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Sample records for adp-glucose pyrophosphorylase uncovered

  1. Multiple forms of ADP-glucose pyrophosphorylase from tomato fruit

    Science.gov (United States)

    Chen, B. Y.; Janes, H. W.

    1997-01-01

    ADP-glucose pyrophosphorylase (AGP) was purified from tomato (Lycopersicon esculentum Mill.) fruit to apparent homogeneity. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis the enzyme migrated as two close bands with molecular weights of 50,000 and 51,000. Two-dimensional polyacrylamide gel electrophoresis analysis of the purified enzyme, however, revealed at least five major protein spots that could be distinguished by their slight differences in net charge and molecular weight. Whereas all of the spots were recognized by the antiserum raised against tomato fruit AGP holoenzyme, only three of them reacted strongly with antiserum raised against the potato tuber AGP large subunit, and the other two spots (with lower molecular weights) reacted specifically with antisera raised against spinach leaf AGP holoenzyme and the potato tuber AGP small subunit. The results suggest the existence of at least three isoforms of the AGP large subunit and two isoforms of the small subunit in tomato fruit in vivo. The native molecular mass of the enzyme determined by gel filtration was 220 +/- 10 kD, indicating a tetrameric structure for AGP from tomato fruit. The purified enzyme is very sensitive to 3-phosphoglycerate/inorganic phosphate regulation.

  2. ADP-Glucose Pyrophosphorylase, a Regulatory Enzyme for Bacterial Glycogen Synthesis

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    Ballicora, Miguel A; Iglesias, Alberto A.; Preiss, Jack

    2003-01-01

    The accumulation of α-1,4-polyglucans is an important strategy to cope with transient starvation conditions in the environment. In bacteria and plants, the synthesis of glycogen and starch occurs by utilizing ADP-glucose as the glucosyl donor for elongation of the α-1,4-glucosidic chain. The main regulatory step takes place at the level of ADP-glucose synthesis, a reaction catalyzed by ADP-Glc pyrophosphorylase (PPase). Most of the ADP-Glc PPases are allosterically regulated by intermediates ...

  3. Activation of the Potato Tuber ADP-glucose Pyrophosphorylase by Thioredoxin

    OpenAIRE

    Ballicora, Miguel A.; Frueauf, Jeremiah B.; Fu, Yingbin; Schürmann, Peter; Preiss, Jack

    2007-01-01

    The potato tuber (Solanum tuberosum L.) ADP-glucose pyrophosphorylase (ADP-GlcPPase) catalyzes the first committed step in starch biosynthesis. The main type of regulation of this enzyme is allosteric, and its activity is controlled by the ratio of activator, 3-phosphoglycerate to inhibitor, Pi. It was reported (Fu, Y., Ballicora, M. A., Leykam, J. F., and Preiss, J. (1998) J. Biol. Chem. 273, 25045-25052) that the enzyme was activated by reduction of the Cys12 disulfide linkage present in t...

  4. Regulatory properties of potato-Arabidopsis hybrid ADP-glucose pyrophosphorylase.

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    Ventriglia, Tiziana; Ballicora, Miguel A; Crevillén, Pedro; Preiss, Jack; Romero, José M

    2007-06-01

    In higher plants, ADP-glucose pyrophosphorylase (ADPGlc-PPase) is a heterotetrameric enzyme comprised of two small and two large subunits. Potato-Arabidopsis hybrid ADPGlc-PPases were generated and their regulatory properties analyzed. We show that ADPGlc-PPase subunits from two different species can interact, producing active enzymes with new regulatory properties. Depending on the subunit combinations, hybrid heterotetramers showed responses to allosteric effectors [3-phosphoglycerate (3-PGA) and Pi] in the micromolar or millimolar range. While hybrid potato small subunit (PSS) and the Arabidopsis large subunit APL1 showed an extremely sensitive response to 3-PGA and Pi, hybrid PSS/Arabidopsis APL2 was very insensitive to them. Intermediate responses were determined for other subunit combinations. PMID:17452341

  5. Substrate binding properties of potato tuber ADP-glucose pyrophosphorylase as determined by isothermal titration calorimetry.

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    Cakir, Bilal; Tuncel, Aytug; Green, Abigail R; Koper, Kaan; Hwang, Seon-Kap; Okita, Thomas W; Kang, ChulHee

    2015-06-01

    Substrate binding properties of the large (LS) and small (SS) subunits of potato tuber ADP-glucose pyrophosphorylase were investigated by using isothermal titration calorimetry. Our results clearly show that the wild type heterotetramer (S(WT)L(WT)) possesses two distinct types of ATP binding sites, whereas the homotetrameric LS and SS variant forms only exhibited properties of one of the two binding sites. The wild type enzyme also exhibited significantly increased affinity to this substrate compared to the homotetrameric enzyme forms. No stable binding was evident for the second substrate, glucose-1-phosphate, in the presence or absence of ATPγS suggesting that interaction of glucose-1-phosphate is dependent on hydrolysis of ATP and supports the Theorell-Chance bi bi reaction mechanism. PMID:25953126

  6. PCR cloning and characterization of multiple ADP-glucose pyrophosphorylase cDNAs from tomato

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    Chen, B. Y.; Janes, H. W.; Gianfagna, T.

    1998-01-01

    Four ADP-glucose pyrophosphorylase (AGP) cDNAs were cloned from tomato fruit and leaves by the PCR techniques. Three of them (agp S1, agp S2, and agp S3) encode the large subunit of AGP, the fourth one (agp B) encodes the small subunit. The deduced amino acid sequences of the cDNAs show very high identities (96-98%) to the corresponding potato AGP isoforms, although there are major differences in tissue expression profiles. All four tomato AGP transcripts were detected in fruit and leaves; the predominant ones in fruit are agp B and agp S1, whereas in leaves they are agp B and agp S3. Genomic southern analysis suggests that the four AGP transcripts are encoded by distinct genes.

  7. Molecular characterization of multiple cDNA clones for ADP-glucose pyrophosphorylase from Arabidopsis thaliana.

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    Villand, P; Olsen, O A; Kleczkowski, L A

    1993-12-01

    PCR amplification of cDNA prepared from poly(A)+ RNA from aerial parts of Arabidopsis thaliana, using degenerate nucleotide primers based on conserved regions between the large and small subunits of ADP-glucose pyrophosphorylase (AGP), yielded four different cDNAs of ca. 550 nucleotides each. Based on derived amino acid sequences, the identities between the clones varied from 49 to 69%. Sequence comparison to previously published cDNAs for AGP from various species and tissues has revealed that three of the amplified cDNAs (ApL1, ApL2 and ApL3) correspond to the large subunit of AGP, and one cDNA (ApS) encodes the small subunit of AGP. Both ApL1 and ApS were subsequently found to be present in a cDNA library made from Arabidopsis leaves. All four PCR products are encoded by single genes, as found by genomic Southern analysis. PMID:8292792

  8. Two Arabidopsis ADP-glucose pyrophosphorylase large subunits (APL1 and APL2) are catalytic.

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    Ventriglia, Tiziana; Kuhn, Misty L; Ruiz, Ma Teresa; Ribeiro-Pedro, Marina; Valverde, Federico; Ballicora, Miguel A; Preiss, Jack; Romero, José M

    2008-09-01

    ADP-glucose (Glc) pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed step in starch biosynthesis. Higher plant ADP-Glc PPase is a heterotetramer (alpha(2)beta(2)) consisting of two small and two large subunits. There is increasing evidence that suggests that catalytic and regulatory properties of the enzyme from higher plants result from the synergy of both types of subunits. In Arabidopsis (Arabidopsis thaliana), two genes encode small subunits (APS1 and APS2) and four large subunits (APL1-APL4). Here, we show that in Arabidopsis, APL1 and APL2, besides their regulatory role, have catalytic activity. Heterotetramers formed by combinations of a noncatalytic APS1 and the four large subunits showed that APL1 and APL2 exhibited ADP-Glc PPase activity with distinctive sensitivities to the allosteric activator (3-phosphoglycerate). Mutation of the Glc-1-P binding site of Arabidopsis and potato (Solanum tuberosum) isoforms confirmed these observations. To determine the relevance of these activities in planta, a T-DNA mutant of APS1 (aps1) was characterized. aps1 is starchless, lacks ADP-Glc PPase activity, APS1 mRNA, and APS1 protein, and is late flowering in long days. Transgenic lines of the aps1 mutant, expressing an inactivated form of APS1, recovered the wild-type phenotype, indicating that APL1 and APL2 have catalytic activity and may contribute to ADP-Glc synthesis in planta. PMID:18614708

  9. Two Arabidopsis ADP-Glucose Pyrophosphorylase Large Subunits (APL1 and APL2) Are Catalytic1

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    Ventriglia, Tiziana; Kuhn, Misty L.; Ruiz, Ma Teresa; Ribeiro-Pedro, Marina; Valverde, Federico; Ballicora, Miguel A.; Preiss, Jack; Romero, José M.

    2008-01-01

    ADP-glucose (Glc) pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed step in starch biosynthesis. Higher plant ADP-Glc PPase is a heterotetramer (α2β2) consisting of two small and two large subunits. There is increasing evidence that suggests that catalytic and regulatory properties of the enzyme from higher plants result from the synergy of both types of subunits. In Arabidopsis (Arabidopsis thaliana), two genes encode small subunits (APS1 and APS2) and four large subunits (APL1–APL4). Here, we show that in Arabidopsis, APL1 and APL2, besides their regulatory role, have catalytic activity. Heterotetramers formed by combinations of a noncatalytic APS1 and the four large subunits showed that APL1 and APL2 exhibited ADP-Glc PPase activity with distinctive sensitivities to the allosteric activator (3-phosphoglycerate). Mutation of the Glc-1-P binding site of Arabidopsis and potato (Solanum tuberosum) isoforms confirmed these observations. To determine the relevance of these activities in planta, a T-DNA mutant of APS1 (aps1) was characterized. aps1 is starchless, lacks ADP-Glc PPase activity, APS1 mRNA, and APS1 protein, and is late flowering in long days. Transgenic lines of the aps1 mutant, expressing an inactivated form of APS1, recovered the wild-type phenotype, indicating that APL1 and APL2 have catalytic activity and may contribute to ADP-Glc synthesis in planta. PMID:18614708

  10. Sucrose regulation of ADP-glucose pyrophosphorylase subunit genes transcript levels in leaves and fruits

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    Li, Xiangyang; Xing, Jinpeng; Gianfagna, Thomas J.; Janes, Harry W.

    2002-01-01

    ADP-glucose pyrophosphorylase (AGPase, EC2.7.7.27) is a key regulatory enzyme in starch biosynthesis. The enzyme is a heterotetramer with two S and two B subunits. In tomato, there are three multiple forms of the S subunit gene. Agp S1, S2 and B are highly expressed in fruit from 10 to 25 days after anthesis. Agp S3 is only weakly expressed in fruit. Sucrose significantly elevates expression of Agp S1, S2 and B in both leaves and fruits. Agp S1 exhibits the highest degree of regulation by sucrose. In fact, sucrose may be required for Agp S1 expression. For excised leaves incubated in water, no transcripts for Agp S1 could be detected in the absence of sucrose, whereas it took up to 16 h in water before transcripts were no longer detectable for Agp S2 and B. Neither Agp S3 nor the tubulin gene is affected by sucrose, demonstrating that this response is specifically regulated by a carbohydrate metabolic signal, and is not due to a general increase in metabolism caused by sucrose treatment. Truncated versions of the promoter for Agp S1 indicate that a specific region 1.3-3.0 kb upstream from the transcription site is responsible for sucrose sensitivity. This region of the S1 promoter contains several cis-acting elements present in the promoters of other genes that are also regulated by sucrose. c2002 Elsevier Science Ireland Ltd. All rights reserved.

  11. Investigation of the interaction between the large and small subunits of potato ADP-glucose pyrophosphorylase.

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    Ibrahim Baris

    2009-10-01

    Full Text Available ADP-glucose pyrophosphorylase (AGPase, a key allosteric enzyme involved in higher plant starch biosynthesis, is composed of pairs of large (LS and small subunits (SS. Current evidence indicates that the two subunit types play distinct roles in enzyme function. Recently the heterotetrameric structure of potato AGPase has been modeled. In the current study, we have applied the molecular mechanics generalized born surface area (MM-GBSA method and identified critical amino acids of the potato AGPase LS and SS subunits that interact with each other during the native heterotetrameric structure formation. We have further shown the role of the LS amino acids in subunit-subunit interaction by yeast two-hybrid, bacterial complementation assay and native gel. Comparison of the computational results with the experiments has indicated that the backbone energy contribution (rather than the side chain energies of the interface residues is more important in identifying critical residues. We have found that lateral interaction of the LS-SS is much stronger than the longitudinal one, and it is mainly mediated by hydrophobic interactions. This study will not only enhance our understanding of the interaction between the SS and the LS of AGPase, but will also enable us to engineer proteins to obtain better assembled variants of AGPase which can be used for the improvement of plant yield.

  12. The different large subunit isoforms of Arabidopsis thaliana ADP-glucose pyrophosphorylase confer distinct kinetic and regulatory properties to the heterotetrameric enzyme.

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    Crevillén, Pedro; Ballicora, Miguel A; Mérida, Angel; Preiss, Jack; Romero, José M

    2003-08-01

    ADP-glucose pyrophosphorylase catalyzes the first and limiting step in starch biosynthesis and is allosterically regulated by the levels of 3-phosphoglycerate and phosphate in plants. ADP-glucose pyrophosphorylases from plants are heterotetramers composed of two types of subunits (small and large). In this study, the six Arabidopsis thaliana genes coding for ADP-glucose pyrophosphorylase isoforms (two small and four large subunits) have been cloned and expressed in an Escherichia coli mutant deficient in ADP-glucose pyrophosphorylase activity. The co-expression of the small subunit APS1 with the different Arabidopsis large subunits (APL1, APL2, APL3, and APL4) resulted in heterotetramers with different regulatory and kinetic properties. Heterotetramers composed of APS1 and APL1 showed the highest sensitivity to the allosteric effectors as well as the highest apparent affinity for the substrates (glucose-1-phosphate and ATP), whereas heterotetramers formed by APS1 and APL2 showed the lower response to allosteric effectors and the lower affinity for the substrates. No activity was detected for the second gene coding for a small subunit isoform (APS2) annotated in the Arabidopsis genome. This lack of activity is possibly due to the absence of essential amino acids involved in catalysis and/or in the binding of glucose-1-phosphate and 3-phosphoglycerate. Kinetic and regulatory properties of the different heterotetramers, together with sequence analysis has allowed us to make a distinction between sink and source enzymes, because the combination of different large subunits would provide a high plasticity to ADP-glucose pyrophosphorylase activity and regulation. This is the first experimental data concerning the role that all the ADP-glucose pyrophosphorylase isoforms play in a single plant species. This phenomenon could have an important role in vivo, because different large subunits would confer distinct regulatory properties to ADP-glucose pyrophosphorylase according

  13. The ancestral activation promiscuity of ADP-glucose pyrophosphorylases from oxygenic photosynthetic organisms

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    Kuhn Misty L

    2013-02-01

    Full Text Available Abstract Background ADP-glucose pyrophosphorylase (ADP-Glc PPase catalyzes the first committed step in the synthesis of glycogen in bacteria and starch in algae and plants. In oxygenic photosynthetic organisms, ADP-Glc PPase is mainly activated by 3-phosphoglycerate (3-PGA and to a lesser extent by other metabolites. In this work, we analyzed the activation promiscuity of ADP-Glc PPase subunits from the cyanobacterium Anabaena PCC 7120, the green alga Ostreococcus tauri, and potato (Solanum tuberosum tuber by comparing a specificity constant for 3-PGA, fructose-1,6-bisphosphate (FBP, fructose-6-phosphate, and glucose-6-phosphate. Results The 3-PGA specificity constant for the enzymes from Anabaena (homotetramer, O. tauri, and potato tuber was considerably higher than for other activators. O. tauri and potato tuber enzymes were heterotetramers comprising homologous small and large subunits. Conversely, the O. tauri small subunit (OtaS homotetramer was more promiscuous because its FBP specificity constant was similar to that for 3-PGA. To explore the role of both OtaS and OtaL (O. tauri large subunit in determining the specificity of the heterotetramer, we knocked out the catalytic activity of each subunit individually by site-directed mutagenesis. Interestingly, the mutants OtaSD148A/OtaL and OtaS/OtaLD171A had higher specificity constants for 3-PGA than for FBP. Conclusions After gene duplication, OtaS seemed to have lost specificity for 3-PGA compared to FBP. This was physiologically and evolutionarily feasible because co-expression of both subunits restored the specificity for 3-PGA of the resulting heterotetrameric wild type enzyme. This widespread promiscuity seems to be ancestral and intrinsic to the enzyme family. Its presence could constitute an efficient evolutionary mechanism to accommodate the ADP-Glc PPase regulation to different metabolic needs.

  14. ADP-glucose pyrophosphorylase is localized to both the cytoplasm and plastids in developing pericarp of tomato fruit

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    Chen, B. Y.; Wang, Y.; Janes, H. W.

    1998-01-01

    The intracellular location of ADP-glucose pyrophosphorylase (AGP) in developing pericarp of tomato (Lycopersicon esculentum Mill) has been investigated by immunolocalization. With the use of a highly specific anti-tomato fruit AGP antibody, the enzyme was localized in cytoplasm as well as plastids at both the light and electron microscope levels. The immunogold particles in plastids were localized in the stroma and at the surface of the starch granule, whereas those in the cytoplasm occurred in cluster-like patterns. Contrary to the fruit, the labeling in tomato leaf cells occurred exclusively in the chloroplasts. These data demonstrate that AGP is localized to both the cytoplasm and plastids in developing pericarp cells of tomato.

  15. ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus.

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    Seng, Shanshan; Wu, Jian; Sui, Juanjuan; Wu, Chenyu; Zhong, Xionghui; Liu, Chen; Liu, Chao; Gong, Benhe; Zhang, Fengqin; He, Junna; Yi, Mingfang

    2016-05-20

    Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus. PMID:27107698

  16. Insights into Glycogen Metabolism in Chemolithoautotrophic Bacteria from Distinctive Kinetic and Regulatory Properties of ADP-Glucose Pyrophosphorylase from Nitrosomonas europaea

    OpenAIRE

    Machtey, Matías; Kuhn, Misty L.; Flasch, Diane A; Aleanzi, Mabel; Ballicora, Miguel A; Iglesias, Alberto A.

    2012-01-01

    Nitrosomonas europaea is a chemolithoautotroph that obtains energy by oxidizing ammonia in the presence of oxygen and fixes CO2 via the Benson-Calvin cycle. Despite its environmental and evolutionary importance, very little is known about the regulation and metabolism of glycogen, a source of carbon and energy storage. Here, we cloned and heterologously expressed the genes coding for two major putative enzymes of the glycogen synthetic pathway in N. europaea, ADP-glucose pyrophosphorylase and...

  17. [Enhancement of photoassimilate utilization by manipulation of ADP-glucose pyrophosphorylase gene]. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1999-04-01

    Part 1 of this research focuses on patterns of gene expression of ADPG-pyrophosphorylase in native and transgenic potato plants. To elucidate the mechanism controlling AGP expression during plant development, the expression of the potato tuber AGP small subunit (sAGP) gene was analyzed in transgenic potato plants using a promoter-{beta}-glucuronidase expression system. Part II evaluated the structure-function relationships of AGP.

  18. Enhanced activity of ADP glucose pyrophosphorylase and formation of starch induced by Azospirillum brasilense in Chlorella vulgaris.

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    Choix, Francisco J; Bashan, Yoav; Mendoza, Alberto; de-Bashan, Luz E

    2014-05-10

    ADP-glucose pyrophosphorylase (AGPase) regulates starch biosynthesis in higher plants and microalgae. This study measured the effect of the bacterium Azospirillum brasilense on AGPase activity in the freshwater microalga Chlorella vulgaris and formation of starch. This was done by immobilizing both microorganisms in alginate beads, either replete with or deprived of nitrogen or phosphorus and all under heterotrophic conditions, using d-glucose or Na-acetate as the carbon source. AGPase activity during the first 72h of incubation was higher in C. vulgaris when immobilized with A. brasilense. This happened simultaneously with higher starch accumulation and higher carbon uptake by the microalgae. Either carbon source had similar effects on enzyme activity and starch accumulation. Starvation either by N or P had the same pattern on AGPase activity and starch accumulation. Under replete conditions, the population of C. vulgaris immobilized alone was higher than when immobilized together, but under starvation conditions A. brasilense induced a larger population of C. vulgaris. In summary, adding A. brasilense enhanced AGPase activity, starch formation, and mitigation of stress in C. vulgaris. PMID:24576433

  19. Inhibition of the ADP-glucose pyrophosphorylase in transgenic potatoes leads to sugar-storing tubers and influences tuber formation and expression of tuber storage protein genes.

    OpenAIRE

    Müller-Röber, B; Sonnewald, U.; Willmitzer, L.

    1992-01-01

    Transgenic potato plants were created in which the expression of ADP-glucose pyrophosphorylase (AGPase) was inhibited by introducing a chimeric gene containing the coding region of one of the subunits of the AGPase linked in an antisense orientation to the CaMV 35S promoter. Partial inhibition of the AGPase enzyme was achieved in leaves and almost complete inhibition in tubers. This resulted in the abolition of starch formation in tubers, thus proving that AGPase has a unique role in starch b...

  20. Carbon Dynamics, Development and Stress Responses in Arabidopsis: Involvement of the APL4 Subunit of ADP-Glucose Pyrophosphorylase (Starch Synthesis)

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    Gouesbet, Gwenola; Ramel, Fanny; Cabello-Hurtado, Francisco; Penno, Christophe; Bechtold, Nicole; Couée, Ivan; El Amrani, Abdelhak

    2011-01-01

    An Arabidopsis thaliana T-DNA insertional mutant was identified and characterized for enhanced tolerance to the singlet-oxygen-generating herbicide atrazine in comparison to wild-type. This enhanced atrazine tolerance mutant was shown to be affected in the promoter structure and in the regulation of expression of the APL4 isoform of ADP-glucose pyrophosphorylase, a key enzyme of the starch biosynthesis pathway, thus resulting in decrease of APL4 mRNA levels. The impact of this regulatory muta...

  1. Sugars and light/dark exposure trigger differential regulation of ADP-glucose pyrophosphorylase genes in Arabidopsis thaliana (thale cress).

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    Sokolov, L N; Déjardin, A; Kleczkowski, L A

    1998-12-15

    Expression of four Arabidopsis (thale cress) genes corresponding to the small (ApS) and large subunits (ApL1, ApL2, ApL3) of ADP-glucose pyrophosphorylase (AGPase), a key enzyme of starch biosynthesis, was found to be profoundly and differentially regulated by sugar and light/dark exposures. Transcript levels of both ApL2 and ApL3, and to a lesser extent ApS, increased severalfold upon feeding sucrose or glucose to the detached leaves in the dark, whereas the mRNA content for ApL1 decreased under the same conditions. Glucose was, in general, less effective than sucrose in inducing regulation of AGPase genes, possibly due to observed limitations in its uptake when compared with sucrose uptake by detached leaves. Osmotic agents [sorbitol, poly(ethylene glycol)] had no effect on ApS, ApL2 and ApL3 transcript level, but they did mimic the effect of sucrose on ApL1 gene, suggesting that the latter is regulated by osmotic pressure rather than any particular sugar. For all the genes the sugar effect was closely mimicked by an exposure of the dark-pre-adapted leaves to the light. Under both dark and light conditions, sucrose fed to the detached leaves was found to be rapidly metabolized to hexoses and, to some extent, starch. Starch production reflected most probably an increase in substrate availability for AGPase reaction rather than being due to changes in AGPase protein content, since both the sugar feeding and light exposure had little or no effect on the activity of AGPase or on the levels of its small and large subunit proteins in leaf extracts. The data suggest tight translational or post-translational control, but they may also reflect spatial control of AGPase gene expression within a leaf. The sugar/light-dependent regulation of AGPase gene expression may represent a part of a general cellular response to the availability/allocation of carbohydrates during photosynthesis. PMID:9841881

  2. Analysis of ADP-glucose pyrophosphorylase expression during turion formation induced by abscisic acid in Spirodela polyrhiza (greater duckweed

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    Wang Wenqin

    2012-01-01

    Full Text Available Abstract Background Aquatic plants differ in their development from terrestrial plants in their morphology and physiology, but little is known about the molecular basis of the major phases of their life cycle. Interestingly, in place of seeds of terrestrial plants their dormant phase is represented by turions, which circumvents sexual reproduction. However, like seeds turions provide energy storage for starting the next growing season. Results To begin a characterization of the transition from the growth to the dormant phase we used abscisic acid (ABA, a plant hormone, to induce controlled turion formation in Spirodela polyrhiza and investigated their differentiation from fronds, representing their growth phase, into turions with respect to morphological, ultra-structural characteristics, and starch content. Turions were rich in anthocyanin pigmentation and had a density that submerged them to the bottom of liquid medium. Transmission electron microscopy (TEM of turions showed in comparison to fronds shrunken vacuoles, smaller intercellular space, and abundant starch granules surrounded by thylakoid membranes. Turions accumulated more than 60% starch in dry mass after two weeks of ABA treatment. To further understand the mechanism of the developmental switch from fronds to turions, we cloned and sequenced the genes of three large-subunit ADP-glucose pyrophosphorylases (APLs. All three putative protein and exon sequences were conserved, but the corresponding genomic sequences were extremely variable mainly due to the invasion of miniature inverted-repeat transposable elements (MITEs into introns. A molecular three-dimensional model of the SpAPLs was consistent with their regulatory mechanism in the interaction with the substrate (ATP and allosteric activator (3-PGA to permit conformational changes of its structure. Gene expression analysis revealed that each gene was associated with distinct temporal expression during turion formation. APL2 and

  3. Isolation and characterization of cDNAs and genomic DNAs encoding ADP-glucose pyrophosphorylase large and small subunits from sweet potato.

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    Zhou, Yu-Xi; Chen, Yu-Xiang; Tao, Xiang; Cheng, Xiao-Jie; Wang, Hai-Yan

    2016-04-01

    Sweet potato [Ipomoea batatas (L.) Lam.], the world's seventh most important food crop, is also a major industrial raw material for starch and ethanol production. In the plant starch biosynthesis pathway, ADP-glucose pyrophosphorylase (AGPase) catalyzes the first, rate-limiting step and plays a pivotal role in regulating this process. In spite of the importance of sweet potato as a starch source, only a few studies have focused on the molecular aspects of starch biosynthesis in sweet potato and almost no intensive research has been carried out on the AGPase gene family in this species. In this study, cDNAs encoding two small subunits (SSs) and four large subunits (LSs) of AGPase isoforms were cloned from sweet potato and the genomic organizations of the corresponding AGPase genes were elucidated. Expression pattern analysis revealed that the two SSs were constitutively expressed, whereas the four LSs displayed differential expression patterns in various tissues and at different developmental stages. Co-expression of SSs with different LSs in Escherichia coli yielded eight heterotetramers showing different catalytic activities. Interactions between different SSs and LSs were confirmed by a yeast two-hybrid experiment. Our findings provide comprehensive information about AGPase gene sequences, structures, expression profiles, and subunit interactions in sweet potato. The results can serve as a foundation for elucidation of molecular mechanisms of starch synthesis in tuberous roots, and should contribute to future regulation of starch biosynthesis to improve sweet potato starch yield. PMID:26499957

  4. Structure Function Relationships of ADP-Glucose Pyrophosphorylase and Branching Enzyme: Manipulation of Their Genes for Alteration of Starch Quanlity and Quantity

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    Jack Preiss

    2006-02-16

    Conversion of the Potato tuber ADP-glucose Pyrophopshorylase Regulatory Subunit into a Catalytic Subunit. ADP-glucose synthesis, a rate-limiting reaction in starch synthesis, is catalyzed by ADP-glucose pyrophosphorylase (ADPGlc PPase). The enzyme in plants is allosterically activated by 3-phosphoglycerate (3PGA) and inhibited by inorganic phosphate (Pi) and is composed of two subunits as a heterotetramer, a2b2. Subunit a is the catalytic subunit and subunit b is designated as the regulatory subunit.The b subunit increases the affinty of the activator for the catalytic subunit. Recent results have shown that the subunits are derived from the same ancestor subunit as the regulatory subunit can be converted to a catalytically subunit via mutation of just two amino acids. Lys44 and Thr54 in the large subunit from potato tuber were converted to the homologous catalytic subunit residues, Arg33 and Lys43. The activity of the large subunit mutants cannot be readily tested with a co-expressed wild-type small (catalytic) subunit because of the intrinsic activity of the latter. We co-expressed the regulatory-subunit mutants with SmallD145N, an inactive S subunit in which the catalytic Asp145 was mutated. The activity of the small (catalytic) subunit was reduced more than three orders of magnitude. Coexpression of the L subunit double mutant LargeK44R/T54K with SmallD145N generated an enzyme with considerable activity, 10% and 18% of the wildtype enzyme, in the ADP-glucose synthetic and pyrophosphorolytic direction, respectively. Replacement of those two residues in the small subunit by the homologous amino acids in the L subunits (mutations R33K and K43T) decreased the activity one and two orders of magnitude. The wild-type enzyme and SmallD145NLargeK44R/T54K had very similar kinetic properties indicating that the substrate site has been conserved. The fact that only two mutations in the L subunit restored enzyme activity is very strong evidence that the large subunit is

  5. Trehalose 6-phosphate regulates starch synthesis via posttranslational redox activation of ADP-glucose pyrophosphorylase

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    Kolbe, A.; Tiessen, A.; Schluepmann, H.; Paul, M; Ulrich, S; Geigenberger, P.

    2005-01-01

    Trehalose is the most widespread disaccharide in nature, occurring in bacteria, fungi, insects, and plants. Its precursor, trehalose 6-phosphate (T6P), is also indispensable for the regulation of sugar utilization and growth, but the sites of action are largely unresolved. Here we use genetic and biochemical approaches to investigate whether T6P acts to regulate starch synthesis in plastids of higher plants. Feeding of trehalose to Arabidopsis leaves led to stimulation of starch synthesis wit...

  6. Biosynthesis of bacterial glycogen: activator specificity of the adenosine diphosphate glucose pyrophosphorylases from the genus Rhodospirillum.

    OpenAIRE

    Preiss, J; Greenberg, E

    1981-01-01

    The adenosine diphosphate (ADP) glucose pyrophosphorylases from Rhodospirillum fulvum, Rhodospirillum molischianum, and Rhodospirillum tenue were partially purified, and their kinetic properties were studied. The enzyme from the three organisms was found to be activated by pyruvate and thus was similar to the Rhodospirillum rubrum enzyme that had been previously studied (C. E. Furlong, and J. Preiss, J. Biol. Chem. 244:2539-2548, 1979). The enzymes from R. fulvum, R. molischianum, and R. tenu...

  7. Identification of the Escherichia coli ADP-glucose synthetase inhibitor binding site(s)

    International Nuclear Information System (INIS)

    The photoaffinity labeling agent 8-azido adenylate (AMP) is an inhibitor site specific probe of the E. coli ADPG synthetase. In the absence of light, 8-azido AMP exhibits the typical reversible allosteric kinetics of the physiological inhibitor AMP. In the presence of light (254 nm), [2-3H]8-azido AMP specifically and covalently incorporates into the enzyme. Photoincorporation is linearly related to loss of catalytic activity up to at least 65% inactivation. The substrate ADP-glucose (ADPG) provides nearly 100% protection from 8-azido AMP photoinactivation, while the substrate AMP provides approximately 50% protection and the inhibitor AMP provides approximately 30% protection. These three adenylate allosteric effects of E. coli ADPG synthetase also protect it from photoincorporation of 8-azido AMP. The reaction site(s) of [2-3H]-azido AMP with the enzyme was identified by reverse phase HPLC isolation and chemical characterization of CNBr and mouse submaxillary arginyl protease generated peptides containing the labeled analog. This site is the same as the major binding region of the substrate site specific probe, 8-azido ADP-[14C]glucose. Conformational analysis of this region predicts that it is a part of a Rossmann fold, the super-secondary structure found in many adenine nucleotide binding proteins. Two minor reaction regions of the enzyme with [2-3H]8-azido AMP were also identified. The three modified peptide regions may be juxtaposed in the enzyme's tertiary structure

  8. Decreased expression of plastidial adenylate kinase in potato tubers results in an enhanced rate of respiration and a stimulation of starch synthesis that is attributable to post-translational redox-activation of ADP-glucose pyrophosphorylase

    OpenAIRE

    Oliver, S.; Tiessen, A.; Fernie, A.; Geigenberger, P.

    2008-01-01

    Adenine nucleotides are of general importance for many aspects of cell function, but their role in the regulation of biosynthetic processes is still unclear. It was previously reported that decreased expression of plastidial adenylate kinase, catalysing the interconversion of ATP and AMP to ADP, leads to increased adenylate pools and starch content in transgenic potato tubers. However, the underlying mechanisms were not elucidated. Here, it is shown that decreased expression of plastidial ade...

  9. A luminescence-based assay of UDP-sugar producing pyrophosphorylases

    OpenAIRE

    Decker, Daniel; Lindberg, Stina; Eriksson, Jonas; Kleczkowski, Leszek A.

    2014-01-01

    A coupled luminescence assay was applied to monitor pyrophosphate (PPi) production by either purified barley UDP-glucose pyrophosphorylase (UGPase) or purified Leishmania UDP-sugar pyrophosphorylase (USPase). In the assay, the PPi produced by the pyrophosphorylases was converted to ATP by ATP-sulfurylase, and the ATP produced was linked to luminescent light formation through the action of firefly luciferase. The assay allowed for a quantitative measurement of UGPase and USPase activities, dow...

  10. Nucleotide sequence and expression analysis of the Acetobacter xylinum uridine diphosphoglucose pyrophosphorylase gene.

    OpenAIRE

    Brede, G; Fjaervik, E; Valla, S

    1991-01-01

    The nucleotide sequence of the Acetobacter xylinum uridine diphosphoglucose pyrophosphorylase gene was determined; this is the first procaryotic uridine diphosphoglucose pyrophosphorylase gene sequence reported. The sequence data indicated that the gene product consists of 284 amino acids. This finding was consistent with the results obtained by expression analysis in vivo and in vitro in Escherichia coli.

  11. Biosynthesis of starch in chloroplasts.

    Science.gov (United States)

    Nomura, T; Nakayama, N; Murata, T; Akazawa, T

    1967-03-01

    The enzymic synthesis of ADP-glucose and UDP-glucose by chloroplastic pyrophosphorylase of bean and rice leaves has been demonstrated by paper chromatographic techniques. In both tissues, the activity of UDP-glucose-pyrophosphorylase was much higher than ADP-glucose-pyrophosphorylase. Glycerate-3-phosphate, phosphoenolpyruvate and fructose-1,6-diphosphate did not stimulate ADP-glucose formation by a pyrophosphorylation reaction. The major metabolic pathway for UDP-glucose utilization appears to be the synthesis of either sucrose or sucrose-P. On the other hand, a specific precursor role of ADP-glucose for synthesizing chloroplast starch by the ADP-glucose-starch transglucosylase reaction is supported by the coupled enzyme system of ADP-glucose-pyrophosphorylase and transglucosylase, isolated from chloroplasts. None of the glycolytic intermediates stimulated the glucose transfer in the enzyme sequence of reaction system employed. PMID:4292567

  12. Crystallization and preliminary X-ray characterization of the Vitis vinifera fucokinase:GDP-fucose pyrophosphorylase

    OpenAIRE

    Quirk, Stephen

    2012-01-01

    The Vitis vinifera dual-activity fucose and nucleotide-sugar metabolizing enzyme l-fucokinase:GDP-fucose pyrophosphorylase (FKP) has been purified to homogeneity and the 118.8 kDa monomeric protein has been crystallized by vapor diffusion in Zeppezauer tubes at 277 K.

  13. UDP-sugar pyrophosphorylase controls the activity of proceeding sugar-1-kinases enzymes

    OpenAIRE

    Geserick, Claudia; Tenhaken, Raimund

    2013-01-01

    Plant cell wall synthesis requires a number of different nucleotide sugars which provide the building blocks of the different polymers. These nucleotide sugars are mainly provided by de novo synthesis but recycling pathways also contribute to the pools. The last enzyme of the recycling pathway is UDP-sugar pyrophosphorylase (USP), a single copy gene in Arabidopsis, of which a knockout is lethal for pollen development. Here we analyze the dependency between USP enzyme activity and the upstream...

  14. Starch-related Enzymes during Potato Tuber Dormancy and Sprouting

    NARCIS (Netherlands)

    Sergeeva, L.I.; Claassens, M.M.J.; Jamar, D.C.L.; Plas, van der L.H.W.; Vreugdenhil, D.

    2012-01-01

    Activities of enzymes presumably involved in starch biosynthesis (ADP-glucose pyrophosphorylase, AGPase) and/or breakdown (starch phosphorylase, STP; amylases) were determined during potato (Solanum tuberosum L.) tuber dormancy and sprouting. Overall activities of all these enzymes decreased during

  15. GenBank blastx search result: AK287557 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287557 J065021C17 DQ021458.1 DQ021458 Nicotiana langsdorffii x Nicotiana sanderae clone agps...-1 ADP glucose pyrophosphorylase small subunit (AGPS-1) mRNA, partial cds. PLN 1e-84 0 ...

  16. The subunit structure of potato tuber ADPglucose pyrophosphorylase. [Solanum tuberosum L

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.; Nakata, P.A.; Anderson, J.M. (Washington State Univ., Pullman (USA)); Sowokinos, J. (Univ. of Minnesota, St. Paul (USA)); Morell, M.; Preiss, J. (Michigan State Univ., East Lansing (USA))

    1990-06-01

    ADPglucose pyrophosphorylase has been extensively purified from potato (Solanum tuberosum L.) tuber tissue to study its structure. By employing a modified published procedure together with Mono Q chromatography, a near homogeneous enzyme preparation was obtained with substantial improvement in enzyme yield and specific activity. In single dimensional sodium dodecyl sulfate polyacrylamide gels, the enzyme migrated as a single polypeptide band with a mobility of about 50,000 daltons. Analysis by two-dimensional polyacrylamide gel electrophoresis, however, revealed the presence of two types of subunits which could be distinguished by their slight differences in net charge and molecular weight. The smaller potato tuber subunit was recognized by antiserum prepared against the smaller spinach leaf 51 kilodalton ADPglucose pyrophosphorylase subunit. In contrast, the anti-54 kilodalton raised against the spinach leaf subunit did not significantly react to the tuber enzyme subunits. The results are consistent with the hypothesis that the potato tuber ADPglucose pyrophosphorylase is not composed of a simple homotetramer as previously suggested, but is a product of two separate and distinct subunits as observed for the spinach leaf and maize enzymes.

  17. Identification of a GDP-mannose pyrophosphorylase gene from Sulfolobus solfataricus.

    Science.gov (United States)

    Sacchetti, Silvana; Bartolucci, Simonetta; Rossi, Mosè; Cannio, Raffaele

    2004-05-12

    An open reading frame (ORF) encoding a putative GDP-mannose pyrophosphorylase (SsoGMPP) was identified on the genome sequence of Sulfolobus solfataricus P2, the predicted gene product showing high amino acid sequence homology to several archaeal, bacterial, and eukaryal GDP-mannose pyrophosphorylases such as guanidine diphosphomannose pyrophosphorylases (GMPPs) from Saccharomyces cerevisiae and Arabidopsis thaliana. The sequence was PCR amplified from genomic DNA of S. solfataricus P2 and heterologous gene expression obtained as a fusion to glutathione S-transferase in Escherichia coli, under conditions suitable to reduce the formation of inclusion bodies. Specific assays performed at 60 degrees C revealed the presence of the archaeal synthesizing GDP-mannose enzyme activity in the cell extracts of the transformed E. coli. As a positive control, the same assays were performed at the mesophilic enzyme optimum temperature on the already characterized yeast recombinant GMPP. The recombinant protein was purified to homogeneity by glutathione sepharose affinity chromatography and its thermophilic nature could be verified. The enzyme was definitively identified by demonstrating its capability to catalyze also the reverse reaction of pyrophosphorolysis and, most interestingly, its high specificity for synthesizing GDP-mannose. PMID:15145064

  18. [Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase gene]. Progress report, [March 15, 1989--April 14, 1990

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1990-12-31

    The long term aim of this project is to assess the feasibility of increasing the conversion of photosynthate into starch via manipulation of the gene that encodes for ADPglucose pyrophosphorylase, a key regulatory enzyme of starch biosynthesis. In developing storage tissues such as cereal seeds and tubers, starch biosynthesis is regulated by the gene activation and expression of ADPglucose pyrophosphorylase, starch synthase, branching enzyme and other ancillary starch modifying enzymes, as well as the allosteric-controlled behavior of ADPglucose pyrophosphorylase activity. During the last two years we have obtained information on the structure of this enzyme from both potato tuber and rice endosperm, using a combination of biochemical and molecular biological approaches. Moreover, we present evidence that this enzyme may be localized at discrete regions of the starch grain within the amyloplast, and plays a role in controlling overall starch biosynthesis in potato tubers.

  19. Crystallization and preliminary X-ray characterization of the Vitis vinifera fucokinase:GDP-fucose pyrophosphorylase

    International Nuclear Information System (INIS)

    The Vitis vinifera dual-activity fucose and nucleotide-sugar metabolizing enzyme l-fucokinase:GDP-fucose pyrophosphorylase (FKP) has been purified to homogeneity and the 118.8 kDa monomeric protein has been crystallized by vapor diffusion in Zeppezauer tubes at 277 K. The Vitis vinifera dual-activity fucose and nucleotide-sugar metabolizing enzyme l-fucokinase:GDP-fucose pyrophosphorylase (FKP) has been purified to homogeneity and the 118.8 kDa monomeric protein has been crystallized by vapor diffusion in Zeppezauer tubes at 277 K. Crystals of the apoenzyme diffracted to 2.6 Å resolution and belonged to the tetragonal space group P41212. There is a single FKP monomer in the asymmetric unit, giving a Matthews coefficient of 3.22 Å3 Da−1 and a solvent content of 61.8%. A complete native data set has been collected as a first step in determining the three-dimensional structure of this enzyme

  20. [Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase gene]. Summary of progress, [April 15, 1991--April 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1992-12-31

    The long term aim of this project is to assess the feasibility of increasing the conversion of photosynthate into starch via manipulation of genes encoding enzymes that may be rate-limiting in starch biosynthesis. In developing storage tissues such as tubers, starch biosynthesis is regulated by the gene activation and expression of ADPglucose pyrophosphorylase, starch synthase, branching enzyme and other ancillary starch modifying enzymes, as well as the allosteric-controlled behavior of ADPglucose pyrophosphorylase activity. In view of the regulatory role of ADPglucose pyrophosphorylase in starch biosynthesis at both the genetic and biochemical level, we have focused our attention on the genes that encode for this enzyme in potato tubers. The proposed objectives of the grant were to (1) analyze the structure of the tuber enzyme, (2) isolate and characterize the structure of its genes, and (3) identify the regulatory elements controlling ADPglucose pyrophosphorylase during plant development. During the last two and 1/2 years we have met or have made considerable progress in achieving these objectives as discussed in more detail below.

  1. Molecular cloning of a novel glucuronokinase/putative pyrophosphorylase from zebrafish acting in an UDP-glucuronic acid salvage pathway.

    Directory of Open Access Journals (Sweden)

    Roman Gangl

    Full Text Available In animals, the main precursor for glycosaminoglycan and furthermore proteoglycan biosynthesis, like hyaluronic acid, is UDP-glucuronic acid, which is synthesized via the nucleotide sugar oxidation pathway. Mutations in this pathway cause severe developmental defects (deficiency in the initiation of heart valve formation. In plants, UDP-glucuronic acid is synthesized via two independent pathways. Beside the nucleotide sugar oxidation pathway, a second minor route to UDP-glucuronic acid exist termed the myo-inositol oxygenation pathway. Within this myo-inositol is ring cleaved into glucuronic acid, which is subsequently converted to UDP-glucuronic acid by glucuronokinase and UDP-sugar pyrophosphorylase. Here we report on a similar, but bifunctional enzyme from zebrafish (Danio rerio which has glucuronokinase/putative pyrophosphorylase activity. The enzyme can convert glucuronic acid into UDP-glucuronic acid, required for completion of the alternative pathway to UDP-glucuronic acid via myo-inositol and thus establishes a so far unknown second route to UDP-glucuronic acid in animals. Glucuronokinase from zebrafish is a member of the GHMP-kinase superfamily having unique substrate specificity for glucuronic acid with a Km of 31 ± 8 µM and accepting ATP as the only phosphate donor (Km: 59 ± 9 µM. UDP-glucuronic acid pyrophosphorylase from zebrafish has homology to bacterial nucleotidyltransferases and requires UTP as nucleosid diphosphate donor. Genes for bifunctional glucuronokinase and putative UDP-glucuronic acid pyrophosphorylase are conserved among some groups of lower animals, including fishes, frogs, tunicates, and polychaeta, but are absent from mammals. The existence of a second pathway for UDP-glucuronic acid biosynthesis in zebrafish likely explains some previous contradictory finding in jekyll/ugdh zebrafish developmental mutants, which showed residual glycosaminoglycans and proteoglycans in knockout mutants of UDP

  2. In silico analysis of a therapeutic target in Leishmania infantum: the guanosine-diphospho-D-mannose pyrophosphorylase

    OpenAIRE

    Pomel S.; Rodrigo J.; Hendra F.; Cavé C.; Loiseau P.M.

    2012-01-01

    Leishmaniases are tropical and sub-tropical diseases for which classical drugs (i.e. antimonials) exhibit toxicity and drug resistance. Such a situation requires to find new chemical series with antileishmanial activity. This work consists in analyzing the structure of a validated target in Leishmania: the GDP-mannose pyrophosphorylase (GDP-MP), an enzyme involved in glycosylation and essential for amastigote survival. By comparing both human and L. infantum GDP-MP 3D homology models, we iden...

  3. Purification, crystallization and preliminary X-ray characterization of the human GTP fucose pyrophosphorylase

    International Nuclear Information System (INIS)

    The human GTP fucose pyrophosphohydrolase protein has been crystallized via the hanging-drop technique over a reservoir of polyethylene glycol (MW 8000) and ethylene glycol. The orthorhombic crystals diffract to 2.8 Å resolution. The human nucleotide-sugar metabolizing enzyme GTP fucose pyrophosphorylase (GFPP) has been purified to homogeneity by an affinity chromatographic procedure that utilizes a novel nucleoside analog. This new purification regime results in a protein preparation that produces significantly better crystals than traditional purification methods. The purified 66.6 kDa monomeric protein has been crystallized via hanging-drop vapor diffusion at 293 K. Crystals of the native enzyme diffract to 2.8 Å and belong to the orthorhombic space group P212121. There is a single GFPP monomer in the asymmetric unit, giving a Matthews coefficient of 2.38 Å3 Da−1 and a solvent content of 48.2%. A complete native data set has been collected as a first step in determining the three-dimensional structure of this enzyme

  4. Purification, crystallization and preliminary X-ray characterization of the human GTP fucose pyrophosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Quirk, Stephen; Seley-Radtke, Katherine L., E-mail: kseley@umbc.edu [Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Chemistry 405C, Baltimore, MD 21250 (United States)

    2006-04-01

    The human GTP fucose pyrophosphohydrolase protein has been crystallized via the hanging-drop technique over a reservoir of polyethylene glycol (MW 8000) and ethylene glycol. The orthorhombic crystals diffract to 2.8 Å resolution. The human nucleotide-sugar metabolizing enzyme GTP fucose pyrophosphorylase (GFPP) has been purified to homogeneity by an affinity chromatographic procedure that utilizes a novel nucleoside analog. This new purification regime results in a protein preparation that produces significantly better crystals than traditional purification methods. The purified 66.6 kDa monomeric protein has been crystallized via hanging-drop vapor diffusion at 293 K. Crystals of the native enzyme diffract to 2.8 Å and belong to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}. There is a single GFPP monomer in the asymmetric unit, giving a Matthews coefficient of 2.38 Å{sup 3} Da{sup −1} and a solvent content of 48.2%. A complete native data set has been collected as a first step in determining the three-dimensional structure of this enzyme.

  5. Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase genes. Progress report, [April 15, 1990--April 14, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1990-12-31

    The long term goal of this project is to assess the feasibility of increasing the conversion of photosynthate a key regulatory enzyme in starch biosynthesis. In developing storage tissues such as cereal seeds and tubers, starch biosynthesis is primarily regulated by the gene activation, expression, and allosteric regulation of ADPglucose pyrophosphorylase, as well as starch synthase, and branching enzyme. During the last year we have elucidated the structure of both subunits which compose this tetrameric enzyme and determined the temporal and spatial expression of the genes encoding each subunit as well as their correlation to starch biosynthesis. Genomic clones to both subunits have also been isolated and the gene structure of the small subunit determined. Transgenic potato plants have been produced containing deletions of the small subunit promoter. Currently, cis acting elements and their involvement in spatial and temporal expression are under investigation.

  6. Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase gene. Progress report, [April 15, 1987--April 14, 1988

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1988-12-31

    Many agronomically important crops are viewed as significant resources of renewable energy. Overall crop productivity could be increased if the efficiency of photoassimilate conversion into dry matter such as starch were improved in storage tissues. Starch production is controlled by the catalytic activity of ADPglucose pyrophosphorylase in the first step of starch biosynthesis. This research focuses on the genetic structure and molecular mechanisms by which it is controlled during plant development and how it is affected by environmental and hormonal conditions. The current goal is to isolate the genes for this enzyme present in both cereal endosperm and potato tuber tissues, and to elucidate its structure and the controlling sequences responsible for gene expression. The long term goal is the improvement of starch production in storage organs by manipulating this gene so that it encodes an enzyme refractive to inorganic phosphate inhibition.

  7. UDP-N-Acetyl glucosamine pyrophosphorylase as novel target for controlling Aedes aegypti – molecular modeling, docking and simulation studies

    Directory of Open Access Journals (Sweden)

    Bhagath Kumar Palaka

    2014-12-01

    Full Text Available Aedes aegypti is a vector that transmits diseases like dengue fever, chikungunya, and yellow fever. It is distributed in all tropical and subtropical regions of the world. According to WHO reports, 40% of the world’s population is currently at risk for dengue fever. As vaccines are not available for such diseases, controlling mosquito population becomes necessary. Hence, this study aims at UDP-N-acetyl glucosamine pyrophosphorylase of Aedes aegypti (AaUAP, an essential enzyme for chitin metabolim in insects, as a drug target. Structure of AaUAP was predicted and validated using in-silico approach. Further, docking studies were performed using a set of 10 inhibitors out of which NAG9 was found to have good docking score, which was further supported by simulation studies. Hence, we propose that NAG9 can be considered as a potential hit in designing new inhibitors to control Aedes aegypti.

  8. In silico analysis of a therapeutic target in Leishmania infantum: the guanosine-diphospho-D-mannose pyrophosphorylase

    Directory of Open Access Journals (Sweden)

    Pomel S.

    2012-02-01

    Full Text Available Leishmaniases are tropical and sub-tropical diseases for which classical drugs (i.e. antimonials exhibit toxicity and drug resistance. Such a situation requires to find new chemical series with antileishmanial activity. This work consists in analyzing the structure of a validated target in Leishmania: the GDP-mannose pyrophosphorylase (GDP-MP, an enzyme involved in glycosylation and essential for amastigote survival. By comparing both human and L. infantum GDP-MP 3D homology models, we identified (i a common motif of amino acids that binds to the mannose moiety of the substrate and, interestingly, (ii a motif that is specific to the catalytic site of the parasite enzyme. This motif could then be used to design compounds that specifically inhibit the leishmanial GDP-MP, without any effect on the human homolog.

  9. Uncovering Plagiarism - Author Profiling at PAN

    OpenAIRE

    Rosso, Paolo; RANGEL PARDO, FRANCISCO MANUEL

    2014-01-01

    PAN is a yearly workshop and evaluation lab on uncovering plagiarism, authorship, and social software misuse. Since 2009, PAN has been organizing benchmark activities on uncovering plagiarism, authorship, and social software misuse . An additional task - author profiling - has also recently been proposed. Author profiling, instead of focusing on individual authors, studies how language is shared by a class of people. Author profiling is a problem of growing importance in applications in foren...

  10. Alginate biosynthetic enzymes in mucoid and nonmucoid Pseudomonas aeruginosa: overproduction of phosphomannose isomerase, phosphomannomutase, and GDP-mannose pyrophosphorylase by overexpression of the phosphomannose isomerase (pmi) gene.

    OpenAIRE

    Sá-Correia, I.; Darzins, A; Wang, S K; Berry, A.; Chakrabarty, A M

    1987-01-01

    The specific activities of phosphomannose isomerase (PMI), phosphomannomutase (PMM), GDP-mannose pyrophosphorylase (GMP), and GDP-mannose dehydrogenase (GMD) were compared in a mucoid cystic fibrosis isolate of Pseudomonas aeruginosa and in two spontaneous nonmucoid revertants. In both revertants some or all of the alginate biosynthetic enzymes we examined appeared to be repressed, indicating that the loss of the mucoid phenotype may be a result of decreased formation of sugar-nucleotide prec...

  11. Plastidic Phosphoglucose Isomerase Is an Important Determinant of Starch Accumulation in Mesophyll Cells, Growth, Photosynthetic Capacity, and Biosynthesis of Plastidic Cytokinins in Arabidopsis

    Czech Academy of Sciences Publication Activity Database

    Bahaji, A.; Sanchez-Lopez, A.M.; De Diego, N.; Munoz, F.J.; Humplík, J.F.; Novák, Ondřej; Spíchal, L.; Doležal, K.; Pozueta-Romero, J.

    2015-01-01

    Roč. 10, č. 3 (2015). E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ADP- GLUCOSE PYROPHOSPHORYLASE * PENTOSE-PHOSPHATE PATHWAY * POSTTRANSLATIONAL REDOX-MODIFICATION Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  12. Plastidic Phosphoglucose Isomerase Is an Important Determinant of Starch Accumulation in Mesophyll Cells, Growth, Photosynthetic Capacity, and Biosynthesis of Plastidic Cytokinins in Arabidopsis

    Czech Academy of Sciences Publication Activity Database

    Bahaji, A.; Sanchez-Lopez, A.M.; De Diego, N.; Munoz, F.J.; Humplík, J.F.; Novák, Ondřej; Spíchal, L.; Doležal, K.; Pozueta-Romero, J.

    2015-01-01

    Roč. 10, č. 3 (2015). E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ADP-GLUCOSE PYROPHOSPHORYLASE * PENTOSE-PHOSPHATE PATHWAY * POSTTRANSLATIONAL REDOX-MODIFICATION Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  13. Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major

    Science.gov (United States)

    Lamerz, Anne-Christin; Damerow, Sebastian; Kleczka, Barbara; Wiese, Martin; van Zandbergen, Ger; Lamerz, Jens; Wenzel, Alexander; Hsu, Fong-Fu; Turk, John; Beverley, Stephen M.; Routier, Françoise H.

    2010-01-01

    The nucleotide sugar UDP-galactose (UDP-Gal) is essential for the biosynthesis of several abundant glycoconjugates forming the surface glycocalyx of the protozoan parasite Leishmania major. Current data suggest that UDP-Gal could arise de novo by epimerization of UDP-glucose (UDP-Glc) or by a salvage pathway involving phosphorylation of Gal and the action of UDP-glucose:α-d-galactose-1-phosphate uridylyltransferase as described by Leloir. Since both pathways require UDP-Glc, inactivation of the UDP-glucose pyrophosphorylase (UGP) catalyzing activation of glucose-1 phosphate to UDP-Glc was expected to deprive parasites of UDP-Gal required for Leishmania glycocalyx formation. Targeted deletion of the gene encoding UGP, however, only partially affected the synthesis of the Gal-rich phosphoglycans. Moreover, no alteration in the abundant Gal-containing glycoinositolphospholipids was found in the deletion mutant. Consistent with these findings, the virulence of the UGP-deficient mutant was only modestly affected. These data suggest that Leishmania elaborates a UDP-Glc independent salvage pathway for UDP-Gal biosynthesis. PMID:20335578

  14. Cloning, expression, and mapping of GDP-D-mannose pyrophosphorylase cDNA from tomato (Lycopersicon esculentum).

    Science.gov (United States)

    Zou, Li-Ping; Li, Han-Xia; Ouyang, Bo; Zhang, Jun-Hong; Ye, Zhi-Biao

    2006-08-01

    GDP-D-mannose pyrophosphorylase (GMP, EC 2.7.7.22) catalyzes the synthesis of GDP-D-mannose and represents the first committed step in plant ascorbic acid biosynthesis. Using potato GMP cDNA sequence as a querying probe, 65 highly homologous tomato ESTs were obtained from dbEST of GenBank and the putative cDNA sequence of tomato GMP was assembled. The full-length GMP cDNA of tomato was cloned by RACE-PCR with primers designed according to the assembled cDNA sequence. The full-length cDNA sequence contained a complete open reading frame (ORF) of 1,086 bp, which encoded 361 amino acid residues. This gene was designated as LeGMP (GenBank accession No. AY605668). Homology analysis of LeGMP showed a 96% identity with potato GMP and the deduced amino acid showed 99%, 97%, 91% and 89% homology with GMP from potato, tobacco, alfalfa and Arabidopsis thaliana, respectively. Northern blot analysis showed that LeGMP was constitutively expressed in roots, stems, leaves, flowers and fruits of tomato; but the expression levels varied. LeGMP was mapped to 3-D using 75 tomato introgression lines (ILs), each containing a single homozygous RFLP-defined chromosome segment from the green-fruited species Lycopersicon pennellii. PMID:16939010

  15. Some Specification Tests of Uncovered Interest Parity

    OpenAIRE

    Ian D. McAVINCHEY; Ronald MacDONALD

    1990-01-01

    Exchange rate theory has recently been concerned with versions of the uncovered interest rate parity (UIP) condition, as an alternative to purchasing power parity. The UIP condition is examined, for the U.S. Dollar, the Deutschemark, the Yen, and the Swiss Franc all against the Pound Sterling, using dynamic specification tests based on residual from the LUS and OLS classes, and selected error orthogonality tests. Market errors for one currency may have an information role for other currencies...

