat characteristics of genetically different sub-populations of P. pungens, and revealed its hybrid zone in natural environment for the first time. We also provided strong evidences about dispersion of the population of clade III to higher latitude in the West Pacific area. Copyright © 2018. Published by Elsevier B.V.

  16. Distribution of nutrients and antinutrients in milled fractions of chickpea and horse gram: seed coat phenolics and their distinct modes of enzyme inhibition.

    Science.gov (United States)

    Sreerama, Yadahally N; Neelam, Dennis A; Sashikala, Vadakkoot B; Pratape, Vishwas M

    2010-04-14

    Milled fractions of chickpea ( Cicer arietinum L.) and horse gram ( Macrotyloma uniflorum L. Verdc.) were evaluated for their nutritional and antinutritional characteristics. Crude protein content of these fractions ranged from 22.6-23.8 g 100(-1) g in cotyledon to 7.3-9.1 g 100(-1) g in seed coat fractions. The fat content of chickpea fractions (1.6-7.8 g 100(-1) g) was higher than that of horse gram fractions (0.6-2.6 g 100(-1) g). Crude fiber content was higher in seed coat fractions of both legumes than embryonic axe and cotyledon fractions. Seed coat fractions had high dietary fiber content (28.2-36.4 g 100(-1) g), made up of mainly insoluble dietary fiber. Most of the phytic acid and oligosaccharides were located in the cotyledon fractions, whereas phenolic compounds in higher concentrations were found in seed coats. Significantly higher concentrations of proteinaceous and phenolic inhibitors of digestive enzymes were found in cotyledon and seed coat fractions, respectively. The kinetic studies, using Michaelis-Menten and Lineweaver-Burk derivations, revealed that seed coat phenolics inhibit alpha-amylase activity by mixed noncompetitive (chickpea) and noncompetitive (horse gram) inhibition mechanisms. In the case of trypsin, chickpea and horse gram seed coat phenolics showed noncompetitive and uncompetitive modes of inhibition, respectively. These results suggest the wide variability in the nutrient and antinutrient composition in different milled fractions of legumes and potential utility of these fractions as ingredients in functional food product development.

  17. Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli

    Science.gov (United States)

    Malone, Kerri M.; Rue-Albrecht, Kévin; Magee, David A.; Conlon, Kevin; Schubert, Olga T.; Nalpas, Nicolas C.; Browne, John A.; Smyth, Alicia; Gormley, Eamonn; Aebersold, Ruedi; MacHugh, David E.; Gordon, Stephen V.

    2018-01-01

    Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M. bovis AF2122/97 and M. tuberculosis H37Rv at both the global transcriptional and the translational level via RNA-sequencing and SWATH MS. Furthermore, a bovine alveolar macrophage infection time course model was used to investigate the shared and divergent host transcriptomic response to infection with M. tuberculosis H37Rv or M. bovis AF2122/97. Significant differential expression of virulence-associated pathways between the two bacilli was revealed, including the ESX-1 secretion system. A divergent transcriptional response was observed between M. tuberculosis H37Rv and M. bovis AF2122/97 infection of bovine alveolar macrophages, in particular cytosolic DNA-sensing pathways at 48 h post-infection, and highlights a distinct engagement of M. bovis with the bovine innate immune system. The work presented here therefore provides a basis for the identification of host innate immune mechanisms subverted by virulent host-adapted mycobacteria to promote their survival during the early stages of infection. PMID:29557774

  18. Phylogenomic and MALDI-TOF MS analysis of Streptococcus sinensis HKU4T reveals a distinct phylogenetic clade in the genus Streptococcus.

    Science.gov (United States)

    Teng, Jade L L; Huang, Yi; Tse, Herman; Chen, Jonathan H K; Tang, Ying; Lau, Susanna K P; Woo, Patrick C Y

    2014-10-20

    Streptococcus sinensis is a recently discovered human pathogen isolated from blood cultures of patients with infective endocarditis. Its phylogenetic position, as well as those of its closely related species, remains inconclusive when single genes were used for phylogenetic analysis. For example, S. sinensis branched out from members of the anginosus, mitis, and sanguinis groups in the 16S ribosomal RNA gene phylogenetic tree, but it was clustered with members of the anginosus and sanguinis groups when groEL gene sequences used for analysis. In this study, we sequenced the draft genome of S. sinensis and used a polyphasic approach, including concatenated genes, whole genomes, and matrix-assisted laser desorption ionization-time of flight mass spectrometry to analyze the phylogeny of S. sinensis. The size of the S. sinensis draft genome is 2.06 Mb, with GC content of 42.2%. Phylogenetic analysis using 50 concatenated genes or whole genomes revealed that S. sinensis formed a distinct cluster with Streptococcus oligofermentans and Streptococcus cristatus, and these three streptococci were clustered with the "sanguinis group." As for phylogenetic analysis using hierarchical cluster analysis of the mass spectra of streptococci, S. sinensis also formed a distinct cluster with S. oligofermentans and S. cristatus, but these three streptococci were clustered with the "mitis group." On the basis of the findings, we propose a novel group, named "sinensis group," to include S. sinensis, S. oligofermentans, and S. cristatus, in the Streptococcus genus. Our study also illustrates the power of phylogenomic analyses for resolving ambiguities in bacterial taxonomy. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. FRET biosensors reveal AKAP-mediated shaping of subcellular PKA activity and a novel mode of Ca(2+)/PKA crosstalk.

    Science.gov (United States)

    Schott, Micah B; Gonowolo, Faith; Maliske, Benjamin; Grove, Bryon

    2016-04-01

    Scaffold proteins play a critical role in cellular homeostasis by anchoring signaling enzymes in close proximity to downstream effectors. In addition to anchoring static enzyme complexes, some scaffold proteins also form dynamic signalosomes that can traffic to different subcellular compartments upon stimulation. Gravin (AKAP12), a multivalent scaffold, anchors PKA and other enzymes to the plasma membrane under basal conditions, but upon [Ca(2+)]i elevation, is rapidly redistributed to the cytosol. Because gravin redistribution also impacts PKA localization, we postulate that gravin acts as a calcium "switch" that modulates PKA-substrate interactions at the plasma membrane, thus facilitating a novel crosstalk mechanism between Ca(2+) and PKA-dependent pathways. To assess this, we measured the impact of gravin-V5/His expression on compartmentalized PKA activity using the FRET biosensor AKAR3 in cultured cells. Upon treatment with forskolin or isoproterenol, cells expressing gravin-V5/His showed elevated levels of plasma membrane PKA activity, but cytosolic PKA activity levels were reduced compared with control cells lacking gravin. This effect required both gravin interaction with PKA and localization at the plasma membrane. Pretreatment with calcium-elevating agents thapsigargin or ATP caused gravin redistribution away from the plasma membrane and prevented gravin from elevating PKA activity levels at the membrane. Importantly, this mode of Ca(2+)/PKA crosstalk was not observed in cells expressing a gravin mutant that resisted calcium-mediated redistribution from the cell periphery. These results reveal that gravin impacts subcellular PKA activity levels through the spatial targeting of PKA, and that calcium elevation modulates downstream β-adrenergic/PKA signaling through gravin redistribution, thus supporting the hypothesis that gravin mediates crosstalk between Ca(2+) and PKA-dependent signaling pathways. Based on these results, AKAP localization dynamics may

  20. FRET biosensors reveal AKAP-mediated shaping of subcellular PKA activity and a novel mode of Ca2+/PKA crosstalk

    Science.gov (United States)

    Schott, Micah; Gonowolo, Faith; Maliske, Ben; Grove, Bryon

    2016-01-01

    Scaffold proteins play a critical role in cellular homeostasis by anchoring signaling enzymes in close proximity to downstream effectors. In addition to anchoring static enzyme complexes, some scaffold proteins also form dynamic signalosomes that can traffic to different subcellular compartments upon stimulation. Gravin (AKAP12), a multivalent scaffold, anchors PKA and other enzymes to the plasma membrane under basal conditions, but upon [Ca2+]i elevation, is rapidly redistributed to the cytosol. Because gravin redistribution also impacts PKA localization, we postulate that gravin acts as a calcium “switch” that modulates PKA-substrate interactions at the plasma membrane, thus facilitating a novel crosstalk mechanism between Ca2+ and PKA-dependent pathways. To assess this, we measured the impact of gravin-V5/His expression on compartmentalized PKA activity using the FRET biosensor AKAR3 in cultured cells. Upon treatment with forskolin or isoproterenol, cells expressing gravin-V5/His showed elevated levels of plasma membrane PKA activity, but cytosolic PKA activity levels were reduced compared with control cells lacking gravin. This effect required both gravin interaction with PKA and localization at the plasma membrane. Pretreatment with calcium-elevating agents thapsigargin or ATP caused gravin redistribution away from the plasma membrane and prevented gravin from elevating PKA activity levels at the membrane. Importantly, this mode of Ca2+/PKA crosstalk was not observed in cells expressing a gravin mutant that resists calcium-mediated redistribution from the cell periphery. These results reveal that gravin impacts subcellular PKA activity levels through the spatial targeting of PKA, and that calcium elevation modulates downstream β-adrenergic/PKA signaling through gravin redistribution, thus supporting the hypothesis that gravin mediates crosstalk between Ca2+ and PKA-dependent signaling pathways. Based on these results, AKAP localization dynamics may

  1. Revealing the Value of “Green” and the Small Group with a Big Heart in Transportation Mode Choice

    Directory of Open Access Journals (Sweden)

    David Gaker

    2013-07-01

    Full Text Available To address issues of climate change, people are more and more being presented with the greenhouse gas emissions associated with their alternatives. Statements of pounds or kilograms of CO2 are showing up in trip planners, car advertisements, and even restaurant menus under the assumption that this information influences behavior. This research contributes to the literature that investigates how travelers respond to such information. Our objective is to better understand the “value of green” or how much travelers are willing to pay in money in order to reduce the CO2 associated with their travel. As with previous work, we designed and conducted a mode choice experiment using methods that have long been used to study value of time. The contributions of this paper are twofold. First, we employ revealed preference data, whereas previous studies have been based on stated preferences. Second, we provide new insight on how the value of green is distributed in the population. Whereas previous work has specified heterogeneity either systematically or with a continuous distribution, we find that a latent class choice model specification better fits the data and also is attractive behaviorally. The best fitting latent class model has two classes: one large class (76% of the sample who are not willing to spend any time or money to reduce their CO2 and a second class (24% of the sample who value reducing their CO2 at a very high rate of $2.68 per pound of reduction—our so-called small group with a big heart. We reanalyzed three datasets that we had previously collected and found considerable robustness of this two class result.

  2. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    Science.gov (United States)

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.; Bælum, Jacob; Taş, Neslihan; Elberling, Bo; Jansson, Janet K.; Semenchuk, Philipp; Priemé, Anders

    2015-01-01

    The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78°N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable organic matter on the bacterial communities. The copy number of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below −10°C. Multivariate statistical analysis of the bacterial diversity data (DNA and cDNA libraries) revealed a season-based clustering of the samples, and, e.g., the relative abundance of potentially active Cyanobacteria peaked in June and Alphaproteobacteria increased over the summer and then declined from October to November. The structure of the bulk (DNA-based) community was significantly correlated with pH and dissolved organic carbon, while the potentially active (RNA-based) community structure was not significantly correlated with any of the measured soil parameters. A large fraction of the 16S rRNA transcripts was assigned to nitrogen-fixing bacteria (up to 24% in June) and phototrophic organisms (up to 48% in June) illustrating the potential importance of nitrogen fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic bacterial activity on the soil surface. PMID:25983731

  3. Comprehensive genetic analyses reveal evolutionary distinction of a mouse (Zapus hudsonius preblei) proposed for delisting from the US Endangered Species Act.

    Science.gov (United States)

    King, Tim L; Switzer, John F; Morrison, Cheryl L; Eackles, Michael S; Young, Colleen C; Lubinski, Barbara A; Cryan, Paul

    2006-12-01

    Zapus hudsonius preblei, listed as threatened under the US Endangered Species Act (ESA), is one of 12 recognized subspecies of meadow jumping mice found in North America. Recent morphometric and phylogenetic comparisons among Z. h. preblei and neighbouring conspecifics questioned the taxonomic status of selected subspecies, resulting in a proposal to delist the Z. h. preblei from the ESA. We present additional analyses of the phylogeographic structure within Z. hudsonius that calls into question previously published data (and conclusions) and confirms the original taxonomic designations. A survey of 21 microsatellite DNA loci and 1380 base pairs from two mitochondrial DNA (mtDNA) regions (control region and cytochrome b) revealed that each Z. hudsonius subspecies is genetically distinct. These data do not support the null hypothesis of a homogeneous gene pool among the five subspecies found within the southwestern portion of the species' range. The magnitude of the observed differentiation was considerable and supported by significant findings for nearly every statistical comparison made, regardless of the genome or the taxa under consideration. Structuring of nuclear multilocus genotypes and subspecies-specific mtDNA haplotypes corresponded directly with the disjunct distributions of the subspecies investigated. Given the level of correspondence between the observed genetic population structure and previously proposed taxonomic classification of subspecies (based on the geographic separation and surveys of morphological variation), we conclude that the nominal subspecies surveyed in this study do not warrant synonymy, as has been proposed for Z. h. preblei, Z. h. campestris, and Z. h. intermedius.

  4. Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

    Directory of Open Access Journals (Sweden)

    Brad A. Friedman

    2018-01-01

    Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

  5. Two distinct mtDNA lineages of the blue crab reveal large-scale population structure in its native Atlantic distribution

    Science.gov (United States)

    Alaniz Rodrigues, Marcos; Dumont, Luiz Felipe Cestari; dos Santos, Cléverson Rannieri Meira; D'Incao, Fernando; Weiss, Steven; Froufe, Elsa

    2017-10-01

    For the first time, a molecular approach was used to evaluate the phylogenetic structure of the disjunct native American distribution of the blue crab Callinectes sapidus. Population structure was investigated by sequencing 648bp of the Cytochrome oxidase subunit 1 (COI), in a total of 138 sequences stemming from individual samples from both the northern and southern hemispheres of the Western Atlantic distribution of the species. A Bayesian approach was used to construct a phylogenetic tree for all samples, and a 95% confidence parsimony network was created to depict the relationship among haplotypes. Results revealed two highly distinct lineages, one containing all samples from the United States and some from Brazil (lineage 1) and the second restricted to Brazil (lineage 2). In addition, gene flow (at least for females) was detected among estuaries at local scales and there is evidence for shared haplotypes in the south. Furthermore, the findings of this investigation support the contemporary introduction of haplotypes that have apparently spread from the south to the north Atlantic.

  6. A comparative study on Ca content and distribution in two Gesneriaceae species reveals distinctive mechanisms to cope with high rhizospheric soluble calcium

    Directory of Open Access Journals (Sweden)

    Wenlong eLi

    2014-11-01

    Full Text Available Excessive Ca is toxic to plants thus significantly affects plant growth and species distribution in Ca-rich karst areas. To understand how plants survive high Ca soil, laboratory experiments were established to compare the physiological responses and internal Ca distribution in organ, tissue, cell and intracellular levels under different Ca levels for Lysionotus pauciflorus and Boea hygrometrica, two karst habitant Gesneriaceae species in Southwest China. In the controlled condition, L. pauciflorus could survive as high as 200 mM rhizospheric soluble Ca, attributed to a series of physiological responses and preferential storage that limited Ca accumulation in chloroplasts of palisade cells. In contrast, B. hygrometrica could survive only 20 mM rhizospheric soluble Ca, but accumulated a high level of internal Ca in both palisade and spongy cells without disturbance on photosynthetic activity. By phenotype screening of transgenic plants expressing high Ca-inducible genes from B. hygrometrica, the expression of BhDNAJC2 in A. thaliana was found to enhance plant growth and photosynthesis under high soluble Ca stress. BhDNAJC2 encodes a recently reported heat shock protein (HSP 40 family DnaJ-domain protein. The Ca-resistant phenotype of BhDNAJC2 highlights the important role of chaperone-mediated protein quality control in Ca tolerance in B. hygrometrica. Taken together, our results revealed that distinctive mechanisms were employed in the two Gesneriaceae karst habitants to cope with a high Ca environment.

  7. The complete chloroplast DNA sequence of the green alga Oltmannsiellopsis viridis reveals a distinctive quadripartite architecture in the chloroplast genome of early diverging ulvophytes

    Directory of Open Access Journals (Sweden)

    Lemieux Claude

    2006-02-01

    Full Text Available Abstract Background The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. The basal position of the Prasinophyceae has been well documented, but the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae is currently debated. The four complete chloroplast DNA (cpDNA sequences presently available for representatives of these classes have revealed extensive variability in overall structure, gene content, intron composition and gene order. The chloroplast genome of Pseudendoclonium (Ulvophyceae, in particular, is characterized by an atypical quadripartite architecture that deviates from the ancestral type by a large inverted repeat (IR featuring an inverted rRNA operon and a small single-copy (SSC region containing 14 genes normally found in the large single-copy (LSC region. To gain insights into the nature of the events that led to the reorganization of the chloroplast genome in the Ulvophyceae, we have determined the complete cpDNA sequence of Oltmannsiellopsis viridis, a representative of a distinct, early diverging lineage. Results The 151,933 bp IR-containing genome of Oltmannsiellopsis differs considerably from Pseudendoclonium and other chlorophyte cpDNAs in intron content and gene order, but shares close similarities with its ulvophyte homologue at the levels of quadripartite architecture, gene content and gene density. Oltmannsiellopsis cpDNA encodes 105 genes, contains five group I introns, and features many short dispersed repeats. As in Pseudendoclonium cpDNA, the rRNA genes in the IR are transcribed toward the single copy region featuring the genes typically found in the ancestral LSC region, and the opposite single copy region harbours genes characteristic of both the ancestral SSC and LSC regions. The 52 genes that were transferred from the ancestral LSC to SSC region include 12 of those observed in Pseudendoclonium cpDNA. Surprisingly, the overall gene organization of

  8. Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer.

    Directory of Open Access Journals (Sweden)

    Sonia Pinho

    2011-04-01

    Full Text Available The amniote organizer (Hensen's node can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct "epochs", or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.

  9. Genetic Structuration, Demography and Evolutionary History of Mycobacterium tuberculosis LAM9 Sublineage in the Americas as Two Distinct Subpopulations Revealed by Bayesian Analyses

    Science.gov (United States)

    Reynaud, Yann; Millet, Julie; Rastogi, Nalin

    2015-01-01

    Tuberculosis (TB) remains broadly present in the Americas despite intense global efforts for its control and elimination. Starting from a large dataset comprising spoligotyping (n = 21183 isolates) and 12-loci MIRU-VNTRs data (n = 4022 isolates) from a total of 31 countries of the Americas (data extracted from the SITVIT2 database), this study aimed to get an overview of lineages circulating in the Americas. A total of 17119 (80.8%) strains belonged to the Euro-American lineage 4, among which the most predominant genotypic family belonged to the Latin American and Mediterranean (LAM) lineage (n = 6386, 30.1% of strains). By combining classical phylogenetic analyses and Bayesian approaches, this study revealed for the first time a clear genetic structuration of LAM9 sublineage into two subpopulations named LAM9C1 and LAM9C2, with distinct genetic characteristics. LAM9C1 was predominant in Chile, Colombia and USA, while LAM9C2 was predominant in Brazil, Dominican Republic, Guadeloupe and French Guiana. Globally, LAM9C2 was characterized by higher allelic richness as compared to LAM9C1 isolates. Moreover, LAM9C2 sublineage appeared to expand close to twenty times more than LAM9C1 and showed older traces of expansion. Interestingly, a significant proportion of LAM9C2 isolates presented typical signature of ancestral LAM-RDRio MIRU-VNTR type (224226153321). Further studies based on Whole Genome Sequencing of LAM strains will provide the needed resolution to decipher the biogeographical structure and evolutionary history of this successful family. PMID:26517715

  10. Whole-genome sequence of a novel Chinese cyprinid herpesvirus 3 isolate reveals the existence of a distinct European genotype in East Asia.

    Science.gov (United States)

    Li, Wei; Lee, Xuezhu; Weng, Shaoping; He, Jianguo; Dong, Chuanfu

    2015-02-25

    Cyprinid herpesvirus 3 (CyHV3), also known as koi herpesvirus (KHV), can be subdivided primarily into European and Asian genotypes, which are represented by CyHV3-U or CyHV3-I and CyHV3-J, respectively. In this study, the whole genome sequence of a novel Chinese CyHV3 isolate (GZ11) was determined and annotated. CyHV3-GZ11 genome was found to contain 295,119 nucleotides with 52.9% G/C content, which is highly similar to those of published CyHV3-U, CyHV3-I, and CyHV3-J strains. With reference to CyHV3-U, CyHV3-I, and CyHV3-J, CyHV3-GZ11 was also classified into 164 open reading frames (ORF), which include eight repeated ORFs. On the basis of the 12 alloherpeviruses core genes, results from phylogenetic analysis showed that CyHV3-GZ11 had closer evolutionary relationships with CyHV3-U and CyHV3-I than with CyHV3/KHV-J, which were also supported by genome wide-based single nucleotide substitution analysis and the use of a series of developed molecular markers. This study was the first to reveal the presence of a distinct European CyHV3 genotype in East and Southeast Asia at a whole genome level, which will evoke new insights on exploring the origin, evolution, and epidemiology of the virus. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins*

    Science.gov (United States)

    Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

    2017-01-01

    Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. PMID:27927989

  12. Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.

    Science.gov (United States)

    Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

    2017-01-20

    Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Empirical study of travel mode forecasting improvement for the combined revealed preference/stated preference data–based discrete choice model

    Directory of Open Access Journals (Sweden)

    Yanfu Qiao

    2016-01-01

    Full Text Available The combined revealed preference/stated preference data–based discrete choice model has provided the actual choice-making restraints as well as reduced the prediction errors. But the random error variance of alternatives belonging to different data would impact its universality. In this article, we studied the traffic corridor between Chengdu and Longquan with the revealed preference/stated preference joint model, and the single stated preference data model separately predicted the choice probability of each mode. We found the revealed preference/stated preference joint model is universal only when there is a significant difference between the random error terms in different data. The single stated preference data would amplify the travelers’ preference and cause prediction error. We proposed a universal way that uses revealed preference data to modify the single stated preference data parameter estimation results to achieve the composite utility and reduce the prediction error. And the result suggests that prediction results are more reasonable based on the composite utility than the results based on the single stated preference data, especially forecasting the mode share of bus. The future metro line will be the main travel mode in this corridor, and 45% of passenger flow will transfer to the metro.

  14. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.

    Science.gov (United States)

    Tamayo, Joel V; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M Tanaka; Gavis, Elizabeth R

    2017-04-04

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

    Directory of Open Access Journals (Sweden)

    Joel V. Tamayo

    2017-04-01

    Full Text Available The Drosophila hnRNP F/H homolog, Glorund (Glo, regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3′ untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

  16. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

    Energy Technology Data Exchange (ETDEWEB)

    Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M. Tanaka; Gavis, Elizabeth R. (Princeton); (NIH)

    2017-04-01

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

  17. Combination of DTI and fMRI reveals the white matter changes correlating with the decline of default-mode network activity in Alzheimer's disease

    Science.gov (United States)

    Wu, Xianjun; Di, Qian; Li, Yao; Zhao, Xiaojie

    2009-02-01

    Recently, evidences from fMRI studies have shown that there was decreased activity among the default-mode network in Alzheimer's disease (AD), and DTI researches also demonstrated that demyelinations exist in white matter of AD patients. Therefore, combining these two MRI methods may help to reveal the relationship between white matter damages and alterations of the resting state functional connectivity network. In the present study, we tried to address this issue by means of correlation analysis between DTI and resting state fMRI images. The default-mode networks of AD and normal control groups were compared to find the areas with significantly declined activity firstly. Then, the white matter regions whose fractional anisotropy (FA) value correlated with this decline were located through multiple regressions between the FA values and the BOLD response of the default networks. Among these correlating white matter regions, those whose FA values also declined were found by a group comparison between AD patients and healthy elderly control subjects. Our results showed that the areas with decreased activity among default-mode network included left posterior cingulated cortex (PCC), left medial temporal gyrus et al. And the damaged white matter areas correlated with the default-mode network alterations were located around left sub-gyral temporal lobe. These changes may relate to the decreased connectivity between PCC and medial temporal lobe (MTL), and thus correlate with the deficiency of default-mode network activity.

  18. 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells.

    Directory of Open Access Journals (Sweden)

    Krzysztof Poterlowicz

    2017-09-01

    Full Text Available Mammalian genomes contain several dozens of large (>0.5 Mbp lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene

  19. Kinetic and structural studies reveal a unique binding mode of sulfite to the nickel center in urease.

    Science.gov (United States)

    Mazzei, Luca; Cianci, Michele; Benini, Stefano; Bertini, Leonardo; Musiani, Francesco; Ciurli, Stefano

    2016-01-01

    Urease is the most efficient enzyme known to date, and catalyzes the hydrolysis of urea using two Ni(II) ions in the active site. Urease is a virulence factor in several human pathogens, while causing severe environmental and agronomic problems. Sporosarcina pasteurii urease has been used extensively in the structural characterization of the enzyme. Sodium sulfite has been widely used as a preservative in urease solutions to prevent oxygen-induced oxidation, but its role as an inhibitor has also been suggested. In the present study, isothermal titration microcalorimetry was used to establish sulfite as a competitive inhibitor for S. pasteurii urease, with an inhibition constant of 0.19mM at pH7. The structure of the urease-sulfite complex, determined at 1.65Å resolution, shows the inhibitor bound to the dinuclear Ni(II) center of urease in a tridentate mode involving bonds between the two Ni(II) ions in the active site and all three oxygen atoms of the inhibitor, supporting the observed competitive inhibition kinetics. This coordination mode of sulfite has never been observed, either in proteins or in small molecule complexes, and could inspire synthetic coordination chemists as well as biochemists to develop urease inhibitors based on this chemical moiety. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. All-atom normal-mode analysis reveals an RNA-induced allostery in a bacteriophage coat protein.

    Science.gov (United States)

    Dykeman, Eric C; Twarock, Reidun

    2010-03-01

    Assembly of the T=3 bacteriophage MS2 is initiated by the binding of a 19 nucleotide RNA stem loop from within the phage genome to a symmetric coat protein dimer. This binding event effects a folding of the FG loop in one of the protein subunits of the dimer and results in the formation of an asymmetric dimer. Since both the symmetric and asymmetric forms of the dimer are needed for the assembly of the protein container, this allosteric switch plays an important role in the life cycle of the phage. We provide here details of an all-atom normal-mode analysis of this allosteric effect. The results suggest that asymmetric contacts between the A -duplex RNA phosphodiester backbone of the stem loop with the EF loop in one coat protein subunit results in an increased dynamic behavior of its FG loop. The four lowest-frequency modes, which encompass motions predominantly on the FG loops, account for over 90% of the increased dynamic behavior due to a localization of the vibrational pattern on a single FG loop. Finally, we show that an analysis of the allosteric effect using an elastic network model fails to predict this localization effect, highlighting the importance of using an all-atom full force field method for this problem.

  1. Specific default mode subnetworks support mentalizing as revealed through opposing network recruitment by social and semantic FMRI tasks.

    Science.gov (United States)

    Hyatt, Christopher J; Calhoun, Vince D; Pearlson, Godfrey D; Assaf, Michal

    2015-08-01

    The ability to attribute mental states to others, or "mentalizing," is posited to involve specific subnetworks within the overall default mode network (DMN), but this question needs clarification. To determine which default mode (DM) subnetworks are engaged by mentalizing processes, we assessed task-related recruitment of DM subnetworks. Spatial independent component analysis (sICA) applied to fMRI data using relatively high-order model (75 components). Healthy participants (n = 53, ages 17-60) performed two fMRI tasks: an interactive game involving mentalizing (Domino), a semantic memory task (SORT), and a resting state fMRI scan. sICA of the two tasks split the DMN into 10 subnetworks located in three core regions: medial prefrontal cortex (mPFC; five subnetworks), posterior cingulate/precuneus (PCC/PrC; three subnetworks), and bilateral temporoparietal junction (TPJ). Mentalizing events increased recruitment in five of 10 DM subnetworks, located in all three core DMN regions. In addition, three of these five DM subnetworks, one dmPFC subnetwork, one PCC/PrC subnetwork, and the right TPJ subnetwork, showed reduced recruitment by semantic memory task events. The opposing modulation by the two tasks suggests that these three DM subnetworks are specifically engaged in mentalizing. Our findings, therefore, suggest the unique involvement of mentalizing processes in only three of 10 DM subnetworks, and support the importance of the dmPFC, PCC/PrC, and right TPJ in mentalizing as described in prior studies. © 2015 Wiley Periodicals, Inc.

  2. STRUCTURAL GLITCHES NEAR THE CORES OF RED GIANTS REVEALED BY OSCILLATIONS IN G-MODE PERIOD SPACINGS FROM STELLAR MODELS

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, M. S.; Avelino, P. P. [Instituto de Astrofísica e Ciências do Espaço, Universidade do Porto, CAUP, Rua das Estrelas, 4150-762 Porto (Portugal); Stello, D. [Sydney Institute for Astronomy (SIfA), School of Physics, University of Sydney, NSW 2006 (Australia); Christensen-Dalsgaard, J. [Stellar Astrophysics Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C (Denmark); Townsend, R. H. D., E-mail: mcunha@astro.up.pt [Department of Astronomy, University of Wisconsin–Madison, 2535 Sterling Hall, 475 N. Charter Street, Madison, WI 53706 (United States)

    2015-06-01

    With recent advances in asteroseismology it is now possible to peer into the cores of red giants, potentially providing a way to study processes such as nuclear burning and mixing through their imprint as sharp structural variations—glitches—in the stellar cores. Here we show how such core glitches can affect the oscillations we observe in red giants. We derive an analytical expression describing the expected frequency pattern in the presence of a glitch. This formulation also accounts for the coupling between acoustic and gravity waves. From an extensive set of canonical stellar models we find glitch-induced variation in the period spacing and inertia of non-radial modes during several phases of red giant evolution. Significant changes are seen in the appearance of mode amplitude and frequency patterns in asteroseismic diagrams such as the power spectrum and the échelle diagram. Interestingly, along the red giant branch glitch-induced variation occurs only at the luminosity bump, potentially providing a direct seismic indicator of stars in that particular evolution stage. Similarly, we find the variation at only certain post-helium-ignition evolution stages, namely, in the early phases of helium core burning and at the beginning of helium shell burning, signifying the asymptotic giant branch bump. Based on our results, we note that assuming stars to be glitch-free, while they are not, can result in an incorrect estimate of the period spacing. We further note that including diffusion and mixing beyond classical Schwarzschild could affect the characteristics of the glitches, potentially providing a way to study these physical processes.

  3. Two distinct binding modes define the interaction of Brox with the C-terminal tails of CHMP5 and CHMP4B.

    Science.gov (United States)

    Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Sette, Paola; Rudd, Victoria; Chuenchor, Watchalee; Bello, Nana F; Bouamr, Fadila; Xiao, Tsan Sam

    2012-05-09

    Interactions of the CHMP protein carboxyl terminal tails with effector proteins play important roles in retroviral budding, cytokinesis, and multivesicular body biogenesis. Here we demonstrate that hydrophobic residues at the CHMP4B C-terminal amphipathic α helix bind a concave surface of Brox, a mammalian paralog of Alix. Unexpectedly, CHMP5 was also found to bind Brox and specifically recruit endogenous Brox to detergent-resistant membrane fractions through its C-terminal 20 residues. Instead of an α helix, the CHMP5 C-terminal tail adopts a tandem β-hairpin structure that binds Brox at the same site as CHMP4B. Additional Brox:CHMP5 interface is furnished by a unique CHMP5 hydrophobic pocket engaging the Brox residue Y348 that is not conserved among the Bro1 domains. Our studies thus unveil a β-hairpin conformation of the CHMP5 protein C-terminal tail, and provide insights into the overlapping but distinct binding profiles of ESCRT-III and the Bro1 domain proteins. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Bayesian network analysis reveals alterations to default mode network connectivity in individuals at risk for Alzheimer's disease.

    Science.gov (United States)

    Li, Rui; Yu, Jing; Zhang, Shouzi; Bao, Feng; Wang, Pengyun; Huang, Xin; Li, Juan

    2013-01-01

    Alzheimer's disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.

  5. Crystal structure of human importin-α1 (Rch1, revealing a potential autoinhibition mode involving homodimerization.

    Directory of Open Access Journals (Sweden)

    Hideyuki Miyatake

    Full Text Available In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB-truncated human importin-α1 (ΔIBB-h-importin-α1 at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.

  6. Magnetoencephalographic alpha band connectivity reveals differential default mode network interactions during focused attention and open monitoring meditation

    Science.gov (United States)

    Marzetti, Laura; Di Lanzo, Claudia; Zappasodi, Filippo; Chella, Federico; Raffone, Antonino; Pizzella, Vittorio

    2014-01-01

    According to several conceptualizations of meditation, the interplay between brain systems associated to self-related processing, attention and executive control is crucial for meditative states and related traits. We used magnetoencephalography (MEG) to investigate such interplay in a highly selected group of “virtuoso” meditators (Theravada Buddhist monks), with long-term training in the two main meditation styles: focused attention (FA) and open monitoring (OM) meditation. Specifically, we investigated the differences between FA meditation, OM meditation and resting state in the coupling between the posterior cingulate cortex, core node of the Default Mode Network (DMN) implicated in mind wandering and self-related processing, and the whole brain, with a recently developed phase coherence approach. Our findings showed a state dependent coupling of posterior cingulate cortex (PCC) to nodes of the DMN and of the executive control brain network in the alpha frequency band (8–12 Hz), related to different attentional and cognitive control processes in FA and OM meditation, consistently with the putative role of alpha band synchronization in the functional mechanisms for attention and consciousness. The coupling of PCC with left medial prefrontal cortex (lmPFC) and superior frontal gyrus characterized the contrast between the two meditation styles in a way that correlated with meditation expertise. These correlations may be related to a higher mindful observing ability and a reduced identification with ongoing mental activity in more expert meditators. Notably, different styles of meditation and different meditation expertise appeared to modulate the dynamic balance between fronto-parietal (FP) and DMN networks. Our results support the idea that the interplay between the DMN and the FP network in the alpha band is crucial for the transition from resting state to different meditative states. PMID:25360102

  7. Characterizing the structure-function relationship reveals the mode of action of a novel antimicrobial peptide, P1, from jumper ant Myrmecia pilosula.

