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Sample records for stable association complexes

  1. On the classification of complex vector bundles of stable rank

    Indian Academy of Sciences (India)

    , the tuples of cohomology classes on a compact, complex manifold, corresponding to the Chern classes of a complex vector bundle of stable rank. This classification becomes more effective on generalized flag manifolds, where the Lie ...

  2. On the classification of complex vector bundles of stable rank

    Indian Academy of Sciences (India)

    In the present paper, we study the classification of stable-rank bundles on some compact complex manifolds. First, we extend ... below the results obtained in this case (see Propositions 4.1–4.3 and Theorems 5.1–5.3 for .... In order to prove the converse inclusion, let (c1,...,cp+1) be a (p + 1)-tuple of coho- mology classes ...

  3. On the classification of complex vector bundles of stable rank

    Indian Academy of Sciences (India)

    a classification of all rank r complex vector bundles on X, for stable rank r ≥ n/2. A few partial answers to this question are known. For instance, a classical result of. Wu asserts that any couple of cohomology classes (c1,c2) ∈ H2(X, Z) × H4(X, Z) coincides with c(E) for a vector bundle E, on a basis X of dimension less than ...

  4. Reactivity of paraquat with sodium salicylate: formation of stable complexes.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge; de Pinho, Paula Guedes; Ferreira, António César Silva; Silva, Artur M S; Afonso, Carlos; Bastos, Maria de Lourdes; Remião, Fernando; Duarte, José Alberto; Carvalho, Félix

    2008-07-30

    Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ.

  5. Reactivity of paraquat with sodium salicylate: Formation of stable complexes

    International Nuclear Information System (INIS)

    Dinis-Oliveira, Ricardo Jorge; Guedes de Pinho, Paula; Ferreira, Antonio Cesar Silva; Silva, Artur M.S.; Afonso, Carlos; Bastos, Maria de Lourdes; Remiao, Fernando; Duarte, Jose Alberto; Carvalho, Felix

    2008-01-01

    Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ

  6. G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase.

    Science.gov (United States)

    Lavine, Natalie; Ethier, Nathalie; Oak, James N; Pei, Lin; Liu, Fang; Trieu, Phan; Rebois, R Victor; Bouvier, Michel; Hebert, Terence E; Van Tol, Hubert H M

    2002-11-29

    A large number of studies have demonstrated co-purification or co-immunoprecipitation of receptors with G proteins. We have begun to look for the presence of effector molecules in these receptor complexes. Co-expression of different channel and receptor permutations in COS-7 and HEK 293 cells in combination with co-immunoprecipitation experiments established that the dopamine D(2) and D(4), and beta(2)-adrenergic receptors (beta(2)-AR) form stable complexes with Kir3 channels. The D(4)/Kir3 and D(2) receptor/Kir3 interaction does not occur when the channel and receptor are expressed separately and mixed prior to immunoprecipitation, indicating that the interaction is not an artifact of the experimental protocol and reflects a biosynthetic event. The observed complexes are stable in that they are not disrupted by receptor activation or modulation of G protein alpha subunit function. However, using a peptide that binds Gbetagamma (betaARKct), we show that Gbetagamma is critical for dopamine receptor-Kir3 complex formation, but not for maintenance of the complex. We also provide evidence that Kir3 channels and another effector, adenylyl cyclase, are stably associated with the beta(2)-adrenergic receptor and can be co-immunoprecipitated by anti-receptor antibodies. Using bioluminescence resonance energy transfer, we have shown that in living cells under physiological conditions, beta(2)AR interacts directly with Kir3.1/3.4 and Kir3.1/3.2c heterotetramers as well as with adenylyl cyclase. All of these interactions are stable in the presence of receptor agonists, suggesting that these signaling complexes persist during signal transduction. In addition, we provide evidence that the receptor-effector complexes are also found in vivo. The observation that several G protein-coupled receptors form stable complexes with their effectors suggests that this arrangement might be a general feature of G protein-coupled signal transduction.

  7. Stable assembly of HIV-1 export complexes occurs cotranscriptionally

    DEFF Research Database (Denmark)

    Nawroth, Isabel; Mueller, Florian; Basyuk, Eugenia

    2014-01-01

    The HIV-1 Rev protein mediates export of unspliced and singly spliced viral transcripts by binding to the Rev response element (RRE) and recruiting the cellular export factor CRM1. Here, we investigated the recruitment of Rev to the transcription sites of HIV-1 reporters that splice either post......- or cotranscriptionally. In both cases, we observed that Rev localized to the transcription sites of the reporters and recruited CRM1. Rev and CRM1 remained at the reporter transcription sites when cells were treated with the splicing inhibitor Spliceostatin A (SSA), showing that the proteins associate with RNA prior...... to or during early spliceosome assembly. Fluorescence recovery after photobleaching (FRAP) revealed that Rev and CRM1 have similar kinetics as the HIV-1 RNA, indicating that Rev, CRM1, and RRE-containing RNAs are released from the site of transcription in one single export complex. These results suggest...

  8. Ranking stability and super-stable nodes in complex networks.

    Science.gov (United States)

    Ghoshal, Gourab; Barabási, Albert-László

    2011-07-19

    Pagerank, a network-based diffusion algorithm, has emerged as the leading method to rank web content, ecological species and even scientists. Despite its wide use, it remains unknown how the structure of the network on which it operates affects its performance. Here we show that for random networks the ranking provided by pagerank is sensitive to perturbations in the network topology, making it unreliable for incomplete or noisy systems. In contrast, in scale-free networks we predict analytically the emergence of super-stable nodes whose ranking is exceptionally stable to perturbations. We calculate the dependence of the number of super-stable nodes on network characteristics and demonstrate their presence in real networks, in agreement with the analytical predictions. These results not only deepen our understanding of the interplay between network topology and dynamical processes but also have implications in all areas where ranking has a role, from science to marketing.

  9. Complex cobordism and stable homotopy groups of spheres

    CERN Document Server

    Ravenel, Douglas C

    2003-01-01

    Since the publication of its first edition, this book has served as one of the few available on the classical Adams spectral sequence, and is the best account on the Adams-Novikov spectral sequence. This new edition has been updated in many places, especially the final chapter, which has been completely rewritten with an eye toward future research in the field. It remains the definitive reference on the stable homotopy groups of spheres. The first three chapters introduce the homotopy groups of spheres and take the reader from the classical results in the field though the computational aspects

  10. Pyridinophane platform for stable lanthanide(III) complexation.

    Science.gov (United States)

    Castro, Goretti; Bastida, Rufina; Macías, Alejandro; Pérez-Lourido, Paulo; Platas-Iglesias, Carlos; Valencia, Laura

    2013-05-20

    A detailed investigation of the solid state and solution structures of lanthanide(III) complexes with the macrocyclic ligand 2,11,20-triaza[3.3.3](2,6)pyridinophane (TPP) is reported. The solid state structures of 14 different Ln(3+) complexes have been determined using X-ray crystallography. The ligand is coordinating to the Ln(3+) ion by using its six nitrogen atoms, while nitrate or triflate anions and water molecules complete the metal coordination environments. The structure of the complexes in solution has been investigated by (1)H and (13)C NMR spectroscopy, as well as by DFT calculations (TPSSh model) performed in aqueous solution. The structures obtained from these calculations for the complexes with the lightest Ln(3+) ions (La-Sm) are in very good agreement with those determined by the analysis of the Ln(3+)-induced paramagnetic shifts. A structural change occurs across the lanthanide series at Sm(3+); the complexes of the large Ln(3+) ions (La-Nd) are chiral due to the nonplanar conformation of the macrocycle, and present effective C3v symmetries in solution as a consequence of a fast interconversion of two enantiomeric forms with C3 symmetry. The activation free energy for this enantiomerization process, as estimated by using DFT calculations, amounts to 33.0 kJ·mol(-1). The TPP ligand in the complexes of the heaviest Ln(3+) ions (Eu-Lu) presents a half-chair conformation, which results in C(s) symmetries in solution.