  16. Lead exposure at uncovered outdoor firing ranges

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, R.L.; Hicks, A.M.; O' Leary, L.M.; London, S. (University of Southern California School of Medicine, Los Angeles (USA))

    1991-06-01

    Excessive lead exposure in shooting instructors at indoor firing ranges and covered outdoor firing ranges has been documented. The City of Los Angeles assessed exposure of its full-time shooting instructors at uncovered outdoor ranges via air monitoring and blood lead-level measurements. Results of these tests revealed that significant lead exposure and absorption can occur at outdoor firing ranges. The use of copper-jacketed ammunition may decrease air lead levels and decrease lead absorption by range instructors.

  17. 'Mystery shoppers' can uncover ED weaknesses.

    Science.gov (United States)

    2006-12-01

    One veteran "mystery shopper" has uncovered several common ED practices that can hurt patient satisfaction. You can learn from her observations to improve your ED's customer service: Be sure to let all of your patients know how long they might expect to wait before seeing a doctor. Wash your hands where the patient can see you, so they can be confident you are practicing good hygiene. Clearly explain all forms and discharge instructions to help ensure patient compliance. PMID:17209484

  18. Uncovering student ideas in physical science

    CERN Document Server

    Keeley, Page

    2014-01-01

    If you and your students can't get enough of a good thing, Volume 2 of Uncovering Student Ideas in Physical Science is just what you need. The book offers 39 new formative assessment probes, this time with a focus on electric charge, electric current, and magnets and electromagnetism. It can help you do everything from demystify electromagnetic fields to explain the real reason balloons stick to the wall after you rub them on your hair.

  19. Clinical role modelling: uncovering hidden knowledge.

    Science.gov (United States)

    Davies, E

    1993-04-01

    Those responsible for the education of nurses are well aware of the need to reconcile the art and science of nursing so that future practitioners can be prepared to offer a humanistic and professional service to society. One way to assist students in this integration is to provide them with opportunities for role modelling as a means of discovering the knowledge embedded in clinical practice. A study of first-year undergraduate students undertaking a course which provides such opportunities in a number of practice settings was carried out to determine whether the observation of clinical role models does lead to knowledge discovery. The study, which used a grounded theory approach, indicated that the major aspect of nursing uncovered by the students through observation of clinical role models was that of provision of direct care. They articulated their values in relation to 'good' and 'bad' care and identified those attributes of nurses which they considered contributed to these care positions. In addition, they were able to recognize creativity and flexibility in practitioners and to relate these attributes to the ability to provide individualized, context-specific care. There was some uncovering of aspects of the nurse's role in maintaining their own professional competence, socializing neophytes into the profession and collaborating with the members of the multi-disciplinary health care team. PMID:8496511

  20. Uncovering the Hidden Decisions that Shape Curricula

    Science.gov (United States)

    Harlow, Danielle Boyd

    2010-10-01

    Developing explanatory models is a central practice to scientific inquiry. When students create and test explanatory models for scientific phenomenon, they develop content knowledge, knowledge of the nature of science, and creative thinking skills. Unfortunately, such instruction rarely occurs in K-12 science. This is, in part, because teachers do not have the opportunity to develop sophisticated understandings of the process of modeling, but also because teaching in this way requires teachers to make real-time instructional decisions that are responsive to students' ideas. This is challenging for teachers, especially because this decision process is often invisible. In this talk, I will highlight the importance of providing opportunities for sophisticated science thinking for our youngest learners and consider how uncovering the decisions that shape physics courses for teachers may benefit their future students.

  1. A Framework to Uncover Multiple Alternative Clusterings

    DEFF Research Database (Denmark)

    Dang, Xuan-Hong; Bailey, James

    Clustering is often referred to as unsupervised learning which aims at uncovering hidden structures from data. Unfortunately, though widely being used as one of the principal tools to understand the data, most conventional clustering techniques are limited in achieving this goal since they only...... attempt to find a single clustering solution from the data. For many real-world applications, especially those being described in high dimensional data, it is common to see that the data can be grouped into different yet meaningful ways. This gives rise to the recently emerging research area of mining...... alternative clusterings. In this paper, we propose a framework named MACL that is capable of discovering multiple alternative clusterings from a given dataset.MACL seeks alternative clusterings in sequence and a novel solution is found by conditioning on all previously known clusterings. The framework takes a...

  2. Hepatitis C virus host cell interactions uncovered

    DEFF Research Database (Denmark)

    Gottwein, Judith; Bukh, Jens

    2007-01-01

      Insights into virus-host cell interactions as uncovered by Randall et al. (1) in a recent issue of PNAS further our understanding of the hepatitis C virus (HCV) life cycle, persistence, and pathogenesis and might lead to the identification of new therapeutic targets. HCV persistently infects 180...... million individuals worldwide, causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The only approved treatment, combination therapy with IFN- and ribavirin, targets cellular pathways (2); however, a sustained virologic response is achieved only in approximately half of the patients...... treated. Therefore, there is a pressing need for the identification of novel drugs against hepatitis C. Although most research focuses on the development of HCV-specific antivirals, such as protease and polymerase inhibitors (3), cellular targets could be pursued and might allow the development of broad...

  3. Cloning a Full-length cDNA Encoding UDP-glucose Pyrophosphorylase from Amorpha fruticosa by PCR-based Methods

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A method based on degenerate Oligo-primed polymerase chain reaction (PCR) and random amplification of cDNA end (RACE) PCR for cloning a full-length cDNA is described. An Amorpha fruticosa cDNA clone encoding UDP-glucose pyrophosphorylase (UGP), a key enzyme producing UDP-glucose in the synthesis of sucrose and cell ulose, is cloned by using this method. We design 5' RACE primers based on UGP A1 fragment, which obtains from degenerate PCR. Inverse PCR and nested PCR enable cloning of the remainder 5' and 3' end fragments of the gene. The deduced amino acid sequence exhibits significant homology with the other UGP genes cloned. This method is more simple and inexpensive than screening cDNA library, and can be easily adapted to clone other genes.

  4. Uncovering Research Topics of Academic Communities of Scientific Collaboration Network

    OpenAIRE

    Hongqi Han; Shuo Xu; Jie Gui; Xiaodong Qiao; Lijun Zhu; Han Zhang

    2014-01-01

    In order to improve the quality of applications, such as recommendation or retrieval in knowledge-based service system, it is very helpful to uncover research topics of academic communities in scientific collaboration network (SCN). Previous research mainly focuses on network characteristics measurement and community evolution, but it remains largely understudied on how to uncover research topics of each community. This paper proposes a nonjoint approach, consisting of three simple steps: (1)...

  5. Macroscopic model for biological fixation and its uncover-ing idea in Chinese Mongolian traditional osteopathy

    Institute of Scientific and Technical Information of China (English)

    ZHAO Namula; LI Xue-en; WANG Mei; HU Da-lai

    2009-01-01

    Splintage external fixation in Chinese Mongolian oste-opathy is a biological macroscopic model. In this model, the ideas of self-life "unity of mind and body" and vital natural "correspondence of nature and human" combine the physi-ological and psychological self-fixation with supplementary external fixation of fracture using small splints. This model implies macroscopic ideas of uncovering fixation and healing: structural stability integrating geometrical "dy-namic" stability with mechanical "dynamic" equilibrium and the stability of state integrating statics with dynamics, and osteoblasts with osteoclasts, and psychological stability in-tegrating closed and open systems of human and nature. These ideas indicate a trend of development in modem osteopathy.

  6. Cloning and sequencing of the Candida albicans homologue of SRB1/PSA1/VIG9, the essential gene encoding GDP-mannose pyrophosphorylase in Saccharomyces cerevisiae.

    Science.gov (United States)

    Warit, S; Walmsley, R M; Stateva, L I

    1998-09-01

    Two genomic fragments have been isolated from Candida albicans which strongly hybridize to SRB1/PSA1/VIG9, an essential gene which encodes GDP-mannose pyrophosphorylase in Saccharomyces cerevisiae. A common 2.5 kb Xbal-Pstl fragment has been identified, which Southern analysis suggests is most likely unique in the C. albicans genome. The fragment contains an ORF, which is 82% identical and 90% homologous to the Srb1p/Psa1p/Vig9p from S. cerevisiae, contains one additional amino acid at position 254 and is able to functionally complement the major phenotypic characteristics of S. cerevisiae srb1 null and conditional mutations. The authors therefore conclude that they have cloned and sequenced from C. albicans the bona fide homologue of SRB1/PSA1/VIG9, named hereafter CaSRB1. Northern analysis data indicate that the gene is expressed in C. albicans under conditions of growth in the yeast and hyphal form and suggest that its expression might be regulated. PMID:9782489

  7. Regulation of starch accumulation by granule-associated plant 14-3-3 proteins

    OpenAIRE

    Sehnke, Paul C.; Chung, Hwa-Jee; Wu, Ke; Ferl, Robert J.

    2001-01-01

    In higher plants the production of starch is orchestrated by chloroplast-localized biosynthetic enzymes, namely starch synthases, ADP-glucose pyrophosphorylase, and starch branching and debranching enzymes. Diurnal regulation of these enzymes, as well as starch-degrading enzymes, influences both the levels and composition of starch, and is dependent in some instances upon phosphorylation-linked regulation. The phosphoserine/threonine-binding 14-3-3 proteins partici...

  8. Isolation and characterisation of starch biosynthesis genes from cassava (Manihot esculenta Crantz).

    OpenAIRE

    Munyikwa, T.R.I.

    1997-01-01

    Cassava (Manihot esculenta Crantz) is a tropical crop grown for its starchy thickened roots, mainly by peasant farmers, in the tropics, for whom it is a staple food. There is an increasing demand for the use of cassava in processed food and feed products, and in the paper and textile industries amongst others. This thesis describes research on the cloning of the genes encoding ADP-glucose pyrophosphorylase small and large subunits (AGPase B and S, respectively) and granule bound starch syntha...

  9. Metabolic consequences of infection of grapevine (Vitis vinifera L. cv. ‘Modra frankinja’ with flavescence dorée phytoplasma

    Directory of Open Access Journals (Sweden)

    Nina ePrezelj

    2016-05-01

    Full Text Available Flavescence dorée, caused by the quarantine phytoplasma FDp, represents the most devastating of the grapevine yellows diseases in Europe. In an integrated study we have explored the FDp–grapevine interaction in infected grapevines of cv. ‘Modra frankinja’ under natural conditions in the vineyard. In FDp-infected leaf vein-enriched tissues, the seasonal transcriptional profiles of 14 genes selected from various metabolic pathways showed an FDp-specific plant response compared to other grapevine yellows and uncovered a new association of the SWEET17a vacuolar transporter of fructose with pathogens. Non-targeted metabolome analysis from leaf vein-enriched tissues identified 22 significantly changed compounds with increased levels during infection. Several metabolites corroborated the gene expression study. Detailed investigation of the dynamics of carbohydrate metabolism revealed significant accumulation of sucrose and starch in the mesophyll of FDp-infected leaves, as well as significant up-regulation of genes involved in their biosynthesis. In addition, infected leaves had high activities of ADP-glucose pyrophosphorylase and, more significantly, sucrose synthase. The data support the conclusion that FDp infection inhibits phloem transport, resulting in accumulation of carbohydrates and secondary metabolites that provoke a source-sink transition and defence response status.

  10. Weaving Social Foundations through Dance Pedagogy: A Pedagogy of Uncovering

    Science.gov (United States)

    Barr, Sherrie; Risner, Doug

    2014-01-01

    Today's dance educators enter classrooms populated by increasingly diverse students in which teachers' pedagogical knowledge necessitates heightened understandings of race, ethnicity, social class, gender, and sexuality. Uncovering taken-for-granted assumptions, dominant stereotypes, and educational structures that reproduce social…

  11. The uncovered parity properties of the Czech Koruna

    Czech Academy of Sciences Publication Activity Database

    Derviz, Alexis

    2002-01-01

    Roč. 11, č. 1 (2002), s. 17-37. ISSN 1210-0455 R&D Projects: GA AV ČR KSK1019101 Institutional research plan: CEZ:AV0Z1075907 Keywords : uncovered parity * asset prices * international consumption-based capital asset pricing model Subject RIV: AH - Economics

  12. Uncovering key data points to improve OR profitability.

    Science.gov (United States)

    Stiefel, Robert A; Greenfield, Howard

    2014-03-01

    Using data analysis to target areas for performance improvement in the operating room (OR) involves: regularly monitoring key OR statistics, such as through use of a dashboard, determining the root causes of problems uncovered by the data analysis, making appropriate corrections and continuing to monitor performance. PMID:24701846

  13. The Uncovered Interest Parity in the Foreign Exchange (FX Markets

    Directory of Open Access Journals (Sweden)

    Silvio Ricardo Micheloto

    2004-12-01

    Full Text Available This work verifies the uncovered interest rates parity (UIP in the FX (foreign exchange emerging markets by using the panel cointegration technique. The data involves several developing countries that compose the EMBI+ Global Index. We compare the results of several panel estimators: OLS (ordinary list square, DOLS (dynamic OLS and FMOLS (fully modified OLS. This new panel technique can handle problems of either non-stationary series (spurious regression or small problem. This latter problem has being considered one of the main causes for distorting the UIP empirical results. By using this approach, we check the UIP in the FX (foreign exchange emerging markets. These markets are more critical because they have been subjected to changing FX regimes and speculative attacks. Our results do not corroborate the uncovered interest parity for the developing countries in the recent years. Thus, the forward premium puzzle may hold in the FX emergent markets.

  14. Uncovering Student Ideas in Astronomy 45 Formative Assessment Probes

    CERN Document Server

    Keeley, Page

    2012-01-01

    What do your students know-or think they know-about what causes night and day, why days are shorter in winter, and how to tell a planet from a star? Find out with this book on astronomy, the latest in NSTA's popular Uncovering Student Ideas in Science series. The 45 astronomy probes provide situations that will pique your students' interest while helping you understand how your students think about key ideas related to the universe and how it operates.

  15. Conditional genome engineering in Toxoplasma gondii uncovers alternative invasion mechanisms

    OpenAIRE

    Andenmatten, Nicole; Egarter, Saskia; Jackson, Allison J.; JULLIEN, Nicolas; Herman, Jean-Paul; Meissner, Markus

    2012-01-01

    We established a conditional site–specific recombination system based on dimerizable Cre–mediated recombination in the apicomplexan parasite Toxoplasma gondii. Using a novel single vector strategy that allows ligand-dependent, efficient removal of a gene of interest, we generated three knockouts of apicomplexan genes considered essential for host-cell invasion. Our findings uncover the existence of an alternative invasion pathway in apicomplexan parasites.

  16. Uncovering the systemic issues that reside in home care

    OpenAIRE

    Giannasi, Wynona

    2012-01-01

    This video clip comprises the Keynote Address: “Uncovering the systemic issues that reside in home care” held at the 21st Annual John K. Friesen Conference, "Innovations in Home Care: A Public Policy Perspective," MAY 16-17, 2012, Vancouver, BC. Presented by Wynona Giannasi, Partner, Howegroup – Public Sector Consultants, Vancouver BC. It is well known that jurisdictions with more comprehensive and integrated home care delivery systems are able to extend independent living for older p...

  17. Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to tolerate water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.

  18. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... changes induced by complex regulatory mechanisms coordinating the activity of different metabolic pathways. It is difficult to map such global transcriptional responses by using traditional methods, because many genes in the metabolic network have relatively small changes at their transcription level. We...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns in...

  19. DOES UNCOVERED INTEREST RATE PARITY HOLD IN TURKEY?

    Directory of Open Access Journals (Sweden)

    Ozcan Karahan

    2012-01-01

    Full Text Available Most of the earlier empirical studies focusing on developed countries failed to give evidence in favor of the Uncovered Interest Rate Parity (UIP. After intensive financial liberalization processes and mostly preferred free exchange rate regimes, a new area of research starts to involve the investigation whether UIP holds for developing economies differently. Accordingly, we tested the UIP for Turkey’s monthly interest rate and exchange rate data between 2002 and 2011. We run conventional regressions in the form of Ordinary Least Squares (OLS and used a simple Generalized Autoregressive Conditional Heteroskedasticity (GARCH analysis. The empirical results of both methods do not support the validity of UIP for Turkey. Thus, together with most of the earlier empirical studies focusing on developed countries and detecting the invalidity of UIP, we can argue that the experience of Turkey and developed economies are not different.

  20. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio;

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues and...... adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

  1. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    Directory of Open Access Journals (Sweden)

    Qi Yuan(Alan

    2010-01-01

    Full Text Available Abstract The problem of uncovering transcriptional regulation by transcription factors (TFs based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ( status and Estrogen Receptor negative ( status, respectively.

  2. Uncover the Ideology Behind News Reports Through Transitivity Analysis

    Institute of Scientific and Technical Information of China (English)

    董亚男

    2015-01-01

    When people read the reports relating to Occupy Central from different news papers, they get completely different feelings towards the event. To find out how this phenomenon happened, this paper is going to apply transitivity analysis to the news reports. The reports are selected from China Daily, CNN and BBC respectively. To have a deep application of this method, only verbal process wil be taken into consideration. This paper wil discuss the proportion of verbal process from the two sides (Occupy Central people as one side and people against them as the other), the message delivered by the verbal process, the sequence and the transformation of verbal process. The purpose is to uncover the ideology hidden behind the seemingly objective news reports through transitivity analysis.

  3. Uncovering Quantum Correlations with Time-Multiplexed Click Detection

    Science.gov (United States)

    Sperling, J.; Bohmann, M.; Vogel, W.; Harder, G.; Brecht, B.; Ansari, V.; Silberhorn, C.

    2015-07-01

    We report on the implementation of a time-multiplexed click detection scheme to probe quantum correlations between different spatial optical modes. We demonstrate that such measurement setups can uncover nonclassical correlations in multimode light fields even if the single mode reductions are purely classical. The nonclassical character of correlated photon pairs, generated by a parametric down-conversion, is immediately measurable employing the theory of click counting instead of low-intensity approximations with photoelectric detection models. The analysis is based on second- and higher-order moments, which are directly retrieved from the measured click statistics, for relatively high mean photon numbers. No data postprocessing is required to demonstrate the effects of interest with high significance, despite low efficiencies and experimental imperfections. Our approach shows that such novel detection schemes are a reliable and robust way to characterize quantum-correlated light fields for practical applications in quantum communications.

  4. Uncovering transcriptional interactions via an adaptive fuzzy logic approach

    Directory of Open Access Journals (Sweden)

    Chen Chung-Ming

    2009-12-01

    Full Text Available Abstract Background To date, only a limited number of transcriptional regulatory interactions have been uncovered. In a pilot study integrating sequence data with microarray data, a position weight matrix (PWM performed poorly in inferring transcriptional interactions (TIs, which represent physical interactions between transcription factors (TF and upstream sequences of target genes. Inferring a TI means that the promoter sequence of a target is inferred to match the consensus sequence motifs of a potential TF, and their interaction type such as AT or RT is also predicted. Thus, a robust PWM (rPWM was developed to search for consensus sequence motifs. In addition to rPWM, one feature extracted from ChIP-chip data was incorporated to identify potential TIs under specific conditions. An interaction type classifier was assembled to predict activation/repression of potential TIs using microarray data. This approach, combining an adaptive (learning fuzzy inference system and an interaction type classifier to predict transcriptional regulatory networks, was named AdaFuzzy. Results AdaFuzzy was applied to predict TIs using real genomics data from Saccharomyces cerevisiae. Following one of the latest advances in predicting TIs, constrained probabilistic sparse matrix factorization (cPSMF, and using 19 transcription factors (TFs, we compared AdaFuzzy to four well-known approaches using over-representation analysis and gene set enrichment analysis. AdaFuzzy outperformed these four algorithms. Furthermore, AdaFuzzy was shown to perform comparably to 'ChIP-experimental method' in inferring TIs identified by two sets of large scale ChIP-chip data, respectively. AdaFuzzy was also able to classify all predicted TIs into one or more of the four promoter architectures. The results coincided with known promoter architectures in yeast and provided insights into transcriptional regulatory mechanisms. Conclusion AdaFuzzy successfully integrates multiple types of

  5. Dicty_cDB: Contig-U03379-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available :none) Uncultured bacterium cosmid IIIE5_... 49 4e-05 ( P39669 ) RecName: Full=Glucose-1-phosphate adenylyl...24 AF030383_1( AF030383 |pid:none) Cucumis melo ADP-glucose pyrophosp... 111 3e-24 ( P55230 ) RecName: Full=...e: Full=Alpha-D-glucose-1-phosphate adenyl transferase; AltName: Full=ADP-glucose pyrophosphorylase; AltNam...2e-15 EF146957_1( EF146957 |pid:none) Populus trichocarpa clone WS01225_... 84 2e-15 (Q9M462) RecName: Full=...ase; ... 83 4e-15 ( P30523 ) RecName: Full=Glucose-1-phosphate adenylyltransferase s... 83 4e-15 AE017126_840( AE017126 |pid

  6. 16 CFR 1610.34 - Only uncovered or exposed parts of wearing apparel to be tested.

    Science.gov (United States)

    2010-01-01

    ... apparel to be tested. 1610.34 Section 1610.34 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... § 1610.34 Only uncovered or exposed parts of wearing apparel to be tested. (a) In determining whether an... uncovered or exposed part of such article of wearing apparel shall be tested according to the...

  7. 16 CFR 1611.34 - Only uncovered or exposed parts of wearing apparel to be tested.

    Science.gov (United States)

    2010-01-01

    ... apparel to be tested. 1611.34 Section 1611.34 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... § 1611.34 Only uncovered or exposed parts of wearing apparel to be tested. In determining whether an... uncovered or exposed part of such article of wearing apparel shall be tested according to the...

  8. Uncovering the mechanism(s) of deep brain stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y [Inspiring Technical Laboratory, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China)

    2005-01-01

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  9. Uncovering the mechanism(s) of deep brain stimulation

    Science.gov (United States)

    Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  10. Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET.

    Science.gov (United States)

    Lee, Shin-Rong; Sang, Lingjie; Yue, David T

    2016-03-29

    Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs). Förster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC), and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R) on PKA's catalytic subunit. We discover that this mutation not only differentially affects PKAcat's binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET. PMID:26997269

  11. Uncovering the Geometry of Barrierless Reactions Using Lagrangian Descriptors.

    Science.gov (United States)

    Junginger, Andrej; Hernandez, Rigoberto

    2016-03-01

    Transition-state theories describing barrierless chemical reactions, or more general activated problems, are often hampered by the lack of a saddle around which the dividing surface can be constructed. For example, the time-dependent transition-state trajectory uncovering the nonrecrossing dividing surface in thermal reactions in the framework of the Langevin equation has relied on perturbative approaches in the vicinity of the saddle. We recently obtained an alternative approach using Lagrangian descriptors to construct time-dependent and recrossing-free dividing surfaces. This is a nonperturbative approach making no reference to a putative saddle. Here we show how the Lagrangian descriptor can be used to obtain the transition-state geometry of a dissipated and thermalized reaction across barrierless potentials. We illustrate the method in the case of a 1D Brownian motion for both barrierless and step potentials; however, the method is not restricted and can be directly applied to different kinds of potentials and higher dimensional systems. PMID:26524392

  12. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    Science.gov (United States)

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-09-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  13. Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET

    Directory of Open Access Journals (Sweden)

    Shin-Rong Lee

    2016-03-01

    Full Text Available Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs. Förster resonance energy transfer (FRET-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC, and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R on PKA’s catalytic subunit. We discover that this mutation not only differentially affects PKAcat’s binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET.

  14. Uncovering the mechanism(s) of deep brain stimulation

    International Nuclear Information System (INIS)

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS

  15. Uncovering Multiple Populations in Globular Clusters with Washington Photometry

    Science.gov (United States)

    Geisler, Douglas; Cummings, Jeff; Villanova, Sandro; Carraro, Giovanni

    2015-01-01

    Globular Clusters (GCs), long considered as ideal Simple Stellar Populations, are now known to harbor a wide variety of chemical inhomogeneities. Multiple populations (MP) are being found in a growing number of Galactic globular clusters (GCs) via both photometric and spectroscopic techniques. Indeed, it has been suggested that a GC is an object that possesses MP. A definitive investigation of MP in GCs will undoubtedly provide a profound improvement in our understanding of their formation and evolution.However, most studies employ either high resolution VLT spectroscopy, HST photometry or inefficient filters from the ground. A ground-based photometric system which is both efficient and effective would be especially excellent for uncovering MP. We demonstrate that the Washington system meets these goals. The Washington C filter, in addition to being specifically designed for the purpose of detecting MPs, is both much broader and redder than competing UV filters, making it far more efficient at detecting MPs and much less sensitive to reddening and extinction.Our analysis of the well-studied GC NGC 1851 shows indeed that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB, using relatively little telescope time on only a 1-meter telescope. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be explained by binaries, field stars, or photometric errors. Detailed analysis shows that the MS distribution is in very good agreement with that seen on the RGB. This is the first time MPs in a MS have been discovered from the ground, and just as strikingly, using only a 1-meter telescope. The Washington system thus proves to be a very powerful tool for investigating MPs, and holds particular promise for extragalactic objects where photons are limited.

  16. Uncovering steroidopathy in women with autism: a latent class analysis

    Science.gov (United States)

    2014-01-01

    Background Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms (‘steroidopathy’) in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC. Methods We tested two groups of women, screened using the Autism Spectrum Quotient - Group 1: n = 415 women with ASC (mean age 36.39 ± 11.98 years); and Group 2: n = 415 controls (mean age 39.96 ± 11.92 years). All participants completed the Testosterone-related Medical Questionnaire online. A multiple-group LCA was used to identify differences in latent class structure between women with ASC and controls. Results There were significant differences in frequency of steroid-related conditions and symptoms between women with ASC and controls. A two-class semi-constrained model best fit the data. Based on response patterns, we identified the classes as ‘Typical’ and ‘Steroidopathic’. The prevalence of the ‘Steroidopathic’ class was significantly increased within the ASC group (ΔG2 = 15, df =1, P = 0.0001). In particular, we confirmed higher frequencies of epilepsy, amenorrhea, dysmenorrhea, severe acne, gender dysphoria, and transsexualism, and differences in sexual preference in women with ASC. Conclusions Women with ASC are at increased risk for symptoms and conditions linked to steroids. LCA revealed this steroidopathy despite the apparent underdiagnosis of PCOS. PMID:24717046

  17. 78 FR 65711 - Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year Reviews

    Science.gov (United States)

    2013-11-01

    ... orders on imports of uncovered innerspring units from South Africa and Vietnam (73 FR 75390 and 75391... uncovered innerspring units from China (74 FR 7661). The Commission is conducting reviews to determine... COMMISSION Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year...

  18. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Science.gov (United States)

    2010-07-01

    ... Treatment for Cryptosporidium Treatment Technique Requirements § 141.714 Requirements for uncovered finished... of at least 4-log virus, 3-log Giardia lamblia, and 2-log Cryptosporidium using a protocol approved... treatment technique requirement. Requirements for Microbial Toolbox Components...

  19. Endoscopic removal of a spontaneously fractured biliary uncovered self-expandable metal stent.

    Science.gov (United States)

    Kawakubo, Kazumichi; Isayama, Hiroyuki; Tsujino, Takeshi; Nakai, Yousuke; Sasahira, Naoki; Kogure, Hirofumi; Hamada, Tsuyoshi; Nagano, Rie; Miyabayashi, Kouji; Yamamoto, Keisuke; Mohri, Dai; Sasaki, Takashi; Ito, Yukiko; Yamamoto, Natsuyo; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

    2012-05-01

    Self-expandable metal stents (SEMS) are widely used for the palliative treatment of unresectable malignant biliary obstruction. However, the long-term durability of SEMSs in biliary strictures is not clear. We describe a case of endoscopic removal of spontaneously fractured uncovered biliary SEMS. A 59-year-old woman presented to our institution with a 1-year history of recurrent cholangitis. Her medical history included a proctectomy for rectal cancer and right hemihepatectomy for liver metastasis 10 years earlier. Five years after these operations, she developed a benign hilar stricture and had an uncovered SEMS placed in another hospital. Endoscopic retrograde cholangiopancreatography demonstrated that the SEMS was torn in half and the distal part of the stent was floating in the dilated common bile duct. The papillary orifice was dilated by endoscopic papillary large balloon dilation (EPLBD) using a 15-mm wire-guided balloon catheter. Subsequently, we inserted biopsy forceps into the bile duct and grasped the distal end of the broken SEMS under fluoroscopy. We successfully removed the fragment of the SEMS from the bile duct, along with the endoscope. The patient was discharged without complications. Placement of an uncovered biliary SEMS is not the preferred treatment for benign biliary strictures. Spontaneous fracture of an uncovered biliary SEMS is an extremely rare complication. We should be aware that stent fracture can occur when placing uncovered biliary SEMSs in patients with a long life expectancy. EPLBD is very useful for retrieving the fractured fragment of SEMS. PMID:22507093

  20. Using Text Mining to Uncover Students' Technology-Related Problems in Live Video Streaming

    Science.gov (United States)

    Abdous, M'hammed; He, Wu

    2011-01-01

    Because of their capacity to sift through large amounts of data, text mining and data mining are enabling higher education institutions to reveal valuable patterns in students' learning behaviours without having to resort to traditional survey methods. In an effort to uncover live video streaming (LVS) students' technology related-problems and to…

  1. Community Mapping in Action: Uncovering Resources and Assets for Young Children and Their Families

    Science.gov (United States)

    Ordonez-Jasis, Rosario; Myck-Wayne, Janice

    2012-01-01

    Community mapping is a promising practice that can assist early intervention/early childhood special education (EI/ECSE) professionals uncover the depth and diversity of community needs, resources, and learning opportunities, in the neighborhoods surrounding their schools. Community mapping is an inquiry-based method that situates learning in the…

  2. Uncovering the Motivating Factors behind Writing in English in en EFL Context

    Science.gov (United States)

    Büyükyavuz, Oya; Çakir, Ismail

    2014-01-01

    Writing in a language, whether the target or native, is regarded as a complex activity operating on multiple cognitive levels. This study aimed to uncover the factors which motivate teacher trainees of English to write in English in an EFL context. The study also investigated the differences in the ways teacher trainees are motivated in terms of…

  3. Uncovering Influence through Social Network Analysis: The Role of Schools in Education for Sustainable Development

    Science.gov (United States)

    Kolleck, Nina

    2016-01-01

    This paper examines the implementation of Education for Sustainable Development (ESD) in Germany and explores the possibilities of Social Network Analysis (SNA) for uncovering influential actors in educational policy innovation processes. From the theoretical perspective, an actor's influence is inferred from its relative position within…

  4. Uncovering Pre-Service Music Teachers' Assumptions of Teaching, Learning, and Music

    Science.gov (United States)

    Bernard, Rhoda

    2009-01-01

    In this study, the author collected narratives from her students in a music teacher education programme. Using narrative analysis, students' assumptions and thoughts about music teaching, music learning and music making were uncovered. Through the presentation of a case study of one student, the author demonstrates some of the ways that the…

  5. Uncovering flux line correlations in superconductors by reverse monte carlo refinement of neutron scattering data

    OpenAIRE

    Laver, M.; Forgan, E. M.; Abrahamsen, Asger Bech; Bowell, C.; Geue, T.; Cubitt, R.

    2008-01-01

    We describe the use of reverse Monte Carlo refinement to extract structural information from angle-resolved data of a Bragg peak. Starting with small-angle neutron scattering data, the positional order of an ensemble of flux lines in superconducting Nb is revealed. We discuss the uncovered correlation functions in the light of topical theories, in particular, the "Bragg glass" paradigm.

  6. Uncovering flux line correlations in superconductors by reverse monte carlo refinement of neutron scattering data

    DEFF Research Database (Denmark)

    Laver, M.; Forgan, E.M.; Abrahamsen, Asger Bech;

    2008-01-01

    We describe the use of reverse Monte Carlo refinement to extract structural information from angle-resolved data of a Bragg peak. Starting with small-angle neutron scattering data, the positional order of an ensemble of flux lines in superconducting Nb is revealed. We discuss the uncovered...... correlation functions in the light of topical theories, in particular, the "Bragg glass" paradigm....

  7. Learning "through" Computers: Uncovering Students' Thought Processes while Solving Physics Problems

    Science.gov (United States)

    Soong, Benson

    2008-01-01

    This paper presents a study that illustrates how the author and an in service secondary school teacher used basic synchronous computer mediated communications (CMC) technology to help them uncover students' physics preconceptions and thought processes (including their misconceptions and misunderstandings) in a real class setting. In this paper, I…

  8. Feminist Approaches to Triangulation: Uncovering Subjugated Knowledge and Fostering Social Change in Mixed Methods Research

    Science.gov (United States)

    Hesse-Biber, Sharlene

    2012-01-01

    This article explores the deployment of triangulation in the service of uncovering subjugated knowledge and promoting social change for women and other oppressed groups. Feminist approaches to mixed methods praxis create a tight link between the research problem and the research design. An analysis of selected case studies of feminist praxis…

  9. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Science.gov (United States)

    2012-02-29

    ... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished... requirement in the Long Term 2 Enhanced Surface Water Treatment Rule (LT2 rule). At this meeting, EPA will... information related to microbial occurrence of Cryptosporidium, Giardia, viruses, and other...

  10. Chemical Analysis: An Indispensable Means for Uncovering Severe Cases of Fraud with Cosmetics and Tattoo Inks.

    Science.gov (United States)

    Hohl, Christopher; Hauri, Urs

    2016-01-01

    Three cases of fraud with commodities containing illegal stealth compounds are presented, which were uncovered by the State Laboratory Basel-City, Switzerland. All three commodities, grapefruit seed extracts, a phytocosmetical skin cream, and tattoo inks, were produced abroad, had forged declarations of ingredients and, in the case of the extracts and the cream, were marketed with far-reaching health claims. While inspections will identify suspicious products and would be able to eliminate health claims to some extent, only chemical analysis can uncover the illegal agents used and give law enforcement bodies the necessary evidence to immediately clamp down on those brands, where the stealth agent presents a serious health hazard to consumers. PMID:27198815

  11. WeSME: Uncovering Mutual Exclusivity of Cancer Drivers and Beyond

    OpenAIRE

    Kim, Yoo-Ah; Madan, Sanna; Przytycka, Teresa M.

    2016-01-01

    Mutual exclusivity is a widely recognized property of many cancer drivers. Knowledge about these relationships can provide important insights into cancer drivers, cancer-driving pathways, and cancer subtypes. It can also be used to predict new functional interactions between cancer driving genes and uncover novel cancer drivers. Currently, most of mutual exclusivity analyses are preformed focusing on a limited set of genes in part due to the computational cost required to rigorously compute p...

  12. Uncovering the Factors behind Comparative Regional Economic Performance: A Dynamic CGE Approach

    OpenAIRE

    James A. Giesecke; John R Madden

    2006-01-01

    Recently a new method has emerged for uncovering the factors driving regional disparities in growth performance. The method involves historical analysis with a multiregional computable general equilibrium model. This paper has three main aims. The first is to demonstrate the capacity of the CGE historical technique to decompose the causes of regional divergence into clearly-specified economic factors. The second is to provide a generic miniature model that can be used as a template for adapti...

  13. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    OpenAIRE

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P

  14. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    OpenAIRE

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P < 10(-6) in 19,979 additional individuals. We i...

  15. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    OpenAIRE

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We ident...

  16. THE SIGNIFICANCE OF CRIMINALISTIC THEORY OF INFORMATION FOR THE PROCESS OF UNCOVERING AND INVESTIGATION OF CRIMES

    OpenAIRE

    Pisarev, Evgeniy

    2014-01-01

    The article proves the necessity of development of general criminalistic theory of information and application of informational approach in the process of uncovering and investigation of the crimes. The place of criminalistic informatiology is determined in general theory of criminalistics as its element. The author proceeds from the fact that the evidence in criminal procedure legislation is determined as the data; this circumstance predetermines the process of collection of evidence as the ...

  17. Genetic algorithms and Gaussian Bayesian networks to uncover the predictive core set of bibliometric indices

    OpenAIRE

    Ibáñez Martín, Alfonso; Armañanzas Arnedillo, Ruben; Bielza Lozoya, Maria Concepcion; Larrañaga Múgica, Pedro

    2015-01-01

    The diversity of bibliometric indices today poses the challenge of exploiting the relationships among them. Our research uncovers the best core set of relevant indices for predicting other bibliometric indices. An added difficulty is to select the role of each variable, that is, which bibliometric indices are predictive variables and which are response variables. This results in a novel multioutput regression problem where the role of each variable (predictor or respon...

  18. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    OpenAIRE

    P. B. Rose; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of act...

  19. Multi-frequency complex network from time series for uncovering oil-water flow structure

    Science.gov (United States)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Fang, Peng-Cheng; Jin, Ning-De; Xia, Cheng-Yi; Hu, Li-Dan

    2015-02-01

    Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective.

  20. Endoscopic management of occluded biliary uncovered metal stents:A multicenter experience

    Institute of Scientific and Technical Information of China (English)

    Panagiotis Katsinelos; Kostas Fasoulas; Stefanos Atmatzidis; Christos Zavos; Jannis Kountouras; Athanasios Beltsis; Grigoris Chatzimavroudis; Dimitris Paikos; George Paroutoglou; Dimitris Kapetanos; Sotiris Terzoudis; Georgia Lazaraki; Ioannis Pilpilidis

    2011-01-01

    AIM:To compare diverse endoscopic interventions in the management of occluded uncovered self-expanding metal stents(SEMSs)that had been placed for palliative treatment of unresectable malignant biliary obstruction.METHODS:A retrospective review was undertaken in 4 tertiary endoscopic centers to determine optimal management of different types of occluded SEMSs.The technical success of performed treatment in occluded SEMSs,the patency of the stent,the need for re-intervention and the financial costs of each treatment were analyzed.RESULTS:Fifty four patients were included in the analysis;21 received Hanaro,19 Wallstent and 14 Flexus.For the relief of obstruction,a plastic stent was inserted in 24 patients,a second SEMS in 25 and mechanical cleaning was performed in 5 patients.The overall median second patency rates between second SEMSs and plastic stents did not differ(133 d for SEMSs vs 106 d for plastic stents;P = 0.856).Similarly,no difference was found between the overall survival of SEMS and plastic stent groups,and no procedure-related complications occurred.Incremental cost analysis showed that successive plastic stenting was a cost-saving strategy at least in Greece.CONCLUSION:Insertion of uncovered SEMSs or plastic stents is a safe and effective treatment for occluded uncovered SEMSs;insertion of plastic stents appears to be the most cost-effective strategy.

  1. 番茄GDP-D-甘露糖焦磷酸化酶cDNA的克隆、表达及定位%Cloning, Expression, and Mapping of GDP-D-mannose Pyrophosphorylase cDNA from Tomato (Lycopersicon esculentum)

    Institute of Scientific and Technical Information of China (English)

    邹礼平; 李汉霞; 欧阳波; 张俊红; 叶志彪

    2006-01-01

    GDP-D-mannose pyrophosphorylase (GMP, EC 2.7.7.22) catalyzes the synthesis of GDP-D-mannose and represents the first committed step in plant ascorbic acid biosynthesis. Using potato GMP cDNA sequence as a querying probe, 65 highly homologous tomato ESTs were obtained from dbEST of GenBank and the putative cDNA sequence of tomato GMP was assembled.The full-length GMP cDNA of tomato was cloned by RACE-PCR with primers designed according to the assembled cDNA sequence. The full-length cDNA sequence contained a complete open reading frame (ORF) of 1 086 bp, which encoded 361 amino acid residues. This gene was designated as LeGMP (GenBank accession No. AY605668). Homology analysis of LeGMP showed a 96% identity with potato GMP and the deduced amino acid showed 99%, 97%, 91% and 89% homology with GMP from potato,tobacco, alfalfa and Arabidopsis thaliana, respectively. Northern blot analysis showed that LeGMP was constitutively expressed in roots, stems, leaves, flowers and fruits of tomato; but the expression levels varied. LeGMP was mapped to 3-D using 75 tomato introgression lines (ILs), each containing a single homozygous RFLP-defined chromosome segment from the green-fruited species Lycopersicon pennellii.%GDP-D-甘露糖焦磷酸化酶催化GDP-D-甘露糖的合成,是植物抗坏血酸生物合成途径中上游的关键酶.以马铃薯GDP-D-甘露糖焦磷酸化酶cDNA序列为信息探针,在GenBank dbEST数据库中找到65条高度同源的番茄EST序列,通过序列拼接及RACE-PCR得到了番茄该基因的全长cDNA序列,命名为LeGMP.LeGMP与马铃薯GDP-D-甘露糖焦磷酸化酶cDNA序列一致率为96%,推导的氨基酸序列与马铃薯、烟草、紫苜蓿、拟南芥的GDP-D-甘露糖焦磷酸化酶基因的一致率分别为99%、97%、91%、89%.经Northern杂交分析,LeGMP在番茄根、茎、叶、花、果实中都有表达,但表达水平有差异.利用75个番茄远缘杂交重组系(IL系)将LeGMP定位在番茄第3

  2. The invisible Web uncovering information sources search engines can't see

    CERN Document Server

    Sherman, Chris

    2001-01-01

    Enormous expanses of the Internet are unreachable with standard web search engines. This book provides the key to finding these hidden resources by identifying how to uncover and use invisible web resources. Mapping the invisible Web, when and how to use it, assessing the validity of the information, and the future of Web searching are topics covered in detail. Only 16 percent of Net-based information can be located using a general search engine. The other 84 percent is what is referred to as the invisible Web-made up of information stored in databases. Unlike pages on the visible Web, informa

  3. Animal models of Huntington's disease: implications in uncovering pathogenic mechanisms and developing therapies

    Institute of Scientific and Technical Information of China (English)

    Lin-hui WANG; Zheng-hong QIN

    2006-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, which is caused by an abnormal expansion of Cytosine Adenine Guanine (CAG) trinucleotide repeat in the gene making huntingtin (Htt). Despite intensive research efforts devoted to investigate molecular mechanisms of pathogenesis, effective therapy for this devastating disease is still not available at present. The development of various animal models of HD has offered alternative approaches in the study of HD molecular pathology. Many HD models, including chemical-induced models and genetic models, mimic some aspects of HD symptoms and pathology. To date, however, there is no ideal model which replicates all of the essential features of neuropathology and progressive motor and cognitive impairments of human HD. As a result, our understanding of molecular mechanisms of pathogenesis in HD is still limited. A new model is needed in order to uncover the pathogenesis and to develop novel therapies for HD. In this review we discussed usefulness and limitations of various animal and cellular models of HD in uncovering molecular mechanisms of pathogenesis and developing novel therapies for HD.

  4. Uncovering Sundanese Values by Analyzing Symbolic Meaning of Ménak Priangan Clothing (1800-1942)

    Science.gov (United States)

    Karmila, M.; Suciati; Widiaty, I.

    2016-04-01

    This study investigates symbolic meanings found in the Sunda ethnic clothing, particularly the Menak Priangan clothing. This study aims to uncover and document those symbolic meanings found in the Menak Priangan clothing as an effort to develop Sunda cultural artefacts of West Java. This study on Menak Priangan clothing applies ethnography (visual) and aesthetic methods. The visual method is utilized in order to uncover local cultural (Sunda) values found in Menak Priangan clothing visualization, including: design, model, name, and representing colours, which then directed towards local Sundanese aesthetic concepts living within the Priangan community. Furthermore, aesthetic method is used to explore role of aesthetic values in empowering visual cultural values within certain community, particularly Sunda aesthetic values. The study results show that since the 19th century, Sunda ethnic clothing was limited to Priangan Sunda only, while traditional clothing wearing by Priangan people reflects their social strata, consisting of: a. Menak Gede (Menak pangluhurna: mayor), bearing raden title, b. Menak Leutik/Santana (mayor assistant), titles: asep, mas, agus, ujang, (Nyimas for woman), c. Somah/Cacah: ordinary people/lower class. Clothing is a cultural phenomenon within certain culture reflecting such society experiences. For Menak people, clothing and its accessories have important meanings. They wear such traditional clothing and accessories as a symbol of power they have within bureaucratic structure and as a symbol of social status they bear within traditional community structure.

  5. Uncovering diversity in the development of central noradrenergic neurons and their efferents.

    Science.gov (United States)

    Robertson, Sabrina D; Plummer, Nicholas W; Jensen, Patricia

    2016-06-15

    Uncovering the mechanisms that underlie central noradrenergic neuron heterogeneity is essential to understanding selective subtype vulnerability to disease and environmental insult. Using recombinase-based intersectional genetic fate mapping we have previously demonstrated that molecularly distinct progenitor populations give rise to mature noradrenergic neurons differing in their anatomical location, axon morphology and efferent projection pattern. Here we review the findings from our previous study and extend our analysis of the noradrenergic subpopulation defined by transient developmental expression of Hoxb1. Using a combination of intersectional genetic fate mapping and analysis of a targeted loss of function mutation in Hoxb1, we have now uncovered additional heterogeneity based on the requirement of some noradrenergic neurons for Hoxb1 expression. By comparing the distribution of noradrenergic neurons derived from the Hoxb1 expression domain in wild-type and mutant mice, we demonstrate that Hoxb1 expression is required by a subset of neurons in the pons. Additional fate mapping, using a Hoxb1 enhancer element that drives Cre recombinase expression exclusively in rhombomere 4 of the hindbrain, reveals the existence of a subpopulation of noradrenergic neurons in the pons with more restricted axonal targets than the full Hoxb1-derived subpopulation. The unique projection profile of this newly defined subpopulation suggests that it may be functionally distinct. These analyses shed new light on the molecular determinants of noradrenergic identity in the pons and the overall complexity of the central noradrenergic system. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26612521

  6. From detecting astrocyte connectivity to uncovering drug effects in living tissues

    CERN Document Server

    Pires, Marcelo; Vaz, Sandra; Sebastião, Ana; Lind, Pedro G

    2013-01-01

    We introduce a simple procedure of multivariate signal analysis to uncover the connectivity structure among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based in the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude if pairs of cells are connected or not and in which direction. After testing the method against synthetic data we apply it to study propagation of $Ca^{2+}$ waves in astrocytes, with the aim of uncovering the cell connectivity structure. Our method shows to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based the statistical analysis of the connec...

  7. Proceedings in uncovering the mechanism behind peroxisome proliferator-induced hepatocarcinogenesis

    International Nuclear Information System (INIS)

    The cancer risk assessment of peroxisome proliferators (PPs) has been a matter of debate for decades. PPs are non-genotoxic carcinogens that cause liver tumours in rodents. There is considerable evidence that humans are refractory to the carcinogenic effect of PPs. Still, some toxicologists argue that these chemicals should be considered carcinogenic until the opposite has been proven. To solve this matter, much work has been dedicated to uncovering the mode of action of PPs. The proceedings are reviewed and it is discussed whether these provide an explanation for the observed interspecies differences and shed a new light on human health risk assessment. The efforts in the past years have significantly increased our understanding of the pathways involved, but have also raised new questions. The question why humans seem to be refractory is yet to be answered. From this point of view, the safety assessment of PPs to humans therefore remains an issue of discussion

  8. Uncovering brain-heart information through advanced signal and image processing.

    Science.gov (United States)

    Valenza, Gaetano; Toschi, Nicola; Barbieri, Riccardo

    2016-05-13

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain-heart physiology and physiopathology. PMID:27044995

  9. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    DEFF Research Database (Denmark)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A;

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered....... Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO....... Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown...

  10. Uncovered Interest Parity in Central and Eastern Europe: Convergence and the Global Financial Crisis

    Directory of Open Access Journals (Sweden)

    Fabio Filipozzi

    2012-12-01

    Full Text Available This paper presents tests of uncovered interest parity in Croatia, the Czech Republic, Hungary, Poland and Romania; all countries in Central and Eastern Europe with floating exchange rates. Data are monthly and the trading horizon is three months. The estimations show that the UIP hypothesis is rejected for the full sample from 1999 to 2011 for all five countries. A number of reasons for the rejection were investigated. Rolling regressions show that standard versions of the UIP essentially lose all explanatory power in 2008-10, which was a period in which the global financial crisis led to instability in currency and interest markets in Central and Eastern Europe. Two indicators of global risk aversion were also found to enter significantly in the many UIP estimations. Finally, the size of the interest rates spread also seems to be of importance, at least for Poland and Romania

  11. Intraductal radiofrequency ablation of tumour ingrowth into an uncovered metal stent used for inoperable cholangiocarcinoma.

    Science.gov (United States)

    Lui, K L; Li, K K

    2013-12-01

    A 91-year-old woman diagnosed to have an inoperable cholangiocarcinoma had an uncovered metal stent inserted for palliative drainage. About 1.5 years later, tumour ingrowth into the metal stent caused cholangitis. Intraductal radiofrequency ablation was applied to create local coagulative tumour necrosis and the necrotic tissue was removed via a balloon catheter. A plastic stent was inserted to empirically treat any ensuing potential bile duct injury. The patient was discharged without complication with good palliative drainage. Intraductal radiofrequency ablation is a new technique for the treatment of metal stent occlusion due to tumour ingrowths. This is the first case report of this relatively safe and feasible new technique for the treatment of tumour ingrowth into a metal stent used as palliation for malignant biliary obstruction. PMID:24310661

  12. Lipidomics Analyses Reveal Temporal and Spatial Lipid Organization and Uncover Daily Oscillations in Intracellular Organelles.

    Science.gov (United States)

    Aviram, Rona; Manella, Gal; Kopelman, Naama; Neufeld-Cohen, Adi; Zwighaft, Ziv; Elimelech, Meytar; Adamovich, Yaarit; Golik, Marina; Wang, Chunyan; Han, Xianlin; Asher, Gad

    2016-05-19

    Cells have evolved mechanisms to handle incompatible processes through temporal organization by circadian clocks and by spatial compartmentalization within organelles defined by lipid bilayers. Recent advances in lipidomics have led to identification of plentiful lipid species, yet our knowledge regarding their spatiotemporal organization is lagging behind. In this study, we quantitatively characterized the nuclear and mitochondrial lipidome in mouse liver throughout the day, upon different feeding regimens, and in clock-disrupted mice. Our analyses revealed potential connections between lipid species within and between lipid classes. Remarkably, we uncovered diurnal oscillations in lipid accumulation in the nucleus and mitochondria. These oscillations exhibited opposite phases and readily responded to feeding time. Furthermore, we found that the circadian clock coordinates the phase relation between the organelles. In summary, our study provides temporal and spatial depiction of lipid organization and reveals the presence and coordination of diurnal rhythmicity in intracellular organelles. PMID:27161994

  13. Uncovering the overlapping community structure of complex networks in nature and society

    CERN Document Server

    Pálla, G; Farkas, I; Vicsek, T; Palla, Gergely; Derenyi, Imre; Farkas, Illes; Vicsek, Tamas

    2005-01-01

    Many complex systems in nature and society can be described in terms of networks capturing the intricate web of connections among the units they are made of. A key question is how to interpret the global organization of such networks as the coexistence of their structural subunits (communities) associated with more highly interconnected parts. Identifying these a priori unknown building blocks (such as functionally related proteins, industrial sectors and groups of people) is crucial to the understanding of the structural and functional properties of networks. The existing deterministic methods used for large networks find separated communities, whereas most of the actual networks are made of highly overlapping cohesive groups of nodes. Here we introduce an approach to analysing the main statistical features of the interwoven sets of overlapping communities that makes a step towards uncovering the modular structure of complex systems. After defining a set of new characteristic quantities for the statistics of...

  14. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2012-04-23

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  15. Uncovering brain–heart information through advanced signal and image processing

    Science.gov (United States)

    Toschi, Nicola; Barbieri, Riccardo

    2016-01-01

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain–heart physiology and physiopathology. PMID:27044995

  16. Systems-level approach to uncovering diffusive states and their transitions from single particle trajectories

    CERN Document Server

    Koo, Peter K

    2016-01-01

    The stochastic motions of a diffusing particle contain information concerning the particle's interactions with binding partners and with its local environment. However, accurate determination of the underlying diffusive properties, beyond normal diffusion, has remained challenging when analyzing particle trajectories on an individual basis. Here, we introduce the maximum likelihood estimator (MLE) for confined diffusion and fractional Brownian motion. We demonstrate that this MLE yields improved estimation over traditional mean square displacement analyses. We also introduce a model selection scheme (that we call mleBIC) that classifies individual trajectories to a given diffusion mode. We demonstrate the statistical limitations of classification via mleBIC using simulated data. To overcome these limitations, we introduce a new version of perturbation expectation-maximization (pEMv2), which simultaneously analyzes a collection of particle trajectories to uncover the system of interactions which give rise to u...

  17. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Surget S

    2013-12-01

    Full Text Available Sylvanie Surget,1,2 Marie P Khoury,1,2 Jean-Christophe Bourdon1,21Dundee Cancer Centre, 2Jacqui Wood Cancer Centre, Ninewells Hospital, University of Dundee, Dundee, UKAbstract: Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets.Keywords: p53, isoforms, p63, p73, alternative splicing, cancer

  18. Metabolism of human insulin after subcutaneous administration: A possible means to uncover insulin misuse.

    Science.gov (United States)

    Thomas, Andreas; Brinkkötter, Paul; Schänzer, Wilhelm; Thevis, Mario

    2015-10-15

    The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases. In vitro experiments with skin tissue lysates (S9 fraction and microsomes), different biological fluids (urine, serum, plasma) and recombinant human insulin were performed and the deriving metabolites were characterized by liquid chromatography coupled to high resolution mass spectrometry (HRMS). Afterwards, authentic blood samples of patients suffering from diabetes mellitus and a control group of healthy humans were analysed. Therefore, a method using protein precipitation, ultrafiltration and antibody-coated magnetic beads for purification with subsequent separation by nano-scale liquid chromatography coupled a Q Exactive mass spectrometer was applied. Several metabolites of insulin with C-terminally truncated sequences of the B-chain (and A-chain in minor extent) were identified within this study. Here, the DesB30 human insulin represents the major metabolite in all experiments. This metabolite is frequently found in urine samples due to degradation processes and, thus, disqualifies this matrix for the intended purposes. In contrast, blood samples do commonly not contain DesB30 insulin, which was corroborated by data obtained from the control group. In post-administration blood samples, minute but distinct amounts (approx. 50 pg mL(-1)) of DesB30 insulin were found and suggest the use of this analyte as potential marker for subcutaneous human insulin administration, supporting the attempts to

  19. Uncovering beat deafness: detecting rhythm disorders with synchronized finger tapping and perceptual timing tasks.

    Science.gov (United States)

    Dalla Bella, Simone; Sowiński, Jakub

    2015-01-01

    A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson's disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder). PMID:25867797

  20. Uncovering Time-Varying Parameters with the Kalman-Filter and the Flexible Least Squares: a Monte Carlo Study

    OpenAIRE

    Zsolt Darvas; Balázs Varga

    2012-01-01

    Using Monte Carlo methods, we compare the ability of the Kalman-filter, the Kalman-smoother and the flexible least squares (FLS) to uncover the parameters of an autoregression. We find that the ordinary least squares (OLS) estimator performs much better that the time-varying coefficient methods when the parameters are in fact constant, but the OLS does very poorly when parameters change. Neither the FLS, nor the Kalman-filter and Kalman-smoother can uncover sudden changes in parameters. But w...

  1. Uncovering the Links between Prospective Teachers' Personal Responsibility, Academic Optimism, Hope, and Emotions about Teaching: A Mediation Analysis

    Science.gov (United States)

    Eren, Altay

    2014-01-01

    Prospective teachers' sense of personal responsibility has not been examined together with their academic optimism, hope, and emotions about teaching in a single study to date. However, to consider hope, academic optimism, and emotions about teaching together with personal responsibility is important to uncover the factors affecting…

  2. Uncovering the pKa dependent fluorescence quenching of carbon dots induced by chlorophenols

    Science.gov (United States)

    Zhang, Yu; Wang, Yu; Guan, Yafeng; Feng, Liang

    2015-03-01

    Fluorescence quenching induced by targets is always an alluring strategy to elucidate the possible photoluminescence origin of carbon dots. In this study, a new kind of N, S co-doped carbon dots (NSCDs) was synthesized and the fluorescence of NSCDs was surprisingly found to be quenched by chlorophenols (CPs) in a pKa dependent mode. Detailed investigation of this behavior demonstrated that phenolate was the responsible species and N and/or S dopants in NSCDs failed to play a role in the fluorescence quenching. Further evidence uncovered that the quenching was a static one, where a non-fluorescent intermediate was formed between electron-deficient C&z.dbd;O on the CDs surface and the electron-rich phenolic oxygen anion of chlorophenolate via nucleophilic addition. Moreover, one of the main photoluminescence origins of this kind of CDs was derived, namely surface emissive sites mostly attributed to carbonyl groups.Fluorescence quenching induced by targets is always an alluring strategy to elucidate the possible photoluminescence origin of carbon dots. In this study, a new kind of N, S co-doped carbon dots (NSCDs) was synthesized and the fluorescence of NSCDs was surprisingly found to be quenched by chlorophenols (CPs) in a pKa dependent mode. Detailed investigation of this behavior demonstrated that phenolate was the responsible species and N and/or S dopants in NSCDs failed to play a role in the fluorescence quenching. Further evidence uncovered that the quenching was a static one, where a non-fluorescent intermediate was formed between electron-deficient C&z.dbd;O on the CDs surface and the electron-rich phenolic oxygen anion of chlorophenolate via nucleophilic addition. Moreover, one of the main photoluminescence origins of this kind of CDs was derived, namely surface emissive sites mostly attributed to carbonyl groups. Electronic supplementary information (ESI) available: Texts, figures and tables giving partial experimental procedures, detailed characterizations

  3. Systematic Triple-Mutant Analysis Uncovers Functional Connectivity between Pathways Involved in Chromosome Regulation

    Directory of Open Access Journals (Sweden)

    James E. Haber

    2013-06-01

    Full Text Available Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed triple-mutant analysis (TMA. We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered through traditional double-mutant analyses.