    Science.gov (United States)

    Tseng, Tien-Sheng; Tsai, Keng-Chang; Chen, Chinpan

    2017-06-01

    Microbial infections of antibiotic-resistant strains cause serious diseases and have a significant impact on public health worldwide, so novel antimicrobial drugs are urgently needed. Insect venoms, a rich source of bioactive components containing antimicrobial peptides (AMPs), are attractive candidates for new therapeutic agents against microbes. Recently, a novel peptide, P1, identified from the venom of the Australian jumper ant Myrmecia pilosula, showed potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, but its structure-function relationship is unknown. Here, we used biochemical and biophysical techniques coupled with computational simulations to explore the mode of action of P1 interaction with dodecylphosphocholine (DPC) micelles as a model membrane system. Our circular dichroism (CD) and NMR studies revealed an amphipathic α-helical structure for P1 upon interaction with DPC micelles. A paramagnetic relaxation enhancement approach revealed that P1 orients its α-helix segment (F6-G14) into DPC micelles. In addition, the α-helix segment could be essential for membrane permeabilization and antimicrobial activity. Moreover, the arginine residues R8, R11, and R15 significantly contribute to helix formation and membrane-binding affinity. The lysine residue K19 of the C-terminus functionally guides P1 to interact with DPC micelles in the early interaction stage. Our study provides insights into the mode of action of P1, which is valuable in modifying and developing potent AMPs as antibiotic drugs.

  8. Raman dispersion spectroscopy on the highly saddled nickel(II)-octaethyltetraphenylporphyrin reveals the symmetry of nonplanar distortions and the vibronic coupling strength of normal modes

    International Nuclear Information System (INIS)

    Schweitzer-Stenner, R.; Stichternath, A.; Dreybrodt, W.; Jentzen, W.; Song, X.; Shelnutt, J.A.; Nielsen, O.F.; Medforth, C.J.; Smith, K.M.

    1997-01-01

    We have measured the polarized Raman cross sections and depolarization ratios of 16 fundamental modes of nickel octaethyltetraphenylporphyrin in a CS 2 solution for 16 fundamental modes, i.e., the A 1g -type vibrations ν 1 , ν 2 , ν 3 , ν 4 , ν 5 , and φ 8 , the B 1g vibrations ν 11 and ν 14 , the B 2g vibrations ν 28 , ν 29 , and ν 30 and the antisymmetric A 2g modes ν 19 , ν 20 , ν 22 , and ν 23 as function of the excitation wavelength. The data cover the entire resonant regions of the Q- and B-bands. They were analyzed by use of a theory which describes intra- and intermolecular coupling in terms of a time-independent nonadiabatic perturbation theory [E. Unger, U. Bobinger, W. Dreybrodt, and R. Schweitzer-Stenner, J. Phys. Chem. 97, 9956 (1993)]. This approach explicitly accounts in a self-consistent way for multimode mixing with all Raman modes investigated. The vibronic coupling parameters obtained from this procedure were then used to successfully fit the vibronic side bands of the absorption spectrum and to calculate the resonance excitation profiles in absolute units. Our results show that the porphyrin macrocycle is subject to B 2u -(saddling) and B 1u -(ruffling) distortions which lower its symmetry to S 4 . Thus, evidence is provided that the porphyrin molecule maintains the nonplanar structure of its crystal phase in an organic solvent. The vibronic coupling parameters indicate a breakdown of the four-orbital model. This notion is corroborated by (ZINDO/S) calculations which reveal that significant configurational interaction occurs between the electronic transitions into |Q right-angle- and |1B right-angle-states and various porphyrin→porphyrin, metal→porphyrin, and porphyrin→metal transitions. (Abstract Truncated)

  9. Surface plasmon resonance imaging reveals multiple binding modes of Agrobacterium transformation mediator VirE2 to ssDNA.

    Science.gov (United States)

    Kim, Sanghyun; Zbaida, David; Elbaum, Michael; Leh, Hervé; Nogues, Claude; Buckle, Malcolm

    2015-07-27

    VirE2 is the major secreted protein of Agrobacterium tumefaciens in its genetic transformation of plant hosts. It is co-expressed with a small acidic chaperone VirE1, which prevents VirE2 oligomerization. After secretion into the host cell, VirE2 serves functions similar to a viral capsid in protecting the single-stranded transferred DNA en route to the nucleus. Binding of VirE2 to ssDNA is strongly cooperative and depends moreover on protein-protein interactions. In order to isolate the protein-DNA interactions, imaging surface plasmon resonance (SPRi) studies were conducted using surface-immobilized DNA substrates of length comparable to the protein-binding footprint. Binding curves revealed an important influence of substrate rigidity with a notable preference for poly-T sequences and absence of binding to both poly-A and double-stranded DNA fragments. Dissociation at high salt concentration confirmed the electrostatic nature of the interaction. VirE1-VirE2 heterodimers also bound to ssDNA, though by a different mechanism that was insensitive to high salt. Neither VirE2 nor VirE1-VirE2 followed the Langmuir isotherm expected for reversible monomeric binding. The differences reflect the cooperative self-interactions of VirE2 that are suppressed by VirE1. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic interplay and distinct functions of PSGL-1, ESL-1 and CD44

    Science.gov (United States)

    Wild, Martin; Vestweber, Dietmar; Frenette, Paul S.

    2014-01-01

    SUMMARY The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro but the complete identification of its physiological ligands has remained elusive. Here, we show using gene- and RNA-targeted loss-of-function that E-selectin ligand-1 (ESL-1), PSGL-1 and CD44 encompass all endothelial selectin ligand activity on neutrophils. PSGL-1 plays a major role in the initial leukocyte capture, while ESL-1 is critical to convert initial tethers into steady slow rolling. CD44 controls rolling velocity and mediates E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. PMID:17442598

  11. An optimized histochemical method to assess skeletal muscle glycogen and lipid stores reveals two metabolically distinct populations of type I muscle fibers

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Nordby, Pernille

    2013-01-01

    Skeletal muscle energy metabolism has been a research focus of physiologists for more than a century. Yet, how the use of intramuscular carbohydrate and lipid energy stores are coordinated during different types of exercise remains a subject of debate. Controversy arises from contradicting data...... preservation of muscle energy stores, air drying cryosections or cycles of freezing-thawing need to be avoided. Furthermore, optimization of the imaging settings in order to specifically image intracellular lipid droplets stained with oil red O or Bodipy-493/503 is shown. When co-staining lipid droplets...... distinct myosin heavy chain I expressing fibers: I-1 fibers have a smaller crossectional area, a higher density of lipid droplets, and a tendency to lower glycogen content compared to I-2 fibers. Type I-2 fibers have similar lipid content than IIA. Exhaustive exercise lead to glycogen depletion in type IIA...

  12. MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action

    DEFF Research Database (Denmark)

    Wen, Jiayu; Parker, Brian J; Jacobsen, Anders

    2011-01-01

    the predictive effect of target flanking features. We observe distinct target determinants between expression-based and CLIP-based data. Target flanking features such as flanking region conservation are an important AGO-binding determinant-we hypothesize that CLIP experiments have a preference for strongly bound......Microarray expression analyses following miRNA transfection/inhibition and, more recently, Argonaute cross-linked immunoprecipitation (CLIP)-seq assays have been used to detect miRNA target sites. CLIP and expression approaches measure differing stages of miRNA functioning-initial binding of the mi...... miRNP-target interactions involving adjacent RNA-binding proteins that increase the strength of cross-linking. In contrast, seed-related features are major determinants in expression-based studies, but less so for CLIP-seq studies, and increased miRNA concentrations typical of transfection studies...

  13. Mutant Allele-Specific Uncoupling of PENETRATION3 Functions Reveals Engagement of the ATP-Binding Cassette Transporter in Distinct Tryptophan Metabolic Pathways1[OPEN

    Science.gov (United States)

    Lu, Xunli; Dittgen, Jan; Piślewska-Bednarek, Mariola; Molina, Antonio; Schneider, Bernd; Doubský, Jan; Schneeberger, Korbinian; Schulze-Lefert, Paul

    2015-01-01

    Arabidopsis (Arabidopsis thaliana) PENETRATION (PEN) genes quantitatively contribute to the execution of different forms of plant immunity upon challenge with diverse leaf pathogens. PEN3 encodes a plasma membrane-resident pleiotropic drug resistance-type ATP-binding cassette transporter and is thought to act in a pathogen-inducible and PEN2 myrosinase-dependent metabolic pathway in extracellular defense. This metabolic pathway directs the intracellular biosynthesis and activation of tryptophan-derived indole glucosinolates for subsequent PEN3-mediated efflux across the plasma membrane at pathogen contact sites. However, PEN3 also functions in abiotic stress responses to cadmium and indole-3-butyric acid (IBA)-mediated auxin homeostasis in roots, raising the possibility that PEN3 exports multiple functionally unrelated substrates. Here, we describe the isolation of a pen3 allele, designated pen3-5, that encodes a dysfunctional protein that accumulates in planta like wild-type PEN3. The specific mutation in pen3-5 uncouples PEN3 functions in IBA-stimulated root growth modulation, callose deposition induced with a conserved peptide epitope of bacterial flagellin (flg22), and pathogen-inducible salicylic acid accumulation from PEN3 activity in extracellular defense, indicating the engagement of multiple PEN3 substrates in different PEN3-dependent biological processes. We identified 4-O-β-d-glucosyl-indol-3-yl formamide (4OGlcI3F) as a pathogen-inducible, tryptophan-derived compound that overaccumulates in pen3 leaf tissue and has biosynthesis that is dependent on an intact PEN2 metabolic pathway. We propose that a precursor of 4OGlcI3F is the PEN3 substrate in extracellular pathogen defense. These precursors, the shared indole core present in IBA and 4OGlcI3F, and allele-specific uncoupling of a subset of PEN3 functions suggest that PEN3 transports distinct indole-type metabolites in distinct biological processes. PMID:26023163

  14. Live cell imaging reveals different modes of cytotoxic action of extracts derived from commonly used luting cements.

    Science.gov (United States)

    Trumpaitė-Vanagienė, Rita; Čebatariūnienė, Alina; Tunaitis, Virginijus; Pūrienė, Alina; Pivoriūnas, Augustas

    2018-02-01

    To compare cytotoxicity of extracts derived from commonly used luting cements: Hoffmann's Zinc Phosphate (ZPC), GC Fuji Plus Resin Modified Glass Ionomer (RMGIC) and 3M ESPE RelyX Unicem Resin Cement (RC) on primary human gingival fibroblasts (HGFs). HGFs were exposed to different concentrations of the ZPC, RMGIC and RC extracts. The cytotoxicity was assessed with the PrestoBlue Cell Viability Reagent and viable cells were counted by a haemocytometer using the trypan blue exclusion test. In order to determine the primary mechanism of the cell death induced by extracts from different luting cements, the real-time monitoring of caspase-3/-7 activity and membrane integrity of cells was employed. The extracts from the RMGIC and ZPC decreased the metabolic activity and numbers of viable cells. Unexpectedly, the extracts from the RC evoked only small effects on the metabolic activity of HGFs with a decreasing number of viable cells in a dose-and time-dependent manner. The live cell imaging revealed that the apoptosis was the primary mechanism of a cell death induced by the extracts derived from the RMGIC, whereas the extracts from the RC and ZPC induced a cell death through a necrotic and caspase-independent pathway. The apoptosis was the primary mechanism of the cell death induced by the extracts derived from the RMGIC, whereas the extracts from the RC and ZPC induced a cell death via a necrotic pathway. We suggest that metabolic assays commonly used to assess the cytotoxicity of luting cements should be validated by alternative methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci.

    Science.gov (United States)

    Smeets, Daniel; Markaki, Yolanda; Schmid, Volker J; Kraus, Felix; Tattermusch, Anna; Cerase, Andrea; Sterr, Michael; Fiedler, Susanne; Demmerle, Justin; Popken, Jens; Leonhardt, Heinrich; Brockdorff, Neil; Cremer, Thomas; Schermelleh, Lothar; Cremer, Marion

    2014-01-01

    A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an 'autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform

  16. Distinct abscisic acid signaling pathways for modulation of guard cell versus mesophyll cell potassium channels revealed by expression studies in Xenopus laevis oocytes

    Science.gov (United States)

    Sutton, F.; Paul, S. S.; Wang, X. Q.; Assmann, S. M.; Evans, M. L. (Principal Investigator)

    2000-01-01

    Regulation of guard cell ion transport by abscisic acid (ABA) and in particular ABA inhibition of a guard cell inward K(+) current (I(Kin)) is well documented. However, little is known concerning ABA effects on ion transport in other plant cell types. Here we applied patch clamp techniques to mesophyll cell protoplasts of fava bean (Vicia faba cv Long Pod) plants and demonstrated ABA inhibition of an outward K(+) current (I(Kout)). When mesophyll cell protoplast mRNA (mesophyll mRNA) was expressed in Xenopus laevis oocytes, I(Kout) was generated that displayed similar properties to I(Kout) observed from direct analysis of mesophyll cell protoplasts. I(Kout) expressed by mesophyll mRNA-injected oocytes was inhibited by ABA, indicating that the ABA signal transduction pathway observed in mesophyll cells was preserved in the frog oocytes. Co-injection of oocytes with guard cell protoplast mRNA and cRNA for KAT1, an inward K(+) channel expressed in guard cells, resulted in I(Kin) that was similarly inhibited by ABA. However, oocytes co-injected with mesophyll mRNA and KAT1 cRNA produced I(Kin) that was not inhibited by ABA. These results demonstrate that the mesophyll-encoded signaling mechanism could not substitute for the guard cell pathway. These findings indicate that mesophyll cells and guard cells use distinct and different receptor types and/or signal transduction pathways in ABA regulation of K(+) channels.

  17. Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

    Science.gov (United States)

    Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

    2016-11-01

    Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

  18. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    Directory of Open Access Journals (Sweden)

    Ding Guohui

    2007-04-01

    Full Text Available Abstract Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD. A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.

  19. Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

  20. Detailed LC-MS/MS analysis of ciguatoxins revealing distinct regional and species characteristics in fish and causative alga from the Pacific.

    Science.gov (United States)

    Yogi, Kentaro; Oshiro, Naomasa; Inafuku, Yasuo; Hirama, Masahiro; Yasumoto, Takeshi

    2011-12-01

    Toxin profiles of representative ciguatera species caught at different locations of Japan were investigated in fish flesh by high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Identification and quantification of 16 toxins were facilitated by the use of 14 reference toxins prepared by either synthesis or isolation from natural sources and the previous LC-MS data thereof. Sodium adduct ions [M + Na](+) were used as parent and product ions. Distinct regional differences were unveiled: ciguatoxin-1B type toxins were found in snappers and groupers from Okinawa, ciguatoxin-3C type toxins were found in a spotted knifejaw, Oplegnathus punctatus, from Miyazaki located 730 km north of Okinawa, and both types of toxins were found in a red snapper, Lutjanus bohar, from Minamitorishima (Marcus) Island. Twelve toxins were identified in a dinoflagellate, Gambierdiscus toxicus, collected as the primary toxin source in French Polynesia. Occurrence of M-seco-toxins in fish and oxidized toxins in the dinoflagellate was confirmed for the first time. The present LC-MS/MS method is rapid, specific, and accurate. It not only outperforms the currently employed mouse bioassays but also enables the study of the toxin dynamics during the food chain transmission.

  1. Phylogenetic analysis consistent with a clinical history of sexual transmission of HIV-1 from a single donor reveals transmission of highly distinct variants

    Directory of Open Access Journals (Sweden)

    McClure Myra

    2011-07-01

    Full Text Available Abstract Background To combat the pandemic of human immunodeficiency virus 1 (HIV-1, a successful vaccine will need to cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viral variants but very little is known about viruses that are likely to be transmitted, or even if there are viral characteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergence consistent with a single transmission event in vivo can represent several years of pre-transmission evolution. Results We describe a highly unusual case consistent with a single donor transmitting highly related but distinct HIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences, present within each recipient, is consistent with the history of a single donor across the viral env, gag and pol genes by maximum likelihood and Bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since the most recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to 4.54 years. Conclusion Our results show that an effective design for a preventative vaccine will need to anticipate extensive HIV-1 diversity within an individual donor as well as diversity at the population level.

  2. Distinct spatio-temporal profiles of beta-oscillations within visual and sensorimotor areas during action recognition as revealed by MEG.

    Science.gov (United States)

    Pavlidou, Anastasia; Schnitzler, Alfons; Lange, Joachim

    2014-05-01

    The neural correlates of action recognition have been widely studied in visual and sensorimotor areas of the human brain. However, the role of neuronal oscillations involved during the process of action recognition remains unclear. Here, we were interested in how the plausibility of an action modulates neuronal oscillations in visual and sensorimotor areas. Subjects viewed point-light displays (PLDs) of biomechanically plausible and implausible versions of the same actions. Using magnetoencephalography (MEG), we examined dynamic changes of oscillatory activity during these action recognition processes. While both actions elicited oscillatory activity in visual and sensorimotor areas in several frequency bands, a significant difference was confined to the beta-band (∼20 Hz). An increase of power for plausible actions was observed in left temporal, parieto-occipital and sensorimotor areas of the brain, in the beta-band in successive order between 1650 and 2650 msec. These distinct spatio-temporal beta-band profiles suggest that the action recognition process is modulated by the degree of biomechanical plausibility of the action, and that spectral power in the beta-band may provide a functional interaction between visual and sensorimotor areas in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Profiling of wheat class III peroxidase genes derived from powdery mildew-attacked epidermis reveals distinct sequence-associated expression patterns.

    Science.gov (United States)

    Liu, Guosheng; Sheng, Xiaoyan; Greenshields, David L; Ogieglo, Adam; Kaminskyj, Susan; Selvaraj, Gopalan; Wei, Yangdou

    2005-07-01

    A cDNA library was constructed from leaf epidermis of diploid wheat (Triticum monococcum) infected with the powdery mildew fungus (Blumeria graminis f. sp. tritici) and was screened for genes encoding peroxidases. From 2,500 expressed sequence tags (ESTs), 36 cDNAs representing 10 peroxidase genes (designated TmPRX1 to TmPRX10) were isolated and further characterized. Alignment of the deduced amino acid sequences and phylogenetic clustering with peroxidases from other plant species demonstrated that these peroxidases fall into four distinct groups. Differential expression and tissue-specific localization among the members were observed during the B. graminis f. sp. tritici attack using Northern blots and reverse-transcriptase polymerase chain reaction analyses. Consistent with its abundance in the EST collection, TmPRX1 expression showed the highest induction during pathogen attack and fluctuated in response to the fungal parasitic stages. TmPRX1 to TmPRX6 were expressed predominantly in mesophyll cells, whereas TmPRX7 to TmPRX10, which feature a putative C-terminal propeptide, were detectable mainly in epidermal cells. Using TmPRX8 as a representative, we demonstrated that its C-terminal propeptide was sufficient to target a green fluorescent protein fusion protein to the vacuoles in onion cells. Finally, differential expression profiles of the TmPRXs after abiotic stresses and signal molecule treatments were used to dissect the potential role of these peroxidases in multiple stress and defense pathways.

  4. Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation.

    LENUS (Irish Health Repository)

    Murphy, Derek M

    2009-01-01

    BACKGROUND: Neuroblastoma, a cancer derived from precursor cells of the sympathetic nervous system, is a major cause of childhood cancer related deaths. The single most important prognostic indicator of poor clinical outcome in this disease is genomic amplification of MYCN, a member of a family of oncogenic transcription factors. METHODOLOGY: We applied MYCN chromatin immunoprecipitation to microarrays (ChIP-chip) using MYCN amplified\\/non-amplified cell lines as well as a conditional knockdown cell line to determine the distribution of MYCN binding sites within all annotated promoter regions. CONCLUSION: Assessment of E-box usage within consistently positive MYCN binding sites revealed a predominance for the CATGTG motif (p<0.0016), with significant enrichment of additional motifs CATTTG, CATCTG, CAACTG in the MYCN amplified state. For cell lines over-expressing MYCN, gene ontology analysis revealed enrichment for the binding of MYCN at promoter regions of numerous molecular functional groups including DNA helicases and mRNA transcriptional regulation. In order to evaluate MYCN binding with respect to other genomic features, we determined the methylation status of all annotated CpG islands and promoter sequences using methylated DNA immunoprecipitation (MeDIP). The integration of MYCN ChIP-chip and MeDIP data revealed a highly significant positive correlation between MYCN binding and DNA hypermethylation. This association was also detected in regions of hemizygous loss, indicating that the observed association occurs on the same homologue. In summary, these findings suggest that MYCN binding occurs more commonly at CATGTG as opposed to the classic CACGTG E-box motif, and that disease associated over expression of MYCN leads to aberrant binding to additional weaker affinity E-box motifs in neuroblastoma. The co-localization of MYCN binding and DNA hypermethylation further supports the dual role of MYCN, namely that of a classical transcription factor affecting the

  5. Distinctive Citizenship

    DEFF Research Database (Denmark)

    Kaur, Ravinder

    2009-01-01

    The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...

  6. Model-Based Analysis of Arabidopsis Leaf Epidermal Cells Reveals Distinct Division and Expansion Patterns for Pavement and Guard Cells1[W][OA

    Science.gov (United States)

    Asl, Leila Kheibarshekan; Dhondt, Stijn; Boudolf, Véronique; Beemster, Gerrit T.S.; Beeckman, Tom; Inzé, Dirk; Govaerts, Willy; De Veylder, Lieven

    2011-01-01

    To efficiently capture sunlight for photosynthesis, leaves typically develop into a flat and thin structure. This development is driven by cell division and expansion, but the individual contribution of these processes is currently unknown, mainly because of the experimental difficulties to disentangle them in a developing organ, due to their tight interconnection. To circumvent this problem, we built a mathematic model that describes the possible division patterns and expansion rates for individual epidermal cells. This model was used to fit experimental data on cell numbers and sizes obtained over time intervals of 1 d throughout the development of the first leaf pair of Arabidopsis (Arabidopsis thaliana). The parameters were obtained by a derivative-free optimization method that minimizes the differences between the predicted and experimentally observed cell size distributions. The model allowed us to calculate probabilities for a cell to divide into guard or pavement cells, the maximum size at which it can divide, and its average cell division and expansion rates at each point during the leaf developmental process. Surprisingly, average cell cycle duration remained constant throughout leaf development, whereas no evidence for a maximum cell size threshold for cell division of pavement cells was found. Furthermore, the model predicted that neighboring cells of different sizes within the epidermis expand at distinctly different relative rates, which could be verified by direct observations. We conclude that cell division seems to occur independently from the status of cell expansion, whereas the cell cycle might act as a timer rather than as a size-regulated machinery. PMID:21693673

  7. A global RNA-seq-driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.

    Science.gov (United States)

    Könitzer, Jennifer D; Müller, Markus M; Leparc, Germán; Pauers, Martin; Bechmann, Jan; Schulz, Patrick; Schaub, Jochen; Enenkel, Barbara; Hildebrandt, Tobias; Hampel, Martin; Tolstrup, Anne B

    2015-09-01

    Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics, BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1, generates antibodies with glycosylation profiles differing from CHO-DG44. Manufacturing process development is significantly influenced by these unique profiles. To investigate the underlying glycosylation related gene expression, we leveraged our CHO host and production cell RNA-seqtranscriptomics and product quality database together with the CHO-K1 genome. We observed that each BI-HEX host and antibody producing cell line has a unique gene expression fingerprint. CHO-DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing antibodies. BI-HEX-K1 cells express ST8Sia6 at host cell level. We detected a link between BI-HEX-1/BI-HEX-2 antibody galactosylation and mannosylation and the gene expression of the B4galt gene family and genes controlling mannose processing. Furthermore, we found major differences between the CHO-DG44 and CHO-K1 lineages in the expression of sialyl transferases and enzymes synthesizing sialic acid precursors, providing a rationale for the lack of immunogenic NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems biotechnology to understand glycoprotein synthesis and product glycoprofiles. Such data improve future production clone selection and process development strategies for better steering of biotherapeutic product quality. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Analysis of the type II-A CRISPR-Cas system of Streptococcus agalactiae reveals distinctive features according to genetic lineages

    Science.gov (United States)

    Lier, Clément; Baticle, Elodie; Horvath, Philippe; Haguenoer, Eve; Valentin, Anne-Sophie; Glaser, Philippe; Mereghetti, Laurent; Lanotte, Philippe

    2015-01-01

    CRISPR-Cas systems (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) are found in 90% of archaea and about 40% of bacteria. In this original system, CRISPR arrays comprise short, almost unique sequences called spacers that are interspersed with conserved palindromic repeats. These systems play a role in adaptive immunity and participate to fight non-self DNA such as integrative and conjugative elements, plasmids, and phages. In Streptococcus agalactiae, a bacterium implicated in colonization and infections in humans since the 1960s, two CRISPR-Cas systems have been described. A type II-A system, characterized by proteins Cas9, Cas1, Cas2, and Csn2, is ubiquitous, and a type I–C system, with the Cas8c signature protein, is present in about 20% of the isolates. Unlike type I–C, which appears to be non-functional, type II-A appears fully functional. Here we studied type II-A CRISPR-cas loci from 126 human isolates of S. agalactiae belonging to different clonal complexes that represent the diversity of the species and that have been implicated in colonization or infection. The CRISPR-cas locus was analyzed both at spacer and repeat levels. Major distinctive features were identified according to the phylogenetic lineages previously defined by multilocus sequence typing, especially for the sequence type (ST) 17, which is considered hypervirulent. Among other idiosyncrasies, ST-17 shows a significantly lower number of spacers in comparison with other lineages. This characteristic could reflect the peculiar virulence or colonization specificities of this lineage. PMID:26124774

  9. Distinct fronto-striatal couplings reveal the double-faced nature of response-outcome relations in instruction-based learning.

    Science.gov (United States)

    Ruge, Hannes; Wolfensteller, Uta

    2015-06-01

    Higher species commonly learn novel behaviors by evaluating retrospectively whether actions have yielded desirable outcomes. By relying on explicit behavioral instructions, only humans can use an acquisition shortcut that prospectively specifies how to yield intended outcomes under the appropriate stimulus conditions. A recent and largely unexplored hypothesis suggests that striatal areas interact with lateral prefrontal cortex (LPFC) when novel behaviors are learned via explicit instruction, and that regional subspecialization exists for the integration of differential response-outcome contingencies into the current task model. Behaviorally, outcome integration during instruction-based learning has been linked to functionally distinct performance indices. This includes (1) compatibility effects, measured in a postlearning test procedure probing the encoding strength of outcome-response (O-R) associations, and (2) increasing response slowing across learning, putatively indicating active usage of O-R associations for the online control of goal-directed action. In the present fMRI study, we examined correlations between these behavioral indices and the dynamics of fronto-striatal couplings in order to mutually constrain and refine the interpretation of neural and behavioral measures in terms of separable subprocesses during outcome integration. We found that O-R encoding strength correlated with LPFC-putamen coupling, suggesting that the putamen is relevant for the formation of both S-R habits and habit-like O-R associations. By contrast, response slowing as a putative index of active usage of O-R associations correlated with LPFC-caudate coupling. This finding highlights the relevance of the caudate for the online control of goal-directed action also under instruction-based learning conditions, and in turn clarifies the functional relevance of the behavioral slowing effect.

  10. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  11. Early transcriptome analyses of Z-3-Hexenol-treated zea mays revealed distinct transcriptional networks and anti-herbivore defense potential of green leaf volatiles.

    Directory of Open Access Journals (Sweden)

    Jurgen Engelberth

    Full Text Available Green leaf volatiles (GLV, which are rapidly emitted by plants in response to insect herbivore damage, are now established as volatile defense signals. Receiving plants utilize these molecules to prime their defenses and respond faster and stronger when actually attacked. To further characterize the biological activity of these compounds we performed a microarray analysis of global gene expression. The focus of this project was to identify early transcriptional events elicited by Z-3-hexenol (Z-3-HOL as our model GLV in maize (Zea mays seedlings. The microarray results confirmed previous studies on Z-3-HOL -induced gene expression but also provided novel information about the complexity of Z-3-HOL -induced transcriptional networks. Besides identifying a distinct set of genes involved in direct and indirect defenses we also found significant expression of genes involved in transcriptional regulation, Ca(2+-and lipid-related signaling, and cell wall reinforcement. By comparing these results with those obtained by treatment of maize seedlings with insect elicitors we found a high degree of correlation between the two expression profiles at this early time point, in particular for those genes related to defense. We further analyzed defense gene expression induced by other volatile defense signals and found Z-3-HOL to be significantly more active than methyl jasmonate, methyl salicylate, and ethylene. The data presented herein provides important information on early genetic networks that are activated by Z-3-HOL and demonstrates the effectiveness of this compound in the regulation of typical plant defenses against insect herbivores in maize.

  12. Comparative Analyses of Three Chlorella Species in Response to Light and Sugar Reveal Distinctive Lipid Accumulation Patterns in the Microalga C. sorokiniana

    Science.gov (United States)

    Barnes, Austin; Noel, Eric A.; Betenbaugh, Michael J.; Oyler, George A.

    2014-01-01

    While photosynthetic microalgae, such as Chlorella, serve as feedstocks for nutritional oils and biofuels, heterotrophic cultivation can augment growth rates, support high cell densities, and increase triacylglycerol (TAG) lipid content. However, these species differ significantly in their photoautotrophic and heterotrophic characteristics. In this study, the phylogeny of thirty Chlorella strains was determined in order to inform bioprospecting efforts and detailed physiological assessment of three species. The growth kinetics and lipid biochemistry of C. protothecoides UTEX 411, C. vulgaris UTEX 265, and C. sorokiniana UTEX 1230 were quantified during photoautotrophy in Bold's basal medium (BBM) and heterotrophy in BBM supplemented with glucose (10 g L−1). Heterotrophic growth rates of UTEX 411, 265, and 1230 were found to be 1.5-, 3.7-, and 5-fold higher than their respective autotrophic rates. With a rapid nine-hour heterotrophic doubling time, Chlorella sorokiniana UTEX 1230 maximally accumulated 39% total lipids by dry weight during heterotrophy compared to 18% autotrophically. Furthermore, the discrete fatty acid composition of each strain was examined in order to elucidate lipid accumulation patterns under the two trophic conditions. In both modes of growth, UTEX 411 and 265 produced 18∶1 as the principal fatty acid while UTEX 1230 exhibited a 2.5-fold enrichment in 18∶2 relative to 18∶1. Although the total lipid content was highest in UTEX 411 during heterotrophy, UTEX 1230 demonstrated a two-fold increase in its heterotrophic TAG fraction at a rate of 28.9 mg L−1 d−1 to reach 22% of the biomass, corresponding to as much as 90% of its total lipids. Interestingly, UTEX 1230 growth was restricted during mixotrophy and its TAG production rate was suppressed to 18.2 mg L−1 d−1. This constraint on carbon flow raises intriguing questions about the impact of sugar and light on the metabolic regulation of microalgal lipid biosynthesis. PMID:24699196

  13. Comparative analyses of three Chlorella species in response to light and sugar reveal distinctive lipid accumulation patterns in the Microalga C. sorokiniana.

    Directory of Open Access Journals (Sweden)

    Julian N Rosenberg

    Full Text Available While photosynthetic microalgae, such as Chlorella, serve as feedstocks for nutritional oils and biofuels, heterotrophic cultivation can augment growth rates, support high cell densities, and increase triacylglycerol (TAG lipid content. However, these species differ significantly in their photoautotrophic and heterotrophic characteristics. In this study, the phylogeny of thirty Chlorella strains was determined in order to inform bioprospecting efforts and detailed physiological assessment of three species. The growth kinetics and lipid biochemistry of C. protothecoides UTEX 411, C. vulgaris UTEX 265, and C. sorokiniana UTEX 1230 were quantified during photoautotrophy in Bold's basal medium (BBM and heterotrophy in BBM supplemented with glucose (10 g L-1. Heterotrophic growth rates of UTEX 411, 265, and 1230 were found to be 1.5-, 3.7-, and 5-fold higher than their respective autotrophic rates. With a rapid nine-hour heterotrophic doubling time, Chlorella sorokiniana UTEX 1230 maximally accumulated 39% total lipids by dry weight during heterotrophy compared to 18% autotrophically. Furthermore, the discrete fatty acid composition of each strain was examined in order to elucidate lipid accumulation patterns under the two trophic conditions. In both modes of growth, UTEX 411 and 265 produced 18:1 as the principal fatty acid while UTEX 1230 exhibited a 2.5-fold enrichment in 18:2 relative to 18:1. Although the total lipid content was highest in UTEX 411 during heterotrophy, UTEX 1230 demonstrated a two-fold increase in its heterotrophic TAG fraction at a rate of 28.9 mg L(-1 d(-1 to reach 22% of the biomass, corresponding to as much as 90% of its total lipids. Interestingly, UTEX 1230 growth was restricted during mixotrophy and its TAG production rate was suppressed to 18.2 mg L-1 d-1. This constraint on carbon flow raises intriguing questions about the impact of sugar and light on the metabolic regulation of microalgal lipid biosynthesis.

  14. Bayesian network analysis revealed the connectivity difference of the default mode network from the resting-state to task-state

    Science.gov (United States)

    Wu, Xia; Yu, Xinyu; Yao, Li; Li, Rui

    2014-01-01

    Functional magnetic resonance imaging (fMRI) studies have converged to reveal the default mode network (DMN), a constellation of regions that display co-activation during resting-state but co-deactivation during attention-demanding tasks in the brain. Here, we employed a Bayesian network (BN) analysis method to construct a directed effective connectivity model of the DMN and compared the organizational architecture and interregional directed connections under both resting-state and task-state. The analysis results indicated that the DMN was consistently organized into two closely interacting subsystems in both resting-state and task-state. The directed connections between DMN regions, however, changed significantly from the resting-state to task-state condition. The results suggest that the DMN intrinsically maintains a relatively stable structure whether at rest or performing tasks but has different information processing mechanisms under varied states. PMID:25309414

  15. A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types

    Science.gov (United States)

    Wagner, Emily C.; Schellenberg, John J.; Links, Matthew G.; van Schalkwyk, Julie; Reid, Gregor; Hemmingsen, Sean M.; Hill, Janet E.; Money, Deborah

    2015-01-01

    The vaginal microbiota is important in women’s reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an “intermediate” CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts. PMID:26266808

  16. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

    Directory of Open Access Journals (Sweden)

    Andrew Parker

    2015-12-01

    Full Text Available Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182 in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

  17. In silico genomic analyses reveal three distinct lineages of Escherichia coli O157:H7, one of which is associated with hyper-virulence.