  11. Complex interferometry potential in case of sufficiently stable diagnostic system

    Science.gov (United States)

    Kalal, M.

    2016-06-01

    Classical interferometry is one of the key methods among active optical diagnostics. Its more advanced version, which allows recording and subsequent reconstruction of up to three sets of data using just one data object —a complex interferogram—was developed in the past and became known as complex interferometry. Employing this diagnostics, not only the usual phase shift, but also the amplitude of the probing beam as well as the fringe contrast (leading directly to the phase shift time derivative) can be reconstructed simultaneously from such a complex interferogram. In this paper it will be demonstrated that even in the case of a not particularly good diagnostic beam quality these three quantities can be reconstructed with a high degree of accuracy provided both the diagnostic beam as well as the corresponding optical line feature a reasonable stability. Such stability requirement is important as in an ideal case four shots need to be gradually recorded (one by one): the signal complex interferogram, the reference interferogram as well as the intensity structures of the signal and reference part of the diagnostic beam. Two examples of complex interferograms obtained in experiments will be analyzed: the laser produced plasma (spark in the air) and the high pressure gas jet. A general ray-tracing based iterative algorithm will be outlined in order to increase a precision of the index of refraction spatial profile taking into account refraction effects (omitted in the Abel inversion) and employing the original reconstructed phase shift and amplitude.

  12. Very stable high molecular mass multiprotein complex with DNase and amylase activities in human milk.

    Science.gov (United States)

    Soboleva, Svetlana E; Dmitrenok, Pavel S; Verkhovod, Timofey D; Buneva, Valentina N; Sedykh, Sergey E; Nevinsky, Georgy A

    2015-01-01

    For breastfed infants, human milk is more than a source of nutrients; it furnishes a wide array of proteins, peptides, antibodies, and other components promoting neonatal growth and protecting infants from viral and bacterial infection. It has been proposed that most biological processes are performed by protein complexes. Therefore, identification and characterization of human milk components including protein complexes is important for understanding the function of milk. Using gel filtration, we have purified a stable high molecular mass (~1000 kDa) multiprotein complex (SPC) from 15 preparations of human milk. Light scattering and gel filtration showed that the SPC was stable in the presence of high concentrations of NaCl and MgCl2 but dissociated efficiently under the conditions that destroy immunocomplexes (2 M MgCl2 , 0.5 M NaCl, and 10 mM DTT). Such a stable complex is unlikely to be a casual associate of different proteins. The relative content of the individual SPCs varied from 6% to 25% of the total milk protein. According to electrophoretic and mass spectrometry analysis, all 15 SPCs contained lactoferrin (LF) and α-lactalbumin as major proteins, whereas human milk albumin and β-casein were present in moderate or minor amounts; a different content of IgGs and sIgAs was observed. All SPCs efficiently hydrolyzed Plasmid supercoiled DNA and maltoheptaose. Some freshly prepared SPC preparations contained not only intact LF but also small amounts of its fragments, which appeared in all SPCs during their prolonged storage; the fragments, similar to intact LF, possessed DNase and amylase activities. LF is found in human epithelial secretions, barrier body fluids, and in the secondary granules of leukocytes. LF is a protein of the acute phase response and nonspecific defense against different types of microbial and viral infections. Therefore, LF complexes with other proteins may be important for its functions not only in human milk. Copyright © 2014

  13. Modelling of the flow of stable air over a complex region

    CSIR Research Space (South Africa)

    Scholtz, MT

    1976-01-01

    Full Text Available The flow of stable air over a general region of complex topography and non-uniform surface temperature has been investigated. In order to gain further understanding of the motion of surface air, it was necessary to study the vertical structure...

  14. Association theories for complex thermodynamics

    DEFF Research Database (Denmark)

    Kontogeorgis, Georgios; Rafiqul Gani

    2013-01-01

    models, we have now come to the understanding that simple one-fluid theories like the cubic equations of state or the various forms of local composition models will never be able to model a wide range of complex systems with sufficient accuracy. While various modern approaches have appeared, one very...

  15. Relation of ABO blood groups to coronary lesion complexity in patients with stable coronary artery disease.

    Science.gov (United States)

    Kaya, Ahmet; Tanboğa, İbrahim Halil; Kurt, Mustafa; Işık, Turgay; Kaya, Yasemin; Günaydın, Zeki Yüksel; Aksakal, Enbiya

    2014-02-01

    We aimed to investigate the relationship between ABO blood groups and complexity of coronary lesions assessed by SYNTAX score (SS) in stable coronary artery disease (CAD) patients. Our cross-sectional and observational study population consisted of 559 stable CAD patients. From all patients, ABO blood group was determined and the SS was calculated as low SYNTAX score (0-22), intermediate SYNTAX (23-32) score and high SYNTAX score (>32). Statistical analysis was performed using Student's t-test or Mann-Whitney U test, ANOVA, or Kruskal-Wallis test and chi-square test. Multiple logistic regression analysis was used to identify the independent predictors of high SS. The analysis between the SS tertiles revealed that the frequency of non-O blood group was significantly higher in the upper SS tertiles (56.2% vs. 75.9 vs. 80.2%, pABO blood groups and complexity of angiographic CAD.

  16. [Complex injuries associated with somnambulism].

    Science.gov (United States)

    Sillesen, Nanna Hylleholt; Nielsen, Lisa Toft; Bonde, Christian

    2010-12-13

    Up to 3% of adults walk in their sleep and some perform complex behaviours. Treatment recommendations for sleepwalking are inconsistent. This case report describes a 64-year-old man who climbed out of a 2nd floor toilet window during somnambulism. He fell 6-8 meters and fractured the tibia, fibula, cervical columna, lumbal columna, calcaneus, costae and suffered a pneumothorax. Evidence to support sleepwalking treatment is lacking and besides benzodiazepines, prevention is the preferred treatment choice according to the literature.

  17. Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.

    Directory of Open Access Journals (Sweden)

    Evgeniya E Burkova

    Full Text Available Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼ 1000 kDa from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs 4-14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions.

  18. Stable incorporation versus dynamic exchange of β subunits in a native Ca2+ channel complex.

    Science.gov (United States)

    Campiglio, Marta; Di Biase, Valentina; Tuluc, Petronel; Flucher, Bernhard E

    2013-05-01

    Voltage-gated Ca(2+) channels are multi-subunit membrane proteins that transduce depolarization into cellular functions such as excitation-contraction coupling in muscle or neurotransmitter release in neurons. The auxiliary β subunits function in membrane targeting of the channel and modulation of its gating properties. However, whether β subunits can reversibly interact with, and thus differentially modulate, channels in the membrane is still unresolved. In the present study we applied fluorescence recovery after photobleaching (FRAP) of GFP-tagged α1 and β subunits expressed in dysgenic myotubes to study the relative dynamics of these Ca(2+) channel subunits for the first time in a native functional signaling complex. Identical fluorescence recovery rates of both subunits indicate stable interactions, distinct recovery rates indicate dynamic interactions. Whereas the skeletal muscle β1a isoform formed stable complexes with CaV1.1 and CaV1.2, the non-skeletal muscle β2a and β4b isoforms dynamically interacted with both α1 subunits. Neither replacing the I-II loop of CaV1.1 with that of CaV2.1, nor deletions in the proximal I-II loop, known to change the orientation of β relative to the α1 subunit, altered the specific dynamic properties of the β subunits. In contrast, a single residue substitution in the α interaction pocket of β1aM293A increased the FRAP rate threefold. Taken together, these findings indicate that in skeletal muscle triads the homologous β1a subunit forms a stable complex, whereas the heterologous β2a and β4b subunits form dynamic complexes with the Ca(2+) channel. The distinct binding properties are not determined by differences in the I-II loop sequences of the α1 subunits, but are intrinsic properties of the β subunit isoforms.