  4. The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared.

    Science.gov (United States)

    Kishimoto, Makoto; Antonucci, Robert; Blaes, Omer; Lawrence, Andy; Boisson, Catherine; Albrecht, Marcus; Leipski, Christian

    2008-07-24

    Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model-an optically thick disk which is heated locally by the dissipation of gravitational binding energy-is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. PMID:18650919

  5. Percutaneous Treatment of Malignant Jaundice Due to Extrahepatic Cholangiocarcinoma: Covered Viabil Stent Versus Uncovered Wallstents

    International Nuclear Information System (INIS)

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

  6. Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents.

    Science.gov (United States)

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-01

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement. PMID:19495871

  7. Uncovering molecular relaxation processes with nonlinear spectroscopies in the deep UV

    International Nuclear Information System (INIS)

    Highlights: • We discuss the outlook for multidimensional spectroscopies in the deep UV. • Photophysics are examined in small DNA components at cryogenic temperatures. • Wavepacket motions are detected in ring-opening systems with 2DUV spectroscopy. • Measurements of electronic wavepacket motions in molecules are proposed. - Abstract: Nonlinear laser spectroscopies in the deep UV spectral range are motivated by studies of biological systems and elementary processes in small molecules. This perspective article discusses recent technical advances in this area with a particular emphasis on diffractive optic based approaches to four-wave mixing spectroscopies. Applications to two classes of systems illustrate present experimental capabilities. First, experiments on DNA components at cryogenic temperatures are used to uncover features of excited state potential energy surfaces and vibrational cooling mechanisms. Second, sub-200 fs internal conversion processes and coherent wavepacket motions are investigated in cyclohexadiene and α-terpinene. Finally, we propose new experimental directions that combine methods for producing few-cycle UV laser pulses in noble gases with incoherent detection methods (e.g., photoionization) in experiments with time resolution near a singlefemtosecond. These measurements are motivated by knowledge of extremely fast non-adiabatic dynamics and the resolution of electronic wavepacket motions in molecules

  8. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    Science.gov (United States)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  9. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    Science.gov (United States)

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-04-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  10. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants.

    Science.gov (United States)

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we "wordify" the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  11. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    Science.gov (United States)

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

  12. Uncovering Multiple Populations with Washington Photometry: I. The Globular Cluster NGC 1851

    CERN Document Server

    Cummings, Jeffrey D; Villanova, S; Carraro, G

    2014-01-01

    The analysis of multiple populations (MPs) in globular clusters (GCs) has become a forefront area of research in astronomy. Multiple red giant branches (RGBs), subgiant branches (SGBs), and even main sequences (MSs) have now been observed photometrically in many GCs. UV photometry has been crucial in discovering and analyzing these MPs, but the Johnson U and the Stromgren and Sloan u filters that have generally been used are relatively inefficient and very sensitive to reddening and atmospheric extinction. In contrast, the Washington C filter is much broader and redder than these competing UV filters. Here we investigate the use of the Washington system to uncover MPs using only a 1-meter telescope. Our analysis of the well-studied GC NGC 1851 finds that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be ...

  13. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs

    Directory of Open Access Journals (Sweden)

    Erica C. Pehrsson

    2013-06-01

    Full Text Available Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens.

  14. Flux Analysis Uncovers Key Role of Functional Redundancy in Formaldehyde Metabolism

    Directory of Open Access Journals (Sweden)

    Marx Christopher J

    2005-01-01

    Full Text Available Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and 14C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.

  15. Unexpected novel relational links uncovered by extensive developmental profiling of nuclear receptor expression.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bertrand

    2007-11-01

    Full Text Available Nuclear receptors (NRs are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily.

  16. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis

    Science.gov (United States)

    Rosenberg, Alan M.; Yeung, Rae S. M.; Morris, Quaid

    2016-01-01

    Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples. PMID:27244050

  17. Proteomic Analysis of Cytokeratin Isoforms Uncovers Association with Survival in Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Tarek G. Gharib

    2002-01-01

    Full Text Available Cytokeratins. (CK are intermediate filaments whose expression is often altered in epithelial cancer. Systematic identification of lung adenocarcinoma proteins using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry has uncovered numerous CK isoforms. In this study, 93 lung adenocarcinomas. (64 stage I and 29 stage III and 10 uninvolved lung samples were quantitatively examined for protein expression. Fourteen of 21 isoforms of CK 7, 8, 18, 19 occurred at significantly higher levels. (P<.05 in tumors compared to uninvolved adjacent tissue. Specific isoforms of the four types of CK identified correlated with either clinical outcome or individual clinical-pathological parameters. All five of the CK7 isoforms associated with patient survival represented cleavage products. Two of five CK7 isoforms. (nos. 2165 and 2091, one of eight CK8 isoforms. (no. 439, one of three CK19 isoforms. (no. 1955 were associated with survival and significantly correlated to their mRNA levels, suggesting that transcription underlies overexpression of these CK isoforms. Our data indicate substantial heterogeneity among CK in lung adenocarcinomas resulting from posttranslational modifications, some of which correlated with patient survival and other clinical parameters. Therefore, specific isoforms of individual CK may have utility as diagnostic or predictive markers in lung adenocarcinomas.

  18. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rose Jr., P.B.; Erickson, A. S.; Mayer, Michael F.; Nattress, J.; Jovanovic , I

    2016-04-18

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  19. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis.

    Directory of Open Access Journals (Sweden)

    Ang Cui

    Full Text Available Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction. This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples.

  20. UNCOVERING THE ORIGINS OF SPIRAL STRUCTURE BY MEASURING RADIAL VARIATION IN PATTERN SPEEDS

    International Nuclear Information System (INIS)

    Current theories of spiral and bar structure predict a variety of pattern speed behaviors, calling for detailed, direct measurement of the radial variation of pattern speeds. Our recently developed Radial Tremaine-Weinberg (TWR) method allows this goal to be achieved for the first time. Here, we present TWR spiral pattern speed estimates for M101, IC 342, NGC 3938, and NGC 3344 in order to investigate whether spiral structure is steady or winding, whether spirals are described by multiple pattern speeds, and the relation between bar and spiral speeds. Where possible, we interpret our pattern speeds estimates according to the resonance radii associated with each (established with the disk angular rotation), and compare these to previous determinations. By analyzing the high-quality H I and CO data cubes available for these galaxies, we show that it is possible to determine directly multiple pattern speeds within these systems, and hence identify the characteristic signatures of the processes that drive the spiral structure. Even this small sample of galaxies reveals a surprisingly complex taxonomy, with the first direct evidence for the presence of resonant coupling of multiple patterns found in some systems, and the measurement of a simple single-pattern speed in others. Overall, this study demonstrates that we are now in a position to uncover more of the apparently complex physics that lies behind spiral structure.

  1. MARS A Cosmic Stepping Stone Uncovering Humanity’s Cosmic Context

    CERN Document Server

    Nolan, Kevin

    2008-01-01

    The questions of our origin and cosmic abundance of life are among the most compelling facing humanity. We have determined much about the nature and origin of the Universe and our place in it, but with virtually all evidence of our origin long since gone from our world and an unimaginably vast Universe still to explore, defining answers are difficult to obtain. For all of the difficulties facing us however, the planet Mars may act as a ‘cosmic stepping stone’ in uncovering some of the answers. Although different today, the origin and early history of both Earth and Mars may have been similar enough to consider an origin to life on both. But because Mars’ planetary processes collapsed over three billion years ago – just as life was beginning to flourish on Earth – a significant and unique record of activity from that era perhaps relevant to the origin of life still resides there today. In recognition of this, both the US and Europe are currently engaged in one of the most ambitious programs of explor...

  2. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    Science.gov (United States)

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  3. Multiple omics uncovers host-gut microbial mutualism during prebiotic fructooligosaccharide supplementation.

    Science.gov (United States)

    Kato, Tamotsu; Fukuda, Shinji; Fujiwara, Akemi; Suda, Wataru; Hattori, Masahira; Kikuchi, Jun; Ohno, Hiroshi

    2014-10-01

    Fructooligosaccharide (FOS), a prebiotic well known for its health-promoting properties, can improve the human gut ecosystem most likely through changes in its microbial composition. However, the detailed mechanism(s) of action of FOS in the modulation of the gut ecosystem remain(s) obscure. Traditional methods of profiling microbes and metabolites could barely show any significant features due to the existence of large interindividual differences, but our novel microbe-metabolite correlation approach, combined with faecal immunoglobulin A (IgA) measurements, has revealed that the induction of mucosal IgA by FOS supplementation correlated with the presence of specific bacteria. Furthermore, the metabolic dynamics of butyrate, L-phenylalanine, L-lysine and tyramine were positively correlated with that of these bacteria and IgA production, whereas p-cresol was negatively correlated. Taken together, our focused intraindividual analysis with omics approaches is a powerful strategy for uncovering the gut molecular network and could provide a new vista for understanding the human gut ecosystem. PMID:24848698

  4. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants

    Science.gov (United States)

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we “wordify” the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  5. Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds.

    Science.gov (United States)

    Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

    2014-12-01

    Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal-habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities. PMID:25558353

  6. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

    Science.gov (United States)

    Loayza-Puch, Fabricio; Rooijers, Koos; Buil, Levi C M; Zijlstra, Jelle; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Hofland, Ingrid; Wesseling, Jelle; van Tellingen, Olaf; Bex, Axel; Agami, Reuven

    2016-02-25

    Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment. PMID:26878238

  7. Uncovering phenotypes of poor-pitch singing: The Sung Performance Battery (SPB

    Directory of Open Access Journals (Sweden)

    Magdalena eBerkowska

    2013-10-01

    Full Text Available Singing is as natural as speaking for humans. Increasing evidence shows that the layman can carry a tune (e.g., when asked to sing a well-known song or to imitate single pitches, intervals and short melodies. Yet, important individual differences exist in the general population with regard to singing proficiency. Some individuals are particularly inaccurate or imprecise in producing or imitating pitch information (poor-pitch singers, thus showing a variety of singing phenotypes. Unfortunately, so far there is not a standard set of tasks for assessing singing proficiency in the general population, allowing to uncover and characterize individual profiles of poor-pitch singing. Different tasks and analysis methods are typically used in various experiments, making the comparison of the results across studies arduous. To fill this gap we propose here a new tool for assessing singing proficiency (the Sung Performance Battery, SPB. The SPB starts from the assessment of participants’ vocal range followed by five tasks: 1 single-pitch matching, 2 pitch-interval matching, 3 novel-melody matching, 4 singing from memory of familiar melodies (with lyrics and on a syllable, and 5 singing of familiar melodies (with lyrics and on a syllable at a slow tempo indicated by a metronome. Data analysis via acoustical methods provides objective measures of pitch accuracy and precision in terms of absolute and relative pitch. The SPB has been tested in a group of 50 occasional singers. The results indicate that the battery is useful for characterizing proficient singing and for detecting cases of inaccurate and/or imprecise singing.

  8. Quick determination of gas pressure before uncovering coal in cross-cuts and shafts

    Institute of Scientific and Technical Information of China (English)

    JIANG Cheng-lin; DENG Su-hua; ZHANG Chao-jie; CHENG Song-li; LV Shu-wen; WANG Chen; LI Xiao-wei; CHEN Yu-jia; XIE Qing-xue; LIU Ying; TANG Jun; YANG Fei-long; WANG Fa-kai

    2008-01-01

    The determination of gas pressure before uncovering coal in cross-cuts and in shafts is one of the important steps in predicting coal and gas outbursts. However, the time spent for testing gas pressure is, at present, very long, seriously affecting the application of outburst prediction techniques in opening coal seams in cross-cuts and shafts. In order to reduce the time needed in gas pressure tests and to improve the accuracy of tests, we analyzed the process of gas pressure tests and examined the effect of the length of boreholes in coal seams in tests. The result shows that 1) the shorter the borehole, the easier the real pressure value of gas can be obtained and 2) the main factors affecting the time spent in gas pressure tests are the length of the borehole in coal seams,the gas emission time after the borehole has been formed and the quality of the borehole-sealing. The longer the length of the borehole, the longer the gas emission time and the larger the pressure-relief circle formed around the borehole, the longer the time needed for pressure tests. By controlling the length of the borehole in a test case in the Huainan mining area, and adopting a quick sealing technique using a sticky liquid method, the sealing quality was clearly improved and the gas emission time as well as the amount of gas discharged greatly decreased. Before the method described, the time required for the gas pressure to increase during the pressure test process, was more than 10 days. With our new method the required time is only 5 hours. In addition, the accuracy of the gas pressure test is greatly improved.

  9. Uncovering China’s transport CO2 emission patterns at the regional level

    International Nuclear Information System (INIS)

    With China’s rapid economic development, its transport sector has experienced a dramatic growth, leading to a large amount of related CO2 emission. This paper aims to uncover China’s transport CO2 emission patterns at the regional and provincial level. We first present the CO2 emission features from transport sector in 30 Chinese provinces, including per capita emissions, emission intensities, and historical evolution of annual CO2 emission. We then quantify the related driving forces by adopting both period-wise and time-series LMDI analysis. Results indicate that significant regional CO2 emission disparities exist in China’s transport sector. The eastern region had higher total CO2 emissions and per capita CO2 emissions, but lower CO2 emission intensities in its transport sector. The western region had higher CO2 emission intensities and experienced a rapid CO2 emission increase. The CO2 emission increments in the eastern provinces were mainly contributed by both economic activity effect and population effect, while energy intensity partially offset the emission growth and energy structure had a marginal effect. However, in the central and western provinces, both economic activity effect and energy intensity effect induced the CO2 emission increases, while the effects from population and energy structure change were limited. - Highlights: • The CO2 emission features from transport sector in 30 Chinese provinces were presented. • The driving forces of CO2 emissions from transport sector were quantified. • Regional disparities on China’s transport sector CO2 emission exist. • Region-specific mitigation policies on transport sector CO2 emission are needed

  10. Uncovering paradoxes from physicians' experiences of patient-centered ward-round.

    Science.gov (United States)

    Bååthe, Fredrik; Ahlborg, Gunnar; Edgren, Lars; Lagström, Annica; Nilsson, Kerstin

    2016-05-01

    Purpose The purpose of this paper is to uncover paradoxes emerging from physicians' experiences of a patient-centered and team-based ward round, in an internal medicine department. Design/methodology/approach Abductive reasoning relates empirical material to complex responsive processes theory in a dialectical process to further understandings. Findings This paper found the response from physicians, to a patient-centered and team-based ward round, related to whether the new demands challenged or confirmed individual physician's professional identity. Two empirically divergent perspectives on enacting the role of physician during ward round emerged: We-perspective and I-perspective, based on where the physician's professional identity was centered. Physicians with more of a We-perspective experienced challenges with the new round, while physicians with more of an I-perspective experienced alignment with their professional identity and embraced the new round. When identity is challenged, anxiety is aroused, and if anxiety is not catered to, then resistance is likely to follow and changes are likely to be hampered. Practical implications For change processes affecting physicians' professional identity, it is important for managers and change leaders to acknowledge paradox and find a balance between new knowledge that needs to be learnt and who the physician is becoming in this new procedure. Originality/value This paper provides increased understanding about how physicians' professional identity is interacting with a patient-centered ward round. It adds to the knowledge about developing health care in line with recent societal requests and with sustainable physician engagement. PMID:27198705

  11. The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

    Science.gov (United States)

    Chao, Qing; Gao, Zhi-Fang; Wang, Yue-Feng; Li, Zhe; Huang, Xia-He; Wang, Ying-Chun; Mei, Ying-Chang; Zhao, Biligen-Gaowa; Li, Liang; Jiang, Yu-Bo; Wang, Bai-Chen

    2016-06-01

    Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future. PMID:26969016

  12. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe.

    Science.gov (United States)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns. PMID:27368782

  13. Mechanisms of heat transfer in the uncovered region of a bundle during the boil-off transient

    International Nuclear Information System (INIS)

    The small break accident which occurred at the TMI-2 plant resulted in partial uncovery of the core. To study the thermal-hydraulic phenomena in the uncovered portion of the core, tests were conducted from the EPRI/SUNY Buffalo 3 x 3 rod bundle. Observations from motion pictures and test data show that liquid entrainment and liquid fallback occur in the upper rod bundle region during the early stage of the boiling dry transient. The liquid entrainment and liquid fallback are the results of flow restrictions in the upper bundle tie-plate and spacer grids. The presence of liquid droplets during the entrainment and the fallback greatly influenced the heat transfer in the uncovered portion of the bundle

  14. Uncovering the Essence of What Animates Us Beneath The Dance: Investigating the Lived Experiences of Bodily Perceptions Generated While Dancing

    OpenAIRE

    Kurnaedy, Karen McKinlay

    2013-01-01

    This dissertation is a phenomenological study in which I endeavour to uncover the essence of what animates us beneath the dance by investigating the lived experiences of bodily perceptions generated while dancing. I present four perspectives to illuminate this essence. In my first perspective, I offer literature from a variety of phenomenologists, dancers and choreographers which substantiate vital and spiritual perceptions generated while dancing. In my second perspective, I conduct an autob...

  15. Effects and Mechanisms of P and K Nutrients on Yield and Protein Content of Fodder Rice

    Institute of Scientific and Technical Information of China (English)

    TANG Xiang-ru; YU Tie-qiao

    2002-01-01

    Effects and mechanisms of P and K nutrients on yield and protein content of Weiyou 56, a fodder hybrid rice combination, were studied through pot experiment and biochemical analysis. The results showed that the increase of P and K nutrients enhanced the activities of PEP carboxylase (PEPC), glutamine synthase (GS) and sucrose phosphate synthase (SPS) in leaves, sucrose synthase (SS), ADP glucose pyrophosphorylase (ADPGP) and GS in grains, and the chlorophyll content in leaves, soluble sugar and starch content in grains,protein N and total N content in leaves and grains. Howerer, they decreased soluble sugar content in leaves and led to an increase of protein content in brown rice, biomass, grain yield and harvest index. Excessive P nutrients slightly reduced SPS and ADPG activity in leaves and grains respectively.

  16. Thioredoxin f1 and NADPH-Dependent Thioredoxin Reductase C Have Overlapping Functions in Regulating Photosynthetic Metabolism and Plant Growth in Response to Varying Light Conditions

    DEFF Research Database (Denmark)

    Thormählen, Ina; Meitzel, Tobias; Groysman, Julia; Öchsner, Alexandra Bianca; von Roepenack-Lahaye, Edda; Naranjo, Belén; Cejudo, Francisco J; Geigenberger, Peter

    2015-01-01

    . In Arabidopsis (Arabidopsis thaliana) mutants, combined, but not single, deficiencies of Trx f1 and NTRC led to severe growth inhibition and perturbed light acclimation, accompanied by strong impairments of Calvin-Benson cycle activity and starch accumulation. Light activation of key enzymes of these...... pathways, fructose-1,6-bisphosphatase and ADP-glucose pyrophosphorylase, was almost completely abolished. The subsequent increase in NADPH-NADP(+) and ATP-ADP ratios led to increased nitrogen assimilation, NADP-malate dehydrogenase activation, and light vulnerability of photosystem I core proteins. In an......Two different thiol redox systems exist in plant chloroplasts, the ferredoxin-thioredoxin (Trx) system, which depends on ferredoxin reduced by the photosynthetic electron transport chain and, thus, on light, and the NADPH-dependent Trx reductase C (NTRC) system, which relies on NADPH and thus may...

  17. No Place to Hide: Missing Primitive Stars Outside Milky Way Uncovered

    Science.gov (United States)

    2010-02-01

    After years of successful concealment, the most primitive stars outside our Milky Way galaxy have finally been unmasked. New observations using ESO's Very Large Telescope have been used to solve an important astrophysical puzzle concerning the oldest stars in our galactic neighbourhood - which is crucial for our understanding of the earliest stars in the Universe. "We have, in effect, found a flaw in the forensic methods used until now," says Else Starkenburg, lead author of the paper reporting the study. "Our improved approach allows us to uncover the primitive stars hidden among all the other, more common stars." Primitive stars are thought to have formed from material forged shortly after the Big Bang, 13.7 billion years ago. They typically have less than one thousandth the amount of chemical elements heavier than hydrogen and helium found in the Sun and are called "extremely metal-poor stars" [1]. They belong to one of the first generations of stars in the nearby Universe. Such stars are extremely rare and mainly observed in the Milky Way. Cosmologists think that larger galaxies like the Milky Way formed from the merger of smaller galaxies. Our Milky Way's population of extremely metal-poor or "primitive" stars should already have been present in the dwarf galaxies from which it formed, and similar populations should be present in other dwarf galaxies. "So far, evidence for them has been scarce," says co-author Giuseppina Battaglia. "Large surveys conducted in the last few years kept showing that the most ancient populations of stars in the Milky Way and dwarf galaxies did not match, which was not at all expected from cosmological models." Element abundances are measured from spectra, which provide the chemical fingerprints of stars [2]. The Dwarf galaxies Abundances and Radial-velocities Team [3] used the FLAMES instrument on ESO's Very Large Telescope to measure the spectra of over 2000 individual giant stars in four of our galactic neighbours, the Fornax

  18. Realizing full coverage of perovskite film on substrate surface during solution processing: Characterization and elimination of uncovered surface

    Science.gov (United States)

    Li, Yan; He, Xue-Long; Ding, Bin; Gao, Li-Li; Yang, Guan-Jun; Li, Cheng-Xin; Li, Chang-Jiu

    2016-07-01

    The full coverage of the perovskite film on the substrate surface is of significant importance for the high performance perovskite solar cells. In order to obtain full coverage perovskite films by one-step deposition method, the microstructures of both uncovered areas and covered areas of the CH3NH3PbI3 film are comparatively investigated. Results show that the uncovered area indeed has an ultra-thin layer of CH3NH3PbI3 film which is too thin to cover the rough surface morphology of the substrate, and the localized solute accumulation due to long crystal growth time is responsible for the non-full coverage of the perovskite film. Then by decreasing the crystal growth time, the localized solute accumulation is eliminated gradually and subsequently a full coverage of perovskite film on substrate surface is realized. As a result, the perovskite solar cells show a conversion efficiency of ∼13% with the uniform and full coverage perovskite film.

  19. A distinctive avian assemblage (Aves: Passeriformes) in Western Darién, Panama is uncovered through a disease surveillance program.

    Science.gov (United States)

    Miller, Matthew J

    2014-06-01

    Basic knowledge about the distribution of flora and fauna is lacking for most tropical areas. Improving our knowledge of the tropical biota will help address contemporary global problems, including emerging tropical diseases. Less appreciated is the role that applied studies can have in improving our understanding of basic biological patterns and processes in the tropics. Here, I describe a novel avifauna assemblage uncovered in Western Darién province in the Republic of Panama that was uncovered during a vector-borne disease surveillance program. I compared the passerine bird species composition at 16 sites using records from recent ornithological expeditions sponsored by the Smithsonian Tropical Research Institute in Central and Eastern Panama. Based on the results of a Mantel test, geographic distance did not correlate with pairwise distinctiveness of sites. instead, based on an index of distinctiveness modified from the Chao-Jaccard index, most sites were more or less similarly distinctive, with one site, Aruza Abajo, significantly more distinctive than the rest. I found that the distinctiveness of this site was due not only to the presence of several rare and range-restricted taxa, but also to the absence of taxa that are common elsewhere. This finding provides more evidence of high species composition turnover (beta-diversity) in the Panamanian biota, which appears to be driven by a combination of soil and climate differences over narrow distances. PMID:25102652

  20. Effects of Variation in Activities of Starch-Sugar Metabolic Enzymes on Reducing Sugar Accumulation and Processing Quality of Potato Tubers

    Institute of Scientific and Technical Information of China (English)

    CHENG Shan-han; SU Zhen-hong; XIE Cong-hua; LIU Jun

    2004-01-01

    The experiment was designed,via storing potato tubers of cv.E-Potatol and E-Potato3 in different temperatures,to explore the variation patterns of reducing sugar(RS)and total sugar(TS)contents and enzyme activities that are involved in the pathway of starch-sugar metabolism aiming at identifying the main factors that influence the chip color.The results showed that low temperature in storage was a main factor that accelerated the accumulation of RS of the stored tubers and a very significant linear relationship existed between RS content and chip color index(CCI)of the tubers.Further analysis elucidated that when tubers stored at 4℃,the activities of ADP glucose pyrophosphorylase(AGPase),UDP glucose pyrophosphorylase(UGPase)and sucrose synthase(SuSy)were negatively exponential to the RS content significantly while that of acid invertase and alkaline invertase was significantly linear to RS content.It suggested that these enzymes could play main roles in the cold sweetening of potato tubers through regulating starch-sugar metabolism.

  1. An uncovered XIII century icon: Particular use of organic pigments and gilding techniques highlighted by analytical methods

    Science.gov (United States)

    Daveri, Alessia; Doherty, Brenda; Moretti, Patrizia; Grazia, Chiara; Romani, Aldo; Fiorin, Enrico; Brunetti, Brunetto Giovanni; Vagnini, Manuela

    2015-01-01

    The restoration of a panel painting depicting a Madonna and Child listed as an unknown Tuscan artist of the nineteenth century, permitted the hidden original version, a XIII century Medieval icon to be uncovered. It is discovery provided the opportunity for an extensive in situ campaign of non-invasive analytical investigations by portable imaging and spectroscopic techniques (infrared, X-ray fluorescence and diffraction, UV-Vis absorption and emission), followed by aimed micro-destructive investigations (Raman and SEM-EDS). This approach permitted characterization of the original ground and paint layers by complementary techniques. Furthermore, this protocol allowed supplementary particularities of great interest to be highlighted. Namely, numerous original gilding techniques have been accentuated in diverse areas and include the use of surrogate gold (disulphur tin), orpiment as a further false gold and an area with an original silver rich layer. Moreover, pigments including azurite mixed with indigo have been non-invasively identified. Micro-invasive analyses also allowed the diagnosis of organic colorants, namely, an animal anthraquinone lake, kermes and an unusual vegetal chalcone pigment, possibly safflower. The identification of the latter is extremely rare as a painting pigment and has been identified using an innovative adaption to surface enhanced Raman techniques on a cross-section. The resulting data contributes new hypotheses to the historic and artistic knowledge of materials and techniques utilized in XIII century icon paintings and ultimately provides scientific technical support of the recent restoration.

  2. Atmospheric pollution history at Linfen (China) uncovered by magnetic and chemical parameters of sediments from a water reservoir

    International Nuclear Information System (INIS)

    We studied magnetic and chemical parameters of sediments from sediments of a water reservoir at Linfen (China) in order to quantitatively reconstruct the atmospheric pollution history in this region. The results show that the main magnetic phases are magnetite and maghemite originating from the surrounding catchment and from anthropogenic activities, and there is a significant positive relationship between magnetic concentration parameters and heavy metals concentrations, indicating that magnetic proxies can be used to monitor the anthropogenic pollution. In order to uncover the atmospheric pollution history, we combined the known events of environmental improvement with variations of magnetic susceptibility (χ) and heavy metals along the cores to obtain a detailed chronological framework. In addition, air comprehensive pollution index (ACPI) was reconstructed from regression equation among magnetic and chemical parameters as well as atmospheric monitoring data. Based on these results, the atmospheric pollution history was successfully reconstructed. - Highlights: • Magnetic proxies can be used to monitor the heavy mental pollution in sediments. • Accurate age model was obtained using known events of environmental improvement. • Regression equation was obtained among sediment records and monitoring data. • Atmospheric pollution history was quantitatively reconstructed. - Atmospheric pollution history was quantitatively reconstructed using magnetic and chemical records of reservoir sediments combined with atmospheric monitoring data

  3. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal

    2014-03-01

    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  4. Uncovering the composition of microbial community structure and metagenomics among three gut locations in pigs with distinct fatness.

    Science.gov (United States)

    Yang, Hui; Huang, Xiaochang; Fang, Shaoming; Xin, Wenshui; Huang, Lusheng; Chen, Congying

    2016-01-01

    Uncovering the phylogenetic composition of microbial community and the potential functional capacity of microbiome in different gut locations is of great importance to pig production. Here we performed a comparative analysis of gut microbiota and metagenomics among jejunum, ileum and cecum in pigs with distinct fatness. 16S rRNA gene sequencing revealed dramatic differences of microbial composition, diversity and species abundance between small intestine and cecum. Clostridium and SMB53 were enriched in the small intestine, while Prevotella, Treponema, Ruminococcus and Faecalibacterium showed a higher abundance in the cecum. Functional capacity analysis of gut microbiome revealed that the microbiome of small intestine plays important roles in the metabolism of small molecule nutrients, while the microbiome of cecum has the stronger ability to degrade xylan, pectin and cellulose. We identified tens of fatness associated-bacterial species including Escherichia spp. that showed a notable increase of relative abundance in all three gut locations of high fatness pigs. We further suggested that the potential pathogens, inflammation process, and microbial metabolism and nutrient sensing are involved in the high fatness of pigs. These results improve our knowledge about microbiota compositions in different gut locations, and give an insight into the effect of gut microbiota on porcine fatness. PMID:27255518

  5. Sporty materials uncovered

    OpenAIRE

    Kevin Edwards

    2004-01-01

    Materials in Sports Equipment is a welcome addition to books on materials engineering, says Kevin Edwards. It fills a gap in coverage of the important sports market, where advances in materials can lead to improved performance.

  6. Uncovering undetected hypoglycemic events

    Directory of Open Access Journals (Sweden)

    Unger J

    2012-03-01

    Full Text Available Jeff UngerCatalina Research Institute, Chino, CA, USAAbstract: Hypoglycemia is the rate-limiting factor that often prevents patients with diabetes from safely and effectively achieving their glycemic goals. Recent studies have reported that severe hypoglycemia is associated with a significant increase in the adjusted risks of major macrovascular events, major microvascular events, and mortality. Minor hypoglycemic episodes can also have serious implications for patient health, psychological well being, and adherence to treatment regimens. Hypoglycemic events can impact the health economics of the patient, their employer, and third-party payers. Insulin treatment is a key predictor of hypoglycemia, with one large population-based study reporting an overall prevalence of 7.1% (type 1 diabetes mellitus and 7.3% (type 2 diabetes mellitus in insulin-treated patients, compared with 0.8% in patients with type 2 diabetes treated with an oral sulfonylurea. Patients with type 1 diabetes typically experience symptomatic hypoglycemia on average twice weekly and severe hypoglycemia once annually. The progressive loss of islet cell function in patients with type 2 diabetes results in a higher risk of both symptomatic and unrecognized hypoglycemia over time. Patients with diabetes who become hypoglycemic are also more susceptible to developing defective counter-regulation, also known as hypoglycemia awareness autonomic failure, which is life-threatening and must be aggressively addressed. In patients unable to recognize hypoglycemia symptoms, frequent home monitoring or use of continuous glucose sensors are critical. Primary care physicians play a key role in the prevention and management of hypoglycemia in patients with diabetes, particularly in those requiring intensive insulin therapy, yet physicians are often unaware of the multitude of consequences of hypoglycemia or how to deal with them. Careful monitoring, adherence to guidelines, and use of optimal treatment combinations are all important steps toward improving care in patients with diabetes. The most important goals are for primary care physicians to recognize that every patient treated with antihyperglycemic medications is at risk of iatrogenic hypoglycemia and to ask patients about hypoglycemia at every visit.Keywords: hypoglycemia, insulin analogs, type 1 diabetes mellitus, type 2 diabetes mellitus

  7. The discovery uncovered

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Almost exactly one hundred years after the publication of Einstein’s paper on General Relativity, the LIGO and Virgo collaborations have published a paper in which they show a gravitational signal emitted by the merger of two black holes. The signal has been observed with 5-sigma accuracy and is the first direct observation of gravitational waves.   On Thursday, 11 February, Barry Clark Barish, one of the fathers of the LIGO experiment, presented the latest results in a packed Auditorium. Ripples in space-time, the fabric of the Universe: this is how we can picture gravitational waves. In his visionary paper published in June 1916, Einstein predicted that masses deform space-time and, therefore, any change in their position causes a distortion that propagates at the speed of light, resulting in gravitational waves.   It wasn’t until 1975, almost 60 years later, that Russell Hulse and Joseph Taylor, who were awarded the Nobel Prize in 1993, inferred t...

  8. Uncovering Prepositional Senses

    DEFF Research Database (Denmark)

    Lassen, Tine

    set of rules. These rules were transformed into a dictionary of prepositional senses, where, given a preposition and a sense, ontological affinities are expressed as restrictions on the ontological types of the arguments. Thus, the essential results of this research is knowledge about the relations...

  9. Uncovering the unarchived web

    OpenAIRE

    Samar, Thaer; Huurdeman, H.C.; Ben-David, A.; Kamps, J.; Vries, de, H.J.C.

    2014-01-01

    Many national and international heritage institutes realize the importance of archiving the web for future culture heritage. Web archiving is currently performed either by harvesting a national domain, or by crawling a pre-defined list of websites selected by the archiving institution. In either method, crawling results in more information being harvested than just the websites intended for preservation; which could be used to reconstruct impressions of pages that existed on the live web of t...

  10. Uncovering the unarchived web

    NARCIS (Netherlands)

    Samar, T.; Huurdeman, H.C.; Ben-David, A.; Kamps, J.; Vries, A.P. de

    2014-01-01

    Many national and international heritage institutes realize the importance of archiving the web for future culture heritage. Web archiving is currently performed either by harvesting a national domain, or by crawling a pre-defined list of websites selected by the archiving institution. In either met

  11. Uncovering Plagiarism Networks

    OpenAIRE

    Freire, Manuel; Cebrian, Manuel; del Rosal, Emilio

    2007-01-01

    Plagiarism detection in educational programming assignments is still a problematic issue in terms of resource waste, ethical controversy, legal risks, and technical complexity. This paper presents AC, a modular plagiarism detection system. The design is portable across platforms and assignment formats and provides easy extraction into the internal assignment representation. Multiple similarity measures have been incorporated, both existing and newly-developed. Statistical analysis and several...

  12. Uncovering the Missing Routes

    DEFF Research Database (Denmark)

    Tsirogiannis, Constantinos; Tsirogiannis, Christos

    2016-01-01

    In the present work we model and analyse the global network of the illegal trade in antiquities. Our goal is to use this network to estimate for any given artefact the potential sequence of people in the network among whom this artefact was traded. For this reason, we have implemented and evaluated...... three different algorithms that estimate potential trade routes within the network. We also evaluate the performance of a popular method that estimates direct links in the network, links which may not have been documented in the police records....

  13. Deschooling Society, Uncovering Illich

    Science.gov (United States)

    Bauer, Norman J.

    1972-01-01

    Critical analysis of the work of Ivan D. Illich, crediting him with providing a significant contribution to current efforts by a number of thinkers to reenergize our cultural consciousness relative to the insidious effects which institutional dependency fosters. (Author/GB)

  14. Uncovering the Cornfield

    DEFF Research Database (Denmark)

    Carter, Dale

    2015-01-01

    Observers agree that a pivotal factor in the abandonment of the Beach Boys’ Smile album in 1967 was the hostility shown by group members to some of Brian Wilson co-writer Van Dyke Parks’s lyrics. The latter still tend, however, to be cited more than they are analyzed. This reading of the song...

  15. Sporty materials uncovered

    Directory of Open Access Journals (Sweden)

    Kevin Edwards

    2004-03-01

    Full Text Available Materials in Sports Equipment is a welcome addition to books on materials engineering, says Kevin Edwards. It fills a gap in coverage of the important sports market, where advances in materials can lead to improved performance.

  16. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice.

    Science.gov (United States)

    Miyata, Haruhiko; Castaneda, Julio M; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M

    2016-07-12

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  17. Uncovering ultrastructural defences in Daphnia magna--an interdisciplinary approach to assess the predator-induced fortification of the carapace.

    Directory of Open Access Journals (Sweden)

    Max Rabus

    Full Text Available The development of structural defences, such as the fortification of shells or exoskeletons, is a widespread strategy to reduce predator attack efficiency. In unpredictable environments these defences may be more pronounced in the presence of a predator. The cladoceran Daphnia magna (Crustacea: Branchiopoda: Cladocera has been shown to develop a bulky morphotype as an effective inducible morphological defence against the predatory tadpole shrimp Triops cancriformis (Crustacea: Branchiopoda: Notostraca. Mediated by kairomones, the daphnids express an increased body length, width and an elongated tail spine. Here we examined whether these large scale morphological defences are accompanied by additional ultrastructural defences, i.e. a fortification of the exoskeleton. We employed atomic force microscopy (AFM based nanoindentation experiments to assess the cuticle hardness along with tapping mode AFM imaging to visualise the surface morphology for predator exposed and non-predator exposed daphnids. We used semi-thin sections of the carapace to measure the cuticle thickness, and finally, we used fluorescence microscopy to analyse the diameter of the pillars connecting the two carapace layers. We found that D. magna indeed expresses ultrastructural defences against Triops predation. The cuticle in predator exposed individuals is approximately five times harder and two times thicker than in control daphnids. Moreover, the pillar diameter is significantly increased in predator exposed daphnids. These predator-cue induced changes in the carapace architecture should provide effective protection against being crushed by the predator's mouthparts and may add to the protective effect of bulkiness. This study highlights the potential of interdisciplinary studies to uncover new and relevant aspects even in extensively studied fields of research.

  18. The defect level and ideal thermal conductivity of graphene uncovered by residual thermal reffusivity at the 0 K limit.

    Science.gov (United States)

    Xie, Yangsu; Xu, Zaoli; Xu, Shen; Cheng, Zhe; Hashemi, Nastaran; Deng, Cheng; Wang, Xinwei

    2015-06-14

    Due to its intriguing thermal and electrical properties, graphene has been widely studied for potential applications in sensor and energy devices. However, the reported value for its thermal conductivity spans from dozens to thousands of W m(-1) K(-1) due to different levels of alternations and defects in graphene samples. In this work, the thermal diffusivity of suspended four-layered graphene foam (GF) is characterized from room temperature (RT) down to 17 K. For the first time, we identify the defect level in graphene by evaluating the inverse of thermal diffusivity (termed "thermal reffusivity": Θ) at the 0 K limit. By using the Debye model of Θ = Θ0 + C× e(-θ/2T) and fitting the Θ-T curve to the point of T = 0 K, we identify the defect level (Θ0) and determine the Debye temperature of graphene. Θ0 is found to be 1878 s m(-2) for the studied GF and 43-112 s m(-2) for three highly crystalline graphite materials. This uncovers a 16-43-fold higher defect level in GF than that in pyrolytic graphite. In GF, the phonon mean free path solely induced by defects and boundary scattering is determined as 166 nm. The Debye temperature of graphene is determined to be 1813 K, which is very close to the average theoretical Debye temperature (1911 K) of the three acoustic phonon modes in graphene. By subtracting the defect effect, we report the ideal thermal diffusivity and conductivity (κideal) of graphene presented in the 3D foam structure in the range of 33-299 K. Detailed physics based on chemical composition and structure analysis are given to explain the κideal-T profile by comparing with those reported for suspended graphene. PMID:25981826

  19. A genome-wide immunodetection screen in S. cerevisiae uncovers novel genes involved in lysosomal vacuole function and morphology.

    Directory of Open Access Journals (Sweden)

    Florante Ricarte

    Full Text Available Vacuoles of yeast Saccharomyces cerevisiae are functionally analogous to mammalian lysosomes. Both are cellular organelles responsible for macromolecular degradation, ion/pH homeostasis, and stress survival. We hypothesized that undefined gene functions remain at post-endosomal stage of vacuolar events and performed a genome-wide screen directed at such functions at the late endosome and vacuole interface - ENV genes. The immunodetection screen was designed to identify mutants that internally accumulate precursor form of the vacuolar hydrolase carboxypeptidase Y (CPY. Here, we report the uncovering and initial characterizations of twelve ENV genes. The small size of the collection and the lack of genes previously identified with vacuolar events are suggestive of the intended exclusive functional interface of the screen. Most notably, the collection includes four novel genes ENV7, ENV9, ENV10, and ENV11, and three genes previously linked to mitochondrial processes - MAM3, PCP1, PPE1. In all env mutants, vesicular trafficking stages were undisturbed in live cells as assessed by invertase and active α-factor secretion, as well as by localization of the endocytic fluorescent marker FM4-64 to the vacuole. Several mutants exhibit defects in stress survival functions associated with vacuoles. Confocal fluorescence microscopy revealed the collection to be significantly enriched in vacuolar morphologies suggestive of fusion and fission defects. These include the unique phenotype of lumenal vesicles within vacuoles in the novel env9Δ mutant and severely fragmented vacuoles upon deletion of GET4, a gene recently implicated in tail anchored membrane protein insertion. Thus, our results establish new gene functions in vacuolar function and morphology, and suggest a link between vacuolar and mitochondrial events.

  20. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

    Science.gov (United States)

    Miyata, Haruhiko; Castaneda, Julio M.; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R.; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L.; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M.; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M.

    2016-01-01

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  1. PPARalpha siRNA-treated expression profiles uncover the causal sufficiency network for compound-induced liver hypertrophy.

    Directory of Open Access Journals (Sweden)

    Xudong Dai

    2007-03-01

    Full Text Available Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs against the gene for peroxisome proliferator-activated receptor alpha (Ppara, our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARalpha-induced liver hypertrophy is supported by their ability to predict non-PPARalpha-induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005. Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug

  2. Risk of Post-ERCP Pancreatitis after placement of Covered versus Uncovered Self-Expandable Biliary Metal Stents: A Systematic Review and Meta-Analysis

    OpenAIRE

    Yaseen Alastal; Tariq Hammad; Muhammad Ali Khan; Khalil, Basmah W.; Sobia Khan; Mohammad Kashif Ismail; Ali Nawras; Aijaz Sofi

    2008-01-01

    Background Self-expandable metal stents are commonly used in the management of malignant biliary obstruction due to higher patency rates compared to plastic stents. Development of covered self-expandable metal stents has led to extended stent patency compared to uncovered self-expandable metal stents. However, there are concerns that deployment of covered self-expandable metal stents may be associated with higher risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis, acute...

  3. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients

    OpenAIRE

    Hsieh, Jennifer; Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Jonathan M Buscaglia

    2015-01-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, r...

  4. Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jinjin Li

    Full Text Available To compare the efficacy of using covered self-expandable metal stents (CSEMSs and uncovered self-expandable metal stents (UCSEMSs to treat objective jaundice caused by an unresectable malignant tumor.We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included.The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR 0.93, 95% confidence interval (CI 0.19-4.53; p = 0.93, I2 = 0%, patient survival (HR 0.77, 95% CI 0.05-10.87; p = 0.85, I2 = 0%, overall stent dysfunction (relative ratio (RR 0.85, M-H, random, 95% CI 0.57-1.25; p = 0.83, I2 = 63%, the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94-1.68; p = 0.12, I2 = 0% or the change in serum bilirubin (weighted mean difference (WMD -0.13, IV fixed, 95% CI 0.56-0.3; p = 0.55, I2 = 0%. However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M-H, random, 95% CI 0.12-0.52; p = 0.002, I2 = 40% but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03-3.02; p = 0.04, I2 = 0%. Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54-34.24; p = 0.008, I2 = 0% and a higher rate of sludge formation (RR 2.47, M-H, fixed, 95% CI 1.36-4.50; p = 0.003, I2 = 0%.Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary

  5. Transcript profiles uncover temporal and stress-induced changes of metabolic pathways in germinating sugar beet seeds

    Directory of Open Access Journals (Sweden)

    Windhövel Andrea

    2008-12-01

    Full Text Available Abstract Background With a cultivation area of 1.75 Mio ha and sugar yield of 16.7 Mio tons in 2006, sugar beet is a crop of great economic importance in Europe. The productivity of sugar beet is determined significantly by seed vigour and field emergence potential; however, little is known about the molecular mechanisms underlying these traits. Both traits exhibit large variations within sugar beet germplasm that have been difficult to ascribe to either environmental or genetic causes. Among potential targets for trait improvement, an enhancement of stress tolerance is considered because of the high negative influence of environmental stresses on trait parameters. Extending our knowledge of genetic and molecular determinants of sugar beet germination, stress response and adaptation mechanisms would facilitate the detection of new targets for breeding crop with an enhanced field emergence potential. Results To gain insight into the sugar beet germination we initiated an analysis of gene expression in a well emerging sugar beet hybrid showing high germination potential under various environmental conditions. A total of 2,784 ESTs representing 2,251 'unigenes' was generated from dry mature and germinating seeds. Analysis of the temporal expression of these genes during germination under non-stress conditions uncovered drastic transcriptional changes accompanying a shift from quiescent to metabolically active stages of the plant life cycle. Assay of germination under stressful conditions revealed 157 genes showing significantly different expression patterns in response to stress. As deduced from transcriptome data, stress adaptation mechanisms included an alteration in reserve mobilization pathways, an accumulation of the osmoprotectant glycine betaine, late embryogenesis abundant proteins and detoxification enzymes. The observed transcriptional changes are supposed to be regulated by ABA-dependent signal transduction pathway. Conclusion This study

  6. Comparative analysis of the Photorhabdus luminescens and the Yersinia enterocolitica genomes: uncovering candidate genes involved in insect pathogenicity

    Directory of Open Access Journals (Sweden)

    Fuchs Thilo M

    2008-01-01

    Full Text Available Abstract Background Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes and is highly pathogenic towards insects but not to humans. In contrast, Y. enterocolitica is widely found in the environment and mainly known to cause gastroenteritis in men, but has only recently been shown to be also toxic for insects. It is expected that both pathogens share an overlap of genetic determinants that play a role within the insect host. Results A selective genome comparison was applied. Proteins belonging to the class of two-component regulatory systems, quorum sensing, universal stress proteins, and c-di-GMP signalling have been analysed. The interorganismic synopsis of selected regulatory systems uncovered common and distinct signalling mechanisms of both pathogens used for perception of signals within the insect host. Particularly, a new class of LuxR-like regulators was identified, which might be involved in detecting insect-specific molecules. In addition, the genetic overlap unravelled a two-component system that is unique for the genera Photorhabdus and Yersinia and is therefore suggested to play a major role in the pathogen-insect relationship. Our analysis also highlights factors of both pathogens that are expressed at low temperatures as encountered in insects in contrast to higher (body temperature, providing evidence that temperature is a yet under-investigated environmental signal for bacterial adaptation to various hosts. Common degradative metabolic pathways are described that might be used to explore nutrients within the insect gut or hemolymph, thus enabling the proliferation of P. luminescens and Y. enterocolitica in their invertebrate hosts. A strikingly higher number of genes encoding insecticidal toxins and other virulence factors in P. luminescens compared to Y. enterocolitica correlates with the higher virulence of P

  7. Risk of Post-ERCP Pancreatitis after placement of Covered versus Uncovered Self-Expandable Biliary Metal Stents: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yaseen Alastal

    2008-09-01

    Full Text Available Background Self-expandable metal stents are commonly used in the management of malignant biliary obstruction due to higher patency rates compared to plastic stents. Development of covered self-expandable metal stents has led to extended stent patency compared to uncovered self-expandable metal stents. However, there are concerns that deployment of covered self-expandable metal stents may be associated with higher risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis, acute cholecystitis and stent migration. Objective We performed this meta-analysis to assess the risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis and other adverse events (acute cholecystitis and stent migration with biliary covered self-expandable metal stents compared to uncovered self-expandable metal stents. We also assessed the proportion of stent patency at 6 and 12 months between the two groups. Methods We searched MedLine, EMBASE, Cochrane database, ISI Web of Science and Scopus from January 1989 through June, 2014, to identify randomized controlled trials and observational studies that provided data on the risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis and other adverse events following the placement of covered self-expandable metal stents versus uncovered self-expandable metal stents in patients with biliary obstruction. The Mantel–Haenszel method was used to pool data of post-endoscopic retrograde cholangio- pancreatography pancreatitis, acute cholecystitis, stent migration and proportion of stent patency over 6 and 12 months into fixed or random effect model of meta-analyses. Odds ratio was used to generate an overall effect estimate of the outcome. Results Eight studies (6 randomized controlled trials and 2 observational studies with a total of 1078 patients were included in the meta-analysis. The pooled odds ratio with 95% confidence intervals for risk of post-endoscopic retrograde cholangio

  8. AB039. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    OpenAIRE

    Li, Zesong

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA...

  9. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress.

    Science.gov (United States)

    Prasad, Kasavajhala V S K; Abdel-Hameed, Amira A E; Xing, Denghui; Reddy, Anireddy S N

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  10. Uncovering Barriers to Teaching Assistants (TAs) Implementing Inquiry Teaching: Inconsistent Facilitation Techniques, Student Resistance, and Reluctance to Share Control over Learning with Students †

    Science.gov (United States)

    Gormally, Cara; Sullivan, Carol Subiño; Szeinbaum, Nadia

    2016-01-01

    Inquiry-based teaching approaches are increasingly being adopted in biology laboratories. Yet teaching assistants (TAs), often novice teachers, teach the majority of laboratory courses in US research universities. This study analyzed the perspectives of TAs and their students and used classroom observations to uncover challenges faced by TAs during their first year of inquiry-based teaching. Our study revealed three insights about barriers to effective inquiry teaching practices: 1) TAs lack sufficient facilitation skills; 2) TAs struggle to share control over learning with students as they reconcile long-standing teaching beliefs with newly learned approaches, consequently undermining their fledgling ability to use inquiry approaches; and 3) student evaluations reinforce teacher-centered behaviors as TAs receive positive feedback conflicting with inquiry approaches. We make recommendations, including changing instructional feedback to focus on learner-centered teaching practices. We urge TA mentors to engage TAs in discussions to uncover teaching beliefs underlying teaching choices and support TAs through targeted feedback and practice. PMID:27158302

  11. Uncovering Barriers to Teaching Assistants (TAs) Implementing Inquiry Teaching: Inconsistent Facilitation Techniques, Student Resistance, and Reluctance to Share Control over Learning with Students.

    Science.gov (United States)

    Gormally, Cara; Sullivan, Carol Subiño; Szeinbaum, Nadia

    2016-05-01

    Inquiry-based teaching approaches are increasingly being adopted in biology laboratories. Yet teaching assistants (TAs), often novice teachers, teach the majority of laboratory courses in US research universities. This study analyzed the perspectives of TAs and their students and used classroom observations to uncover challenges faced by TAs during their first year of inquiry-based teaching. Our study revealed three insights about barriers to effective inquiry teaching practices: 1) TAs lack sufficient facilitation skills; 2) TAs struggle to share control over learning with students as they reconcile long-standing teaching beliefs with newly learned approaches, consequently undermining their fledgling ability to use inquiry approaches; and 3) student evaluations reinforce teacher-centered behaviors as TAs receive positive feedback conflicting with inquiry approaches. We make recommendations, including changing instructional feedback to focus on learner-centered teaching practices. We urge TA mentors to engage TAs in discussions to uncover teaching beliefs underlying teaching choices and support TAs through targeted feedback and practice. PMID:27158302

  12. 人工环境下无覆盖土壤散湿量计算%Uncovered soil moisture gain calculation in artificial environment

    Institute of Scientific and Technical Information of China (English)

    胡晨炯; 邓辉炼

    2012-01-01

    Considering the situation of a ruins protection hall with a large floor proportion of uncovered soil in Guangzhou and borrowing some ideas from the calculation method and well-developed empirical formula of groundwater evaporation rate in hydro science, puts forward a method for calculating the uncovered soil moisture gain in artificial environment. In this method, outside evaporation capacity is characterized with the evaporation of exposed water surface and the water supply capacity of soil is characterized with groundwater evaporation coefficient. The design effect of the project indicates that the precision of the calculation method can meet the demand of engineering.%针对广州某遗址保护大厅内多为裸露土壤的情况,借鉴水利科学中潜水蒸发量的计算方法及成熟的相关经验公式,提出了人工环境下无覆盖土壤散湿量的计算方法.在该计算方法中,用暴露水面的蒸发量来表征外界蒸发能力,用潜水蒸发系数来表征土壤的输水能力.设计效果表明,该方法的计算精度能满足工程实际的需要.

  13. Uncovering the secret lives of sewer rats (Rattus norvegicus): Movements, distribution and population dynamics revealed by a capture-mark-recapture study

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte; Sluydts, Vincent; Leirs, Herwig E.l.

    2012-01-01

    behaviour of these populations. Aims.: The study aimed to uncover the population dynamics, movements and distribution of rats in populations living in sewers. Methods.: We studied rats in a capture–mark–recapture study in two adjacent but separate sewer systems in suburban Copenhagen, Denmark, covering a...... surface area of 30 Ha. Multiple-capture live traps were placed in manholes in public sewers; animals were marked individually and data were collected every fourth week for a period of almost 3 years. Key results.: In total, 332 individual rats were trapped. Approximately one-third were only caught once...... dimensions. Juvenile rats were captured more in the smaller and drier sewer sections. Activity areas of rats of both sexes overlapped partially, and observations of bite wounds were rare, suggesting a high degree of tolerance. The average maximal distance covered by rats was ~200 m for both sexes. Day...

  14. Palliation of Pyloric Stenosis Caused by Gastric Cancer Using an Endoscopically Placed Covered Ultraflex Stent: Covered Stent Inside an Occluded Uncovered Stent

    International Nuclear Information System (INIS)

    A 71-year-old man developed pyloric stenosis caused by gastric cancer. Vomiting and nausea resolved after the insertion of an uncovered Ultraflex stent (length 10 cm, inner diameter 18u23 mm) through a 7-cm-long stenosis, and the patient was able to eat a soft diet. After 6 weeks, stent occlusion occurred due to tumor ingrowth and accumulation of food residue. Endoscopic observation showed a very narrow residual lumen. A covered Ultraflex stent (length 10 cm, inner diameter 18u23 mm) was inserted through the first stent and expanded to its maximum diameter over the next 2 days. The patient's vomiting and nausea improved rapidly. He died 6 months after the second stenting procedure, from metastatic tumor spread, having remained free of nausea and vomiting. In this case, a covered metallic stent prevented tumor ingrowth and maintained gastrointestinal patency

  15. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients.

    Science.gov (United States)

    Hsieh, Jennifer; Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Buscaglia, Jonathan M

    2015-10-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, retrospective case series of all patients who underwent bilateral placement of uncovered Wallflex(TM) biliary stents between July 2008 and July 2014, we evaluate the feasibility, technical success, and safety of patients undergoing serial insertion of bilateral UCSEMS using the 8 Fr Wallflex(TM) biliary system for malignant hilar obstruction. A total of 17 patients were included. Primary cholangiocarcinoma, Bismuth IV, was the most common diagnosis. Mean procedure time was 54.4 minutes. Overall procedural technical success was achieved in 17/17 patients. Stricture dilation was necessary prior to Wallflex(TM) insertion in 8/17 patients (47.1%). Transpapillary extension of two stents was performed in all patients. There were no cases of stent deployment malfunction, or inability to insert or deploy the 2(nd) stent. Nine of 17 patients (52.9%) required inpatient hospitalization following ERCP; the most common indications were abdominal pain and need for IV antibiotics. There was one case of ERCP-related cholangitis otherwise; there were no other major complications. Bilateral, serial insertion of UCSEMS using the 8 Fr Wallflex(TM) biliary system in malignant hilar obstruction is feasible with an excellent technical success profile. Using this device for side-by-side deployment of UCSEMS appears to be safe in the majority of patients. PMID:26605283

  16. Integration of small RNAs, degradome and transcriptome sequencing in hyperaccumulator Sedum alfredii uncovers a complex regulatory network and provides insights into cadmium phytoremediation.