    Science.gov (United States)

    Laing, Chad R; Buchanan, Cody; Taboada, Eduardo N; Zhang, Yongxiang; Karmali, Mohamed A; Thomas, James E; Gannon, Victor Pj

    2009-06-29

    Many approaches have been used to study the evolution, population structure and genetic diversity of Escherichia coli O157:H7; however, observations made with different genotyping systems are not easily relatable to each other. Three genetic lineages of E. coli O157:H7 designated I, II and I/II have been identified using octamer-based genome scanning and microarray comparative genomic hybridization (mCGH). Each lineage contains significant phenotypic differences, with lineage I strains being the most commonly associated with human infections. Similarly, a clade of hyper-virulent O157:H7 strains implicated in the 2006 spinach and lettuce outbreaks has been defined using single-nucleotide polymorphism (SNP) typing. In this study an in silico comparison of six different genotyping approaches was performed on 19 E. coli genome sequences from 17 O157:H7 strains and single O145:NM and K12 MG1655 strains to provide an overall picture of diversity of the E. coli O157:H7 population, and to compare genotyping methods for O157:H7 strains. In silico determination of lineage, Shiga-toxin bacteriophage integration site, comparative genomic fingerprint, mCGH profile, novel region distribution profile, SNP type and multi-locus variable number tandem repeat analysis type was performed and a supernetwork based on the combination of these methods was produced. This supernetwork showed three distinct clusters of strains that were O157:H7 lineage-specific, with the SNP-based hyper-virulent clade 8 synonymous with O157:H7 lineage I/II. Lineage I/II/clade 8 strains clustered closest on the supernetwork to E. coli K12 and E. coli O55:H7, O145:NM and sorbitol-fermenting O157 strains. The results of this study highlight the similarities in relationships derived from multi-locus genome sampling methods and suggest a "common genotyping language" may be devised for population genetics and epidemiological studies. Future genotyping methods should provide data that can be stored centrally and

  18. In silico genomic analyses reveal three distinct lineages of Escherichia coli O157:H7, one of which is associated with hyper-virulence

    Directory of Open Access Journals (Sweden)

    Karmali Mohamed A

    2009-06-01

    Full Text Available Abstract Background Many approaches have been used to study the evolution, population structure and genetic diversity of Escherichia coli O157:H7; however, observations made with different genotyping systems are not easily relatable to each other. Three genetic lineages of E. coli O157:H7 designated I, II and I/II have been identified using octamer-based genome scanning and microarray comparative genomic hybridization (mCGH. Each lineage contains significant phenotypic differences, with lineage I strains being the most commonly associated with human infections. Similarly, a clade of hyper-virulent O157:H7 strains implicated in the 2006 spinach and lettuce outbreaks has been defined using single-nucleotide polymorphism (SNP typing. In this study an in silico comparison of six different genotyping approaches was performed on 19 E. coli genome sequences from 17 O157:H7 strains and single O145:NM and K12 MG1655 strains to provide an overall picture of diversity of the E. coli O157:H7 population, and to compare genotyping methods for O157:H7 strains. Results In silico determination of lineage, Shiga-toxin bacteriophage integration site, comparative genomic fingerprint, mCGH profile, novel region distribution profile, SNP type and multi-locus variable number tandem repeat analysis type was performed and a supernetwork based on the combination of these methods was produced. This supernetwork showed three distinct clusters of strains that were O157:H7 lineage-specific, with the SNP-based hyper-virulent clade 8 synonymous with O157:H7 lineage I/II. Lineage I/II/clade 8 strains clustered closest on the supernetwork to E. coli K12 and E. coli O55:H7, O145:NM and sorbitol-fermenting O157 strains. Conclusion The results of this study highlight the similarities in relationships derived from multi-locus genome sampling methods and suggest a "common genotyping language" may be devised for population genetics and epidemiological studies. Future genotyping

  19. Variation in Phytochemical Composition Reveals Distinct Divergence of Aloe vera (L.) Burm.f. From Other Aloe Species: Rationale Behind Selective Preference of Aloe vera in Nutritional and Therapeutic Use

    Science.gov (United States)

    Dey, Priyankar; Dutta, Somit; Chowdhury, Anurag; Das, Abhaya Prasad; Chaudhuri, Tapas Kumar

    2017-01-01

    In the present study, we have phytochemically characterized 5 different abundant Aloe species, including Aloe vera (L.) Burm.f., using silylation followed by Gas Chromatography-Mass Spectrometry technique and compared the data using multivariate statistical analysis. The results demonstrated clear distinction of the overall phytochemical profile of A vera, highlighted by its divergent spatial arrangement in the component plot. Lowest correlation of the phytochemical profiles were found between A vera and A aristata Haw. (−0.626), whereas highest correlation resided between A aristata and A aspera Haw. (0.899). Among the individual phytochemicals, palmitic acid was identified in highest abundance cumulatively, and carboxylic acids were the most predominant phytochemical species in all the Aloe species. Compared to A vera, linear correlation analysis revealed highest and lowest correlation with A aspera (R 2 = 0.9162) and A aristata (R 2 = 0.6745), respectively. Therefore, A vera demonstrated distinct spatial allocation, reflecting its greater phytochemical variability. PMID:29228808

  20. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

    Science.gov (United States)

    Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

    2015-12-01

    Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

  1. Global Metabolomics of the Placenta Reveals Distinct Metabolic Profiles between Maternal and Fetal Placental Tissues Following Delivery in Non-Labored Women

    Directory of Open Access Journals (Sweden)

    Jacquelyn M. Walejko

    2018-01-01

    Full Text Available We evaluated the metabolic alterations in maternal and fetal placental tissues from non-labored women undergoing cesarean section using samples collected from 5 min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that significantly differed between maternal and fetal placental tissues (FDR-corrected p-value < 0.05, with 12 metabolites elevated in the maternal tissue, reflecting the flux of these metabolites from mother to fetus. In the maternal tissue, 4 metabolites were significantly altered at 15 min, 10 metabolites at 30 min, and 16 metabolites at 1 h postdelivery, while 11 metabolites remained stable over 24 h. In contrast, in the fetal placenta tissue, 1 metabolite was significantly altered at 15 min, 2 metabolites at 30 min, and 4 metabolites at 1 h postdelivery, while 22 metabolites remained stable over 24 h. Our study provides information on the metabolic profiles of maternal and fetal placental tissues delivered by cesarean section and reveals that there are different metabolic alterations in the maternal and fetal tissues of the placenta following delivery.

  2. Human 45,X fibroblast transcriptome reveals distinct differentially expressed genes including long noncoding RNAs potentially associated with the pathophysiology of Turner syndrome.

    Directory of Open Access Journals (Sweden)

    Shriram N Rajpathak

    Full Text Available Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s in the establishment of Turner syndrome phenotypes.

  3. Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

    Directory of Open Access Journals (Sweden)

    Cedric S Wesley

    Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

  4. Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

    Science.gov (United States)

    Wesley, Cedric S.; Guo, Heng; Chaudhry, Kanita A.; Thali, Markus J.; Yin, Jerry C.; Clason, Todd; Wesley, Umadevi V.

    2011-01-01

    Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions. PMID:21750738

  5. High-resolution analysis of a QTL for resistance to Stagonospora nodorum glume blotch in wheat reveals presence of two distinct resistance loci in the target interval.

    Science.gov (United States)

    Shatalina, Margarita; Messmer, Monika; Feuillet, Catherine; Mascher, Fabio; Paux, Etienne; Choulet, Frédéric; Wicker, Thomas; Keller, Beat

    2014-03-01

    Stagonospora nodorum glume blotch (SNG), caused by the necrotrophic fungus Stagonospora nodorum, is one of the economically important diseases of bread wheat (Triticum aestivum L.). Resistance to SNG is known to be quantitative and previous studies of a recombinant inbred line (RIL) population identified a major quantitative trait locus (QTL) for resistance to SNG on the short arm of chromosome 3B. To localize this QTL (QSng.sfr-3BS) with high resolution, we constructed a genetic map for the QTL target region using information from sequenced flow-sorted chromosomes 3B of the two parental cultivars 'Arina' and 'Forno', the physical map of chromosome 3B of cultivar 'Chinese Spring' and BAC-clone sequences. The mapping population of near-isogenic lines (NIL) was evaluated for SNG resistance in field infection tests. NILs segregated for disease resistance as well as for plant height; additionally, we observed a high environmental influence on the trait. Our analysis detected a strong negative correlation of SNG resistance and plant height. Further analysis of the target region identified two linked loci associated with SNG resistance. One of them was also associated with plant height, revealing an effect of QSng.sfr-3BS on plant height that was hidden in the RIL population. This result demonstrates an unexpectedly high genetic complexity of resistance controlled by QSng.sfr-3BS and shows the importance of the study of QTL in mendelized form in NILs.

  6. Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

    Science.gov (United States)

    Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

    2016-01-01

    To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

  7. Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.

    Science.gov (United States)

    Bouts, Mark J R J; Westmoreland, Susan V; de Crespigny, Alex J; Liu, Yutong; Vangel, Mark; Dijkhuizen, Rick M; Wu, Ona; D'Arceuil, Helen E

    2015-12-15

    Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

  8. Sequencing of emerging canine distemper virus strain reveals new distinct genetic lineage in the United States associated with disease in wildlife and domestic canine populations.

    Science.gov (United States)

    Riley, Matthew C; Wilkes, Rebecca P

    2015-12-18

    Recent outbreaks of canine distemper have prompted examination of strains from clinical samples submitted to the University of Tennessee College of Veterinary Medicine (UTCVM) Clinical Virology Lab. We previously described a new strain of CDV that significantly diverged from all genotypes reported to date including America 2, the genotype proposed to be the main lineage currently circulating in the US. The aim of this study was to determine when this new strain appeared and how widespread it is in animal populations, given that it has also been detected in fully vaccinated adult dogs. Additionally, we sequenced complete viral genomes to characterize the strain and determine if variation is confined to known variable regions of the genome or if the changes are also present in more conserved regions. Archived clinical samples were genotyped using real-time RT-PCR amplification and sequencing. The genomes of two unrelated viruses from a dog and fox each from a different state were sequenced and aligned with previously published genomes. Phylogenetic analysis was performed using coding, non-coding and genome-length sequences. Virus neutralization assays were used to evaluate potential antigenic differences between this strain and a vaccine strain and mixed ANOVA test was used to compare the titers. Genotyping revealed this strain first appeared in 2011 and was detected in dogs from multiple states in the Southeast region of the United States. It was the main strain detected among the clinical samples that were typed from 2011-2013, including wildlife submissions. Genome sequencing demonstrated that it is highly conserved within a new lineage and preliminary serologic testing showed significant differences in neutralizing antibody titers between this strain and the strain commonly used in vaccines. This new strain represents an emerging CDV in domestic dogs in the US, may be associated with a stable reservoir in the wildlife population, and could facilitate vaccine

  9. Systematic analysis of phloem-feeding insect-induced transcriptional reprogramming in Arabidopsis highlights common features and reveals distinct responses to specialist and generalist insects.

    Science.gov (United States)

    Foyer, Christine H; Verrall, Susan R; Hancock, Robert D

    2015-02-01

    Phloem-feeding insects (PFIs), of which aphids are the largest group, are major agricultural pests causing extensive damage to crop plants. In contrast to chewing insects, the nature of the plant response to PFIs remains poorly characterized. Scrutiny of the literature concerning transcriptional responses of model and crop plant species to PFIs reveals surprisingly little consensus with respect to the transcripts showing altered abundance following infestation. Nevertheless, core features of the transcriptional response to PFIs can be defined in Arabidopsis thaliana. This comparison of the PFI-associated transcriptional response observed in A. thaliana infested by the generalists Myzus persicae and Bemisia tabaci with the specialist Brevicoryne brassicae highlights the importance of calcium-dependent and receptor kinase-associated signalling. We discuss these findings within the context of the complex cross-talk between the different hormones regulating basal immune response mechanisms in plants. We identify PFI-responsive genes, highlighting the importance of cell wall-associated kinases in plant-PFI interactions, as well as the significant role of kinases containing the domain of unknown function 26. A common feature of plant-PFI interaction is enhanced abundance of transcripts encoding WRKY transcription factors. However, significant divergence was observed with respect to secondary metabolism dependent upon the insect attacker. Transcripts encoding enzymes and proteins associated with glucosinolate metabolism were decreased following attack by the generalist M. persicae but not by the specialist B. brassicae. This analysis provides a comprehensive overview of the molecular patterns associated with the plant response to PFIs and suggests that plants recognize and respond to perturbations in the cell wall occurring during PFI infestation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  10. Sequence-based Screening for Rare Enzymes: New Insights into the World of AMDases Reveal a Conserved Motif and 58 Novel Enzymes Clustering in Eight Distinct Families.

    Directory of Open Access Journals (Sweden)

    Janine Maimanakos

    2016-08-01

    Full Text Available Arylmalonate-Decarboxylases (AMDases, EC 4.1.1.76 are very rare and mostly underexplored enzymes. Currently only four known and biochemically characterized representatives exist. However, their ability to decarboxylate α-disubstituted malonic acid derivatives to optically pure products without cofactors makes them attractive and promising candidates for the use as biocatalysts in industrial processes. Until now, AMDases could not be separated from other members of the aspartate/glutamate racemase superfamily based on their gene sequences. Within this work, a search algorithm was developed that enables a reliable prediction of AMDase activity for potential candidates. Based on specific sequence patterns and screening methods 58 novel AMDase candidate genes could be identified in this work. Thereby, AMDases with the conserved sequence pattern of Bordetella bronchiseptica’s prototype appeared to be limited to the classes of Alpha-, Beta- and Gammaproteobacteria. Amino acid homologies and comparison of gene surrounding sequences enabled the classification of eight enzyme clusters. Particularly striking is the accumulation of genes coding for different transporters of the TTT family, TRAP transporters and ABC transporters as well as genes coding for mandelate racemases/muconate lactonizing enzymes that might be involved in substrate uptake or degradation of AMDase products. Further, three novel AMDases were characterized which showed a high enantiomeric excess (>99% of the (R-enantiomer of flurbiprofen. These are the recombinant AmdA and AmdV from Variovorax sp. strains HH01 and HH02, originated from soil, and AmdP from Polymorphum gilvum found by a data base search. Altogether our findings give new insights into the class of AMDases and reveal many previously unknown enzyme candidates with high potential for bioindustrial processes.

  11. A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments.

    Directory of Open Access Journals (Sweden)

    Hannah L Albritton

    Full Text Available Chlamydia trachomatis (CT is the leading sexually transmitted bacterial infection. The continued global burden of CT infection strongly predicates the need for a vaccine to supplement current chlamydial control programs. The correlates of protection against CT are currently unknown, but they must be carefully defined to guide vaccine design. The localized nature of chlamydial infection in columnar epithelial cells of the genital tract necessitates investigation of immunity at the site of infection. The purpose of this study was to develop a sensitive whole bacterial enzyme-linked immunosorbent assay (ELISA to quantify and compare CT-specific IgG and IgA in sera and genital secretions from CT-infected women. To achieve this, elementary bodies (EBs from two of the most common genital serovars (D and E were attached to poly-L-lysine-coated microtiter plates with glutaraldehyde. EB attachment and integrity were verified by the presence of outer membrane antigens and the absence of bacterial cytoplasmic antigens. EB-specific IgG and IgA standards were developed by pooling sera with high titers of CT-specific antibodies from infected women. Serum, endocervical and vaginal secretions, and endocervical cytobrush specimens from CT-infected women were used to quantify CT-specific IgG and IgA which were then normalized to total IgG and IgA, respectively. Analyses of paired serum and genital samples revealed significantly higher proportions of EB-specific antibodies in genital secretions compared to sera. Cervical and vaginal secretions and cytobrush specimens had similar proportions of EB-specific antibodies, suggesting any one of these genital sampling techniques could be used to quantify CT-specific antibodies when appropriate normalization methodologies are implemented. Overall, these results illustrate the need to investigate genital tract CT antibody responses, and our assay provides a useful quantitative tool to assess natural immunity in defined

  12. Multi-gene phylogenetic analysis reveals that shochu-fermenting Saccharomyces cerevisiae strains form a distinct sub-clade of the Japanese sake cluster.

    Science.gov (United States)

    Futagami, Taiki; Kadooka, Chihiro; Ando, Yoshinori; Okutsu, Kayu; Yoshizaki, Yumiko; Setoguchi, Shinji; Takamine, Kazunori; Kawai, Mikihiko; Tamaki, Hisanori

    2017-10-01

    Shochu is a traditional Japanese distilled spirit. The formation of the distinguishing flavour of shochu produced in individual distilleries is attributed to putative indigenous yeast strains. In this study, we performed the first (to our knowledge) phylogenetic classification of shochu strains based on nucleotide gene sequences. We performed phylogenetic classification of 21 putative indigenous shochu yeast strains isolated from 11 distilleries. All of these strains were shown or confirmed to be Saccharomyces cerevisiae, sharing species identification with 34 known S. cerevisiae strains (including commonly used shochu, sake, ale, whisky, bakery, bioethanol and laboratory yeast strains and clinical isolate) that were tested in parallel. Our analysis used five genes that reflect genome-level phylogeny for the strain-level classification. In a first step, we demonstrated that partial regions of the ZAP1, THI7, PXL1, YRR1 and GLG1 genes were sufficient to reproduce previous sub-species classifications. In a second step, these five analysed regions from each of 25 strains (four commonly used shochu strains and the 21 putative indigenous shochu strains) were concatenated and used to generate a phylogenetic tree. Further analysis revealed that the putative indigenous shochu yeast strains form a monophyletic group that includes both the shochu yeasts and a subset of the sake group strains; this cluster is a sister group to other sake yeast strains, together comprising a sake-shochu group. Differences among shochu strains were small, suggesting that it may be possible to correlate subtle phenotypic differences among shochu flavours with specific differences in genome sequences. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections.

    Science.gov (United States)

    Chalmet, Kristen; Staelens, Delfien; Blot, Stijn; Dinakis, Sylvie; Pelgrom, Jolanda; Plum, Jean; Vogelaers, Dirk; Vandekerckhove, Linos; Verhofstede, Chris

    2010-09-07

    The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission. Baseline HIV-1 pol sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics. Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with Chlamydia (p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p HIV (p = 0.017). Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.

  14. A novel method for measuring cellular antibody uptake using imaging flow cytometry reveals distinct uptake rates for two different monoclonal antibodies targeting L1.

    Science.gov (United States)

    Hazin, John; Moldenhauer, Gerhard; Altevogt, Peter; Brady, Nathan R

    2015-08-01

    Monoclonal antibodies (mAbs) have emerged as a promising tool for cancer therapy. Differing approaches utilize mAbs to either deliver a drug to the tumor cells or to modulate the host's immune system to mediate tumor kill. The rate by which a therapeutic antibody is being internalized by tumor cells is a decisive feature for choosing the appropriate treatment strategy. We herein present a novel method to effectively quantitate antibody uptake of tumor cells by using image-based flow cytometry, which combines image analysis with high throughput of sample numbers and sample size. The use of this method is established by determining uptake rate of an anti-EpCAM antibody (HEA125), from single cell measurements of plasma membrane versus internalized antibody, in conjunction with inhibitors of endocytosis. The method is then applied to two mAbs (L1-9.3, L1-OV52.24) targeting the neural cell adhesion molecule L1 (L1CAM) at two different epitopes. Based on median cell population responses, we find that mAb L1-OV52.24 is rapidly internalized by the ovarian carcinoma cell line SKOV3ip while L1 mAb 9.3 is mainly retained at the cell surface. These findings suggest the L1 mAb OV52.24 as a candidate to be further developed for drug-delivery to cancer cells, while L1-9.3 may be optimized to tag the tumor cells and stimulate immunogenic cancer cell killing. Furthermore, when analyzing cell-to-cell variability, we observed L1 mAb OV52.24 rapidly transition into a subpopulation with high-internalization capacity. In summary, this novel high-content method for measuring antibody internalization rate provides a high level of accuracy and sensitivity for cell population measurements and reveals further biologically relevant information when taking into account cellular heterogeneity. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

    Directory of Open Access Journals (Sweden)

    Abu Bakar Ali Asad

    Full Text Available Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8. BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail.Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate

  16. Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine.

    Science.gov (United States)

    Sherwood, Cara L; Boitano, Scott

    2016-05-17

    The potential for adverse respiratory effects following exposure to electronic (e-) cigarette liquid (e-liquid) flavorings remains largely unexplored. Given the multitude of flavor permutations on the market, identification of those flavor constituents that negatively impact the respiratory tract is a daunting task. In this study we examined the impact of common e-liquid flavoring chemicals on the airway epithelium, the cellular monolayer that provides the first line of defense against inhaled particulates, pathogens, and toxicants. We used the xCELLigence real-time cell analyzer (RTCA) as a primary high-capacity screening tool to assess cytotoxicity thresholds and physiological effects of common e-liquid flavoring chemicals on immortalized human bronchial epithelial cells (16HBE14o-). The RTCA was used secondarily to assess the capability of 16HBE14o- cells to respond to cellular signaling agonists following a 24 h exposure to select flavoring chemicals. Finally, we conducted biophysical measurements of well-differentiated primary mouse tracheal epithelial (MTE) cells with an Ussing chamber to measure the effects of e-cigarette flavoring constituents on barrier function and ion conductance. In our high-capacity screens five of the seven flavoring chemicals displayed changes in cellular impedance consistent with cell death at concentrations found in e-liquid. Vanillin and the chocolate flavoring 2,5-dimethylpyrazine caused alterations in cellular physiology indicative of a cellular signaling event. At subcytotoxic levels, 24 h exposure to 2,5-dimethylpyrazine compromised the ability of airway epithelial cells to respond to signaling agonists important in salt and water balance at the airway surface. Biophysical measurements of 2,5-dimethylpyrazine on primary MTE cells revealed alterations in ion conductance consistent with an efflux at the apical airway surface that was accompanied by a transient loss in transepithelial resistance. Mechanistic studies confirmed

  17. Deep sequencing of small RNA libraries from human prostate epithelial and stromal cells reveal distinct pattern of microRNAs primarily predicted to target growth factors.

    Science.gov (United States)

    Singh, Savita; Zheng, Yun; Jagadeeswaran, Guru; Ebron, Jey Sabith; Sikand, Kavleen; Gupta, Sanjay; Sunker, Ramanjulu; Shukla, Girish C

    2016-02-28

    Complex epithelial and stromal cell interactions are required during the development and progression of prostate cancer. Regulatory small non-coding microRNAs (miRNAs) participate in the spatiotemporal regulation of messenger RNA (mRNA) and regulation of translation affecting a large number of genes involved in prostate carcinogenesis. In this study, through deep-sequencing of size fractionated small RNA libraries we profiled the miRNAs of prostate epithelial (PrEC) and stromal (PrSC) cells. Over 50 million reads were obtained for PrEC in which 860,468 were unique sequences. Similarly, nearly 76 million reads for PrSC were obtained in which over 1 million were unique reads. Expression of many miRNAs of broadly conserved and poorly conserved miRNA families were identified. Sixteen highly expressed miRNAs with significant change in expression in PrSC than PrEC were further analyzed in silico. ConsensusPathDB showed the target genes of these miRNAs were significantly involved in adherence junction, cell adhesion, EGRF, TGF-β and androgen signaling. Let-7 family of tumor-suppressor miRNAs expression was highly pervasive in both, PrEC and PrSC cells. In addition, we have also identified several miRNAs that are unique to PrEC or PrSC cells and their predicted putative targets are a group of transcription factors. This study provides perspective on the miRNA expression in PrEC and PrSC, and reveals a global trend in miRNA interactome. We conclude that the most abundant miRNAs are potential regulators of development and differentiation of the prostate gland by targeting a set of growth factors. Additionally, high level expression of the most members of let-7 family miRNAs suggests their role in the fine tuning of the growth and proliferation of prostate epithelial and stromal cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Multigene phylogeny of the scyphozoan jellyfish family Pelagiidae reveals that the common U.S. Atlantic sea nettle comprises two distinct species (Chrysaora quinquecirrha and C. chesapeakei

    Directory of Open Access Journals (Sweden)

    Keith M. Bayha

    2017-10-01

    Full Text Available Background Species of the scyphozoan family Pelagiidae (e.g., Pelagia noctiluca, Chrysaora quinquecirrha are well-known for impacting fisheries, aquaculture, and tourism, especially for the painful sting they can inflict on swimmers. However, historical taxonomic uncertainty at the genus (e.g., new genus Mawia and species levels hinders progress in studying their biology and evolutionary adaptations that make them nuisance species, as well as ability to understand and/or mitigate their ecological and economic impacts. Methods We collected nuclear (28S rDNA and mitochondrial (cytochrome c oxidase I and 16S rDNA sequence data from individuals of all four pelagiid genera, including 11 of 13 currently recognized species of Chrysaora. To examine species boundaries in the U.S. Atlantic sea nettle Chrysaora quinquecirrha, specimens were included from its entire range along the U.S. Atlantic and Gulf of Mexico coasts, with representatives also examined morphologically (macromorphology and cnidome. Results Phylogenetic analyses show that the genus Chrysaora is paraphyletic with respect to other pelagiid genera. In combined analyses, Mawia, sampled from the coast of Senegal, is most closely related to Sanderia malayensis, and Pelagia forms a close relationship to a clade of Pacific Chrysaora species (Chrysaora achlyos, Chrysaora colorata, Chrysaora fuscescens, and Chrysaora melanaster. Chrysaora quinquecirrha is polyphyletic, with one clade from the U.S. coastal Atlantic and another in U.S. Atlantic estuaries and Gulf of Mexico. These genetic differences are reflected in morphology, e.g., tentacle and lappet number, oral arm length, and nematocyst dimensions. Caribbean sea nettles (Jamaica and Panama are genetically similar to the U.S. Atlantic estuaries and Gulf of Mexico clade of Chrysaora quinquecirrha. Discussion Our phylogenetic hypothesis for Pelagiidae contradicts current generic definitions, revealing major disagreements between DNA-based and

  19. Structures of the APC–ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners

    Science.gov (United States)

    Zhang, Zhenyi; Akyildiz, Senem; Xiao, Yafei; Gai, Zhongchao; An, Ying; Behrens, Jürgen; Wu, Geng

    2015-01-01

    The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC–Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC–ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC–ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC–ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC–ARM binding partners. PMID:27462415

  20. Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners.

    Science.gov (United States)

    Zhang, Zhenyi; Akyildiz, Senem; Xiao, Yafei; Gai, Zhongchao; An, Ying; Behrens, Jürgen; Wu, Geng

    2015-01-01

    The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC-Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC-ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC-ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC-ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC-ARM binding partners.

  1. Divergent and convergent modes of interaction between wheat and Puccinia graminis f. sp. tritici isolates revealed by the comparative gene co-expression network and genome analyses.

    Science.gov (United States)

    Rutter, William B; Salcedo, Andres; Akhunova, Alina; He, Fei; Wang, Shichen; Liang, Hanquan; Bowden, Robert L; Akhunov, Eduard

    2017-04-12

    Two opposing evolutionary constraints exert pressure on plant pathogens: one to diversify virulence factors in order to evade plant defenses, and the other to retain virulence factors critical for maintaining a compatible interaction with the plant host. To better understand how the diversified arsenals of fungal genes promote interaction with the same compatible wheat line, we performed a comparative genomic analysis of two North American isolates of Puccinia graminis f. sp. tritici (Pgt). The patterns of inter-isolate divergence in the secreted candidate effector genes were compared with the levels of conservation and divergence of plant-pathogen gene co-expression networks (GCN) developed for each isolate. Comprative genomic analyses revealed substantial level of interisolate divergence in effector gene complement and sequence divergence. Gene Ontology (GO) analyses of the conserved and unique parts of the isolate-specific GCNs identified a number of conserved host pathways targeted by both isolates. Interestingly, the degree of inter-isolate sub-network conservation varied widely for the different host pathways and was positively associated with the proportion of conserved effector candidates associated with each sub-network. While different Pgt isolates tended to exploit similar wheat pathways for infection, the mode of plant-pathogen interaction varied for different pathways with some pathways being associated with the conserved set of effectors and others being linked with the diverged or isolate-specific effectors. Our data suggest that at the intra-species level pathogen populations likely maintain divergent sets of effectors capable of targeting the same plant host pathways. This functional redundancy may play an important role in the dynamic of the "arms-race" between host and pathogen serving as the basis for diverse virulence strategies and creating conditions where mutations in certain effector groups will not have a major effect on the pathogen

  2. Gravity Modes Reveal the Internal Rotation of a Post-mass-transfer Gamma Doradus/Delta Scuti Hybrid Pulsator in Kepler Eclipsing Binary KIC 9592855

    Science.gov (United States)

    Guo, Z.; Gies, D. R.; Matson, R. A.

    2017-12-01

    We report the discovery of a post-mass-transfer Gamma Doradus/Delta Scuti hybrid pulsator in the eclipsing binary KIC 9592855. This binary has a circular orbit, an orbital period of 1.2 days, and contains two stars of almost identical masses ({M}1=1.72 {M}⊙ ,{M}2=1.71 {M}⊙ ). However, the cooler secondary star is more evolved ({R}2=1.96 {R}⊙ ), while the hotter primary is still on the zero-age-main-sequence ({R}1=1.53 {R}⊙ ). Coeval models from single-star evolution cannot explain the observed masses and radii, and binary evolution with mass-transfer needs to be invoked. After subtracting the binary light curve, the Fourier spectrum shows low-order pressure-mode pulsations, and more dominantly, a cluster of low-frequency gravity modes at about 2 day-1. These g-modes are nearly equally spaced in period, and the period spacing pattern has a negative slope. We identify these g-modes as prograde dipole modes and find that they stem from the secondary star. The frequency range of unstable p-modes also agrees with that of the secondary. We derive the internal rotation rate of the convective core and the asymptotic period spacing from the observed g-modes. The resulting values suggest that the core and envelope rotate nearly uniformly, i.e., their rotation rates are both similar to the orbital frequency of this synchronized binary.

  3. Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

    Science.gov (United States)

    Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

    2014-01-01

    Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

  4. Terahertz spectra revealing the collective excitation mode in charge-density-wave single crystal LuFe{sub 2}O{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiumei; Jin, Zuanming; Lin, Xian; Ma, Guohong [Department of Physics, Shanghai University (China); Cheng, Zhenxiang [Institute for Superconducting and Electronic Materials, University of Wollongong, NSW (Australia); Balakrishnan, Geetha [Department of Physics, University of Warwick, Coventry (United Kingdom)

    2017-09-15

    A low-energy collective excitation mode in charge-ordered multiferroic LuFe{sub 2}O{sub 4} is reported via terahertz time-domain spectroscopy. Upon cooling from 300 to 40 K, the central resonance frequency showed a pronounced hardening from 0.85 to 1.15 THz. In analogy to the well-known low-energy optical properties of LuFe{sub 2}O{sub 4}, this emerging resonance was attributed to the charge-density-wave (CDW) collective excitations. By using the Drude-Lorentz model fitting, the CDW collective mode becomes increasingly damped with the increasing temperature. Furthermore, the kinks of the CDW collective mode at the magnetic transition temperature are analyzed, which indicate the coupling of spin order with electric polarization. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Quantitative mass spectrometry of histones H3.2 and H3.3 in Suz12-deficient mouse embryonic stem cells reveals distinct, dynamic post-translational modifications at Lys-27 and Lys-36

    DEFF Research Database (Denmark)

    Jung, Hye Ryung; Pasini, Diego; Helin, Kristian

    2010-01-01

    distinct coexisting modifications. In certain cases, high mass accuracy LTQ-Orbitrap MS/MS allowed precise localization of near isobaric coexisting PTMs such as trimethylation and acetylation within individual peptides. ETD MS/MS facilitated sequencing and annotation of phosphorylated histone peptides....... The combined use of ETD and CID MS/MS increased the total number of identified modified peptides. Comparative quantitative analysis of histones from wild type and Suz12-deficient ESCs using stable isotope labeling with amino acids in cell culture and LC-MS/MS revealed a dramatic reduction of H3K27me2 and H3K27......me3 and an increase of H3K27ac, thereby uncovering an antagonistic methyl/acetyl switch at H3K27. The reduction in H3K27 methylation and increase in H3K27 acetylation was accompanied by H3K36 acetylation and methylation. Estimation of the global isoform percentage of unmodified and modified histone...

  6. Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region.

    Science.gov (United States)

    Hernández, Candela L; Reales, Guillermo; Dugoujon, Jean-Michel; Novelletto, Andrea; Rodríguez, Juan Nicolás; Cuesta, Pedro; Calderón, Rosario

    2014-01-24

    The archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region. The mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population. The maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to those terrestrial movements

  7. Synapsis-defective mutants reveal a correlation between chromosome conformation and the mode of double-strand break repair during Caenorhabditis elegans meiosis.

    Science.gov (United States)

    Smolikov, Sarit; Eizinger, Andreas; Hurlburt, Allison; Rogers, Eric; Villeneuve, Anne M; Colaiácovo, Mónica P

    2007-08-01

    SYP-3 is a new structural component of the synaptonemal complex (SC) required for the regulation of chromosome synapsis. Both chromosome morphogenesis and nuclear organization are altered throughout the germlines of syp-3 mutants. Here, our analysis of syp-3 mutants provides insights into the relationship between chromosome conformation and the repair of meiotic double-strand breaks (DSBs). Although crossover recombination is severely reduced in syp-3 mutants, the production of viable offspring accompanied by the disappearance of RAD-51 foci suggests that DSBs are being repaired in these synapsis-defective mutants. Our studies indicate that once interhomolog recombination is impaired, both intersister recombination and nonhomologous end-joining pathways may contribute to repair during germline meiosis. Moreover, our studies suggest that the conformation of chromosomes may influence the mode of DSB repair employed during meiosis.

  8. Patterns of altered neural synchrony in the default mode network in autism spectrum disorder revealed with magnetoencephalography (MEG): Relationship to clinical symptomatology.