  19. Highly active and stable oxaloacetate decarboxylase Na⁺ pump complex for structural analysis.

    Science.gov (United States)

    Inoue, Michio; Li, Xiaodan

    2015-11-01

    The oxaloacetate decarboxylase primary Na(+) pump (Oad) produces energy for the surviving of some pathogenic bacteria under anaerobic conditions. Oad composes of three subunits: Oad-α, a biotinylated soluble subunit and catalyzes the decarboxylation of oxaloacetate; Oad-β, a transmembrane subunit and functions as a Na(+) pump; and Oad-γ, a single transmembrane α-helical anchor subunit and assembles Oad-α/β/γ complex. The molecular mechanism of Oad complex coupling the exothermic decarboxylation to generate the Na(+) electrochemical gradient remains unsolved. Our biophysical and biochemical studies suggested that the stoichiometry of Oad complex from Vibrio cholerae composed of α, β, γ in 4:2:2 stoichiometry not that of 4:4:4. The high-resolution structure determination of the Oad complex would reveal the energetic transformation mechanism from the catalytical soluble α subunit to membrane β subunit. Sufficient amount stable, conformational homogenous and active Oad complex with the right stoichiometry is the prerequisite for structural analysis. Here we report an easy and reproducible protocol to obtain high quantity and quality Oad complex protein for structural analysis. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Water-stable fac-{TcO₃}⁺ complexes - a new field of technetium chemistry.

    Science.gov (United States)

    Braband, Henrik

    2011-01-01

    The development of technetium chemistry has been lagging behind that of its heavier congener rhenium, primarily because the inherent radioactivity of all Tc isotopes has limited the number of laboratories that can study the chemistry of this fascinating element. Although technetium is an artificial element, it is not rare. Significant amounts of the isotope (99)Tc are produced every day as a fission byproduct in nuclear power plants. Therefore, a fundamental understanding of the chemistry of (99)Tc is essential to avoid its release into the environment. In this article the chemistry of technetium at its highest oxidation state (+VII) is reviewed with a special focus on recent developments which make water-stable complexes of the general type [TcO(3)(tacn-R)](+) (tacn-R = 1,4,7-triazacyclononane or derivatives) accessible. Complexes containing the fac-{TcO(3)}(+) core display a unique reactivity. In analogy to [OsO(4)] and [RuO(4)], complexes containing the fac-{TcO(3)}(+) core undergo with alkenes metal-mediated, vicinal cis-dihydroxylation reactions (alkene-glycol interconversion) in water via a (3+2)-cycloaddition reaction. Therefore, water-stable fac-{(99m)TcO(3)}(+) complexes pave the way for a new labeling strategy for radiopharmaceutical applications, based on (3+2)-cycloaddition reactions. This new concept for the labeling of biomolecules with small [(99m)TcO(3)(tacn-R)](+)-type complexes by way of a (3+2)-cycloaddition with alkenes is discussed in detail. The herein reported developments in high-valent technetium chemistry create a new field of research with this artificial element. This demonstrates the potential of fundamental research to provide new impetus of innovation for the development of new methods for radiopharmaceutical applications.

  1. Cohesin rings devoid of Scc3 and Pds5 maintain their stable association with the DNA.

    Directory of Open Access Journals (Sweden)

    Irina Kulemzina

    Full Text Available Cohesin is a protein complex that forms a ring around sister chromatids thus holding them together. The ring is composed of three proteins: Smc1, Smc3 and Scc1. The roles of three additional proteins that associate with the ring, Scc3, Pds5 and Wpl1, are not well understood. It has been proposed that these three factors form a complex that stabilizes the ring and prevents it from opening. This activity promotes sister chromatid cohesion but at the same time poses an obstacle for the initial entrapment of sister DNAs. This hindrance to cohesion establishment is overcome during DNA replication via acetylation of the Smc3 subunit by the Eco1 acetyltransferase. However, the full mechanistic consequences of Smc3 acetylation remain unknown. In the current work, we test the requirement of Scc3 and Pds5 for the stable association of cohesin with DNA. We investigated the consequences of Scc3 and Pds5 depletion in vivo using degron tagging in budding yeast. The previously described DHFR-based N-terminal degron as well as a novel Eco1-derived C-terminal degron were employed in our study. Scc3 and Pds5 associate with cohesin complexes independently of each other and require the Scc1 "core" subunit for their association with chromosomes. Contrary to previous data for Scc1 downregulation, depletion of either Scc3 or Pds5 had a strong effect on sister chromatid cohesion but not on cohesin binding to DNA. Quantity, stability and genome-wide distribution of cohesin complexes remained mostly unchanged after the depletion of Scc3 and Pds5. Our findings are inconsistent with a previously proposed model that Scc3 and Pds5 are cohesin maintenance factors required for cohesin ring stability or for maintaining its association with DNA. We propose that Scc3 and Pds5 specifically function during cohesion establishment in S phase.

  2. A Stable Coordination Complex of Rh(IV) in an N,O-Donor Environment

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Shashi B. [Department of Chemistry, Yale University, 225 Prospect; Shopov, Dimitar Y. [Department of Chemistry, Yale University, 225 Prospect; Sharninghausen, Liam S. [Department of Chemistry, Yale University, 225 Prospect; Vinyard, David J. [Department of Chemistry, Yale University, 225 Prospect; Mercado, Brandon Q. [Department of Chemistry, Yale University, 225 Prospect; Brudvig, Gary W. [Department of Chemistry, Yale University, 225 Prospect; Crabtree, Robert H. [Department of Chemistry, Yale University, 225 Prospect

    2015-12-10

    We describe facial and meridional isomers of [RhIII(pyalk)3], as well as meridional [RhIV(pyalk)3]+ {pyalk =2-(2-pyridyl)-2-propanoate}, the first coordination complex in an N,O-donor environment to show a clean, reversible RhIII/IV redox couple and to have a stable Rh(IV) form, which we characterize by EPR and UV–visible spectroscopy as well as X-ray crystallography. The unprecedented stability of the Rh(IV) species is ascribed to the exceptional donor strength of the ligands, their oxidation resistance, and the meridional coordination geometry.

  3. Distribution tactics for success in turbulent versus stable environments: A complexity theory approach

    Directory of Open Access Journals (Sweden)

    Roger Bruce Mason

    2013-05-01

    Full Text Available This article proposes that the external environment influences the choice of distribution tactics. Since businesses and markets are complex adaptive systems, using complexity theory to understand such environments is necessary, but it has not been widely researched. A qualitative case method using in-depth interviews investigated four successful, versus less successful, companies in turbulent versus stable environments. The results tentatively confirmed that the more successful company, in a turbulent market, sees distribution activities as less important than other aspects of the marketing mix, but uses them to stabilise customer relationships and to maintain distribution processes. These findings can benefit marketers by emphasising a new way to consider place activities. How marketers can be assisted, and suggestions for further research, are provided.

  4. Distribution tactics for success in turbulent versus stable environments: A complexity theory approach

    Directory of Open Access Journals (Sweden)

    Roger Bruce Mason

    2013-11-01

    Full Text Available This article proposes that the external environment influences the choice of distribution tactics. Since businesses and markets are complex adaptive systems, using complexity theory to understand such environments is necessary, but it has not been widely researched. A qualitative case method using in-depth interviews investigated four successful, versus less successful, companies in turbulent versus stable environments. The results tentatively confirmed that the more successful company, in a turbulent market, sees distribution activities as less important than other aspects of the marketing mix, but uses them to stabilise customer relationships and to maintain distribution processes. These findings can benefit marketers by emphasising a new way to consider place activities. How marketers can be assisted, and suggestions for further research, are provided.