    Science.gov (United States)

    Han, Xiaojiao; Yin, Hengfu; Song, Xixi; Zhang, Yunxing; Liu, Mingying; Sang, Jiang; Jiang, Jing; Li, Jihong; Zhuo, Renying

    2016-06-01

    The hyperaccumulating ecotype of Sedum alfredii Hance is a cadmium (Cd)/zinc/lead co-hyperaccumulating species of Crassulaceae. It is a promising phytoremediation candidate accumulating substantial heavy metal ions without obvious signs of poisoning. However, few studies have focused on the regulatory roles of miRNAs and their targets in the hyperaccumulating ecotype of S. alfredii. Here, we combined analyses of the transcriptomics, sRNAs and the degradome to generate a comprehensive resource focused on identifying key regulatory miRNA-target circuits under Cd stress. A total of 87 721 unigenes and 356 miRNAs were identified by deep sequencing, and 79 miRNAs were differentially expressed under Cd stress. Furthermore, 754 target genes of 194 miRNAs were validated by degradome sequencing. A gene ontology (GO) enrichment analysis of differential miRNA targets revealed that auxin, redox-related secondary metabolism and metal transport pathways responded to Cd stress. An integrated analysis uncovered 39 pairs of miRNA targets that displayed negatively correlated expression profiles. Ten miRNA-target pairs also exhibited negative correlations according to a real-time quantitative PCR analysis. Moreover, a coexpression regulatory network was constructed based on profiles of differentially expressed genes. Two hub genes, ARF4 (auxin response factor 4) and AAP3 (amino acid permease 3), which might play central roles in the regulation of Cd-responsive genes, were uncovered. These results suggest that comprehensive analyses of the transcriptomics, sRNAs and the degradome provided a useful platform for investigating Cd hyperaccumulation in S. alfredii, and may provide new insights into the genetic engineering of phytoremediation. PMID:26801211

  17. DIANA-mirExTra v2.0: Uncovering microRNAs and transcription factors with crucial roles in NGS expression data.

    Science.gov (United States)

    Vlachos, Ioannis S; Vergoulis, Thanasis; Paraskevopoulou, Maria D; Lykokanellos, Filopoimin; Georgakilas, Georgios; Georgiou, Penny; Chatzopoulos, Serafeim; Karagkouni, Dimitra; Christodoulou, Foteini; Dalamagas, Theodore; Hatzigeorgiou, Artemis G

    2016-07-01

    Differential expression analysis (DEA) is one of the main instruments utilized for revealing molecular mechanisms in pathological and physiological conditions. DIANA-mirExTra v2.0 (http://www.microrna.gr/mirextrav2) performs a combined DEA of mRNAs and microRNAs (miRNAs) to uncover miRNAs and transcription factors (TFs) playing important regulatory roles between two investigated states. The web server uses as input miRNA/RNA-Seq read count data sets that can be uploaded for analysis. Users can combine their data with 350 small-RNA-Seq and 65 RNA-Seq in-house analyzed libraries which are provided by DIANA-mirExTra v2.0.The web server utilizes miRNA:mRNA, TF:mRNA and TF:miRNA interactions derived from extensive experimental data sets. More than 450 000 miRNA interactions and 2 000 000 TF binding sites from specific or high-throughput techniques have been incorporated, while accurate miRNA TSS annotation is obtained from microTSS experimental/in silico framework. These comprehensive data sets enable users to perform analyses based solely on experimentally supported information and to uncover central regulators within sequencing data: miRNAs controlling mRNAs and TFs regulating mRNA or miRNA expression. The server also supports predicted miRNA:gene interactions from DIANA-microT-CDS for 4 species (human, mouse, nematode and fruit fly). DIANA-mirExTra v2.0 has an intuitive user interface and is freely available to all users without any login requirement. PMID:27207881

  18. Enzymes in biogenesis of plant cell wall polysaccharides. Enzyme characterization using tracer techniques

    International Nuclear Information System (INIS)

    Enzymes and metabolic pathways, by which starch and cell wall polysaccharides are formed, were investigated in order to learn how these processes are regulated and to identify the enzymatic regulatory mechanisms involved. Germinating lily pollen was used for studies of cell wall formation, and pollen and maize endosperm for studies of starch biosynthesis. Hexokinase being the first step in conversion of hexoses to starch, wall polysaccharides and respiratory substrates, maize endosperm enzyme was assayed by its conversion of 14C-hexose to 14C-hexose-6-P, and rapid separation of the two labelled compounds on anion-exchange paper. This enzyme did not appear to be under tight regulation by feed-back inhibition or activation, nor to be severely inhibited by glucose-6-P or activated by citrate. ADP-glucose pyrophosphorylase and other pyrophosphorylases were assayed radiochemically with 14C-glucose-1-P (forward direction) or 32-PPsub(i) (reverse direction). They showed that the maize endosperm enzyme was activated by the glycolytic intermediates fructose-6-P and 3-phosphoglycerate, and that low levels of the enzyme were present in the high sucrose-low starch mutant named shrunken-2. Under optimal in-vitro assay conditions, the pollen enzyme reacted four times faster than the observed in-vivo rate of starch accumulation. Biogenesis of plant cell wall polysaccharides requires the conversion of hexose phosphates to various sugar nucleotides and utilization of the latter by the appropriate polysaccharide synthetases. Lily pollen possesses a β-1,3-glucan synthetase which is activated up to six-fold by β-linked oligosaccharides. Hence, the in-vivo activity of this enzyme may be modulated by such effector molecules

  19. Structure, function and regulation of the enzymes in the starch biosynthetic pathway.

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, Jim

    2013-11-30

    structure of ADP- Glucose pyrophosphorylase from potato in its inhibited conformation, and bound to both ATP and ADP-glucose. In addition, we have determined the first structure of glycogen synthase in its "closed", catalytically active conformation bound to ADP-glucose. We also determined the structure of glycogen synthase bound to malto-oligosaccharides, showing for the first time that an enzyme in the starch biosynthetic pathway recognizes glucans not just in its active site but on binding sites on the surface of the enzyme ten’s of Angstroms from the active site. In addition our structure of a glycogen branching enzyme bound to malto-oligosaccharides identified seven distinct binding sites distributed about the surface of the enzyme. We will now determine the function of these sites to get a molecular-level picture of exactly how these enzymes interact with their polymeric substrates and confer specificity leading to the complex structure of the starch granule. We will extend our studies to other isoforms of the enzymes, to understand how their structures give rise to their distinct function. Our goal is to understand what accounts for the various functional differences between SS and SBE isoforms at a molecular level.

  20. Changes in photosynthesis and pigmentation in an agp deletion mutant of the cyanobacterium Synechocystis sp.

    Science.gov (United States)

    Miao, Xiaoling; Wu, Qingyu; Wu, Guifang; Zhao, Nanming

    2003-03-01

    The agp gene encoding ADP-glucose pyrophosphorylase is involved in cyanobacterial glycogen synthesis. By in vitro DNA recombination technology, agp deletion mutant (agp-) of cyanobacterium Synechocystis sp. PCC 6803 was constructed. This mutation led to a complete absence of glycogen biosynthesis. As compared with WT (wild type), a 60% decrease in ratio of the c-phycocyanine/chlorophyll a and no significant change in the carotenoid/chlorophyll a were observed in agp- cells. The agp- mutant had 38% less photosynthetic capacity when grown in light over 600 micromol m(-2) s(-1). Under lower light intensity, the final biomass of the mutant strain was only 1.1 times of that of the WT strain under mixotrophic condition after 6 d culture. Under higher light intensity, however, the final biomass of the WT strain under mixotrophic conditions was 3 times that of the mutant strain after 6 d culture and 1.5 times under photoautotrophic conditions. The results indicate that there is a minimum requirement for glycogen synthesis for normal growth and development in cyanobacteria. PMID:12882559

  1. Effects of microgravity and clinorotation on stress ethylene production in two starchless mutants of Arabidopsis thaliana

    Science.gov (United States)

    Gallegos, Gregory L.; Hilaire, Emmanuel M.; Peterson, Barbara V.; Brown, Christopher S.; Guikema, James A.

    1995-01-01

    Starch filled plastids termed amyloplasts, contained within columella cells of the root caps of higher plant roots, are believed to play a statolith-like role in the gravitropic response of roots. Plants having amyloplasts containing less starch exhibit a corresponding reduction in gravitropic response. We have observed enhanced ethylene production by sweet clover (Melilotus alba L.) seedlings grown in the altered gravity condition of a slow rotating clinostat, and have suggested that this is a stress response resulting from continuous gravistimulation rather than as a result of the simulation of a microgravity condition. If so, we expect that plants deficient in starch accumulation in amyloplasts may produce less stress ethylene when grown on a clinostat. Therefore, we have grown Arabidopsis thaliana in the small, closed environment of the Fluid Processing Apparatus (FPA). In this preliminary report we compare stationary plants with clinorotated and those grown in microgravity aboard Discovery during the STS-63 flight in February 1995. In addition to wildtype, two mutants deficient in starch biosynthesis, mutants TC7 and TL25, which are, respectively, deficient in the activity of amyloplast phosphoglucomutase and ADP-glucose pyrophosphorylase, were grown for three days before being fixed within the FPA. Gas samples were aspirated from the growth chambers and carbon dioxide and ethylene concentations were measured using a gas chromatograph. The fixed tissue is currently undergoing further morphologic and microscopic characterization.

  2. Effect of Soil Texture on Starch Accumulation and Activities of Key Enzymes of Starch Synthesis in the Kernel of ZM 9023

    Institute of Scientific and Technical Information of China (English)

    WANG Wen-jing; ZHAN Hai-hong

    2008-01-01

    Three kinds of soil texture (clay-loam, mid-loam, and sand-loam soil) were used to study the effects of soil texture on starch accumulating rate and the changes in activities of the key enzymes of starch synthesis in the kernel during grain filling in high gluten content wheat ZM 9023, under conditions of pond culture. The content of starch and its components were measured according to the method of double-wave length described by Bao (1996). ADP-glucose pyrophosphorylase (AGPP) activity was tested according to the method described by Doehlert et al. (1988). Soluble starch synthase (SSS) and starch branching enzyme (SBE) activities were tested according to the method described by Nakamura et al. (1989). The amylose, amylopectin, and total starch accumulating rate in the kernel of ZM 9023 were found to be a single-peak curve in three different soil textures during grain filling, and peaked 20, 15, and 15 d after anthesis, respectively. The activities of the enzymes, AGPP, SSS, and SBE, in the kernel of ZM 9023 had a single-peaked curve, which peaked 20, 15, and 15 d after anthesis, respectively. The activities of the above three enzymes of ZM 9023 were higher in the sand-loam soil. The accumulating peak of amylose formed later compared to that of amylopectin. The sand-loam soil could help high gluten content cultivars to synthesize starch.

  3. Expression Profiling of Cassava Storage Roots Reveals an Active Process of Glycolysis/Gluconeogenesis

    Institute of Scientific and Technical Information of China (English)

    Jun Yang; Dong An; Peng Zhang

    2011-01-01

    Mechanisms related to the development of cassava storage roots and starch accumulation remain largely unknown. To evaluate genome-wide expression patterns during tuberization, a 60 mer oligonucleotide microarray representing 20 840 cassava genes was designed to identify differentially expressed transcripts in fibrous roots, developing storage roots and mature storage roots. Using a random variance model and the traditional twofold change method for statistical analysis, 912 and 3 386 upregulated and downregulated genes related to the three developmental phases were identified. Among 25 significantly changed pathways identified, glycolysislgluconeogenesis was the most evident one. Rate-limiting enzymes were identified from each individual pathway, for example, enolase, L-lactate dehydrogenase and aldehyde dehydrogenase for glycolysis/gluconeogenesis, and ADP-glucose pyrophosphorylase, starch branching enzyme and glucan phosphorylase for sucrose and starch metabolism. This study revealed that dynamic changes in at least 16% of the total transcripts, including transcription fac-tors, oxidoreductasesltransferaseslhydrolases, hormone-related genes, and effectors of homeostasis. The reliability of these differentially expressed genes was verified by quantitative real-time reverse transcription-polymerase chain reaction. These studies should facilitate our understanding of the storage root formation and cassava improvement.

  4. Structural Comparison, Substrate Specificity, and Inhibitor Binding of AGPase Small Subunit from Monocot and Dicot: Present Insight and Future Potential

    Directory of Open Access Journals (Sweden)

    Kishore Sarma

    2014-01-01

    Full Text Available ADP-glucose pyrophosphorylase (AGPase is the first rate limiting enzyme of starch biosynthesis pathway and has been exploited as the target for greater starch yield in several plants. The structure-function analysis and substrate binding specificity of AGPase have provided enormous potential for understanding the role of specific amino acid or motifs responsible for allosteric regulation and catalytic mechanisms, which facilitate the engineering of AGPases. We report the three-dimensional structure, substrate, and inhibitor binding specificity of AGPase small subunit from different monocot and dicot crop plants. Both monocot and dicot subunits were found to exploit similar interactions with the substrate and inhibitor molecule as in the case of their closest homologue potato tuber AGPase small subunit. Comparative sequence and structural analysis followed by molecular docking and electrostatic surface potential analysis reveal that rearrangements of secondary structure elements, substrate, and inhibitor binding residues are strongly conserved and follow common folding pattern and orientation within monocot and dicot displaying a similar mode of allosteric regulation and catalytic mechanism. The results from this study along with site-directed mutagenesis complemented by molecular dynamics simulation will shed more light on increasing the starch content of crop plants to ensure the food security worldwide.

  5. Changes in Activities of Key Enzymes for Starch Synthesis and Glutamine Synthetase in Grains of Progenies from a Rice Cross During Grain Filling

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-guang; LIU Hai-ying; JIN Zheng-xun; LIU Hong-liang; HUANG Xing; XU Mei-lan; ZHANG Feng-zhuan

    2010-01-01

    The progenies differed in amylose and protein contents in grains, which derived from a rice cross, Dongnong 423×Toukei 180, were used to study changes in the activities of ADP-glucose pyrophosphorylase (AGPP), soluble starch synthetase (SSS), starch branching enzyme (SBE) and glutamine synthetase (GS) in rice grains during grain filling. The activities of AGPP, SSS and SBE gradually increased and then declined as a single-peak curve with the process of grain filling in the progenies with high and low amylose contents in grains. The progenies with high amylose content peaked earlier in the AGPP, SSS and SBE activities and had higher AGPP, SSS and SBE activities at the early grain filling stage than those with low amylose content. The GS activity peaked earlier and was higher at the late stage of grain filling in the progenies with high protein content than in those with low protein content. It is suggested that the activities of key enzymes for starch synthesis and glutamine synthetase could be changed in oriented breeding for amylose and protein contents in grains.

  6. Can fast-growing plantation trees escape biochemical down-regulation of photosynthesis when grown throughout their complete production cycle in the open air under elevated carbon dioxide?

    Science.gov (United States)

    Davey, P A; Olcer, H; Zakhleniuk, O; Bernacchi, C J; Calfapietra, C; Long, S P; Raines, C A

    2006-07-01

    Poplar trees sustain close to the predicted increase in leaf photosynthesis when grown under long-term elevated CO2 concentration ([CO2]). To investigate the mechanisms underlying this response, carbohydrate accumulation and protein expression were determined over four seasons of growth. No increase in the levels of soluble carbohydrates was observed in the young expanding or mature sun leaves of the three poplar genotypes during this period. However, substantial increases in starch levels were observed in the mature leaves of all three poplar genotypes grown in elevated [CO2]. Despite the very high starch levels, no changes in the expression of photosynthetic Calvin cycle proteins, or in the starch biosynthetic enzyme ADP-glucose pyrophosphorylase (AGPase), were observed. This suggested that no long-term photosynthetic acclimation to CO2 occurred in these plants. Our data indicate that poplar trees are able to 'escape' from long-term, acclimatory down-regulation of photosynthesis through a high capacity for starch synthesis and carbon export. These findings show that these poplar genotypes are well suited to the elevated [CO2] conditions forecast for the middle of this century and may be particularly suited for planting for the long-term carbon sequestration into wood. PMID:17080946

  7. OsMADS6 plays an essential role in endosperm nutrient accumulation and is subject to epigenetic regulation in rice (Oryza sativa).

    Science.gov (United States)

    Zhang, Jian; Nallamilli, Babi R; Mujahid, Hana; Peng, Zhaohua

    2010-11-01

    MADS-box transcription factors are known for their roles in plant growth and development. The regulatory mechanisms of spatial and temporal specific expression of MADS-box genes and the function of MADS-box genes in other biological processes are still to be explored. Here, we report that OsMADS6 is highly expressed in flower and endosperm in Oryza sativa (rice). In addition to displaying a homeotic organ identity phenotype in all the four whorls of the flowers, the endosperm development is severely affected in its mutant. At least 32% of the seeds lacked starch filling and aborted. For seeds that have starch filling and develop to maturity, the starch content is reduced by at least 13%. In addition, the seed shape changes from elliptical to roundish, and the protein content increases from 12.1 to 15.0% (P < 0.05). Further investigation shows that ADP-glucose pyrophosphorylase genes, encoding the rate-limiting step enzyme in the starch synthesis pathway, are subject to the regulation of OsMADS6. Chromatin immunoprecipitation (ChIP)-PCR analyses on the chromatin of the OsMADS6 gene find that H3K27 is trimethylated in tissues where OsMADS6 is silenced, and that H3K36 is trimethylated in tissues where OsMADS6 is highly activated. Point mutation analysis reveals that leucine at position 83 is critical to OsMADS6 function. PMID:20822505

  8. Experiment 9: ASTROCULTURE: Growth and Starch Accumulation of Potato Tuber

    Science.gov (United States)

    Tibbitts, Theodore W.; Brown, Christopher S.; Croxdale, Judith G.; Wheeler, Raymond M.

    1998-01-01

    Potato explants (leaf, small stem section, and axillary bud) flown on STS-73 developed tubers of 1.5 cm diameter and 1.7 g mass during the 16-day period of space flight. The experiment was undertaken in the ASTROCULTURE(TM) experiment package under controlled temperature, humidity, lighting, and carbon dioxide concentrations. The tubers that formed in the explant system under microgravity had the same gross morphology, the same anatomical configuration of cells and tissues, and the same sizes, shapes, and surface character of starch granules as tubers formed in a 1 g environment. The total accumulation of starch and other energy containing compounds was similar in space flight and ground control tubers. Enzyme activity of starch synthase, starch phosphorylase, and total hydrolase was similar in space flight and ground controls, but activity of ADP-glucose pyrophosphorylase was reduced in the space flight tuber tissue. This experiment documented that potatoes will metabolize and accumulate starch as effectively in space flight as on the ground. Thus, this data provides the potential for effective utilization of potatoes in life support systems of space bases.

  9. Characterization and Expression Analysis of Starch Branching Enzymes in Sweet Potato

    Institute of Scientific and Technical Information of China (English)

    QIN Hua; ZHOU Shuang; ZHANG Yi-zheng

    2013-01-01

    Spatial and temporal expression patterns of Sbe1 and Sbe2 that encode starch branching enzyme (SBE) I and II, respectively, in sweet potato (Ipomoea batatas L.) were analyzed. Expression of both genes in Escherichia coli indicate that both genes encoded active SBE. Analysis with real-time quantitative polymerase chain reaction technique indicates that IbSbe1 mRNA was expressed at very low levels in leaves but was the predominant isoform in tuberous root while the reverse case was found for IbSbe2. The expression pattern of IbSbe1, closely resembles that of AGPase S, a gene coding for one of the subunits of ADP-glucose pyrophosphorylase, which is the key regulatory enzyme in the starch biosynthetic pathway. Western analysis detected at least two isoforms of SBE I in tuberous roots, those two isoforms showed adverse expression patterns with the development of the tuberous roots. Expression of the two IbSbe genes exhibited a diurnal rhythm during a 12-h cycle when fed a continuous solution of sucrose. Abscisic acid (ABA) was aother potent inducer of IbSbe expression, but bypassed the semidian oscillator.

  10. Space Experiment on Tuber Development and Starch Accumulation for CELSS

    Science.gov (United States)

    Tibbitts,Theodore W.; Croxdale, Judith C.; Brown, Christopher S.

    1997-01-01

    Potato explants (leaf, small stem section, and axillary bud), flown on STS-73, developed tubers of 1.5 cm diameter and 1.7 g mass during the 16 day period of spaceflight. The experiment was undertaken in the ASTROCULTURE(Trademark) experiment package under controlled temperature, humidity, lighting, and carbon dioxide concentrations. The tubers formed in the explant system under microgravity had the same gross morphology, the same anatomical configuration of cells and tissues, and the same sizes, shapes, and surface character of starch granules as tubers formed in a 1 g environment. The total accumulation of starch and other energy containing compounds was singular in space flight and ground control tubers. Enzyme activity of starch synthase, starch phosphorylase, and total hydrolase was similar in spaceflight and ground controls but activity of ADP-glucose pyrophosphorylase was reduced in the spaceflight tuber tissue. This experiment documented that potatoes will metabolize and accumulate starch as effectively in spaceflight as on the ground and thus this data provides the potential for effective utilization of potatoes in life support systems of space bases.

  11. Systematic Analysis of Pericarp Starch Accumulation and Degradation during Wheat Caryopsis Development.

    Directory of Open Access Journals (Sweden)

    Xurun Yu

    Full Text Available Although wheat (Triticum aestivum L. pericarp starch granule (PSG has been well-studied, our knowledge of its features and mechanism of accumulation and degradation during pericarp growth is poor. In the present study, developing wheat caryopses were collected and starch granules were extracted from their pericarp to investigate the morphological and structural characteristics of PSGs using microscopy, X-ray diffraction and Fourier transform infrared spectroscopy techniques. Relative gene expression levels of ADP-glucose pyrophosphorylase (APGase, granule-bound starch synthase II (GBSS II, and α-amylase (AMY were quantified by quantitative real-time polymerase chain reaction. PSGs presented as single or multiple starch granules and were synthesized both in the amyloplast and chloroplast in the pericarp. PSG degradation occurred in the mesocarp, beginning at 6 days after anthesis. Amylose contents in PSGs were lower and relative degrees of crystallinity were higher at later stages of development than at earlier stages. Short-range ordered structures in the external regions of PSGs showed no differences in the developing pericarp. When hydrolyzed by α-amylase, PSGs at various developmental stages showed high degrees of enzymolysis. Expression levels of AGPase, GBSS II, and AMY were closely related to starch synthesis and degradation. These results help elucidate the mechanisms of accumulation and degradation as well as the functions of PSG during wheat caryopsis development.

  12. Leaf Photosynthesis in Response to Removing Fruit During Different Phenological Stages of Fruit Development in Peach Trees

    Institute of Scientific and Technical Information of China (English)

    LI Wei-dong; LI Shao-hua; WU Ben-hong; YANG Jian-min; WANG Hong-qing

    2005-01-01

    Removing fruit (RF) and retaining fruit (CK) were carried out during different phenological stages of fruit development on one-year-old shoot of Okubo peach trees [Prunus persica (L.) Batsch.] under preventing exportation of the assimilates to the non experimental parts of the tree by girdling one-year-old shoot and keeping the same leaves between RF and CK.The results showed that fruit removal significantly decreased net photosynthetic rate (Pn), stomatal conductance (Gs)and transpiration rate (E), but significantly increased leaf surface temperature (TLeaf) at about midday as compared with CK.Internal CO2 concentration, soluble sugar content, reductive sugar content, starch content except that during the final rapid fruit growth stage, ADP-glucose pyrophosphorylase and amylase activities in source leaves were not significantly affected by fruit removal. There was a significantly positive parabolic correlation between Pn and Gs, and a strong positive linear correlation between Pn and E. Moreover, Pn increased with increased TLeaf if Tieaf was below 38℃, then decreased sharply when TLeaf exceeded the above critical temperature for both RF and CK. Pn of RF was lower, however,than that of CK in the same TLea, especially if TLeaf exceeded 38℃. It is suggested that the decreased stomatal aperture and increased TLeaf may be the important mechanism in regulating photosynthesis under a decreased strength of sink demand by RF in fruit trees.

  13. Effects of the activities of key enzymes involved in starch biosynthesis on the fine structure of amylopectin in developing rice (Oryza sativa L.) endosperms

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The dynamic changes of the activities of enzymes involving in starch biosynthesis, including ADP-glucose pyrophosphorylase (AGPase), soluble starch synthases (SSS), starch branching enzyme (SBE) and starch debranching enzymes (DBE) were studied, and changes of fine structure of amy- lopectin were characterized by isoamylase treatment during rice grain development, using trans anti-waxy gene rice plants. The relationships between the activities of those key enzymes were also analyzed. The amylose synthesis was significantly inhibited in transgenic Wanjing 9522, but the total starch content and final grain weight were less affected as compared with those of non-transgenic Wanjing 9522 rice cultivar. Analyses on the changes of activities of enzymes involving in starch bio- synthesis showed that different enzyme activities were expressed differently during rice endosperm development. Soluble starch synthase is relatively highly expressed in earlier stage of endosperm de- velopment, whilst maximal expression of granule-bound starch synthase (GBSS) occurred in mid-stage of endosperm development. No obvious differences in changes of the activities of AGPase and SBE between two rice cultivars investigated, except the DBEs. Distribution patterns of branches of amy- lopectin changed continually during the development of rice grains and varied between two rice culti- vars. It was suggested that amylopectin synthesis be prior to the synthesis of amylose and different enzymes have different roles in controlling syntheses of branches of amylopectin.

  14. Effects of Weak Light on Starch Accumulation and Starch Synthesis Enzyme Activities in Rice at the Grain Filling Stage

    Institute of Scientific and Technical Information of China (English)

    LI Tian; Ryu OHSUGI; Tohru YAMAGISHI; Haruto SASAKI

    2006-01-01

    Dynamic changes of starch, amylose, sucrose contents and the activities of starch synthesis enzymes under shading treatments after flowering were studied using two dce varieties IR72 (indica) and Nipponbare (japonica) as materials. Under shading treatments, the starch,amylose and sucrose contents decreased, while ADP-glucose pyrophosphorylase (ADPGPPase) activity only changed a little, soluble starch synthase activity and granule bound starch synthase activity decreased, soluble starch branching enzyme (SSBE, Q-enzyme) activity and granule bound starch branching enzyme (GBSBE, Q-enzyme) activity increased, and starch debranching enzyme (DBE, R-enzyme) activity vaded with varieties. Correlation analyses showed that the changes of starch content were positively and significantly correlated with the changes of sucrose content in the weak light. Both ADPGPPase activity and SSBE activity were positively and significantly correlated with starch accumulation rate. It was implied that the decline of starch synthase activities was related to the decrease of starch content and the increase of the activity of starch branching enzyme played an important role in the decrease of the ratio of amylose to the total starch under the weak light.

  15. Proteomic Analysis Reveals Key Proteins and Phosphoproteins upon Seed Germination of Wheat (Triticum aestivum L.).

    Science.gov (United States)

    Dong, Kun; Zhen, Shoumin; Cheng, Zhiwei; Cao, Hui; Ge, Pei; Yan, Yueming

    2015-01-01

    Wheat (Triticum aestivum L.) is one of the oldest cultivated crops and the second most important food crop in the world. Seed germination is the key developmental process in plant growth and development, and poor germination directly affects plant growth and subsequent grain yield. In this study, we performed the first dynamic proteome analysis of wheat seed germination using a two-dimensional differential gel electrophoresis (2D-DIGE)-based proteomic approach. A total of 166 differentially expressed protein (DEP) spots representing 73 unique proteins were identified, which are mainly involved in storage, stress/defense/detoxification, carbohydrate metabolism, photosynthesis, cell metabolism, and transcription/translation/transposition. The identified DEPs and their dynamic expression profiles generally correspond to three distinct seed germination phases after imbibition: storage degradation, physiological processes/morphogenesis, and photosynthesis. Some key DEPs involved in storage substance degradation and plant defense mechanisms, such as globulin 3, sucrose synthase type I, serpin, beta-amylase, and plastid ADP-glucose pyrophosphorylase (AGPase) small subunit, were found to be phosphorylated during seed germination. Particularly, the phosphorylation site Ser(355) was found to be located in the enzyme active region of beta-amylase, which promotes substrate binding. Phosphorylated modification of several proteins could promote storage substance degradation and environmental stress defense during seed germination. The central metabolic pathways involved in wheat seed germination are proposed herein, providing new insights into the molecular mechanisms of cereal seed germination. PMID:26635843

  16. Underlying Mechanisms of Zymographic Diversity in Starch Synthase I and Pullulanase in Rice-Developing Endosperm.

    Science.gov (United States)

    Chen, Yaling; Bao, Jinsong

    2016-03-01

    Amylopectin is synthesized by the coordinated actions of many (iso)enzymes, including ADP-glucose pyrophosphorylase (AGPase), starch synthases (SSs), branching enzymes (BEs), and debranching enzymes (DBEs). Here, two polymorphic forms of starch synthase I (SSI) and pullulanase (PUL) in rice-developing seeds, designated as SSI-1/SSI-2 and PUL-1/PUL-2, were discovered for the first time by zymographic analysis. The SSI and PUL polymorphisms were strongly associated with the SSI microsatellite marker (p = 3.6 × 10(-37)) and PUL insertion/deletion (InDel) markers (p SSI and PUL enzymes. Only one non-synonymous variation in SSI DNA sequence (the SNP A/G) causing the change of the amino acid K438 to E438 was observed, which coincided well with the polymorphic forms of SSI. Nine non-synonymous variations were found between PUL-1 and PUL-2. Two non-synonymous variations of PUL (F316L and D770E) were identified by mass spectrometric analysis, but all of the variations did not change the structure of PUL. The co-immunoprecipitation results revealed the differences in protein-protein interaction patterns, i.e., strong or weaker signals of SSI-BEI and SSI-BEIIb, between the two forms of SSI. The results will enhance our understanding of SSI and PUL properties and provide helpful information to understand their functions in starch biosynthesis in rice endosperm. PMID:26860852

  17. Changes in carbohydrate metabolism in Plasmopara viticola-infected grapevine leaves.

    Science.gov (United States)

    Gamm, Magdalena; Héloir, Marie-Claire; Bligny, Richard; Vaillant-Gaveau, Nathalie; Trouvelot, Sophie; Alcaraz, Gérard; Frettinger, Patrick; Clément, Christophe; Pugin, Alain; Wendehenne, David; Adrian, Marielle

    2011-09-01

    The oomycete Plasmopara viticola is responsible for downy mildew, a severe grapevine disease. In infected grapevine leaves, we have observed an abnormal starch accumulation at the end of the dark period, suggesting modifications in starch metabolism. Therefore, several complementary approaches, including transcriptomic analyses, measurements of enzyme activities, and sugar quantification, were performed in order to investigate and to understand the effects of P. viticola infection on leaf starch and-to a larger extent-carbohydrate metabolism. Our results indicate that starch accumulation is associated with an increase in ADP-glucose pyrophosphorylase (AGPase) activity and modifications in the starch degradation pathway, especially an increased α-amylase activity. Together with these alterations in starch metabolism, we have observed an accumulation of hexoses, an increase in invertase activity, and a reduction of photosynthesis, indicating a source-to-sink transition in infected leaf tissue. Additionally, we have measured an accumulation of the disaccharide trehalose correlated to an increased trehalase gene expression and enzyme activity. Altogether, these results highlight a dramatic alteration of carbohydrate metabolism correlated with later stages of P. viticola development in leaves. PMID:21649510

  18. Systematic Analysis of Pericarp Starch Accumulation and Degradation during Wheat Caryopsis Development.

    Science.gov (United States)

    Yu, Xurun; Li, Bo; Wang, Leilei; Chen, Xinyu; Wang, Wenjun; Wang, Zhong; Xiong, Fei

    2015-01-01

    Although wheat (Triticum aestivum L.) pericarp starch granule (PSG) has been well-studied, our knowledge of its features and mechanism of accumulation and degradation during pericarp growth is poor. In the present study, developing wheat caryopses were collected and starch granules were extracted from their pericarp to investigate the morphological and structural characteristics of PSGs using microscopy, X-ray diffraction and Fourier transform infrared spectroscopy techniques. Relative gene expression levels of ADP-glucose pyrophosphorylase (APGase), granule-bound starch synthase II (GBSS II), and α-amylase (AMY) were quantified by quantitative real-time polymerase chain reaction. PSGs presented as single or multiple starch granules and were synthesized both in the amyloplast and chloroplast in the pericarp. PSG degradation occurred in the mesocarp, beginning at 6 days after anthesis. Amylose contents in PSGs were lower and relative degrees of crystallinity were higher at later stages of development than at earlier stages. Short-range ordered structures in the external regions of PSGs showed no differences in the developing pericarp. When hydrolyzed by α-amylase, PSGs at various developmental stages showed high degrees of enzymolysis. Expression levels of AGPase, GBSS II, and AMY were closely related to starch synthesis and degradation. These results help elucidate the mechanisms of accumulation and degradation as well as the functions of PSG during wheat caryopsis development. PMID:26394305

  19. Functional analysis of NtMPK2 uncovers its positive role in response to Pseudomonas syringae pv. tomato DC3000 in tobacco.

    Science.gov (United States)

    Zhang, Xingtan; Wang, Genhong; Gao, Junping; Nie, Mengyun; Liu, Wenshan; Xia, Qingyou

    2016-01-01

    Mitogen-activated protein kinase cascades are highly conserved signaling modules downstream of receptors/sensors and play pivotal roles in signaling plant defense against pathogen attack. Extensive studies on Arabidopsis MPK4 have implicated that the MAP kinase is involved in multilayered plant defense pathways. In this study, we identified tobacco NtMPK2 as an ortholog of AtMPK4. Transgenic tobacco overexpressing NtMPK2 markedly enhances resistance to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) virulent and avirulent strains. Transcriptome analysis of NtMPK2-dependent genes shows that possibly the basal resistance system is activated by NtMPK2 overexpression. In addition to NtMPK2-mediated resistance, multiple pathways are involved in response to the avirulent bacteria based on analysis of Pst-responding genes, including SA and ET pathways. Notably, it is possible that biosynthesis of antibacterial compounds is responsible for inhibition of Pst DC3000 avirulent strain when programmed cell death processes in the host. Our results uncover that NtMPK2 positively regulate tobacco defense response to Pst DC3000 and improve our understanding of plant molecular defense mechanism. PMID:26482478

  20. Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

    KAUST Repository

    Kleftogiannis, Dimitrios A.

    2013-06-01

    Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3\\'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

  1. Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis

    Directory of Open Access Journals (Sweden)

    Kolquist Kathryn A

    2011-11-01

    Full Text Available Abstract Background Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL. We performed oligonucleotide-based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence in situ hybridization (FISH. Results Using a custom designed microarray that targets >1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases. These included gains and losses of genes associated with cell cycle regulation, apoptosis and susceptibility loci on 3p21.31, 5q35.2q35.3, 10q23.31q23.33, 11q22.3, and 22q11.23. Conclusions Our results show that microarray analysis will detect known aberrations, including microscopic and cryptic alterations. In addition, novel genomic changes will be uncovered that may become important prognostic predictors or treatment targets for CLL in the future.

  2. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs).

    Science.gov (United States)

    Liu, Xiao; Li, Zesong; Su, Zheng; Zhang, Junjie; Li, Honggang; Xie, Jun; Xu, Hanshi; Jiang, Tao; Luo, Liya; Zhang, Ruifang; Zeng, Xiaojing; Xu, Huaiqian; Huang, Yi; Mou, Lisha; Hu, Jingchu; Qian, Weiping; Zeng, Yong; Zhang, Xiuqing; Xiong, Chengliang; Yang, Huanming; Kristiansen, Karsten; Cai, Zhiming; Wang, Jun; Gui, Yaoting

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID:26907467

  3. AB039. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    Science.gov (United States)

    Li, Zesong

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.

  4. Transcriptomic profiling of Yersinia pseudotuberculosis reveals reprogramming of the Crp regulon by temperature and uncovers Crp as a master regulator of small RNAs.

    Science.gov (United States)

    Nuss, Aaron M; Heroven, Ann Kathrin; Waldmann, Barbara; Reinkensmeier, Jan; Jarek, Michael; Beckstette, Michael; Dersch, Petra

    2015-03-01

    One hallmark of pathogenic yersiniae is their ability to rapidly adjust their life-style and pathogenesis upon host entry. In order to capture the range, magnitude and complexity of the underlying gene control mechanisms we used comparative RNA-seq-based transcriptomic profiling of the enteric pathogen Y. pseudotuberculosis under environmental and infection-relevant conditions. We identified 1151 individual transcription start sites, multiple riboswitch-like RNA elements, and a global set of antisense RNAs and previously unrecognized trans-acting RNAs. Taking advantage of these data, we revealed a temperature-induced and growth phase-dependent reprogramming of a large set of catabolic/energy production genes and uncovered the existence of a thermo-regulated 'acetate switch', which appear to prime the bacteria for growth in the digestive tract. To elucidate the regulatory architecture linking nutritional status to virulence we also refined the CRP regulon. We identified a massive remodelling of the CRP-controlled network in response to temperature and discovered CRP as a transcriptional master regulator of numerous conserved and newly identified non-coding RNAs which participate in this process. This finding highlights a novel level of complexity of the regulatory network in which the concerted action of transcriptional regulators and multiple non-coding RNAs under control of CRP adjusts the control of Yersinia fitness and virulence to the requirements of their environmental and virulent life-styles. PMID:25816203

  5. Climate change adaptation: Uncovering constraints to the use of adaptation strategies among food crop farmers in South-west, Nigeria using principal component analysis (PCA

    Directory of Open Access Journals (Sweden)

    Moradeyo Adebanjo Otitoju

    2016-12-01

    Full Text Available This study focused on the constraints to the use of climate variability/change adaptation strategies in South-west Nigeria. Multistage random technique was employed to select the location and the respondents. Descriptive statistics and principal component analysis (PCA were the analytical tools engaged in this study. The constraints to climate variability and change examined before did not use PCA but generalized factor analysis. Hence, there is need to examine these constraints extensively using PCA. Uncovering the constraints to the use of climate variability/change adaptation strategies among crop framers is important to give a realistic direction in the development of farmer-inclusive climate policies in Nigeria. The PCA result showed that the principal constraints that the farmers faced in climate change adaptation were public, institutional and labour constraint; land, neighbourhood norms and religious beliefs constraint; high cost of inputs, technological and information constraint; farm distance, access to climate information, off-farm job and credit constraint; and poor agricultural programmes and service delivery constraint. These findings pointed out the need for both the government and non-government organizations to intensify efforts on institutional, technological and farmers’ friendly land tenure and information systems as effective measures to guide inclusive climate change adaptation policies and development in South-west Nigeria.

  6. Why do most Gitano/Romani students not complete compulsory secondary education in Spain? Uncovering the view of the educational community using concept mapping

    Directory of Open Access Journals (Sweden)

    Álvarez Arturo

    2016-01-01

    Full Text Available This paper describes the results of research that used Concept Mapping to study the causes of the high rates of school failure among the students of the Gitano or Spanish Romani minority. A sample of 52 members of a school community—pupils, families and teachers—participated in the research. Data were collected in focus groups. Generated ideas were sorted and rated by participants. A multidimensional scaling of sorted data resulted in a map of points. A cluster analysis with the points’ coordinates was run. The results uncovered a model of six clusters: ethnic differences, families, adolescent risk behaviours, students’ attitudes and values, curriculum gap, and finally effects of compensatory education and attention to diversity programmes. The relationships among the clusters point to three sources of concern: cultural and gender issues within the family setting that encourage girls to drop out of school; lack of motivation and educational orientation of the students; and structural problems of the educational system that contribute to maintain the educational gap between minority and majority students.

  7. A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development.

    Science.gov (United States)

    Perualila-Tan, Nolen; Kasim, Adetayo; Talloen, Willem; Verbist, Bie; Göhlmann, Hinrich W H; Shkedy, Ziv

    2016-08-01

    The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery. PMID:27269248

  8. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.

    Science.gov (United States)

    Li, Wanbo; Sartelet, Arnaud; Tamma, Nico; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2016-02-01

    In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed. PMID:26582259

  9. Uncover the recruiter in you!

    CERN Multimedia

    2013-01-01

    2013 saw the launch of the one-day training course "Selecting the best person for CERN". So far, 10 courses have taken place and over 100 participants have taken part in this interactive, hands on experience.   The course has been met with much enthusiasm and positive feedback, with participants not only feeling better prepared and organised for the recruitment boards, but also equipped with concrete tools on how to prepare and conduct an effective selection interview. Following on from this success, further sessions are planned in 2014: we look forward to welcoming recruiting supervisors and board members who are likely to take part in a recruitment process, whether for LD or LD2IC, and who are interested in finding out more about how to get the most out of this important process! To enrol to this course, please follow this link: "Selecting the best person for CERN".

  10. Uncovering your hidden occupancy costs.

    Science.gov (United States)

    Apgar, M

    1993-01-01

    Senior managers at large companies may not believe that they can have much impact on the "bricks and mortar" of their cost structure. They may even think that occupancy costs are too insignificant to worry about, too technical to analyze, and too fixed to control. But as real estate consultant Mahlon Apgar argues, occupancy costs can hurt a company's earnings, share value, and overall performance. On the other hand, every dollar saved drops straight to the bottom line. Shearson Lehman Brothers, for example, has found that it can save as much as $20 million annually by reducing occupancy costs in its branch offices and headquarters. Managing occupancy costs isn't easy. But it is timely. As companies strive to improve productivity by consolidating functions and downsizing staff, they are saddled with excess office space. Expansions abroad present completely different market conditions that put a premium on reducing occupancy costs. At the same time, the changing nature of work is challenging deeply held beliefs about the workplace, and, consequently, traditional expectations of office space are giving way to innovations that are less costly and more productive. To manage occupancy costs, managers must be able to identify their components, measure their impact, understand what drives them, and develop options to change them. Four basic tools help diagnose problems: a cost history, a loss analysis, a component analysis, and a lease aging profile. Understanding cost drivers like leasing, location, and layout can give executives the insights they need to reduce occupancy costs while improving the effectiveness of facilities to support day-to-day operations. PMID:10126151

  11. Uncovering Settler Grammars in Curriculum

    Science.gov (United States)

    Calderon, Dolores

    2014-01-01

    In this article, I focus on making settler colonialism explicit in education. I turn to social studies curriculum as a clear example of how settler colonialism is deeply embedded in educational knowledge production in the United States that is rooted in a dialectic of Indigenous presence and absence. I argue that the United States, and the…

  12. Disordered Collarettes and Uncovered Tables

    DEFF Research Database (Denmark)

    Nørgaard, Nina

    2007-01-01

    This article examines the use of negative polarity as a stylistic device in James Joyce's short story, "Two Gallants" (1992 [1914]). The article begins with a brief account of various approaches to negative polarity, focusing in particular on theoretical paradigms that favour the pragmatic...

  13. Uncovering Blue Diffuse Dwarf Galaxies

    CERN Document Server

    James, Bethan L; Stark, Daniel P; Belokurov, Vasily; Pettini, Max; Olszewski, Edward W

    2014-01-01

    Extremely metal poor (XMP) galaxies are known to be very rare, despite the large numbers of low-mass galaxies predicted by the local galaxy luminosity function. This paper presents a sub-sample of galaxies that were selected via a morphology-based search on SDSS images with the aim of finding these elusive XMP galaxies. By using the recently discovered extremely metal-poor galaxy, Leo P, as a guide, we obtained a collection of faint, blue systems, each with isolated HII regions embedded in a diffuse continuum, that have remained undetected until now. Here we show the first results from optical spectroscopic follow-up observations of 12 of ~100 of these blue, diffuse dwarf (BDD) galaxies yielded by our search algorithm. Oxygen abundances were obtained via the direct method for eight galaxies, and found to be in the range 7.45<12+log(O/H)<8.0, with two galaxies being classified as XMPs. All BDDs were found to currently have a young star-forming population (<10 Myr) and relatively high ionisation parame...

  14. ESA uncovers Geminga's `hot spot'

    Science.gov (United States)

    2004-07-01

    16 July 2004 Astronomers using ESA’s X-ray observatory XMM-Newton have detected a small, bright ‘hot spot’ on the surface of the neutron star called Geminga, 500 light-years away. The hot spot is the size of a football field and is caused by the same mechanism producing Geminga’s X-ray tails. This discovery identifies the missing link between the X-ray and gamma-ray emission from Geminga. hi-res Size hi-res: 1284 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot This figure shows the effects of charged particles accelerated in the magnetosphere of Geminga. Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (in red) hit the star’s magnetic poles like in an ‘own goal’. Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degrees hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. An animated version of the entire sequence can be found at: Click here for animated GIF [low resolution, animated GIF, 5536 KB] Click here for AVI [high resolution, AVI with DIVX compression, 19128 KB] hi-res Size hi-res: 371 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (a) Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. hi-res Size hi-res: 377 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (b) Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (red) hit the star’s magnetic poles like in an ‘own goal’. hi-res Size hi-res: 435 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (c) Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). hi-res Size hi-res: 121 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (d) Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degree hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. Neutron stars are the smallest kind of stars known. They are the super-dense remnants of massive stars that died in cataclysmic explosions called supernovae. They have been thrown through space like cannonballs and set spinning at a furious rate, with magnetic fields hundreds of billions of times stronger than Earth’s. In the case of Geminga, this cannonball contains one and a half times the mass of the Sun, squeezed into a sphere just 20 kilometres across and spinning four times every second. A cloud bustling with electrically charged particles surrounds Geminga. These particles are shepherded by its magnetic and electric fields. ESA’s XMM-Newton observatory had already discovered that some of these particles are ejected into space, forming tails that stream behind the neutron star as it hurtles along. Scientists did not know whether Geminga’s tails are formed by electrons or by their twin particles with an opposite electrical charge, called positrons. Nevertheless, they expected that, if for instance electrons are kicked into space, then the positrons should be funnelled down towards the neutron star itself, like in an ‘own goal’. Where these particles strike the surface of the star, they ought to create a hot spot, a region considerably hotter than the surroundings. An international team of astronomers, lead by Patrizia Caraveo, IASF-CNR, Italy, has now reported the detection of such a hot spot on Geminga using ESA’s XMM-Newton observatory. With a temperature of about two million degrees, this hot spot is considerably hotter than the one half million degrees of the surrounding surface. According to this new work, Geminga’s hot spot is just 60 metres in radius. "This hot spot is the size of a football field," said Caraveo, "and is the smallest object ever detected outside of our Solar System." Details of this size can presently be measured only on the Moon and Mars and, even then, only from a spacecraft in orbit around them. The presence of a hot spot was suspected in the late 1990s but only now can we see it ‘live’, emitting X-rays as Geminga rotates, thanks to the superior sensitivity of ESA’s X-ray observatory, XMM-Newton. The team used the European Photon Imaging Cameras (EPIC) to conduct a study of Geminga, lasting about 28 consecutive hours and recording the arrival time and energy of every X-ray photon that Geminga emitted within XMM-Newton’s grasp. "In total, this amounted to 76 850 X-ray counts - twice as many as have been collected by all previous observations of Geminga, since the time of the Roman Empire," said Caraveo. Knowing the rotation rate of Geminga and the time of each photon’s arrival meant that astronomers could identify which photons were coming from each region of the neutron star as it rotates. When they compared photons coming from different regions of the star, they found that the ‘colour’ of the X-rays, which corresponds to their energy, changed as Geminga rotated. In particular, they could clearly see a distinct colour change when the hot spot came into view and then disappeared behind the star. This research closes the gap between the X-ray and gamma-ray emission from neutron stars. XMM-Newton has shown that they both can originate through the same physical mechanism, namely the acceleration of charged particles in the magnetosphere of these degenerate stars. "XMM-Newton’s Geminga observation has been particularly fruitful," said Norbert Schartel, ESA’s Project Scientist for XMM-Newton. "Last year, it yielded the discovery of the source tails and now it has found its rotating hot spot." Caraveo is already applying this new technique to other pulsating neutron stars observed by XMM-Newton looking for hot spots. This research represents an important new tool for understanding the physics of neutron stars. Notes for editors The original paper appeared on 16 July 2004, in Science magazine, under the title 'Phase-resolved spectroscopy of Geminga shows rotating hotspot(s)'. Besides P. Caraveo, the author list includes A. De Luca, S. Mereghetti, A. Pellizzoni and G. Bignami. During the search to track down this elusive celestial object, a co-author on the paper, Giovanni Bignami, named it Geminga almost 30 years ago. He was Principal Investigator of XMM-Newton's EPIC camera from 1987 to 1997 and is now Director of the Centre d'Etude Spatiale des Rayonnements (CESR, Toulouse). Geminga was first glimpsed as a mysterious source of gamma rays, coming from somewhere in the constellation Gemini by NASA's SAS-2 spacecraft in 1973. While searching to pin down its exact location and nature, Bignami named it Geminga because it was a ‘Gemini gamma-ray source’. As an astronomer in Milan, Italy, he was also aware that in his native dialect ‘gh'èminga’ means ‘it is not there’, which he found amusing. It was also remarkably apt, for it was not until 1993 that he succeeded in finally ‘seeing’ and therefore pinpointing Geminga, using optical wavelengths. While it lacked radio emissions, the pulsating X-ray and gamma-ray emissions meant Geminga could only belong to a new class of objects, the radio-quiet neutron stars. The original announcement of the discovery of Geminga’s tails, issued on 25 July 2003, can be found at: http://www.esa.int/esaSC/Pr_11_2003_s_en.html More about XMM-Newton XMM-Newton can detect more X-ray sources than any previous observatory and is helping to solve many cosmic mysteries of the violent Universe, from black holes to the formation of galaxies. It was launched on 10 December 1999, using an Ariane-5 rocket from French Guiana. It is expected to return data for a decade. XMM-Newton’s high-tech design uses over 170 wafer-thin cylindrical mirrors spread over three telescopes. Its orbit takes it almost a third of the way to the Moon, so that astronomers can enjoy long, uninterrupted views of celestial objects. More information on XMM-Newton can be found at: http://www.esa.int/esaSC/SEMM8IGHZTD_1_spk.html

  15. Uncovering your customer's hidden needs

    OpenAIRE

    Goffin, Keith; Lemke, Fred

    2004-01-01

    Capturing the ‘voice of the customer’ is an essential stage of any new product development. However, the way companies ‘listen’ to their customers is changing as managers realise end users are often unable to articulate their needs and focus groups seldom lead to breakthrough product ideas. The SONY Walkman is a clear example of a new product that resulted from insights into customers’ hidden needs rather than from market research. It is not that market research is bad per s...

  16. DISCOVER: Dutch Iliac Stent trial: COVERed balloon-expandable versus uncovered balloon-expandable stents in the common iliac artery: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bekken Joost A

    2012-11-01

    Full Text Available Abstract Background Iliac artery atherosclerotic disease may cause intermittent claudication and critical limb ischemia. It can lead to serious complications such as infection, amputation and even death. Revascularization relieves symptoms and prevents these complications. Historically, open surgical repair, in the form of endarterectomy or bypass, was used. Over the last decade, endovascular repair has become the first choice of treatment for iliac arterial occlusive disease. No definitive consensus has emerged about the best endovascular strategy and which type of stent, if any, to use. However, in more advanced disease, that is, long or multiple stenoses or occlusions, literature is most supportive of primary stenting with a balloon-expandable stent in the common iliac artery (Jongkind V et al., J Vasc Surg 52:1376-1383,2010. Recently, a PTFE-covered balloon-expandable stent (Advanta V12, Atrium Medical Inc., Hudson, NH, USA has been introduced for the iliac artery. Covering stents with PTFE has been shown to lead to less neo-intimal hyperplasia and this might lower restenosis rates (Dolmatch B et al. J Vasc Interv Radiol 18:527-534,2007, Marin ML et al. J Vasc Interv Radiol 7:651-656,1996, Virmani R et al. J Vasc Interv Radiol 10:445-456,1999. However, only one RCT, of mediocre quality has been published on this stent in the common iliac artery (Mwipatayi BP et al. J Vasc Surg 54:1561-1570,2011, Bekken JA et al. J Vasc Surg 55:1545-1546,2012. Our hypothesis is that covered balloon-expandable stents lead to better results when compared to uncovered balloon-expandable stents. Methods/Design This is a prospective, randomized, controlled, double-blind, multi-center trial. The study population consists of human volunteers aged over 18 years, with symptomatic advanced atherosclerotic disease of the common iliac artery, defined as stenoses longer than 3 cm and occlusions. A total of 174 patients will be included. The control group will undergo

  17. Genome-wide analyses of Nkx2-1 binding to transcriptional target genes uncover novel regulatory patterns conserved in lung development and tumors.

    Directory of Open Access Journals (Sweden)

    Jean-Bosco Tagne

    Full Text Available The homeodomain transcription factor Nkx2-1 is essential for normal lung development and homeostasis. In lung tumors, it is considered a lineage survival oncogene and prognostic factor depending on its expression levels. The target genes directly bound by Nkx2-1, that could be the primary effectors of its functions in the different cellular contexts where it is expressed, are mostly unknown. In embryonic day 11.5 (E11.5 mouse lung, epithelial cells expressing Nkx2-1 are predominantly expanding, and in E19.5 prenatal lungs, Nkx2-1-expressing cells are predominantly differentiating in preparation for birth. To evaluate Nkx2-1 regulated networks in these two cell contexts, we analyzed genome-wide binding of Nkx2-1 to DNA regulatory regions by chromatin immunoprecipitation followed by tiling array analysis, and intersected these data to expression data sets. We further determined expression patterns of Nkx2-1 developmental target genes in human lung tumors and correlated their expression levels to that of endogenous NKX2-1. In these studies we uncovered differential Nkx2-1 regulated networks in early and late lung development, and a direct function of Nkx2-1 in regulation of the cell cycle by controlling the expression of proliferation-related genes. New targets, validated in Nkx2-1 shRNA transduced cell lines, include E2f3, Cyclin B1, Cyclin B2, and c-Met. Expression levels of Nkx2-1 direct target genes identified in mouse development significantly correlate or anti-correlate to the levels of endogenous NKX2-1 in a dosage-dependent manner in multiple human lung tumor expression data sets, supporting alternative roles for Nkx2-1 as a transcriptional activator or repressor, and direct regulator of cell cycle progression in development and tumors.

  18. MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response.

    Science.gov (United States)

    Mancini, F; Pieroni, L; Monteleone, V; Lucà, R; Fici, L; Luca, E; Urbani, A; Xiong, S; Soddu, S; Masetti, R; Lozano, G; Pontecorvi, A; Moretti, F

    2016-01-14

    The p53 inhibitor, MDM4 (MDMX) is a cytoplasmic protein with p53-activating function under DNA damage conditions. Particularly, MDM4 promotes phosphorylation of p53 at Ser46, a modification that precedes different p53 activities. We investigated the mechanism by which MDM4 promotes this p53 modification and its consequences in untransformed mammary epithelial cells and tissues. In response to severe DNA damage, MDM4 stimulates p53Ser46(P) by binding and stabilizing serine-threonine kinase HIPK2. Under these conditions, the p53-inhibitory complex, MDM4/MDM2, dissociates and this allows MDM4 to promote p53/HIPK2 functional interaction. Comparative proteomic analysis of DNA damage-treated cells versus -untreated cells evidenced a diffuse downregulation of proteins with anti-apoptotic activity, some of which were targets of p53Ser46(P)/HIPK2 repressive activity. Importantly, MDM4 depletion abolishes the downregulation of these proteins indicating the requirement of MDM4 to promote p53-mediated transcriptional repression. Consistently, MDM4-mediated HIPK2/p53 activation precedes HIPK2/p53 nuclear translocation and activity. Noteworthy, repression of these proteins was evident also in mammary glands of mice subjected to γ-irradiation and was significantly enhanced in transgenic mice overexpressing MDM4. This study evidences the flexibility of MDM2/MDM4 heterodimer, which allows the development of a positive activity of cytoplasmic MDM4 towards p53-mediated transcriptional function. Noteworthy, this activity uncovers coordinated repression of molecules with shared anti-apoptotic function which precedes active cell apoptosis and that are frequently overexpressed and/or markers of tumour phenotype in human cancer. PMID:25961923

  19. Phylogenetic tree-informed microRNAome analysis uncovers conserved and lineage-specific miRNAs in Camellia during floral organ development.

    Science.gov (United States)

    Yin, Hengfu; Fan, Zhengqi; Li, Xinlei; Wang, Jiangying; Liu, Weixin; Wu, Bin; Ying, Zhen; Liu, Liping; Liu, Zhongchi; Li, Jiyuan

    2016-04-01

    In plants, miRNAs are endogenous small RNAs derived from single-stranded precursors with hairpin structures. The evolution of miRNAs and their targets represents one of the most dynamic circuits directing gene expression, which may play fundamental roles in shaping the development of distinct plant organs. Here we performed high-throughput small RNA sequencing in five organ types of Camellia azalea to capture the spatial profile of small non-coding RNA. In total we obtained >227 million high-quality reads and identified 175 miRNAs with mature and precursor sequences. We aligned the miRNAs to known miRNA databases and revealed some conserved as well as 'newly evolved' miRNA genes. Twelve miRNAs were identified to be specific in the genus Camellia, supporting the lineage-specific manner of expansion of 'young' miRNAs. Through differential expression analysis, we showed that many miRNAs were preferentially abundant in certain organ types. Moreover, hierarchical clustering analysis revealed distinctive expression patterns of tissue-specific miRNAs. Gene Ontology enrichment analysis of targets of stamen- and carpel-specific miRNA subclusters showed that miRNA-target regulatory circuits were involved in many important biological processes, enabling their proper specification and organogenesis, such as 'DNA integration' and 'fruit development'. Further, quantitative PCR of key miRNAs and their target genes revealed anti-correlated patterns, and uncovered the functions of key miRNA-target pairs in different floral organs. Taken together, this work yielded valuable information on miRNA-target regulation in the control of floral organ development and sheds light on the evolution of lineage-specific miRNAs in Camellia. PMID:26951373

  20. The fallacy of coverage: uncovering disparities to improve immunization rates through evidence. Results from the Canadian International Immunization Initiative Phase 2 - Operational Research Grants.

    Science.gov (United States)

    Mhatre, Sharmila L; Schryer-Roy, Anne-Marie

    2009-01-01

    Immunization can and does save lives. However, the presence of vaccines does not easily translate into every child being vaccinated, and this is what the studies in this journal supplement reveal. From South Asia to West Africa,the evidence presented here reveals what we are calling the fallacy of coverage, going beyond uncovering the real vaccination rates to providing evidence on the reasons for the lack of effective coverage.The evidence for the fallacy of coverage is part of an operational research program entitled the Canadian International Immunization Initiative Phase 2 (CIII2). Through a competitive peer review process, six research grants were awarded to increase access to and enhance immunization services. This journal supplement provides a forum for the presentation of the results of five of the six studies.The story of the fallacy of coverage is made up of five theme areas of evidence - timeliness of immunization, social and gender inequities, vaccine efficacy, understanding demand side issues to tailor interventions, and national data sets masking actual district level coverage rates - that reveal the discrepancies in immunization coverage rates and the reasons behind these discrepancies. As part of the story, and to turn around the fallacy of coverage, the studies also provide proof of effective and locally relevant solutions.Policies and funding, while keeping an eye on future diseases, clearly need to maintain and increase support to address existing vaccine-preventable diseases to increase coverage such that by 2015 we can achieve 90% national vaccination coverage and reach the MDG of reducing mortality rates among children under five by two-thirds.The results from the operational research grants of the CIII2 offer some answers on how to reach this goal by demonstrating how locally generated evidence can inform immunization strategies to ensure that children who need to get vaccinated will get vaccinated, and vaccinated on time. PMID:19828053

  1. Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence.

    Science.gov (United States)

    Schoberle, Taylor J; Chung, Lawton K; McPhee, Joseph B; Bogin, Ben; Bliska, James B

    2016-04-01

    PathogenicYersiniaspecies utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promoteYersiniapathogenesis. In turn,Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior toYersinia pseudotuberculosisinfection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of aY. pseudotuberculosisyopMmutant was compared to that of ayopJ yopM,yopE yopM,yopH yopM,yopT yopM, orypkA yopMmutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1β (IL-1β), and pyroptosis in LPS-activated macrophages infected with wild-type or mutantY. pseudotuberculosisstrains. Results show enhanced activation of caspase-1 after infection with theyopJ yopMmutant relative to infection by any other single or double mutant. Similar results were obtained with theyopJ,yopM, andyopJ yopMmutants ofYersinia pestis Following intravenous infection of mice, theY. pseudotuberculosisyopJmutant was as virulent as the wild type, while theyopJ yopMmutant was significantly more attenuated than theyopMmutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promotingYersiniavirulence. PMID:26810037

  2. ModuleFinder and CoReg: alternative tools for linking gene expression modules with promoter sequences motifs to uncover gene regulation mechanisms in plants

    OpenAIRE

    Whelan James; Millar A Harvey; Holt Kathryn E

    2006-01-01

    Abstract Background Uncovering the key sequence elements in gene promoters that regulate the expression of plant genomes is a huge task that will require a series of complementary methods for prediction, substantial innovations in experimental validation and a much greater understanding of the role of combinatorial control in the regulation of plant gene expression. Results To add to this larger process and to provide alternatives to existing prediction methods, we have developed several tool...