    Science.gov (United States)

    Lajiness-O'Neill, Renée; Brennan, Jonathan R; Moran, John E; Richard, Annette E; Flores, Ana-Mercedes; Swick, Casey; Goodcase, Ryan; Andersen, Tiffany; McFarlane, Kaitlyn; Rusiniak, Kenneth; Kovelman, Ioulia; Wagley, Neelima; Ugolini, Maggie; Albright, Jeremy; Bowyer, Susan M

    2018-03-01

    Disrupted neural synchrony may be a primary electrophysiological abnormality in autism spectrum disorders (ASD), altering communication between discrete brain regions and contributing to abnormalities in patterns of connectivity within identified neural networks. Studies exploring brain dynamics to comprehensively characterize and link connectivity to large-scale cortical networks and clinical symptoms are lagging considerably. Patterns of neural coherence within the Default Mode Network (DMN) and Salience Network (SN) during resting state were investigated in 12 children with ASD (M Age  = 9.2) and 13 age and gender-matched neurotypicals (NT) (M Age  = 9.3) with magnetoencephalography. Coherence between 231 brain region pairs within four frequency bands (theta (4-7 Hz), alpha, (8-12 Hz), beta (13-30 Hz), and gamma (30-80 Hz)) was calculated. Relationships between neural coherence and social functioning were examined. ASD was characterized by lower synchronization across all frequencies, reaching clinical significance in the gamma band. Lower gamma synchrony between fronto-temporo-parietal regions was observed, partially consistent with diminished default mode network (DMN) connectivity. Lower gamma coherence in ASD was evident in cross-hemispheric connections between: angular with inferior/middle frontal; middle temporal with middle/inferior frontal; and within right-hemispheric connections between angular, middle temporal, and inferior/middle frontal cortices. Lower gamma coherence between left angular and left superior frontal, right inferior/middle frontal, and right precuneus and between right angular and inferior/middle frontal cortices was related to lower social/social-communication functioning. Results suggest a pattern of lower gamma band coherence in a subset of regions within the DMN in ASD (angular and middle temporal cortical areas) related to lower social/social-communicative functioning. Autism Res 2018, 11: 434-449. © 2017 International

  9. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

    Science.gov (United States)

    Corrada, Dario; Soshilov, Anatoly A; Denison, Michael S; Bonati, Laura

    2016-06-01

    The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

  10. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

    Directory of Open Access Journals (Sweden)

    Dario Corrada

    2016-06-01

    Full Text Available The Aryl hydrocarbon Receptor (AhR is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT protein, occurring through the Helix-Loop-Helix (HLH and PER-ARNT-SIM (PAS domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms

  11. Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells.

    Science.gov (United States)

    Bodero, Marcia; Hoogenboom, Ron L A P; Bovee, Toine F H; Portier, Liza; de Haan, Laura; Peijnenburg, Ad; Hendriksen, Peter J M

    2018-02-01

    A study with DNA microarrays was performed to investigate the effects of two diarrhetic and one azaspiracid shellfish poison, okadaic acid (OA), dinophysistoxin-1 (DTX-1) and azaspiracid-1 (AZA-1) respectively, on the whole-genome mRNA expression of undifferentiated intestinal Caco-2 cells. Previously, the most responding genes were used to develop a dedicated array tube test to screen shellfish samples on the presence of these toxins. In the present study the whole genome mRNA expression was analyzed in order to reveal modes of action and obtain hints on potential biomarkers suitable to be used in alternative bioassays. Effects on key genes in the most affected pathways and processes were confirmed by qPCR. OA and DTX-1 induced almost identical effects on mRNA expression, which strongly indicates that OA and DTX-1induce similar toxic effects. Biological interpretation of the microarray data indicates that both compounds induce hypoxia related pathways/processes, the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. The gene expression profile of AZA-1 is different and shows increased mRNA expression of genes involved in cholesterol synthesis and glycolysis, suggesting a different mode of action for this toxin. Future studies should reveal whether identified pathways provide suitable biomarkers for rapid detection of DSPs in shellfish. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Intake and transformation to a glycoside of (Z)-3-hexenol from infested neighbors reveals a mode of plant odor reception and defense

    Science.gov (United States)

    Sugimoto, Koichi; Matsui, Kenji; Iijima, Yoko; Akakabe, Yoshihiko; Muramoto, Shoko; Ozawa, Rika; Uefune, Masayoshi; Sasaki, Ryosuke; Alamgir, Kabir Md.; Akitake, Shota; Nobuke, Tatsunori; Galis, Ivan; Aoki, Koh; Shibata, Daisuke; Takabayashi, Junji

    2014-01-01

    Plants receive volatile compounds emitted by neighboring plants that are infested by herbivores, and consequently the receiver plants begin to defend against forthcoming herbivory. However, to date, how plants receive volatiles and, consequently, how they fortify their defenses, is largely unknown. In this study, we found that undamaged tomato plants exposed to volatiles emitted by conspecifics infested with common cutworms (exposed plants) became more defensive against the larvae than those exposed to volatiles from uninfested conspecifics (control plants) in a constant airflow system under laboratory conditions. Comprehensive metabolite analyses showed that only the amount of (Z)-3-hexenylvicianoside (HexVic) was higher in exposed than control plants. This compound negatively affected the performance of common cutworms when added to an artificial diet. The aglycon of HexVic, (Z)-3-hexenol, was obtained from neighboring infested plants via the air. The amount of jasmonates (JAs) was not higher in exposed plants, and HexVic biosynthesis was independent of JA signaling. The use of (Z)-3-hexenol from neighboring damaged conspecifics for HexVic biosynthesis in exposed plants was also observed in an experimental field, indicating that (Z)-3-hexenol intake occurred even under fluctuating environmental conditions. Specific use of airborne (Z)-3-hexenol to form HexVic in undamaged tomato plants reveals a previously unidentified mechanism of plant defense. PMID:24778218

  13. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  14. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes

    DEFF Research Database (Denmark)

    Petrovic, Natasa; Walden, Tomas B; Shabalina, Irina G

    2009-01-01

    The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain...... physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis...... associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells...

  15. Revealing the radial modes in vortex beams

    CSIR Research Space (South Africa)

    Sephton, Bereneice C

    2016-10-01

    Full Text Available Light beams that carry orbital angular momentum are often approximated by modulating an initial beam, usually Gaussian, with an azimuthal phase variation to create a vortex beam. Such vortex beams are well defined azimuthally, but the radial profile...

  16. Proteomic Analysis Reveals Distinct Metabolic Differences Between Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) Grown Macrophages Derived from Murine Bone Marrow Cells.

    Science.gov (United States)

    Na, Yi Rang; Hong, Ji Hye; Lee, Min Yong; Jung, Jae Hun; Jung, Daun; Kim, Young Won; Son, Dain; Choi, Murim; Kim, Kwang Pyo; Seok, Seung Hyeok

    2015-10-01

    Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Melton, Elaina M. [Department of Biochemistry, University of Nebraska, Lincoln, NE (United States); Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (United States); Cerny, Ronald L. [Department of Chemistry, University of Nebraska, Lincoln, NE (United States); DiRusso, Concetta C. [Department of Biochemistry, University of Nebraska, Lincoln, NE (United States); Black, Paul N., E-mail: pblack2@unl.edu [Department of Biochemistry, University of Nebraska, Lincoln, NE (United States)

    2013-11-01

    Highlights: •Roles of FATP2 in fatty acid transport/activation contribute to lipid homeostasis. •Use of 13C- and D-labeled fatty acids provide novel insights into FATP2 function. •FATP2-dependent trafficking of FA into phospholipids results in distinctive profiles. •FATP2 functions in the transport and activation pathways for exogenous fatty acids. -- Abstract: In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4 h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The

  18. Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids

    International Nuclear Information System (INIS)

    Melton, Elaina M.; Cerny, Ronald L.; DiRusso, Concetta C.; Black, Paul N.

    2013-01-01

    Highlights: •Roles of FATP2 in fatty acid transport/activation contribute to lipid homeostasis. •Use of 13C- and D-labeled fatty acids provide novel insights into FATP2 function. •FATP2-dependent trafficking of FA into phospholipids results in distinctive profiles. •FATP2 functions in the transport and activation pathways for exogenous fatty acids. -- Abstract: In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4 h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The

  19. Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage.

    Science.gov (United States)

    Hilton, Matthew J; Tu, Xiaolin; Long, Fanxin

    2007-08-01

    Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development by signaling to both chondrocytes and perichondrial cells. Previous efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated ablation of Smoothened (Smo, encoding a transmembrane protein indispensable for Ihh signaling) has been only partially successful, due to the inability to discriminate between chondrocytes and perichondrial cells. Here we report a transgenic line (Col2-Cre) expressing under the control of the Colalpha1(II) promoter an inert form of Cre that is activatable by exogenous tamoxifen (TM); TM administration at proper times during embryogenesis induced Cre activity in chondrocytes but not in the perichondrium. By using this mouse line, we deleted Smo within subsets of chondrocytes without affecting the perichondrium and found that Smo removal led to localized disruption of the expression of parathyroid hormone-related protein (PTHrP) and the morphology of chondrocytes. Unexpectedly, TM invariably induced Cre activity in a subset of cells associated with the trabecular bone surface of long bones. These cells, when genetically marked and cultured in vitro, were capable of producing bone nodules. Expression of the Col2-Cre transgene in these cells likely reflected the endogenous Colalpha1(II) promoter activity as similar cells were found to express the IIA isoform of Colalpha1(II) mRNA endogenously. In summary, the present study has not only provided evidence that Ihh signaling directly controls PTHrP expression and chondrocyte morphology in the growth region cartilage, but has also uncovered a distinct cell type associated with the trabecular bone that appears to possess osteogenic potential.

  20. Multispectroscopic methods reveal different modes of interaction of anti cancer drug mitoxantrone with Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT).

    Science.gov (United States)

    Awasthi, Pamita; Dogra, Shilpa; Barthwal, Ritu

    2013-10-05

    The interaction of mitoxantrone with alternating Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT) duplex has been studied by absorption, fluorescence and Circular Dichroism (CD) spectroscopy at Drug to Phosphate base pair ratios D/P=20.0-0.04. Binding to GC polymer occurs in two distinct modes: partial stacking characterized by red shifts of 18-23nm at D/P=0.2-0.8 and external binding at D/P=1.0-20.0 whereas that to AT polymer occurs externally in the entire range of D/P. The binding constant and number of binding sites is 3.7×10(5)M(-1), 0.3 and 1.3× 10(4)M(-1), 1.5 in GC and AT polymers, respectively at low D/P ratios. CD binding isotherms show breakpoints at D/P=0.1, 0.5 and 0.25, 0.5 in GC and AT polymers, respectively. The intrinsic CD bands indicate that the distortions in GC polymer are significantly higher than that in AT polymer. Docking studies show partial insertion of mitoxantrone rings between to GC base pairs in alternating GC polymer. Side chains of mitoxantrone interact specifically with base pairs and DNA backbone. The studies are relevant to the understanding of suppression or inhibition of DNA cleavage on formation of ternary complex with topoisomerase-II enzyme and hence the anti cancer action. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Oxidative stress provokes distinct transcriptional responses in the stress-tolerant atr7 and stress-sensitive loh2 Arabidopsis thaliana mutants as revealed by multi-parallel quantitative real-time PCR analysis of ROS marker and antioxidant genes.

    Science.gov (United States)

    Mehterov, Nikolay; Balazadeh, Salma; Hille, Jacques; Toneva, Valentina; Mueller-Roeber, Bernd; Gechev, Tsanko

    2012-10-01

    The Arabidopsis thaliana atr7 mutant is tolerant to oxidative stress induced by paraquat (PQ) or the catalase inhibitor aminotriazole (AT), while its original background loh2 and wild-type plants are sensitive. Both, AT and PQ, which stimulate the intracellular formation of H₂O₂ or superoxide anions, respectively, trigger cell death in loh2 but do not lead to visible damage in atr7. To study gene expression during oxidative stress and ROS-induced programmed cell death, two platforms for multi-parallel quantitative real-time PCR (qRT-PCR) analysis of 217 antioxidant and 180 ROS marker genes were employed. The qRT-PCR analyses revealed AT- and PQ-induced expression of many ROS-responsive genes mainly in loh2, confirming that an oxidative burst plays a role in the activation of the cell death in this mutant. Some of the genes were specifically regulated by either AT or PQ, serving as markers for particular types of ROS. Genes significantly induced by both AT and PQ in loh2 included transcription factors (ANAC042/JUB1, ANAC102, DREB19, HSFA2, RRTF1, ZAT10, ZAT12, ethylene-responsive factors), signaling compounds, ferritins, alternative oxidases, and antioxidant enzymes. Many of these genes were upregulated in atr7 compared to loh2 under non-stress conditions at the first time point, indicating that higher basal levels of ROS and higher antioxidant capacity in atr7 are responsible for the enhanced tolerance to oxidative stress and suggesting a possible tolerance against multiple stresses of this mutant. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling*

    Science.gov (United States)

    Liu, Rui; Kenney, Justin W.; Manousopoulou, Antigoni; Johnston, Harvey E.; Kamei, Makoto; Woelk, Christopher H.; Xie, Jianling; Schwarzer, Michael; Proud, Christopher G.

    2016-01-01

    Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other nondividing primary cells. To study the rates of accumulation of specific proteins in these cells, we developed an optimized version of the Quantitative Noncanonical Amino acid Tagging LC/MS proteomic method to label and selectively enrich newly synthesized proteins in these primary cells while eliminating the suppressive effects of pre-existing and highly abundant nonisotope-tagged polypeptides. Our data revealed that a classical pathologic (phenylephrine; PE) and the recently identified insulin stimulus that also contributes to the development of pathological cardiac hypertrophy (insulin), both increased the synthesis of proteins involved in, e.g. glycolysis, the Krebs cycle and beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was up-regulated by signaling through mammalian target of rapamycin complex 1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was up-regulated in rat hearts following TAC. This isoform possesses specific regulatory

  3. Plasma Modes

    Science.gov (United States)

    Dubin, D. H. E.

    This chapter explores several aspects of the linear electrostatic normal modes of oscillation for a single-species non-neutral plasma in a Penning trap. Linearized fluid equations of motion are developed, assuming the plasma is cold but collisionless, which allow derivation of the cold plasma dielectric tensor and the electrostatic wave equation. Upper hybrid and magnetized plasma waves in an infinite uniform plasma are described. The effect of the plasma surface in a bounded plasma system is considered, and the properties of surface plasma waves are characterized. The normal modes of a cylindrical plasma column are discussed, and finally, modes of spheroidal plasmas, and finite temperature effects on the modes, are briefly described.

  4. Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α′

    Directory of Open Access Journals (Sweden)

    Jennifer Hochscherf

    2017-12-01

    Full Text Available Protein kinase CK2, a member of the eukaryotic protein kinase superfamily, is associated with cancer and other human pathologies and thus an attractive drug target. The indeno[1,2-b]indole scaffold is a novel lead structure to develop ATP-competitive CK2 inhibitors. Some indeno[1,2-b]indole-based CK2 inhibitors additionally obstruct ABCG2, an ABC half transporter overexpressed in breast cancer and co-responsible for drug efflux and resistance. Comprehensive derivatization studies revealed substitutions of the indeno[1,2-b]indole framework that boost either the CK2 or the ABCG2 selectivity or even support the dual inhibition potential. The best indeno[1,2-b]indole-based CK2 inhibitor described yet (IC50 = 25 nM is 5-isopropyl-4-(3-methylbut-2-enyl-oxy-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4p. Herein, we demonstrate the membrane permeability of 4p and describe co-crystal structures of 4p with CK2α and CK2α′, the paralogs of human CK2 catalytic subunit. As expected, 4p occupies the narrow, hydrophobic ATP site of CK2α/CK2α′, but surprisingly with a unique orientation: its hydrophobic substituents point towards the solvent while its two oxo groups are hydrogen-bonded to a hidden water molecule. An equivalent water molecule was found in many CK2α structures, but never as a critical mediator of ligand binding. This unexpected binding mode is independent of the interdomain hinge/helix αD region conformation and of the salt content in the crystallization medium.

  5. Tacoma mode

    International Nuclear Information System (INIS)

    Courant, E.D.; Ruth, R.D.; Wang, J.M.

    1979-01-01

    The name Tacoma refers to the Tacoma Narrows Bridge which collapsed on November 8, 1940 due to massive oscillations caused by high winds. One of the destructive modes was a torsion mode which was excited by transverse wind, a dipole force, and continued until the bridge collapsed. The name is used to refer to a coherent mode of oscillation of a spectrum of oscillators in which the amplitude vs frequency graph contains one node, where the node occurs near the driving frequency and a ω is not symmetric about zero. When this result is applied to vertical instabilities in coasting beams, it implies the existence of a coherent skew quadrupole moment, Q/sub xy/, whenever a coherent dipole oscillation exists

  6. Tacoma mode

    International Nuclear Information System (INIS)

    Courant, E.D.; Ruth, R.D.; Wang, J.M.

    1979-01-01

    The name Tacoma refers to the Tacoma Narrows Bridge which collapsed on November 8, 1940 due to massive oscillations caused by high winds. One of the destructive modes was a torsion mode which was excited by transverse wind, a dipole force, and continued until the bridge collapsed. The name is used to refer to a coherent mode of oscillation of a spectrum of oscillators in which the amplitude vs frequency graph contains one node, where the node occurs near the driving frequency and a(ω) is not symmetric about zero. When this result is applied to vertical instabilities in coasting beams, it implies the existence of a coherent skew quadrupole moment, whenever a coherent dipole oscillation exists

  7. Vibrio cholerae Classical Biotype Strains Reveal Distinct Signatures in Mexico

    OpenAIRE

    Alam, Munirul; Islam, M. Tarequl; Rashed, Shah Manzur; Johura, Fatema-tuz; Bhuiyan, Nurul A.; Delgado, Gabriela; Morales, Rosario; Mendez, Jose Luis; Navarro, Armando; Watanabe, Haruo; Hasan, Nur-A; Colwell, Rita R.; Cravioto, Alejandro

    2012-01-01

    Vibrio cholerae O1 classical (CL) biotype caused the fifth and sixth pandemics, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the seventh pandemic in Asia in the 1970s by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia and although it had never been reported from Latin America, V. cholerae CL and ET biotypes, including a hybrid ET, were found associated with areas of cholera endemicity in Mexico between 199...

  8. Genomic Perturbations Reveal Distinct Regulatory Networks in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Nepal, Chirag; O'Rourke, Colm J; Oliveira, Douglas Vnp

    2018-01-01

    Intrahepatic cholangiocarcinoma (iCCA) remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequen...

  9. Metabolomics reveals distinct neurochemical profiles associated with stress resilience

    Directory of Open Access Journals (Sweden)

    Brooke N. Dulka

    2017-12-01

    Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings suggest that a metabolomics approach can identify functional groups of neurochemicals that may serve as novel targets for the diagnosis, treatment, or prevention of stress-related mental illness. Keywords: Metabolomics, Biomarkers, Resilience, Stress, Oxidative stress, Social defeat

  10. Failure Modes

    DEFF Research Database (Denmark)

    Jakobsen, K. P.; Burcharth, H. F.; Ibsen, Lars Bo

    1999-01-01

    The present appendix contains the derivation of ten different limit state equations divided on three different failure modes. Five of the limit state equations can be used independently of the characteristics of the subsoil, whereas the remaining five can be used for either drained or undrained s...

  11. Mode Combinations and International Operations

    DEFF Research Database (Denmark)

    Benito, Gabriel R. G.; Petersen, Bent; Welch, Lawrence S.

    2011-01-01

    reveals that companies tend to combine modes of operation; thereby producing unique foreign operation mode “packages” for given activities and/or countries, and that the packages are liable to be modified over time – providing a potentially important optional path for international expansion. Our data...... key markets (China, UK and USA) as the basis for an exploration of the extent to which, and how and why, companies combine clearly different foreign operation modes. We examine their use of foreign operation mode combinations within given value activities as well as within given countries. The study...

  12. Mode Combinations and International Operations

    DEFF Research Database (Denmark)

    Benito, Gabriel R. G.; Petersen, Bent; Welch, Lawrence S.

    2011-01-01

    reveals that companies tend to combine modes of operation; thereby producing unique foreign operation mode “packages” for given activities and/or countries, and that the packages are liable to be modified over time—providing a potentially important optional path for international expansion. The data show...... markets (China, UK and USA) is used as the basis for an exploration of the extent to which, and how and why, companies combine clearly different foreign operation modes. We examine their use of foreign operation mode combinations within given value activities as well as within given countries. The study...

  13. Propagating annular modes

    Science.gov (United States)

    Sheshadri, A.; Plumb, R. A.

    2017-12-01

    The leading "annular mode", defined as the dominant EOF of surface pressure or of zonal mean zonal wind variability, appears as a dipolar structure straddling the mean midlatitude jet and thus seems to describe north-south wobbling of the jet latitude. However, extratropical zonal wind anomalies frequently tend to migrate poleward. This behavior can be described by the first two EOFs, the first (AM1) being the dipolar structure, and the second (AM2) having a tripolar structure centered on the mean jet. Taken in isolation, AM1 thus describes a north-south wobbling of the jet position, while AM2 describes a strengthening and narrowing of the jet. However, despite the fact that they are spatially orthogonal, and their corresponding time series temporally orthogonal, AM1 and AM2 are not independent, but show significant lag-correlations which reveal the propagation. The EOFs are not modes of the underlying dynamical system governing the zonal flow evolution. The true modes can be estimated using principal oscillation pattern (POP) analysis. In the troposphere, the leading POPs manifest themselves as a pair of complex conjugate structures with conjugate eigenvalues thus, in reality, constituting a single, complex, mode that describes propagating anomalies. Even though the principal components associated with the two leading EOFs decay at different rates, each decays faster than the true mode. These facts have implications for eddy feedback and the susceptibility of the mode to external perturbations. If one interprets the annular modes as the modes of the system, then simple theory predicts that the response to steady forcing will usually be dominated by AM1 (with the longest time scale). However, such arguments should really be applied to the true modes. Experiments with a simplified GCM show that climate response to perturbations do not necessarily have AM1 structures. Implications of these results for stratosphere-troposphere interactions are explored. The POP

  14. Touch communicates distinct emotions.

    Science.gov (United States)

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. (c) 2006 APA, all rights reserved

  15. Spin modes

    International Nuclear Information System (INIS)

    Gaarde, C.

    1985-01-01

    An analysis of spectra of (p,n) reactions showed that they were very selective in exciting spin modes. Charge exchange reactions at intermediate energies give important new understanding of the M1-type of excitations and of the spin structure of continuum p spectra in general. In this paper, the author discusses three charge exchange reactions: (p,n); ( 3 H,t); and (d,2p) at several targets. Low-lying states and the Δ region are discussed separately. Finally, the charge exchange reaction with heavy ion beams is briefly discussed. (G.J.P./Auth.)

  16. Microtearing modes

    International Nuclear Information System (INIS)

    Garbet, X.; Mourgues, F.; Samain, A.; Zou, X.

    1990-01-01

    A serious degradation of confinement with additional heating is commonly observed on most tokamaks. The microtearing modes could provide an explanation for this experimental fact. They are driven linearly unstable by diamagnetism in collisional regimes, but it may be shown that the collisions in non linear regimes provide a small diffusion coefficient which can be only significant at the plasme edge. In the bulk of the plasma, the microtearing turbulence could play a basic role if it is unstable in the collisionless regime. While it is linearly stable without collisions, it could be driven unstable in realistic regimes by the radial diffusion it induces. To study this effect, we have used a model where the non linear action of the modes on a given helicity component is represented by a diffusion operator. They are found unstable for reasonable β p =2μ o nT/B 2 p , with a special radial profile of the potential vector A. The problem arises the validity of this model where non linearities in the trajectories behaviour are replaced by the diffusion which broadens resonances. To test this procedure, we calculate the actual electron distribution function when it is determined by the ergodicity of the field lines. We compute the correlations of the distribution function with the magnetic perturbation and compare them with the analytical expressions derived from the resonance broadening model. (author) 3 refs., 2 figs

  17. Dispersion engineering of mode-locked fibre lasers

    Science.gov (United States)

    Woodward, R. I.

    2018-03-01

    Mode-locked fibre lasers are important sources of ultrashort pulses, where stable pulse generation is achieved through a balance of periodic amplitude and phase evolutions. A range of distinct cavity pulse dynamics have been revealed, arising from the interplay between dispersion and nonlinearity in addition to dissipative processes such as filtering. This has led to the discovery of numerous novel operating regimes, offering significantly improved laser performance. In this Topical Review, we summarise the main steady-state pulse dynamics reported to date through cavity dispersion engineering, including average solitons, dispersion-managed solitons, dissipative solitons, giant-chirped pulses and similaritons. Characteristic features and the stabilisation mechanism of each regime are described, supported by numerical modelling, in addition to the typical performance and limitations. Opportunities for further pulse energy scaling are discussed, in addition to considering other recent advances including automated self-tuning cavities and fluoride-fibre-based mid-infrared mode-locked lasers.

  18. Normal modes of Bardeen discs

    International Nuclear Information System (INIS)

    Verdaguer, E.

    1983-01-01

    The short wavelength normal modes of self-gravitating rotating polytropic discs in the Bardeen approximation are studied. The discs' oscillations can be seen in terms of two types of modes: the p-modes whose driving forces are pressure forces and the r-modes driven by Coriolis forces. As a consequence of differential rotation coupling between the two takes place and some mixed modes appear, their properties can be studied under the assumption of weak coupling and it is seen that they avoid the crossing of the p- and r-modes. The short wavelength analysis provides a basis for the classification of the modes, which can be made by using the properties of their phase diagrams. The classification is applied to the large wavelength modes of differentially rotating discs with strong coupling and to a uniformly rotating sequence with no coupling, which have been calculated in previous papers. Many of the physical properties and qualitative features of these modes are revealed by the analysis. (author)

  19. Default Mode of Brain Function in Monkeys

    Science.gov (United States)

    Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

    2013-01-01

    Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

  20. Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line.

    Science.gov (United States)

    Ishihara, Keiko; Ehara, Tsuguhisa

    2004-04-01

    The strong inward rectifier K(+) current, I(K1), shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward I(K1) is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K(+) channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current-voltage (I-V) relationships of Kir2.1, obtained with 5-10 microm spermine or 10-100 microm spermidine, were similar to the steady-state outward I-V relationship of I(K1), showing a peak at a level that is approximately 20 mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1 microm spermine/spermidine or 0.1 microm spermine, respectively. In the chord conductance-voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5-10 microm spermine or 10-100 microm spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1-10 microm

  1. The energy spectrum of electromagnetic normal modes in dissipative media: modes between two metal half spaces

    International Nuclear Information System (INIS)

    Sernelius, Bo E

    2008-01-01

    The energy spectrum of electromagnetic normal modes plays a central role in the theory of the van der Waals and Casimir interaction. Here we study the modes in connection with the van der Waals interaction between two metal half spaces. Neglecting dissipation leads to distinct normal modes with real-valued frequencies. Including dissipation seems to have the effect that these distinct modes move away from the real axis into the complex frequency plane. The summation of the zero-point energies of these modes render a complex-valued result. Using the contour integration, resulting from the use of the generalized argument principle, gives a real-valued and different result. We resolve this contradiction and show that the spectrum of true normal modes forms a continuum with real frequencies

  2. Conformational variability of the stationary phase survival protein E from Xylella fastidiosa revealed by X-ray crystallography, small-angle X-ray scattering studies, and normal mode analysis.

    Science.gov (United States)

    Machado, Agnes Thiane Pereira; Fonseca, Emanuella Maria Barreto; Reis, Marcelo Augusto Dos; Saraiva, Antonio Marcos; Santos, Clelton Aparecido Dos; de Toledo, Marcelo Augusto Szymanski; Polikarpov, Igor; de Souza, Anete Pereira; Aparicio, Ricardo; Iulek, Jorge

    2017-10-01

    Xylella fastidiosa is a xylem-limited bacterium that infects a wide variety of plants. Stationary phase survival protein E is classified as a nucleotidase, which is expressed when bacterial cells are in the stationary growth phase and subjected to environmental stresses. Here, we report four refined X-ray structures of this protein from X. fastidiosa in four different crystal forms in the presence and/or absence of the substrate 3'-AMP. In all chains, the conserved loop verified in family members assumes a closed conformation in either condition. Therefore, the enzymatic mechanism for the target protein might be different of its homologs. Two crystal forms exhibit two monomers whereas the other two show four monomers in the asymmetric unit. While the biological unit has been characterized as a tetramer, differences of their sizes and symmetry are remarkable. Four conformers identified by Small-Angle X-ray Scattering (SAXS) in a ligand-free solution are related to the low frequency normal modes of the crystallographic structures associated with rigid body-like protomer arrangements responsible for the longitudinal and symmetric adjustments between tetramers. When the substrate is present in solution, only two conformers are selected. The most prominent conformer for each case is associated to a normal mode able to elongate the protein by moving apart two dimers. To our knowledge, this work was the first investigation based on the normal modes that analyzed the quaternary structure variability for an enzyme of the SurE family followed by crystallography and SAXS validation. The combined results raise new directions to study allosteric features of XfSurE protein. © 2017 Wiley Periodicals, Inc.

  3. Strategy revealing phenotypic differences among synthetic oscillator designs.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2014-09-19

    Considerable progress has been made in identifying and characterizing the component parts of genetic oscillators, which play central roles in all organisms. Nonlinear interaction among components is sufficiently complex that mathematical models are required to elucidate their elusive integrated behavior. Although natural and synthetic oscillators exhibit common architectures, there are numerous differences that are poorly understood. Utilizing synthetic biology to uncover basic principles of simpler circuits is a way to advance understanding of natural circadian clocks and rhythms. Following this strategy, we address the following questions: What are the implications of different architectures and molecular modes of transcriptional control for the phenotypic repertoire of genetic oscillators? Are there designs that are more realizable or robust? We compare synthetic oscillators involving one of three architectures and various combinations of the two modes of transcriptional control using a methodology that provides three innovations: a rigorous definition of phenotype, a procedure for deconstructing complex systems into qualitatively distinct phenotypes, and a graphical representation for illuminating the relationship between genotype, environment, and the qualitatively distinct phenotypes of a system. These methods provide a global perspective on the behavioral repertoire, facilitate comparisons of alternatives, and assist the rational design of synthetic gene circuitry. In particular, the results of their application here reveal distinctive phenotypes for several designs that have been studied experimentally as well as a best design among the alternatives that has yet to be constructed and tested.

  4. Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively

    OpenAIRE

    Nowak, Jakub Stanislaw; Hobor, Fruzsina; Downie Ruiz Velasco, Angela; Choudhury, Nila Roy; Heikel, Gregory; Kerr, Alastair; Ramos, Andres; Michlewski, Gracjan

    2017-01-01

    Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3’-5’ exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We presen...

  5. Common and distinct brain networks underlying verbal and visual creativity.

    Science.gov (United States)

    Zhu, Wenfeng; Chen, Qunlin; Xia, Lingxiang; Beaty, Roger E; Yang, Wenjing; Tian, Fang; Sun, Jiangzhou; Cao, Guikang; Zhang, Qinglin; Chen, Xu; Qiu, Jiang

    2017-04-01

    Creativity is imperative to the progression of human civilization, prosperity, and well-being. Past creative researches tends to emphasize the default mode network (DMN) or the frontoparietal network (FPN) somewhat exclusively. However, little is known about how these networks interact to contribute to creativity and whether common or distinct brain networks are responsible for visual and verbal creativity. Here, we use functional connectivity analysis of resting-state functional magnetic resonance imaging data to investigate visual and verbal creativity-related regions and networks in 282 healthy subjects. We found that functional connectivity within the bilateral superior parietal cortex of the FPN was negatively associated with visual and verbal creativity. The strength of connectivity between the DMN and FPN was positively related to both creative domains. Visual creativity was negatively correlated with functional connectivity within the precuneus of the pDMN and right middle frontal gyrus of the FPN, and verbal creativity was negatively correlated with functional connectivity within the medial prefrontal cortex of the aDMN. Critically, the FPN mediated the relationship between the aDMN and verbal creativity, and it also mediated the relationship between the pDMN and visual creativity. Taken together, decreased within-network connectivity of the FPN and DMN may allow for flexible between-network coupling in the highly creative brain. These findings provide indirect evidence for the cooperative role of the default and executive control networks in creativity, extending past research by revealing common and distinct brain systems underlying verbal and visual creative cognition. Hum Brain Mapp 38:2094-2111, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  7. Resonance properties of a three-level atom with quantized field modes

    International Nuclear Information System (INIS)

    Yoo, H.I.

    1984-01-01

    A system of one three-level atom and one or two quantized electro-magnetic field modes coupled to each other by the dipole interaction, with the rotating wave approximation is studied. All three atomic configurations, i.e., cascade Lambda- and V-types, are treated simultaneously. The system is treated as closed, i.e., no interaction with the external radiation field modes, to reveal the internal structures and symmetries in the system. The general dynamics of the system are investigated under several distinct initial conditions and their similarities and differences with the dynamics of the Jaynes-Cummings model are revealed. Also investigated is the possibility of so-called coherent trapping of the atom in the quantized field modes in a resonator. An atomic state of coherent trapping exists only for limited cases, and it generally requires the field to be in some special states, depending on the system. The discussion of coherent trapping is extended into a system of M identical three-level atoms. The stability of a coherent-trapping state when fluorescence can take place is discussed. The distinction between a system with resonator field modes and one with ideal laser modes is made clear, and the atomic relaxation to the coherent-trapping atomic state when a Lambda-type atom is irradiated by two ideal laser beams is studied. The experimental prospects to observe the collapse-revival phenomena in the atomic occupation probabilities, which is characteristic of a system with quantized resonator field modes is discussed

  8. The DNA-recognition mode shared by archaeal feast/famine-regulatory proteins revealed by the DNA-binding specificities of TvFL3, FL10, FL11 and Ss-LrpB

    Science.gov (United States)

    Yokoyama, Katsushi; Nogami, Hideki; Kabasawa, Mamiko; Ebihara, Sonomi; Shimowasa, Ai; Hashimoto, Keiko; Kawashima, Tsuyoshi; Ishijima, Sanae A.; Suzuki, Masashi

    2009-01-01

    The DNA-binding mode of archaeal feast/famine-regulatory proteins (FFRPs), i.e. paralogs of the Esherichia coli leucine-responsive regulatory protein (Lrp), was studied. Using the method of systematic evolution of ligands by exponential enrichment (SELEX), optimal DNA duplexes for interacting with TvFL3, FL10, FL11 and Ss-LrpB were identified as TACGA[AAT/ATT]TCGTA, GTTCGA[AAT/ATT]TCGAAC, CCGAAA[AAT/ATT]TTTCGG and TTGCAA[AAT/ATT]TTGCAA, respectively, all fitting into the form abcdeWWWedcba. Here W is A or T, and e.g. a and a are bases complementary to each other. Apparent equilibrium binding constants of the FFRPs and various DNA duplexes were determined, thereby confirming the DNA-binding specificities of the FFRPs. It is likely that these FFRPs recognize DNA in essentially the same way, since their DNA-binding specificities were all explained by the same pattern of relationship between amino-acid positions and base positions to form chemical interactions. As predicted from this relationship, when Gly36 of TvFL3 was replaced by Thr, the b base in the optimal DNA duplex changed from A to T, and, when Thr36 of FL10 was replaced by Ser, the b base changed from T to G/A. DNA-binding characteristics of other archaeal FFRPs, Ptr1, Ptr2, Ss-Lrp and LysM, are also consistent with the relationship. PMID:19468044

  9. Distinction

    OpenAIRE

    2010-01-01

    Pr Serge Haroche La Médaille d’or 2009 du CNRS est décernée au Pr Serge Haroche, titulaire de la chaire de Physique quantique depuis 2001. Serge Haroche est spécialiste de physique atomique et d’optique quantique. Il est l’un des fondateurs de l’électrodynamique quantique en cavité, domaine qui permet, par des expériences conceptuellement simples, d’éclairer les fondements de la théorie quantique et de réaliser des prototypes de systèmes de traitement quantique de l’information. Serge Haroche...