  5. Indefinitely stable iron(IV) cage complexes formed in water by air oxidation

    Science.gov (United States)

    Tomyn, Stefania; Shylin, Sergii I.; Bykov, Dmytro; Ksenofontov, Vadim; Gumienna-Kontecka, Elzbieta; Bon, Volodymyr; Fritsky, Igor O.

    2017-01-01

    In nature, iron, the fourth most abundant element of the Earth's crust, occurs in its stable forms either as the native metal or in its compounds in the +2 or +3 (low-valent) oxidation states. High-valent iron (+4, +5, +6) compounds are not formed spontaneously at ambient conditions, and the ones obtained synthetically appear to be unstable in polar organic solvents, especially aqueous solutions, and this is what limits their studies and use. Here we describe unprecedented iron(IV) hexahydrazide clathrochelate complexes that are assembled in alkaline aqueous media from iron(III) salts, oxalodihydrazide and formaldehyde in the course of a metal-templated reaction accompanied by air oxidation. The complexes can exist indefinitely at ambient conditions without any sign of decomposition in water, nonaqueous solutions and in the solid state. We anticipate that our findings may open a way to aqueous solution and polynuclear high-valent iron chemistry that remains underexplored and presents an important challenge.

  6. Concord grape pomace polyphenols complexed to soy protein isolate are stable and hypoglycemic in diabetic mice.

    Science.gov (United States)

    Roopchand, Diana E; Kuhn, Peter; Krueger, Christian G; Moskal, Kristin; Lila, Mary Ann; Raskin, Ilya

    2013-11-27

    Polyphenols extracted from Concord grape pomace were stabilized by complexation to soy protein isolate (SPI) to produce grape polyphenol-SPI complex (GP-SPI) containing 5% or 10% grape polyphenols. LC-MS and MALDI-TOF analysis showed that a broad range of phytochemicals were present in the grape pomace extract. Anthocyanins and total polyphenols in the GP-SPI complex were stable after a 16-week incubation at 37 °C but were reduced by up 60% in dried grape pomace extract. Compared to vehicle (236 ± 34 mg/dL), a single dose of 300 mg/kg GP-SPI (184 ± 32 mg/dL) or 500 mg/kg GP-SPI (177 ± 28 mg/dL) having 5% grape polyphenols significantly lowered blood glucose in obese and hyperglycemic C57BL/6 mice 6 h after administration. GP-SPI allows the capture of grape pomace polyphenols in a protein-rich food matrix and may be useful as a functional food ingredient for the management of blood glucose levels.

  7. Behavioural responses of stable flies to cattle manure slurry associated odourants

    Science.gov (United States)

    Stable flies (Stomoxys calcitrans [Diptera: Muscidae] L.) are blood-feeding synanthropic pests, which cause significant economic losses in livestock. Stable fly antennae contain olfactory sensilla responsive to host and host environment-associated odours. Field observation indicated that the abundan...

  8. Differential Associations Between Specific Depressive Symptoms and Cardiovascular Prognosis in Patients With Stable Coronary Heart Disease

    NARCIS (Netherlands)

    Hoen, Petra W.; Whooley, Mary A.; Martens, Elisabeth J.; Na, Beeya; van Melle, Joost P.; de Jonge, Peter

    2010-01-01

    Objectives The purpose of this research was to evaluate the relationship between cognitive and somatic depressive symptoms and cardiovascular prognosis. Background Depression in patients with stable coronary heart disease (CHD) is associated with poor cardiac prognosis. Whether certain depressive

  9. New glyme-cyclic imide lithium salt complexes as thermally stable electrolytes for lithium batteries

    Science.gov (United States)

    Tamura, Takashi; Hachida, Takeshi; Yoshida, Kazuki; Tachikawa, Naoki; Dokko, Kaoru; Watanabe, Masayoshi

    New glyme-Li salt complexes were prepared by mixing equimolar amounts of a novel cyclic imide lithium salt LiN(C 2F 4S 2O 4) (LiCTFSI) and a glyme (triglyme (G3) or tetraglyme (G4)). The glyme-Li salt complexes, [Li(G3)][CTFSI] and [Li(G4)][CTFSI], are solid and liquid, respectively, at room temperature. The thermal stability of [Li(G4)][CTFSI] is much higher than that of pure G4, and the vapor pressure of [Li(G4)][CTFSI] is negligible at temperatures lower than 100 °C. Although the viscosity of [Li(G4)][CTFSI] is high (132.0 mPa s at 30 °C), because of its high molar concentration (ca. 3 mol dm -3), its ionic conductivity at 30 °C is relatively high, i.e., 0.8 mS cm -1, which is slightly lower than that of a conventional organic electrolyte solution (1 mol dm -3 LiTFSI dissolved in propylene carbonate). The self-diffusion coefficients of a Li + cation, a CTFSI - anion, and a glyme molecule were measured by the pulsed gradient spin-echo NMR method (PGSE-NMR). The ionicity (dissociativity) of [Li(G4)][CTFSI] at 30 °C is ca. 0.5, as estimated from the PGSE-NMR diffusivity measurements and the ionic conductivity measurements. Results of linear sweep voltammetry revealed that [Li(G4)][CTFSI] is electrochemically stable in an electrode potential range of 0-4.5 V vs. Li/Li +. The reversible deposition-stripping behavior of lithium was observed by cyclic voltammetry. The [LiCoO 2|[Li(G4)][CTFSI]|Li metal] cell showed a stable charge-discharge cycling behavior during 50 cycles, indicating that the [Li(G4)][CTFSI] complex is applicable to a 4 V class lithium secondary battery.

  10. Stable cellular senescence is associated with persistent DDR activation.

    Science.gov (United States)

    Fumagalli, Marzia; Rossiello, Francesca; Mondello, Chiara; d'Adda di Fagagna, Fabrizio

    2014-01-01

    The DNA damage response (DDR) is activated upon DNA damage generation to promote DNA repair and inhibit cell cycle progression in the presence of a lesion. Cellular senescence is a permanent cell cycle arrest characterized by persistent DDR activation. However, some reports suggest that DDR activation is a feature only of early cellular senescence that is then lost with time. This challenges the hypothesis that cellular senescence is caused by persistent DDR activation. To address this issue, we studied DDR activation dynamics in senescent cells. Here we show that normal human fibroblasts retain DDR markers months after replicative senescence establishment. Consistently, human fibroblasts from healthy aged donors display markers of DDR activation even three years in culture after entry into replicative cellular senescence. However, by extending our analyses to different human cell strains, we also observed an apparent DDR loss with time following entry into cellular senescence. This though correlates with the inability of these cell strains to survive in culture upon replicative or irradiation-induced cellular senescence. We propose a model to reconcile these results. Cell strains not suffering the prolonged in vitro culture stress retain robust DDR activation that persists for years, indicating that under physiological conditions persistent DDR is causally involved in senescence establishment and maintenance. However, cell strains unable to maintain cell viability in vitro, due to their inability to cope with prolonged cell culture-associated stress, show an only-apparent reduction in DDR foci which is in fact due to selective loss of the most damaged cells.

  11. Calculation of equilibrium stable isotope partition function ratios for aqueous zinc complexes and metallic zinc

    Science.gov (United States)

    Black, Jay R.; Kavner, Abby; Schauble, Edwin A.