  3. ModuleFinder and CoReg: alternative tools for linking gene expression modules with promoter sequences motifs to uncover gene regulation mechanisms in plants

    Directory of Open Access Journals (Sweden)

    Whelan James

    2006-04-01

    Full Text Available Abstract Background Uncovering the key sequence elements in gene promoters that regulate the expression of plant genomes is a huge task that will require a series of complementary methods for prediction, substantial innovations in experimental validation and a much greater understanding of the role of combinatorial control in the regulation of plant gene expression. Results To add to this larger process and to provide alternatives to existing prediction methods, we have developed several tools in the statistical package R. ModuleFinder identifies sets of genes and treatments that we have found to form valuable sets for analysis of the mechanisms underlying gene co-expression. CoReg then links the hierarchical clustering of these co-expressed sets with frequency tables of promoter elements. These promoter elements can be drawn from known elements or all possible combinations of nucleotides in an element of various lengths. These sets of promoter elements represent putative cis-acting regulatory elements common to sets of co-expressed genes and can be prioritised for experimental testing. We have used these new tools to analyze the response of transcripts for nuclear genes encoding mitochondrial proteins in Arabidopsis to a range of chemical stresses. ModuleFinder provided a subset of co-expressed gene modules that are more logically related to biological functions than did subsets derived from traditional hierarchical clustering techniques. Importantly ModuleFinder linked responses in transcripts for electron transport chain components, carbon metabolism enzymes and solute transporter proteins. CoReg identified several promoter motifs that helped to explain the patterns of expression observed. Conclusion ModuleFinder identifies sets of genes and treatments that form useful sets for analysis of the mechanisms behind co-expression. CoReg links the clustering tree of expression-based relationships in these sets with frequency tables of promoter

  4. CoCoRaHS (The Community Collaborative Rain, Hail and Snow Network): Analysis of Participant Survey Data to Uncover Learning through Participation

    Science.gov (United States)

    Holzer, M. A.; Zimmerman, T.; Doesken, N. J.; Reges, H. W.; Newman, N.; Turner, J.; Schwalbe, Z.

    2010-12-01

    CoCoRaHS (The Community Collaborative Rain, Hail and Snow network) is based out of Fort Collins Colorado and is an extremely successful citizen science project with over 15,000 volunteers collecting valuable precipitation data. Forecasters and scientists use data from this dense network to illuminate and illustrate the high small-scale variability of precipitation across the nation. This presentation will discuss the results of a survey of CoCoRaHS participants as related to 1) citizen scientists’ motivation and learning; 2) the challenges of identifying how people learn science in citizen science projects; and 3) a potential research-based framework for how people learn through engaging in the data collection within in a citizen science project. A comprehensive survey of 14,500 CoCoRaHS observers was recently conducted to uncover participant perceptions of numerous aspects of the CoCoRaHS program, including its goal of increasing climate literacy. The survey yielded a response rate of over 50%, and included measures of motivation, engagement and learning. In relationship to motivation and learning, the survey revealed that most (57.1%) observers would make precipitation observations regardless of being a CoCoRaHS volunteer, therefore their motivation is related to their inherent level of interest in weather. Others are motivated by their desire to learn more about weather and climate, they want to contribute to a scientific project, they think its fun, and/or it provides a sense of community. Because so many respondents already had knowledge and interest in weather and climate, identifying how and what people learn through participating was a challenge. However, the narrow project focus of collecting and reporting of local precipitation assisted in identifying aspects of learning. For instance, most (46.4%) observers said they increased their knowledge about the local variability in precipitation even though they had been collecting precipitation data for many

  5. Impact Of The Ban On Uncovered SCDS Trade On the Interdependencies Between The CDS Market And Other Sectors Of Financial Markets. The Case Of Safe And Developed Versus Risky And Developing European Markets

    Directory of Open Access Journals (Sweden)

    Kliber Agata

    2016-03-01

    Full Text Available The aim of the article is to verify the impact of the ban on uncovered sCDS trade in Europe on the interdependencies between the sCDS market and other sectors of financial markets. We analyse two European markets: the safe and developed Swedish market, and the risky and developing Hungarian one. The study covers the period from October 2008 to October 2013. We analyse changes in the interdependencies between the sCDS market and the bond market, as well as between the sCDS market and the stock exchange. We found out that in the case of the safe Swedish market, the strength of relationships of each sector of financial markets with the sCDS one was much weaker than in the case of Hungary, which may suggest that the Swedish market is less prone to crisis transmission arising from herd behaviour or speculative attacks. In the end we show that in the two economies, the influence of the sCDS market on the other sectors of financial market indeed diminished following introduction of the ban on uncovered sCDS trade.

  6. Purification, crystallization and preliminary X-ray characterization of the human GTP fucose pyrophosphorylase

    OpenAIRE

    Quirk, Stephen; Seley-Radtke, Katherine L.

    2006-01-01

    The human GTP fucose pyrophosphohydrolase protein has been crystallized via the hanging-drop technique over a reservoir of polyethylene glycol (MW 8000) and ethylene glycol. The orthorhombic crystals diffract to 2.8 Å resolution.

  7. Leishmania UDP-sugar Pyrophosphorylase: THE MISSING LINK IN GALACTOSE SALVAGE?

    OpenAIRE

    Damerow, Sebastian; Lamerz, Anne-Christin; Haselhorst, Thomas; Führing, Jana; Zarnovican, Patricia; von Itzstein, Mark; Routier, Françoise H.

    2009-01-01

    The Leishmania parasite glycocalyx is rich in galactose-containing glycoconjugates that are synthesized by specific glycosyltransferases that use UDP-galactose as a glycosyl donor. UDP-galactose biosynthesis is thought to be predominantly a de novo process involving epimerization of the abundant nucleotide sugar UDP-glucose by the UDP-glucose 4-epimerase, although galactose salvage from the environment has been demonstrated for Leishmania major. Here, we present the characterization of an L. ...

  8. 高瓦斯突出煤层组井筒快速揭煤关键技术%The key technology of uncovering coal quickly on the shaft in the outburst coal seam group with high gas

    Institute of Scientific and Technical Information of China (English)

    吴爱军; 程国军; 王法凯

    2015-01-01

    The first auxiliary shaft of Panyidong project department is served for minting area above-850m ,it will cross the high gas and outburst group be made of 13-1coal and 12coal . The In order to accelerate uncovering coal safely ,a number of new technology of outburst prevention were adopted by Project department :At first ,the coal seam gas pressure has been rapidly determined used the method of high gas inflation;At the same time ,the self-developed corer was used to achieve complete coal-core ,and the specific information of coal seam were mastered .After the uncovered coal has been verified and has no outburst ,large diameter drillings were constructed by the expansion slot hole and were used to speed up the gas emissions . After a series of rigorous organization and tight construction ,the whole process of uncovering coal is in less than 20 days ,and nearly a third of the time was shorten compared with conventional process ,a win-win situation of the economic and security benefits are gained .%潘一东项目部第一副井主要是服务于-850m以上的开采水平,该井筒要穿越13-1煤与12煤组成的高瓦斯突出煤层组,为了实现安全快速的揭煤,该项目部根据现场的实际情况,采用了多项新技术实施防突措施:首先使用高压充气法快速测定了煤层瓦斯压力,与此同时利用自行研制的取芯器实现完整钻取煤芯,掌握了煤层具体信息;在验证所揭煤层无突出危险性后,再利用扩槽钻头施工大直径的钻孔以加快瓦斯的排放。经过一系列严密组织和紧张施工,整个揭煤过程不到20天,较常规工艺缩短了近1/3的时间,取得了经济效益和安全效益的双赢。

  9. Starch Accumulation and Enzyme Activities Associated with Starch Synthesis in Maize Kernels

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hai-yan; DONG Shu-ting; GAO Rong-qi; SUN Qing-quan

    2007-01-01

    The filling rate and the starch accumulation in developing maize kernel were analyzed. The changes of enzyme activities associated with sucrose metabolism and starch biosynthesis were investigated. The purpose is to discuss the enzymatic mechanisms responsible for starch synthesis. Two types of maize cultivars (Zea mays), high starch maize (Feiyu 3) and normal maize (Yuyu 22), were grown in a corn field. The factors involved in starch synthesis were performed during the growth period. The kernel filling rate, the sucrose content, the starch accumulating rates and the activities of SS (sucrose synthase), GBSS (granule-bound starch synthase), SBE (starch branching enzyme) of Feiyu 3, which has high starch content, were significantly higher than those of Yuyu 22, which has low starch content, after 10 DAP (days after pollination).Correlation analysis indicated that ADPGPPase (ADP-glucose pyrophosphorylase) and DBE (starch debranching enzyme)were not correlated with the starch accumulating rates and the kernel filling rate, but the SS activity at the middle and late period were highly significantly correlated with the starch accumulating rates and the kernel filling rate. The GBSS activity was highly significantly correlated with the amylose accumulating rate, but not correlated with the kernel filling rate. The SBE activity was highly significantly correlated with the amylopectin accumulating rate and the kernel filling rate. It was not ADPGPPase and DBE, but SS was the rate-limiting factor of starch biosynthesis in developing maize kernels. GBSS had an important effect on amylose accumulation, and SBE had a significant effect on amylopectin accumulation.

  10. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape During In Vitro Culture

    Energy Technology Data Exchange (ETDEWEB)

    Schwender, Jorg [Brookhaven National Lab. (BNL), Upton, NY (United States); Hebbelmann, Inga [Brookhaven National Lab. (BNL), Upton, NY (United States); Heinzel, Nicholas [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany); Hildebrandt, Tatjana [Univ. of Hannover (Germany); Rogers, Alistair [Brookhaven National Lab. (BNL), Upton, NY (United States); Naik, Dhiraj [Brookhaven National Lab. (BNL), Upton, NY (United States); Indian Inst. of Advanced Research Koba, Gujarat (India); Klapperstuck, Matthias [Monash Univ., Melbourne, VIC (Australia); Braun, Hans -Peter [Univ. of Hannover (Germany); Schreiber, Falk [Monash Univ., Melbourne, VIC (Australia); Univ. Halle-Wittenberg, Melbourne (Australia); Denolf, Peter [Bayer CropScience (Belgium); Borisjuk, Ljudmilla [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany); Rolletschek, Hardy [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany)

    2015-07-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. We observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Also, quantitative data were used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism..

  11. Impeded Carbohydrate Metabolism in Rice Plants under Submergence Stress

    Institute of Scientific and Technical Information of China (English)

    Malay Kumar ADAK; Nirmalya GHOSH; Dilip Kumar DASGUPTA; Sudha GUPTA

    2011-01-01

    The detrimental effects of submergence on physiological performances of some rice varieties with special references to carbohydrate metabolisms and their allied enzymes during post-flowering stages have been documented and clarified in the present investigation.It was found that photosynthetic rate and concomitant translocation of sugars into the panicles were both related to the yield.The detrimental effects of the complete submergence were recorded in generation of sucrose,starch,sucrose phosphate synthase and phosphorylase activity in the developing panicles of the plants as compared to those under normal or control (i.e.non-submerged) condition.The accumulation of starch was significantly lower in plants under submergence and that was correlated with ADP-glucose pyrophosphorylase activity.Photosynthetic rate was most affected under submergence in varying days of post-flowering and was also related to the down regulation of Ribulose bisphosphate carboxylase activity.However,under normal or control condition,there recorded a steady maintenance of photosynthetic rate at the post-flowering stages and significantly higher values of Ribulose bisphosphate carboxylase activity.Still,photosynthetic rate of the plants under both control and submerged conditions had hardly any significant correlation with sugar accumulation and other enzymes of carbohydrate metabolism like invertase with grain yield.Finally,plants under submergence suffered significant loss of yield by poor grain filling which was related to impeded carbohydrate metabolism in the tissues.It is evident that loss of yield under submergence is attributed both by lower sink size or sink capacity (number of panicles,in this case) as well as subdued carbohydrate metabolism in plants and its subsequent partitioning into the grains.

  12. The intrinsically disordered protein LEA7 from Arabidopsis thaliana protects the isolated enzyme lactate dehydrogenase and enzymes in a soluble leaf proteome during freezing and drying.

    Science.gov (United States)

    Popova, Antoaneta V; Rausch, Saskia; Hundertmark, Michaela; Gibon, Yves; Hincha, Dirk K

    2015-10-01

    The accumulation of Late Embryogenesis Abundant (LEA) proteins in plants is associated with tolerance against stresses such as freezing and desiccation. Two main functions have been attributed to LEA proteins: membrane stabilization and enzyme protection. We have hypothesized previously that LEA7 from Arabidopsis thaliana may stabilize membranes because it interacts with liposomes in the dry state. Here we show that LEA7, contrary to this expectation, did not stabilize liposomes during drying and rehydration. Instead, it partially preserved the activity of the enzyme lactate dehydrogenase (LDH) during drying and freezing. Fourier-transform infrared (FTIR) spectroscopy showed no evidence of aggregation of LDH in the dry or rehydrated state under conditions that lead to complete loss of activity. To approximate the complex influence of intracellular conditions on the protective effects of a LEA protein in a convenient in-vitro assay, we measured the activity of two Arabidopsis enzymes (glucose-6-P dehydrogenase and ADP-glucose pyrophosphorylase) in total soluble leaf protein extract (Arabidopsis soluble proteome, ASP) after drying and rehydration or freezing and thawing. LEA7 partially preserved the activity of both enzymes under these conditions, suggesting its role as an enzyme protectant in vivo. Further FTIR analyses indicated the partial reversibility of protein aggregation in the dry ASP during rehydration. Similarly, aggregation in the dry ASP was strongly reduced by LEA7. In addition, mixtures of LEA7 with sucrose or verbascose reduced aggregation more than the single additives, presumably through the effects of the protein on the H-bonding network of the sugar glasses. PMID:25988244

  13. Glycogen synthase isoforms in Synechocystis sp. PCC6803: identification of different roles to produce glycogen by targeted mutagenesis.

    Directory of Open Access Journals (Sweden)

    Sang-Ho Yoo

    Full Text Available Synechocystis sp. PCC6803 belongs to cyanobacteria which carry out photosynthesis and has recently become of interest due to the evolutionary link between bacteria and plant species. Similar to other bacteria, the primary carbohydrate storage source of Synechocystis sp. PCC6803 is glycogen. While most bacteria are not known to have any isoforms of glycogen synthase, analysis of the genomic DNA sequence of Synechocystis sp. PCC6803 predicts that this strain encodes two isoforms of glycogen synthase (GS for synthesizing glycogen structure. To examine the functions of the putative GS genes, each gene (sll1393 or sll0945 was disrupted by double cross-over homologous recombination. Zymogram analysis of the two GS disruption mutants allowed the identification of a protein band corresponding to each GS isoform. Results showed that two GS isoforms (GSI and GSII are present in Synechocystis sp. PCC6803, and both are involved in glycogen biosynthesis with different elongation properties: GSI is processive and GSII is distributive. Total GS activities in the mutant strains were not affected and were compensated by the remaining isoform. Analysis of the branch-structure of glycogen revealed that the sll1393- mutant (GSI- produced glycogen containing more intermediate-length chains (DP 8-18 at the expense of shorter and longer chains compared with the wild-type strain. The sll0945- mutant (GSII- produced glycogen similar to the wild-type, with only a slightly higher proportion of short chains (DP 4-11. The current study suggests that GS isoforms in Synechocystis sp. PCC6803 have different elongation specificities in the biosynthesis of glycogen, combined with ADP-glucose pyrophosphorylase and glycogen branching enzyme.

  14. Metabolic and enzymatic changes associated with carbon mobilization, utilization and replenishment triggered in grain amaranth (Amaranthus cruentus in response to partial defoliation by mechanical injury or insect herbivory

    Directory of Open Access Journals (Sweden)

    Castrillón-Arbeláez Paula

    2012-09-01

    Full Text Available Abstract Background Amaranthus cruentus and A. hypochondriacus are crop plants grown for grain production in subtropical countries. Recently, the generation of large-scale transcriptomic data opened the possibility to study representative genes of primary metabolism to gain a better understanding of the biochemical mechanisms underlying tolerance to defoliation in these species. A multi-level approach was followed involving gene expression analysis, enzyme activity and metabolite measurements. Results Defoliation by insect herbivory (HD or mechanical damage (MD led to a rapid and transient reduction of non-structural carbohydrates (NSC in all tissues examined. This correlated with a short-term induction of foliar sucrolytic activity, differential gene expression of a vacuolar invertase and its inhibitor, and induction of a sucrose transporter gene. Leaf starch in defoliated plants correlated negatively with amylolytic activity and expression of a β-amylase-1 gene and positively with a soluble starch synthase gene. Fatty-acid accumulation in roots coincided with a high expression of a phosphoenolpyruvate/phosphate transporter gene. In all tissues there was a long-term replenishment of most metabolite pools, which allowed damaged plants to maintain unaltered growth and grain yield. Promoter analysis of ADP-glucose pyrophosphorylase and vacuolar invertase genes indicated the presence of cis-regulatory elements that supported their responsiveness to defoliation. HD and MD had differential effects on transcripts, enzyme activities and metabolites. However, the correlation between transcript abundance and enzymatic activities was very limited. A better correlation was found between enzymes, metabolite levels and growth and reproductive parameters. Conclusions It is concluded that a rapid reduction of NSC reserves in leaves, stems and roots followed by their long-term recovery underlies tolerance to defoliation in grain amaranth. This requires the

  15. Lauric acid production in a glycogen-less Synechococcus sp. PCC 7002 mutant

    Directory of Open Access Journals (Sweden)

    Victoria H. Work

    2015-04-01

    Full Text Available The cyanobacterium Synechococcus sp. PCC 7002 was genetically engineered to synthesize biofuel compatible medium-chain fatty acids during photoautotrophic growth. Expression of a heterologous lauroyl-acyl carrier protein (C12:0-ACP thioesterase with concurrent deletion of the endogenous putative acyl-ACP synthetase led to secretion of transesterifiable C12:0 fatty acid in CO2-supplemented batch cultures. When grown at steady state over a range of light intensities in an LED turbidostat photobioreactor, the C12-secreting mutant exhibited a modest reduction in growth rate and increased O2 evolution relative to the wildtype. Inhibition of i glycogen synthesis by deletion of the glgC-encoded ADP-glucose pyrophosphorylase (AGPase, and ii protein synthesis by nitrogen deprivation were investigated as potential mechanisms for metabolite redistribution to increase fatty acid synthesis. Deletion of AGPase led to a ten-fold decrease in reducing carbohydrates and secretion of organic acids during nitrogen deprivation consistent with an energy spilling phenotype. When the carbohydrate-deficient background (∆glgC was modified for C12 secretion, no increase in C12 was achieved during nutrient replete growth, and no C12 was recovered from any strain upon nitrogen deprivation under the conditions used. At steady state, the growth rate of the ∆glgC strain saturated at a lower light intensity than the wildtype, but O2 evolution was not compromised and became increasingly decoupled from growth rate with rising irradiance. Photophysiological properties of the ∆glgC strain suggest energy dissipation from photosystem II and reconfiguration of electron flow at the level of the plastoquinone pool.

  16. Metabolic engineering of sugarcane to accumulate energy-dense triacylglycerols in vegetative biomass.

    Science.gov (United States)

    Zale, Janice; Jung, Je Hyeong; Kim, Jae Yoon; Pathak, Bhuvan; Karan, Ratna; Liu, Hui; Chen, Xiuhua; Wu, Hao; Candreva, Jason; Zhai, Zhiyang; Shanklin, John; Altpeter, Fredy

    2016-02-01

    Elevating the lipid content in vegetative tissues has emerged as a new strategy for increasing energy density and biofuel yield of crops. Storage lipids in contrast to structural and signaling lipids are mainly composed of glycerol esters of fatty acids, also known as triacylglycerol (TAG). TAGs are one of the most energy-rich and abundant forms of reduced carbon available in nature. Therefore, altering the carbon-partitioning balance in favour of TAG in vegetative tissues of sugarcane, one of the highest yielding biomass crops, is expected to drastically increase energy yields. Here we report metabolic engineering to elevate TAG accumulation in vegetative tissues of sugarcane. Constitutive co-expression of WRINKLED1 (WRI1), diacylglycerol acyltransferase1-2 (DGAT1-2) and oleosin1 (OLE1) and simultaneous cosuppression of ADP-glucose pyrophosphorylase (AGPase) and a subunit of the peroxisomal ABC transporter1 (PXA1) in transgenic sugarcane elevated TAG accumulation in leaves or stems by 95- or 43-fold to 1.9% or 0.9% of dry weight (DW), respectively, while expression or suppression of one to three of the target genes increased TAG levels by 1.5- to 9.5-fold. Accumulation of TAG in vegetative progeny plants was consistent with the results from primary transgenics and contributed to a total fatty acid content of up to 4.7% or 1.7% of DW in mature leaves or stems, respectively. Lipid droplets were visible within mesophyll cells of transgenic leaves by confocal fluorescence microscopy. These results provide the basis for optimizations of TAG accumulation in sugarcane and other high yielding biomass grasses and will open new prospects for biofuel applications. PMID:26058948

  17. Cumulative effect of heterologous AtWRI1 gene expression and endogenous BjAGPase gene silencing increases seed lipid content in Indian mustard Brassica juncea.

    Science.gov (United States)

    Bhattacharya, Surajit; Das, Natasha; Maiti, Mrinal K

    2016-10-01

    The production of vegetable oil in many countries of the world, including India has not been able to keep pace with the increasing requirement, leading to a very large gap in the demand-supply chain. Thus, there is an urgent need to increase the yield potential of the oilseed crops so as to enhance the storage lipid productivity. The present study describes a novel metabolic engineering ploy involving the constitutive down-regulation of endogenous ADP-glucose pyrophosphorylase (BjAGPase) enzyme and the seed-specific expression of WRINKLED1 transcription factor (AtWRI1) from Arabidopsis thaliana in Indian mustard (Brassica juncea) with an aim to divert the photosynthetically fixed carbon pool from starch to lipid synthesis in the seeds for the enhanced production of storage lipids in the seeds of transgenic mustard plants. The starch content, in both the vegetative leaf and developing seed tissues of the transgenic B. juncea lines exhibited a reduction by about 45-53% compared to the untransformed control, whereas the soluble sugar content was increased by 2.4 and 1.3-fold in the leaf and developing seed tissues, respectively. Consequently, the transgenic lines showed a significant enhancement in total seed lipid content ranging between 7.5 and 16.9%. The results indicate that the adopted metabolic engineering strategy was successful in significantly increasing the seed oil content. Therefore, findings of our research suggest that the metabolic engineering strategy adopted in this study for shifting the anabolic carbon flux from starch synthesis to lipid biosynthesis can be employed for increasing the storage lipid content of seeds in other plant species. PMID:27314514

  18. Responses of ethylene and ACC in rice grains to soil moisture and their relations to grain filling

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The objectives of this study were to-investigate ethylene and 1-aminocylopropane-1-carboxylic acid (ACC) in rice grains and root bleeding sap during the grain filling period and their relationship to the grain filling rate.Two high lodging-resistant rice (Oryza sativa L.) cultivars were grown in pots or tanks.Three treatments,including well watered (WW),moderate soil-drying (MD) and severe soil-drying (SD),were conducted from 9 days of post-anthesis until maturity.The effects of chemical regulators on the concentrations of ethylene and ACC in the grains were also studied.The results show that MD significantly increased the grainfilling rate and grain weight,whereas SD significantly reduced the grain-filling rate and grain weight.Concentrations of ethylene and ACC in the grains were very high at the early grain filling stage and then sharply decreased during the linear period of grain growth.MD reduced the ACC concentrations and ethylene evolution rate,whereas SD remarkably increased the ACC concentrations and ethylene evolution rate.Both the ethylene evolution rate in rice grains and the ACC concentrations in the root-bleeding sap were significantly and positively correlated with the ACC concentrations in rice grains.The ethylene evolution rate was significantly and negatively correlated with the grain-filling rate.The application of amino-ethoxyvinylglycine (AVG),an inhibitor of ethylene synthesis,at 9-13 days of postanthesis significantly reduced the ACC concentrations and ethylene evolution rate of grains,but significantly enhanced the activities of sucrose synthase,ADP glucose pyrophosphorylase and soluble starch synthase.The results were reversed when ethephon,an ethylenereleasing agent,was applied.The results suggest that moderate soil drying during the grain-filling period in rice could inhibit the production of ethylene and ACC and therefore accelerate grain filling and increase grain weight.

  19. Leaf Responses of Micropropagated Apple Plants to Water Stress: Changes in Endogenous Hormones and Their Influence on Carbohydrate Metabolism

    Institute of Scientific and Technical Information of China (English)

    LI Tian-hong; LI Shao-hua

    2007-01-01

    The changes in the concentrations of endogenous hormones and their influence on carbohydrate metabolism in leaves of micropropagated Fuji apple plants were studied under water deficiency stress. The results showed that water stress induced a rapid increase in the concentration of abscisic acid (ABA) and led to a decrease in concentrations of both zeatin and gibberellins (GAs). The concentration of indole-3-acetic acid (IAA) changed in an independent manner, which was not correlated with the different levels of water stress. With regard to the carbohydrates, the contents of sorbitol and sucrose increased, whereas the content of starch decreased. The increase in the concentration of ABA was significantly correlated with both the increase in the activity of aldose-6-phosphate reductase (A6PR) and the decrease in the activity of sorbitol dehydrogenase (SDH), indicating that ABA played a regulatory role in sorbitol metabolism. The concentration of ABA was positively correlated to the activity of sucrose-phosphate synthase (SPS) but negatively correlated to the activities of acid invertase (AI) and ADP-glucose-pyrophosphorylase (ADPGppase) in water-stressed plants, which indicated that ABA promoted sucrose synthesis and inhibited sucrose degradation and starch synthesis at the same time. Under conditions of water stress, the decrease in the level of zeatin was accompanied by a decrease in the activities of SDH and ADPGPPase. GAs concentration showed positive correlation with ADPGPPase activity. IAA showed no significant correlation with any of the enzymes tested in this study. The results of this study suggested that ABA might be one of the key factors regulating the distribution of carbohydrates under water stress. The metabolism of sorbitol and starch under conditions of water stress might be regulated by the combined action of many plant hormones.

  20. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape during in Vitro Culture.

    Science.gov (United States)

    Schwender, Jörg; Hebbelmann, Inga; Heinzel, Nicolas; Hildebrandt, Tatjana; Rogers, Alistair; Naik, Dhiraj; Klapperstück, Matthias; Braun, Hans-Peter; Schreiber, Falk; Denolf, Peter; Borisjuk, Ljudmilla; Rolletschek, Hardy

    2015-07-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. Overall, we observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Quantitative data were also used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism. PMID:25944824

  1. Factors Altering Pyruvate Excretion in a Glycogen Storage Mutant of the Cyanobacterium, Synechococcus PCC7942.

    Science.gov (United States)

    Benson, Phoebe J; Purcell-Meyerink, Diane; Hocart, Charles H; Truong, Thy T; James, Gabriel O; Rourke, Loraine; Djordjevic, Michael A; Blackburn, Susan I; Price, G D

    2016-01-01

    Interest in the production of carbon commodities from photosynthetically fixed CO2 has focused attention on cyanobacteria as a target for metabolic engineering and pathway investigation. We investigated the redirection of carbon flux in the model cyanobacterial species, Synechococcus elongatus PCC 7942, under nitrogen deprivation, for optimized production of the industrially desirable compound, pyruvate. Under nitrogen limited conditions, excess carbon is naturally stored as the multi-branched polysaccharide, glycogen, but a block in glycogen synthesis, via knockout mutation in the gene encoding ADP-glucose pyrophosphorylase (glgC), results in the accumulation of the organic acids, pyruvate and 2-oxoglutarate, as overflow excretions into the extracellular media. The ΔglgC strain, under 48 h of N-deprivation was shown to excrete pyruvate for the first time in this strain. Additionally, by increasing culture pH, to pH 10, it was possible to substantially elevate excretion of pyruvate, suggesting the involvement of an unknown substrate/proton symporter for export. The ΔglgC mutant was also engineered to express foreign transporters for glucose and sucrose, and then grown photomixotrophically with exogenous organic carbon supply, as added 5 mM glucose or sucrose during N- deprivation. Under these conditions we observed a fourfold increase in extracellular pyruvate excretion when glucose was added, and a smaller increase with added sucrose. Although the magnitude of pyruvate excretion did not correlate with the capacity of the ΔglgC strain for bicarbonate-dependent photosynthetic O2 evolution, or with light intensity, there was, however, a positive correlation observed between the density of the starter culture prior to N-deprivation and the final extracellular pyruvate concentration. The factors that contribute to enhancement of pyruvate excretion are discussed, as well as consideration of whether the source of carbon for pyruvate excretion might be derived from

  2. Photosynthesis Activates Plasma Membrane H+-ATPase via Sugar Accumulation.

    Science.gov (United States)

    Okumura, Masaki; Inoue, Shin-Ichiro; Kuwata, Keiko; Kinoshita, Toshinori

    2016-05-01

    Plant plasma membrane H(+)-ATPase acts as a primary transporter via proton pumping and regulates diverse physiological responses by controlling secondary solute transport, pH homeostasis, and membrane potential. Phosphorylation of the penultimate threonine and the subsequent binding of 14-3-3 proteins in the carboxyl terminus of the enzyme are required for H(+)-ATPase activation. We showed previously that photosynthesis induces phosphorylation of the penultimate threonine in the nonvascular bryophyte Marchantia polymorpha However, (1) whether this response is conserved in vascular plants and (2) the process by which photosynthesis regulates H(+)-ATPase phosphorylation at the plasma membrane remain unresolved issues. Here, we report that photosynthesis induced the phosphorylation and activation of H(+)-ATPase in Arabidopsis (Arabidopsis thaliana) leaves via sugar accumulation. Light reversibly phosphorylated leaf H(+)-ATPase, and this process was inhibited by pharmacological and genetic suppression of photosynthesis. Immunohistochemical and biochemical analyses indicated that light-induced phosphorylation of H(+)-ATPase occurred autonomously in mesophyll cells. We also show that the phosphorylation status of H(+)-ATPase and photosynthetic sugar accumulation in leaves were positively correlated and that sugar treatment promoted phosphorylation. Furthermore, light-induced phosphorylation of H(+)-ATPase was strongly suppressed in a double mutant defective in ADP-glucose pyrophosphorylase and triose phosphate/phosphate translocator (adg1-1 tpt-2); these mutations strongly inhibited endogenous sugar accumulation. Overall, we show that photosynthesis activated H(+)-ATPase via sugar production in the mesophyll cells of vascular plants. Our work provides new insight into signaling from chloroplasts to the plasma membrane ion transport mechanism. PMID:27016447

  3. Photosynthesis Activates Plasma Membrane H+-ATPase via Sugar Accumulation1[OPEN

    Science.gov (United States)

    Okumura, Masaki; Inoue, Shin-ichiro; Kuwata, Keiko

    2016-01-01

    Plant plasma membrane H+-ATPase acts as a primary transporter via proton pumping and regulates diverse physiological responses by controlling secondary solute transport, pH homeostasis, and membrane potential. Phosphorylation of the penultimate threonine and the subsequent binding of 14-3-3 proteins in the carboxyl terminus of the enzyme are required for H+-ATPase activation. We showed previously that photosynthesis induces phosphorylation of the penultimate threonine in the nonvascular bryophyte Marchantia polymorpha. However, (1) whether this response is conserved in vascular plants and (2) the process by which photosynthesis regulates H+-ATPase phosphorylation at the plasma membrane remain unresolved issues. Here, we report that photosynthesis induced the phosphorylation and activation of H+-ATPase in Arabidopsis (Arabidopsis thaliana) leaves via sugar accumulation. Light reversibly phosphorylated leaf H+-ATPase, and this process was inhibited by pharmacological and genetic suppression of photosynthesis. Immunohistochemical and biochemical analyses indicated that light-induced phosphorylation of H+-ATPase occurred autonomously in mesophyll cells. We also show that the phosphorylation status of H+-ATPase and photosynthetic sugar accumulation in leaves were positively correlated and that sugar treatment promoted phosphorylation. Furthermore, light-induced phosphorylation of H+-ATPase was strongly suppressed in a double mutant defective in ADP-glucose pyrophosphorylase and triose phosphate/phosphate translocator (adg1-1 tpt-2); these mutations strongly inhibited endogenous sugar accumulation. Overall, we show that photosynthesis activated H+-ATPase via sugar production in the mesophyll cells of vascular plants. Our work provides new insight into signaling from chloroplasts to the plasma membrane ion transport mechanism. PMID:27016447

  4. 石门揭露突出煤层冻结温度场数值模拟研究%Research on numerical simulation of freezing temperature field in uncovering outburst coal seam in cross-cut

    Institute of Scientific and Technical Information of China (English)

    谢雄刚; 冯涛

    2011-01-01

    Aiming at a new-presented outburst-proof method by injecting liquid and freezing in uncovering coal seam in cross-cut in this paper,with the ANSYS numerical simulation software,according to the operation parameters in the work face of uncovering coal seam at No.2 cross-cut of-400 m level in Longjiashan Mine,the authors established the numerical simulation calculation model of the temperature field in freezing section,analyzed its expand nephogram in different period,decided the effective range,average temperature,closure time of ice zone and expand velocity.The simulation shows that the more near to the freezing center,the more fast the temperature of the No.6 coal seam will decline.At the same time,the temperature in coal seam of frozen tubes in center cross-section and vertical-section is lowest.After 35~40 days,reached the frozen control temperature of-15 ℃ for outburst-proof.The No.6 coal in freezing zone is strong enough to prevent coal and gas outburst.The feasibility of injecting liquid and freezing as a new outburst-proof method was proved.%针对新提出的石门揭煤注液冻结防突方法,根据龙家山煤矿-400 m水平2号石门揭煤工作面施工参数,应用ANSYS数值模拟软件,建立了石门揭煤冻结温度场数值模拟计算模型,分析了不同时期冻结区温度扩展云图,得出不同冻结时间冻结区有效范围、平均温度、交圈时间及温度扩展速度。数值模拟表明:距离中心越近,冻结区煤层温度下降越快;相同冻结时间,竖向中排冻结管断面和横向中排冻结管断面处煤层温度最低。该石门揭煤工作面需要35~40 d冻结时间来满足-15℃煤层控制温度的防突工程要求。证明石门揭煤注液冻结防突技术是可行性的。

  5. 大型露天停车场雷电灾害分析与防护措施的研究%Lightning Hazard Analysis and Protective Measures of Large Uncovered Parking

    Institute of Scientific and Technical Information of China (English)

    赵涛; 李斐

    2014-01-01

    近年来,由于气候变化使强对流性天气不断增多,雷击事件频发。特别是空旷地区防雷设施不完善,防雷设施的缺乏,致使雷击造成人员伤亡和经济损失的事故时有发生。通过武汉经济技术开发区神龙汽车公司的露天停车场两次成品车遭受雷击事故的实地调查,就该村地理位置、气象资料、雷灾产生的原因进行了分析,提出了相应的雷电防护对策及建议。%In recent years, the climate change makes strong convective weather increasing and frequent lightning events. Especially in open areas, the lightning protection facilities in open areas are imperfect, even lack of lightning protection facilities, so the lightning casualties and economic losses occurred often. Through the fieldwork of the two lightning accident of finished car in uncovered parking of Shenlong Car company in Wuhan Economic and Technological Development Zone, the paper analyzes the location, meteorological data and the reasons of lightning disaster, and puts forward the corresponding countermeasures and suggestions for lightning protection.

  6. Uncovering the nucleus candidate for NGC 253

    CERN Document Server

    Günthardt, G I; Camperi, J A; Díaz, R J; Gomez, P L; Bosch, G; Schirmer, M

    2015-01-01

    NGC253 is the nearest spiral galaxy with a nuclear starburst which becomes the best candidate to study the relationship between starburst and AGN activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus. The near infrared spectroscopy could be advantageous in order to shed light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis and through the brightest infrared source. We present evidence showing that the brightest near infrared and mid infrared source in the central region, already known as radio source TH7 and so far considered just a stellar supercluster, in fact, presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. It is the most massive compact infrared object in the central region, located at 2.0" of the symmetry center of the galactic bar. Moreover, our data indicate that this object i...

  7. The Great 1787 Corralero, Oaxaca, Tsunami Uncovered

    Science.gov (United States)

    Ramirez-Herrera, M.; Lagos, M.; Goguitchaichrili, A.; Aguilar, B.; Machain-Castillo, M. L.; Caballero, M.; Ruíz-Fernández, A. C.; Suarez, G.; Ortuño, M.

    2013-05-01

    In 28th March 1787, more than two centuries ago, a deadly tsunami (related to the the San Sixto earthquake) poured over the coast of Oaxaca, Guerrero, and Chiapas, along more than 500 km of the Mexican Pacific coast and up to 6 km inland, the tsunami destroyed mostly farmlands, and livestock and few villages since the density of population was sparse at the time, according to known historical accounts. We report the first geological evidence from the Corralero (Alotengo) lagoon coastal area to support these historical accounts. A transect was made with coring and test pits every 100 m from the coastline and up to 1.6 km inland. The test pits showed an anomalous sand layer that had been deposited in a single event in the swales of a series of beach ridges. The anomalous layer is continuous along the transect, about a 1000 m-long, and is formed of coarse to medium sand, at about 36 to 64 cm depth. It thickness varies, averaging 28 cm in the middle of a swale. Based on the accounts of the 1787 earthquake (M 8.6) and tsunami, we deduced that this might be the evidence of its existence. As the only major tsunami described at that time, the San Sixto earthquake-triggered tsunami. We used the stratigraphy, grain size, microfossils (foraminifera and diatoms), magnetic properties such as magnetic susceptibility, remanent magnetization analyses to reveal the nature of this anomalous sand layer. These proxies support a sudden and rapid event, consisting of sands transported by an extreme sea-wave inland. Further analysis will confirm the estimated age of this event.

  8. η Carinae Baby Homunculus uncovered by ALMA

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, Zulema; Beaklini, Pedro P. B. [Instituto de Astronomia, Geofísica e Ciências Atmosféricas, Universidade de São Paulo, R. do Matão 1226, Cidade Universitária, CEP 05508-900 São Paulo, SP (Brazil); Falceta-Gonçalves, Diego, E-mail: zulema.abraham@iag.usp.br [Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, R. Arlindo Bettio 1000, 03828-000 São Paulo, SP (Brazil)

    2014-08-20

    We report observations of η Carinae obtained with ALMA in the continuum of 100, 230, 280, and 660 GHz in 2012 November, with a resolution that varied from 2.''88 to 0.''45 for the lower and higher frequencies, respectively. The source is not resolved, even at the highest frequency; its spectrum is characteristic of thermal bremsstrahlung of a compact source, but different from the spectrum of optically thin wind. The recombination lines H42α, He42α, H40α, He40α, H50β, H28α, He28α, H21α, and He21α were also detected, and their intensities reveal non-local thermodynamic equilibrium effects. We found that the line profiles could only be fit by an expanding shell of dense and ionized gas, which produces a slow shock in the surroundings of η Carinae. Combined with fittings to the continuum, we were able to constrain the shell size, radius, density, temperature, and velocity. The detection of the He recombination lines is compatible with the high-temperature gas and requires a high-energy ionizing photon flux, which must be provided by the companion star. The mass-loss rate and wind velocity, necessary to explain the formation of the shell, are compatible with an luminous blue variable eruption. The position, velocity, and physical parameters of the shell coincide with those of the Weigelt blobs. The dynamics found for the expanding shell correspond to matter ejected by η Carinae in 1941 in an event similar to that which formed the Little Homunculus; for that reason, we called the new ejecta the 'Baby Homunculus'.

  9. Uncovering the Hidden Costs of Offshoring

    DEFF Research Database (Denmark)

    Larsen, Marcus M.; Manning, Stephan; Pedersen, Torben

    2013-01-01

    This study investigates estimation errors due to hidden costs—the costs of implementation that are neglected in strategic decision-making processes—in the context of services offshoring. Based on data from the Offshoring Research Network, we find that decision makers are more likely to make cost-estimation...... errors given increasing configuration and task complexity in captive offshoring and offshore outsourcing, respectively. Moreover, we show that experience and a strong orientation toward organizational design in the offshoring strategy reduce the cost-estimation errors that follow from complexity. Our...

  10. Uncovering dengue in India: morbidity estimates

    Directory of Open Access Journals (Sweden)

    Ananda Amarasinghe

    2014-05-01

    Full Text Available Over the last few decades, reporting of dengue cases has dramatically spread over almost entire India but the disease burden is grossly under-estimated under the current surveillance system. This review based on literature searches in PubMed and Medline for the period 1961-2012 describes changing epidemiological patterns, emerging challenges to public health intervention for control of dengue transmission in India and estimates magnitude of under-reporting. The annual reported numbers in 10 selected states/Union Territories with the highest number of cases during the years 2008-2012 and the surveillance system estimated expansion factor of 8.9-9.6 derived from Thailand and Cambodia data respectively were used for new estimates of dengue morbidity in India. The reporting incidence of dengue is as low as 4/100,000 in 2012. The estimated crude incidence of dengue for 2012 is 53/100,000 to 58.83/100,000 and the country annual health care facility based case load would be around 700,000. India needs to expand surveillance activities to non-hospitalized cases and to the distribution and abundance of Aedes aegypti throughout country and review state and local vector control activities for Aedes aegypti and Aedes albopictus. Knowledge of vector prevalence is essential to estimate the geographical distribution of dengue infection and associated disease.

  11. Uncovering History for Future History Teachers

    Science.gov (United States)

    Fischer, Fritz

    2010-01-01

    The art of history teaching is at a crossroads. Recent scholarship focuses on the need to change the teaching of history so students can better learn history, and insists that history teachers must move beyond traditional structures and methods of teaching in order to improve their students' abilities to think with history. This article presents…

  12. Uncovering the Matter-Neutrino Resonance

    CERN Document Server

    Vaananen, D

    2015-01-01

    Matter Neutrino Resonances (MNRs) can drastically modify neutrino flavor evolution in astrophysical environments and may significantly impact nucleosynthesis. Here we further investigate the underlying physics of MNR type flavor transitions. We provide generalized resonance conditions and make analytical predictions for the behavior of the system. We discuss the adiabatic evolution of these transitions, considering both Symmetric and Standard scenarios. Symmetric MNR transitions differ from Standard MNR transitions in that both neutrinos and antineutrinos can completely transform to other flavors simultaneously. We provide an example of the simplest system in which such transitions can occur with a neutrino and an antineutrino having a single energy and emission angle. We further apply linearized stability analysis to predict the location of self-induced nutation type (or bipolar) oscillations due to neutrino-neutrino interactions in the regions where MNR is ineffective. In all cases, we compare our analytica...

  13. uncovering the everyday moral knowledge of nurses

    Directory of Open Access Journals (Sweden)

    Elizabeth Peter

    2007-01-01

    Full Text Available En el presente artículo exploramos el uso de la perspectiva metafísica de Margaret Urban Walter, particularmente el uso de narrativas, para informar sobre el desarrollo de un abordaje de investigación que revela el conocimiento moral cotidiano de las enfermeras. Un método basado en el trabajo de Walter permite analizar las dimensiones de poder inherentes en la experiencia moral de las enfermeras, así como fundamentar con una moral epistemológica robusta, el abordaje narrativo ético de la enfermería, y distinguir los diferentes tipos de narrativas. Un número de cuestiones analíticas basadas en el trabajo de Walker son aquí presentadas y empleadas para analizar la práctica narrativa e ilustrar cómo las narrativas pueden ser usadas para delinear el conocimiento moral de las enfermeras dentro del contexto de su trabajo real.

  14. Uncovering the nutritional landscape of food

    CERN Document Server

    Kim, Seunghyeon; Foo, Mathias; Jin, Yong-Su; Kim, Pan-Jun

    2014-01-01

    The study of foods and nutrients is essential for designing healthy diets. This can be facilitated through quantitative, data-driven approaches that utilize massive nutritional information collected for many different foods. Using information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. Such nutrient balance within a food was quantified herein as nutritional fitness, using the food's frequency of occurrence in nutritionally-adequate food combinations. Nutritional fitness offers prioritization of recommendable foods within a food network, in which foods are connected based on similarities of nutrient compositions. We found a number of key nutrients, such as choline and \\alpha-linolenic acid, whose levels in foods can critically affect the foods' nutritional fitness. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can impact nutritional fitness synergistically, although the i...

  15. Tracing lineages to uncover neuronal identity

    OpenAIRE

    Perlmann Thomas; Panman Lia

    2011-01-01

    Abstract Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the dev...

  16. Tracing lineages to uncover neuronal identity

    Directory of Open Access Journals (Sweden)

    Perlmann Thomas

    2011-07-01

    Full Text Available Abstract Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain. See research article http://www.neuraldevelopment.com/content/6/1/29

  17. Uncovering Social Network Sybils in the Wild

    OpenAIRE

    Yang, Zhi; Wilson, Christo; Wang, Xiao; Gao, Tingting; Ben Y. Zhao; Dai, Yafei

    2011-01-01

    Sybil accounts are fake identities created to unfairly increase the power or resources of a single malicious user. Researchers have long known about the existence of Sybil accounts in online communities such as file-sharing systems, but have not been able to perform large scale measurements to detect them or measure their activities. In this paper, we describe our efforts to detect, characterize and understand Sybil account activity in the Renren online social network (OSN). We use ground tru...

  18. Uncovering the white place: whitewashing at work

    OpenAIRE

    Reitman, Meredith

    2006-01-01

    Recent work exploring the racialization of place tends to focus on the racialization of marginalized group space. This paper shifts attention toward the racialization of dominant group space, namely, the creation and maintenance of white places. Using the case study of the software workplace, I argue that white places are formed through a process of whitewashing, which simultaneously denies race and superimposes white culture. Whitewashing wields language and invisibility to deny race and pro...

  19. The crisis has uncovered the Slovak helplessness

    International Nuclear Information System (INIS)

    In this paper author deals with problems connected with close of transport of nature gas through the gas pipeline from Russia via Ukraine to the Slovak Republic. Russia-Ukraine gas dispute fully revealed as unreliable suppliers Moscow and Kiev as the carrier gas. Slovakia for the worse, imports it from Russia a long time covering almost a hundred percent of domestic consumption. From mouth of politicians and representatives of the Slovak Gas Industry (SPP) has repeatedly resounded that Gazprom is a reliable partner who offers the best conditions including prices. Events of other days reliability refuted the argument. A theory of the best terms and the lowest prices are valid until there are not empty tubes.

  20. Uncovering the Costs of the Iraq War

    OpenAIRE

    Fred E. Foldvary

    2008-01-01

    Fred Foldvary reviews the recent book by Joseph Stiglitz and Linda Bilmes, The Three Trillion Dollar War: The True Cost of the Iraq Conflict. Foldvary commends the book for its assembly of both the budgeted and implicit costs of the war, and its analysis of the economic impact of the war. The review posits that the better knowledge and accounting of the war costs as provided by this work will aid in establishing a more coherent dialog on policy for dealing with this and future conflicts abroad.

  1. Uncovering the 2010 Haiti earthquake death toll

    Directory of Open Access Journals (Sweden)

    J. E. Daniell

    2013-05-01

    Full Text Available Casualties are estimated for the 12 January 2010 earthquake in Haiti using various reports calibrated by observed building damage states from satellite imagery and reconnaissance reports on the ground. By investigating various damage reports, casualty estimates and burial figures, for a one year period from 12 January 2010 until 12 January 2011, there is also strong evidence that the official government figures of 316 000 total dead and missing, reported to have been caused by the earthquake, are significantly overestimated. The authors have examined damage and casualties report to arrive at their estimation that the median death toll is less than half of this value (±137 000$. The authors show through a study of historical earthquake death tolls, that overestimates of earthquake death tolls occur in many cases, and is not unique to Haiti. As death toll is one of the key elements for determining the amount of aid and reconstruction funds that will be mobilized, scientific means to estimate death tolls should be applied. Studies of international aid in recent natural disasters reveal that large distributions of aid which do not match the respective needs may cause oversupply of help, aggravate corruption and social disruption rather than reduce them, and lead to distrust within the donor community.

  2. Uncovering Racial Bias in Nursing Fundamentals Textbooks.

    Science.gov (United States)

    Byrne, Michelle M.

    2001-01-01

    The portrayal of African Americans in nursing fundamentals textbooks was analyzed, resulting in 11 themes in the areas of history, culture, and physical assessment. Few African American leaders were included, and racial bias and stereotyping were apparent. Differences were often discussed using Eurocentric norms, and language tended to minimize…

  3. Model tuning in engineering: uncovering the logic

    OpenAIRE

    Steele, Katie; Werndl, Charlotte

    2016-01-01

    In engineering, as in other scientific fields, researchers seek to confirm their models with real-world data. It is common practice to assess models in terms of the distance between the model outputs and the corresponding experimental observations. An important question that arises is whether the model should then be ‘tuned’, in the sense of estimating the values of free parameters to get a better fit with the data, and furthermore whether the tuned model can be confirmed with the same data u...

  4. Data smashing: uncovering lurking order in data

    OpenAIRE

    Chattopadhyay, Ishanu; Lipson, Hod

    2014-01-01

    From automatic speech recognition to discovering unusual stars, underlying almost all automated discovery tasks is the ability to compare and contrast data streams with each other, to identify connections and spot outliers. Despite the prevalence of data, however, automated methods are not keeping pace. A key bottleneck is that most data comparison algorithms today rely on a human expert to specify what ‘features' of the data are relevant for comparison. Here, we propose a new principle for e...

  5. Comet mission hopes to uncover Earth's origins

    CERN Multimedia

    Henderson, M

    2004-01-01

    "A European spacecraft that will hunt down a comet in search of clues to the origin of life on Earth will blast off tomorrow from the Kourou spaceport in French Guiana. The Rosetta probe will take 12 years to catch up with Churyumov-Gerasimenko before becoming the first spacecraft to make a soft, controlled landing on a comet's nucleus" (1 page).

  6. Uncovering Conceptual Gaps in Introductory IS Textbooks

    Science.gov (United States)

    Hassan, Nik R.; Becker, Jack D.

    2007-01-01

    This study performs an exploration of the relationship between introductory IS textbooks and the body of knowledge represented by the set of "super classic" IS publications. Textbooks play a critical role of introducing the IS field to IS majors, describing what constitutes mainstream IS knowledge and communicating to other disciplines and their…

  7. Uncovering ecosystem service bundles through social preferences.

    Directory of Open Access Journals (Sweden)

    Berta Martín-López

    Full Text Available Ecosystem service assessments have increasingly been used to support environmental management policies, mainly based on biophysical and economic indicators. However, few studies have coped with the social-cultural dimension of ecosystem services, despite being considered a research priority. We examined how ecosystem service bundles and trade-offs emerge from diverging social preferences toward ecosystem services delivered by various types of ecosystems in Spain. We conducted 3,379 direct face-to-face questionnaires in eight different case study sites from 2007 to 2011. Overall, 90.5% of the sampled population recognized the ecosystem's capacity to deliver services. Formal studies, environmental behavior, and gender variables influenced the probability of people recognizing the ecosystem's capacity to provide services. The ecosystem services most frequently perceived by people were regulating services; of those, air purification held the greatest importance. However, statistical analysis showed that socio-cultural factors and the conservation management strategy of ecosystems (i.e., National Park, Natural Park, or a non-protected area have an effect on social preferences toward ecosystem services. Ecosystem service trade-offs and bundles were identified by analyzing social preferences through multivariate analysis (redundancy analysis and hierarchical cluster analysis. We found a clear trade-off among provisioning services (and recreational hunting versus regulating services and almost all cultural services. We identified three ecosystem service bundles associated with the conservation management strategy and the rural-urban gradient. We conclude that socio-cultural preferences toward ecosystem services can serve as a tool to identify relevant services for people, the factors underlying these social preferences, and emerging ecosystem service bundles and trade-offs.

  8. Cobalamins uncovered by modern electronic structure calculations

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta; Ryde, Ulf

    electronic-structure calculations, in particular density functional methods, the understanding of the molecular mechanism of cobalamins has changed dramatically, going from a dominating view of trans-steric strain effects to a much more complex view involving an arsenal of catalytic strategies. Among these...

  9. Uncovering Mass Generation Through Higgs Flavor Violation

    CERN Document Server

    Altmannshofer, Wolfgang; Kagan, Alexander L; Silvestrini, Luca; Zupan, Jure

    2015-01-01

    If the flavor violating decay h --> tau mu is observed at the LHC, extra sources of electroweak symmetry breaking (EWSB) beyond the Higgs would be required in order to reconcile it with the bounds from tau --> mu gamma, barring fine-tuned cancellations. In fact, an h --> tau mu decay rate at a level indicated by the CMS measurement is easily realized if the muon and electron masses are due to a new source of EWSB, while the tau mass is due to the Higgs. We illustrate this with two examples: a two Higgs doublet model, and a model in which the Higgs is partially composite, with EWSB triggered by a technicolor sector. The 1st and 2nd generation quark masses and CKM mixing can also be assigned to the new EWSB source. Large deviations in the flavor diagonal lepton and quark Higgs Yukawa couplings are generic. If m_mu is due to a rank 1 mass matrix contribution, a novel Yukawa coupling sum rule holds, providing a precision test of our framework. Flavor violating quark and lepton (pseudo)scalar couplings combine to ...

  10. The SSR-based molecular profile of 1005 grapevine (Vitis vinifera L.) accessions uncovers new synonymy and parentages, and reveals a large admixture amongst varieties of different geographic origin.

    Science.gov (United States)

    Cipriani, Guido; Spadotto, Alessandro; Jurman, Irena; Di Gaspero, Gabriele; Crespan, Manna; Meneghetti, Stefano; Frare, Enrica; Vignani, Rita; Cresti, Mauro; Morgante, Michele; Pezzotti, Mario; Pe, Enrico; Policriti, Alberto; Testolin, Raffaele

    2010-11-01

    A collection of 1005 grapevine accessions was genotyped at 34 microsatellite loci (SSR) with the aim of analysing genetic diversity and exploring parentages. The comparison of molecular profiles revealed 200 groups of synonymy. The removal of perfect synonyms reduced the database to 745 unique genotypes, on which population genetic parameters were calculated. The analysis of kinship uncovered 74 complete pedigrees, with both parents identified. Many of these parentages were not previously known and are of considerable historical interest, e.g. Chenin blanc (Sauvignon × Traminer rot), Covè (Harslevelu selfed), Incrocio Manzoni 2-14 and 2-15 (Cabernet franc × Prosecco), Lagrein (Schiava gentile × Teroldego), Malvasia nera of Bolzano (Perera × Schiava gentile), Manzoni moscato (Raboso veronese × Moscato d'Amburgo), Moscato violetto (Moscato bianco × Duraguzza), Muscat of Alexandria (Muscat blanc à petit grain × Axina de tres bias) and others. Statistical robustness of unexpected pedigrees was reinforced with the analysis of an additional 7-30 SSRs. Grouping the accessions by profile resulted in a weak correlation with their geographical origin and/or current area of cultivation, revealing a large admixture of local varieties with those most widely cultivated, as a result of ancient commerce and population flow. The SSRs with tri- to penta-nucleotide repeats adopted for the present study showed a great capacity for discriminating amongst accessions, with probabilities of identity by chance as low as 1.45 × 10(-27) and 9.35 × 10(-12) for unrelated and full sib individuals, respectively. A database of allele frequencies and SSR profiles of 32 reference cultivars are provided. PMID:20689905

  11. Revelando sentidos na prática docente: a abordagem de corpus na análise do discurso Uncovering meanings in pedagogical practice: the corpus approach in discourse analysis

    Directory of Open Access Journals (Sweden)

    Vander Viana

    2011-01-01

    Full Text Available Este artigo discute a viabilidade da utilização de ferramentas da Linguística de Corpus na análise do discurso pedagógico. Para tanto, são apresentados dois estudos de caso. O primeiro focaliza o discurso de professores de língua inglesa de um renomado curso de idiomas do Rio de Janeiro acerca da implementação de recursos tecnológicos na sala de aula. O segundo estudo, por sua vez, busca perceber qual é o posicionamento de professores universitários de literaturas em língua inglesa sobre literatura e seu ensino. Os resultados apontam para a riqueza dos dados contextuais que podem ser depreendidos a partir de uma análise linguística de base empírica. Em última análise, o artigo revela a importância e a flexibilidade da abordagem de corpus na análise do discurso, que pode ser aplicada a inúmeros contextos.This paper discusses the feasibility of using Corpus Linguistics tools in the analysis of pedagogic discourse. For doing this, two case studies are presented. The first one focuses on the discourse of English language teachers of a well-known languages course in Rio de Janeiro about the implementation of technological resources in the classroom. The second study, in its turn, seeks to realize the position held by university professors of literatures in English language with regard to literature and its teaching. The results point out to the richness of contextual data which can be inferred from a linguistic analysis with an empirical basis. All in all, the paper uncovers the importance and flexibility of the corpus approach in discourse analysis, which may be applied to several contexts.

  12. Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.

    Science.gov (United States)

    Phirke, Prasad; Efimenko, Evgeni; Mohan, Swetha; Burghoorn, Jan; Crona, Filip; Bakhoum, Mathieu W; Trieb, Maria; Schuske, Kim; Jorgensen, Erik M; Piasecki, Brian P; Leroux, Michel R; Swoboda, Peter

    2011-09-01

    Cilia are ubiquitous cell surface projections that mediate various sensory- and motility-based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. To identify new components required for cilium biogenesis and function, we sought to further define and validate the transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using embryos staged to when the cell types developing cilia in the worm, the ciliated sensory neurons (CSNs), still differentiate. Comparisons between the two populations revealed 881 differentially regulated genes with greater than a 1.5-fold increase or decrease in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional GFP fusions revealed CSN-specific expression patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate genes, termed dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related serine/threonine kinase that is necessary for the proper function of intraflagellar transport, a process critical for cilium biogenesis. Together, our microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover-in addition to DYF-17 and DYF-18-cellular components important for cilium formation and function. PMID:21740898

  13. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    Science.gov (United States)

    Sankaranarayanan, Preethi; Schomay, Theodore E; Aiello, Katherine A; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq, PABPC5

  14. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    Directory of Open Access Journals (Sweden)

    Preethi Sankaranarayanan

    Full Text Available The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD, which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs. We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival

  15. 石门揭露突出煤层冻结温度场的实验研究%Experimental study of freezing temperature field in uncovering outburst coal seam in cross-cut

    Institute of Scientific and Technical Information of China (English)

    冯涛; 谢雄刚; 刘河清

    2011-01-01

    针对新提出的石门揭煤注液冻结防突方法,设计了室内水泥槽模型煤体冻结实验,分析了注液冻结后水泥槽中煤体温度、物理力学性能与冻结时间的关系。实验表明:槽中煤体形成以冻结管中心为圆心、半径为R沿径向随时间扩展的冻煤圆柱。槽中煤、瓦斯和水三相体最终变成坚硬冻结体,极大提高了其抗压强度和弹性模量等力学性能。实验论证了注液冻结石门揭煤工作面冻结区的形成,距离冻结管越近,煤体温度越低,最终能降到石门揭煤防突工程所需的-15℃煤层控制温度。%Aiming at a new-presented proof-outburst method by injecting liquid and freezing in uncovering coal seam in cross-cut,designed the coal freezing experimentation in cement trough model,analyzed the relation between the coal temperature,mechanical property and freezing time.Through the coal freezing experimentation in cement trough model,it shows that the freezing section,whose radius is R,is revolved around the freezing tube centre.The formed frozen coal column is patulous with the freezing time.The coal,gas,and water in the trough is frozen into the firm freezing structure finally,so the uniaxial compression strengths and elastic modulus of coal models and the other mechanical property are greatly increased.Through the experiment it proved the formation of freezing area in the cross-cut working face.The more near to the freezing tube,the more low the coal temperature is,reaching to the frozen control temperature of-15 ℃ for proof-outburst.