  10. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  11. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  12. Anomalous normal mode oscillations in semiconductor microcavities

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H. [Univ. of Oregon, Eugene, OR (United States). Dept. of Physics; Hou, H.Q.; Hammons, B.E. [Sandia National Labs., Albuquerque, NM (United States)

    1997-04-01

    Semiconductor microcavities as a composite exciton-cavity system can be characterized by two normal modes. Under an impulsive excitation by a short laser pulse, optical polarizations associated with the two normal modes have a {pi} phase difference. The total induced optical polarization is then expected to exhibit a sin{sup 2}({Omega}t)-like oscillation where 2{Omega} is the normal mode splitting, reflecting a coherent energy exchange between the exciton and cavity. In this paper the authors present experimental studies of normal mode oscillations using three-pulse transient four wave mixing (FWM). The result reveals surprisingly that when the cavity is tuned far below the exciton resonance, normal mode oscillation in the polarization is cos{sup 2}({Omega}t)-like, in contrast to what is expected form the simple normal mode model. This anomalous normal mode oscillation reflects the important role of virtual excitation of electronic states in semiconductor microcavities.

  13. Identification of dominant flow structures in rapidly rotating convection of liquid metals using Dynamic Mode Decomposition

    Science.gov (United States)

    Horn, S.; Schmid, P. J.; Aurnou, J. M.

    2016-12-01

    The Earth's metal core acts as a dynamo whose efficiency in generating and maintaining the magnetic field is essentially determined by the rotation rate and the convective motions occurring in its outer liquid part. For the description of the primary physics in the outer core the idealized system of rotating Rayleigh-Bénard convection is often invoked, with the majority of studies considering only working fluids with Prandtl numbers of Pr ≳ 1. However, liquid metals are characterized by distinctly smaller Prandtl numbers which in turn result in an inherently different type of convection. Here, we will present results from direct numerical simulations of rapidly rotating convection in a fluid with Pr ≈ 0.025 in cylindrical containers and Ekman numbers as low as 5 × 10-6. In this system, the Coriolis force is the source of two types of inertial modes, the so-called wall modes, that also exist at moderate Prandtl numbers, and cylinder-filling oscillatory modes, that are a unique feature of small Prandtl number convection. The obtained flow fields were analyzed using the Dynamic Mode Decomposition (DMD). This technique allows to extract and identify the structures that govern the dynamics of the system as well as their corresponding frequencies. We have investigated both the regime where the flow is purely oscillatory and the regime where wall modes and oscillatory modes co-exist. In the purely oscillatory regime, high and low frequency oscillatory modes characterize the flow. When both types of modes are present, the DMD reveals that the wall-attached modes dominate the flow dynamics. They precess with a relatively low frequency in retrograde direction. Nonetheless, also in this case, high frequency oscillations have a significant contribution.

  14. Distinct types of eigenvector localization in networks

    Science.gov (United States)

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q-γ, localization occurs on the largest hub if γ > 5/2 for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  15. Mode Selection in Flame-Vortex driven Combustion Instabilities

    KAUST Repository

    Speth, Ray; Hong, Seung Hyuck; Shanbogue, Santosh; Ghoniem, Ahmed

    2011-01-01

    is governed by a combustion-related time delay inversely proportional to the flame speed. Our model predicts the transition between distinct operating modes. We introduce non-dimensional parameters characterizing the flame speed and stretch rate, and develop a

  16. H-mode physics

    International Nuclear Information System (INIS)

    Itoh, Sanae.

    1991-06-01

    After the discovery of the H-mode in ASDEX ( a tokamak in Germany ) the transition between the L-mode ( Low confinement mode ) and H-mode ( High confinement mode ) has been observed in many tokamaks in the world. The H-mode has made a breakthrough in improving the plasma parameters and has been recognized to be a universal phenomena. Since its discovery, the extensive studies both in experiments and in theory have been made. The research on H-mode has been casting new problems of an anomalous transport across the magnetic surface. This series of lectures will provide a brief review of experiments for explaining H-mode and a model theory of H-mode transition based on the electric field bifurcation. If the time is available, a new theoretical model of the temporal evolution of the H-mode will be given. (author)

  17. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  18. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells.

    Science.gov (United States)

    Maldonado, Paloma P; Angulo, María Cecilia

    2015-06-01

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity is a signaling pathway controlling OPC proliferation/differentiation, influencing the myelination process. However, new evidences describing non-synaptic mechanisms of communication between neurons and OPCs have revealed that neuron-OPC interactions are more complex than expected. The activation of extrasynaptic receptors by ambient neurotransmitter or local spillover and the ability of OPCs to sense neuronal activity through a potassium channel suggest that distinct modes of communication mediate different functions of OPCs in the CNS. This review discusses different mechanisms used by OPCs to interact with neurons and their potential roles during postnatal development and in brain disorders. © The Author(s) 2014.

  19. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  20. H-mode study in CHS

    International Nuclear Information System (INIS)

    Toi, K.; Morisaki, T.; Sakakibara, S.

    1995-02-01

    In CHS rapid H-mode transition is observed in NBI heated deuterium and hydrogen plasmas without obvious isotope effect, when a net plasma current is ramped up to increase the external rotational transform. The H-mode of CHS has many similarities with those in tokamaks. Recent measurement with fast response Langmuir probes has revealed that the rapid change in floating potential occurs at the transition, but the change follows the formation of edge transport barrier. The presence of ι/2π = 1 surface near the edge and sawtooth crash triggered by internal modes may play an important role for determining the H-mode transition in CHS. (author)

  1. Interaction of tearing modes

    International Nuclear Information System (INIS)

    Satya, Y.; Schmidt, G.

    1979-01-01

    A fully developed tearing mode modifies the magnetic field profile. The effect of this profile modification on the linear growth rate of a different tearing mode in a slab and cylindrical geometry is investigated

  2. VH mode accessibility and global H-mode properties in previous and present JET configurations

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T T.C.; Ali-Arshad, S; Bures, M; Christiansen, J P; Esch, H P.L. de; Fishpool, G; Jarvis, O N; Koenig, R; Lawson, K D; Lomas, P J; Marcus, F B; Sartori, R; Schunke, B; Smeulders, P; Stork, D; Taroni, A; Thomas, P R; Thomsen, K [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking

    1994-07-01

    In JET VH modes, there is a distinct confinement transition following the cessation of ELMs, observed in a wide variety of tokamak operating conditions, using both NBI and ICRF heating methods. Important factors which influence VH mode accessibility such as magnetic configuration and vessel conditions have been identified. The new JET pumped divertor configuration has much improved plasma shaping control and power and particle exhaust capability and should permit exploitation of plasmas with VH confinement properties over an even wider range of operating regimes, particularly at high plasma current; first H-modes have been obtained in the 1994 JET operating period and initial results are reported. (authors). 7 refs., 6 figs.

  3. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  4. Fingerprinting of traditional Chinese medicines on the C18-Diol mixed-mode column in online or offline two-dimensional liquid chromatography on the single column modes.

    Science.gov (United States)

    Wang, Qing; Tong, Ling; Yao, Lin; Zhang, Peng; Xu, Li

    2016-06-05

    In the present study, a mixed-mode stationary phase, C18-Diol, was applied for fingerprint analysis of traditional Chinese medicines. Hydrophobic, hydrogen bonding and electrostatic interactions were demonstrated to contribute the retention separately or jointly, which endowed the C18-Diol stationary phase with distinct selectivity compared to the bare C18 one. The separation of total alkaloids extracted from Fritillaria hupehensis was compared on the C18-Diol and conventional C18 column with the greater resolving power and better symmetry responses on the former one. Besides, a novel two-dimensional liquid chromatography on the single column (2D-LC-1C) was realized on C18-Diol with the offline mode for the alcohol extract of Fritillaria hupehensis and online mode for Ligusticum chuanxiong Hort. The early co-eluted extracted components with great polarity on the first dimension were reinjected on the same column and well separated on the second dimension. The results exhibited that the two complementary RPLC and HILIC modes on C18-Diol stationary phase enhanced the separation capacity and revealed more abundant chemical information of the sample, which was a powerful tool in analyzing complex herbal medicines. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The neural signatures of distinct psychopathic traits.

    Science.gov (United States)

    Carré, Justin M; Hyde, Luke W; Neumann, Craig S; Viding, Essi; Hariri, Ahmad R

    2013-01-01

    Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward-related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy.

  6. Streaming tearing mode

    Science.gov (United States)

    Shigeta, M.; Sato, T.; Dasgupta, B.

    1985-01-01

    The magnetohydrodynamic stability of streaming tearing mode is investigated numerically. A bulk plasma flow parallel to the antiparallel magnetic field lines and localized in the neutral sheet excites a streaming tearing mode more strongly than the usual tearing mode, particularly for the wavelength of the order of the neutral sheet width (or smaller), which is stable for the usual tearing mode. Interestingly, examination of the eigenfunctions of the velocity perturbation and the magnetic field perturbation indicates that the streaming tearing mode carries more energy in terms of the kinetic energy rather than the magnetic energy. This suggests that the streaming tearing mode instability can be a more feasible mechanism of plasma acceleration than the usual tearing mode instability.

  7. Generation of compressible modes in MHD turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jungyeon [Chungnam National Univ., Daejeon (Korea); Lazarian, A. [Univ. of Wisconsin, Madison, WI (United States)

    2005-05-01

    Astrophysical turbulence is magnetohydrodynamic (MHD) in nature. We discuss fundamental properties of MHD turbulence and in particular the generation of compressible MHD waves by Alfvenic turbulence and show that this process is inefficient. This allows us to study the evolution of different types of MHD perturbations separately. We describe how to separate MHD fluctuations into three distinct families: Alfven, slow, and fast modes. We find that the degree of suppression of slow and fast modes production by Alfvenic turbulence depends on the strength of the mean field. We review the scaling relations of the modes in strong MHD turbulence. We show that Alfven modes in compressible regime exhibit scalings and anisotropy similar to those in incompressible regime. Slow modes passively mimic Alfven modes. However, fast modes exhibit isotropy and a scaling similar to that of acoustic turbulence both in high and low {beta} plasmas. We show that our findings entail important consequences for star formation theories, cosmic ray propagation, dust dynamics, and gamma ray bursts. We anticipate many more applications of the new insight to MHD turbulence and expect more revisions of the existing paradigms of astrophysical processes as the field matures. (orig.)

  8. Presidential address: distinction or extinction.

    Science.gov (United States)

    Pressman, Barry D

    2008-10-01

    Despite its continuing scientific successes in imaging, radiology as a specialty is faced with a very difficult and competitive environment. Nonradiologists are more and more interested in vertically integrating imaging into their practices, while teleradiology and picture archiving and communication systems are resulting in the greater isolation of radiologists. Commoditization is a realistic and devastating threat to the survival and professionalism of the specialty. To remain viable as a specialty, radiologists must elevate their practice by subspecializing, becoming more involved with clinical care, and actively interacting with patients and referring clinicians. Distinction will prevent extinction.

  9. Single-Mode VCSELs

    Science.gov (United States)

    Larsson, Anders; Gustavsson, Johan S.

    The only active transverse mode in a truly single-mode VCSEL is the fundamental mode with a near Gaussian field distribution. A single-mode VCSEL produces a light beam of higher spectral purity, higher degree of coherence and lower divergence than a multimode VCSEL and the beam can be more precisely shaped and focused to a smaller spot. Such beam properties are required in many applications. In this chapter, after discussing applications of single-mode VCSELs, we introduce the basics of fields and modes in VCSELs and review designs implemented for single-mode emission from VCSELs in different materials and at different wavelengths. This includes VCSELs that are inherently single-mode as well as inherently multimode VCSELs where higher-order modes are suppressed by mode selective gain or loss. In each case we present the current state-of-the-art and discuss pros and cons. At the end, a specific example with experimental results is provided and, as a summary, the most promising designs based on current technologies are identified.

  10. Reynolds stress of localized toroidal modes

    International Nuclear Information System (INIS)

    Zhang, Y.Z.; Mahajan, S.M.

    1995-02-01

    An investigation of the 2D toroidal eigenmode problem reveals the possibility of a new consistent 2D structure, the dissipative BM-II mode. In contrast to the conventional ballooning mode, the new mode is poloidally localized at π/2 (or -π/2), and possesses significant radial asymmetry. The radial asymmetry, in turn, allows the dissipative BM-II to generate considerably larger Reynolds stress as compared to the standard slab drift type modes. It is also shown that a wide class of localized dissipative toroidal modes are likely to be of the dissipative BM-II nature, suggesting that at the tokamak edge, the fluctuation generated Reynolds stress (a possible source of poloidal flow) can be significant

  11. Reynolds stress of localized toroidal modes

    International Nuclear Information System (INIS)

    Zhang, Y.Z.; Mahajan, S.M.

    1995-01-01

    An investigation of the 2D toroidal eigenmode problem reveals the possibility of a new consistent 2D structure, the dissipative BM-II mode. In contrast to the conventional ballooning mode, the new mode is poloidally localized at π/2 (or -π/2), and possesses significant radial asymmetry. The radial asymmetry, in turn, allows the dissipative BM-II to generate considerably larger Reynolds stress as compared to the standard slab drift type modes. It is also shown that a wide class of localized dissipative toroidal modes are likely to be of the dissipative BM-II nature, suggesting that at the tokamak edge, the fluctuation generated Reynolds stress (a possible source of poloidal flow) can be significant. (author). 15 refs

  12. Third abrasive wear mode: is it possible?

    Directory of Open Access Journals (Sweden)

    Ronaldo Câmara Cozza

    2014-04-01

    Full Text Available The objective of this paper is to propose an initial discussion on the characterization of a third abrasive wear mode. The results obtained in a previous work [1] under different test conditions revealed the occurrence of the superposition of the “rolling” and “grooving” abrasive wear modes. This phenomenon was denoted “micro-rolling abrasion” due to the observation that “rolling abrasion” was found to act on “grooving abrasion”.

  13. ELM phenomenon as an interaction between bootstrap-current driven peeling modes and pressure-driven ballooning modes

    International Nuclear Information System (INIS)

    Saarelma, S.; Kurki-Suonio, T.; Guenter, S.; Zehrfeld, H.-P.

    2000-01-01

    An ELMy ASDEX Upgrade plasma equilibrium is reconstructed taking into account the bootstrap current. The peeling mode stability of the equilibrium is numerically analysed using the GATO [1] code, and it is found that the bootstrap current can drive the plasma peeling mode unstable. A high-n ballooning mode stability analysis of the equilibria revealed that, while destabilizing the peeling modes, the bootstrap current has a stabilizing effect on the ballooning modes. A combination of these two instabilities is a possible explanation for the type I ELM phenomenon. A triangularity scan showed that increasing triangularity stabilizes the peeling modes and can produce ELM-free periods observed in the experiments. (author)

  14. Double-mode pulsation

    International Nuclear Information System (INIS)

    Cox, A.N.

    1982-01-01

    Double mode pulsation is a very pervasive phenomenon in stars all over the Hertzsprung-Russell diagram. In order of increasing radius, examples are: ZZ Ceti stars, the sun, the delta Scuti stars, RR Lyrae variables, the β Cephei variables and those related to them, Cepheids, and maybe even the Mira stars. These many modes have been interpreted as both radial and nonradial modes, but in many cases the actual mode has not been clearly identified. Yellow giants seem to be the most simple pulsators with a large majority of the RR Lyrae variables and Cepheids showing only one pulsation period. We limit this review to those very few cases for classical Cepheids and RR Lyrae variables which display two modes. For these we know many facts about these stars, but the actual cause of the pulsation in two modes simultaneously remains unknown

  15. Streaming gravity mode instability

    International Nuclear Information System (INIS)

    Wang Shui.

    1989-05-01

    In this paper, we study the stability of a current sheet with a sheared flow in a gravitational field which is perpendicular to the magnetic field and plasma flow. This mixing mode caused by a combined role of the sheared flow and gravity is named the streaming gravity mode instability. The conditions of this mode instability are discussed for an ideal four-layer model in the incompressible limit. (author). 5 refs

  16. Modes of failures: primary and secondary stresses

    International Nuclear Information System (INIS)

    Roche, R.L.

    1987-07-01

    The paper begins with a reminder that the purpose of stress classification is to ensure suitable margins with respect to failure modes. The distinction between primary stresses and secondary stresses is then examined and a method is given for assessing the degree of elastic follow up in the elastic plastic field. The importance of elastic follow up is then highlighted by an examination of the effect of primary and secondary stresses on crack behavior

  17. Raman intensity and vibrational modes of armchair CNTs

    Science.gov (United States)

    Hur, Jaewoong; Stuart, Steven J.

    2017-07-01

    Raman intensity changes and frequency patterns have been studied using the various armchair (n, n) to understand the variations of bond polarizability, in regard to changing diameters, lengths, and the number of atoms in the (n, n). The Raman intensity trends of the (n, n) are validated by those of Cn isomers. For frequency trends, similar frequency patterns and frequency inward shifts for the (n, n) are characterized. Also, VDOS trends of the (n, n) expressing Raman modes are interpreted. The decomposition of vibrational modes in the (n, n) into radial, longitudinal, and tangential mode is beneficially used to recognize the distinct characteristics of vibrational modes.

  18. Dual-Mode Combustor

    Science.gov (United States)

    Trefny, Charles J (Inventor); Dippold, Vance F (Inventor)

    2013-01-01

    A new dual-mode ramjet combustor used for operation over a wide flight Mach number range is described. Subsonic combustion mode is usable to lower flight Mach numbers than current dual-mode scramjets. High speed mode is characterized by supersonic combustion in a free-jet that traverses the subsonic combustion chamber to a variable nozzle throat. Although a variable combustor exit aperture is required, the need for fuel staging to accommodate the combustion process is eliminated. Local heating from shock-boundary-layer interactions on combustor walls is also eliminated.

  19. Antipastorialism : Resistant Georgic Mode

    National Research Council Canada - National Science Library

    Zimmerman, Donald

    2000-01-01

    .... Abolitionists, women, Afro-British slaves, and those who protested land enclosure developed a multivalent, resistant mode of writing, which I name 'antipastoralism', that countered orthodox, poetical...

  20. Nonlinear drift tearing mode

    International Nuclear Information System (INIS)

    Zelenyj, L.M.; Kuznetsova, M.M.

    1989-01-01

    Nonlinear study of magnetic perturbation development under single-mode conditions in collision-free plasma in configurations with the magnetic field shear is investigated. Results are obtained with regard of transverse component of electrical field and its effect on ion dynamics within wide range of ion Larmor radius value and values of magnetic field shear. Increments of nonlinear drift tearing mode are obtained and it is shown that excitation drastic conditions of even linearly stable modes are possible. Mechanism of instability nonlinear stabilization is considered and the value of magnetic island at the saturation threshold is estimeted. Energy of nonlinear drift tearing mode is discussed

  1. Representing Operational Modes for Situation Awareness

    Science.gov (United States)

    Kirchhübel, Denis; Lind, Morten; Ravn, Ole

    2017-01-01

    Operating complex plants is an increasingly demanding task for human operators. Diagnosis of and reaction to on-line events requires the interpretation of real time data. Vast amounts of sensor data as well as operational knowledge about the state and design of the plant are necessary to deduct reasonable reactions to abnormal situations. Intelligent computational support tools can make the operator’s task easier, but they require knowledge about the overall system in form of some model. While tools used for fault-tolerant control design based on physical principles and relations are valuable tools for designing robust systems, the models become too complex when considering the interactions on a plant-wide level. The alarm systems meant to support human operators in the diagnosis of the plant-wide situation on the other hand fail regularly in situations where these interactions of systems lead to many related alarms overloading the operator with alarm floods. Functional modelling can provide a middle way to reduce the complexity of plant-wide models by abstracting from physical details to more general functions and behaviours. Based on functional models the propagation of failures through the interconnected systems can be inferred and alarm floods can potentially be reduced to their root-cause. However, the desired behaviour of a complex system changes due to operating procedures that require more than one physical and functional configuration. In this paper a consistent representation of possible configurations is deduced from the analysis of an exemplary start-up procedure by functional models. The proposed interpretation of the modelling concepts simplifies the functional modelling of distinct modes. The analysis further reveals relevant links between the quantitative sensor data and the qualitative perspective of the diagnostics tool based on functional models. This will form the basis for the ongoing development of a novel real-time diagnostics system based

  2. Representing Operational Modes for Situation Awareness

    International Nuclear Information System (INIS)

    Kirchhübel, Denis; Lind, Morten; Ravn, Ole

    2017-01-01

    Operating complex plants is an increasingly demanding task for human operators. Diagnosis of and reaction to on-line events requires the interpretation of real time data. Vast amounts of sensor data as well as operational knowledge about the state and design of the plant are necessary to deduct reasonable reactions to abnormal situations. Intelligent computational support tools can make the operator’s task easier, but they require knowledge about the overall system in form of some model. While tools used for fault-tolerant control design based on physical principles and relations are valuable tools for designing robust systems, the models become too complex when considering the interactions on a plant-wide level. The alarm systems meant to support human operators in the diagnosis of the plant-wide situation on the other hand fail regularly in situations where these interactions of systems lead to many related alarms overloading the operator with alarm floods. Functional modelling can provide a middle way to reduce the complexity of plant-wide models by abstracting from physical details to more general functions and behaviours. Based on functional models the propagation of failures through the interconnected systems can be inferred and alarm floods can potentially be reduced to their root-cause. However, the desired behaviour of a complex system changes due to operating procedures that require more than one physical and functional configuration. In this paper a consistent representation of possible configurations is deduced from the analysis of an exemplary start-up procedure by functional models. The proposed interpretation of the modelling concepts simplifies the functional modelling of distinct modes. The analysis further reveals relevant links between the quantitative sensor data and the qualitative perspective of the diagnostics tool based on functional models. This will form the basis for the ongoing development of a novel real-time diagnostics system based

  3. Coupled seismoacoustic modes on the seafloor

    Science.gov (United States)

    Butler, Rhett; Lomnitz, Cinna

    2002-05-01

    Wave-to-wave coupling arises when an acoustic pulse selects a Rayleigh mode of the same speed and both travel together swapping energy across an interface [Ewing et al., 1957]. A distinctive signal is observed at the Hawaii-2 Observatory for purely oceanic paths from earthquakes on the Blanco and Mendocino Fracture Zones, off the coast of North America. The signal appears to be a composite of undispersed higher Rayleigh modes propagating along the ocean floor both in the sediments and in the water. The new coupled modes are identified by their frequency composition and their phase and group velocities. Seismoacoustic coupling at the seafloor is conditioned on (a) the presence of a low-velocity interface at the ocean floor, and (b) the wavelength of the Rayleigh component being shorter than the depth of the water layer.

  4. Minireview: Mode of action of meta-diamide insecticides.

    Science.gov (United States)

    Nakao, Toshifumi; Banba, Shinichi

    2015-06-01

    Meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor noncompetitive antagonists showing high insecticidal activity against Spodoptera litura. The mode of action of the meta-diamides was demonstrated to be distinct from that of conventional noncompetitive antagonists (NCAs) such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. It was suggested that meta-diamides act at or near G336 in the M3 region of the Drosophila RDL GABA receptor. Although the site of action of the meta-diamides appears to overlap with that of macrocyclic lactones including avermectins and milbemycins, differential effects of mutations on the actions of the meta-diamides and the macrocyclic lactones were observed. Molecular modeling studies revealed that the meta-diamides may bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor better when in the closed state, which is distinct from the NCA-binding site, which is in a channel formed by M2s. In contrast, the macrocyclic lactones were suggested to bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor when in the open state. Furthermore, mechanisms underlying the high selectivity of meta-diamides are discussed. This minireview highlights the unique features of novel meta-diamide insecticides and demonstrates why meta-diamides are anticipated to become prominent insecticides that are effective against pests resistant to cyclodienes and fipronil. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Confluence for classical logic through the distinction between values and computations

    Directory of Open Access Journals (Sweden)

    José Espírito Santo

    2014-09-01

    Full Text Available We apply an idea originated in the theory of programming languages - monadic meta-language with a distinction between values and computations - in the design of a calculus of cut-elimination for classical logic. The cut-elimination calculus we obtain comprehends the call-by-name and call-by-value fragments of Curien-Herbelin's lambda-bar-mu-mu-tilde-calculus without losing confluence, and is based on a distinction of "modes" in the proof expressions and "mode" annotations in types. Modes resemble colors and polarities, but are quite different: we give meaning to them in terms of a monadic meta-language where the distinction between values and computations is fully explored. This meta-language is a refinement of the classical monadic language previously introduced by the authors, and is also developed in the paper.

  6. Microwave plasma mode conversion

    International Nuclear Information System (INIS)

    Torres, H.S.; Sakanaka, P.H.; Villarroel, C.H.

    1985-01-01

    The behavior of hot electrons during the process of laser-produced plasma is studied. The basic equations of mode conversion from electromagnetic waves to electrostatic waves are presented. It is shown by mode conversion, that, the resonant absorption and parametric instabilities appear simultaneously, but in different plasma regions. (M.C.K.) [pt

  7. Excursions through KK modes

    Energy Technology Data Exchange (ETDEWEB)

    Furuuchi, Kazuyuki [Manipal Centre for Natural Sciences, Manipal University,Manipal, Karnataka 576104 (India)

    2016-07-07

    In this article we study Kaluza-Klein (KK) dimensional reduction of massive Abelian gauge theories with charged matter fields on a circle. Since local gauge transformations change position dependence of the charged fields, the decomposition of the charged matter fields into KK modes is gauge dependent. While whole KK mass spectrum is independent of the gauge choice, the mode number depends on the gauge. The masses of the KK modes also depend on the field value of the zero-mode of the extra dimensional component of the gauge field. In particular, one of the KK modes in the KK tower of each massless 5D charged field becomes massless at particular values of the extra-dimensional component of the gauge field. When the extra-dimensional component of the gauge field is identified with the inflaton, this structure leads to recursive cosmological particle productions.

  8. Excursions through KK modes

    International Nuclear Information System (INIS)

    Furuuchi, Kazuyuki

    2016-01-01

    In this article we study Kaluza-Klein (KK) dimensional reduction of massive Abelian gauge theories with charged matter fields on a circle. Since local gauge transformations change position dependence of the charged fields, the decomposition of the charged matter fields into KK modes is gauge dependent. While whole KK mass spectrum is independent of the gauge choice, the mode number depends on the gauge. The masses of the KK modes also depend on the field value of the zero-mode of the extra dimensional component of the gauge field. In particular, one of the KK modes in the KK tower of each massless 5D charged field becomes massless at particular values of the extra-dimensional component of the gauge field. When the extra-dimensional component of the gauge field is identified with the inflaton, this structure leads to recursive cosmological particle productions.

  9. Supramolecular Isomers of Metal-Organic Frameworks Derived from a Partially Flexible Ligand with Distinct Binding Motifs

    KAUST Repository

    Abdul Halim, Racha Ghassan

    2016-01-04

    Three novel metal-organic frameworks (MOFs) were isolated upon reacting a heterofunctional ligand 4 (pyrimidin-5 yl)benzoic acid (4,5-pmbc) with mixed valence Cu(I,II) under solvothermal conditions. X-ray crystal structural analysis reveals that the first compound is a layered structure composed of one type of inorganic building block, dinuclear paddlewheel [Cu2(O2C–)4], which are linked through 4,5-pmbc ligands. The two other supramolecular isomers are composed of the same Cu(II) dinuclear paddlewheel and a dinuclear Cu2I2 cluster, which are linked via the 4,5-pmbc linkers to yield two different 3-periodic frameworks with underlying topologies related to lvt and nbo. The observed structural diversity in these structures is due to the distinct coordination modes of the two coordinating moieties (the carboxylate group on the phenyl ring and the N-donor atoms from the pyrimidine moiety).

  10. Supramolecular Isomers of Metal-Organic Frameworks Derived from a Partially Flexible Ligand with Distinct Binding Motifs

    KAUST Repository

    AbdulHalim, Rasha; Shkurenko, Aleksander; Al Kordi, Mohamed; Eddaoudi, Mohamed

    2016-01-01

    Three novel metal-organic frameworks (MOFs) were isolated upon reacting a heterofunctional ligand 4 (pyrimidin-5 yl)benzoic acid (4,5-pmbc) with mixed valence Cu(I,II) under solvothermal conditions. X-ray crystal structural analysis reveals that the first compound is a layered structure composed of one type of inorganic building block, dinuclear paddlewheel [Cu2(O2C–)4], which are linked through 4,5-pmbc ligands. The two other supramolecular isomers are composed of the same Cu(II) dinuclear paddlewheel and a dinuclear Cu2I2 cluster, which are linked via the 4,5-pmbc linkers to yield two different 3-periodic frameworks with underlying topologies related to lvt and nbo. The observed structural diversity in these structures is due to the distinct coordination modes of the two coordinating moieties (the carboxylate group on the phenyl ring and the N-donor atoms from the pyrimidine moiety).

  11. Effect of modes interaction on the resistive wall mode stability

    International Nuclear Information System (INIS)

    Chen Longxi; Wu Bin

    2013-01-01

    Effects of modes interaction on the resistive wall mode (RWM) stability are studied. When considering the modes interaction effects, the linear growth rate of the most unstable (3, 1) mode decreases. After linear evolution, the RWM saturates at the nonlinear phase. The saturation can be attributed to flux piling up on the resistive wall. When some modes exist, the (3, 1) mode saturates at lower level compared with single mode evolution. Meanwhile, the magnetic energy of the (5, 2) mode increases correspondingly, but the magnetic energy saturation level of the (2, 1) mode changes weakly. (authors)

  12. Hydromagnetic quasi-geostrophic modes in rapidly rotating planetary cores

    DEFF Research Database (Denmark)

    Canet, E.; Finlay, Chris; Fournier, A.

    2014-01-01

    The core of a terrestrial-type planet consists of a spherical shell of rapidly rotating, electrically conducting, fluid. Such a body supports two distinct classes of quasi-geostrophic (QG) eigenmodes: fast, primarily hydrodynamic, inertial modes with period related to the rotation time scale...... decreases toward the outer boundary in a spherical shell, QG modes tend to be compressed towards the outer boundary. Including magnetic dissipation, we find a continuous transition from diffusionless slow magnetic modes into quasi-free decay magnetic modes. During that transition (which is controlled......, or shorter than, their oscillation time scale.Based on our analysis, we expect Mercury to be in a regime where the slow magnetic modes are of quasi-free decay type. Earth and possibly Ganymede, with their larger Elsasser numbers, may possess slow modes that are in the transition regime of weak diffusion...

  13. Surface modes in physics

    CERN Document Server

    Sernelius, Bo E

    2011-01-01

    Electromagnetic surface modes are present at all surfaces and interfaces between material of different dielectric properties. These modes have very important effects on numerous physical quantities: adhesion, capillary force, step formation and crystal growth, the Casimir effect etc. They cause surface tension and wetting and they give rise to forces which are important e.g. for the stability of colloids.This book is a useful and elegant approach to the topic, showing how the concept of electromagnetic modes can be developed as a unifying theme for a range of condensed matter physics. The

  14. Study of complex modes

    International Nuclear Information System (INIS)

    Pastrnak, J.W.

    1986-01-01

    This eighteen-month study has been successful in providing the designer and analyst with qualitative guidelines on the occurrence of complex modes in the dynamics of linear structures, and also in developing computer codes for determining quantitatively which vibration modes are complex and to what degree. The presence of complex modes in a test structure has been verified. Finite element analysis of a structure with non-proportional dumping has been performed. A partial differential equation has been formed to eliminate possible modeling errors

  15. Switch mode power supply

    International Nuclear Information System (INIS)

    Kim, Hui Jun

    1993-06-01

    This book concentrates on switch mode power supply. It has four parts, which are introduction of switch mode power supply with DC-DC converter such as Buck converter boost converter, Buck-boost converter and PWM control circuit, explanation for SMPS with DC-DC converter modeling and power mode control, resonance converter like resonance switch, converter, multi resonance converter and series resonance and parallel resonance converters, basic test of SMPS with PWM control circuit, Buck converter, Boost converter, flyback converter, forward converter and IC for control circuit.

  16. Higher Order Mode Fibers

    DEFF Research Database (Denmark)

    Israelsen, Stine Møller

    This PhD thesis considers higher order modes (HOMs) in optical fibers. That includes their excitation and characteristics. Within the last decades, HOMs have been applied both for space multiplexing in optical communications, group velocity dispersion management and sensing among others......-radial polarization as opposed to the linear polarization of the LP0X modes. The effect is investigated numerically in a double cladding fiber with an outer aircladding using a full vectorial modesolver. Experimentally, the bowtie modes are excited using a long period grating and their free space characteristics...... and polarization state are investigated. For this fiber, the onset of the bowtie effect is shown numerically to be LP011. The characteristics usually associated with Bessel-likes modes such as long diffraction free length and selfhealing are shown to be conserved despite the lack of azimuthal symmetry...