    2011-02-01

    The goal of this study is to determine reduced partition function ratios for a variety of species of zinc, both as a metal and in aqueous solutions in order to calculate equilibrium stable isotope partitioning. We present calculations of the magnitude of Zn stable-isotope fractionation ( 66,67,68Zn/ 64Zn) between aqueous species and metallic zinc using measured vibrational spectra (fit from neutron scattering studies of metallic zinc) and a variety of electronic structure models. The results show that the reduced metal, Zn(0), will be light in equilibrium with oxidized Zn(II) aqueous species, with the best estimates for the Zn(II)-Zn(0) fractionation between hexaquo species and metallic zinc being Δ 66/64Zn aq-metal ˜ 1.6‰ at 25 °C, and Δ 66/64Zn aq-metal ˜ 0.8‰ between the tetrachloro zinc complex and metallic zinc at 25 °C using B3LYP/aug-cc-pVDZ level of theory and basis set. To examine the behavior of zinc in various aqueous solution chemistries, models for Zn(II) complex speciation were used to determine which species are thermodynamically favorable and abundant under a variety of different conditions relevant to natural waters, experimental and industrial solutions. The optimal molecular geometries for [Zn(H 2O) 6] 2+, [Zn(H 2O) 6]·SO 4, [ZnCl 4] 2- and [Zn(H 2O) 3(C 3H 5O(COO) 3)] - complexes in various states of solvation, protonation and coordination were calculated at various levels of electronic structure theory and basis set size. Isotopic reduced partition function ratios were calculated from frequency analyses of these optimized structures. Increasing the basis set size typically led to a decrease in the calculated reduced partition function ratios of ˜0.5‰ with values approaching a plateau using the aug-cc-pVDZ basis set or larger. The widest range of species were studied at the B3LYP/LAN2DZ/6-31G ∗ level of theory and basis-set size for comparison. Aqueous zinc complexes where oxygen is bound to the metal center tended to have the

  12. On the interconnection of stable protein complexes: inter-complex hubs and their conservation in Saccharomyces cerevisiae and Homo sapiens networks.

    Science.gov (United States)

    Guerra, Concettina

    2015-01-01

    Protein complexes are key molecular entities that perform a variety of essential cellular functions. The connectivity of proteins within a complex has been widely investigated with both experimental and computational techniques. We developed a computational approach to identify and characterise proteins that play a role in interconnecting complexes. We computed a measure of inter-complex centrality, the crossroad index, based on disjoint paths connecting proteins in distinct complexes and identified inter-complex hubs as proteins with a high value of the crossroad index. We applied the approach to a set of stable complexes in Saccharomyces cerevisiae and in Homo sapiens. Just as done for hubs, we evaluated the topological and biological properties of inter-complex hubs addressing the following questions. Do inter-complex hubs tend to be evolutionary conserved? What is the relation between crossroad index and essentiality? We found a good correlation between inter-complex hubs and both evolutionary conservation and essentiality.

  13. Human Cytomegalovirus gH/gL Forms a Stable Complex with the Fusion Protein gB in Virions.

    Directory of Open Access Journals (Sweden)

    Adam L Vanarsdall

    2016-04-01

    Full Text Available Human cytomegalovirus (HCMV is a ubiquitous virus that is a major pathogen in newborns and immunocompromised or immunosuppressed patients. HCMV infects a wide variety of cell types using distinct entry pathways that involve different forms of the gH/gL glycoprotein: gH/gL/gO and gH/gL/UL128-131 as well as the viral fusion glycoprotein, gB. However, the minimal or core fusion machinery (sufficient for cell-cell fusion is just gH/gL and gB. Here, we demonstrate that HCMV gB and gH/gL form a stable complex early after their synthesis and in the absence of other viral proteins. gH/gL can interact with gB mutants that are unable to mediate cell-cell fusion. gB-gH/gL complexes included as much as 16-50% of the total gH/gL in HCMV virus particles. In contrast, only small amounts of gH/gL/gO and gH/gL/UL128-131 complexes were found associated with gB. All herpesviruses express gB and gH/gL molecules and most models describing herpesvirus entry suggest that gH/gL interacts with gB to mediate membrane fusion, although there is no direct evidence for this. For herpes simplex virus (HSV-1 it has been suggested that after receptor binding gH/gL binds to gB either just before, or coincident with membrane fusion. Therefore, our results have major implications for these models, demonstrating that HCMV gB and gH/gL forms stable gB-gH/gL complexes that are incorporated virions without receptor binding or membrane fusion. Moreover, our data is the best support to date for the proposal that gH/gL interacts with gB.

  14. Foraging Strategies of Laysan Albatross Inferred from Stable Isotopes: Implications for Association with Fisheries.

    Directory of Open Access Journals (Sweden)

    Ann E Edwards

    Full Text Available Fatal entanglement in fishing gear is the leading cause of population decline for albatross globally, a consequence of attraction to bait and fishery discards of commercial fishing operations. We investigated foraging strategies of Laysan albatross (Phoebastria immutabilis, as inferred from nitrogen and carbon isotope values of primary feathers, to determine breeding-related, seasonal, and historic factors that may affect the likelihood of association with Alaskan or Hawaiian longline fisheries. Feather samples were collected from live birds monitored for breeding status and breeding success on Midway Atoll in the northwestern Hawaiian Islands, birds salvaged as fisheries-bycatch, and birds added to museum collections before 1924. During the chick-rearing season (sampled April-May, means and variances of stable isotope values of birds with the highest, most consistent reproductive success were distinct from less productive conspecifics and completely different from birds caught in Hawaiian or Alaskan longline fisheries, suggesting birds with higher multi-annual reproductive success were less likely to associate with these fisheries. Contemporary birds with the highest reproductive success had mean values most similar to historic birds. Values of colony-bound, courting prebreeders were similar to active breeders but distinct from prebreeders caught in Alaskan longline fisheries. During the breeding season, δ15N values were highly variable for both contemporary and historic birds. Although some historic birds exhibited extremely low δ15N values unmatched by contemporary birds (< 11.2‰, others had values as high as the highest fishery-associated contemporary birds. During the non-breeding season (sampled July-September, isotopic variability coalesced into a more narrow set of values for both contemporary and historic birds. Our results suggest that foraging strategies of Laysan albatross are a complex function of season, breeding status, and

  15. Raf-1 forms a stable complex with Mek1 and activates Mek1 by serine phosphorylation.

    OpenAIRE

    Huang, W; Alessandrini, A; Crews, C M; Erikson, R L

    1993-01-01

    Recombinant Mek1 and Raf-1 proteins produced in Sf9 cells undergo a tight association both in vivo and in vitro, which apparently does not depend on additional factors or the kinase activity of Mek1 or Raf-1. The complex can be disrupted by two polyclonal antibodies raised against Raf-1 peptides. Coinfection with Raf-1 activates Mek1 > 150-fold, and coinfection with Raf-1 and Mek1 activates Erk1 approximately 90-fold. The activation of Mek1 by Raf-1 involves only serine phosphorylation, which...

  16. Extension of association models to complex chemicals

    DEFF Research Database (Denmark)

    Avlund, Ane Søgaard

    ; CPA and sPC-SAFT. Phase equilibrium and monomer fraction calculations with sPC-SAFT for methanol are used in the thesis to illustrate the importance of parameter estimation when using SAFT. Different parameter sets give similar pure component vapor pressure and liquid density results, whereas very......Summary of “Extension of association models to complex chemicals”. Ph.D. thesis by Ane Søgaard Avlund The subject of this thesis is application of SAFT type equations of state (EoS). Accurate and predictive thermodynamic models are important in many industries including the petroleum industry...... not account for steric self-hindrance for tree-like structures. An important practical problem is how to obtain optimal and consistent parameters. Moreover, multifunctional associating molecules represent a special challenge. In this work two equations of state using the SAFT theory for association are used...