  16. Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major

    OpenAIRE

    Lamerz, Anne-Christin; Damerow, Sebastian; Kleczka, Barbara; Wiese, Martin; van Zandbergen, Ger; Lamerz, Jens; Wenzel, Alexander; Hsu, Fong-Fu; Turk, John; Beverley, Stephen M.; Routier, Françoise H.

    2010-01-01

    The nucleotide sugar UDP-galactose (UDP-Gal) is essential for the biosynthesis of several abundant glycoconjugates forming the surface glycocalyx of the protozoan parasite Leishmania major. Current data suggest that UDP-Gal could arise de novo by epimerization of UDP-glucose (UDP-Glc) or by a salvage pathway involving phosphorylation of Gal and the action of UDP-glucose:α-d-galactose-1-phosphate uridylyltransferase as described by Leloir. Since both pathways require UDP-Glc, inactivation of t...

  17. 全覆膜与非覆膜金属支架治疗胆道恶性梗阻随机对照研究%Covered versus uncovered self-expandable metal stents for malignant biliary obstruction: a randomized, controlled study

    Institute of Scientific and Technical Information of China (English)

    冀明; 王拥军; 李鹏; 吕富靖; 李巍; 张澍田

    2012-01-01

    目的 比较全覆膜金属支架与非覆膜金属支架治疗胆道恶性梗阻的有效性和安全性.方法 2010年10月至2012年8月无法手术根治性切除胆道恶性梗阻病例,随机分为两组,A组置入全覆膜金属支架,B组置入非覆膜金属支架,观察治疗效果及并发症情况.结果 共入组81例患者,其中A组41例,B组40例,两组均成功置入支架,达到有效引流目的.A组支架开放中位时间182.5 d,B组支架开放中位时间195.0 d,两组间支架开放时间差异无统计学意义(P=0.616).A组发生并发症3例(7.3%),B组发生4例(10%).结论 全覆膜金属支架与非覆膜金属支架治疗胆道恶性梗阻均安全有效,通畅时间相似.%Objective To compare therapeutic efficacy and safety of covered and uncovered self-expandable metal stents for malignant biliary obstruction.Methods From October 2010 to August 2012,patients with unresectable malignant biliary obstruction were recruited and divided into 2 groups to receive covered metal stents (group A) or uncovered metal stents (group B).Efficacy and complication of the procedure were compared.Results A total of 81 patients were recruited,with 41 in group A and 40 in group B.Stents were placed successfully in all patients.The median patency time of stent in group A was 182.5 d,which was not significantly different from that of group B (195.0 d,P =0.616).Complications occurred in 3 patients of group A (7.3%) and 4 of group B (10%).Conclusion Covered and uncovered metal stents are both safe and effective for treatment of malignant biliary obstruction with same patency time.

  18. Defects in leaf carbohydrate metabolism compromise acclimation to high light and lead to a high chlorophyll fluorescence phenotype in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Schmitz Jessica

    2012-01-01

    Full Text Available Abstract Background We have studied the impact of carbohydrate-starvation on the acclimation response to high light using Arabidopsis thaliana double mutants strongly impaired in the day- and night path of photoassimilate export from the chloroplast. A complete knock-out mutant of the triose phosphate/phosphate translocator (TPT; tpt-2 mutant was crossed to mutants defective in (i starch biosynthesis (adg1-1, pgm1 and pgi1-1; knock-outs of ADP-glucose pyrophosphorylase, plastidial phosphoglucomutase and phosphoglucose isomerase or (ii starch mobilization (sex1-3, knock-out of glucan water dikinase as well as in (iii maltose export from the chloroplast (mex1-2. Results All double mutants were viable and indistinguishable from the wild type when grown under low light conditions, but - except for sex1-3/tpt-2 - developed a high chlorophyll fluorescence (HCF phenotype and growth retardation when grown in high light. Immunoblots of thylakoid proteins, Blue-Native gel electrophoresis and chlorophyll fluorescence emission analyses at 77 Kelvin with the adg1-1/tpt-2 double mutant revealed that HCF was linked to a specific decrease in plastome-encoded core proteins of both photosystems (with the exception of the PSII component cytochrome b559, whereas nuclear-encoded antennae (LHCs accumulated normally, but were predominantly not attached to their photosystems. Uncoupled antennae are the major cause for HCF of dark-adapted plants. Feeding of sucrose or glucose to high light-grown adg1-1/tpt-2 plants rescued the HCF- and growth phenotypes. Elevated sugar levels induce the expression of the glucose-6-phosphate/phosphate translocator2 (GPT2, which in principle could compensate for the deficiency in the TPT. A triple mutant with an additional defect in GPT2 (adg1-1/tpt-2/gpt2-1 exhibited an identical rescue of the HCF- and growth phenotype in response to sugar feeding as the adg1-1/tpt-2 double mutant, indicating that this rescue is independent from the

  19. A diagnostic trap potentially lethal: chordomas uncovered by C3 large osseous destruction inconspicuous on bis-phosphonates-({sup 99}Tc) bone scintigraphy; Un piege diagnostique potentiellement letal: chordome revele par une vaste lesion lytique de C3 normofixante a la scintigraphie osseuse aux bisphosphonates-({sup 99}Tc)

    Energy Technology Data Exchange (ETDEWEB)

    Paycha, F.; Ramadan, A.; Akrout, L. [Hopital Louis Mourier, Unite de Medecine Nucleaire, 92 - Colombes (France); Dion, E. [Hopital Louis Mourier, Service de Radiologie, 92 - Colombes (France); Grossin, M. [Hopital Louis Mourier, Service d' Anatomie Pathologique, 92 - Colombes (France); Gazals-Hatem, D. [Hopital Beaujon, Service d' Anatomie Pathologique, 92 - Clichy (France)

    2006-07-15

    The authors describe a case report of a brachialgy uncovering a solitary bone destruction of C3 associated with epidural involvement. CT and MRI properly depicted the lesion and the loco-regional extension but failed to entertain the diagnosis of the causative tumor, a chordoma. Bis-phosphonates-({sup 99m}Tc) bone scintigraphy proved unconspicuous. Diagnosis was eventually established from the resection specimen, after decision of C3 spondyl-ectomy, C4 hemi-superior spondyl-ectomy and epidural extension excision. Immunohistochemistry study of the material was decisive in identifying the tumor. Cervical chordoma is a tricky diagnosis. Discussion underscores that the crux of diagnostic process is the double discrepancy firstly between extra-osseous and intra-osseous tumoral expansion, secondly between large tumoral mass obvious on multi-slice morphological imaging and negativity of bone scintigraphy, SPECT study included. Among the armamentarium of conventional scintigraphies and PET studies, methionine-({sup 11}C) PET emerges as the most promising anatomo-metabolic procedure to assess loco-regional tumoral expansion, tumoral viability, therapy efficiency, and, potentially, to search for metastases in chordoma. (author)

  20. Uncovering Portuguese teachers’ difficulties in implementing sciences curriculum

    Directory of Open Access Journals (Sweden)

    Clara Vasconcelos

    2015-12-01

    Full Text Available Many countries recognize the positive and effective results of improving science education through the introduction of reforms in the sciences curriculum. However, some important issues are generally neglected like, for example, the involvement of the teachers in the reform process. Taking the sciences curriculum reform under analysis and benefitting from 10 years of teachers’ experiences in teaching sciences based on this curriculum, 19 semi-structure interviews were applied so as to identify the major difficulties felt by science teachers when implementing the Portuguese sciences curriculum in the third cycle of middle school (pupils’ age range of 12–15. Some of the difficulties depicted by the data analysis include: length of the curriculum, lack of time, unsuitable laboratory facilities, insufficient means and materials for experimental work, pupils’ indiscipline and little interest in learning sciences. Although less frequently mentioned, the lack of professional development was also referred to as a constraint that seems to play an essential role in this process. Some recommendations for improving the success of sciences curriculum reforms’ implementation are given: defining and conceptualizing curricular policies by relating the reality of both the schools and the science classrooms; reorganizing and restructuring pre-service teachers’ courses; organizing professional development courses for in-service teachers.

  1. Uncovering MIT wind myths through micro-climatological CFD analysis

    CERN Document Server

    Kalmikov, Alexander

    2013-01-01

    Popular campus myths of unusually strong pedestrian level winds are investigated with a Computational Fluid Dynamics (CFD) approach. The numerical simulations confirm the existence of the reported phenomena and provide a qualitative explanation of their physical mechanisms.

  2. Book Review, Waste: Uncovering the Global Food Scandal

    Science.gov (United States)

    Could curbing food waste significantly reduce world hunger and environmental pressures? Tristram Stuart argues cogently that it could in his book Waste, which details the global food-waste scandal and delves into questions such as how much food is available globally? How much is needed and used, a...

  3. Uncovering the single top: observation of electroweak top quark production

    Energy Technology Data Exchange (ETDEWEB)

    Benitez, Jorge Armando [Michigan State Univ., East Lansing, MI (United States)

    2009-01-01

    The top quark is generally produced in quark and anti-quark pairs. However, the Standard Model also predicts the production of only one top quark which is mediated by the electroweak interaction, known as 'Single Top'. Single Top quark production is important because it provides a unique and direct way to measure the CKM matrix element Vtb, and can be used to explore physics possibilities beyond the Standard Model predictions. This dissertation presents the results of the observation of Single Top using 2.3 fb-1 of Data collected with the D0 detector at the Fermilab Tevatron collider. The analysis includes the Single Top muon+jets and electron+jets final states and employs Boosted Decision Tress as a method to separate the signal from the background. The resulting Single Top cross section measurement is: (1) σ(p$\\bar{p}$→ tb + X, tqb + X) = 3.74-0.74+0.95 pb, where the errors include both statistical and systematic uncertainties. The probability to measure a cross section at this value or higher in the absence of signal is p = 1.9 x 10-6. This corresponds to a standard deviation Gaussian equivalence of 4.6. When combining this result with two other analysis methods, the resulting cross section measurement is: (2) σ(p$\\bar{p}$ → tb + X, tqb + X) = 3.94 ± 0.88 pb, and the corresponding measurement significance is 5.0 standard deviations.

  4. Unique small RNA signatures uncovered in the tammar wallaby genome

    Directory of Open Access Journals (Sweden)

    Lindsay James

    2012-10-01

    Full Text Available Abstract Background Small RNAs have proven to be essential regulatory molecules encoded within eukaryotic genomes. These short RNAs participate in a diverse array of cellular processes including gene regulation, chromatin dynamics and genome defense. The tammar wallaby, a marsupial mammal, is a powerful comparative model for studying the evolution of regulatory networks. As part of the genome sequencing initiative for the tammar, we have explored the evolution of each of the major classes of mammalian small RNAs in an Australian marsupial for the first time, including the first genome-scale analysis of the newest class of small RNAs, centromere repeat associated short interacting RNAs (crasiRNAs. Results Using next generation sequencing, we have characterized the major classes of small RNAs, micro (mi RNAs, piwi interacting (pi RNAs, and the centromere repeat associated short interacting (crasi RNAs in the tammar. We examined each of these small RNA classes with respect to the newly assembled tammar wallaby genome for gene and repeat features, salient features that define their canonical sequences, and the constitution of both highly conserved and species-specific members. Using a combination of miRNA hairpin predictions and co-mapping with miRBase entries, we identified a highly conserved cluster of miRNA genes on the X chromosome in the tammar and a total of 94 other predicted miRNA producing genes. Mapping all miRNAs to the tammar genome and comparing target genes among tammar, mouse and human, we identified 163 conserved target genes. An additional nine genes were identified in tammar that do not have an orthologous miRNA target in human and likely represent novel miRNA-regulated genes in the tammar. A survey of the tammar gonadal piRNAs shows that these small RNAs are enriched in retroelements and carry members from both marsupial and tammar-specific repeat classes. Lastly, this study includes the first in-depth analyses of the newly discovered crasiRNAs. These small RNAs are derived largely from centromere-enriched retroelements, including a novel SINE. Conclusions This study encompasses the first analyses of the major classes of small RNAs for the newly completed tammar genome, validates preliminary annotations using deep sequencing and computational approaches, and provides a foundation for future work on tammar-specific as well as conserved, but previously unknown small RNA progenitors and targets identified herein. The characterization of new miRNA target genes and a unique profile for crasiRNAs has allowed for insight into multiple RNA mediated processes in the tammar, including gene regulation, species incompatibilities, centromere and chromosome function.

  5. Uncovering the Mechanism of Aggregation of Human Transthyretin*

    OpenAIRE

    Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.; Sawaya, Michael R.; Cascio, Duilio; Ruchala, Piotr; Whitelegge, Julian; Jiang, Lin; Riek, Roland; Eisenberg, David S.

    2015-01-01

    Background: Transthyretin (TTR) aggregation is associated with systemic amyloidosis. Results: Residue replacements on the F and H strands hinder TTR aggregation. Conclusion: The F and H strands are aggregation-driving segments of TTR. The binding of designed peptides inhibits protein aggregation. Significance: We point the way to new therapeutic approaches against TTR aggregation by using peptides to block amyloid segments.

  6. Starting to Uncover the Mystery of Interdisciplinary Research in Kinesiology

    Science.gov (United States)

    Schary, David P.; Cardinal, Bradley J.

    2016-01-01

    The multidisciplinary nature of kinesiology seems to be an ideal configuration for conducting interdisciplinary research. Proposed as a potential solution to overcome fragmentation, interdisciplinary research has a role within kinesiology that remains unknown. In this study, we explored kinesiologists' perceptions of interdisciplinary research,…

  7. Uncovering spatio-temporal patterns in environmental data

    NARCIS (Netherlands)

    Wachowicz, M.

    2002-01-01

    The integration of data mining and geographic visualization techniques facilitates the identification and the interpretation of spatio-temporal patterns – a process recognized as knowledge construction. Knowledge construction is a dynamic process of manipulating `data' to find, relate, and interpret

  8. Uncovering Biological Network Function via Graphlet Degree Signatures

    Directory of Open Access Journals (Sweden)

    Nataša Pržulj

    2008-01-01

    Full Text Available Motivation: Proteins are essential macromolecules of life and thus understanding their function is of great importance. The number of functionally unclassified proteins is large even for simple and well studied organisms such as baker’s yeast. Methods for determining protein function have shifted their focus from targeting specific proteins based solely on sequence homology to analyses of the entire proteome based on protein-protein interaction (PPI networks. Since proteins interact to perform a certain function, analyzing structural properties of PPI networks may provide useful clues about the biological function of individual proteins, protein complexes they participate in, and even larger subcellular machines.Results: We design a sensitive graph theoretic method for comparing local structures of node neighborhoods that demonstrates that in PPI networks, biological function of a node and its local network structure are closely related. The method summarizes a protein’s local topology in a PPI network into the vector of graphlet degrees called the signature of the protein and computes the signature similarities between all protein pairs. We group topologically similar proteins under this measure in a PPI network and show that these protein groups belong to the same protein complexes, perform the same biological functions, are localized in the same subcellular compartments, and have the same tissue expressions. Moreover, we apply our technique on a proteome-scale network data and infer biological function of yet unclassified proteins demonstrating that our method can provide valuable guidelines for future experimental research such as disease protein prediction.Availability: Data is available upon request.

  9. Uncovering the footprints of malicious traffic in cellular data networks

    OpenAIRE

    Raghuramu, A; Zang, H.; Chuah, CN

    2015-01-01

    © Springer International Publishing Switzerland 2015. In this paper, we present a comprehensive characterization of malicious traffic generated by mobile devices using Deep Packet Inspection (DPI) records and security event logs from a large US based cellular provider network. Our analysis reveals that 0.17% of mobile devices in the cellular network are affected by security threats. This proportion, while small, is orders of magnitude higher than the last reported (in 2013) infection rate of ...

  10. Uncovering Recovery: The Resistible Rise of Recovery and Resilience

    Directory of Open Access Journals (Sweden)

    David Harper

    2012-10-01

    Full Text Available Discourses of recovery and resilience have risen to positions of dominance in the mental health field. Models of recovery and resilience enjoy purchase, in both policy and practice, across a range of settings from self-described psychiatric survivors through to mental health charities through to statutory mental health service providers. Despite this ubiquity, there is confusion about what recovery means. In this article we problematize notions of recovery and resilience, and consider what, if anything, should be recovered from these concepts. We focus on three key issues, i individualization, ii the persistence of a deficit model, and iii collective approaches to recovery. Through documentary analysis we consider these issues across third sector organizations, and public and mental health policy. Firstly, definitional debates about recovery reflect wider ideological debates about the nature of mental health. The vagueness of these concepts and implicit assumptions inherent in dominant recovery and resilience discourses render them problematic because they individualize what are social problems. Secondly, these discourses, despite being seen as inherently liberatory are conceptually dependent on a notion of deficit in that talk of “positives” and “strengths” requires the existence of “negatives” and “weaknesses” for these concepts to make sense.  We argue that this does little to substantially transform dominant understandings of psychological distress. Thirdly, these issues combine to impact upon the progressive potential of recovery. It comes to be seen as an individualistic experiential narrative accompaniment to medical understandings where the structural causes of distress are obscured. This in turn impacts upon the potential for recovery to be used to explore more collective, political aspects of emotional distress. Drawing on the work of Fraser, we use this critique to characterize “recovery” as a “struggle for recognition,” founded on a model of identity politics which displaces and marginalizes the need for social, political and economic redistribution to address many of the underlying causes of emotional distress. We conclude by stating that it is only when the collective, structural experiences of inequality and injustice are explicitly linked to processes of emotional distress that recovery will be possible. 

  11. Uncovering Mass Segregation with Galaxy Analogues in Dark Matter Simulations

    CERN Document Server

    Joshi, Gandhali D; Wadsley, James

    2016-01-01

    We investigate mass segregation in group and cluster environments by identifying galaxy analogues in high-resolution dark matter simulations. Subhalos identified by the AHF and ROCKSTAR halo finders have similar mass functions, independent of resolution, but different radial distributions due to significantly different subhalo hierarchies. We propose a simple way to classify subhalos as galaxy analogues. The radial distributions of galaxy analogues agree well at large halo-centric radii for both AHF and ROCKSTAR but disagree near parent halo centres where the phase-space information used by ROCKSTAR is essential. We see clear mass segregation at small radii (within $0.5\\,r_{vir}$) with average galaxy analogue mass decreasing with radius. Beyond the virial radius, we find a mild trend where the average galaxy analogue mass increases with radius. These mass segregation trends are strongest in small groups and dominated by the segregation of low mass analogues. The lack of mass segregation in massive galaxy anal...

  12. Uncovering Substance: Teaching Revision in High School Classrooms

    Science.gov (United States)

    Early, Jessica Singer; Saidy, Christina

    2014-01-01

    This article shares the process and outcomes from a three-day revision workshop designed and implemented in a diverse high school language arts classroom. The revision workshop included: direct instruction, self-reflection, and peer feedback to provide struggling writers with opportunities to take part in substantive revision. The authors examine…

  13. Uncovering steroidopathy in women with autism: a latent class analysis

    OpenAIRE

    Pohl, Alexa; Cassidy, Sarah; Auyeung, Bonnie; Baron-Cohen, Simon

    2014-01-01

    Background Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms (‘steroidopathy’) in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use...

  14. HIDDEN WEB EXTRACTOR DYNAMIC WAY TO UNCOVER THE DEEP WEB

    OpenAIRE

    DR. ANURADHA; BABITA AHUJA

    2012-01-01

    In this era of digital tsunami of information on the web, everyone is completely dependent on the WWW for information retrieval. This has posed a challenging problem in extracting relevant data. Traditional web crawlers focus only on the surface web while the deep web keeps expanding behind the scene. The web databases are hidden behind the query interfaces. In this paper, we propose a Hidden Web Extractor (HWE) that can automatically discover and download data from the Hidden Web databases. ...

  15. HIDDEN WEB EXTRACTOR DYNAMIC WAY TO UNCOVER THE DEEP WEB

    Directory of Open Access Journals (Sweden)

    DR. ANURADHA

    2012-06-01

    Full Text Available In this era of digital tsunami of information on the web, everyone is completely dependent on the WWW for information retrieval. This has posed a challenging problem in extracting relevant data. Traditional web crawlers focus only on the surface web while the deep web keeps expanding behind the scene. The web databases are hidden behind the query interfaces. In this paper, we propose a Hidden Web Extractor (HWE that can automatically discover and download data from the Hidden Web databases. Since the only “entry point” to a Hidden Web site is a query interface, the main challenge that a Hidden WebExtractor has to face is how to automatically generate meaningful queries for the unlimited number of website pages.

  16. Uncovering the magnetic environment of our solar system

    CERN Document Server

    Ben-Jaffel, Lotfi

    2012-01-01

    Since its formation 4.6 billion years ago, our solar system has most likely crossed numerous magnetized interstellar clouds and bubbles of different sizes and contents on its path through the Milky Way. Having a reference model for how the heliosphere and interstellar winds interact is critical for understanding our current Galactic environment, and it requires untangling the roles of two major actors: the time-variable solar wind and the local interstellar magnetic field. Numerical simulations predict a distortion of the heliosphere caused by both solar wind anisotropy and interstellar magnetic field orientation. However, model comparison to deep space probes' measurements led to contradictory reports by Voyager 1 and Voyager 2 of both several crossings of the solar wind's termination shock and of the strength of the local interstellar field, with values ranging from 1.8 to 5.7 {\\mu}G. Here, we show that Voyager 1 & 2 plasma, fields, and Lyman-{\\alpha} sky background measurements, as well as space observ...

  17. Uncovering the dynamics of interaction in development cooperation

    DEFF Research Database (Denmark)

    Fejerskov, Adam Moe; Lundsgaarde, Erik; Cold-Ravnkilde, Signe

    critically reflects on the substantial body of scholarship that seeks to document the characteristics of new actors in international development and chart the consequences of their engagement for global development governance. This review underlines the importance of questioning the homogeneity of actor......The rising prominence of new state and non-state actors in international politics has stimulated extensive discussion in the social sciences over the last decade and development cooperation has been a central arena for conceptualising the encounter between old and new powers. This working paper...... constellations, relationships and ideas. Specifically, it addresses the extent to which the commonly-used binary concepts of development cooperation provider groups adequately capture relevant distinctions among the actors and add analytical value to research on development cooperation. The paper advocates...

  18. Uncovering the foundational heritage of Irish occupational therapy

    OpenAIRE

    O'Riordan, Yvonne

    2013-01-01

    non-peer-reviewed Background: This study arose from a wider University of Limerick, Clinical Therapies Departmental project, seeking to plot Irish occupational therapy history. Dr. Eamonn O???Sullivan???s, ??? A Textbook of Occupational Therapy with Chief Reference to Psychological Medicine??? emerged as a primary document outlining occupational therapy in Ireland at the beginning of the 20th Century. Objective: The study aims to identify the philosophical assumptions of occ...

  19. Uncovering the Genetic Landscape for Multiple Sleep-Wake Traits

    OpenAIRE

    Winrow, Christopher J.; Deanna L Williams; Andrew Kasarskis; Joshua Millstein; Laposky, Aaron D.; Yang, He S.; Karrie Mrazek; Lili Zhou; Owens, Joseph R.; Daniel Radzicki; Fabian Preuss; Schadt, Eric E.; Kazuhiro Shimomura; Martha H Vitaterna; Chunsheng Zhang

    2009-01-01

    Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL) analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining...

  20. Uncovering the end uses of the rare earth elements

    International Nuclear Information System (INIS)

    The rare earth elements (REE) are a group of fifteen elements with unique properties that make them indispensable for a wide variety of emerging and conventional established technologies. However, quantitative knowledge of REE remains sparse, despite the current heightened interest in future availability of the resources. Mining is heavily concentrated in China, whose monopoly position and potential restriction of exports render primary supply vulnerable to short term disruption. We have drawn upon the published literature and unpublished materials in different languages to derive the first quantitative annual domestic production by end use of individual rare earth elements from 1995 to 2007. The information is illustrated in Sankey diagrams for the years 1995 and 2007. Other years are available in the supporting information. Comparing 1995 and 2007, the production of the rare earth elements in China, Japan, and the US changed dramatically in quantities and structure. The information can provide a solid foundation for industries, academic institutions and governments to make decisions and develop strategies. - Highlights: • We have derived the first quantitative end use information of the rare earths (REE). • The results are for individual REE from 1995 to 2007. • The end uses of REE in China, Japan, and the US changed dramatically in quantities and structure. • This information can provide solid foundation for decision and strategy making

  1. UNCOVERING FACTORS INFLUENCING PUBLIC PERCEPTIONS OF FOOD BIOTECHNOLOGY

    OpenAIRE

    Hossain, Ferdaus; Onyango, Benjamin M.; Adelaja, Adesoji O.; Schilling, Brian J.; Hallman, William K.

    2002-01-01

    Significant divergence exists in public opinions about biotechnology. Although there is broad support for plant biotechnology for health benefits, opinions differ on the issue of animal genetics for pure economic benefits. While some are opposed to it, many are undecided about genetically modified foods. Considerable skepticism exists about scientists, corporations and government which have negative influence on public acceptance of food biotechnology. Consumers' personal attributes have sign...

  2. The Rosenberg Trial: Uncovering the Layers of History

    Science.gov (United States)

    Ragsdale, Bruce A.

    2013-01-01

    The trial of Julius and Ethel Rosenberg on charges of conspiring to spy for the Soviet Union remains one of the defining moments of the Cold War era. The dramatic allegations of stolen atomic secrets and networks of Communist spies riveted the public's attention. The determination of government prosecutors reflected a widely shared belief…

  3. Uncovering the components of the Francisella tularensis Virulence stealth strategy

    Directory of Open Access Journals (Sweden)

    Bradley D Jones

    2014-03-01

    Full Text Available Over the last decade, studies on the virulence of the highly pathogenic intracellular bacterial pathogen Francisella tularensis have increased dramatically. The organism produces an inert LPS, a capsule, escapes the phagosome to grow in the cytosol (encoded by the FPI genes of a variety of host cell types that include epithelial, endothelial, dendritic, macrophage and neutrophil. This review focuses on the work that has identified and characterized individual virulence factors of this organism and we hope to highlight how these factors collectively function to produce the pathogenic strategy of this pathogen. In addition, several recent studies have been published characterizing F. tularensis mutants that induce host immune responses not observed in wild type F. tularensis strains that can induce protection against challenge with virulent F. tularensis. As more detailed studies with attenuated strains are performed, it will be possible to see how host models develop acquired immunity to Francisella. Collectively, detailed insights into the mechanisms of virulence of this pathogen are emerging that will allow the design of anti-infective strategies.

  4. Uncovering Spatial Variation in Acoustic Environments Using Sound Mapping.

    Science.gov (United States)

    Job, Jacob R; Myers, Kyle; Naghshineh, Koorosh; Gill, Sharon A

    2016-01-01

    Animals select and use habitats based on environmental features relevant to their ecology and behavior. For animals that use acoustic communication, the sound environment itself may be a critical feature, yet acoustic characteristics are not commonly measured when describing habitats and as a result, how habitats vary acoustically over space and time is poorly known. Such considerations are timely, given worldwide increases in anthropogenic noise combined with rapidly accumulating evidence that noise hampers the ability of animals to detect and interpret natural sounds. Here, we used microphone arrays to record the sound environment in three terrestrial habitats (forest, prairie, and urban) under ambient conditions and during experimental noise introductions. We mapped sound pressure levels (SPLs) over spatial scales relevant to diverse taxa to explore spatial variation in acoustic habitats and to evaluate the number of microphones needed within arrays to capture this variation under both ambient and noisy conditions. Even at small spatial scales and over relatively short time spans, SPLs varied considerably, especially in forest and urban habitats, suggesting that quantifying and mapping acoustic features could improve habitat descriptions. Subset maps based on input from 4, 8, 12 and 16 microphones differed slightly ( 4 dBA/pixel) from full maps than the remaining subset maps, but maps with input from eight microphones resulted in smaller differences. Thus, acoustic environments varied over small spatial scales and variation could be mapped with input from 4-8 microphones. Mapping sound in different environments will improve understanding of acoustic environments and allow us to explore the influence of spatial variation in sound on animal ecology and behavior. PMID:27467503

  5. Uncovering the interaction between empathetic pain and cognition.

    Science.gov (United States)

    Hu, Kesong; Fan, Zhiwei; He, Shuchang

    2015-11-01

    Recent studies have demonstrated that empathizing with pain involves both cognitive and affective components of pain. How does empathetic pain impact cognition? To investigate this question, in the present study, participants performed a classic color-word Stroop task that followed a pain portraying or a corresponding control image. We found that observing pain experience in another had a basic slowing down effect on Reaction times (RTs) during neutral Stroop trials. Further, it affected cognition in a way that it decreased interference and increased facilitation. Moreover, our findings revealed that RTs during the incongruent and congruent trials were essentially unchanged by pain observing (empathy vs. control). The data are best accounted by a two-opposing effect model that empathetic pain impacts cognition through two different ways: it slows down performance in general, and facilitates performance during incongruent and congruent trials in particular. In this way, the present study also lends support to an idea that all components of empathy should be understood from an integrative approach. PMID:25476997

  6. Uncovering Mental Representations with Markov Chain Monte Carlo

    Science.gov (United States)

    Sanborn, Adam N.; Griffiths, Thomas L.; Shiffrin, Richard M.

    2010-01-01

    A key challenge for cognitive psychology is the investigation of mental representations, such as object categories, subjective probabilities, choice utilities, and memory traces. In many cases, these representations can be expressed as a non-negative function defined over a set of objects. We present a behavioral method for estimating these…

  7. Uncovering the features of spin dynamics in hadronic physics

    International Nuclear Information System (INIS)

    We summarize the program pursued by Michael J. Moravicsik and the authors on spin amplitude analyses and interpretation. We present the recent observations that 'phase histograms' reveal striking peaks corresponding to spin amplitudes that tend to have definite simple phase relations. An interpretation is proposed in which the spin amplitudes receive a coherent and an incoherent contribution over large ranges of energies and angles. Continuing research directions are reported. (Authors)

  8. Uncovering the features of spin dynamics in hadronic physics

    Science.gov (United States)

    Goldstein, G. R.; Arash, F.

    1990-06-01

    We summarize the program pursued by Michael J. Moravcsik and the authors on spin amplitude analyses and interpretation. We present the recent observations that “phase histograms” reveal striking peaks corresponding to spin amplitudes that tend to have definite simple phase relations. An interpretation is proposed in which the spin amplitudes receive a coherent and an incoherent contribution over large ranges of energies and angles. Continuing research directions are reported.

  9. Challenges in uncovering the origin of the proton's spin

    Science.gov (United States)

    Thomas, A. W.

    2010-09-01

    One of the most fascinating challenges facing modern strong interaction physics is to understand the origin of the spin of the nucleon in terms of the spin and orbital angular momentum of the quarks and gluons. We review recent progress on this problem as well as some of the uncertainties associated with state of the art lattice QCD simulations. In particular, we explain the importance of the corrections associated with chiral extrapolation and finite volume corrections, especially for the term B(0) extracted from the appropriate low moment of the deeply virtual Compton scattering amplitude.

  10. From horizon to torus: Uncovering supermassive black hole systems

    Science.gov (United States)

    Murphy, Kendrah

    2009-06-01

    The complexity of the structure and behavior of AGNs is often imprinted in the Fe K line emission in their X-ray spectra. We present a study of the Seyfert galaxy NGC 2992 with RXTE and Suzaku , which highlights this complexity, as we find evidence of both persistent emission from the accretion disk and from matter more distant from the central black hole (i.e., the putative obscuring torus), as well as short-term flaring emission from the accretion disk. Future X-ray instrumentation is expected to allow us to significantly improve the constraints derived from the Fe K lines in AGN, such as the black-hole angular momentum (spin) and the inclination angle of the putative accretion disk. However, significant model-dependence and degeneracy will persist with radially-integrated Fe K line profiles, so we have investigated the feasibility of utilizing Fe K line emission from localized orbiting flares ("hotspots") to provide a more robust measure of black-hole spin. In addition to affecting the persistent and transient Fe K line emission, the physical structure, geometry, and orientation of the central engine harboring the black hole furthermore effect the observed continuum in specific ways. It is therefore necessary to self-consistently model the continuum and emission lines in order to derive constraints on the physical parameters of the system. Improved X-ray spectral data quality has facilitated the ability to disentangle some of the spectral components, but the increased spectral complexity creates a need for more sophisticated models. Such a need has arisen with respect to the X-ray spectra of obscured AGN. To that end, we describe a new X-ray spectral model, based on Monte-Carlo simulations of the toroidal reprocessor, that will allow one to self-consistently fit for the line emission from distant matter as well as the associated Compton-scattered continuum. The model is valid for arbitrary incident spectra and can therefore be combined with models of relativistic broadening and reflection components of the disk emission to comprehensively fit the broadband spectra of AGN.

  11. Challenges in uncovering the origin of the proton's spin

    International Nuclear Information System (INIS)

    One of the most fascinating challenges facing modern strong interaction physics is to understand the origin of the spin of the nucleon in terms of the spin and orbital angular momentum of the quarks and gluons. We review recent progress on this problem as well as some of the uncertainties associated with state of the art lattice QCD simulations. In particular, we explain the importance of the corrections associated with chiral extrapolation and finite volume corrections, especially for the term B(0) extracted from the appropriate low moment of the deeply virtual Compton scattering amplitude. (author)

  12. Uncovering the single top: Observation of electroweak top quark production

    Science.gov (United States)

    Benitez, Jorge Armando

    The top quark is generally produced in quark and anti-quark pairs. However, the Standard Model also predicts the production of only one top quark which is mediated by the electroweak interaction, known as "Single Top." Single Top quark production is important because it provides a unique and direct way to measure the CKM matrix element Vtb, and can be used to explore physics possibilities beyond the Standard Model predictions. This dissertation presents the results of the observation of Single Top using 2.3 fb-1 of Data collected with the DO detector at the Fermilab Tevatron collider. The analysis includes the Single Top muon+jets and electron+jets final states and employs Boosted Decision Tress as a method to separate the signal from the background. The resulting Single Top cross section measurement is: spp→tb+X,tqb+X =3.74+0.95-0.74pb, 1 where the errors include both statistical and systematic uncertainties. The probability to measure a cross section at this value or higher in the absence of signal is p = 1.9 x 10-6. This corresponds to a standard deviation Gaussian equivalence of 4.6. When combining this result with two other analysis methods, the resulting cross section measurement is: spp→tb+X,tqb+X =3.94+/-0.88pb, 2 and the corresponding measurement significance is 5.0 standard deviations.

  13. Uncovering Oscillations, Complexity, and Chaos in Chemical Kinetics Using Mathematica

    Science.gov (United States)

    Ferreira, M. M. C.; Ferreira, W. C., Jr.; Lino, A. C. S.; Porto, M. E. G.

    1999-06-01

    Unlike reactions with no peculiar temporal behavior, in oscillatory reactions concentrations can rise and fall spontaneously in a cyclic or disorganized fashion. In this article, the software Mathematica is used for a theoretical study of kinetic mechanisms of oscillating and chaotic reactions. A first simple example is introduced through a three-step reaction, called the Lotka model, which exhibits a temporal behavior characterized by damped oscillations. The phase plane method of dynamic systems theory is introduced for a geometric interpretation of the reaction kinetics without solving the differential rate equations. The equations are later numerically solved using the built-in routine NDSolve and the results are plotted. The next example, still with a very simple mechanism, is the Lotka-Volterra model reaction, which oscillates indefinitely. The kinetic process and rate equations are also represented by a three-step reaction mechanism. The most important difference between this and the former reaction is that the undamped oscillation has two autocatalytic steps instead of one. The periods of oscillations are obtained by using the discrete Fourier transform (DFT)-a well-known tool in spectroscopy, although not so common in this context. In the last section, it is shown how a simple model of biochemical interactions can be useful to understand the complex behavior of important biological systems. The model consists of two allosteric enzymes coupled in series and activated by its own products. This reaction scheme is important for explaining many metabolic mechanisms, such as the glycolytic oscillations in muscles, yeast glycolysis, and the periodic synthesis of cyclic AMP. A few of many possible dynamic behaviors are exemplified through a prototype glycolytic enzymatic reaction proposed by Decroly and Goldbeter. By simply modifying the initial concentrations, limit cycles, chaos, and birhythmicity are computationally obtained and visualized.

  14. Fast and frugal food choices: uncovering individual decision heuristics

    OpenAIRE

    Scheibehenne, Benjamin; Todd, Peter M.; Miesler, Linda

    2007-01-01

    Research on food decision making is often based on the assumption that people take many different aspects into account and weight and add them according to their personally assessed importance. Yet there is a growing body of research suggesting that people's decisions can often be better described by simple heuristics—rules of thumb that people use to make choices based on only a few important pieces of information. To test empirically whether a simple heuristic is able to account for individ...

  15. The Burqa Ban's Dark Side. Uncovering Face Covering Bans

    Czech Academy of Sciences Publication Activity Database

    Agha, Petr

    Vol. 2. Gent: Centre for Critical Philosophy . Ghent University., 2015 - (Acosta, E.; Steszak, G.), s. 45-57. (Book Series) Institutional support: RVO:68378122 Subject RIV: AG - Legal Sciences http://www.rethinking-europe.ugent.be/books/2/pdf/Re-Thinking%20Europe%20-%20Volume%20II%20(2015).pdf

  16. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter.

    Directory of Open Access Journals (Sweden)

    Eric M Clark

    Full Text Available Twitter has become the "wild-west" of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, "kid-friendly" flavors, algorithmically generated false testimonials, and free samples.All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching.The overwhelming majority (80% of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013, up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014 due to a relative increase in the negative words 'ban', 'tobacco', 'doesn't', 'drug', 'against', 'poison', 'tax' and a relative decrease in the positive words like 'haha', 'good', 'cool'. Automated tweets are more positive than organic (6.17 versus 5.84 due to a relative increase in the marketing words like 'best', 'win', 'buy', 'sale', 'health', 'discount' and a relative decrease in negative words like 'bad', 'hate', 'stupid', 'don't'.Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media marketing.

  17. Laryngopharyngeal reflux COPD to uncover reflux and columnar lined esophagus

    OpenAIRE

    Kristo I; Riegler M; Schoppmann SF

    2015-01-01

    Ivan Kristo, Martin Riegler, Sebastian F Schoppmann Upper-GI-Service, Gastroesophageal Tumor Unit, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, AustriaWith interest we read the article by Jung et al1 published in the recent issue of the International Journal of Chronic Obstructive Pulmonary Disease. An important finding of the study was the positive correlation between symptoms of gastroesophageal reflux disease (GERD), endoscopic signs for laryng...

  18. Obesity and psychotic disorders: uncovering common mechanisms through metabolomics

    Directory of Open Access Journals (Sweden)

    Matej Orešič

    2012-09-01

    Full Text Available Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. This review covers how recent metabolomic studies have advanced biomarker discovery and the elucidation of mechanisms underlying obesity and its co-morbidities, with a specific focus on metabolic syndrome and psychotic disorders. The importance of identifying metabolic markers of disease-associated intermediate phenotypes – traits modulated but not encoded by the DNA sequence – is emphasized. Such markers would be applicable as diagnostic tools in a personalized healthcare setting and might also open up novel therapeutic avenues.

  19. Obesity and psychotic disorders: uncovering common mechanisms through metabolomics

    OpenAIRE

    Oresic, M.

    2012-01-01

    Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small mole...

  20. Uncovering deep mysteries: the underwater life of an amphibious louse.

    Science.gov (United States)

    Leonardi, Maria Soledad; Aznar, F Javier; Crespo, Enrique A; Lazzari, Claudio R

    2014-12-01

    Despite the incredible success of insects in colonizing almost every habitat, they remain virtually absent in one major environment--the open sea. A variety of hypotheses have been raised to explain why just a few insect species are present in the ocean, but none of them appears to be fully explanatory. Lice belonging to the family Echinophthiriidae are ectoparasites on different species of pinnipeds and river otters, i.e. they have amphibious hosts, who regularly perform long excursions into the open sea reaching depths of hundreds of meters (thousands of feets). Consequently, lice must be able to support not only changes in their surrounding media, but also extreme variations in hydrostatic pressure as well as breathing in a low oxygen atmosphere. In order to shed some light on the way lice can survive during the diving excursions of their hosts, we have performed a series of experiments to test the survival capability of different instars of Antarctophthirus microchir (Phthiraptera: Anoplura) from South American sea lions Otaria flavescens, when submerged into seawater. These experiments were aimed at analyzing: (a) immersion tolerance along the louse life; (b) lice's ability to obtain oxygen from seawater; (c) physiological responses and mechanisms involved in survival underwater. Our experiments showed that the forms present in non-diving pups--i.e. eggs and first-instar nymphs--were unable to tolerate immersion in water, while following instars and adults, all usually found in diving hosts, supported it very well. Furthermore, as long as the level of oxygen dissolved in water was higher, the lice survival capability underwater increased, and the recovery period after returning to air declined. These results are discussed in relation to host ecology, host exploitation and lice functional morphology. PMID:25449903

  1. Uncovering the single top: observation of electroweak top quark production

    Energy Technology Data Exchange (ETDEWEB)

    Benitez, Jorge Armando; /Michigan State U.

    2009-08-01

    The top quark is generally produced in quark and anti-quark pairs. However, the Standard Model also predicts the production of only one top quark which is mediated by the electroweak interaction, known as 'Single Top'. Single Top quark production is important because it provides a unique and direct way to measure the CKM matrix element V{sub tb}, and can be used to explore physics possibilities beyond the Standard Model predictions. This dissertation presents the results of the observation of Single Top using 2.3 fb{sup -1} of Data collected with the D0 detector at the Fermilab Tevatron collider. The analysis includes the Single Top muon+jets and electron+jets final states and employs Boosted Decision Tress as a method to separate the signal from the background. The resulting Single Top cross section measurement is: (1) {sigma}(p{bar p} {yields} tb + X, tqb + X) = 3.74{sub -0.74}{sup +0.95} pb, where the errors include both statistical and systematic uncertainties. The probability to measure a cross section at this value or higher in the absence of signal is p = 1.9 x 10{sup -6}. This corresponds to a standard deviation Gaussian equivalence of 4.6. When combining this result with two other analysis methods, the resulting cross section measurement is: (2) {sigma}(p{bar p} {yields} tb + X, tqb + X) = 3.94 {+-} 0.88 pb, and the corresponding measurement significance is 5.0 standard deviations.

  2. Uncovering middle managers' role in healthcare innovation implementation

    Directory of Open Access Journals (Sweden)

    Birken Sarah A

    2012-04-01

    Full Text Available Abstract Background Middle managers have received little attention in extant health services research, yet they may have a key role in healthcare innovation implementation. The gap between evidence of effective care and practice may be attributed in part to poor healthcare innovation implementation. Investigating middle managers' role in healthcare innovation implementation may reveal an opportunity for improvement. In this paper, we present a theory of middle managers' role in healthcare innovation implementation to fill the gap in the literature and to stimulate research that empirically examines middle managers' influence on innovation implementation in healthcare organizations. Discussion Extant healthcare innovation implementation research has primarily focused on the roles of physicians and top managers. Largely overlooked is the role of middle managers. We suggest that middle managers influence healthcare innovation implementation by diffusing information, synthesizing information, mediating between strategy and day-to-day activities, and selling innovation implementation. Summary Teamwork designs have become popular in healthcare organizations. Because middle managers oversee these team initiatives, their potential to influence innovation implementation has grown. Future research should investigate middle managers' role in healthcare innovation implementation. Findings may aid top managers in leveraging middle managers' influence to improve the effectiveness of healthcare innovation implementation.

  3. Uncovering zoonoses awareness in an emerging disease ‘hotspot’

    OpenAIRE

    Paige, Sarah B.; Malave, Carly; Mbabazi, Edith; Mayer, Jonathan; Goldberg, Tony L.

    2014-01-01

    Emerging infectious diseases from animals pose significant and increasing threats to human health; places of risk are simultaneously viewed as conservation and emerging disease ‘hotspots’. The One World/One Health paradigm is an ‘assemblage’ discipline. Extensive research from the natural and social sciences, as well as public health have contributed to designing surveillance and response policy within the One World/One Health framework. However, little research has been undertaken that consi...

  4. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter

    OpenAIRE

    Clark, Eric M.; Jones, Chris A.; Williams, Jake Ryland; Kurti, Allison N; Nortotsky, Michell Craig; Danforth, Christopher M.; Dodds, Peter Sheridan

    2015-01-01

    Background: Twitter has become the "wild-west" of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, "kid-friendly" flavors, algorithmically generated false testimonials, and free samples. Methods:All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets) were identified and categorized as Au...

  5. Uncovering Low-Dimensional Topological Structure in the QCD Vacuum

    International Nuclear Information System (INIS)

    Recently, we have pointed out that sign-coherent 4-dimensional structures can not dominate topological charge fluctuations in QCD vacuum at all scales. Here we show that an enhanced lower-dimensional coherence is possible. In pure SU(3) lattice gauge theory we find that in a typical equilibrium configuration about 80% of space-time points are covered by two oppositely-charged connected structures built of elementary 3-dimensional coherent hypercubes. The hypercubes within the structure are connected through 2-dimensional common faces. We suggest that this coherence is a manifestation of a low-dimensional order present in the QCD vacuum. The use of a topological charge density associated with Ginsparg-Wilson fermions (''chiral smoothing'') is crucial for observing this structure

  6. Uncovering Embedded Face Threat Mitigation in Landscape Architecture Critique Feedback

    Science.gov (United States)

    Housley Gaffney, Amy L.

    2015-01-01

    Receiving public feedback on academic work may threaten students' face, particularly when such feedback is critical. One way that feedback may be cushioned is through face-threat mitigation techniques. I analyzed the use of such techniques in the feedback given by faculty and professionals to landscape architecture students as preparation for…

  7. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    OpenAIRE

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin,...

  8. Scratching below the surface to uncover HRM practices in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Ulhøi, John Parm

    2010-01-01

    Is HRM in Denmark behind the times and only now beginning to be prioritized by Danish firms? Or is it possible that managers are successfully capitalizing on characteristics of the Danish society and the Danish workforce? We propose quite adamantly that HRM practices indeed are alive in Danish...

  9. Uncovering Interaction Structures in a Brief Psychodynamic Psychotherapy

    Directory of Open Access Journals (Sweden)

    Fernanda Barcellos Serralta

    2016-08-01

    Full Text Available Abstract Interaction structures refers to the repetitive ways of interaction between the patient-therapist dyad over the course of treatment. This construct is operationalized by the repeated application of the Psychotherapy Process Q-Set (PQS to psychotherapy sessions. Studies in this line of research have so far focused only on long-term treatment. The present study examines whether interaction structures can be detected empirically in short-term psychotherapies. All sessions (N = 31 of a successful case of brief psychodynamic psychotherapy were coded with the Psychotherapy Process Q-Set (PQS. The application of Q type factor analysis procedures with varimax rotation revealed five interaction structures: resistance, alliance, facing depression, expectation of change, and introspection and hearing. The analysis of variation of these structures over the course of the treatment showed that these interactions are nonlinear, may be positively or negatively protruding in different sessions, or be predominant at some treatment phase.

  10. Uncovering Our Feminist Pedagogy: A Co/Autoethnography

    Science.gov (United States)

    Coia, Lesley; Taylor, Monica

    2013-01-01

    What does it mean to be a feminist educator? How would we know if we were? We call ourselves feminist teachers and yet we have not focused on this identification and its influence on our teaching in some time. In this self-study, we set out to look at our practice-using co/autoethnography. As our study progressed, we began to realize that our…

  11. Uncovering high-strain rate protection mechanism in nacre

    OpenAIRE

    Huang, Zaiwang; Li, Haoze; Pan, Zhiliang; Wei, Qiuming; Chao, Yuh J.; Li, Xiaodong

    2011-01-01

    Under high-strain-rate compression (strain rate ∼103 s−1), nacre (mother-of-pearl) exhibits surprisingly high fracture strength vis-à-vis under quasi-static loading (strain rate 10−3 s−1). Nevertheless, the underlying mechanism responsible for such sharply different behaviors in these two loading modes remains completely unknown. Here we report a new deformation mechanism, adopted by nacre, the best-ever natural armor material, to protect itself against predatory penetrating impacts. It invol...

  12. Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

    Science.gov (United States)

    Andersen, Kristian G; Shapiro, B Jesse; Matranga, Christian B; Sealfon, Rachel; Lin, Aaron E; Moses, Lina M; Folarin, Onikepe A; Goba, Augustine; Odia, Ikponmwonsa; Ehiane, Philomena E; Momoh, Mambu; England, Eleina M; Winnicki, Sarah; Branco, Luis M; Gire, Stephen K; Phelan, Eric; Tariyal, Ridhi; Tewhey, Ryan; Omoniwa, Omowunmi; Fullah, Mohammed; Fonnie, Richard; Fonnie, Mbalu; Kanneh, Lansana; Jalloh, Simbirie; Gbakie, Michael; Saffa, Sidiki; Karbo, Kandeh; Gladden, Adrianne D; Qu, James; Stremlau, Matthew; Nekoui, Mahan; Finucane, Hilary K; Tabrizi, Shervin; Vitti, Joseph J; Birren, Bruce; Fitzgerald, Michael; McCowan, Caryn; Ireland, Andrea; Berlin, Aaron M; Bochicchio, James; Tazon-Vega, Barbara; Lennon, Niall J; Ryan, Elizabeth M; Bjornson, Zach; Milner, Danny A; Lukens, Amanda K; Broodie, Nisha; Rowland, Megan; Heinrich, Megan; Akdag, Marjan; Schieffelin, John S; Levy, Danielle; Akpan, Henry; Bausch, Daniel G; Rubins, Kathleen; McCormick, Joseph B; Lander, Eric S; Günther, Stephan; Hensley, Lisa; Okogbenin, Sylvanus; Schaffner, Stephen F; Okokhere, Peter O; Khan, S Humarr; Grant, Donald S; Akpede, George O; Asogun, Danny A; Gnirke, Andreas; Levin, Joshua Z; Happi, Christian T; Garry, Robert F; Sabeti, Pardis C

    2015-08-13

    The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT. PMID:26276630

  13. Uncovering collective listening habits and music genres in bipartite networks

    CERN Document Server

    Lambiotte, R

    2005-01-01

    In this paper, we analyze web-downloaded data on people sharing their music library, that we use as their individual musical signatures (IMS). The system is represented by a bipartite network, nodes being the music groups and the listeners. Music groups audience size behaves like a power law, but the individual music library size is an exponential with deviations at small values. In order to extract structures from the network, we focus on correlation matrices, that we filter by removing the least correlated links. This percolation idea-based method reveals the emergence of social communities and music genres, that are visualised by a branching representation. Evidence of collective listening habits that do not fit the neat usual genres defined by the music industry indicates an alternative way of classifying listeners/music groups. The structure of the network is also studied by a more refined method, based upon a random walk exploration of its properties. Finally, a personal identification - community imita...

  14. Uncovering the etiology of conversion disorder: insights from functional neuroimaging

    Directory of Open Access Journals (Sweden)

    Ejareh dar M

    2016-01-01

    Full Text Available Maryam Ejareh dar, Richard AA Kanaan Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, VIC, Australia Abstract: Conversion disorder (CD is a syndrome of neurological symptoms arising without organic cause, arguably in response to emotional stress, but the exact neural substrates of these symptoms and the underlying mechanisms remain poorly understood with the hunt for a biological basis afoot for centuries. In the past 15 years, novel insights have been gained with the advent of functional neuroimaging studies in patients suffering from CDs in both motor and nonmotor domains. This review summarizes recent functional neuroimaging studies including functional magnetic resonance imaging (fMRI, single photon emission computerized tomography (SPECT, and positron emission tomography (PET to see whether they bring us closer to understanding the etiology of CD. Convergent functional neuroimaging findings suggest alterations in brain circuits that could point to different mechanisms for manifesting functional neurological symptoms, in contrast with feigning or healthy controls. Abnormalities in emotion processing and in emotion-motor processing suggest a diathesis, while differential reactions to certain stressors implicate a specific response to trauma. No comprehensive theory emerges from these clues, and all results remain preliminary, but functional neuroimaging has at least given grounds for hope that a model for CD may soon be found. Keywords: conversion disorder, neuroimaging, functional neurology, hysteria, mechanisms 

  15. Uncover the electroluminescence in wide band gap polymers

    Science.gov (United States)

    Qiao, B.; Teyssedre, G.; Laurent, C.

    2015-10-01

    Due to the rapidly increasing demand of electric power, insulating materials used in electrical components are pushed up to their limits, where their electronic properties are of fundamental importance. Electroluminescence provides an elegant way to investigate electronic properties, high field effects and electrical ageing of polymers although the emission spectrum is still poorly understood. Unlike in organic semi-conductors, electroluminescence spectra of large band gap polymers exhibit specific spectral features that cannot be interpreted on the basis of the photo-physical properties of the material. By irradiating polypropylene thin films with electrons up to a few keV and by analyzing the emitted light, we were able to isolate the elementary components of the emission and to reconstruct the electroluminescence spectrum. For the first time, a comprehensive study of electroluminescence in polymers is provided and the underlying mechanisms of the emission are discussed. The results herein provide an univocal demonstration that the electroluminescence from wide band gap polymers results in part from chemical reactions, opening the way to the diagnosis and prognosis of polymeric materials under electrical stress.

  16. Uncovering Cultural Prototypes : Old Men in Japanese Folktales and Culture

    OpenAIRE

    ニコリッチ細中, ネベンカ; ニコリッチホソナカ, ネベンカ; Nevenka, Nikolic Hosonaka

    2004-01-01

    This paper is a progress report on the preliminary stages of a larger project that aims to find out if Japanese children's concepts of old men would change through exposure to the images of old men in Western folktales. It is the old men's characterization that differs most in the two cultures, as seen in traditional folktales. Research showed both Japanese adults' and the 2-3^ graders' familiarity with the folktales representative of the Japanese culture. Their concepts of old men were compa...

  17. Uncovering "Threshold Concepts" in Web Development: An Instructor Perspective

    Science.gov (United States)

    Alston, Peter; Walsh, David; Westhead, Gary

    2015-01-01

    The field of Web development has evolved and diversified significantly in recent years, and narrowing the gap between the requirements of academia and the demands of industry remains a challenge. Moreover, many faculty members often struggle with knowing "how much" of a particular subject they should teach to their students and at what…

  18. Uncovering the Secret: Medieval Women, Magic and the Other

    Directory of Open Access Journals (Sweden)

    Ludwikowska Joanna

    2015-01-01

    Full Text Available For medieval audiences women occupied a specific, designated cultural area which, while they could freely form it according to their will and nature, was in fact imaginary and immaterial. Women in social, legal, and religious contexts were mostly counted among the receptive, inactive, and non-ruling groups. On both levels, there was a group of features universally defining all women: the strong, virtuous and independent model Aquinas lamented was replaced in real life by the sinful, carnal and weak stereotype, and the erotic, emotional, mysterious, and often wild type present predominantly in literature. Indeed, women were a source of scientific, theological, and cultural fascination because of their uncanny and complex nature, producing both fear and desire of the source and nature of the unattainable and inaccessible femininity. In social contexts, however, the enchantress seems to lose that veil of allure and, instead, is forced to re-define her identity by suppressing, denying, or losing her supernatural features. With the example of Saint Agnes from the South English Legendary Life of Saint Agnes, and Melior from Partonope of Blois (ca. 1450, the article will explore how medieval texts dealt with the complex and unruly female supernatural, and how its neutralization and subduing fitted into the moral, scientific, and cultural norms of medieval society.

  19. Systems Biology of Metabolic Networks: Uncovering Regulatory and stoichiometric Principles

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb

    2007-01-01

    I forbindelse med industriel udnyttelse af mikroorganismer til produktion af kemikalier er der stor interesse for at analysere funktionen af metabolske netværk, herunder specielt opnå indsigt i hvordan aktiviteten af forskellige grene i sådanne netværk er reguleret. Idet metabolismen spiller en c...

  20. Uncovering the Connections Among Sustainability,Governance and GDP

    Institute of Scientific and Technical Information of China (English)

    Tan Xiaomei; Brett Rose

    2007-01-01

    This paper examines the connections among sustainability, governance and GDP, using the data from 123 countries.Sustainability is found to be related with GDP in two contradictory ways. On the one hand, growth in GDP strengthens a nation's ability to maintain favorable environmental conditions into the future. On the other hand, GDP growth is built on more consumption of natural resources, and therefore generates a larger "footprint" on the Earth. Governance plays a key role in sustainable development. However, it is not helping to reduce our footprint on the Earth. In fact, good governance is linked to a larger footprint.This reflects our materialist value and human impulse. When a society prefers the comfort and well-being of human beings to the welfare of its environment, democratic governance might be used as an effective tool against nature.

  1. HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas

    OpenAIRE

    Wiweger, Malgorzata I; Zhao, Zhe; van Merkesteyn, Richard J. P.; Roehl, Henry H.; Hogendoorn, Pancras C. W.