  17. Are empathy and concern psychologically distinct?

    Science.gov (United States)

    Jordan, Matthew R; Amir, Dorsa; Bloom, Paul

    2016-12-01

    Researchers have long been interested in the relationship between feeling what you believe others feel-often described as empathy-and caring about the welfare of others-often described as compassion or concern. Many propose that empathy is a prerequisite for concern and is therefore the ultimate motivator of prosocial actions. To assess this hypothesis, the authors developed the Empathy Index, which consists of 2 novel scales, and explored their relationship to a measure of concern as well as to measures of cooperative and altruistic behavior. A series of factor analyses reveal that empathy and concern consistently load on different factors. Furthermore, they show that empathy and concern motivate different behaviors: concern for others is a uniquely positive predictor of prosocial action whereas empathy is either not predictive or negatively predictive of prosocial actions. Together these studies suggest that empathy and concern are psychologically distinct and empathy plays a more limited role in our moral lives than many believe. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. Electrochemical AC impedance model of a solid oxide fuel cell and its application to diagnosis of multiple degradation modes

    Energy Technology Data Exchange (ETDEWEB)

    Gazzarri, J.I.; Kesler, O. [Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC V6T 1Z4 (Canada)

    2007-05-01

    A finite element model of the impact of diverse degradation mechanisms on the impedance spectrum of a solid oxide fuel cell is presented as a tool for degradation mode identification. Among the degradation mechanisms that cause electrode active area loss, the attention is focused on electrode delamination and uniformly distributed surface area loss, which were found to cause distinct and specific changes in the impedance spectrum. Degradation mechanisms resulting in uniformly distributed reactive surface area loss include sintering, sulphur poisoning, and possibly incipient coke formation at the anode, and chromium deposition at the cathode. Parametric studies reveal the extent and limits of applicability of the model and detectability of the different degradation modes, as well as the influence of different cell geometries on the change in impedance behaviour resulting from the loss of active area. It is expected that this technique could form the basis of a useful diagnostic tool for both solid oxide fuel cell developers and users. (author)

  19. Nonlinear optics in the LP(02) higher-order mode of a fiber.

    Science.gov (United States)

    Chen, Y; Chen, Z; Wadsworth, W J; Birks, T A

    2013-07-29

    The distinct disperion properties of higher-order modes in optical fibers permit the nonlinear generation of radiation deeper into the ultraviolet than is possible with the fundamental mode. This is exploited using adiabatic, broadband mode convertors to couple light efficiently from an input fundamental mode and also to return the generated light to an output fundamental mode over a broad spectral range. For example, we generate visible and UV supercontinuum light in the LP(02) mode of a photonic crystal fiber from sub-ns pulses with a wavelength of 532 nm.

  20. Two distinct origins for Archean greenstone belts

    Science.gov (United States)

    Smithies, R. Hugh; Ivanic, Tim J.; Lowrey, Jack R.; Morris, Paul A.; Barnes, Stephen J.; Wyche, Stephen; Lu, Yong-Jun

    2018-04-01

    Applying the Th/Yb-Nb/Yb plot of Pearce (2008) to the well-studied Archean greenstone sequences of Western Australia shows that individual volcanic sequences evolved through one of two distinct processes reflecting different modes of crust-mantle interaction. In the Yilgarn Craton, the volcanic stratigraphy of the 2.99-2.71 Ga Youanmi Terrane mainly evolved through processes leading to Th/Yb-Nb/Yb trends with a narrow range of Th/Nb ('constant-Th/Nb' greenstones). In contrast, the 2.71-2.66 Ga volcanic stratigraphy of the Eastern Goldfields Superterrane evolved through processes leading to Th/Yb-Nb/Yb trends showing a continuous range in Th/Nb ('variable-Th/Nb' greenstones). Greenstone sequences of the Pilbara Craton show a similar evolution, with constant-Th/Nb greenstone evolution between 3.13 and 2.95 Ga and variable-Th/Nb greenstone evolution between 3.49 and 3.23 Ga and between 2.77 and 2.68 Ga. The variable-Th/Nb trends dominate greenstone sequences in Australia and worldwide, and are temporally associated with peaks in granite magmatism, which promoted crustal preservation. The increasing Th/Nb in basalts correlates with decreasing εNd, reflecting variable amounts of crustal assimilation during emplacement of mantle-derived magmas. These greenstones are typically accompanied in the early stages by komatiite, and can probably be linked to mantle plume activity. Thus, regions such as the Eastern Goldfields Superterrane simply developed as plume-related rifts over existing granite-greenstone crust - in this case the Youanmi Terrane. Their Th/Nb trends are difficult to reconcile with modern-style subduction processes. The constant-Th/Nb trends may reflect derivation from a mantle source already with a high and constant Th/Nb ratio. This, and a lithological association including boninite-like lavas, basalts, and calc-alkaline andesites, all within a narrow Th/Nb range, resembles compositions typical of modern-style subduction settings. These greenstones are very

  1. From current-driven to neoclassically driven tearing modes.

    Science.gov (United States)

    Reimerdes, H; Sauter, O; Goodman, T; Pochelon, A

    2002-03-11

    In the TCV tokamak, the m/n = 2/1 island is observed in low-density discharges with central electron-cyclotron current drive. The evolution of its width has two distinct growth phases, one of which can be linked to a "conventional" tearing mode driven unstable by the current profile and the other to a neoclassical tearing mode driven by a perturbation of the bootstrap current. The TCV results provide the first clear observation of such a destabilization mechanism and reconcile the theory of conventional and neoclassical tearing modes, which differ only in the dominant driving term.

  2. Threshold condition for nonlinear tearing modes in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Zabiego, M.F. [Association Euratom-CEA, Centre d`Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee; Callen, J.D. [Wisconsin Univ., Madison, WI (United States). Dept. of Nuclear Engineering and Engineering Physics

    1996-04-01

    Low-mode-number tearing mode nonlinear evolution is analyzed emphasizing the need for a threshold condition, to account for observations in tokamaks. The discussion is illustrated by two models recently introduced in the literature. Introducing a threshold condition in the tearing mode stability analysis is found to reveal some bifurcation points and thus domains of intrinsic stability in the island dynamics operational space. (author). 19 refs.

  3. Threshold condition for nonlinear tearing modes in tokamaks

    International Nuclear Information System (INIS)

    Zabiego, M.F.; Callen, J.D.

    1996-04-01

    Low-mode-number tearing mode nonlinear evolution is analyzed emphasizing the need for a threshold condition, to account for observations in tokamaks. The discussion is illustrated by two models recently introduced in the literature. Introducing a threshold condition in the tearing mode stability analysis is found to reveal some bifurcation points and thus domains of intrinsic stability in the island dynamics operational space. (author)

  4. A normal mode treatment of semi-diurnal body tides on an aspherical, rotating and anelastic Earth

    Science.gov (United States)

    Lau, Harriet C. P.; Yang, Hsin-Ying; Tromp, Jeroen; Mitrovica, Jerry X.; Latychev, Konstantin; Al-Attar, David

    2015-08-01

    Normal mode treatments of the Earth's body tide response were developed in the 1980s to account for the effects of Earth rotation, ellipticity, anelasticity and resonant excitation within the diurnal band. Recent space-geodetic measurements of the Earth's crustal displacement in response to luni-solar tidal forcings have revealed geographical variations that are indicative of aspherical deep mantle structure, thus providing a novel data set for constraining deep mantle elastic and density structure. In light of this, we make use of advances in seismic free oscillation literature to develop a new, generalized normal mode theory for the tidal response within the semi-diurnal and long-period tidal band. Our theory involves a perturbation method that permits an efficient calculation of the impact of aspherical structure on the tidal response. In addition, we introduce a normal mode treatment of anelasticity that is distinct from both earlier work in body tides and the approach adopted in free oscillation seismology. We present several simple numerical applications of the new theory. First, we compute the tidal response of a spherically symmetric, non-rotating, elastic and isotropic Earth model and demonstrate that our predictions match those based on standard Love number theory. Second, we compute perturbations to this response associated with mantle anelasticity and demonstrate that the usual set of seismic modes adopted for this purpose must be augmented by a family of relaxation modes to accurately capture the full effect of anelasticity on the body tide response. Finally, we explore aspherical effects including rotation and we benchmark results from several illustrative case studies of aspherical Earth structure against independent finite-volume numerical calculations of the semi-diurnal body tide response. These tests confirm the accuracy of the normal mode methodology to at least the level of numerical error in the finite-volume predictions. They also demonstrate

  5. Collective Lyapunov modes

    International Nuclear Information System (INIS)

    Takeuchi, Kazumasa A; Chaté, Hugues

    2013-01-01

    We show, using covariant Lyapunov vectors in addition to standard Lyapunov analysis, that there exists a set of collective Lyapunov modes in large chaotic systems exhibiting collective dynamics. Associated with delocalized Lyapunov vectors, they act collectively on the trajectory and hence characterize the instability of its collective dynamics. We further develop, for globally coupled systems, a connection between these collective modes and the Lyapunov modes in the corresponding Perron–Frobenius equation. We thereby address the fundamental question of the effective dimension of collective dynamics and discuss the extensivity of chaos in the presence of collective dynamics. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Lyapunov analysis: from dynamical systems theory to applications’. (paper)

  6. Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

    Science.gov (United States)

    Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

    2016-07-15

    The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation.

  7. Distinct modes of transmission of tuberculosis in aboriginal and non-aboriginal populations in Taiwan.

    Directory of Open Access Journals (Sweden)

    Yih-Yuan Chen

    Full Text Available Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ≤20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR = 5.98, p<0.0001. MTB lineages with high clustering were EAI (54.9% among southern people, and Beijing (62.5% and Haarlem (52.9% among eastern aborigines. Resistance to first-line drugs and multidrug resistance (MDR were significantly higher among eastern aborigines (≥15% than in any other geographic and ethnic group (p<0.05; MDR was detected in 5 of 28 eastern aboriginal patients ≤20 years old. Among patients from the eastern region, clustered strains (p = 0.01 and aboriginal ethnicity (p = 0.04 were independent risk factors for MDR. The lifestyles of aborigines in eastern Taiwan may explain why the percentage of infected aborigines is much higher than for their Han Chinese counterparts. The significantly higher percentage of the MDR-MTB strains in the aboriginal population warrants close attention to control policy and vaccination strategy.

  8. Modes of correlated angular motion in live cells across three distinct time scales

    International Nuclear Information System (INIS)

    Harrison, Andrew W; Kenwright, David A; Woodman, Philip G; Allan, Victoria J; Waigh, Thomas A

    2013-01-01

    Particle tracking experiments with high speed digital microscopy yield the positions and trajectories of lipid droplets inside living cells. Angular correlation analysis shows that the lipid droplets have uncorrelated motion at short time scales (τ 10 ms, becomes persistent, indicating directed movement. The motion at all time scales is associated with the lipid droplets being tethered to and driven along the microtubule network. The point at which the angular correlation changes from anti-persistent to persistent motion corresponds to the cross over between sub-diffusive and super diffusive motion, as observed by mean square displacement analysis. Correct analysis of the angular correlations of the detector noise is found to be crucial in modelling the observed phenomena. (paper)

  9. Salmonella Enterica Serovar Typhimurium BipA Exhibits Two Distinct Ribosome Binding Modes

    Energy Technology Data Exchange (ETDEWEB)

    deLivron, M.; Robinson, V

    2008-01-01

    BipA is a highly conserved prokaryotic GTPase that functions to influence numerous cellular processes in bacteria. In Escherichia coli and Salmonella enterica serovar Typhimurium, BipA has been implicated in controlling bacterial motility, modulating attachment and effacement processes, and upregulating the expression of virulence genes and is also responsible for avoidance of host defense mechanisms. In addition, BipA is thought to be involved in bacterial stress responses, such as those associated with virulence, temperature, and symbiosis. Thus, BipA is necessary for securing bacterial survival and successful invasion of the host. Steady-state kinetic analysis and pelleting assays were used to assess the GTPase and ribosome-binding properties of S. enterica BipA. Under normal bacterial growth, BipA associates with the ribosome in the GTP-bound state. However, using sucrose density gradients, we demonstrate that the association of BipA and the ribosome is altered under stress conditions in bacteria similar to those experienced during virulence. The data show that this differential binding is brought about by the presence of ppGpp, an alarmone that signals the onset of stress-related events in bacteria.

  10. Two distinct modes for propagation of histone PTMs across the cell cycle

    DEFF Research Database (Denmark)

    Alabert, Constance; Barth, Teresa K; Reverón-Gómez, Nazaret

    2015-01-01

    Epigenetic states defined by chromatin can be maintained through mitotic cell division. However, it remains unknown how histone-based information is transmitted. Here we combine nascent chromatin capture (NCC) and triple-SILAC (stable isotope labeling with amino acids in cell culture) labeling...... to track histone modifications and histone variants during DNA replication and across the cell cycle. We show that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and trimethylation marks are diluted twofold upon DNA replication, as a consequence...... of new histone deposition. Importantly, within one cell cycle, all PTMs are restored. In general, new histones are modified to mirror the parental histones. However, H3K9 trimethylation (H3K9me3) and H3K27me3 are propagated by continuous modification of parental and new histones because the establishment...

  11. Sliding mode control and observation

    CERN Document Server

    Shtessel, Yuri; Fridman, Leonid; Levant, Arie

    2014-01-01

    The sliding mode control methodology has proven effective in dealing with complex dynamical systems affected by disturbances, uncertainties and unmodeled dynamics. Robust control technology based on this methodology has been applied to many real-world problems, especially in the areas of aerospace control, electric power systems, electromechanical systems, and robotics. Sliding Mode Control and Observation represents the first textbook that starts with classical sliding mode control techniques and progresses toward newly developed higher-order sliding mode control and observation algorithms and their applications. The present volume addresses a range of sliding mode control issues, including: *Conventional sliding mode controller and observer design *Second-order sliding mode controllers and differentiators *Frequency domain analysis of conventional and second-order sliding mode controllers *Higher-order sliding mode controllers and differentiators *Higher-order sliding mode observers *Sliding mode disturbanc...

  12. Mode selection laser

    DEFF Research Database (Denmark)

    2014-01-01

    spatial reflector variations, may be combined to generate a laser beam containing a plurality of orthogonal modes. The laser beam may be injected into a few- mode optical fiber, e.g. for the purpose of optical communication. The VCSEL may have intra-cavity contacts (31,37) and a Tunnel junction (33......) for current confinement into the active layer (34). An air-gap layer (102) may be provided between the upper reflector (15) and the SOI wafer (50) acting as a substrate. The lower reflector may be designed as a high-contrast grating (51) by etching....

  13. Distinct genetic alterations in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Hassan Ashktorab

    Full Text Available BACKGROUND: Colon cancer (CRC development often includes chromosomal instability (CIN leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes. There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.

  14. Two distinct neural mechanisms underlying indirect reciprocity.

    Science.gov (United States)

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  15. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  16. Simultaneous Observations of p-mode Light Walls and Magnetic Reconnection Ejections above Sunspot Light Bridges

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Yijun; Zhang, Jun; Li, Ting; Yang, Shuhong; Li, Xiaohong, E-mail: yijunhou@nao.cas.cn, E-mail: zjun@nao.cas.cn [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

    2017-10-10

    Recent high-resolution observations from the Interface Region Imaging Spectrograph reveal bright wall-shaped structures in active regions (ARs), especially above sunspot light bridges. Their most prominent feature is the bright oscillating front in the 1400/1330 Å channel. These structures are named light walls and are often interpreted to be driven by p-mode waves. Above the light bridge of AR 12222 on 2014 December 06, we observed intermittent ejections superimposed on an oscillating light wall in the 1400 Å passband. At the base location of each ejection, the emission enhancement was detected in the Solar Dynamics Observatory 1600 Å channel. Thus, we suggest that in wall bases (light bridges), in addition to the leaked p-mode waves consistently driving the oscillating light wall, magnetic reconnection could happen intermittently at some locations and eject the heated plasma upward. Similarly, in the second event occurring in AR 12371 on 2015 June 16, a jet was simultaneously detected in addition to the light wall with a wave-shaped bright front above the light bridge. At the footpoint of this jet, lasting brightening was observed, implying magnetic reconnection at the base. We propose that in these events, two mechanisms, p-mode waves and magnetic reconnection, simultaneously play roles in the light bridge, and lead to the distinct kinetic features of the light walls and the ejection-like activities, respectively. To illustrate the two mechanisms and their resulting activities above light bridges, in this study we present a cartoon model.

  17. Modes and orders of market entry

    DEFF Research Database (Denmark)

    Ulhøi, John Parm

    2012-01-01

    (first-mover or follower). Invention is understood as the conversion of human creativity, time and financial resources into new ideas. Innovation in turn reflects the practical and financial return on such investments. While there is little disagreement about what an innovator strategy is, imitative......This paper focuses on the initial questions of how and when to enter a market from the perspective of a firm. By entry mode is meant a firm’s strategy (innovation or imitation) for entering the market in response to environmental changes. Entry order refers to the related issue of market timing...... strategies are more ambiguous. Based on a corporate technology and innovation strategy perspective, the paper reconceptualises and extends existing modes and orders of market entry, and in particular clarifies the ambiguity associated with imitative strategies. Four distinct imitator strategies...

  18. Magnon dark modes and gradient memory.

    Science.gov (United States)

    Zhang, Xufeng; Zou, Chang-Ling; Zhu, Na; Marquardt, Florian; Jiang, Liang; Tang, Hong X

    2015-11-16

    Extensive efforts have been expended in developing hybrid quantum systems to overcome the short coherence time of superconducting circuits by introducing the naturally long-lived spin degree of freedom. Among all the possible materials, single-crystal yttrium iron garnet has shown up recently as a promising candidate for hybrid systems, and various highly coherent interactions, including strong and even ultrastrong coupling, have been demonstrated. One distinct advantage in these systems is that spins form well-defined magnon modes, which allows flexible and precise tuning. Here we demonstrate that by dissipation engineering, a non-Markovian interaction dynamics between the magnon and the microwave cavity photon can be achieved. Such a process enables us to build a magnon gradient memory to store information in the magnon dark modes, which decouple from the microwave cavity and thus preserve a long lifetime. Our findings provide a promising approach for developing long-lifetime, multimode quantum memories.

  19. Ire1 Has Distinct Catalytic Mechanisms for XBP1/HAC1 Splicing and RIDD

    Directory of Open Access Journals (Sweden)

    Arvin B. Tam

    2014-11-01

    Full Text Available An evolutionarily conserved unfolded protein response (UPR component, IRE1, cleaves XBP1/HAC1 introns in order to generate spliced mRNAs that are translated into potent transcription factors. IRE1 also cleaves endoplasmic-reticulum-associated RNAs leading to their decay, an activity termed regulated IRE1-dependent decay (RIDD; however, the mechanism by which IRE1 differentiates intron cleavage from RIDD is not well understood. Using in vitro experiments, we found that IRE1 has two different modes of action: XBP1/HAC1 is cleaved by IRE1 subunits acting cooperatively within IRE1 oligomers, whereas a single subunit of IRE1 performs RIDD without cooperativity. Furthermore, these distinct activities can be separated by complementation of catalytically inactive IRE1 RNase and mutations at oligomerization interfaces. Using an IRE1 RNase inhibitor, STF-083010, selective inhibition of XBP1 splicing indicates that XBP1 promotes cell survival, whereas RIDD leads to cell death, revealing modulation of IRE1 activities as a drug-development strategy.

  20. Two chiroptical modes of silver nanospirals

    International Nuclear Information System (INIS)

    Bai, Fan; Deng, Junhong; Fu, Junxue; Ng, Jack; Huang, Zhifeng; Yang, Mengsu

    2016-01-01

    As an emerging three-dimensional chiral metamaterial, plasmonic nanospirals (NSs) possess inherent chiroptical activity that has attracted increasing attention for developing potential photonic applications. However, the study of chiroptical activity of plasmonic NSs is still in its infancy, especially for NSs made of silver, which is a typical plasmonic material with high plasmonic quality. Herein, we present a systematic study of circular dichroism (CD) of silver NSs (AgNSs) that are fabricated and engineered in helical lengths by glancing-angle deposition (GLAD) and dispersed in ethanol. The CD spectrum is composed of a bisignated mode of two peaks, one in the UV regime and the other in the visible. The UV mode has a resonance wavelength saturating at ∼375 nm and a linewidth decoupled from the helical elongation, while the visible mode tends to have a redshift and its linewidth broadens linearly with the elongation of AgNS. Helical elongation generally amplifies the chiroptical activity of both modes. Finite-element simulation shows good agreement with the experimental CD results, and accounts for the wavelength-related chiroptical distinction in terms of the resonance wavelength. This work contributes to understanding the bisignated chiroptical responses of plasmonic nanospirals, and introduces a simple method to tailor the visible chiroptical activity that is strongly desired to explore a wide range of chirality-related bio-applications. (paper)

  1. Absorption and emission from mode conversion theory

    International Nuclear Information System (INIS)

    Swanson, D.G.

    1995-02-01

    The effects of mode conversion theory on emission have led to some surprising results. The classical expressions were originally derived from models which did not include mode conversion or its attendant reflection. When mode conversion was included, the first surprise was that the transmission coefficient is totally independent of absorption and due exclusively to tunneling. The other surprise is that the observed emission arises from two distinct sources, one direct, and one from an indirect Bernstein wave source which is partially converted in the cyclotron layer to outgoing electromagnetic waves, with the net result that mode conversion cancels out for the electron case. The only corrections to electron cyclotron emission are then due to reflection effects, and these have been shown to be small for laboratory plasmas, leading to the validation of the classical formula, but via an entirely new paradigm in its interpretation. This paper includes a summary of the absorption process for electron cyclotron harmonics, and reviews the emission physics, including both potential error estimates and a discussion of the spatial emission source distribution

  2. Magnetic modes in superlattices

    International Nuclear Information System (INIS)

    Oliveira, F.A.

    1990-04-01

    A first discussion of reciprocal propagation of magnetic modes in a superlattice is presented. In the absence of an applied external magnetic field a superllatice made of alternate layers of the type antiferromagnetic-non-magnetic materials presents effects similar to those of phonons in a dielectric superlattice. (A.C.A.S.) [pt

  3. Thermodynamics of Radiation Modes

    Science.gov (United States)

    Pina, Eduardo; de la Selva, Sara Maria Teresa

    2010-01-01

    We study the equilibrium thermodynamics of the electromagnetic radiation in a cavity of a given volume and temperature. We found three levels of description, the thermodynamics of one mode, the thermodynamics of the distribution of frequencies in a band by summing over the frequencies in it and the global thermodynamics by summing over all the…

  4. Thermal Operating Modes

    International Nuclear Information System (INIS)

    Bechtel SAIC Company

    2002-01-01

    Higher and lower temperature operating modes (e.g., above and below the boiling point of water) are alternative approaches to managing the heat produced by the radioactive decay of spent nuclear fuel. Current analyses indicate that a repository at the Yucca Mountain site is likely to comply with applicable safety standards regardless of the particular thermal operating mode. Both modes have potential advantages and disadvantages. With a higher temperature operating mode (HTOM), waste packages (WPs) can be placed closer together. This reduces the number of drifts, the required emplacement area, construction costs, and occupational risks to construction workers. In addition, the HTOM would minimize the amount of water that might contact the waste for hundreds of years after closure. On the other hand, higher temperatures introduce uncertainties in the understanding of the long-term performance of the repository because of uncertainties in the thermal effects on WP lifetime and the near-field environment around the drifts. A lower temperature operating mode (LTOM) has the potential to reduce uncertainties in long-term performance of the repository by limiting the effects of temperature on WP lifetime and on the near-field environment around the drifts. Depending on the combination of operating parameters, a LTOM could require construction of additional drifts, a larger emplacement area, increased construction costs, increased occupational risks to construction works, and a longer period of ventilation than a HTOM. The repository design for the potential Yucca Mountain site is flexible and can be constructed and operated in various operating modes to achieve specific technical objectives, accommodate future policy decisions, and use of new information. For example, the flexible design can be operated across a range of temperatures and can be tailored to achieve specific thermal requirements in the future. To accommodate future policy decisions, the repository can be

  5. Threshold condition for nonlinear tearing modes in tokamaks

    International Nuclear Information System (INIS)

    Zabiego, M.F.; Callen, J.D.

    1996-03-01

    Low-mode-number tearing, mode nonlinear evolution is analyzed emphasizing the need for a threshold condition, to account for observations in tokamaks. The discussion is illustrated by two models recently introduced in the literature. The models can be compared with the available data and/or serve as a basis for planning some experiments in order to either test theory (by means of beta-limit scaling laws, as proposed in this paper) or attempt to control undesirable tearing modes. Introducing a threshold condition in the tearing mode stability analysis is found to reveal some bifurcation points and thus domains of intrinsic stability in the island dynamics operational space

  6. Comprehensive comparison of macro-strain mode and displacement mode based on different sensing technologies

    Science.gov (United States)

    Hong, Wan; Zhang, Jian; Wu, Gang; Wu, Zhishen

    2015-01-01

    A comprehensive comparison of macro-strain mode and displacement mode obtained from distributed macro-strain sensing and high-density point sensing (such as accelerometers) technologies is presented in this paper. Theoretical derivation reveals that displacement mode shape from accelerometers and modal macro-strain from distributed macro-strain sensors can be converted into each other. However, it is realized that displacement mode shape as global behavior of a structure can still be calculated with high-precision from modal macro-strain considering measurement errors in practical monitoring, whereas modal macro-strain can hardly be accurately achieved from displacement mode shape when signals are corrupted with noise in practical monitoring. Simulation and experiment results show that the calculated displacement mode shapes are very close to the actual ones even if the noise level reaches 5%. Meanwhile, damage index using measured modal macro-strain is still effective when the measurements are corrupted with 5% noise which is reliable for damage detection in practical monitoring. Calculating modal macro-strain from noise-polluted displacement mode shape will cause an unacceptable error if the noise level reaches only 0.5%, which has been verified in the simulation.

  7. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

    2001-09-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  8. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    International Nuclear Information System (INIS)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E.; Halvorsen, O.J.; Gjelland, K.; Engebretsen, L.

    2001-01-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  9. Observations on resistive wall modes

    International Nuclear Information System (INIS)

    Gerwin, R.A.; Finn, J.M.

    1996-01-01

    Several results on resistive wall modes and their application to tokamaks are presented. First, it is observed that in the presence of collisional parallel dynamics there is an exact cancellation to lowest order of the dissipative and sound wave effects for an ideal Ohm's law. This is easily traced to the fact that the parallel dynamics occurs along the perturbed magnetic field lines for such electromagnetic modes. Such a cancellation does not occur in the resistive layer of a tearing-like mode. The relevance to models for resistive wall modes using an electrostatic Hammett-Perkins type operator to model Landau damping will be discussed. Second, we observe that with an ideal Ohm's law, resistive wall modes can be destabilized by rotation in that part of parameter space in which the ideal MHD modes are stable with the wall at infinity. This effect can easily be explained by interpreting the resistive wall instability in terms of mode coupling between the backward stable MHD mode and a stable mode locked into the wall. Such an effect can occur for very small rotation for tearing-resistive wall modes in which inertia dominates viscosity in the layer, but the mode is stabilized by further rotation. For modes for which viscosity dominates in the layer, rotation is purely stabilizing. For both tearing models, a somewhat higher rotation frequency gives stability essentially whenever the tearing mode is stable with a perfectly conducting wall. These tearing/resistive wall results axe also simply explained in terms of mode coupling. It has been shown that resonant external ideal modes can be stabilized in the presence of resistive wall and resistive plasma with rotation of order the nominal tearing mode growth rate. We show that these modes behave as resistive wall tearing modes in the sense above. This strengthens the suggestion that rotational stabilization of the external kink with a resistive wall is due to the presence of resistive layers, even for ideal modes

  10. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  11. Visual distinctiveness can enhance recency effects.

    Science.gov (United States)

    Bornstein, B H; Neely, C B; LeCompte, D C

    1995-05-01

    Experimental efforts to meliorate the modality effect have included attempts to make the visual stimulus more distinctive. McDowd and Madigan (1991) failed to find an enhanced recency effect in serial recall when the last item was made more distinct in terms of its color. In an attempt to extend this finding, three experiments were conducted in which visual distinctiveness was manipulated in a different manner, by combining the dimensions of physical size and coloration (i.e., whether the stimuli were solid or outlined in relief). Contrary to previous findings, recency was enhanced when the size and coloration of the last item differed from the other items in the list, regardless of whether the "distinctive" item was larger or smaller than the remaining items. The findings are considered in light of other research that has failed to obtain a similar enhanced recency effect, and their implications for current theories of the modality effect are discussed.

  12. Boosting Majorana Zero Modes

    Directory of Open Access Journals (Sweden)

    Torsten Karzig

    2013-11-01

    Full Text Available One-dimensional topological superconductors are known to host Majorana zero modes at domain walls terminating the topological phase. Their non-Abelian nature allows for processing quantum information by braiding operations that are insensitive to local perturbations, making Majorana zero modes a promising platform for topological quantum computation. Motivated by the ultimate goal of executing quantum-information processing on a finite time scale, we study domain walls moving at a constant velocity. We exploit an effective Lorentz invariance of the Hamiltonian to obtain an exact solution of the associated quasiparticle spectrum and wave functions for arbitrary velocities. Essential features of the solution have a natural interpretation in terms of the familiar relativistic effects of Lorentz contraction and time dilation. We find that the Majorana zero modes remain stable as long as the domain wall moves at subluminal velocities with respect to the effective speed of light of the system. However, the Majorana bound state dissolves into a continuous quasiparticle spectrum after the domain wall propagates at luminal or even superluminal velocities. This relativistic catastrophe implies that there is an upper limit for possible braiding frequencies even in a perfectly clean system with an arbitrarily large topological gap. We also exploit our exact solution to consider domain walls moving past static impurities present in the system.

  13. The structure of ideal MHD Alfven modes

    International Nuclear Information System (INIS)

    Turnbull, A.D.; Chu, M.S.; Lao, L.L.; Greene, J.M.; Strait, E.J.; Chance, M.S.

    1991-01-01

    Continuum Alfven modes have undergone a resurgence in interest with the recent realization that so-called Toroidicity-Induced Alfven Eigenmodes (TAE modes) can be destabilized either by energetic beam ions in a strongly heated plasma or by alpha particles in a burning plasma. The GATO Ideal MHD Stability code, which minimizes the potential energy according to a variational formulation, has now been modified to isolate and calculate stable continuum eigenmodes. The existence of the TAE mode and its associated gap has been verified, using this code, for a circular cross-section, finite aspect ratio equilibrium. Moreover, the eigenfrequencies and eigenmodes obtained from this variational calculation are found to be in extremely good quantitative agreement with those obtained from the non-variational NOVA code. A systematic survey of the stable continuum has further revealed a surprising diversity in the structure of the continuum Alfven modes; the logarithmic singularity can be so broad, in some cases, as to occupy the whole cross-section. This has important implications for heating experiments which aim to locally excite the plasma by rf waves in the Alfven frequency range. The structure of several representative examples is discussed. The Alfven continuum, in general, and the TAE mode and its associated gap, in particular, are also found to be strongly modified by cross-sectional shaping. The dependence of the spectrum on various shaping factors is explored

  14. Educational Modes of Thinking in Neo-Confucianism: A Traditional Lens for Rethinking Modern Education

    Science.gov (United States)

    Hwang, Keumjoong

    2013-01-01

    This article discusses the distinctive educational modes of thinking in Neo-Confucianism, with an interest of extracting Confucian reflective views for modern education of traditionally Confucian East Asia. Neo-Confucian typical modes of thinking on education are characterized as "heart-mind centered" and "learning as…

  15. Photonic and plasmonic guided modes in graphene-silicon photonic crystals

    DEFF Research Database (Denmark)

    Gu, Tingyi; Andryieuski, Andrei; Hao, Yufeng

    2016-01-01

    We report the results of systematic studies of plasmonic and photonic guided modes in large-area single-layer graphene integrated into a nanostructured silicon substrate. The interaction of light with graphene and substrate photonic crystals can be classified in distinct regimes of plasmonic...... and photonic modes....

  16. Guaranteed performance in reaching mode of sliding mode ...

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    addresses the design of constant plus proportional rate reaching law-based SMC for second-order ... Reaching mode; sliding mode controlled systems; output tracking ... The uncertainty in the input distribution function g is expressed as.

  17. Genomic Analysis Reveals Distinct Concentration-Dependent Evolutionary Trajectories for Antibiotic Resistance in Escherichia coli

    Science.gov (United States)

    Mogre, Aalap; Sengupta, Titas; Veetil, Reshma T.; Ravi, Preethi; Seshasayee, Aswin Sai Narain

    2014-01-01

    Evolution of bacteria under sublethal concentrations of antibiotics represents a trade-off between growth and resistance to the antibiotic. To understand this trade-off, we performed in vitro evolution of laboratory Escherichia coli under sublethal concentrations of the aminoglycoside kanamycin over short time durations. We report that fixation of less costly kanamycin-resistant mutants occurred earlier in populations growing at lower sublethal concentration of the antibiotic, compared with those growing at higher sublethal concentrations; in the latter, resistant mutants with a significant growth defect persisted longer. Using deep sequencing, we identified kanamycin resistance-conferring mutations, which were costly or not in terms of growth in the absence of the antibiotic. Multiple mutations in the C-terminal end of domain IV of the translation elongation factor EF-G provided low-cost resistance to kanamycin. Despite targeting the same or adjacent residues of the protein, these mutants differed from each other in the levels of resistance they provided. Analysis of one of these mutations showed that it has little defect in growth or in synthesis of green fluorescent protein (GFP) from an inducible plasmid in the absence of the antibiotic. A second class of mutations, recovered only during evolution in higher sublethal concentrations of the antibiotic, deleted the C-terminal end of the ATP synthase shaft. This mutation confers basal-level resistance to kanamycin while showing a strong growth defect in the absence of the antibiotic. In conclusion, the early dynamics of the development of resistance to an aminoglycoside antibiotic is dependent on the levels of stress (concentration) imposed by the antibiotic, with the evolution of less costly variants only a matter of time. PMID:25281544

  18. Climate sensitivity of Mediterranean pine growth reveals distinct east-west dipole

    Czech Academy of Sciences Publication Activity Database

    Seim, A.; Treydte, K.; Trouet, V.; Frank, D.; Fonti, P.; Tegel, W.; Panayotov, M.; Fernandez-Donado, L.; Krusic, P.; Büntgen, Ulf

    2015-01-01

    Roč. 35, č. 9 (2015), s. 2503-2513 ISSN 0899-8418 R&D Projects: GA MŠk(CZ) EE2.3.20.0248 Institutional support: RVO:67179843 Keywords : tree-ring width * scots pine * wood formation * ice core * variability * drought * precipitation * reconstructions * circulation * dynamics * climate dynamics * dendroclimatology * drought response * Mediterranean east-west dipole * palaeoclimatology * Pinus spp * principal component analysis * tree-ring width Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 3.609, year: 2015

  19. Superresolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes

    Science.gov (United States)

    Fournier, David; Redl, Stefan; Best, Gerrit; Borsos, Máté; Tiwari, Vijay K.; Tachibana-Konwalski, Kikuë; Ketting, René F.; Parekh, Sapun H.; Cremer, Christoph; Birk, Udo J.