  17. Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-10-01

    Full Text Available Yutong Wang,1–3,* Liping Huang,1,2,* Yan Shen,1,2,* Lidan Tang,1,2,4 Runing Sun,1,5 Di Shi,6 Thomas J Webster,6 Jiasheng Tu,1,2 Chunmeng Sun1,2 1Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, China Pharmaceutical University, 2State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 3Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 4Changzhou Second People’s Hospital, Changzhou, 5School of Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: To achieve enhanced physical stability of poly(ethylene glycol-poly(D,L-lactide polymeric micelles (PEG-PDLLA PMs, a mixture of methoxy PEG-PDLLA-polyglutamate (mPEG-PDLLA-PLG and mPEG-PDLLA-poly(L-lysine (mPEG-PDLLA-PLL copolymers was applied to self-assembled stable micelles with polyion-stabilized cores. Prior to micelle preparation, the synthetic copolymers were characterized by 1H-nuclear magnetic resonance (NMR and infrared spectroscopy (IR, and their molecular weights were calculated by 1H-NMR and gel permeation chromatography (GPC. Dialysis was used to prepare PMs with deoxypodophyllotoxin (DPT. Transmission electron microscopy (TEM images showed that DPT polyion complex micelles (DPT-PCMs were spherical, with uniform distribution and particle sizes of 36.3±0.8 nm. In addition, compared with nonpeptide-modified DPT-PMs, the stability of DPT-PCMs was significantly improved under various temperatures. In the meantime, the pH sensitivity induced by charged peptides allowed them to have a stronger antitumor effect and a pH-triggered release profile. As a result, the dynamic characteristic of DPT-PCM was retained, and high biocompatibility of DPT-PCM was observed in an in vivo study. These results

  18. Foraging Strategies of Laysan Albatross Inferred from Stable Isotopes: Implications for Association with Fisheries.

    Science.gov (United States)

    Edwards, Ann E; Fitzgerald, Shannon M; Parrish, Julia K; Klavitter, John L; Romano, Marc D

    2015-01-01

    Fatal entanglement in fishing gear is the leading cause of population decline for albatross globally, a consequence of attraction to bait and fishery discards of commercial fishing operations. We investigated foraging strategies of Laysan albatross (Phoebastria immutabilis), as inferred from nitrogen and carbon isotope values of primary feathers, to determine breeding-related, seasonal, and historic factors that may affect the likelihood of association with Alaskan or Hawaiian longline fisheries. Feather samples were collected from live birds monitored for breeding status and breeding success on Midway Atoll in the northwestern Hawaiian Islands, birds salvaged as fisheries-bycatch, and birds added to museum collections before 1924. During the chick-rearing season (sampled April-May), means and variances of stable isotope values of birds with the highest, most consistent reproductive success were distinct from less productive conspecifics and completely different from birds caught in Hawaiian or Alaskan longline fisheries, suggesting birds with higher multi-annual reproductive success were less likely to associate with these fisheries. Contemporary birds with the highest reproductive success had mean values most similar to historic birds. Values of colony-bound, courting prebreeders were similar to active breeders but distinct from prebreeders caught in Alaskan longline fisheries. During the breeding season, δ15N values were highly variable for both contemporary and historic birds. Although some historic birds exhibited extremely low δ15N values unmatched by contemporary birds (isotopic variability coalesced into a more narrow set of values for both contemporary and historic birds. Our results suggest that foraging strategies of Laysan albatross are a complex function of season, breeding status, and multi-annual breeding success, factors that likely affect the probability of association with fisheries.

  19. Association between Nitrogen Stable Isotope Ratios in Human Hair and Serum Levels of Leptin.

    Science.gov (United States)

    Ahn, Song Vogue; Koh, Sang-Baek; Lee, Kwang-Sik; Bong, Yeon-Sik; Park, Jong-Ku

    2017-10-01

    Stable isotope ratios have been reported to be potential biomarkers of dietary intake and nutritional status. High serum levels of leptin, a hormone which regulates energy metabolism and food intake, are associated with insulin resistance and metabolic syndrome. However, little is known about the association between stable isotope ratios and the metabolic risk in humans. We investigated whether the carbon and nitrogen stable isotope ratios in hair are associated with serum leptin levels. Hair samples were collected from 399 healthy adults (233 men and 166 women) aged 40 to 70 years of a community-based cohort in Korea and the bulk stable isotope ratios of carbon (δ 13 C) and nitrogen (δ 15 N) were measured for all hair samples. Serum leptin levels were analyzed by radioimmunoassay. δ 15 N showed positive correlations with serum leptin levels. In multivariate models, increasing δ 15 N were associated with elevated serum leptin levels (defined as ≥ the median values), whereas δ 13 C were not significantly associated with serum leptin levels. The odds ratio (95% confidence interval) per 1‰ increase in δ 15 N for an elevated serum leptin level was 1.58 (1.11-2.26). In participants with high body mass index, δ 15 N showed positive associations with serum leptin levels, whereas these associations were not seen in participants with low body mass index. The nitrogen stable isotopic ratio in hair is positively associated with serum leptin levels. The hair δ 15 N could be used as a clinical marker to estimate metabolic risk.

  20. Interactions between HIV-1 reverse transcriptase and the downstream template strand in stable complexes with primer-template.

    Directory of Open Access Journals (Sweden)

    Wiriya Rutvisuttinunt

    Full Text Available Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT forms stable ternary complexes in which RT is bound tightly at fixed positions on the primer-template (P/T. We have probed downstream interactions between RT and the template strand in the complex containing the incoming dNTP (+1 dNTP*RT*P/T complex and in the complex containing the pyrophosphate analog, foscarnet (foscarnet*RT*P/T complex.UV-induced cross-linking between RT and the DNA template strand was most efficient when a bromodeoxyuridine residue was placed in the +2 position (the first template position downstream from the incoming dNTP. Furthermore, formation of the +1 dNTP*RT*P/T complex on a biotin-containing template inhibited binding of streptavidin when biotin was in the +2 position on the template but not when the biotin was in the +3 position. Streptavidin pre-bound to a biotin residue in the template caused RT to stall two to three nucleotides upstream from the biotin residue. The downstream border of the complex formed by the stalled RT was mapped by digestion with exonuclease RecJ(F. UV-induced cross-linking of the complex formed by the pyrophosphate analog, foscarnet, with RT and P/T occurred preferentially with bromodeoxyuridine in the +1 position on the template in keeping with the location of RT one base upstream in the foscarnet*RT*P/T complex (i.e., in the pre-translocation position.For +1 dNTP*RT*P/T and foscarnet*RT*P/T stable complexes, tight interactions were observed between RT and the first unpaired template nucleotide following the bound dNTP or the primer terminus, respectively.

  1. Letter Report: Stable Hydrogen and Oxygen Isotope Analysis of B-Complex Perched Water Samples

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Brady D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moran, James J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Nims, Megan K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Saunders, Danielle L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2017-04-13

    Fine-grained sediments associated with the Cold Creek Unit at Hanford have caused the formation of a perched water aquifer in the deep vadose zone at the B Complex area, which includes waste sites in the 200-DV-1 Operable Unit and the single-shell tank farms in Waste Management Area B-BX-BY. High levels of contaminants, such as uranium, technetium-99, and nitrate, make this aquifer a continuing source of contamination for the groundwater located a few meters below the perched zone. Analysis of deuterium (2H) and 18-oxygen (18O) of nine perched water samples from three different wells was performed. Samples represent time points from hydraulic tests performed on the perched aquifer using the three wells. The isotope analyses showed that the perched water had δ2H and δ18O ratios consistent with the regional meteoric water line, indicating that local precipitation events at the Hanford site likely account for recharge of the perched water aquifer. Data from the isotope analysis can be used along with pumping and recovery data to help understand the perched water dynamics related to aquifer size and hydraulic control of the aquifer in the future.