    2012-01-01

    Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondar...

  2. HSPG-deficient zebrafish uncovers dental aspect of multiple osteochondromas.

    Directory of Open Access Journals (Sweden)

    Malgorzata I Wiweger

    Full Text Available Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2 are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2⁻/⁻ fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2⁻/⁻ fish. Histological analysis reveals that ext2⁻/⁻ fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2⁻/⁻ fish have a single tooth at the end of the 5(th pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2⁻/⁻ teeth have abnormal morphology (they were shorter and thicker than in the WT and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2⁺/⁻ adults. The tooth morphology in ext2⁻/⁻ was partially rescued by FGF8 administered locally (bead implants. Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems.

  3. Uncovering Circumbinary Planetary Architectural Properties from Selection Biases

    CERN Document Server

    Li, Gongjie; Tao, Molei

    2016-01-01

    The new discoveries of circumbinary planetary systems shed light on the understanding of planetary system formation. Learning the architectural properties of these systems is essential for constraining the different formation mechanisms. We first revisit the stability limit of circumbinary planets. Next, we focus on eclipsing stellar binaries and obtain an analytical expression for the transit probability in a realistic setting, where finite observation period and planetary orbital precession are included. Then, understanding of the architectural properties of the currently observed transiting systems is refined, based on Bayesian analysis and a series of hypothesis tests. We find 1) it is not a selection bias that the innermost planets reside near the stability limit for eight of the nine observed systems, and this is consistent with a log uniform distribution of the planetary semi-major axis; 2) it is not a selection bias that the planetary and stellar orbits are nearly coplanar ($\\lesssim 3^\\circ$), and th...

  4. Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins.

    Science.gov (United States)

    Maeda, Kenji; Anand, Kanchan; Chiapparino, Antonella; Kumar, Arun; Poletto, Mattia; Kaksonen, Marko; Gavin, Anne-Claude

    2013-09-12

    The internal organization of eukaryotic cells into functionally specialized, membrane-delimited organelles of unique composition implies a need for active, regulated lipid transport. Phosphatidylserine (PS), for example, is synthesized in the endoplasmic reticulum and then preferentially associates--through mechanisms not fully elucidated--with the inner leaflet of the plasma membrane. Lipids can travel via transport vesicles. Alternatively, several protein families known as lipid-transfer proteins (LTPs) can extract a variety of specific lipids from biological membranes and transport them, within a hydrophobic pocket, through aqueous phases. Here we report the development of an integrated approach that combines protein fractionation and lipidomics to characterize the LTP-lipid complexes formed in vivo. We applied the procedure to 13 LTPs in the yeast Saccharomyces cerevisiae: the six Sec14 homology (Sfh) proteins and the seven oxysterol-binding homology (Osh) proteins. We found that Osh6 and Osh7 have an unexpected specificity for PS. In vivo, they participate in PS homeostasis and the transport of this lipid to the plasma membrane. The structure of Osh6 bound to PS reveals unique features that are conserved among other metazoan oxysterol-binding proteins (OSBPs) and are required for PS recognition. Our findings represent the first direct evidence, to our knowledge, for the non-vesicular transfer of PS from its site of biosynthesis (the endoplasmic reticulum) to its site of biological activity (the plasma membrane). We describe a new subfamily of OSBPs, including human ORP5 and ORP10, that transfer PS and propose new mechanisms of action for a protein family that is involved in several human pathologies such as cancer, dyslipidaemia and metabolic syndrome. PMID:23934110

  5. Uncovering the multiple objectives behind national energy efficiency planning

    International Nuclear Information System (INIS)

    This work seeks to identify the fundamental objectives behind the development of energy efficiency (EE) plans for countries. It also presents a method to quantify the degree of achievement of each objective, through the identification and operationalization of attributes. This was achieved by applying Keeney's value-focused thinking approach. For that purpose, three key decision makers in EE planning were interviewed along with a bibliographic review on the subject. From this process six fundamental objectives were identified formalizing the problem as a multi-objective one: (i) to minimize the influence of energy use on climate change; (ii) to minimize the financial risk from the investment; (iii) to maximize the security of energy supply; (iv) to minimize investment costs; (v) to minimize the impacts of building new power plants and transmission infrastructures and (vi) to maximize the local air quality. The respective attributes were: (i) CO2 emissions savings; (ii) payback; (iii) imported energy savings; (iv) investment cost; (v) electricity savings; and (vi) total suspended particles savings. To show the usefulness of the work, the objectives and attributes identified were used to show the possible outcomes from five hypothetical EE plans for Portugal

  6. Multicolored words: Uncovering the relationship between reading mechanisms and synesthesia.

    Science.gov (United States)

    Blazej, Laura J; Cohen-Goldberg, Ariel M

    2016-02-01

    Grapheme-color and lexical-color synesthesia, the association of colors with letters and words, respectively, are some of the most commonly studied forms of synesthesia, yet relatively little is known about how synesthesia arises from and interfaces with the reading process. To date, synesthetic experiences in reading have only been reported in relation to a word's graphemes and meaning. We present a case study of WBL, a 21-year old male who experiences synesthetic colors for letters and words. Over 3 months, we obtained nearly 3000 color judgments for visually presented monomorphemic, prefixed, suffixed, and compound words as well as judgments for pseudocompound words (e.g., carpet), and nonwords. In Experiment 1, we show that word color is nearly always determined by the color of the first letter. Furthermore, WBL reported two separate colors for prefixed and compound words approximately 14% of the time, with the additional color determined by the first letter of the second morpheme. In Experiment 2, we further investigated how various morphological factors influenced WBL's percepts using the compound norms of Juhasz, Lai, and Woodcock (2014). In a logistic regression analysis of color judgments for nearly 400 compounds, we observed that the likelihood that WBL would perceive a compound as bearing 1 lexical color or 2 lexical colors was influenced by a variety of factors including stem frequency, compound frequency, and the relationship between the meaning of the compound and the meaning of its stems. This constitutes the first study reporting an effect of morphological structure in synesthesia and demonstrates that synesthetic colors result from a complex interaction of perceptual, graphemic, morphological, and semantic factors. PMID:26794531

  7. Chandra Observatory Uncovers Hot Stars In The Making

    Science.gov (United States)

    2000-11-01

    Cambridge, Mass.--In resolving the hot core of one of the Earth's closest and most massive star-forming regions, the Chandra X-ray Observatory showed that almost all the young stars' temperatures are more extreme than expected. Orion Trapezium JPEG, TIFF, PS The Orion Trapezium as observed on October 31st UT 05:47:21 1999. The colors represent energy, where blue and white indicate very high energies and therefore exterme temperatures. The size of the X-ray source in the image also reflects its brightness, i.e. more bright sources appear larger in size. The is an artifact caused by the limiting blur of the telescope optics. The projected diameter of the field of view is about 80 light days. Credit: NASA/MIT Orion Trapezium JPEG, TIFF, PS The Orion Trapezium as observed on November 24th UT 05:37:54 1999. The colors represent energy, where blue and white indicate very high energies and therefore exterme temperatures. The size of the X-ray source in the image also reflects its brightness, i.e. more bright sources appear larger in size. The is an artifact caused by the limiting blur of the telescope optics. The projected diameter of the field of view is about 80 light days. Credit: NASA/MIT The Orion Trapezium Cluster, only a few hundred thousand years old, offers a prime view into a stellar nursery. Its X-ray sources detected by Chandra include several externally illuminated protoplanetary disks ("proplyds") and several very massive stars, which burn so fast that they will die before the low mass stars even fully mature. One of the major highlights of the Chandra observations are identification of proplyds as X-ray point source in the near vicinity of the most massive star in the Trapezium. Previous observations did not have the ability to separate the contributions of the different objects. "We've seen high temperatures in stars before, but what clearly surprised us was that nearly all the stars we see appear at rather extreme temperatures in X-rays, independent of their type," said Norbert S. Schulz, MIT research scientist at the Chandra X-ray Center, who leads the Orion Project. "And by extreme, we mean temperatures which are in some cases well above 60 million degrees." The hottest massive star known so far has been around 25 million degrees. The great Orion Nebula harbors the Orion Nebula Cluster (ONC), a loose association of around 2,000 mostly very young stars of a wide range of mass confined within a radius of less than 10 light years. The Orion Trapezium Cluster is a younger subgroup of stars at the core of the ONC confined within a radius of about 1.5 light years. Its median age is around 300,000 years. The constant bright light of the Trapezium and its surrounding stars at the heart of the Orion nebula (M42) are visible to the naked eye on clear nights. In X-rays, these young stars are constantly active and changing in brightness, sometimes within half a day, sometimes over weeks. "Never before Chandra have we seen images of stellar activity with such brilliance," said Joel Kastner, professor at the Chester F. Carlson Center for Imaging Science at the Rochester Institute of Technology. "Here the combination of very high angular resolution, with high quality spectra that Chandra offers, clearly pays off." The observation was performed using the High Energy Transmission Grating Spectrometer (HETGS) and the X-ray spectra were recorded with the spectroscopic array of the Advanced CCD Imaging Spectrometer (ACIS). The ACIS detector is a sophisticated version of the CCD detectors commonly used in video cameras or digital cameras. The orion stars are so bright in X-rays that they easily saturate the ccds. Here the team used the gratings as a blocking filter. Orion Trapezium - X-ray & Optical JPEG, TIFF, PS X-ray contours of the Chandra observation overlaid onto the optical Hubble image (courtesy of J. Bally, CASA Colorado). The field of view is 30"x30". Besides the bright main Trapezium stars, which were found to be extremely hot massive stars, several externally illuminated objects are also X-ray emitters. Some of them with temperatures up to 100 Million degrees. The ones that do not show X-ray contours are probably too faint to be detected in these particular Chandra observations. Credit: J. Bally, CASA Colorad It is generally assumed that low-mass stars like our Sun, when they are young, are more than 1,000 times more luminous in X-rays. The X-ray emission here is thought to arise from magnetic activity in connection with stellar rotation. Consequently, high temperatures would be observed in very violent and giant flares. Here temperatures as high as 60 million degrees have been observed in very few cases. The absence of many strong flares in the light curves, as well as temperatures in the Chandra ACIS spectra wich exceed the ones in giant flares, could mean that they are either young protostars (i.e stars in the making), or a special class of more evolved, hot young stars. Schulz concedes that although astronomers have gathered many clues in recent years about the X-ray behavior of very young stellar objects, "we are far from being able to uniquely classify evolutionary stages of their X-ray emission." The five main young and massive Trapezium stars are responsible for the illumination of the entire Orion Nebula. These stars are born with masses 15 to 30 times larger than the mass of our Sun. X-rays in such stars are thought to be produced by shocks that occur when high velocity stellar winds ram into slower dense material. The Chandra spectra show a temperature component of about 5 million to 10 million degrees, which is consistent with this model. However, four of these five stars also show additional components between 30 million and 60 million degrees. "The fact that some of these massive stars show such a hot component and some not, and that a hot component seems to be more common than previously assumed, is an important new aspect in the spectral behavior of these stars," said David Huenemoerder, research physicist at the MIT Center for Space Research. Standard shock models cannot explain such high temperatures, which may be caused by magnetically confined plasmas, which are generally only attributed to stars like the Sun. Such an effect would support the suspicion that some aspects in the X-ray emission of massive stars may not be different from our Sun, which also has a hot corona. More study is needed to confirm this conclusion. The latest in NASA's series of Great Observatories. Chandra is the "X-ray Hubble," launched in July 1999 into a deep-space orbit around the Earth. Chandra carries a large X-ray telescope to focus X-rays from objects in the sky. An X-ray telescope cannot work on the ground because the X-rays are absorbed by the Earth's atmosphere. The HETGS was built by the Massachusetts Institute of Technology with Bruno Rossi Professor Claude Canizares as Principal Investigator. The ACIS X-ray camera was conceived and developed for NASA by Penn State and the Massachusetts Institute of Technology under the leadership of Gordon Garmire, Evan Pugh Professor of Astronomy and Astrophysics at Penn State. The Orion observation was part of Prof. Canizares guaranteed observing time during the first round of Chandra observations. NASA's Marshall Space Flight Center in Huntsville, Alabama, manages the Chandra program. TRW Inc., Redondo Beach, California, is the prime contractor for the spacecraft. The Smithsonian's Chandra X-ray Center controls science and flight operations from Cambridge, Massachusetts. Orion Trapezium Handout Constellation Orion To follow Chandra's progress, visit the Chandra site at: http://chandra.harvard.edu AND http://chandra.nasa.gov Various Images for this release and a postscript version of a preprint of the accepted science paper (The Astrophysical Main Journal) can be downloaded from http://space.mit.edu/~nss/orion/orion.html

  8. An improvement of the fast uncovering community algorithm

    Science.gov (United States)

    Wang, Li; Wang, Jiang; Shen, Hua-Wei; Cheng, Xue-Qi

    2013-10-01

    Community detection methods have been used in computer, sociology, physics, biology, and brain information science areas. Many methods are based on the optimization of modularity. The algorithm proposed by Blondel et al. (Blondel V D, Guillaume J L, Lambiotte R and Lefebvre E 2008 J. Stat. Mech. 10 10008) is one of the most widely used methods because of its good performance, especially in the big data era. In this paper we make some improvements to this algorithm in correctness and performance. By tests we see that different node orders bring different performances and different community structures. We find some node swings in different communities that influence the performance. So we design some strategies on the sweeping order of node to reduce the computing cost made by repetition swing. We introduce a new concept of overlapping degree (OV) that shows the strength of connection between nodes. Three improvement strategies are proposed that are based on constant OV, adaptive OV, and adaptive weighted OV, respectively. Experiments on synthetic datasets and real datasets are made, showing that our improved strategies can improve the performance and correctness.

  9. Uncovering the complexity of Tourette syndrome, little by little.

    Science.gov (United States)

    Gorman, Daniel A; Abi-Jaoude, Elia

    2014-01-01

    The aetiology of Tourette syndrome is highly complex and still poorly understood. In this issue, using data from a large, prospective, population-based cohort of children, Mathews et al examine associations of pre- and perinatal exposures with Tourette syndrome and other chronic tic disorders. Their work illustrates the importance of environmental factors in the aetiology of neuropsychiatric conditions and the value of replication in science. PMID:24385458

  10. Biological Ferroelectricity Uncovered in Aortic Walls by Piezoresponse Force Microscopy

    OpenAIRE

    Liu, Yuanming; Zhang, Yanhang; Chow, Ming-Jay; Chen, Qian Nataly; Li, Jiangyu

    2012-01-01

    Many biological tissues are piezoelectric and pyroelectric with spontaneous polarization. Ferroelectricity, however, has not been reported in soft biological tissues yet. Using piezoresponse force microscopy, we discover that the porcine aortic walls are not only piezoelectric, but also ferroelectric, with the piezoelectric coefficient in the order of 1 pm/V and coercive voltage approximately 10 V. Through detailed switching spectroscopy mapping and relaxation studies, we also find that the p...

  11. Uncovering the transcriptional control of "Bartonella henselae" host adaptation factors

    OpenAIRE

    Québatte, Maxime

    2014-01-01

    A recurrent theme in bacterial pathogenicity is the understanding of the regulatory events necessary for a given pathogen to progress through its infection cycle while resisting the host defense mechanisms. This progression typically requires the coordinated expression of defined sub-portions of the virulence repertoire at the same time as others need to be tightly repressed or degraded. This so-called adaptive response is ultimately linked to the ability of the pathogen to sense its direct e...

  12. Simplivariate Models: Uncovering the Underlying Biology in Functional Genomics Data

    OpenAIRE

    Edoardo Saccenti; Westerhuis, Johan A.; Smilde, Age K.; van der Werf, Mariët J; Jos A Hageman; Hendriks, Margriet M. W. B.

    2011-01-01

    One of the first steps in analyzing high-dimensional functional genomics data is an exploratory analysis of such data. Cluster Analysis and Principal Component Analysis are then usually the method of choice. Despite their versatility they also have a severe drawback: they do not always generate simple and interpretable solutions. On the basis of the observation that functional genomics data often contain both informative and non-informative variation, we propose a method that finds sets of va...

  13. Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.

    Science.gov (United States)

    Donati, Claudio; Zolfo, Moreno; Albanese, Davide; Tin Truong, Duy; Asnicar, Francesco; Iebba, Valerio; Cavalieri, Duccio; Jousson, Olivier; De Filippo, Carlotta; Huttenhower, Curtis; Segata, Nicola

    2016-01-01

    Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments. PMID:27572971

  14. Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide

    Science.gov (United States)

    Freudenthal, Bret D.; Beard, William A.; Perera, Lalith; Shock, David D.; Kim, Taejin; Schlick, Tamar; Wilson, Samuel H.

    2015-01-01

    Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine. Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol β, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate.

  15. Uncovering urban human mobility from large scale taxi GPS data

    Science.gov (United States)

    Tang, Jinjun; Liu, Fang; Wang, Yinhai; Wang, Hua

    2015-11-01

    Taxi GPS trajectories data contain massive spatial and temporal information of urban human activity and mobility. Taking taxi as mobile sensors, the information derived from taxi trips benefits the city and transportation planning. The original data used in study are collected from more than 1100 taxi drivers in Harbin city. We firstly divide the city area into 400 different transportation districts and analyze the origin and destination distribution in urban area on weekday and weekend. The Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is used to cluster pick-up and drop-off locations. Furthermore, four spatial interaction models are calibrated and compared based on trajectories in shopping center of Harbin city to study the pick-up location searching behavior. By extracting taxi trips from GPS data, travel distance, time and average speed in occupied and non-occupied status are then used to investigate human mobility. Finally, we use observed OD matrix of center area in Harbin city to model the traffic distribution patterns based on entropy-maximizing method, and the estimation performance verify its effectiveness in case study.

  16. Uncovering Concerns with Developing a Scoring System at ETS.

    Science.gov (United States)

    Stires, Susan

    1995-01-01

    Describes an expert panel member's experiences in working with Educational Testing Service to redesign the scoring for the National Board for Professional Teaching Standards Early Adolescence/English Language Arts Assessment. Maintains that a less mechanistic and more valid scoring system could have been developed if criticism and open discussion…

  17. Uncovering the genetic landscape for multiple sleep-wake traits.

    Directory of Open Access Journals (Sweden)

    Christopher J Winrow

    Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits and emphasize the need for a systems biology approach for elucidating the full extent of the genetic regulatory mechanisms of this complex and universal behavior.

  18. Uncovering the dynamics of citations of scientific papers

    CERN Document Server

    Golosovsky, Michael

    2014-01-01

    We demonstrate a comprehensive framework that accounts for citation dynamics of scientific papers and for the age distribution of references. We show that citation dynamics of scientific papers is nonlinear and this nonlinearity has far-reaching consequences, such as diverging citation distributions and runaway papers. We propose a nonlinear stochastic dynamic model of citation dynamics based on link copying/redirection mechanism. The model is fully calibrated by empirical data and does not contain free parameters. This model can be a basis for quantitative probabilistic prediction of citation dynamics of individual papers and of the journal impact factor.

  19. An improvement of the fast uncovering community algorithm

    International Nuclear Information System (INIS)

    Community detection methods have been used in computer, sociology, physics, biology, and brain information science areas. Many methods are based on the optimization of modularity. The algorithm proposed by Blondel et al. (Blondel V D, Guillaume J L, Lambiotte R and Lefebvre E 2008 J. Stat. Mech. 10 10008) is one of the most widely used methods because of its good performance, especially in the big data era. In this paper we make some improvements to this algorithm in correctness and performance. By tests we see that different node orders bring different performances and different community structures. We find some node swings in different communities that influence the performance. So we design some strategies on the sweeping order of node to reduce the computing cost made by repetition swing. We introduce a new concept of overlapping degree (OV) that shows the strength of connection between nodes. Three improvement strategies are proposed that are based on constant OV, adaptive OV, and adaptive weighted OV, respectively. Experiments on synthetic datasets and real datasets are made, showing that our improved strategies can improve the performance and correctness. (interdisciplinary physics and related areas of science and technology)

  20. Uncovering space-independent communities in spatial networks

    OpenAIRE

    Expert, Paul; Evans, Tim S.; Vincent D. Blondel; Lambiotte, Renaud

    2010-01-01

    Many complex systems are organized in the form of a network embedded in space. Important examples include the physical Internet infrastucture, road networks, flight connections, brain functional networks and social networks. The effect of space on network topology has recently come under the spotlight because of the emergence of pervasive technologies based on geo-localization, which constantly fill databases with people's movements and thus reveal their trajectories and spatial behaviour. Ex...

  1. Uncovering the roles of PINK1 and parkin in mitophagy

    OpenAIRE

    Matsuda, Noriyuki; Tanaka, Keiji

    2010-01-01

    Parkinson disease (PD) is the second most prevalent neurodegenerative disorder, and thus elucidation of the pathogenic mechanism and establishment of a fundamental cure is essential in terms of public welfare. Fortunately, our understanding of the pathogenesis of two types of recessive familial PDs—early-onset familial PD caused by dysfunction of the PTEN-induced putative kinase 1 (PINK1) gene and autosomal recessive juvenile Parkinsonism (ARJP) caused by a mutation in the Parkin gene—has evo...

  2. Uncovering product development competence by applying the laddering technique

    DEFF Research Database (Denmark)

    Jensen, Bjarne; Harmsen, Hanne

    This paper addresses companies' lack of implementation of success factors in new product development. Drawing on theories in the competence perspective and an exploratory empirical study, the paper points to two major areas that have not been covered by previous studies on new product development...

  3. Beyond the power law: Uncovering stylized facts in interbank networks

    Science.gov (United States)

    Vandermarliere, Benjamin; Karas, Alexei; Ryckebusch, Jan; Schoors, Koen

    2015-06-01

    We use daily data on bilateral interbank exposures and monthly bank balance sheets to study network characteristics of the Russian interbank market over August 1998-October 2004. Specifically, we examine the distributions of (un)directed (un)weighted degree, nodal attributes (bank assets, capital and capital-to-assets ratio) and edge weights (loan size and counterparty exposure). We search for the theoretical distribution that fits the data best and report the "best" fit parameters. We observe that all studied distributions are heavy tailed. The fat tail typically contains 20% of the data and can be mostly described well by a truncated power law. Also the power law, stretched exponential and log-normal provide reasonably good fits to the tails of the data. In most cases, however, separating the bulk and tail parts of the data is hard, so we proceed to study the full range of the events. We find that the stretched exponential and the log-normal distributions fit the full range of the data best. These conclusions are robust to (1) whether we aggregate the data over a week, month, quarter or year; (2) whether we look at the "growth" versus "maturity" phases of interbank market development; and (3) with minor exceptions, whether we look at the "normal" versus "crisis" operation periods. In line with prior research, we find that the network topology changes greatly as the interbank market moves from a "normal" to a "crisis" operation period.

  4. Budagovsky 9 rootstock: uncovering a novel resistance to fire blight

    Science.gov (United States)

    Budagovsky 9 (B.9) apple rootstock, displayed a high level of susceptibility (similar to M.9 rootstock) to fire blight bacteria (Erwinia amylovora) when leaves of non-grafted B.9 plants were inoculated. However, when older B.9 rootstock tissue was inoculated directly with E. amylovora, rootstock tis...

  5. Autism Spectrum Disorder: Uncovering Clues to a Complicated Condition

    Science.gov (United States)

    ... autism. One NIH-funded team found that the brain waves of some 2-year-olds with autism can have a distinctive pattern when they listen to familiar words. The children with ... in the brain region that processes language. Follow-up studies showed ...

  6. In the minds of OSCE examiners: uncovering hidden assumptions.

    Science.gov (United States)

    Chahine, Saad; Holmes, Bruce; Kowalewski, Zbigniew

    2016-08-01

    The Objective Structured Clinical Exam (OSCE) is a widely used method of assessment in medical education. Rater cognition has become an important area of inquiry in the medical education assessment literature generally, and in the OSCE literature specifically, because of concerns about potential compromises of validity. In this study, a novel approach to mixed methods that combined Ordinal Logistic Hierarchical Linear Modeling and cognitive interviews was used to gain insights about what examiners were thinking during an OSCE. This study is based on data from the 2010 to 2014 administrations of the Clinician Assessment for Practice Program OSCE for International Medical Graduates (IMGs) in Nova Scotia. An IMG is a physician trained outside of Canada who was a licensed practitioner in a different country. The quantitative data were examined alongside four follow-up cognitive interviews of examiners conducted after the 2014 administration. The quantitative results show that competencies of (1) Investigation and Management and (2) Counseling were highly predictive of the Overall Global score. These competencies were also described in the cognitive interviews as the most salient parts of OSCE. Examiners also found Communication Skills and Professional Behavior to be relevant but the quantitative results revealed these to be less predictive of the Overall Global score. The interviews also reveal that there is a tacit sequence by which IMGs are expected to proceed in an OSCE, starting with more basic competencies such as History Taking and building up to Investigation Management and Counseling. The combined results confirm that a hidden pattern exists with respect to how examiners rate candidates. This study has potential implications for research into rater cognition, and the design and scoring of practice-ready OSCEs. PMID:26661783

  7. Uncovering Students' Incorrect Ideas about Foundational Concepts for Biochemistry

    Science.gov (United States)

    Villafane, Sachel M.; Loertscher, Jennifer; Minderhout, Vicky; Lewis, Jennifer E.

    2011-01-01

    This paper presents preliminary data on how an assessment instrument with a unique structure can be used to identify common incorrect ideas from prior coursework at the beginning of a biochemistry course, and to determine whether these ideas have changed by the end of the course. The twenty-one multiple-choice items address seven different…

  8. High-Throughput Screening Uncovers Novel Botulinum Neurotoxin Inhibitor Chemotypes.

    Science.gov (United States)

    Bompiani, Kristin M; Caglič, Dejan; Krutein, Michelle C; Benoni, Galit; Hrones, Morgan; Lairson, Luke L; Bian, Haiyan; Smith, Garry R; Dickerson, Tobin J

    2016-08-01

    Botulism is caused by potent and specific bacterial neurotoxins that infect host neurons and block neurotransmitter release. Treatment for botulism is limited to administration of an antitoxin within a short time window, before the toxin enters neurons. Alternatively, current botulism drug development targets the toxin light chain, which is a zinc-dependent metalloprotease that is delivered into neurons and mediates long-term pathology. Several groups have identified inhibitory small molecules, peptides, or aptamers, although no molecule has advanced to the clinic due to a lack of efficacy in advanced models. Here we used a homogeneous high-throughput enzyme assay to screen three libraries of drug-like small molecules for new chemotypes that modulate recombinant botulinum neurotoxin light chain activity. High-throughput screening of 97088 compounds identified numerous small molecules that activate or inhibit metalloprotease activity. We describe four major classes of inhibitory compounds identified, detail their structure-activity relationships, and assess their relative inhibitory potency. A previously unreported chemotype in any context of enzyme inhibition is described with potent submicromolar inhibition (Ki = 200-300 nM). Additional detailed kinetic analyses and cellular cytotoxicity assays indicate the best compound from this series is a competitive inhibitor with cytotoxicity values around 4-5 μM. Given the potency and drug-like character of these lead compounds, further studies, including cellular activity assays and DMPK analysis, are justified. PMID:27314875

  9. Uncovering the true identity of naive pluripotent stem cells

    NARCIS (Netherlands)

    Welling, M.; Geijsen, N.

    2013-01-01

    Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass (ICM) of blastocyst embryos. Although first characterized over 30 years ago, the ontology of these cells remains elusive. Identifying the in vivo counterpart of murine ESCs will be essential for the derivation of

  10. Uncovering the intrinsic variability of gamma-ray bursts

    Energy Technology Data Exchange (ETDEWEB)

    Golkhou, Vahid Z.; Butler, Nathaniel R., E-mail: vgolkhou@asu.edu, E-mail: natbutler@asu.edu [Cosmology Initiative, Arizona State University, Tempe, AZ 85287, USA. (United States)

    2014-05-20

    We develop a robust technique to determine the minimum variability timescale for gamma-ray burst (GRB) light curves, utilizing Haar wavelets. Our approach averages over the data for a given GRB, providing an aggregate measure of signal variation while also retaining sensitivity to narrow pulses within complicated time series. In contrast to previous studies using wavelets, which simply define the minimum timescale in reference to the measurement noise floor, our approach identifies the signature of temporally smooth features in the wavelet scaleogram and then additionally identifies a break in the scaleogram on longer timescales as a signature of a true, temporally unsmooth light curve feature or features. We apply our technique to the large sample of Swift GRB gamma-ray light curves and for the first time—due to the presence of a large number of GRBs with measured redshift—determine the distribution of minimum variability timescales in the source frame. We find a median minimum timescale for long-duration GRBs in the source frame of Δt {sub min} = 0.5 s, with the shortest timescale found being on the order of 10 ms. This short timescale suggests a compact central engine (3 × 10{sup 3} km). We discuss further implications for the GRB fireball model and present a tantalizing correlation between the minimum timescale and redshift, which may in part be due to cosmological time dilation.

  11. New incompatibilities uncovered using the Promega DNA IQ™ chemistry.

    Science.gov (United States)

    Laurin, Nancy; Célestin, Florence; Clark, Meagan; Wilkinson, Della; Yamashita, Brian; Frégeau, Chantal

    2015-12-01

    Over the years, the Promega DNA IQ™ System was proven an effective technology for the production of clean DNA from a wide variety of casework specimens. The capture of DNA using the DNA IQ™ paramagnetic beads, however, was shown to be affected by a few specific chemicals that could be present on exhibits submitted to the laboratory. In this study, various blood and latent fingerprint enhancement reagents/methods, marker pens and adhesive tapes, applied at the crime scene or in the forensic laboratory on casework exhibits or used to collect biological material, were tested for their compatibility with the DNA IQ™ technology. Although no impact on DNA recovery was observed for most reagents, the MAGNA™ Jet Black fingerprint powder and three 3M Scotch(®) adhesive tapes were shown to severely or completely inhibit DNA binding onto the DNA IQ™ beads. The effect of MAGNA™ Jet Black on DNA recovery could be counteracted by separating the magnetic powder from the lysates by centrifugation or filtration, prior to DNA extraction. High quality STR profiles were obtained from samples subjected to MAGNA™ Jet Black suggesting it does not impact DNA integrity. PMID:26295931

  12. Scientists uncover speedometer for crystal growth controlled by biomolecule properties

    OpenAIRE

    Trulove, Susan

    2006-01-01

    From gemstones to transistors, crystals are everywhere in our daily lives. Crystals also make up the mineralized skeletons of all organisms, including seashells and our own teeth and bones. Perhaps the most widely used biominerals are found in the calcium carbonate family. Understanding how this mineral forms is of particular interest because of its widespread occurrence over geologic history and its close relation to the calcium phosphate found in the bones and teeth of all mammals.

  13. Diabetes insipidus uncovered during conservative management of complicated acute appendicitis

    OpenAIRE

    Mamtani, Anita; Odom, Stephen R.; Butler, Kathryn L.

    2016-01-01

    Key Clinical Message Diabetes insipidus (DI) arises from impaired function of antidiuretic hormone, characterized by hypovolemia, hypernatremia, polyuria, and polydipsia. This case is a reminder of the rare but challenging obstacle that undiagnosed DI poses in fasting surgical patients, requiring prompt recognition and vigilant management of marked homeostatic imbalances.

  14. Diabetes insipidus uncovered during conservative management of complicated acute appendicitis.

    Science.gov (United States)

    Mamtani, Anita; Odom, Stephen R; Butler, Kathryn L

    2016-05-01

    Diabetes insipidus (DI) arises from impaired function of antidiuretic hormone, characterized by hypovolemia, hypernatremia, polyuria, and polydipsia. This case is a reminder of the rare but challenging obstacle that undiagnosed DI poses in fasting surgical patients, requiring prompt recognition and vigilant management of marked homeostatic imbalances. PMID:27190614

  15. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter

    Science.gov (United States)

    Jones, Chris A.; Williams, Jake Ryland; Kurti, Allison N.; Norotsky, Mitchell Craig; Danforth, Christopher M.; Dodds, Peter Sheridan

    2016-01-01

    Background Twitter has become the “wild-west” of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, “kid-friendly” flavors, algorithmically generated false testimonials, and free samples. Methods All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets) were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching. Results The overwhelming majority (80%) of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013), up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human) classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014) due to a relative increase in the negative words ‘ban’, ‘tobacco’, ‘doesn’t’, ‘drug’, ‘against’, ‘poison’, ‘tax’ and a relative decrease in the positive words like ‘haha’, ‘good’, ‘cool’. Automated tweets are more positive than organic (6.17 versus 5.84) due to a relative increase in the marketing words like ‘best’, ‘win’, ‘buy’, ‘sale’, ‘health’, ‘discount’ and a relative decrease in negative words like ‘bad’, ‘hate’, ‘stupid’, ‘don’t’. Conclusions Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media marketing. PMID:27410031

  16. Uncovering attribute-based determinants of loyalty in cigarette brands

    DEFF Research Database (Denmark)

    Krystallis Krontalis, Athanasios

    2013-01-01

    brand loyalty at the attribute level using the Dirichlet model as a benchmark tool. Data based on the Juster Probability Scale were collected from a sample of n ¼ 155 young smokers in Iceland. Findings – Product differentiation strategies operate differently. Light nicotine and tar content encourages...... of categorization prevail in the category: first, a family brand-based, mainly relevant for large brands; and second, an attribute-driven, apparent for small family brands. Two types of switching behaviors can also be considered: first within family brands, switching among product attributes for the larger brands....... Originality/value – Not much research has been done on loyalty within the tobacco category, possibly due to the ethical considerations accompanying managerial suggestions about smoking. The contribution of the present work lies in the provisions of evidence-based insights to help brand managers and other...

  17. Phytophthora Genome Sequences Uncover Evolutionary Origins and Mechanisms of Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tyler, Brett M.; Tripathy, Sucheta; Zhang, Xuemin; Dehal, Paramvir; Jiang, Rays H. Y.; Aerts, Andrea; Arredondo, Felipe D.; Baxter, Laura; Bensasson, Douda; Beynon, JIm L.; Chapman, Jarrod; Damasceno, Cynthia M. B.; Dorrance, Anne E.; Dou, Daolong; Dickerman, Allan W.; Dubchak, Inna L.; Garbelotto, Matteo; Gijzen, Mark; Gordon, Stuart G.; Govers, Francine; Grunwald, NIklaus J.; Huang, Wayne; Ivors, Kelly L.; Jones, Richard W.; Kamoun, Sophien; Krampis, Konstantinos; Lamour, Kurt H.; Lee, Mi-Kyung; McDonald, W. Hayes; Medina, Monica; Meijer, Harold J. G.; Nordberg, Erik K.; Maclean, Donald J.; Ospina-Giraldo, Manuel D.; Morris, Paul F.; Phuntumart, Vipaporn; Putnam, Nicholas J.; Rash, Sam; Rose, Jocelyn K. C.; Sakihama, Yasuko; Salamov, Asaf A.; Savidor, Alon; Scheuring, Chantel F.; Smith, Brian M.; Sobral, Bruno W. S.; Terry, Astrid; Torto-Alalibo, Trudy A.; Win, Joe; Xu, Zhanyou; Zhang, Hongbin; Grigoriev, Igor V.; Rokhsar, Daniel S.; Boore, Jeffrey L.

    2006-04-17

    Draft genome sequences have been determined for the soybean pathogen Phytophthora sojae and the sudden oak death pathogen Phytophthora ramorum. Oömycetes such as these Phytophthora species share the kingdom Stramenopila with photosynthetic algae such as diatoms, and the presence of many Phytophthora genes of probable phototroph origin supports a photosynthetic ancestry for the stramenopiles. Comparison of the two species' genomes reveals a rapid expansion and diversification of many protein families associated with plant infection such as hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in particular, a superfamily of 700 proteins with similarity to known oömycete avirulence genes.

  18. Emperical Laws in Economics Uncovered Using Methods in Statistical Mechanics

    Science.gov (United States)

    Stanley, H. Eugene

    2001-06-01

    In recent years, statistical physicists and computational physicists have determined that physical systems which consist of a large number of interacting particles obey universal "scaling laws" that serve to demonstrate an intrinsic self-similarity operating in such systems. Further, the parameters appearing in these scaling laws appear to be largely independent of the microscopic details. Since economic systems also consist of a large number of interacting units, it is plausible that scaling theory can be usefully applied to economics. To test this possibility using realistic data sets, a number of scientists have begun analyzing economic data using methods of statistical physics [1]. We have found evidence for scaling (and data collapse), as well as universality, in various quantities, and these recent results will be reviewed in this talk--starting with the most recent study [2]. We also propose models that may lead to some insight into these phenomena. These results will be discussed, as well as the overall rationale for why one might expect scaling principles to hold for complex economic systems. This work on which this talk is based is supported by BP, and was carried out in collaboration with L. A. N. Amaral S. V. Buldyrev, D. Canning, P. Cizeau, X. Gabaix, P. Gopikrishnan, S. Havlin, Y. Lee, Y. Liu, R. N. Mantegna, K. Matia, M. Meyer, C.-K. Peng, V. Plerou, M. A. Salinger, and M. H. R. Stanley. [1.] See, e.g., R. N. Mantegna and H. E. Stanley, Introduction to Econophysics: Correlations & Complexity in Finance (Cambridge University Press, Cambridge, 1999). [2.] P. Gopikrishnan, B. Rosenow, V. Plerou, and H. E. Stanley, "Identifying Business Sectors from Stock Price Fluctuations," e-print cond-mat/0011145; V. Plerou, P. Gopikrishnan, L. A. N. Amaral, X. Gabaix, and H. E. Stanley, "Diffusion and Economic Fluctuations," Phys. Rev. E (Rapid Communications) 62, 3023-3026 (2000); P. Gopikrishnan, V. Plerou, X. Gabaix, and H. E. Stanley, "Statistical Properties of Share Volume Traded in Financial Markets," Phys. Rev. E (Rapid Communications) 62, 4493-4496 (2000).

  19. Hidden Stories: Uncovering the Visual Metaphor for Education and Communication

    Science.gov (United States)

    Hube, Amy M.; Tremblay, Kenneth R., Jr.; Leigh, Katharine E.

    2015-01-01

    Design solutions have become increasingly complex and based on a rapidly growing body of knowledge. In order to articulate a design solution to a client, the graphic use of the design narrative can effectively communicate complex ideas. Two case study interventions were conducted in an interior design program in which students were introduced to…

  20. Correlation of Activities of the Enzymes α-Phosphoglucomutase, UDP-Galactose 4-Epimerase, and UDP-Glucose Pyrophosphorylase with Exopolysaccharide Biosynthesis by Streptococcus thermophilus LY03

    OpenAIRE

    Degeest, Bart; De Vuyst, Luc

    2000-01-01

    The effects of different carbohydrates or mixtures of carbohydrates as substrates on bacterial growth and exopolysaccharide (EPS) production were studied for the yoghurt starter culture Streptococcus thermophilus LY03. This strain produces two heteropolysaccharides with the same monomeric composition (galactose and glucose in the ratio 4:1) but with different molecular masses. Lactose and glucose were fermented by S. thermophilus LY03 only when they were used as sole energy and carbohydrate s...

  1. Yeast Interacting Proteins Database: YML064C, YKL035W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available th this bait as prey (0) YKL035W UGP1 UDP-glucose pyrophosphorylase (UGPase), catalyses the reversible forma... gene name UGP1 Prey description UDP-glucose pyrophosphorylase (UGPase), catalyses the reversible

  2. Efeitos a curto prazo de "stents" não recobertos e recobertos com politetrafluoroetileno em aorta de suínos: um modelo experimental Short-term effects of polytetrafluoroethylene covered and uncovered metallic "stents" in pig aorta: an experimental model

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Grüdtner

    2004-04-01

    -expandable uncovered metallic stent. On group III animals (n=10 an auto-expandable stent covered with PTFE was inserted. After four weeks the animals were killed, the specimens were harvested and the intimal thickening was quantified by morphometric analysis. RESULTS: In the comparison among groups I, II and III referring to intimal, medial area and intimal index, it was not observed statistically significant variation. Differences were identified among groups referring to luminal proximal (p=0,036 and distal areas (p=0,044. Through multiple comparison tests for Kruskal-Wallis it was identified a difference between groups I and II. However, when these variables were controlled by weigh factor (luminal area/weigh relation, this difference was not observed anymore. CONCLUSION: In this short term study, the PTFE covering is not associated to further intimal thickening besides that promoted by the metallic mesh in large arteries and in high flow conditions.

  3. 水稻淀粉合成相关基因SSⅠ、SSⅢ-1和PUL对稻米品质的影响%Effects of the Starch-synthesizing Genes SSⅠ, SSⅢ-1 and PUL on Rice (Oryza sativa L.) Quality

    Institute of Scientific and Technical Information of China (English)

    康翠芳; 向珣朝; 龙小林; 苏文丽; 许顺菊

    2015-01-01

    可溶性淀粉合成酶基因(soluble starch synthase Ⅰ gene,SSⅠ)和SSⅢ-1以及极限糊精酶基因(pullulanase,PUL)是淀粉合成过程中参与支链淀粉合成的关键基因.为了研究SS Ⅰ、SSⅢ-1和PUL对稻米(Oryza sativa L.)品质的影响,本研究以颗粒结合淀粉合成酶基因(granule bound starch synthas,Wx)与SSⅡ-3均相同的籼型(indica)光温敏核不育系广占63S与潜力三系恢复系CG173R为亲本构建的B1C1F9株系作为供试材料,分析回交重组自交系(backcross inbred lines,BILs)各株系的蒸煮食味品质.结果表明,双亲仅在焦磷酸化酶基因大亚基基因(ADP-glucose pyrophos-phorylase large subunit ADPG,AGPlar)、分支酶3基因(starch branching enzymeⅢgene,SBE3)、PUL、SSⅠ和SSⅢ-1基因位点存在差异;SS Ⅰ、SSⅢ-1和PUL基因在B1C1F9株系中分离对蒸煮品质指标具有显著影响.SSⅢ-1基因在后代分离过程中,不同基因型之间碱消值(alkaline spreading value,ASV)、峰值粘度(peak viscosity,PKV)、崩解值(breakdown value,BDV)和峰值时间(peak time,PeT)4个指标具有显著性差异;PUL基因在后代分离过程中,不同基因型之间,胶稠度(gel consistency,GC)和回复值(consistence value,CSV)具有显著性差异(P<0.05);在SSⅢ-1和SSⅠ基因同时分离的株系中,裂区试验分析表明,SSⅢ-1和SSⅠ基因的互作效应对糊化温度(gelatinization temperature,GT)的效应达极显著水平(P<0.01),对表观直链淀粉含量(apparent amylose content,AAC)、GC、PKV和ASV的效应达显著水平(P<0.05).说明SSⅢ-1和PUL基因对稻米蒸煮食味品质的部分理化指标有显著影响,且SSⅢ-1和SSⅠ基因之间存在显著的互作效应.在相同Wx和SSⅡ-3基因基因背景下,研究稻米淀粉合成途径效应较小的基因对稻米食味品质的影响,对改良稻米蒸煮食味品质和加快稻米品质育种研究具有重要意义.

  4. 番木瓜GDP-D-甘露糖焦磷酸化酶基因的克隆及分析%Cloning and analysis of GDP-D-mannose pyrophosphorylase gene from papaya

    Institute of Scientific and Technical Information of China (English)

    申艳红; 陈晓静; 卢秉国; 何玮毅

    2011-01-01

    The full-length GMP cDNA was cloned by RACE-PCR from papaya and the gene was designated as CpGMP ( C enBank accession No. FJ4896.52). Open reading frame which encoded 361 amino acids was cloned from cDNA. DNA sequence including4extrons and 3 introns was cloned from genomic DNA. Sequencing analysis showed that the amino acid sequence was 90.30%,89.47%, 88.92%, 88.09%, 85.87% homologous with GMP from Malpighia glabra, peach, tomato, Arabidopsis thaliana and rice, respectively. Semi-quantitative RT-PCR analysis showed that the expression of CpGMP increased gradually with papaya fruit maturating and decreased when fruit began to soften.%采用cDNA末端快速扩增方法,获得了番木瓜果实GDP-D-甘露糖焦磷酸化酶(GMP)基因的cDNA全长序列,将其命名为CpGMP,GenBank登录号为FJ489652.然后,根据拼接序列设计开放性阅读框上、下游引物,扩增得到了CpGMP基因的开放性阅读框序列和DNA序列.ORF序列编码361个氨基酸,DNA序列包含4个外显子和3个内含子.序列分析表明,番木瓜GMP与大果黄褥花、桃、番茄、拟南芥、水稻GMP的同源性分别为90.30%、89.47%、88.92%、88.09%、85.87%.半定量RT-PCR分析表明,CpGMP基因随着番木瓜果实的成熟表达量逐渐增加,软化时又逐渐降低.

  5. Proteins Encoded by Sphingomonas elodea ATCC 31461 rmlA and ugpG Genes, Involved in Gellan Gum Biosynthesis, Exhibit both dTDP- and UDP-Glucose Pyrophosphorylase Activities

    OpenAIRE

    Silva, Elisabete; Marques, Ana Rita; Fialho, Arsénio Mendes; Granja, Ana Teresa; Sá-Correia, Isabel

    2005-01-01

    The commercial gelling agent gellan is a heteropolysaccharide produced by Sphingomonas elodea ATCC 31461. In this work, we carried out the biochemical characterization of the enzyme encoded by the first gene (rmlA) of the rml 4-gene cluster present in the 18-gene cluster required for gellan biosynthesis (gel cluster). Based on sequence homology, the putative rml operon is presumably involved in the biosynthesis of dTDP-rhamnose, the sugar necessary for the incorporation of rhamnose in the gel...

  6. Uncovering a Latent Multinomial: Analysis of Mark-Recapture Data with Misidentification

    Science.gov (United States)

    Link, W.A.; Yoshizaki, J.; Bailey, L.L.; Pollock, K.H.

    2009-01-01

    Natural tags based on DNA fingerprints or natural features of animals are now becoming very widely used in wildlife population biology. However, classic capture-recapture models do not allow for misidentification of animals which is a potentially very serious problem with natural tags. Statistical analysis of misidentification processes is extremely difficult using traditional likelihood methods but is easily handled using Bayesian methods. We present a general framework for Bayesian analysis of categorical data arising from a latent multinomial distribution. Although our work is motivated by a specific model for misidentification in closed population capture-recapture analyses, with crucial assumptions which may not always be appropriate, the methods we develop extend naturally to a variety of other models with similar structure. Suppose that observed frequencies f are a known linear transformation f=A'x of a latent multinomial variable x with cell probability vector pi= pi(theta). Given that full conditional distributions [theta | x] can be sampled, implementation of Gibbs sampling requires only that we can sample from the full conditional distribution [x | f, theta], which is made possible by knowledge of the null space of A'. We illustrate the approach using two data sets with individual misidentification, one simulated, the other summarizing recapture data for salamanders based on natural marks.

  7. Uncovering Local Trends in Genetic Effects of Multiple Phenotypes via Functional Linear Models.

    Science.gov (United States)

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Barondess, David A; Tong, Xiaoren; Jadhav, Sneha; Lu, Qing

    2016-04-01

    Recent technological advances equipped researchers with capabilities that go beyond traditional genotyping of loci known to be polymorphic in a general population. Genetic sequences of study participants can now be assessed directly. This capability removed technology-driven bias toward scoring predominantly common polymorphisms and let researchers reveal a wealth of rare and sample-specific variants. Although the relative contributions of rare and common polymorphisms to trait variation are being debated, researchers are faced with the need for new statistical tools for simultaneous evaluation of all variants within a region. Several research groups demonstrated flexibility and good statistical power of the functional linear model approach. In this work we extend previous developments to allow inclusion of multiple traits and adjustment for additional covariates. Our functional approach is unique in that it provides a nuanced depiction of effects and interactions for the variables in the model by representing them as curves varying over a genetic region. We demonstrate flexibility and competitive power of our approach by contrasting its performance with commonly used statistical tools and illustrate its potential for discovery and characterization of genetic architecture of complex traits using sequencing data from the Dallas Heart Study. PMID:27027515

  8. Uncovering High Thermoelectric Figure of Merit in (Hf,Zr)NiSn Half-Heusler Alloys

    OpenAIRE

    Chen, L.; Gao, S; Zeng, X; Dehkordi, A. M.; Tritt, T. M; Poon, S. J.

    2015-01-01

    Half-Heusler alloys (MgAgSb structure) are promising thermoelectric materials. RNiSn half-Heusler phases (R=Hf, Zr, Ti) are the most studied in view of their thermal stability. The highest dimensionless figure of merit (ZT) obtained is ~1 in the temperature range ~450-900oC, primarily achieved in nanostructured alloys. Through proper annealing, ZT~1.2 has been obtained in a previous ZT~1 n-type (Hf,Zr)NiSn phase without the nanostructure. There is an appreciable increase in the power factor, ...

  9. Uncovering molecular processes in crystal nucleation and growth by using molecular simulation.

    Science.gov (United States)

    Anwar, Jamshed; Zahn, Dirk

    2011-02-25

    Exploring nucleation processes by molecular simulation provides a mechanistic understanding at the atomic level and also enables kinetic and thermodynamic quantities to be estimated. However, whilst the potential for modeling crystal nucleation and growth processes is immense, there are specific technical challenges to modeling. In general, rare events, such as nucleation cannot be simulated using a direct "brute force" molecular dynamics approach. The limited time and length scales that are accessible by conventional molecular dynamics simulations have inspired a number of advances to tackle problems that were considered outside the scope of molecular simulation. While general insights and features could be explored from efficient generic models, new methods paved the way to realistic crystal nucleation scenarios. The association of single ions in solvent environments, the mechanisms of motif formation, ripening reactions, and the self-organization of nanocrystals can now be investigated at the molecular level. The analysis of interactions with growth-controlling additives gives a new understanding of functionalized nanocrystals and the precipitation of composite materials. PMID:21271625

  10. Uncovered: Progenitors of globular clusters showing off their multiple stellar populations

    Science.gov (United States)

    de Grijs, Richard; Li, Chengyuan; Deng, Licai; Geller, Aaron M.; Xin, Yu; Hu, Yi; Faucher-Giguere, Claude-Andre

    2016-01-01

    Stars in star clusters are thought to form in a single burst from a common progenitor cloud of molecular gas, resulting in so-called simple stellar populations. However, old, massive globular clusters—with ages greater than 10 billion years—often host multiple stellar populations, indicating that more than one star-forming event may have occurred during their lifetimes. The most popular scenario for their formation invokes colliding stellar winds from late-stage, asymptotic-giant-branch stars. If this were correct, the initial globular cluster masses should be at least 10 times more massive than their current masses of typically a few x 105 Msun. However, large populations of clusters with masses greater than a few x 106 Msun are not found in the local Universe. Here we present Hubble Space Telescope observations of three 1-2 billion-year-old, massive star clusters in the Magellanic Clouds which show unequivocal evidence of burst-like star-formation activity that occurred a few x 108 years after their initial formation era. The spatial distributions of the younger stellar generations suggest that they may have originated from ambient gas clouds accreted by the clusters while orbiting in the disks of their host galaxies rather than from colliding stellar winds. Simple models imply that such clusters could indeed accrete sufficient gas reservoirs to form these stars. This may eventually give rise to the appearance of multiple stellar populations in globular clusters.

  11. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets

    DEFF Research Database (Denmark)

    Grarup, Niels; Sulem, Patrick; Sandholt, Camilla H;

    2013-01-01

    the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B12 (B12) and folate. Up to 22.9 million sequence variants were analyzed...... in combined samples of 45,576 and 37,341 individuals with serum B12 and folate measurements, respectively. We found six novel loci associating with serum B12 (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT......, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B12 and folate pathways. Contrary to epidemiological studies we did not find...

  12. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.

    Science.gov (United States)

    Grarup, Niels; Sulem, Patrick; Sandholt, Camilla H; Thorleifsson, Gudmar; Ahluwalia, Tarunveer S; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F; Magnusson, Olafur T; Sparsø, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi; Nie, Chao; Kristiansen, Karsten; Husemoen, Lise Lotte; Thuesen, Betina; Li, Yingrui; Nielsen, Rasmus; Linneberg, Allan; Olafsson, Isleifur; Eyjolfsson, Gudmundur I; Jørgensen, Torben; Wang, Jun; Hansen, Torben; Thorsteinsdottir, Unnur; Stefánsson, Kari; Pedersen, Oluf

    2013-06-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations. PMID:23754956

  13. Using giant scarlet runner bean embryos to uncover regulatory networks controlling suspensor gene activity

    Directory of Open Access Journals (Sweden)

    Kelli F. Henry

    2015-02-01

    Full Text Available One of the major unsolved issues in plant development is understanding the regulatory networks that control the differential gene activity that is required for the specification and development of the two major embryonic regions, the embryo proper and suspensor. Historically, the giant embryo of scarlet runner bean (SRB, Phaseolus coccineus, has been used as a model system to investigate the physiological events that occur early in embryogenesis – focusing on the question of what role the suspensor region plays. A major feature distinguishing SRB embryos from those of other plants is a highly enlarged suspensor containing at least 200 cells that synthesize growth regulators required for subsequent embryonic development. Recent studies have exploited the giant size of the SRB embryo to micro-dissect the embryo proper and suspensor regions in order to use genomics-based approaches to identify regulatory genes that may be involved in controlling suspensor and embryo proper differentiation, as well as the cellular processes that may be unique to each embryonic region. Here we review the current genomics resources that make SRB embryos a compelling model system for studying the early events required to program embryo development.

  14. Yeast Model Uncovers Dual Roles of Mitochondria in the Action of Artemisinin.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Artemisinins, derived from the wormwood herb Artemisia annua, are the most potent antimalarial drugs currently available. Despite extensive research, the exact mode of action of artemisinins has not been established. Here we use yeast, Saccharamyces cerevisiae, to probe the core working mechanism of this class of antimalarial agents. We demonstrate that artemisinin's inhibitory effect is mediated by disrupting the normal function of mitochondria through depolarizing their membrane potential. Moreover, in a genetic study, we identify the electron transport chain as an important player in artemisinin's action: Deletion of NDE1 or NDI1, which encode mitochondrial NADH dehydrogenases, confers resistance to artemisinin, whereas overexpression of NDE1 or NDI1 dramatically increases sensitivity to artemisinin. Mutations or environmental conditions that affect electron transport also alter host's sensitivity to artemisinin. Sensitivity is partially restored when the Plasmodium falciparum NDI1 ortholog is expressed in yeast ndi1 strain. Finally, we showed that artemisinin's inhibitory effect is mediated by reactive oxygen species. Our results demonstrate that artemisinin's effect is primarily mediated through disruption of membrane potential by its interaction with the electron transport chain, resulting in dysfunctional mitochondria. We propose a dual role of mitochondria played during the action of artemisinin: the electron transport chain stimulates artemisinin's effect, most likely by activating it, and the mitochondria are subsequently damaged by the locally generated free radicals.

  15. Arcaine uncovers dual interactions of polyamines with the N-methyl-D-aspartate receptor

    International Nuclear Information System (INIS)

    This study investigated the interaction between the polyamines spermine and spermidine and the N-methyl-D-aspartate (NMDA) receptor by using (+)-[3H]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine maleate ([3H]MK801) binding to well washed rat brain membranes. The actions of arcaine, agmatine, diethylenetriamine and 1,8-octanediamine as polyamine antagonists were compared to use as tools in this study. Arcaine was found to be the antagonist of choice due to its greater potency. Several divalent cations, including Ba++, Ca++ and Sr++, but not Zn++, decreased the apparent potency of arcaine. These cations enhance [3H]MK801 binding in a similar fashion to spermidine and spermine suggesting that they may share a common site and mechanism of action. Moreover, arcaine competitively reduced the enhancement of [3H]MK801 binding produced by Sr++ did not alter the inhibition produced by higher concentrations of this cation, a phenomenon that also occurs with spermidine. The distinct arcaine sensitivity of the two separate phases of the concentration-response curves of both spermidine and Sr++ suggests two separate mechanisms underlying the action of spermidine-like drugs on the NMDA receptor. Further investigation of the increase in [3H]MK801 binding produced by spermidine revealed that spermidine increased the equilibrium affinity of this ligand by 2-fold without significantly altering the density of binding sites. In contrast, polyamine induced increases in the dissociation of [3H]MK801 required higher polyamine concentrations than necessary to increase ligand binding and were relatively insensitive to arcaine. These findings suggest that polyamines do not activate or promote the activation of the NMDA receptor, but instead enhance [3H]MK801 binding by allosterically increasing ligand affinity

  16. The evolution of the literature on entrepreneurship. Uncovering some under researched themes

    OpenAIRE

    Cristina Santos; Aurora A.C. Teixeira

    2009-01-01

    Recently bibliometrics techniques are being widely used to complement traditional qualitative reviews of the literature in given scientific areas. The majority of these reviews are based in large databases of articles published in ISI indexed journals, overlooking the richness of studies that are being published in key handbooks and books. This is particularly true in the case of entrepreneurship field. In the present paper we provide a survey of the literature based on an in-depth analysis o...

  17. Uncovering the Stabilization Mechanism in Bimetallic Ruthenium-Iridium Anodes for Proton Exchange Membrane Electrolyzers.

    Science.gov (United States)

    Saveleva, Viktoriia A; Wang, Li; Luo, Wen; Zafeiratos, Spyridon; Ulhaq-Bouillet, Corinne; Gago, Aldo S; Friedrich, K Andreas; Savinova, Elena R

    2016-08-18

    Proton exchange membrane (PEM) electrolyzers are attracting an increasing attention as a promising technology for the renewable electricity storage. In this work, near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) is applied for in situ monitoring of the surface state of membrane electrode assemblies with RuO2 and bimetallic Ir0.7Ru0.3O2 anodes during water splitting. We demonstrate that Ir protects Ru from the formation of an unstable hydrous Ru(IV) oxide thereby rendering bimetallic Ru-Ir oxide electrodes with higher corrosion resistance. We further show that the water splitting occurs through a surface Ru(VIII) intermediate, and, contrary to common opinion, the presence of Ir does not hinder its formation. PMID:27477824

  18. Uncovering Critical Research Agendas for School Psychology: Conceptual Dimensions and Future Directions.

    Science.gov (United States)

    Kratochwill, Thomas R.; Stoiber, Karen Callan

    2000-01-01

    Considers research agendas for moving the school psychology profession forward by yielding unique contributions in the millennium, while enabling school psychologists to enhance outcomes for children and families with greater precision and effectiveness. Specifically examines some research agendas in the areas of diagnosis and assessment,…

  19. PREREQUISITES TO UNCOVERING THE REGULARITIES OF THE FATIGUE RESISTANCE OF ANCHORAGE OF CURTAIN WALL SYSTEMS

    Directory of Open Access Journals (Sweden)

    Alisultanov Ramidin Semedovich

    2016-04-01

    Full Text Available Curtain wall systems are subjected to the influence of air flow, which is changing in its direction and speed. Such an influence gives rise to variable forces, which leads to fluctuating stresses in the structures of curtain wall systems. In case of fluctuating stresses the structural element is destroyed at lower loads, than in case of constant stresses. This fracture is called the fatigue. The fatigue fractures lead to drastic consequences because of their sudden emergence. The fracture mode of structural materials depends on the number of loading cycles. The authors state the notions of multicycle and low-cycle fatigue of materials. Some types of fatigue curves are offered. The authors hypothesize on the absence of horizontal areas of Wehler curve in case of plastic materials.