    2015-01-01

    During meiosis, homologous chromosomes associate to form the synaptonemal complex (SC), a structure essential for fertility. Information about the epigenetic features of chromatin within this structure at the level of superresolution microscopy is largely lacking. We combined single-molecule localization microscopy (SMLM) with quantitative analytical methods to describe the epigenetic landscape of meiotic chromosomes at the pachytene stage in mouse oocytes. DNA is found to be nonrandomly distributed along the length of the SC in condensed clusters. Periodic clusters of repressive chromatin [trimethylation of histone H3 at lysine (Lys) 27 (H3K27me3)] are found at 500-nm intervals along the SC, whereas one of the ends of the SC displays a large and dense cluster of centromeric histone mark [trimethylation of histone H3 at Lys 9 (H3K9me3)]. Chromatin associated with active transcription [trimethylation of histone H3 at Lys 4 (H3K4me3)] is arranged in a radial hair-like loop pattern emerging laterally from the SC. These loops seem to be punctuated with small clusters of H3K4me3 with an average spread larger than their periodicity. Our findings indicate that the nanoscale structure of the pachytene chromosomes is constrained by periodic patterns of chromatin marks, whose function in recombination and higher order genome organization is yet to be elucidated. PMID:26561583

  20. Comment on "Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage".

    Science.gov (United States)

    Nakagome, Shigeki; Mano, Shuhei; Hasegawa, Masami

    2013-03-29

    Based on nuclear and mitochondrial DNA, Hailer et al. (Reports, 20 April 2012, p. 344) suggested early divergence of polar bears from a common ancestor with brown bears and subsequent introgression. Our population genetic analysis that traces each of the genealogies in the independent nuclear loci does not support the evolutionary model proposed by the authors.

  1. Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage.

    Science.gov (United States)

    Hailer, Frank; Kutschera, Verena E; Hallström, Björn M; Klassert, Denise; Fain, Steven R; Leonard, Jennifer A; Arnason, Ulfur; Janke, Axel

    2012-04-20

    Recent studies have shown that the polar bear matriline (mitochondrial DNA) evolved from a brown bear lineage since the late Pleistocene, potentially indicating rapid speciation and adaption to arctic conditions. Here, we present a high-resolution data set from multiple independent loci across the nuclear genomes of a broad sample of polar, brown, and black bears. Bayesian coalescent analyses place polar bears outside the brown bear clade and date the divergence much earlier, in the middle Pleistocene, about 600 (338 to 934) thousand years ago. This provides more time for polar bear evolution and confirms previous suggestions that polar bears carry introgressed brown bear mitochondrial DNA due to past hybridization. Our results highlight that multilocus genomic analyses are crucial for an accurate understanding of evolutionary history.

  2. Simultaneous attentional guidance by working-memory and selection history reveals two distinct sources of attention.

    Science.gov (United States)

    Schwark, Jeremy D; Dolgov, Igor; Sandry, Joshua; Volkman, C Brooks

    2013-10-01

    Recent theories of attention have proposed that selection history is a separate, dissociable source of information that influences attention. The current study sought to investigate the simultaneous involvement of selection history and working-memory on attention during visual search. Experiments 1 and 2 used target feature probability to manipulate selection history and found significant effects of both working-memory and selection history, although working-memory dominated selection history when they cued different locations. Experiment 3 eliminated the contribution of voluntary refreshing of working-memory and replicated the main effects, although selection history became dominant. Using the same methodology, but with reduced probability cue validity, both effects were present in Experiment 4 and did not significantly differ in their contribution to attention. Effects of selection history and working-memory never interacted. These results suggest that selection history and working-memory are separate influences on attention and have little impact on each other. Theoretical implications for models of attention are discussed. © 2013.

  3. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian

    2016-09-26

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer is synthesized to study its localization within PlSNs by analyzing the elemental distribution of chlorine. The functionalized nanohybrid structures are analyzed by scanning transmission electron microscopy, electron energy loss spectroscopy, and spectrum imaging. The results show that the RAFT (reversible addition-fragmentation chain transfer) polymers\\' sulfur containing end groups are colocalized at the gold cores, both within nanohybrids of simple core-shell morphology and within higher order PlSNs, providing microscopic evidence for the affinity of the RAFT group toward gold surfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA., Weinheim.

  4. Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

    Science.gov (United States)

    Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

    2017-06-01

    Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian; Roddatis, Vladimir; Lopatin, Sergei; Vana, Philipp

    2016-01-01

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer

  6. Coral transcriptome and bacterial community profiles reveal distinct Yellow Band Disease states in Orbicella faveolata

    KAUST Repository

    Closek, Collin J.; Sunagawa, Shinichi; DeSalvo, Michael K.; Piceno, Yvette M.; Desantis, Todd Z.; Brodie, Eoin L.; Weber, Michele X.; Voolstra, Christian R.; Andersen, Gary L.; Medina, Mó nica M.

    2014-01-01

    marked each health state. Diseased samples were associated with two to three times more bacterial diversity. HD samples had the highest bacterial richness, which included components associated with HH and DD, as well as additional unique families

  7. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations.

    Science.gov (United States)

    Montagnani, Valentina; Benelli, Matteo; Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

    2016-05-24

    Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression.

  8. Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns

    DEFF Research Database (Denmark)

    Hummelshøj, Tina; Munthe-Fog, Lea; Madsen, Hans O

    2008-01-01

    -Xaa-Yaa repeats and a Trp279STOP introduces a stop codon, thereby destroying the fibrinogen-like domain of Ficolin-1. In contrast to FCN1 and FCN2, the number of SNPs in FCN3 was very low. In conclusion, large ethnic differences in the FCN genes that will affect the concentration, structure, and function...

  9. Analysis of exocyst subunit EXO70 family reveals distinct membrane polar domains in Tobacco pollen tubes

    Czech Academy of Sciences Publication Activity Database

    Sekereš, Juraj; Pejchar, Přemysl; Šantrůček, J.; Vukašinović, Nemanja; Žárský, Viktor; Potocký, Martin

    2017-01-01

    Roč. 173, č. 3 (2017), s. 1659-1675 ISSN 0032-0889 R&D Projects: GA ČR GA13-19073S; GA ČR GA15-24711S Grant - others:OPPK(XE) CZ.2.16/3.1.00/21519 Institutional support: RVO:61389030 Keywords : PLASMA-MEMBRANE * ARABIDOPSIS-THALIANA * CELL-MIGRATION Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 6.456, year: 2016

  10. Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles

    NARCIS (Netherlands)

    de Bruijne, Joep; Schinkel, Janke; Prins, Maria; Koekkoek, Sylvie M.; Aronson, Sem J.; van Ballegooijen, Marijn W.; Reesink, Hendrik W.; Molenkamp, Richard; van de Laar, Thijs J. W.

    2009-01-01

    Hepatitis C virus (HCV) genotype 4 (HCV-4) infection is considered to be difficult to treat and has become increasingly prevalent in European countries, including The Netherlands. Using a molecular epidemiological approach, the present study investigates the genetic diversity and evolutionary origin

  11. Distinct Rayleigh scattering from hot spot mutant p53 proteins reveals cancer cells.

    Science.gov (United States)

    Jun, Ho Joon; Nguyen, Anh H; Kim, Yeul Hong; Park, Kyong Hwa; Kim, Doyoun; Kim, Kyeong Kyu; Sim, Sang Jun

    2014-07-23

    The scattering of light redirects and resonances when an electromagnetic wave interacts with electrons orbits in the hot spot core protein and oscillated electron of the gold nanoparticles (AuNP). This report demonstrates convincingly that resonant Rayleigh scattering generated from hot spot mutant p53 proteins is correspondence to cancer cells. Hot spot mutants have unique local electron density changes that affect specificity of DNA binding affinity compared with wild types. Rayleigh scattering changes introduced by hot-spot mutations were monitored by localized surface plasmon resonance (LSPR) shift changes. The LSPR λmax shift for hot-spot mutants ranged from 1.7 to 4.2 nm for mouse samples and from 0.64 nm to 2.66 nm for human samples, compared to 9.6 nm and 15 nm for wild type and mouse and human proteins, respectively with a detection sensitivity of p53 concentration at 17.9 nM. It is interesting that hot-spot mutants, which affect only interaction with DNA, launches affinitive changes as considerable as wild types. These changes propose that hot-spot mutants p53 proteins can be easily detected by local electron density alterations that disturbs the specificity of DNA binding of p53 core domain on the surface of the DNA probed-nanoplasmonic sensor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. High-copy sequences reveal distinct evolution of the rye B chromosome

    Czech Academy of Sciences Publication Activity Database

    Klemme, S.; Banaei-Moghaddam, A.M.; Macas, Jiří; Wicker, T.; Novák, Petr; Houben, A.

    2013-01-01

    Roč. 199, č. 2 (2013), s. 550-558 ISSN 0028-646X R&D Projects: GA ČR GBP501/12/G090 Institutional support: RVO:60077344 Keywords : satellite DNA * nondisjunction control region * B chromosome * Secale cereale (rye) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.545, year: 2013

  13. Cytological and Morphological Analyses Reveal Distinct Features of Intestinal Development during Xenopus tropicalis Metamorphosis

    Science.gov (United States)

    Matsuura, Kazuo; Shi, Yun-Bo

    2012-01-01

    Background The formation and/or maturation of adult organs in vertebrates often takes place during postembryonic development, a period around birth in mammals when thyroid hormone (T3) levels are high. The T3-dependent anuran metamorphosis serves as a model to study postembryonic development. Studies on the remodeling of the intestine during Xenopus (X.) laevis metamorphosis have shown that the development of the adult intestine involves de novo formation of adult stem cells in a process controlled by T3. On the other hand, X. tropicalis, highly related to X. laevis, offers a number of advantages for studying developmental mechanisms, especially at genome-wide level, over X. laevis, largely due to its shorter life cycle and sequenced genome. To establish X. tropicalis intestinal metamorphosis as a model for adult organogenesis, we analyzed the morphological and cytological changes in X. tropicalis intestine during metamorphosis. Methodology/Principal Findings We observed that in X. tropicalis, the premetamorphic intestine was made of mainly a monolayer of larval epithelial cells surrounded by little connective tissue except in the single epithelial fold, the typhlosole. During metamorphosis, the larval epithelium degenerates and adult epithelium develops to form a multi-folded structure with elaborate connective tissue and muscles. Interestingly, typhlosole, which is likely critical for adult epithelial development, is present along the entire length of the small intestine in premetamorphic tadpoles, in contrast to X. laevis, where it is present only in the anterior 1/3. T3-treatment induces intestinal remodeling, including the shortening of the intestine and the typhlosole, just like in X. laevis. Conclusions/Significance Our observations indicate that the intestine undergoes similar metamorphic changes in X. laevis and X. tropicalis, making it possible to use the large amount of information available on X. laevis intestinal metamorphosis and the genome sequence information and genetic advantages of X. tropicalis to dissect the pathways governing adult intestinal development. PMID:23071801

  14. Quantitative Proteomics Reveals Distinct Differences in the Protein Content of Outer Membrane Vesicle Vaccines

    NARCIS (Netherlands)

    Waterbeemd, van de B.; Mommen, G.P.M.; Pennings, J.L.A.; Eppink, M.H.M.; Wijffels, R.H.; Pol, van der L.A.; Jong, de A.P.J.M.

    2013-01-01

    At present, only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. These vaccines however require detergent-extraction to remove endotoxin, which changes immunogenicity and causes production difficulties. To investigate this in

  15. Distinct role of hydration water in protein misfolding and aggregation revealed by fluctuating thermodynamics analysis.

    Science.gov (United States)

    Chong, Song-Ho; Ham, Sihyun

    2015-04-21

    Protein aggregation in aqueous cellular environments is linked to diverse human diseases. Protein aggregation proceeds through a multistep process initiated by conformational transitions, called protein misfolding, of monomer species toward aggregation-prone structures. Various forms of aggregate species are generated through the association of misfolded monomers including soluble oligomers and amyloid fibrils. Elucidating the molecular mechanisms and driving forces involved in the misfolding and subsequent association has been a central issue for understanding and preventing protein aggregation diseases such as Alzheimer's, Parkinson's, and type II diabetes. In this Account, we provide a thermodynamic perspective of the misfolding and aggregation of the amyloid-beta (Aβ) protein implicated in Alzheimer's disease through the application of fluctuating thermodynamics. This approach "dissects" the conventional thermodynamic characterization of the end states into the one of the fluctuating processes connecting them, and enables one to analyze variations in the thermodynamic functions that occur during the course of protein conformational changes. The central quantity in this approach is the solvent-averaged effective energy, f = Eu + Gsolv, comprising the protein potential energy (Eu) and the solvation free energy (Gsolv), whose time variation reflects the protein dynamics on the free energy landscape. Protein configurational entropy is quantified by the magnitude of fluctuations in f. We find that misfolding of the Aβ monomer when released from a membrane environment to an aqueous phase is driven by favorable changes in protein potential energy and configurational entropy, but it is also accompanied by an unfavorable increase in solvation free energy. The subsequent dimerization of the misfolded Aβ monomers occurs in two steps. The first step, where two widely separated monomers come into contact distance, is driven by water-mediated attraction, that is, by a decrease in solvation free energy, harnessing the monomer solvation free energy earned during the misfolding. The second step, where a compact dimer structure is formed, is driven by direct protein-protein interactions, but again it is accompanied by an increase in solvation free energy. The increased solvation free energy of the dimer will function as the driving force to recruit another Aβ protein in the approach stage of subsequent oligomerizations. The fluctuating thermodynamics analysis of the misfolding and dimerization of the Aβ protein indicates that the interaction of the protein with surrounding water plays a critical role in protein aggregation. Such a water-centric perspective is further corroborated by demonstrating that, for a large number of Aβ mutants and mutants of other protein systems, the change in the experimental aggregation propensity upon mutation has a significant correlation with the protein solvation free energy change. We also find striking discrimination between the positively and negatively charged residues on the protein surface by surrounding water molecules, which is shown to play a crucial role in determining the protein aggregation propensity. We argue that the protein total charge dictates such striking behavior of the surrounding water molecules. Our results provide new insights for understanding and predicting the protein aggregation propensity, thereby offering novel design principles for producing aggregation-resistant proteins for biotherapeutics.

  16. Identifying a "default" visual search mode with operant conditioning.

    Science.gov (United States)

    Kawahara, Jun-ichiro

    2010-09-01

    The presence of a singleton in a task-irrelevant domain can impair visual search. This impairment, known as the attentional capture depends on the set of participants. When narrowly searching for a specific feature (the feature search mode), only matching stimuli capture attention. When searching broadly (the singleton detection mode), any oddball captures attention. The present study examined which strategy represents the "default" mode using an operant conditioning approach in which participants were trained, in the absence of explicit instructions, to search for a target in an ambiguous context in which one of two modes was available. The results revealed that participants behaviorally adopted the singleton detection as the default mode but reported using the feature search mode. Conscious strategies did not eliminate capture. These results challenge the view that a conscious set always modulates capture, suggesting that the visual system tends to rely on stimulus salience to deploy attention.

  17. Edge-localized mode avoidance and pedestal structure in I-mode plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Walk, J. R., E-mail: jrwalk@psfc.mit.edu; Hughes, J. W.; Hubbard, A. E.; Terry, J. L.; Whyte, D. G.; White, A. E.; Baek, S. G.; Reinke, M. L.; Theiler, C.; Churchill, R. M.; Rice, J. E. [MIT Plasma Science and Fusion Center, Cambridge, MA 02139-4307 (United States); Snyder, P. B.; Osborne, T. [General Atomics, San Diego, CA 92186-5608 (United States); Dominguez, A [Princeton Plasma Physics Laboratory, Princeton, NJ 08543-0451 (United States); Cziegler, I. [UCSD Center for Momentum Transport and Flow Organization, La Jolla, CA 92093-0417 (United States)

    2014-05-15

    I-mode is a high-performance tokamak regime characterized by the formation of a temperature pedestal and enhanced energy confinement, without an accompanying density pedestal or drop in particle and impurity transport. I-mode operation appears to have naturally occurring suppression of large Edge-Localized Modes (ELMs) in addition to its highly favorable scalings of pedestal structure and overall performance. Extensive study of the ELMy H-mode has led to the development of the EPED model, which utilizes calculations of coupled peeling-ballooning MHD modes and kinetic-ballooning mode (KBM) stability limits to predict the pedestal structure preceding an ELM crash. We apply similar tools to the structure and ELM stability of I-mode pedestals. Analysis of I-mode discharges prepared with high-resolution pedestal data from the most recent C-Mod campaign reveals favorable pedestal scalings for extrapolation to large machines—pedestal temperature scales strongly with power per particle P{sub net}/n{sup ¯}{sub e}, and likewise pedestal pressure scales as the net heating power (consistent with weak degradation of confinement with heating power). Matched discharges in current, field, and shaping demonstrate the decoupling of energy and particle transport in I-mode, increasing fueling to span nearly a factor of two in density while maintaining matched temperature pedestals with consistent levels of P{sub net}/n{sup ¯}{sub e}. This is consistent with targets for increased performance in I-mode, elevating pedestal β{sub p} and global performance with matched increases in density and heating power. MHD calculations using the ELITE code indicate that I-mode pedestals are strongly stable to edge peeling-ballooning instabilities. Likewise, numerical modeling of the KBM turbulence onset, as well as scalings of the pedestal width with poloidal beta, indicates that I-mode pedestals are not limited by KBM turbulence—both features identified with the trigger for large ELMs

  18. Pad-mode-induced instantaneous mode instability for simple models of brake systems

    Science.gov (United States)

    Oberst, S.; Lai, J. C. S.

    2015-10-01

    Automotive disc brake squeal is fugitive, transient and remains difficult to predict. In particular, instantaneous mode squeal observed experimentally does not seem to be associated with mode coupling and its mechanism is not clear. The effects of contact pressures, friction coefficients as well as material properties (pressure and temperature dependency and anisotropy) for brake squeal propensity have not been systematically explored. By analysing a finite element model of an isotropic pad sliding on a plate similar to that of a previously reported experimental study, pad modes have been identified and found to be stable using conventional complex eigenvalue analysis. However, by subjecting the model to contact pressure harmonic excitation for a range of pressures and friction coefficients, a forced response analysis reveals that the dissipated energy for pad modes is negative and becomes more negative with increasing contact pressures and friction coefficients, indicating the potential for instabilities. The frequency of the pad mode in the sliding direction is within the range of squeal frequencies observed experimentally. Nonlinear time series analysis of the vibration velocity also confirms the evolution of instabilities induced by pad modes as the friction coefficient increases. By extending this analysis to a more realistic but simple brake model in the form of a pad-on-disc system, in-plane pad-modes, which a complex eigenvalue analysis predicts to be stable, have also been identified by negative dissipated energy for both isotropic and anisotropic pad material properties. The influence of contact pressures on potential instabilities has been found to be more dominant than changes in material properties owing to changes in pressure or temperature. Results here suggest that instantaneous mode squeal is likely caused by in-plane pad-mode instabilities.

  19. Mode-to-mode energy transfers in convective patterns

    Indian Academy of Sciences (India)

    Abstract. We investigate the energy transfer between various Fourier modes in a low- dimensional model for thermal convection. We have used the formalism of mode-to-mode energy transfer rate in our calculation. The evolution equations derived using this scheme is the same as those derived using the hydrodynamical ...

  20. Azimuthal decomposition of optical modes

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2012-07-01

    Full Text Available This presentation analyses the azimuthal decomposition of optical modes. Decomposition of azimuthal modes need two steps, namely generation and decomposition. An azimuthally-varying phase (bounded by a ring-slit) placed in the spatial frequency...

  1. Localized Acoustic Surface Modes

    KAUST Repository

    Farhat, Mohamed

    2015-08-04

    We introduce the concept of localized acoustic surface modes (ASMs). We demonstrate that they are induced on a two-dimensional cylindrical rigid surface with subwavelength corrugations under excitation by an incident acoustic plane wave. Our results show that the corrugated rigid surface is acoustically equivalent to a cylindrical scatterer with uniform mass density that can be represented using a Drude-like model. This, indeed, suggests that plasmonic-like acoustic materials can be engineered with potential applications in various areas including sensing, imaging, and cloaking.

  2. Mode coupling in nonlinear Rayleigh--Taylor instability

    International Nuclear Information System (INIS)

    Ofer, D.; Shvarts, D.; Zinamon, Z.; Orszag, S.A.

    1992-01-01

    This paper studies the interaction of a small number of modes in the two-fluid Rayleigh--Taylor instability at relatively late stages of development, i.e., the nonlinear regime, using a two-dimensional hydrodynamic code incorporating a front-tracking scheme. It is found that the interaction of modes can greatly affect the amount of mixing and may even reduce the width of the mixing region. This interaction is both relatively long range in wave-number space and also acts in both directions, i.e., short wavelengths affect long wavelengths and vice versa. Three distinct stages of interaction have been identified, including substantial interaction among modes some of which may still be in their classical (single mode) ''linear'' phase

  3. Distinctiveness of Saudi Arabian EFL Learners

    Directory of Open Access Journals (Sweden)

    Manssour Habbash

    2016-04-01

    Full Text Available In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs (Preparatory Year Programs in Saudi Arabia. This study examines the distinctiveness with regard to the learning attitudes of Saudi students that are often cultivated by the culture and academic environment in their homeland. Employing an emic approach for collecting the required data an analysis was carried out in light of the other studies on ‘education’ in Saudi Arabia that have particular reference to the factors that can positively influence student motivation, student success and the academic environment. The findings were used in constructing the rationale behind such distinctiveness. Assuming that the outcome of the discussion on the findings of this exploration can be helpful for teachers in adapting their teaching methodology and improving their teacher efficacy in dealing with students both from the kingdom and in the kingdom, some recommendations are made. Keywords: China Distinctiveness, Saudi Arabian University context, Expatriate teachers’ perspective, Distinctiveness Theory

  4. Tripartite entanglement of bosonic systems in a noninertial frame beyond the single- mode approximation

    Directory of Open Access Journals (Sweden)

    M Soltani

    2015-12-01

    Full Text Available In this work, we generalize the entanglement of three-qbit Bosonic systems beyond the single-mode approximation when one of the observers is accelerated. For this purpose, we review the effects of acceleration on field modes and quantum states. The single-mode approximation and beyond the single-mode approximation methods are introduced. After this brief introduction, the main problem of this paper, tripartite entanglement of bosonic systems in a noninertial frame beyond the single- mode approximation is investigated. The tripartite entangled states have different classes with GHZ and W states being most important. Here, we choose &pi-tangle as a measure of tripartite entanglement. If the three parties share GHZ state, the corresponding &pi-tangle will increase by increasing acceleration for some Unruh modes. This phenomenon, increasing entanglement, has never been observed in the single-mode approximation for bosonic case. Moreover, the &pi-tangle dose not exhibit a monotonic behavior with increasing acceleration. In the infinite acceleration limit, the &pi-tangle goes to different nonzero values for distinct Unruh modes. Unlike GHZ state, the entanglement of the W state shows only monotonically increasing and decreasing behaviors with increasing acceleration. Also, the entanglement for all possible choices of Unruh modes approaches only 0.176 in the high acceleration limit. Therefore, according to the quantum entanglement, there is no distinction between the single-mode approximation and beyond the single-mode approximation methods in this limit.

  5. Raman amplification of OAM modes

    DEFF Research Database (Denmark)

    Ingerslev, Kasper; Gregg, Patrick; Galili, Michael

    2017-01-01

    The set of fibre modes carrying orbital angular momentum (OAM) is a possible basis for mode division multiplexing. In this regard, fibres supporting OAM modes have been fabricated [1], and optical communication using these fibres, has been demonstrated [2]. A vital part of any long range...

  6. ACCA College English Teaching Mode

    Science.gov (United States)

    Ding, Renlun

    2008-01-01

    This paper elucidates a new college English teaching mode--"ACCA" (Autonomous Cooperative Class-teaching All-round College English Teaching Mode). Integrated theories such as autonomous learning and cooperative learning into one teaching mode, "ACCA", which is being developed and advanced in practice as well, is the achievement…

  7. Fluxon modes in superconducting multilayers

    DEFF Research Database (Denmark)

    Pedersen, Niels Falsig; Madsen, Søren Peder

    2004-01-01

    We show how to construct fluxon modes from plasma modes in the inductively coupled stacked Josephson junctions, and consider some special cases of these fluxon modes analytically. In some cases we can find exact analytical solutions when we choose the bias current in a special way. We also consid...

  8. Standardization of Keyword Search Mode

    Science.gov (United States)

    Su, Di

    2010-01-01

    In spite of its popularity, keyword search mode has not been standardized. Though information professionals are quick to adapt to various presentations of keyword search mode, novice end-users may find keyword search confusing. This article compares keyword search mode in some major reference databases and calls for standardization. (Contains 3…

  9. Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

    Directory of Open Access Journals (Sweden)

    Damien C Tully

    2016-05-01

    Full Text Available Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU, we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

  10. Spin and isospin modes

    International Nuclear Information System (INIS)

    Suzuki, T.; Sagawa, H.

    2000-01-01

    Complete text of publication follows. Spin and isospin modes in nuclei are investigated. We discuss some of the following topics. 1. Spin-dipole excitations in 12 C and 16 O are studied (1). Effects of tensor and spin-orbit interactions on the distribution of the strengths are investigated, and neutral current neutrino scattering cross sections in 16 O are obtained for heavy-flavor neutrinos from the supernovae. 2. Gamow-Teller (GT) and spin-dipole (SD) modes in 208 Bi are investigated. Quenching and fragmentation of the GT strength are discussed (2). SD excitations and electric dipole (E1) transitions between the GT and SD states are studied (3). Calculated E1 strengths are compared with the sum rule values obtained within the 1p-1h and 1p-1h + 2p-2h configuration spaces. 3. Coulomb displacement energy (CDE) of the IAS of 14 Be is calculated, and the effects of the halo on the CDE and the configuration of the halo state are investigated. 4. Spreading width of IAS and isospin dependence of the width are investigated (4). Our formula for the width explains very well the observed isospin dependence (5). (author)

  11. Modes of fossil preservation

    Science.gov (United States)

    Schopf, J.M.

    1975-01-01

    The processes of geologic preservation are important for understanding the organisms represented by fossils. Some fossil differences are due to basic differences in organization of animals and plants, but the interpretation of fossils has also tended to be influenced by modes of preservation. Four modes of preservation generally can be distinguished: (1) Cellular permineralization ("petrifaction") preserves anatomical detail, and, occasionally, even cytologic structures. (2) Coalified compression, best illustrated by structures from coal but characteristic of many plant fossils in shale, preserves anatomical details in distorted form and produces surface replicas (impressions) on enclosing matrix. (3) Authigenic preservation replicates surface form or outline (molds and casts) prior to distortion by compression and, depending on cementation and timing, may intergrade with fossils that have been subject to compression. (4) Duripartic (hard part) preservation is characteristic of fossil skeletal remains, predominantly animal. Molds, pseudomorphs, or casts may form as bulk replacements following dissolution of the original fossil material, usually by leaching. Classification of the kinds of preservation in fossils will aid in identifying the processes responsible for modifying the fossil remains of both animals and plants. ?? 1975.

  12. On Hobbes’s distinction of accidents

    Directory of Open Access Journals (Sweden)

    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  13. What makes health promotion research distinct?

    Science.gov (United States)

    Woodall, James; Warwick-Booth, Louise; South, Jane; Cross, Ruth

    2018-02-01

    There have been concerns about the decline of health promotion as a practice and discipline and, alongside this, calls for a clearer articulation of health promotion research and what, if anything, makes it distinct. This discussion paper, based on a review of the literature, the authors' own experiences in the field, and a workshop delivered by two of the authors at the 8th Nordic Health Promotion Conference, seeks to state the reasons why health promotion research is distinctive. While by no means exhaustive, the paper suggests four distinctive features. The paper hopes to be a catalyst to enable health promotion researchers to be explicit in their practice and to begin the process of developing an agreed set of research principles.

  14. Intergroup Leadership Across Distinct Subgroups and Identities.

    Science.gov (United States)

    Rast, David E; Hogg, Michael A; van Knippenberg, Daan

    2018-03-01

    Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

  15. Distinctive Dynamic Capabilities for New Business Creation

    DEFF Research Database (Denmark)

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow...... and fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  16. Fermionic bound states in distinct kinklike backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, Paraiba (Brazil); Mohammadi, A. [Universidade Federal de Campina Grande, Departamento de Fisica, Caixa Postal 10071, Campina Grande, Paraiba (Brazil)

    2017-04-15

    This work deals with fermions in the background of distinct localized structures in the two-dimensional spacetime. Although the structures have a similar topological character, which is responsible for the appearance of fractionally charged excitations, we want to investigate how the geometric deformations that appear in the localized structures contribute to the change in the physical properties of the fermionic bound states. We investigate the two-kink and compact kinklike backgrounds, and we consider two distinct boson-fermion interactions, one motivated by supersymmetry and the other described by the standard Yukawa coupling. (orig.)

  17. Mode regularization of the supersymmetric sphaleron and kink: Zero modes and discrete gauge symmetry

    International Nuclear Information System (INIS)

    Goldhaber, Alfred Scharff; Litvintsev, Andrei; Nieuwenhuizen, Peter van

    2001-01-01

    To obtain the one-loop corrections to the mass of a kink by mode regularization, one may take one-half the result for the mass of a widely separated kink-antikink (or sphaleron) system, where the two bosonic zero modes count as two degrees of freedom, but the two fermionic zero modes as only one degree of freedom in the sums over modes. For a single kink, there is one bosonic zero mode degree of freedom, but it is necessary to average over four sets of fermionic boundary conditions in order (i) to preserve the fermionic Z 2 gauge invariance ψ→-ψ, (ii) to satisfy the basic principle of mode regularization that the boundary conditions in the trivial and the kink sector should be the same, (iii) that the energy stored at the boundaries cancels and (iv) to avoid obtaining a finite, uniformly distributed energy which would violate cluster decomposition. The average number of fermionic zero-energy degrees of freedom in the presence of the kink is then indeed 1/2. For boundary conditions leading to only one fermionic zero-energy solution, the Z 2 gauge invariance identifies two seemingly distinct 'vacua' as the same physical ground state, and the single fermionic zero-energy solution does not correspond to a degree of freedom. Other boundary conditions lead to two spatially separated ω∼0 solutions, corresponding to one (spatially delocalized) degree of freedom. This nonlocality is consistent with the principle of cluster decomposition for correlators of observables

  18. Surface tearing modes in tokamaks

    International Nuclear Information System (INIS)

    Takizuka, Tomonori; Kurita, Gen-ichi; Azumi, Masafumi; Takeda, Tatsuoki

    1985-10-01

    Surface tearing modes in tokamaks are studied numerically and analytically. The eigenvalue problem is solved to obtain the growth rate and the mode structure. We investigate in detail dependences of the growth rate of the m/n = 2/1 resistive MHD modes on the safety factor at the plasma surface, current profile, wall position, and resistivity. The surface tearing mode moves the plasma surface even when the wall is close to the surface. The stability diagram for these modes is presented. (author)

  19. Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Obmolova, Galina; Teplyakov, Alexey; Malia, Thomas J.; Wunderler, Nicole; Kwok, Deborah; Barone, Linda; Sweet, Raymond; Ort, Tatiana; Scully, Michael; Gilliland, Gary L. (Janssen)

    2017-03-01

    CD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-κB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent. To identify the epitopes, we determined the crystal structure of the ternary complex between CD27 and the Fab fragments of these non-competing antibodies. The structure reveals the binding modes of the antibodies suggesting that their mechanisms of action are distinctly different and provides a possible explanation of the in vivo data.

  20. Revealing a steroid receptor ligand as a unique PPAR[gamma] agonist

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Shengchen; Han, Ying; Shi, Yuzhe; Rong, Hui; Zheng, Songyang; Jin, Shikan; Lin, Shu-Yong; Lin, Sheng-Cai; Li, Yong (Pitt); (Xiamen)

    2012-06-28

    Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPAR{gamma} agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPAR{gamma} target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPAR{gamma} ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPAR{gamma} ligands in the treatment of insulin resistance.

  1. Common and distinct components in data fusion

    DEFF Research Database (Denmark)

    Smilde, Age Klaas; Mage, Ingrid; Næs, Tormod

    2016-01-01

    and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework and some practical examples are given...

  2. Knowledge Affords Distinctive Processing in Memory

    Science.gov (United States)

    Hunt, R. Reed; Rawson, Katherine A.