  2. Warm Parenting Associated with Decreasing or Stable Child BMI during Treatment.

    Science.gov (United States)

    Rhee, Kyung E; Jelalian, Elissa; Boutelle, Kerri; Dickstein, Susan; Seifer, Ronald; Wing, Rena

    2016-04-01

    While authoritative parenting, which includes high levels of warmth and behavioral control, has been associated with lower risk of obesity, little is known about how general parenting impacts child weight loss during treatment. Our goal was to examine the relationship between several general parenting dimensions and 'decreasing /stable' child BMI during a 16-week family-based behavioral weight control program. Forty-four overweight parent-child dyads (child age 8 to 12 years) enrolled in the program. Families were videotaped at baseline eating dinner in their home. Using the General Parenting Observational Scale (GPOS), meals were coded for several general parenting dimensions. Primary outcome was percent of children whose BMI 'decreased or stayed the same.' Multivariable logistic regression was used to determine the relationship between general parenting and decreasing/stable child BMI. Forty families (91%) completed the program. Children had a mean BMI change of -0.40 (SD 1.57), which corresponds to a -0.15 (SD 0.20) change in BMI z-score (BMI-Z); 75% of children had decreasing/stable BMI. In the unadjusted models, lower parent BMI, higher parent education, and higher levels of parental warmth were significantly associated with decreasing/stable child BMI. In the multivariable model, only higher level of warmth was associated with increased odds of decreasing/stable child BMI (OR = 1.28; 95% CI, 1.01, 1.62). Baseline parental warmth may influence a child's ability to lower/maintain BMI during a standard family-based behavioral weight control program. Efforts to increase parent displays of warmth and emotional support towards their overweight child may help to increase the likelihood of treatment success.

  3. Fractional flow reserve is not associated with inflammatory markers in patients with stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Jan-Willem E M Sels

    Full Text Available BACKGROUND: Atherosclerosis is an inflammatory condition and increased blood levels of inflammatory biomarkers have been observed in acute coronary syndromes. In addition, high expression of inflammatory markers is associated with worse prognosis of coronary artery disease. The presence and extent of inducible ischemia in patients with stable angina has previously been shown to have strong prognostic value. We hypothesized that evidence of inducible myocardial ischemia by local lesions, as measured by fractional flow reserve (FFR, is associated with increased levels of blood based inflammatory biomarkers. METHODS: Whole blood samples of 89 patients with stable angina pectoris and 16 healthy controls were analyzed. The patients with stable angina pectoris underwent coronary angiography and FFR of all coronary lesions. We analyzed plasma levels of cytokines IL-6, IL-8 and TNF-α and membrane expression of Toll-like receptor 2 and 4, CD11b, CD62L and CD14 on monocytes and granulocytes as markers of inflammation. Furthermore, we quantified the severity of hemodynamically significant coronary artery disease by calculating Functional Syntax Score (FSS, an extension of the Syntax Score. RESULTS: For the majority of biomarkers, we observed lower levels in the healthy control group compared with patients with stable angina who underwent coronary catheterization. We found no difference for any of the selected biomarkers between patients with a positive FFR (≤ 0.75 and negative FFR (>0.80. We observed no relationship between the investigated biomarkers and FSS. CONCLUSION: The presence of local atherosclerotic lesions that result in inducible myocardial ischemia as measured by FFR in patients with stable coronary artery disease is not associated with increased plasma levels of IL-6, IL-8 and TNF-α or increased expression of TLR2 and TLR4, CD11b, CD62L and CD14 on circulating leukocytes.

  4. Short-Term Protein Stable Isotope Probing of Microbial Communities to Associate Functions with Taxa (Invited)

    Science.gov (United States)

    Lipton, M. S.; Slysz, G. W.; Steinke, L. A.; Ward, D. M.; Klatt, C. G.; Clauss, T. R.; Purvine, S. O.; Anderson, G. A.; Payne, S. H.; Bryant, D. A.

    2013-12-01

    Determining which taxa in a community perform which functions is essential for understanding metabolite fluxes and metabolic interactions among community members. Specific taxa will alter their metabolism in order to acclimate to changing environmental factors such as light through the diel cycle, changing temperature and other factors. Monitoring which proteins are being expressed, and the quantitative protein expression patterns in the individual taxa as a response to external stimuli is key to understanding these mechanisms. Protein stable isotope probing (Pro-SIP) has strong potential for revealing key metabolizing taxa in complex microbial communities. In Pro-SIP studies, label incorporation is determined by the extent of the change in the isotopic profile of peptides when measured by mass spectrometry. While most Pro-SIP work to date has been performed under controlled laboratory conditions to allow extensive isotope labeling of the target organism(s), these techniques have not been applied to short term in situ studies due to the small degree of partial labeling of the proteins. We have applied Pro-SIP to study the assimilation of a labeled substrate into proteins to determine which taxa are responsible for sequestration of dissolved inorganic carbon in microbial mats associated with the alkaline siliceous hot springs of Yellowstone National Park. This community is fueled by sunlight as it transitions from dark to light; the aim was to understand the light-dependent pathway of inorganic carbon incorporation into different taxa during the early morning hours when the mat was in low light and anoxic. Each mat sample was incubated with 13C-bicarbonate for 3 h. Substrate assimilation was determined through standard proteomic techniques along with the use of SIPPER, a collection of algorithms that sensitively measure small changes in peptide isotopic patterns, allowing the determination of which taxa assimilated the substrate during this period. For the

  5. Phosphorescent Pt(II) and Pd(II) Complexes for Efficient, High-Color-Quality, and Stable OLEDs.

    Science.gov (United States)

    Fleetham, Tyler; Li, Guijie; Li, Jian

    2017-02-01

    Phosphorescent organic light-emitting diodes (OLEDs) are leading candidates for next-generation displays and solid-state lighting technologies. Much of the academic and commercial pursuits in phosphorescent OLEDs have been dominated by Ir(III) complexes. Over the past decade recent developments have enabled square planar Pt(II) and Pd(II) complexes to meet or exceed the performance of Ir complexes in many aspects. In particular, the development of N-heterocyclic carbene-based emitters and tetradentate cyclometalated Pt and Pd complexes have significantly improved the emission efficiency and reduced their radiative lifetimes making them competitive with the best reported Ir complexes. Furthermore, their unique and diverse molecular design possibilities have enabled exciting photophysical attributes including narrower emission spectra, excimer -based white emission, and thermally activated delayed fluorescence. These developments have enabled the fabrication of efficient and "pure" blue OLEDs, single-doped white devices with EQEs of over 25% and high CRI, and device operational lifetimes which show early promise that square planar metal complexes can be stable enough for commercialization. These accomplishments have brought Pt complexes to the forefront of academic research. The molecular design strategies, photophysical characteristics, and device performance resulting from the major advancements in emissive Pt and Pd square planar complexes are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Pyridine and phosphonate containing ligands for stable lanthanide complexation. An experimental and theoretical study to assess the solution structure.