  20. Uncovering brain–heart information through advanced signal and image processing

    OpenAIRE

    Valenza, Gaetano; Toschi, Nicola; Barbieri, Riccardo

    2016-01-01

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme iss...

  1. Uncovering the prevalence and diversity of integrating conjugative elements in actinobacteria.

    Directory of Open Access Journals (Sweden)

    Mariana Gabriela Ghinet

    Full Text Available Horizontal gene transfer greatly facilitates rapid genetic adaptation of bacteria to shifts in environmental conditions and colonization of new niches by allowing one-step acquisition of novel functions. Conjugation is a major mechanism of horizontal gene transfer mediated by conjugative plasmids and integrating conjugative elements (ICEs. While in most bacterial conjugative systems DNA translocation requires the assembly of a complex type IV secretion system (T4SS, in Actinobacteria a single DNA FtsK/SpoIIIE-like translocation protein is required. To date, the role and diversity of ICEs in Actinobacteria have received little attention. Putative ICEs were searched for in 275 genomes of Actinobacteria using HMM-profiles of proteins involved in ICE maintenance and transfer. These exhaustive analyses revealed 144 putative FtsK/SpoIIIE-type ICEs and 17 putative T4SS-type ICEs. Grouping of the ICEs based on the phylogenetic analyses of maintenance and transfer proteins revealed extensive exchanges between different sub-families of ICEs. 17 ICEs were found in Actinobacteria from the genus Frankia, globally important nitrogen-fixing microorganisms that establish root nodule symbioses with actinorhizal plants. Structural analysis of ICEs from Frankia revealed their unexpected diversity and a vast array of predicted adaptive functions. Frankia ICEs were found to excise by site-specific recombination from their host's chromosome in vitro and in planta suggesting that they are functional mobile elements whether Frankiae live as soil saprophytes or plant endosymbionts. Phylogenetic analyses of proteins involved in ICEs maintenance and transfer suggests that active exchange between ICEs cargo-borne and chromosomal genes took place within the Actinomycetales order. Functionality of Frankia ICEs in vitro as well as in planta lets us anticipate that conjugation and ICEs could allow the development of genetic manipulation tools for this challenging microorganism and for many other Actinobacteria.

  2. Uncovering the Prevalence and Diversity of Integrating Conjugative Elements in Actinobacteria

    OpenAIRE

    Mariana Gabriela Ghinet; Eric Bordeleau; Julie Beaudin; Ryszard Brzezinski; Sébastien Roy; Vincent Burrus

    2011-01-01

    Horizontal gene transfer greatly facilitates rapid genetic adaptation of bacteria to shifts in environmental conditions and colonization of new niches by allowing one-step acquisition of novel functions. Conjugation is a major mechanism of horizontal gene transfer mediated by conjugative plasmids and integrating conjugative elements (ICEs). While in most bacterial conjugative systems DNA translocation requires the assembly of a complex type IV secretion system (T4SS), in Actinobacteria a sing...

  3. The Ethics of Uncovering Something Else in Histoire(s du cinema

    Directory of Open Access Journals (Sweden)

    Jiewon Baek

    2014-09-01

    Full Text Available In lieu of an abstract, here is the essay's opening paragraph:Marguerite Duras prefaces the second edition of Le navire night, from which an excerpt is cited above, by explaining that after writing the story of a man named J.M., everything came too late, including the realization of the film version of Le navire night. Once the event has been written and the common night of history been closed up, did she have the right to flash a light into the darkness to go back and see? The only seeing through cinema that was possible, she continues, was to film the failure, the disaster of the film. But how does one film the failure of realizing a film adaptation of a written text, which itself was transcribed from an oral re-telling of a story, which itself was adapted from memory? The event already took place – writing, “this history here” –, leaving cinema to film what never took place, namely, the film itself. As Jean-Luc Godard confirms in a chapter titled Seul le cinéma in Histoire(s du cinéma, not only in the form of his project as a whole but also more explicitly in one shot that positions two close-up photographs of his face with the sound of Paul Hindemith’s “Funeral Music” and this text: “Faire une description précise de ce qui n’a jamais eu lieu est le travail de l’historien.” Describing the rise of the film Le navire night from its disastrous death, Duras writes: “On a mis la caméra à l’envers et on a filmé ce qui entrait dedans, de la nuit, de l’air, des projecteurs, des routes, des visages aussi.” The camera turned upside-down, or in the other sense, inside-out, Duras films the entrance of the exterior, a sort of a Levinasian visage. The question no longer is one of having the right but of the duty to re-write history, as is insinuated by the reference to “The Critic as Artist” written across one of the photographs mentioned above, which is again a gesture of Godard’s positioning himself as the critic whose role Oscar Wilde defined: “The one duty we owe to history is to rewrite it.”

  4. Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega-6 Fatty Acids

    Directory of Open Access Journals (Sweden)

    Jennifer L. Watts

    2016-02-01

    Full Text Available The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids.

  5. Uncovering Mechanisms of Coronal Magnetism via Advanced 3D Modeling of Flares and Active Regions

    CERN Document Server

    Fleishman, Gregory; Nita, Gelu; Alexander, David; Aschwanden, Markus; Bastian, Tim; Hudson, Hugh; Hurford, Gordon; Kontar, Eduard; Longcope, Dana; Mikic, Zoran; DeRosa, Marc; Ryan, James; White, Stephen

    2010-01-01

    The coming decade will see the routine use of solar data of unprecedented spatial and spectral resolution, time cadence, and completeness. To capitalize on the new (or soon to be available) facilities such as SDO, ATST and FASR, and the challenges they present in the visualization and synthesis of multi-wavelength datasets, we propose that realistic, sophisticated, 3D active region and flare modeling is timely and critical, and will be a forefront of coronal studies over the coming decade. To make such modeling a reality, a broad, concerted effort is needed to capture the wealth of information resulting from the data, develop a synergistic modeling effort, and generate the necessary visualization, interpretation and model-data comparison tools to accurately extract the key physics.

  6. Student Newspapers and University Libraries: Uncovering Your Library's Reputation and Promoting Its Services

    Science.gov (United States)

    Bodnar, Jonathan; Mathews, Brian

    2008-01-01

    To help librarians use their campus newspapers more effectively as a communications tool, this paper discusses the type of information about campus libraries that ten student newspapers published over the course of one year and discusses strategies that librarians can use to build more productive, collaborative relationships with the people who…

  7. Uncovering molecular structural mechanisms of signaling mediated by the prion protein

    International Nuclear Information System (INIS)

    The glycosyl phosphatidylinositol (GPI) - anchored prion protein (PrPc), usually associated with neurodegenerative diseases, modulates various cellular responses and may scaffold multiprotein cell surface signaling complexes. Engagement of PrPc with the secretable cochaperone hop/STI 1 induces neurotrophic transmembrane signals through unknown molecular mechanisms. We addressed whether interaction of Pr Pc and hop STI 1 entails structural rearrangements relevant for signaling. Circular dichroism and fluorescence spectroscopy showed that PrPc:hop/STI 1 interaction triggers loss of PrP helical structures, involving at least a perturbation of the Pr Pc143-153 beta-helix. Novel SAXS models revealed a significant C-terminal compaction of hop/STI 1 when bound to PrPc. Differing from a recent dimeric model of human hop/STI 1, both size exclusion chromatography and SAXS data support a monomeric form of free murine hop/STI 1. Changes in the Pr Pc143-153 beta-helix may engage the transmembrane signaling protein laminin receptor precursor and neural cell adhesion molecule, both of which bind that domain of Pr Pc, and further ligands may be engaged by the tertiary structural changes of hop/STI 1. These reciprocal structural modifications indicate a versatile mechanism for signaling mediated by Pr Pc:hop/STI 1 interaction, consistent with the hypothesis that Pr Pc scaffolds multiprotein signaling complexes at the cell surface. (author)

  8. Transcriptome atlas of eight liver cell types uncovers effects of histidine catabolites on rat liver regeneration

    Indian Academy of Sciences (India)

    C. F. Chang; J. Y. Fan; F. C. Zhang; J. Ma; C. S. Xu

    2010-12-01

    Eight liver cell types were isolated using the methods of Percoll density gradient centrifugation and immunomagnetic beads to explore effects of histidine catabolites on rat liver regeneration. Rat Genome 230 2.0 Array was used to detect the expression profiles of genes associated with metabolism of histidine and its catabolites for the above-mentioned eight liver cell types, and bioinformatic and systems biology approaches were employed to analyse the relationship between above genes and rat liver regeneration. The results showed that the urocanic acid (UA) was degraded from histidine in Kupffer cells, acts on Kupffer cells itself and dendritic cells to generate immune suppression by autocrine and paracrine modes. Hepatocytes, biliary epithelia cells, oval cells and dendritic cells can convert histidine to histamine, which can promote sinusoidal endothelial cells proliferation by GsM pathway, and promote the proliferation of hepatocytes and biliary epithelia cells by GqM pathway.

  9. NIH study uncovers new mechanism of action for class of chemotherapy drugs

    Science.gov (United States)

    NIH researchers have discovered a significant new mechanism of action for a class of chemotherapy drugs known as poly (ADP-ribose) polymerase inhibitors, or PARP inhibitors. They have also identified differences in the toxic capabilities of three drugs in

  10. Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires' disease.

    Directory of Open Access Journals (Sweden)

    Christel Cazalet

    2010-02-01

    Full Text Available Legionella pneumophila and L. longbeachae are two species of a large genus of bacteria that are ubiquitous in nature. L. pneumophila is mainly found in natural and artificial water circuits while L. longbeachae is mainly present in soil. Under the appropriate conditions both species are human pathogens, capable of causing a severe form of pneumonia termed Legionnaires' disease. Here we report the sequencing and analysis of four L. longbeachae genomes, one complete genome sequence of L. longbeachae strain NSW150 serogroup (Sg 1, and three draft genome sequences another belonging to Sg1 and two to Sg2. The genome organization and gene content of the four L. longbeachae genomes are highly conserved, indicating strong pressure for niche adaptation. Analysis and comparison of L. longbeachae strain NSW150 with L. pneumophila revealed common but also unexpected features specific to this pathogen. The interaction with host cells shows distinct features from L. pneumophila, as L. longbeachae possesses a unique repertoire of putative Dot/Icm type IV secretion system substrates, eukaryotic-like and eukaryotic domain proteins, and encodes additional secretion systems. However, analysis of the ability of a dotA mutant of L. longbeachae NSW150 to replicate in the Acanthamoeba castellanii and in a mouse lung infection model showed that the Dot/Icm type IV secretion system is also essential for the virulence of L. longbeachae. In contrast to L. pneumophila, L. longbeachae does not encode flagella, thereby providing a possible explanation for differences in mouse susceptibility to infection between the two pathogens. Furthermore, transcriptome analysis revealed that L. longbeachae has a less pronounced biphasic life cycle as compared to L. pneumophila, and genome analysis and electron microscopy suggested that L. longbeachae is encapsulated. These species-specific differences may account for the different environmental niches and disease epidemiology of these two Legionella species.

  11. Silencing the Majority of Cerebellar Granule Cells Uncovers Their Essential Role in Motor Learning and Consolidation

    Directory of Open Access Journals (Sweden)

    Elisa Galliano

    2013-04-01

    Full Text Available Cerebellar granule cells (GCs account for more than half of all neurons in the CNS of vertebrates. Theoretical work has suggested that the abundance of GCs is advantageous for sparse coding during memory formation. Here, we minimized the output of the majority of GCs by selectively eliminating their CaV2.1 (P/Q-type Ca2+ channels, which mediate the bulk of their neurotransmitter release. This resulted in reduced GC output to Purkinje cells (PCs and stellate cells (SCs as well as in impaired long-term plasticity at GC-PC synapses. As a consequence modulation amplitude and regularity of simple spike (SS output were affected. Surprisingly, the overall motor performance was intact, whereas demanding motor learning and memory consolidation tasks were compromised. Our findings indicate that a minority of functionally intact GCs is sufficient for the maintenance of basic motor performance, whereas acquisition and stabilization of sophisticated memories require higher numbers of normal GCs controlling PC firing.

  12. An Engaged Pragmatist: Uncovering and Assessing Ernest Horn's View of Moral Education

    Science.gov (United States)

    Schul, James E.; Hamot, Gregory E.

    2011-01-01

    Ernest Horn was a curriculum professor at The University of Iowa in the early to mid-twentieth century. Predominantly known at the time for his spelling research, Horn also made important contributions to the field of social studies education. This historical inquiry illuminates one of Horn's contributions to social studies education by examining…

  13. Uncovering multiple orbitals influence in high harmonic generation from aligned N$_2$

    OpenAIRE

    Le, Anh-Thu; Lucchese, R. R.; C.D. Lin

    2009-01-01

    Recent measurements on high-order harmonic generation (HHG) from N$_2$ aligned perpendicular to the driving laser polarization [B. K. McFarland {\\it el al}, Science {\\bf 322}, 1232 (2008)] have shown a maximum at the rotational half-revival. This has been interpreted as the signature of the HHG contribution from the molecular orbital just below the highest occupied molecular orbital (HOMO). By using the recently developed quantitative rescattering theory combined with accurate photoionization...

  14. Transcriptional Profiles Uncover Aspergillus flavus-Induced Resistance in Maize Kernels

    Directory of Open Access Journals (Sweden)

    Zhi-Yuan Chen

    2011-06-01

    Full Text Available Aflatoxin contamination caused by the opportunistic pathogen A. flavus is a major concern in maize production prior to harvest and through storage. Previous studies have highlighted the constitutive production of proteins involved in maize kernel resistance against A. flavus’ infection. However, little is known about induced resistance nor about defense gene expression and regulation in kernels. In this study, maize oligonucleotide arrays and a pair of closely-related maize lines varying in aflatoxin accumulation were used to reveal the gene expression network in imbibed mature kernels in response to A. flavus’ challenge. Inoculated kernels were incubated 72 h via the laboratory-based Kernel Screening Assay (KSA, which highlights kernel responses to fungal challenge. Gene expression profiling detected 6955 genes in resistant and 6565 genes in susceptible controls; 214 genes induced in resistant and 2159 genes induced in susceptible inoculated kernels. Defense related and regulation related genes were identified in both treatments. Comparisons between the resistant and susceptible lines indicate differences in the gene expression network which may enhance our understanding of the maize-A. flavus interaction.

  15. The Extended Halo of Centaurus A: Uncovering Satellites, Streams, and Substructures

    Science.gov (United States)

    Crnojević, D.; Sand, D. J.; Spekkens, K.; Caldwell, N.; Guhathakurta, P.; McLeod, B.; Seth, A.; Simon, J. D.; Strader, J.; Toloba, E.

    2016-05-01

    We present the widest-field resolved stellar map to date of the closest (D∼ 3.8 Mpc) massive elliptical galaxy NGC 5128 (Centaurus A; Cen A), extending out to a projected galactocentric radius of ∼150 kpc. The data set is part of our ongoing Panoramic Imaging Survey of Centaurus and Sculptor (PISCeS) utilizing the Magellan/Megacam imager. We resolve a population of old red giant branch (RGB) stars down to ∼1.5 mag below the tip of the RGB, reaching surface brightness limits as low as {μ }V,0∼ 32 mag arcsec‑2. The resulting spatial stellar density map highlights a plethora of previously unknown streams, shells, and satellites, including the first tidally disrupting dwarf around Cen A (CenA-MM-Dw3), which underline its active accretion history. We report 13 previously unknown dwarf satellite candidates, of which 9 are confirmed to be at the distance of Cen A (the remaining 4 are not resolved into stars), with magnitudes in the range {M}V=-7.2 to ‑13.0, central surface brightness values of {μ }V,0=25.4{--}26.9 mag arcsec‑2, and half-light radii of {r}h=0.22{--}2.92 {{kpc}}. These values are in line with Local Group dwarfs but also lie at the faint/diffuse end of their distribution; interestingly, CenA-MM-Dw3 has similar properties to the recently discovered ultradiffuse galaxies in Virgo and Coma. Most of the new dwarfs are fainter than the previously known Cen A satellites. The newly discovered dwarfs and halo substructures are discussed in light of their stellar populations, and they are compared to those discovered by the PAndAS survey of M31. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  16. Uncovering microRNA-mediated response to SO2 stress in Arabidopsis thaliana by deep sequencing.

    Science.gov (United States)

    Li, Lihong; Xue, Meizhao; Yi, Huilan

    2016-10-01

    Sulfur dioxide (SO2) is a major air pollutant and has significant impacts on plants. MicroRNAs (miRNAs) are a class of gene expression regulators that play important roles in response to environmental stresses. In this study, deep sequencing was used for genome-wide identification of miRNAs and their expression profiles in response to SO2 stress in Arabidopsis thaliana shoots. A total of 27 conserved miRNAs and 5 novel miRNAs were found to be differentially expressed under SO2 stress. qRT-PCR analysis showed mostly negative correlation between miRNA accumulation and target gene mRNA abundance, suggesting regulatory roles of these miRNAs during SO2 exposure. The target genes of SO2-responsive miRNAs encode transcription factors and proteins that regulate auxin signaling and stress response, and the miRNAs-mediated suppression of these genes could improve plant resistance to SO2 stress. Promoter sequence analysis of genes encoding SO2-responsive miRNAs showed that stress-responsive and phytohormone-related cis-regulatory elements occurred frequently, providing additional evidence of the involvement of miRNAs in adaption to SO2 stress. This study represents a comprehensive expression profiling of SO2-responsive miRNAs in Arabidopsis and broads our perspective on the ubiquitous regulatory roles of miRNAs under stress conditions. PMID:27232729

  17. Network-Based Analysis on Orthogonal Separation of Human Plasma Uncovers Distinct High Density Lipoprotein Complexes.

    Science.gov (United States)

    Li, Hailong; Gordon, Scott M; Zhu, Xiaoting; Deng, Jingyuan; Swertfeger, Debi K; Davidson, W Sean; Lu, L Jason

    2015-08-01

    High density lipoprotein (HDL) particles are blood-borne complexes whose plasma levels have been associated with protection from cardiovascular disease (CVD). Recent studies have demonstrated the existence of distinct HDL subspecies; however, these have been difficult to isolate and characterize biochemically. Here, we present the first report that employs a network-based approach to systematically infer HDL subspecies. Healthy human plasma was separated into 58 fractions using our previously published three orthogonal chromatography techniques. Similar local migration patterns among HDL proteins were captured with a novel similarity score, and individual comigration networks were constructed for each fraction. By employing a graph mining algorithm, we identified 183 overlapped cliques, among which 38 were further selected as candidate HDL subparticles. Each of these 38 subparticles had at least two literature supports. In addition, GO function enrichment analysis showed that they were enriched with fundamental biological and CVD protective functions. Furthermore, gene knockout experiments in mouse model supported the validity of these subparticles related to three apolipoproteins. Finally, analysis of an apoA-I deficient human patient's plasma provided additional support for apoA-I related complexes. Further biochemical characterization of these putative subspecies may facilitate the mechanistic research of CVD and guide targeted therapeutics aimed at its mitigation. PMID:26057100

  18. Metal accumulation in mosses across national boundaries: Uncovering and ranking causes of spatial variation

    International Nuclear Information System (INIS)

    This study aimed at cross-border mapping metal loads in mosses in eight European countries in 1990, 1995, and 2000 and at investigating confounding factors. Geostatistics was used for mapping, indicating high local variances but clear spatial autocorrelations. Inference statistics identified differences of metal concentrations in mosses on both sides of the national borders. However, geostatistical analyses did not ascertain discontinuities of metal concentrations in mosses at national borders due to sample analysis in different laboratories applying a range of analytical techniques. Applying Classification and Regression Trees (CART) to the German moss data as an example, the local variation in metal concentrations in mosses were proved to depend mostly on different moss species, potential local emission sources, canopy drip and precipitation. - Factors affecting the spatial variation in metal accumulation in mosses were mapped by geostatistics and ranked by CART

  19. Uncovering transcriptional regulation of glycerol metabolism in Aspergilli through genome-wide gene expression data anlysis

    DEFF Research Database (Denmark)

    Salazar, Margarita Pena; Vongsangnak, Wanwipa; Panagiotou, Gianni;

    2009-01-01

    Glycerol is catabolized by a wide range of microorganisms including Aspergillus species. To identify the transcriptional regulation of glycerol metabolism in Aspergillus, we analyzed data from triplicate batch fermentations of three different Aspergilli (Aspergillus nidulans, Aspergillus oryzae and...... Aspergillus niger) with glucose and glycerol as carbon sources. Protein comparisons and cross-analysis with gene expression data of all three species resulted in the identification of 88 genes having a conserved response across the three Aspergilli. A promoter analysis of the up-regulated genes led to the...... identification of a conserved binding site for a putative regulator to be 5′-TGCGGGGA-3′, a binding site that is similar to the binding site for Adr1 in yeast and humans. We show that this Adr1 consensus binding sequence was over-represented on promoter regions of several genes in A. nidulans, A. oryzae and A...

  20. Uncovering the genetic history of the present-day greenlandic population

    DEFF Research Database (Denmark)

    Moltke, Ida; Fumagalli, Matteo; Korneliussen, Thorfinn Sand; Crawford, Jacob E; Bjerregaard, Peter; Jørgensen, Marit E; Grarup, Niels; Gulløv, Hans Christian; Linneberg, Allan René; Pedersen, Oluf Borbye; Hansen, Torben; Nielsen, Rasmus; Albrechtsen, Anders

    2015-01-01

    Because of past limitations in samples and genotyping technologies, important questions about the history of the present-day Greenlandic population remain unanswered. In an effort to answer these questions and in general investigate the genetic history of the Greenlandic population, we analyzed...

  1. Cryptic speciation patterns in Iranian rock lizards uncovered by integrative taxonomy.

    Directory of Open Access Journals (Sweden)

    Faraham Ahmadzadeh

    Full Text Available While traditionally species recognition has been based solely on morphological differences either typological or quantitative, several newly developed methods can be used for a more objective and integrative approach on species delimitation. This may be especially relevant when dealing with cryptic species or species complexes, where high overall resemblance between species is coupled with comparatively high morphological variation within populations. Rock lizards, genus Darevskia, are such an example, as many of its members offer few diagnostic morphological features. Herein, we use a combination of genetic, morphological and ecological criteria to delimit cryptic species within two species complexes, D. chlorogaster and D. defilippii, both distributed in northern Iran. Our analyses are based on molecular information from two nuclear and two mitochondrial genes, morphological data (15 morphometric, 16 meristic and four categorical characters and eleven newly calculated spatial environmental predictors. The phylogeny inferred for Darevskia confirmed monophyly of each species complex, with each of them comprising several highly divergent clades, especially when compared to other congeners. We identified seven candidate species within each complex, of which three and four species were supported by Bayesian species delimitation within D. chlorogaster and D. defilippii, respectively. Trained with genetically determined clades, Ecological Niche Modeling provided additional support for these cryptic species. Especially those within the D. defilippii-complex exhibit well-differentiated niches. Due to overall morphological resemblance, in a first approach PCA with mixed variables only showed the separation between the two complexes. However, MANCOVA and subsequent Discriminant Analysis performed separately for both complexes allowed for distinction of the species when sample size was large enough, namely within the D. chlorogaster-complex. In conclusion, the results support four new species, which are described herein.

  2. Chocolate provides a unique sensory experience: uncovering the secret of the ‘chocolate craving’

    OpenAIRE

    Mara P. Squicciarini; Swinnen, Johan

    2016-01-01

    We are constantly being told that chocolate is bad for our health– but is it bad for our mind? Mara P. Squicciarini and Johan Swinnen share an excerpt from their book, The Economics of Chocolate, which provides an economic analysis, as well as an interdisciplinary overview on all things chocolate. Here they explore the benefits of chocolate consumption and the impact chocolate cravings have on our moods.

  3. Uncovering the Structure of and Gender and Developmental Differences in Cyber Bullying

    Science.gov (United States)

    Griezel, Lucy; Finger, Linda R.; Bodkin-Andrews, Gawaian H.; Craven, Rhonda G.; Yeung, Alexander Seeshing

    2012-01-01

    Although literature on traditional bullying is abundant, a limited body of sound empirical research exists regarding its newest form: cyber bullying. The sample comprised Australian secondary students (N = 803) and aimed to identify the underlying structure of cyber bullying, and differences in traditional and cyber bullying behaviors across…

  4. From hypothesis to mechanism: uncovering nuclear pore complex links to gene expression.

    Science.gov (United States)

    Burns, Laura T; Wente, Susan R

    2014-06-01

    The gene gating hypothesis put forth by Blobel in 1985 was an alluring proposal outlining functions for the nuclear pore complex (NPC) in transcription and nuclear architecture. Over the past several decades, collective studies have unveiled a full catalog of nucleoporins (Nups) that comprise the NPC, structural arrangements of Nups in the nuclear pore, and mechanisms of nucleocytoplasmic transport. With this foundation, investigations of the gene gating hypothesis have now become possible. Studies of several model organisms provide credence for Nup functions in transcription, mRNA export, and genome organization. Surprisingly, Nups are not only involved in transcriptional events that occur at the nuclear periphery, but there are also novel roles for dynamic Nups within the nucleoplasmic compartment. Several tenants of the original gene gating hypothesis have yet to be addressed. Knowledge of whether the NPC impacts the organization of the genome to control subsets of genes is limited, and the cooperating molecular machinery or specific genomic anchoring sequences are not fully resolved. This minireview summarizes the current evidence for gene gating in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mammalian model systems. These examples highlight new and unpredicted mechanisms for Nup impacts on transcription and questions that are left to be explored. PMID:24615017

  5. Uncovering the planets and stellar activity of CoRoT-7 using only radial velocities

    CERN Document Server

    Faria, J P; Brewer, B J; Figueira, P; Oshagh, M; Santerne, A; Santos, N C

    2016-01-01

    Stellar activity can induce signals in the radial velocities of stars, complicating the detection of orbiting low-mass planets. We present a method to determine the number of planetary signals present in radial-velocity datasets of active stars, using only radial-velocity observations. Instead of considering separate fits with different number of planets, we use a birth-death Markov chain Monte Carlo algorithm to infer the posterior distribution for the number of planets in a single run. In a natural way, the marginal distributions for the orbital parameters of all planets are also inferred. This method is applied to HARPS data of CoRoT-7. We confidently recover both CoRoT-7b and CoRoT-7c although the data show evidence for additional signals.

  6. Using giant scarlet runner bean embryos to uncover regulatory networks controlling suspensor gene activity

    OpenAIRE

    Henry, Kelli F.; Goldberg, Robert B.

    2015-01-01

    One of the major unsolved issues in plant development is understanding the regulatory networks that control the differential gene activity that is required for the specification and development of the two major embryonic regions, the embryo proper and suspensor. Historically, the giant embryo of scarlet runner bean (SRB), Phaseolus coccineus, has been used as a model system to investigate the physiological events that occur early in embryogenesis—focusing on the question of what role the susp...

  7. Uncovering the volatile nature of tropical coastal marine ecosystems in a changing world.

    Science.gov (United States)

    Exton, Dan A; McGenity, Terry J; Steinke, Michael; Smith, David J; Suggett, David J

    2015-04-01

    Biogenic volatile organic compounds (BVOCs), in particular dimethyl sulphide (DMS) and isoprene, have fundamental ecological, physiological and climatic roles. Our current understanding of these roles is almost exclusively established from terrestrial or oceanic environments but signifies a potentially major, but largely unknown, role for BVOCs in tropical coastal marine ecosystems. The tropical coast is a transition zone between the land and ocean, characterized by highly productive and biodiverse coral reefs, seagrass beds and mangroves, which house primary producers that are amongst the greatest emitters of BVOCs on the planet. Here, we synthesize our existing understanding of BVOC emissions to produce a novel conceptual framework of the tropical marine coast as a continuum from DMS-dominated reef producers to isoprene-dominated mangroves. We use existing and previously unpublished data to consider how current environmental conditions shape BVOC production across the tropical coastal continuum, and in turn how BVOCs can regulate environmental stress tolerance or species interactions via infochemical networks. We use this as a framework to discuss how existing predictions of future tropical coastal BVOC emissions, and the roles they play, are effectively restricted to present day 'baseline' trends of BVOC production across species and environmental conditions; as such, there remains a critical need to focus research efforts on BVOC responses to rapidly accelerating anthropogenic impacts at local and regional scales. We highlight the complete lack of current knowledge required to understand the future ecological functioning of these important systems, and to predict whether feedback mechanisms are likely to regulate or exacerbate current climate change scenarios through environmentally and ecologically mediated changes to BVOC budgets at the ecosystem level. PMID:25311223

  8. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

    Directory of Open Access Journals (Sweden)

    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  9. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates

    OpenAIRE

    Daniel Boloc; Sergio Castillo-Lara; Gemma Marfany; Roser Gonzàlez-Duarte; Abril, Josep F

    2015-01-01

    BACKGROUND: Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD g...

  10. Wave energy budget analysis in the Earth's radiation belts uncovers a missing energy

    OpenAIRE

    Artemyev, A.V.; Agapitov, O. V.; D. Mourenas; Krasnoselskikh, V. V.; Mozer, F. S.

    2015-01-01

    Whistler-mode emissions are important electromagnetic waves pervasive in the Earth's magnetosphere, where they continuously remove or energize electrons trapped by the geomagnetic field, controlling radiation hazards to satellites and astronauts and the upper-atmosphere ionization or chemical composition. Here, we report an analysis of 10-year Cluster data, statistically evaluating the full wave energy budget in the Earth's magneto-sphere, revealing that a significant fraction of the energy c...

  11. Uncovering co-expression gene network regulating fruit acidity in diverse apples

    Science.gov (United States)

    Acidity is a major contributor to fruit quality. Several organic acids are present in apple fruit, but malic acid is predominant and determines fruit acidity. The trait is largely controlled by the Malic acid (Ma) locus, underpinning which Ma1 that encodes an Aluminum-activated Malate Transporter1 (...

  12. Uncovering the true nature of deformation microstructures using 3D analysis methods

    Science.gov (United States)

    Ferry, M.; Quadir, M. Z.; Afrin, N.; Xu, W.; Loeb, A.; Soe, B.; McMahon, C.; George, C.; Bassman, L.

    2015-08-01

    Three-dimensional electron backscatter diffraction (3D EBSD) has emerged as a powerful technique for generating 3D crystallographic information in reasonably large volumes of a microstructure. The technique uses a focused ion beam (FIB) as a high precision serial sectioning device for generating consecutive ion milled surfaces of a material, with each milled surface subsequently mapped by EBSD. The successive EBSD maps are combined using a suitable post-processing method to generate a crystallographic volume of the microstructure. The first part of this paper shows the usefulness of 3D EBSD for understanding the origin of various structural features associated with the plastic deformation of metals. The second part describes a new method for automatically identifying the various types of low and high angle boundaries found in deformed and annealed metals, particularly those associated with grains exhibiting subtle and gradual variations in orientation. We have adapted a 2D image segmentation technique, fast multiscale clustering, to 3D EBSD data using a novel variance function to accommodate quaternion data. This adaptation is capable of segmenting based on subtle and gradual variation as well as on sharp boundaries within the data. We demonstrate the excellent capabilities of this technique with application to 3D EBSD data sets generated from a range of cold rolled and annealed metals described in the paper.

  13. Land Markets & Terrorism: Uncovering Perceptions of Risk by Examining Land Price Changes Following 9/11

    OpenAIRE

    Christian L. Redfearn

    2004-01-01

    This paper addresses the market's perception of risk from terrorism by examining the prices of single-family homes before and after the terrorist attacks on September 11th, 2001. In the wake of the attacks, government officials responded by raising security at sites considered to be likely targets of future attacks. In the greater Los Angeles metropolitan area, these included the Ports of Long Beach and Los Angeles, Los Angeles International airport, and several local civic centers, among oth...

  14. Uncovering phonological and orthographic selectivity across the reading network using fMRI-RA.

    Science.gov (United States)

    Glezer, Laurie S; Eden, Guinevere; Jiang, Xiong; Luetje, Megan; Napoliello, Eileen; Kim, Judy; Riesenhuber, Maximilian

    2016-09-01

    Reading has been shown to rely on a dorsal brain circuit involving the temporoparietal cortex (TPC) for grapheme-to-phoneme conversion of novel words (Pugh et al., 2001), and a ventral stream involving left occipitotemporal cortex (OTC) (in particular in the so-called "visual word form area", VWFA) for visual identification of familiar words. In addition, portions of the inferior frontal cortex (IFC) have been posited to be an output of the dorsal reading pathway involved in phonology. While this dorsal versus ventral dichotomy for phonological and orthographic processing of words is widely accepted, it is not known if these brain areas are actually strictly sensitive to orthographic or phonological information. Using an fMRI rapid adaptation technique we probed the selectivity of the TPC, OTC, and IFC to orthographic and phonological features during single word reading. We found in two independent experiments using different task conditions in adult normal readers, that the TPC is exclusively sensitive to phonology and the VWFA in the OTC is exclusively sensitive to orthography. The dorsal IFC (BA 44), however, showed orthographic but not phonological selectivity. These results support the theory that reading involves a specific phonological-based temporoparietal region and a specific orthographic-based ventral occipitotemporal region. The dorsal IFC, however, was not sensitive to phonological processing, suggesting a more complex role for this region. PMID:27252037

  15. Uncovering a law of corresponding states for electron tunneling in molecular junctions

    Science.gov (United States)

    Bâldea, Ioan; Xie, Zuoti; Frisbie, C. Daniel

    2015-06-01

    Laws of corresponding states known so far demonstrate that certain macroscopic systems can be described in a universal manner in terms of reduced quantities, which eliminate specific substance properties. To quantitatively describe real systems, all these laws of corresponding states contain numerical factors adjusted empirically. Here, we report a law of corresponding states deduced analytically for charge transport via tunneling in molecular junctions, which we validate against current-voltage measurements for conducting probe atomic force microscope junctions based on benchmark molecular series (oligophenylenedithiols and alkanedithiols) and electrodes (silver, gold, and platinum), as well as against transport data for scanning tunneling microscope junctions. Two salient features distinguish the present law of corresponding states from all those known previously. First, it is expressed by a universal curve free of empirical parameters. Second, it demonstrates that a universal behavior is not necessarily affected by strong stochastic fluctuations often observed in molecular electronics. An important and encouraging message of this finding is that transport behavior across different molecular platforms can be similar and extraordinarily reproducible.Laws of corresponding states known so far demonstrate that certain macroscopic systems can be described in a universal manner in terms of reduced quantities, which eliminate specific substance properties. To quantitatively describe real systems, all these laws of corresponding states contain numerical factors adjusted empirically. Here, we report a law of corresponding states deduced analytically for charge transport via tunneling in molecular junctions, which we validate against current-voltage measurements for conducting probe atomic force microscope junctions based on benchmark molecular series (oligophenylenedithiols and alkanedithiols) and electrodes (silver, gold, and platinum), as well as against transport data for scanning tunneling microscope junctions. Two salient features distinguish the present law of corresponding states from all those known previously. First, it is expressed by a universal curve free of empirical parameters. Second, it demonstrates that a universal behavior is not necessarily affected by strong stochastic fluctuations often observed in molecular electronics. An important and encouraging message of this finding is that transport behavior across different molecular platforms can be similar and extraordinarily reproducible. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02225h

  16. Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging.

    Directory of Open Access Journals (Sweden)

    Aviv Bergman

    2007-08-01

    Full Text Available An unrealized potential to understand the genetic basis of aging in humans, is to consider the immense survival advantage of the rare individuals who live 100 years or more. The Longevity Gene Study was initiated in 1998 at the Albert Einstein College of Medicine to investigate longevity genes in a selected population: the "oldest old" Ashkenazi Jews, 95 years of age and older, and their children. The study proved the principle that some of these subjects are endowed with longevity-promoting genotypes. Here we reason that some of the favorable genotypes act as mechanisms that buffer the deleterious effect of age-related disease genes. As a result, the frequency of deleterious genotypes may increase among individuals with extreme lifespan because their protective genotype allows disease-related genes to accumulate. Thus, studies of genotypic frequencies among different age groups can elucidate the genetic determinants and pathways responsible for longevity. Borrowing from evolutionary theory, we present arguments regarding the differential survival via buffering mechanisms and their target age-related disease genes in searching for aging and longevity genes. Using more than 1,200 subjects between the sixth and eleventh decades of life (at least 140 subjects in each group, we corroborate our hypotheses experimentally. We study 66 common allelic site polymorphism in 36 candidate genes on the basis of their phenotype. Among them we have identified a candidate-buffering mechanism and its candidate age-related disease gene target. Previously, the beneficial effect of an advantageous cholesteryl ester transfer protein (CETP-VV genotype on lipoprotein particle size in association with decreased metabolic and cardiovascular diseases, as well as with better cognitive function, have been demonstrated. We report an additional advantageous effect of the CETP-VV (favorable genotype in neutralizing the deleterious effects of the lipoprotein(a (LPA gene. Finally, using literature-based interaction discovery methods, we use the set of longevity genes, buffering genes, and their age-related target disease genes to construct the underlying subnetwork of interacting genes that is expected to be responsible for longevity. Genome wide, high-throughput hypothesis-free analyses are currently being utilized to elucidate unknown genetic pathways in many model organisms, linking observed phenotypes to their underlying genetic mechanisms. The longevity phenotype and its genetic mechanisms, such as our buffering hypothesis, are similar; thus, the experimental corroboration of our hypothesis provides a proof of concept for the utility of high-throughput methods for elucidating such mechanisms. It also provides a framework for developing strategies to prevent some age-related diseases by intervention at the appropriate level.

  17. Uncovering the secrets of the 2d random-bond Blume-Capel model

    OpenAIRE

    Malakis, A.; Berker, A. Nihat; Hadjiagapiou, I. A.; Fytas, N. G.; Papakonstantinou, T.

    2009-01-01

    The effects of bond randomness on the ground-state structure, phase diagram and critical behavior of the square lattice ferromagnetic Blume-Capel (BC) model are discussed. The calculation of ground states at strong disorder and large values of the crystal field is carried out by mapping the system onto a network and we search for a minimum cut by a maximum flow method. In finite temperatures the system is studied by an efficient two-stage Wang-Landau (WL) method for several values of the crys...

  18. Yellowhammers.net: Citizen science projects uncovering mysteries of distribution of Yellowhammer (Emberiza citrinella) song dialects

    Czech Academy of Sciences Publication Activity Database

    Diblíková, L.; Pipek, P.; Svoboda, J.; Vermouzek, Z.; Telenský, T.; Procházka, Petr; Petrusek, A.; Petrusková, T.

    Newcastle: Newcastle University, 2013. P258. [International Ethological Conference /33./. 04.08.2013-08.08.2013, Newcastle-Gateshead] Institutional support: RVO:68081766 Keywords : Yellowhammer Subject RIV: EG - Zoology http://iec2013.com/downloads/abstractbook.pdf

  19. Connectivity mapping uncovers small molecules that modulate neurodegeneration in Huntington’s disease models

    OpenAIRE

    Joshua L Smalley; Breda, Carlo; Mason, Robert P.; Kooner, Gurdeep; Luthi-Carter, Ruth; Gant, Timothy W.; Giorgini, Flaviano

    2015-01-01

    Abstract Huntington’s disease (HD) is a genetic disease caused by a CAG trinucleotide repeat expansion encoding a polyglutamine tract in the huntingtin (HTT) protein, ultimately leading to neuronal loss and consequent cognitive decline and death. As no treatments for HD currently exist, several chemical screens have been performed using cell-based models of mutant HTT toxicity. These screens measured single disease-related endpoints, such as cell death, but had low ‘hit rates’ and limited dim...

  20. Uncovering Norway’s regional disparities with respect to natural riches

    Directory of Open Access Journals (Sweden)

    Sevil Acar

    2015-03-01

    Full Text Available This study aims at unveiling regional development differences in Norway with respect to various natural resource-based activities that take place in the NUTS 3 regions. Norway’s natural riches range from agricultural and forest resources to fisheries, mines, petroleum and gas. Considering the possible spatial links for various regional characteristics of the Norwegian economy, this study does not only reveal the wide-ranging distribution of resource-based activities, but also sheds light on divergent income and population patterns in the Norwegian regions. Besides, these patterns are investigated through a number of models that test the impact of employment, investment and value added in natural resource sectors on regional differences. The main findings suggest that mining and quarrying as well as oil and gas extraction activities generate significant advantages for regional income generation whereas each resource type affects the distribution of population in a different way.

  1. Uncovering underlying processes of semantic priming by correlating item-level effects.

    Science.gov (United States)

    Heyman, Tom; Hutchison, Keith A; Storms, Gert

    2016-04-01

    The current study examines the underlying processes of semantic priming using the largest priming database available (i.e., Semantic Priming Project, Hutchison et al. Behavior Research Methods, 45(4), 1099-1114, 2013). Specifically, it compares priming effects in two tasks: lexical decision and pronunciation. Task similarities were assessed at two different stimulus onset asynchronies (SOAs) (i.e., 200 and 1,200 ms) and for both primary and other associates. To evaluate how consistent priming is across these two tasks, item-level priming effects obtained in each task were correlated for each condition separately. The results revealed significant correlations at the short SOA for both primary and other associates. The correlations at the long SOA were significantly smaller and only reached significance when z-transformed response times were used. Furthermore, this pattern remained essentially the same when only asymmetric forward associates (e.g., panda-bear) were considered, suggesting that the cross-task stability at the short SOA was not merely caused by retrospective processes such as semantic matching. Instead, these findings provide evidence for a rapidly operating, item-based, relational characteristic such as spreading activation. PMID:26335412

  2. The extended halo of Centaurus A: uncovering satellites, streams and substructures

    CERN Document Server

    Crnojević, D; Spekkens, K; Caldwell, N; Guhathakurta, P; McLeod, B; Seth, A; Simon, J; Strader, J; Toloba, E

    2015-01-01

    We present the widest-field resolved stellar map to date of the closest ($D\\sim3.8$ Mpc) massive elliptical galaxy NGC 5128 (Centaurus A; Cen A), extending out to a projected galactocentric radius of $\\sim150$ kpc. The dataset is part of our ongoing Panoramic Imaging Survey of Centaurus and Sculptor (PISCeS) utilizing the Magellan/Megacam imager. We resolve a population of old red giant branch stars down to $\\sim1.5$ mag below the tip of the red giant branch, reaching surface brightness limits as low as $\\mu_{V,0}\\sim32$ mag arcsec$^{-2}$. The resulting spatial stellar density map highlights a plethora of previously unknown streams, shells, and satellites, including the first tidally disrupting dwarf around Cen A, which underline its active accretion history. We report 13 previously unknown dwarf satellite candidates, of which 9 are confirmed to be at the distance of Cen A (the remaining 4 are not resolved into stars), with magnitudes in the range $M_V=-7.2$ to $-13.0$, central surface brightness values of $\\...

  3. Uncovering sibling species in Radiolaria: evidence for ecological partitioning in a marine planktonic protist.

    Science.gov (United States)

    Ishitani, Yoshiyuki; Ujiié, Yurika; Takishita, Kiyotaka

    2014-09-01

    Phylogeography of unicellular plankton, as representative pelagic organisms, is fundamental to understanding their evolution in the ocean. Historically, these microplankton were believed to have cosmopolitan distributions achieved through passive transport and little potential for speciation because of a lack of geographic barriers in the oceans. Recent phylogeographic studies of these microplankton, however, have often revealed high diversity and fine-scale geographic distributions. These apparent contradictions may result from poor knowledge of the spatial distributions of pelagic microplankton in the water column. More information about both geographic and vertical distributions of pelagic populations could reveal the dispersal pathways, gene flow, and resulting diversifications in the open ocean. Here we demonstrate that two genetic types of the radiolarian morphospecies Spongotrochus glacialis with morphological differences are vertically segregated into the upper and lower surface waters within the pycnocline of the North Pacific Subtropical Water. This vertically separated distribution of two sister species is associated with distinct ecological partitioning. These two species could survive on different food resources from their respective environments: one in oligotrophic surface waters by using nutrients from symbionts, and the other at greater depths by depending on both heterotrophic and symbiotic nutrition. Moreover, molecular divergence-time estimates suggest that the two species diverged during the period of oligotrophic surface-water development in the Pacific Ocean. Our findings suggest that genetic isolation in the vertical dimension occurs through ecological partitioning even in the absence of physical barriers in the pelagic oceans. PMID:24862224

  4. HerMES: Clusters of Dusty Galaxies Uncovered by Herschel and Planck

    CERN Document Server

    Clements, D L; Hyde, A; Perez-Fournon, I; Bock, J; Cava, A; Chapman, S; Conley, A; Cooray, A; Farrah, D; Solares, E A Gonzalez; Marchetti, L; Marsden, G; Oliver, S J; Roseboom, I G; Schulz, B; Smith, A J; Vaccari, M; Vieira, J; Viero, M; Wang, L; Wardlow, J; Zemcov, M; de Zotti, G

    2013-01-01

    The potential for Planck to detect clusters of dusty, star-forming galaxies at z greater than 1 is tested by examining the Herschel-SPIRE images of Planck Early Release Compact Source Catalog (ERCSC) sources lying in fields observed by the HerMES survey. Of the 16 Planck sources that lie in the roughly 90 sq. deg. examined, we find that twelve are associated with single bright Herschel sources. The remaining four are associated with overdensities of Herschel sources, making them candidate clusters of dusty, starforming galaxies. We use complementary optical and NIR data for these clumps to test this idea, and find evidence for the presence of galaxy clusters in all four cases. We use photometric redshifts and red sequence galaxies to estimate the redshifts of these clusters, finding that they range from 0.8 to 2.3. These redshifts imply that the Herschel sources in these clusters, which contribute to the detected Planck flux, are forming stars very rapidly, with typical total cluster star formation rates grea...

  5. Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise

    Directory of Open Access Journals (Sweden)

    Catarina Correia

    2014-09-01

    Full Text Available Hundreds of genetic variants have been associated to common diseases through genome-wide association studies (GWAS, yet there are limits to current approaches in detecting true small effect risk variants against a background of false positive findings. Here we addressed the missing heritability problem, aiming to test whether there are indeed risk variants within GWAS statistical noise and to develop a systematic strategy to retrieve these hidden variants. Employing an integrative approach, which combines protein-protein interactions with association data from GWAS for 6 common diseases, we found that associated-genes at less stringent significance levels (p < 0.1 with any of these diseases are functionally connected beyond noise expectation. This functional coherence was used to identify disease-relevant subnetworks, which were shown to be enriched in known genes, outperforming the selection of top GWAS genes. As a proof of principle, we applied this approach to breast cancer, supporting well-known breast cancer genes, while pinpointing novel susceptibility genes for experimental validation. This study reinforces the idea that GWAS are under-analyzed and that missing heritability is rather hidden. It extends the use of protein networks to reveal this missing heritability, thus leveraging the large investment in GWAS that produced so far little tangible gain.

  6. Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise

    OpenAIRE

    Catarina Correia; Yoan Diekmann; Vicente, Astrid M; Pereira-Leal, José B.

    2014-01-01

    Hundreds of genetic variants have been associated to common diseases through genome-wide association studies (GWAS), yet there are limits to current approaches in detecting true small effect risk variants against a background of false positive findings. Here we addressed the missing heritability problem, aiming to test whether there are indeed risk variants within GWAS statistical noise and to develop a systematic strategy to retrieve these hidden variants. Employing an integrative approach,...

  7. Kinds versus continua: a review of psychometric approaches to uncover the structure of psychiatric constructs.

    Science.gov (United States)

    Borsboom, D; Rhemtulla, M; Cramer, A O J; van der Maas, H L J; Scheffer, M; Dolan, C V

    2016-06-01

    The question of whether psychopathology constructs are discrete kinds or continuous dimensions represents an important issue in clinical psychology and psychiatry. The present paper reviews psychometric modelling approaches that can be used to investigate this question through the application of statistical models. The relation between constructs and indicator variables in models with categorical and continuous latent variables is discussed, as are techniques specifically designed to address the distinction between latent categories as opposed to continua (taxometrics). In addition, we examine latent variable models that allow latent structures to have both continuous and categorical characteristics, such as factor mixture models and grade-of-membership models. Finally, we discuss recent alternative approaches based on network analysis and dynamical systems theory, which entail that the structure of constructs may be continuous for some individuals but categorical for others. Our evaluation of the psychometric literature shows that the kinds-continua distinction is considerably more subtle than is often presupposed in research; in particular, the hypotheses of kinds and continua are not mutually exclusive or exhaustive. We discuss opportunities to go beyond current research on the issue by using dynamical systems models, intra-individual time series and experimental manipulations. PMID:26997244

  8. An orphan gyrB in the Mycobacterium smegmatis genome uncovered by comparative genomics

    Indian Academy of Sciences (India)

    P. Jain; V. Nagaraja

    2002-11-01

    DNA gyrase is an essential topoisomerase found in all bacteria. It is encoded by gyrB and gyrA genes. These genes are organized differently in different bacteria. Direct comparison of Mycobacterium tuberculosis and Mycobacterium smegmatis genomes reveals presence of an additional gyrB in M. smegmatis flanked by novel genes. Analysis of the amino acid sequence of GyrB from different organisms suggests that the orphan GyrB in M. smegmatis may have an important cellular role.

  9. The emotional Stroop-task: towards uncovering emotional picture-word interference

    OpenAIRE

    Sutmuller, A.D.

    2008-01-01

    This report is an exploration of the emotional (affective) picture-word variant of the well-known Stroop-task, The Stroop ‘concept’ is that human information processing takes longer when conflicting (emotional) information is presented. By measuring reaction-times in well-controlled experiments, it offers a relatively simple and objectiveway to probe the human mind. An experiment was conducted in which 8participants were presented with emotionally charged images and superimposed words. The em...

  10. Uncovering the Hidden Web, Part I: Finding What the Search Engines Don't. ERIC Digest.

    Science.gov (United States)

    Mardis, Marcia

    Currently, the World Wide Web contains an estimated 7.4 million sites (OCLC, 2001). Yet even the most experienced searcher, using the most robust search engines, can access only about 16% of these pages (Dahn, 2001). The other 84% of the publicly available information on the Web is referred to as the "hidden,""invisible," or "deep" Web. This…

  11. NIH mice study uncovers pathway critical for UV-induced melanoma

    Science.gov (United States)

    Scientists have made an unanticipated discovery in mice that interferon-gamma, a type of protein primarily used by the immune system for intercellular communication, acts as a promoter for the deadly form of skin cancer known as melanoma.

  12. Uncovering the Spectral Energy Distribution in Active Galaxies Using High Ionization Mid-Infrared Emission Lines

    Science.gov (United States)

    Melendez, M.; Kraemer, S. B.; Weaver, K. A.; Mushotzky, R. F.

    2011-01-01

    The shape of the spectral energy distribution of active galaxies in the EUV soft X-ray band (13.6 eV to 1 keV) is uncertain because obscuration by dust and gas can hamper our view of the continuum. To investigate the shape of the spectral energy distribution in this energy band, we have generated a set of photoionization models which reproduce the small dispersion found in correlations between high-ionization mid-infrared emission lines in a sample of hard X-ray selected AGN. Our calculations show that a broken power-law continuum model is sufficient to reproduce the [Ne V]14.32 microns/[Ne III], [Ne V]24.32 microns/[O IV]25.89 micron and [O IV] 25.89 microns/[Ne III] ratios, and does not require the addition of a "big bump" EUV model component. We constrain the EUV-soft X-ray slope, alpha(sub i), to be between 1.5 - 2.0 and derive a best fit of alpha(sub i) approx. 1.9 for Seyfert 1 galaxies, consistent with previous studies of intermediate redshift quasars. If we assume a blue bump model, most sources in our sample have derived temperatures between T(sub BB) = 10(exp 5.18) K to 10(exp 5.7) K, suggesting that the peak of this component spans a large range of energies extending from approx. (Lambda)600 A to > (Lambda)1900 A. In this case, the best fitting peak energy that matches the mid-infrared line ratios of Seyfert 1 galaxies occurs between approx. (Lambda)700-(Lambda)1000 A. Despite the fact that our results do not rule out the presence of an EUV bump, we conclude that our power-law model produces enough photons with energies > 4 Ry to generate the observed amount of mid-infrared emission in our sample of BAT AGN.

  13. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Yannan Fan

    Full Text Available The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet knock-in context (Del-R26(Met reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an RTK when occurring in its endogenous domain of activity.

  14. Uncovering Spatio-Temporal Cluster Patterns Using Massive Floating Car Data

    Directory of Open Access Journals (Sweden)

    Yifang Ban

    2013-05-01

    Full Text Available In this paper, we explore spatio-temporal clusters using massive floating car data from a complex network perspective. We analyzed over 85 million taxicab GPS points (floating car data collected in Wuhan, Hubei, China. Low-speed and stop points were selected to generate spatio-temporal clusters, which indicated the typical stop-and-go movement pattern in real-world traffic congestion. We found that the sizes of spatio-temporal clusters exhibited a power law distribution. This implies the presence of a scaling property; i.e., they can be naturally divided into a strong hierarchical structure: long time-duration ones (a low percentage whose values lie above the mean value and short ones (a high percentage whose values lie below. The spatio-temporal clusters at different levels represented the degree of traffic congestions, for example the higher the level, the worse the traffic congestions. Moreover, the distribution of traffic congestions varied spatio-temporally and demonstrated a multinuclear structure in urban road networks, which suggested there is a correlation to the corresponding internal mobile regularities of an urban system.

  15. Developing Guidance Material To Uncover a Mathematics Profile of Adult Participants on a Crane Course.

    Science.gov (United States)

    Lindenskov, Lena

    This paper reports on a pilot study in the Danish "Profile in Mathematics" project implemented by the Directorate General for Employment, Placement and Vocational Training and the Ministry of Education. The pilot study develops and tests specific guidance materials to guide participants and teachers through a course for crane workers that teaches…

  16. SNP and Mutation Data on the Web – Hidden Treasures for Uncovering

    OpenAIRE

    Barnes, Michael R.

    2002-01-01

    SNP data has grown exponentially over the last two years, SNP database evolution has matched this growth, as initial development of several independent SNP databases has given way to one central SNP database, dbSNP. Other SNP databases have instead evolved to complement this central database by providing gene specific focus and an increased level of curation and analysis on subsets of data, derived from the central data set. By contrast, human mutation data, which has been collected over many...

  17. 9 Sgr: uncovering an O-type spectroscopic binary with an 8.6 year period

    OpenAIRE

    Rauw, G.; Sana, H.; Spano, M; Gosset, E.; Mahy, L.; Becker, M.; Eenens, P.

    2012-01-01

    The O-type object 9 Sgr is a well-known synchrotron radio emitter. This feature is usually attributed to colliding-wind binary systems, but 9 Sgr was long considered a single star. We have conducted a long-term spectroscopic monitoring of this star to investigate its multiplicity and search for evidence for wind-wind interactions. Radial velocities are determined and analysed using various period search methods. Spectral disentangling is applied to separate the spectra of the components of th...

  18. Searching for behavioral indicators of welfare in zoos: uncovering anticipatory behavior.

    Science.gov (United States)

    Watters, Jason V

    2014-01-01

    A current focus of zoo-based research aims to identify indicators of animal welfare. Reliable behavioral indicators of welfare are highly desirable as behavioral observation is non invasive and requires little in the way of specialized equipment and other costly resources-save for observer time. Anticipatory behavior is an indicator of an animal's sensitivity to reward and as such, it is a real-time indicator of animals' own perceptions of their well-being. In fact, anticipatory behavior may generate a positive affective state and thus be at least a brief manifestation of good welfare itself. The husbandry conditions of most captive animals are such that food acquisition and other positive outcomes are highly scheduled and easily signaled. These conditions promote the development of anticipatory behavior, yet little research has either documented or interpreted this behavior in zoo and aquarium animals. This commentary suggests that anticipatory behavior could be a useful tool for assessing welfare and calls upon zoo and aquarium researchers to begin to develop this tool by describing the behavior and the circumstances that lead to its modulation. PMID:25042907

  19. Uncovering surface area and micropores in almond shell biochars by rainwater wash.

    Science.gov (United States)

    Thomas Klasson, K; Uchimiya, Minori; Lima, Isabel M

    2014-09-01

    Biochars have been considered for adsorption of contaminants in soil and water, as well as conditioning and improving soil quality. Pore surface area is an important property of biochar. Biochars were created from shells of two almond varieties with different ash content. The pyrolysis was performed at 650 and 800°C for 40-240min. Significant surface areas developed at the higher temperature and at pyrolysis times of 120min and longer. Washing the materials in synthetic rainwater removed ash and exposed additional surface area, particularly in small-diameter pores. When results from low-ash almond shell biochars were compared with high-ash almond shell biochars, it was found that the pore distribution was more uniform for the high-ash starting material and almost independent of pyrolysis time or washing. The result from the washing study is important as it suggested that adsorptive properties may change once biochars are exposed to rainwater. PMID:24997909

  20. Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation.

    Science.gov (United States)

    Yamano, Koji; Queliconi, Bruno B; Koyano, Fumika; Saeki, Yasushi; Hirokawa, Takatsugu; Tanaka, Keiji; Matsuda, Noriyuki

    2015-10-16

    Damaged mitochondria are eliminated through autophagy machinery. A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser(65) by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. PMID:26260794