    2011-01-01

    The effect of knowledge on memory generally is processing. However, both conceptual and empirical reasons exist to suspect that the organizational account is incomplete. Recently a revised version of that account has been proposed under the rubric of distinctiveness theory (Rawson & Van Overschelde, 2008). The goal of the experiments reported…

  3. Distinctiveness of Saudi Arabian EFL Learners

    Science.gov (United States)

    Habbash, Manssour; Idapalapati, Srinivasa Rao

    2016-01-01

    In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs…

  4. The Integrated Mode Management Interface

    Science.gov (United States)

    Hutchins, Edwin

    1996-01-01

    Mode management is the processes of understanding the character and consequences of autoflight modes, planning and selecting the engagement, disengagement and transitions between modes, and anticipating automatic mode transitions made by the autoflight system itself. The state of the art is represented by the latest designs produced by each of the major airframe manufacturers, the Boeing 747-400, the Boeing 777, the McDonnell Douglas MD-11, and the Airbus A320/A340 family of airplanes. In these airplanes autoflight modes are selected by manipulating switches on the control panel. The state of the autoflight system is displayed on the flight mode annunciators. The integrated mode management interface (IMMI) is a graphical interface to autoflight mode management systems for aircraft equipped with flight management computer systems (FMCS). The interface consists of a vertical mode manager and a lateral mode manager. Autoflight modes are depicted by icons on a graphical display. Mode selection is accomplished by touching (or mousing) the appropriate icon. The IMMI provides flight crews with an integrated interface to autoflight systems for aircraft equipped with flight management computer systems (FMCS). The current version is modeled on the Boeing glass-cockpit airplanes (747-400, 757/767). It runs on the SGI Indigo workstation. A working prototype of this graphics-based crew interface to the autoflight mode management tasks of glass cockpit airplanes has been installed in the Advanced Concepts Flight Simulator of the CSSRF of NASA Ames Research Center. This IMMI replaces the devices in FMCS equipped airplanes currently known as mode control panel (Boeing), flight guidance control panel (McDonnell Douglas), and flight control unit (Airbus). It also augments the functions of the flight mode annunciators. All glass cockpit airplanes are sufficiently similar that the IMMI could be tailored to the mode management system of any modern cockpit. The IMMI does not replace the

  5. Local vibrational modes of the water dimer - Comparison of theory and experiment

    Science.gov (United States)

    Kalescky, R.; Zou, W.; Kraka, E.; Cremer, D.

    2012-12-01

    Local and normal vibrational modes of the water dimer are calculated at the CCSD(T)/CBS level of theory. The local H-bond stretching frequency is 528 cm-1 compared to a normal mode stretching frequency of just 143 cm-1. The adiabatic connection scheme between local and normal vibrational modes reveals that the lowering is due to mass coupling, a change in the anharmonicity, and coupling with the local HOH bending modes. The local mode stretching force constant is related to the strength of the H-bond whereas the normal mode stretching force constant and frequency lead to an erroneous underestimation of the H-bond strength.

  6. Examining the Distinctiveness and the Socio-Emotional Correlates of Anxious-Withdrawal and Unsociability during Early Adolescence in Finland

    Science.gov (United States)

    Ojanen, Tiina; Findley-Van Nostrand, Danielle; Bowker, Julie C.; Markovic, Andrea

    2017-01-01

    This study examined the distinctiveness of and the correlates associated with anxious-withdrawal and unsociability during early adolescence in Finland (N = 384; 12-14 years; 53% girls). As expected, confirmatory factor analyses revealed that anxious-withdrawal and unsociability were distinct and moderately positively correlated constructs. Only…

  7. Laboratory exercises on oscillation modes of pipes

    Science.gov (United States)

    Haeberli, Willy

    2009-03-01

    This paper describes an improved lab setup to study the vibrations of air columns in pipes. Features of the setup include transparent pipes which reveal the position of a movable microphone inside the pipe; excitation of pipe modes with a miniature microphone placed to allow access to the microphone stem for open, closed, or conical pipes; and sound insulation to avoid interference between different setups in a student lab. The suggested experiments on the modes of open, closed, and conical pipes, the transient response of a pipe, and the effect of pipe diameter are suitable for introductory physics laboratories, including laboratories for nonscience majors and music students, and for more advanced undergraduate laboratories. For honors students or for advanced laboratory exercises, the quantitative relation between the resonance width and damping time constant is of interest.

  8. Kinetic slow mode-type solitons

    Directory of Open Access Journals (Sweden)

    K. Baumgärtel

    2005-01-01

    Full Text Available One-dimensional hybrid code simulations are presented, carried out in order both to study solitary waves of the slow mode branch in an isotropic, collisionless, medium-β plasma (βi=0.25 and to test the fluid based soliton interpretation of Cluster observed strong magnetic depressions (Stasiewicz et al., 2003; Stasiewicz, 2004 against kinetic theory. In the simulations, a variety of strongly oblique, large amplitude, solitons are seen, including solitons with Alfvenic polarization, similar to those predicted by the Hall-MHD theory, and robust, almost non-propagating, solitary structures of slow magnetosonic type with strong magnetic field depressions and perpendicular ion heating, which have no counterpart in fluid theory. The results support the soliton-based interpretation of the Cluster observations, but reveal substantial deficiencies of Hall-MHD theory in describing slow mode-type solitons in a plasma of moderate beta.

  9. Linear stability of tearing modes

    International Nuclear Information System (INIS)

    Cowley, S.C.; Kulsrud, R.M.; Hahm, T.S.

    1986-05-01

    This paper examines the stability of tearing modes in a sheared slab when the width of the tearing layer is much smaller than the ion Larmor radius. The ion response is nonlocal, and the quasineutrality retains its full integal form. An expansion procedure is introduced to solve the quasineutrality equation in powers of the width of the tearing layer over the ion Larmor radius. The expansion procedure is applied to the collisionless and semi-collisional tearing modes. The first order terms in the expansion we find to be strongly stabilizing. The physics of the mode and of the stabilization is discussed. Tearing modes are observed in experiments even though the slab theory predicts stability. It is proposed that these modes grow from an equilibrium with islands at the rational surfaces. If the equilibrium islands are wider than the ion Larmor radius, the mode is unstable when Δ' is positive

  10. Distinct Domestication Trajectories in Top-Fermenting Beer Yeasts and Wine Yeasts.

    Science.gov (United States)

    Gonçalves, Margarida; Pontes, Ana; Almeida, Pedro; Barbosa, Raquel; Serra, Marta; Libkind, Diego; Hutzler, Mathias; Gonçalves, Paula; Sampaio, José Paulo

    2016-10-24

    Beer is one of the oldest alcoholic beverages and is produced by the fermentation of sugars derived from starches present in cereal grains. Contrary to lager beers, made by bottom-fermenting strains of Saccharomyces pastorianus, a hybrid yeast, ale beers are closer to the ancient beer type and are fermented by S. cerevisiae, a top-fermenting yeast. Here, we use population genomics to investigate (1) the closest relatives of top-fermenting beer yeasts; (2) whether top-fermenting yeasts represent an independent domestication event separate from those already described; (3) whether single or multiple beer yeast domestication events can be inferred; and (4) whether top-fermenting yeasts represent non-recombinant or recombinant lineages. Our results revealed that top-fermenting beer yeasts are polyphyletic, with a main clade composed of at least three subgroups, dominantly represented by the German, British, and wheat beer strains. Other beer strains were phylogenetically close to sake, wine, or bread yeasts. We detected genetic signatures of beer yeast domestication by investigating genes previously linked to brewing and using genome-wide scans. We propose that the emergence of the main clade of beer yeasts is related with a domestication event distinct from the previously known cases of wine and sake yeast domestication. The nucleotide diversity of the main beer clade more than doubled that of wine yeasts, which might be a consequence of fundamental differences in the modes of beer and wine yeast domestication. The higher diversity of beer strains could be due to the more intense and different selection regimes associated to brewing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Decay modes of high-lying excitations in nuclei

    International Nuclear Information System (INIS)

    Gales, S.

    1993-01-01

    Inelastic, charge-exchange and transfer reactions induced by hadronic probes at intermediate energies have revealed a rich spectrum of new high-lying modes embedded in the nuclear continuum. The investigation of their decay properties is believed to be a severe test of their microscopic structure as predicted by nuclear models. In addition the degree of damping of these simple modes in the nuclear continuum can be obtained by means of the measured branching ratios to the various decay channels as compared to statistical model calculations. As illustrative examples the decay modes of high-spin single-particle states and isovector resonances are discussed. (author) 23 refs.; 14 figs

  12. On the phase between pressure and heat release fluctuations for propane/hydrogen flames and its role in mode transitions

    KAUST Repository

    Hong, Seunghyuck; Shanbhogue, Santosh J.; Speth, Raymond L.; Ghoniem, Ahmed F.

    2013-01-01

    and preheat temperatures. The combustor exhibits distinct acoustic response and dynamic flame shape (collectively referred to as "dynamic modes") depending on the operating conditions. We simultaneously measure the dynamic pressure and flame chemiluminescence

  13. Audit mode change, corporate governance

    OpenAIRE

    Limei Cao; Wanfu Li; Limin Zhang

    2015-01-01

    This study investigates changes in audit strategy in China following the introduction of risk-based auditing standards rather than an internal control-based audit mode. Specifically, we examine whether auditors are implementing the risk-based audit mode to evaluate corporate governance before distributing audit resources. The results show that under the internal control-based audit mode, the relationship between audit effort and corporate governance was weak. However, implementation of the ri...

  14. Embarrassment: its distinct form and appeasement functions.

    Science.gov (United States)

    Keltner, D; Buswell, B N

    1997-11-01

    The authors address 2 questions about embarrassment. First, Is embarrassment a distinct emotion? The evidence indicates that the antecedents, experience, and display of embarrassment, and to a limited extent its autonomic physiology, are distinct from shame, guilt, and amusement and share the dynamic, temporal characteristics of emotion. Second, What are the theoretical accounts of embarrassment? Three accounts focus on the causes of embarrassment, positioning that it follows the loss of self-esteem, concern for others' evaluations, or absence of scripts to guide interactions. A fourth account focuses on the effects of the remedial actions of embarrassment, which correct preceding transgressions. A fifth account focuses on the functional parallels between embarrassment and nonhuman appeasement. The discussion focuses on unanswered questions about embarrassment.

  15. Distinctive skeletal dysplasia in Cockayne syndrome

    International Nuclear Information System (INIS)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-01-01

    Cockayne syndrom is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvment of the spine. (orig.)

  16. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  17. Army nurses in wartime: distinction and pride.

    Science.gov (United States)

    Higgins, L P

    1996-08-01

    Nurses have served with distinction in wartime since Florence Nightingale went to the Crimea. Women often accompanied their husbands to battle during the Revolutionary and Civil Wars, caring for the sick and wounded. Although not officially given officer status until 1920, Army nurses served in the Spanish-American War and World War I. As officers, thousands of nurses served in subsequent wars, distinguishing themselves by their heroism, devotion to duty, and sheer tenacity of spirit.

  18. Causality analysis of leading singular value decomposition modes identifies rotor as the dominant driving normal mode in fibrillation

    Science.gov (United States)

    Biton, Yaacov; Rabinovitch, Avinoam; Braunstein, Doron; Aviram, Ira; Campbell, Katherine; Mironov, Sergey; Herron, Todd; Jalife, José; Berenfeld, Omer

    2018-01-01

    Cardiac fibrillation is a major clinical and societal burden. Rotors may drive fibrillation in many cases, but their role and patterns are often masked by complex propagation. We used Singular Value Decomposition (SVD), which ranks patterns of activation hierarchically, together with Wiener-Granger causality analysis (WGCA), which analyses direction of information among observations, to investigate the role of rotors in cardiac fibrillation. We hypothesized that combining SVD analysis with WGCA should reveal whether rotor activity is the dominant driving force of fibrillation even in cases of high complexity. Optical mapping experiments were conducted in neonatal rat cardiomyocyte monolayers (diameter, 35 mm), which were genetically modified to overexpress the delayed rectifier K+ channel IKr only in one half of the monolayer. Such monolayers have been shown previously to sustain fast rotors confined to the IKr overexpressing half and driving fibrillatory-like activity in the other half. SVD analysis of the optical mapping movies revealed a hierarchical pattern in which the primary modes corresponded to rotor activity in the IKr overexpressing region and the secondary modes corresponded to fibrillatory activity elsewhere. We then applied WGCA to evaluate the directionality of influence between modes in the entire monolayer using clear and noisy movies of activity. We demonstrated that the rotor modes influence the secondary fibrillatory modes, but influence was detected also in the opposite direction. To more specifically delineate the role of the rotor in fibrillation, we decomposed separately the respective SVD modes of the rotor and fibrillatory domains. In this case, WGCA yielded more information from the rotor to the fibrillatory domains than in the opposite direction. In conclusion, SVD analysis reveals that rotors can be the dominant modes of an experimental model of fibrillation. Wiener-Granger causality on modes of the rotor domains confirms their

  19. Fermionic quasinormal modes for two-dimensional Horava-Lifshitz black holes

    Energy Technology Data Exchange (ETDEWEB)

    Stetsko, M.M. [Ivan Franko National University of Lviv, Department for Theoretical Physics, Lviv (Ukraine)

    2017-06-15

    To obtain fermionic quasinormal modes, the Dirac equation for two types of black holes is investigated. It is shown that two different geometries lead to distinctive types of quasinormal modes, while the boundary conditions imposed on the solutions in both cases are identical. For the first type of black hole, the quasinormal modes have continuous spectrum with negative imaginary part that provides the stability of perturbations. For the second type of the black hole, the quasinormal modes have a discrete spectrum and are completely imaginary. (orig.)

  20. Zero modes and entanglement entropy

    Energy Technology Data Exchange (ETDEWEB)

    Yazdi, Yasaman K. [Perimeter Institute for Theoretical Physics,31 Caroline St. N., Waterloo, ON, N2L 2Y5 (Canada); Department of Physics and Astronomy, University of Waterloo,200 University Avenue West, Waterloo, ON, N2L 3G1 (Canada)

    2017-04-26

    Ultraviolet divergences are widely discussed in studies of entanglement entropy. Also present, but much less understood, are infrared divergences due to zero modes in the field theory. In this note, we discuss the importance of carefully handling zero modes in entanglement entropy. We give an explicit example for a chain of harmonic oscillators in 1D, where a mass regulator is necessary to avoid an infrared divergence due to a zero mode. We also comment on a surprising contribution of the zero mode to the UV-scaling of the entanglement entropy.

  1. Magnetorheological dampers in shear mode

    International Nuclear Information System (INIS)

    Wereley, N M; Cho, J U; Choi, Y T; Choi, S B

    2008-01-01

    In this study, three types of shear mode damper using magnetorheological (MR) fluids are theoretically analyzed: linear, rotary drum, and rotary disk dampers. The damping performance of these shear mode MR dampers is characterized in terms of the damping coefficient, which is the ratio of the equivalent viscous damping at field-on status to the damping at field-off status. For these three types of shear mode MR damper, the damping coefficient or dynamic range is derived using three different constitutive models: the Bingham–plastic, biviscous, and Herschel–Bulkley models. The impact of constitutive behavior on shear mode MR dampers is theoretically presented and compared

  2. ELM Dynamics in TCV H-modes

    Science.gov (United States)

    Degeling, A. W.; Martin, Y. R.; Lister, J. B.; Llobet, X.; Bak, P. E.

    2003-06-01

    TCV (Tokamak à Configuration Variable, R = 0.88 m, a limited and diverted plasmas, with the primary aim of investigating the effects of plasma shape and current profile on tokamak physics and performance. L-mode to H-mode transitions are regularly obtained in TCV over a wide range of configurations. Under most conditions, the H-mode is ELM-free and terminates in a high density disruption. The conditions required for a transition to an ELMy H-mode were investigated in detail, and a reliable gateway in parameter space for the transition was identified. Once established, the ELMy H-mode is robust to changes in plasma current, elongation, divertor geometry and plasma density over ranges that are much wider than the size of the gateway in these parameters. There exists marked irregularity in the time interval between consecutive ELMs. Transient signatures in the time-series revealing the existence of an underlying chaotic dynamical system are repeatedly observed in a sizable group of discharges [1]. The properties of these signatures (called unstable periodic orbits, or UPOs) are found to vary systematically with parameters such as the plasma current, density and inner plasma — wall gap. A link has also been established between the dynamics of ELMs and sawteeth in TCV: under certain conditions a clear preference is observed in the phase between ELMs and sawtooth crashes, and the ratio of the ELM frequency (felm) to sawtooth frequency (fst) is found to prefer simple rational values (e.g. 1/1, 2/1 or 1/2). An attempt to control the ELM dynamics was made by applying a perturbation signal to the radial field coils used for vertical stabilisation. Phase synchronisation was found with the external perturbation, and felm was found to track limited scans in the driver frequency about the unperturbed value, albeit with intermittent losses in phase lock.

  3. ELM Dynamics in TCV H-modes

    International Nuclear Information System (INIS)

    Degeling, A.W.; Martin, Y.R.; Lister, J.B.; Llobet, X.; Bak, P.E.

    2003-01-01

    TCV (Tokamak a Configuration Variable, R = 0.88 m, a < 0.25 m, BT < 1.54 T) is a highly elongated tokamak, capable of producing limited and diverted plasmas, with the primary aim of investigating the effects of plasma shape and current profile on tokamak physics and performance. L-mode to H-mode transitions are regularly obtained in TCV over a wide range of configurations. Under most conditions, the H-mode is ELM-free and terminates in a high density disruption. The conditions required for a transition to an ELMy H-mode were investigated in detail, and a reliable gateway in parameter space for the transition was identified. Once established, the ELMy H-mode is robust to changes in plasma current, elongation, divertor geometry and plasma density over ranges that are much wider than the size of the gateway in these parameters. There exists marked irregularity in the time interval between consecutive ELMs. Transient signatures in the time-series revealing the existence of an underlying chaotic dynamical system are repeatedly observed in a sizable group of discharges [1]. The properties of these signatures (called unstable periodic orbits, or UPOs) are found to vary systematically with parameters such as the plasma current, density and inner plasma -- wall gap. A link has also been established between the dynamics of ELMs and sawteeth in TCV: under certain conditions a clear preference is observed in the phase between ELMs and sawtooth crashes, and the ratio of the ELM frequency (felm) to sawtooth frequency (fst) is found to prefer simple rational values (e.g. 1/1, 2/1 or 1/2). An attempt to control the ELM dynamics was made by applying a perturbation signal to the radial field coils used for vertical stabilisation. Phase synchronisation was found with the external perturbation, and felm was found to track limited scans in the driver frequency about the unperturbed value, albeit with intermittent losses in phase lock

  4. Ballooning modes or Fourier modes in a toroidal plasma?

    International Nuclear Information System (INIS)

    Connor, J.W.; Taylor, J.B.

    1987-01-01

    The relationship between two different descriptions of eigenmodes in a torus is investigated. In one the eigenmodes are similar to Fourier modes in a cylinder and are highly localized near a particular rational surface. In the other they are the so-called ballooning modes that extend over many rational surfaces. Using a model that represents both drift waves and resistive interchanges the transition from one of these structures to the other is investigated. In this simplified model the transition depends on a single parameter which embodies the competition between toroidal coupling of Fourier modes (which enhances ballooning) and variation in frequency of Fourier modes from one rational surface to another (which diminishes ballooning). As the coupling is increased each Fourier mode acquires a sideband on an adjacent rational surface and these sidebands then expand across the radius to form the extended mode described by the conventional ballooning mode approximation. This analysis shows that the ballooning approximation is appropriate for drift waves in a tokamak but not for resistive interchanges in a pinch. In the latter the conventional ballooning effect is negligible but they may nevertheless show a ballooning feature. This is localized near the same rational surface as the primary Fourier mode and so does not lead to a radially extended structure

  5. Mode Selection in Flame-Vortex driven Combustion Instabilities

    KAUST Repository

    Speth, Ray

    2011-01-04

    In this paper, we investigate flame-vortex interaction in a lean premixed, laboratory scale, backward-facing step combustor. Two series of tests were conducted, using propane/hydrogen mixtures and carbon monoxide/hydrogen mixtures as fuels, respectively. Pressure measurements and high speed particle imaging velocimetry (PIV) were employed to generate pressure response curves as well as the images of the velocity field and the flame brush. We demonstrate that the step combustor exhibits several operating modes depending on the inlet conditions and fuel composition, characterized by the amplitude and frequency of pressure oscillations along with distinct dynamic flame shapes. We propose a model in which the combustor\\'s selection of the acoustic mode is governed by a combustion-related time delay inversely proportional to the flame speed. Our model predicts the transition between distinct operating modes. We introduce non-dimensional parameters characterizing the flame speed and stretch rate, and develop a relationship between these quantities at the operating conditions corresponding to each mode transition. Based on this relationship, we show that numerically-calculated density-weighted strained flame speed can be used to collapse the combustion dynamics data over the full range of conditions (inlet temperature, fuel composition, and equivalence ratio). Finally, we validate our strain flame based model by measuring the strain rate using the flame image and the velocity field from the PIV measurement. Our results show that the measured strain rates lie in the same range as the critical values at the transitions among distinct modes as those predicted by our model.

  6. Physical characterization of diesel exhaust nucleation mode particles

    Energy Technology Data Exchange (ETDEWEB)

    Lahde, T.

    2013-11-01

    An increasing concern of the adverse health effects of aerosol particles is forcing the combustion engine industry to develop engines with lower particle emissions. The industry has put most of their efforts into soot control and has achieved a significant reduction in diesel exhaust particle mass. Nevertheless, it is not clear that the large particles, dominating the mass, cause the harmfulness of the exhaust particles in the biological interaction. Nowadays, the harmful potential of diesel exhaust particles often connects with the particle surface area, and the view has turned to particle number below 100 nm size range. Unfortunately, the achieved low exhaust particle mass does not necessarily imply a low particle number. This text focuses on the physical characteristics of diesel exhaust nucleation model particles. The volatility characteristics and the electrical charge state of the particles are studied first. Second, the relation between the nonvolatile nucleation mode emissions and the soot, the nitrogen oxide (NO{sub x}) emissions and the engine parameters are covered. The nucleation mode particles had distinctively different physical characteristics with different after-treatment systems. The nucleation mode was volatile and electrically neutral with a diesel particle filter after-treatment system. Without an after-treatment system or with an after-treatment system with low particle removal efficiency, the nucleation mode was partly nonvolatile and included an electrical charge. The difference suggests different formation routes for the nucleation particles with different after-treatment systems. The existence of the nonvolatile nucleation mode particles also affected the soot mode charge state. The soot charge state was positively biased when the nonvolatile nucleation mode was detected but slightly negatively biased when the nonvolatile nucleation mode was absent. The nonvolatile nucleation mode was always negatively biased. This electrical charge

  7. A new class of g-modes in neutron stars

    Science.gov (United States)

    Reisenegger, Andreas; Goldreich, Peter

    1992-01-01

    Because a neutron star is born hot, its internal composition is close to chemical equilibrium. In the fluid core, this implies that the ratio of the number densities of charged particles (protons and electrons) to neutrons is an increasing function of the mass density. This composition gradient stably stratifies the matter giving rise to a Brunt-Vaisala frequency N of about 500/s. Consequently, a neutron star core provides a cavity that supports gravity modes (g-modes). These g-modes are distinct from those previously identified with the thermal stratification of the surface layers and the chemical stratification of the crust. We compute the lowest-order, quadrupolar, g-modes for cold, Newtonian, neutron star models with M/solar M = 0.581 and M/solar M = 1.405, and show that the crustal and core g-modes have similar periods. We also discuss damping mechanisms and estimate damping rates for the core g-modes. Particular attention is paid to damping due to the emission of gravitational radiation.

  8. Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight

    Directory of Open Access Journals (Sweden)

    Natalia Zamorano Cuervo

    2018-01-01

    Full Text Available The mitochondrial antiviral signaling (MAVS adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondrial-associated endoplasmic reticulum membranes. Structural and functional studies have revealed that MAVS activity relies on the formation of functional high molecular weight prion-like aggregates. The formation of protein aggregates typically relies on a dynamic transition between oligomerization and aggregation states. The existence of intermediate state(s of MAVS polymers, other than aggregates, has not yet been documented. Here, we used a combination of non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE to resolve whole cell extract preparations to distinguish MAVS polymerization states. While SDD-AGE analysis of whole cell extracts revealed the formation of previously described high molecular weight prion-like aggregates upon constitutively active RIG-I ectopic expression and virus infection, non-reducing SDS-PAGE allowed us to demonstrate the induction of lower molecular weight oligomers. Cleavage of MAVS using the NS3/4A protease revealed that anchoring to intracellular membranes is required for the appropriate polymerization into active high molecular weight aggregates. Altogether, our data suggest that RIG-I-dependent MAVS activation involves the coexistence of MAVS polymers with distinct molecular weights.

  9. Maternal mode of living and child health

    Directory of Open Access Journals (Sweden)

    Jane L.G. Dytz

    2002-02-01

    Full Text Available ln this article, maternal mode of living is investigated, examining both socioeconomic conditions and lifestyle factors, in order to identify to what extent health policies are tangibly meeting the needs of low income Brazilian mothers and children. Data are derived from unstructured interviews with 17 mothers with children underage 6, residing in the Federal District, Brazil. Their stories reveal a life marked by economic difficulties and inadequate living conditions, aggravated by early reproductive behavior, confinement to the home and no leisure. Although they have access to primary health care, the quality is inadequate. Increased awareness to the mother's situation is necessary in order to improve the health of young children.

  10. Spatial-mode switchable ring fiber laser based on low mode-crosstalk all-fiber mode MUX/DEMUX

    Science.gov (United States)

    Ren, Fang; Yu, Jinyi; Wang, Jianping

    2018-05-01

    We report an all-fiber ring laser that emits linearly polarized (LP) modes based on the intracavity all-fiber mode multiplexer/demultiplexer (MUX/DEMUX). Multiple LP modes in ring fiber laser are generated by taking advantage of mode MUX/DEMUX. The all-fiber mode MUX/DEMUX are composed of cascaded mode-selective couplers (MSCs). The output lasing mode of the ring fiber laser can be switched among the three lowest-order LP modes by employing combination of a mode MUX and a simple N × 1 optical switch. The slope efficiencies, optical spectra and mode profiles are measured.

  11. Development of the Modes of Collaboration framework

    Science.gov (United States)

    Pawlak, Alanna; Irving, Paul W.; Caballero, Marcos D.

    2018-01-01

    Group work is becoming increasingly common in introductory physics classrooms. Understanding how students engage in these group learning environments is important for designing and facilitating productive learning opportunities for students. We conducted a study in which we collected video of groups of students working on conceptual electricity and magnetism problems in an introductory physics course. In this setting, students needed to negotiate a common understanding and coordinate group decisions in order to complete the activity successfully. We observed students interacting in several distinct ways while solving these problems. Analysis of these observations focused on identifying the different ways students interacted and articulating what defines and distinguishes them, resulting in the development of the modes of collaboration framework. The modes of collaboration framework defines student interactions along three dimensions: social, discursive, and disciplinary content. This multidimensional approach offers a unique lens through which to consider group work and provides a flexibility that could allow the framework to be adapted for a variety of contexts. We present the framework and several examples of its application here.

  12. A versatile setup for ultrafast broadband optical spectroscopy of coherent collective modes in strongly correlated quantum systems

    Directory of Open Access Journals (Sweden)

    Edoardo Baldini

    2016-11-01

    Full Text Available A femtosecond pump-probe setup is described that is optimised for broadband transient reflectivity experiments on solid samples over a wide temperature range. By combining high temporal resolution and a broad detection window, this apparatus can investigate the interplay between coherent collective modes and high-energy electronic excitations, which is a distinctive characteristic of correlated electron systems. Using a single-shot readout array detector at frame rates of 10 kHz allows resolving coherent oscillations with amplitudes <10−4. We demonstrate its operation on the charge-transfer insulator La2CuO4, revealing coherent phonons with frequencies up to 13 THz and providing access into their Raman matrix elements.

  13. Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

    Science.gov (United States)

    Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

    2018-05-01

    Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.

  14. Fuel-coolant interactions in a jet contact mode

    International Nuclear Information System (INIS)

    Konishi, K.; Isozaki, M.; Imahori, S.; Kondo, S.; Furutani, A.; Brear, D.J.

    1994-01-01

    Molten fuel-coolant interactions in a jet contact mode was studied with respect to the safety of liquid-metal-cooled fast reactors (LMFRs). From a series of molten Wood's metal (melting point: 79 deg. C, density: -8400 kg/m 3 ) jet-water interaction experiments, several distinct modes of interaction behaviors were observed for various combinations of initial temperature conditions of the two fluids. A semi-empirical model for a minimum film boiling temperature criterion was developed and used to reasonably explain the different interaction modes. It was concluded that energetic jet-water interactions are only possible under relatively narrow initial thermal conditions. Preliminary extrapolation of the present results in an oxide fuel-sodium system suggests that mild interactions with short breakup length and coolable debris formation should be most likely in LMFRs. (author)

  15. Generation of high order modes

    CSIR Research Space (South Africa)

    Ngcobo, S

    2012-07-01

    Full Text Available with the location of the Laguerre polynomial zeros. The Diffractive optical element is used to shape the TEM00 Gassian beam and force the laser to operate on a higher order TEMp0 Laguerre-Gaussian modes or high order superposition of Laguerre-Gaussian modes...

  16. Homogeneous modes of cosmological instantons

    Energy Technology Data Exchange (ETDEWEB)

    Gratton, Steven; Turok, Neil

    2001-06-15

    We discuss the O(4) invariant perturbation modes of cosmological instantons. These modes are spatially homogeneous in Lorentzian spacetime and thus not relevant to density perturbations. But their properties are important in establishing the meaning of the Euclidean path integral. If negative modes are present, the Euclidean path integral is not well defined, but may nevertheless be useful in an approximate description of the decay of an unstable state. When gravitational dynamics is included, counting negative modes requires a careful treatment of the conformal factor problem. We demonstrate that for an appropriate choice of coordinate on phase space, the second order Euclidean action is bounded below for normalized perturbations and has a finite number of negative modes. We prove that there is a negative mode for many gravitational instantons of the Hawking-Moss or Coleman{endash}De Luccia type, and discuss the associated spectral flow. We also investigate Hawking-Turok constrained instantons, which occur in a generic inflationary model. Implementing the regularization and constraint proposed by Kirklin, Turok and Wiseman, we find that those instantons leading to substantial inflation do not possess negative modes. Using an alternate regularization and constraint motivated by reduction from five dimensions, we find a negative mode is present. These investigations shed new light on the suitability of Euclidean quantum gravity as a potential description of our universe.

  17. Homogeneous modes of cosmological instantons

    International Nuclear Information System (INIS)

    Gratton, Steven; Turok, Neil

    2001-01-01

    We discuss the O(4) invariant perturbation modes of cosmological instantons. These modes are spatially homogeneous in Lorentzian spacetime and thus not relevant to density perturbations. But their properties are important in establishing the meaning of the Euclidean path integral. If negative modes are present, the Euclidean path integral is not well defined, but may nevertheless be useful in an approximate description of the decay of an unstable state. When gravitational dynamics is included, counting negative modes requires a careful treatment of the conformal factor problem. We demonstrate that for an appropriate choice of coordinate on phase space, the second order Euclidean action is bounded below for normalized perturbations and has a finite number of negative modes. We prove that there is a negative mode for many gravitational instantons of the Hawking-Moss or ColemanendashDe Luccia type, and discuss the associated spectral flow. We also investigate Hawking-Turok constrained instantons, which occur in a generic inflationary model. Implementing the regularization and constraint proposed by Kirklin, Turok and Wiseman, we find that those instantons leading to substantial inflation do not possess negative modes. Using an alternate regularization and constraint motivated by reduction from five dimensions, we find a negative mode is present. These investigations shed new light on the suitability of Euclidean quantum gravity as a potential description of our universe

  18. Intelligence and musical mode preference

    DEFF Research Database (Denmark)

    Bonetti, Leonardo; Costa, Marco

    2016-01-01

    The relationship between fluid intelligence and preference for major–minor musical mode was investigated in a sample of 80 university students. Intelligence was assessed by the Raven’s Advanced Progressive Matrices. Musical mode preference was assessed by presenting 14 pairs of musical stimuli...... differences at the cognitive and personality level related to the enjoyment of sad music....

  19. Two Distinct Moral Mechanisms for Ascribing and Denying Intentionality.

    Science.gov (United States)

    Ngo, Lawrence; Kelly, Meagan; Coutlee, Christopher G; Carter, R McKell; Sinnott-Armstrong, Walter; Huettel, Scott A

    2015-12-04

    Philosophers and legal scholars have long theorized about how intentionality serves as a critical input for morality and culpability, but the emerging field of experimental philosophy has revealed a puzzling asymmetry. People judge actions leading to negative consequences as being more intentional than those leading to positive ones. The implications of this asymmetry remain unclear because there is no consensus regarding the underlying mechanism. Based on converging behavioral and neural evidence, we demonstrate that there is no single underlying mechanism. Instead, two distinct mechanisms together generate the asymmetry. Emotion drives ascriptions of intentionality for negative consequences, while the consideration of statistical norms leads to the denial of intentionality for positive consequences. We employ this novel two-mechanism model to illustrate that morality can paradoxically shape judgments of intentionality. This is consequential for mens rea in legal practice and arguments in moral philosophy pertaining to terror bombing, abortion, and euthanasia among others.

  20. Two Distinct Moral Mechanisms for Ascribing and Denying Intentionality

    Science.gov (United States)

    Ngo, Lawrence; Kelly, Meagan; Coutlee, Christopher G.; Carter, R. McKell; Sinnott-Armstrong, Walter; Huettel, Scott A.

    2015-01-01

    Philosophers and legal scholars have long theorized about how intentionality serves as a critical input for morality and culpability, but the emerging field of experimental philosophy has revealed a puzzling asymmetry. People judge actions leading to negative consequences as being more intentional than those leading to positive ones. The implications of this asymmetry remain unclear because there is no consensus regarding the underlying mechanism. Based on converging behavioral and neural evidence, we demonstrate that there is no single underlying mechanism. Instead, two distinct mechanisms together generate the asymmetry. Emotion drives ascriptions of intentionality for negative consequences, while the consideration of statistical norms leads to the denial of intentionality for positive consequences. We employ this novel two-mechanism model to illustrate that morality can paradoxically shape judgments of intentionality. This is consequential for mens rea in legal practice and arguments in moral philosophy pertaining to terror bombing, abortion, and euthanasia among others. PMID:26634909

  1. Metal transport across biomembranes: emerging models for a distinct chemistry.

    Science.gov (United States)

    Argüello, José M; Raimunda, Daniel; González-Guerrero, Manuel

    2012-04-20

    Transition metals are essential components of important biomolecules, and their homeostasis is central to many life processes. Transmembrane transporters are key elements controlling the distribution of metals in various compartments. However, due to their chemical properties, transition elements require transporters with different structural-functional characteristics from those of alkali and alkali earth ions. Emerging structural information and functional studies have revealed distinctive features of metal transport. Among these are the relevance of multifaceted events involving metal transfer among participating proteins, the importance of coordination geometry at transmembrane transport sites, and the presence of the largely irreversible steps associated with vectorial transport. Here, we discuss how these characteristics shape novel transition metal ion transport models.