    Science.gov (United States)

    Mato-Iglesias, Marta; Balogh, Edina; Platas-Iglesias, Carlos; Tóth, Eva; de Blas, Andrés; Rodríguez Blas, Teresa

    2006-12-07

    We report an experimental and theoretical study of the stability and solution structure of lanthanide complexes with two novel ligands containing pyridine units and phosphonate pendant arms on either ethane-1,2-diamine (L2) or cyclohexane-1,2-diamine (L3) backbones. Potentiometric studies have been carried out to determine the protonation constants of the ligands and the stability constants of the complexes with Gd(III) and the endogenous metal ions Zn(II) and Cu(II). While the stability constant of the GdL2 complex is too high to be determined by direct pH-potentiometric titrations, the cyclohexyl derivative GdL3 has a lower and assessable stability (log K(GdL3)=17.62). Due to the presence of the phosphonate groups, various protonated species can be detected up to pH approximately 8 for both ligands and all metal ions studied. The molecular clusters [Ln(L)(H2O)](3-).19H2O (Ln=La, Nd, Ho or Lu; L=L2 or L3) were characterized by theoretical calculations at the HF level. Our calculations provide two minimum energy geometries where the ligand adopts different conformations: twist-wrap (tw), in which the ligand wraps around the metal ion by twisting the pyridyl units relative to each other, and twist-fold (tf), where the slight twisting of the pyridyl units is accompanied by an overall folding of the two pyridine units towards one of the phosphonate groups. The relative free energies of the tw and tf conformations of [Ln(L)(H2O)]3- (L=L2, L3) complexes calculated in aqueous solution (C-PCM) by using the B3LYP model indicate that the tw form is the most stable one along the whole lanthanide series for the complexes of L3, while for those of L2 only the Gd(III) complex is more stable in the tf conformation by ca. 0.5 kcal mol-1. 1H NMR studies of the Eu(III) complex of L3 show the initial formation of the tf complex in aqueous solution, which slowly converts to the thermodynamically stable tw form. The structures calculated for the Nd(III) complexes are in reasonably

  7. Stable producer cell lines for adeno-associated virus (AAV) assembly.

    Science.gov (United States)

    Chadeuf, Gilliane; Salvetti, Anna

    2010-10-01

    Stable producer cell lines containing both the rep and cap genes and recombinant adeno-associated virus (rAAV) vectors can be infected with a helper virus to provide reliable and efficient production of rAAV stocks. However, the development of these cell lines is time-consuming. The procedure described here is therefore recommended only for studies requiring the production of high amounts of rAAV, such as preclinical studies performed in large animals.

  8. Characteristics of the turbulence in the stable boundary layer over complex terrain of the Loess Plateau, China

    Science.gov (United States)

    Liang, J.; Zhang, L.; Yuan, G.

    2017-12-01

    Accurate determination of surface turbulent fluxes in a stable boundary layer is of great practical importance in weather prediction and climate simulations, as well as applications related to air pollution. To gain an insight into the characteristics of turbulence in a stable boundary layer over the complex terrain of the Loess Plateau, we analyzed the data from the Semi-Arid Climate and Environment Observatory of Lanzhou University (SACOL). We proposed a method to identify and efficiently isolate nonstationary motions from turbulence series, and examined the characteristics of nonstationary motions (nonstationary motions refer to gusty events on a greater scale than local shear-generated turbulence). The occurrence frequency of nonstationary motions was found to depend on the mean flow, being more frequent in weak wind conditions and vanishing when the wind speed, U, was greater than 3.0 m s-1. When U exceeded the threshold value of 1.0 m s-1 for the gradient Richardson number Ri ≤ 0.3 and 1.5 m s-1 for Ri > 0.3, local shear-generated turbulence depended systematically on U with an average rate of 0.05 U. However, for the weak wind condition, neither the mean wind speed nor the stability was an important factor for local turbulence. Under the weak wind stable condition, affected by topography-induced nonstationary motions, the local turbulence was anisotropic with a strong horizontal fluctuation and a weak vertical fluctuation, resulting in weakened heat mixing in the vertical direction and stronger un-closure of energy. These findings accessed the validity of similarity theory in the stable boundary layer over complex terrain, and revealed one reason for the stronger un-closure of energy in the night.

  9. A stable gold(i)-enyne species obtained by alkyne carboauration in a complex rearrangement.

    Science.gov (United States)

    Cámara, Jéssica; Blanco, M Carmen; Laguna, Antonio; Naumov, Panče; Gimeno, M Concepción

    2017-08-15

    An unprecedented tetranuclear gold derivative with unusual gold-enyne moieties is prepared by a mild and neat rearrangement of a dinuclear gold complex with a bridging bis(diphenylphosphino)alkyne and terminal alkynyl ligands. The complex originates as a consequence of an intramolecular addition of the AuC[triple bond, length as m-dash]CTol fragment to the internal diphosphine triple bond Ph 2 PC[triple bond, length as m-dash]CPPh 2 . The crystal structure of the tetranuclear complex shows a dinuclear metallacycle with a very short AuAu bond interaction and bridging phosphino-enyne ligands. This disposition clearly stabilises the elusive vinyl gold species omnipresent as intermediates in gold-catalysed reactions.

  10. Destruction of chemical warfare agent simulants by air and moisture stable metal NHC complexes.

    Science.gov (United States)

    Weetman, Catherine; Notman, Stuart; Arnold, Polly L

    2018-02-20

    The cooperative effect of both NHC and metal centre has been found to destroy chemical warfare agent (CWA) simulants. Choice of both the metal and NHC is key to these transformations as simple, monodentate N-heterocyclic carbenes in combination with silver or vanadium can promote stoichiometric destruction, whilst bidentate, aryloxide-tethered NHC complexes of silver and alkali metals promote breakdown under mild heating. Iron-NHC complexes generated in situ are competent catalysts for the destruction of each of the three targetted CWA simulants.

  11. The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein

    DEFF Research Database (Denmark)

    Alcalay, M; Tomassoni, L; Colombo, E

    1998-01-01

    by the expression of PML-RAR alpha. We report that PML colocalizes with the nonphosphorylated fraction of the retinoblastoma protein (pRB) within nuclear bodies and that pRB is delocalized by PML-RAR alpha expression. Both PML and PML-RAR alpha form complexes with the nonphosphorylated form of pRB in vivo...

  12. Stable dipole solitons and soliton complexes in the nonlinear Schrödinger equation with periodically modulated nonlinearity

    Energy Technology Data Exchange (ETDEWEB)

    Lebedev, M. E., E-mail: gloriouslair@gmail.com, E-mail: galfimov@yahoo.com; Alfimov, G. L., E-mail: gloriouslair@gmail.com, E-mail: galfimov@yahoo.com [National Research University of Electronic Technology MIET, Zelenograd, Moscow 124498 (Russian Federation); Malomed, Boris A., E-mail: malomed@post.tau.ac.il [Department of Physical Electronics, School of Electrical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); Laboratory of Nonlinear-Optical Informatics, ITMO University, St. Petersburg 197101 (Russian Federation)

    2016-07-15

    We develop a general classification of the infinite number of families of solitons and soliton complexes in the one-dimensional Gross-Pitaevskii/nonlinear Schrödinger equation with a nonlinear lattice pseudopotential, i.e., periodically modulated coefficient in front of the cubic term, which takes both positive and negative local values. This model finds direct implementations in atomic Bose-Einstein condensates and nonlinear optics. The most essential finding is the existence of two branches of dipole solitons (DSs), which feature an antisymmetric shape, being essentially squeezed into a single cell of the nonlinear lattice. This soliton species was not previously considered in nonlinear lattices. We demonstrate that one branch of the DS family (namely, which obeys the Vakhitov-Kolokolov criterion) is stable, while unstable DSs spontaneously transform into stable fundamental solitons (FSs). The results are obtained in numerical and approximate analytical forms, the latter based on the variational approximation. Some stable bound states of FSs are found too.

  13. Evolutionary Search for Globally Optimal Stable Multicycles in Complex Systems with Inventory Couplings

    Directory of Open Access Journals (Sweden)

    M. Skowron

    2009-01-01

    Full Text Available This note is devoted to multiperiodically operated complex system with inventory couplings transferring waste products from some subsystems as useful components to other subsystems. The flexibility of the inventory couplings is used to force each of the subsystems with its own period and to exploit its particular dynamic properties. This enhances the performance of the complex system endowed with many recycling loops, which reduce the amount of waste products endangering the natural environment. The subsystems are characterized by generalized populations composed of the individuals (the cycles, each of them encompasses its period, its initial state, its local control, and its inventory interaction. An evolutionary optimization algorithm employing such generalized populations coordinated on the basis of the inventory interaction constraints is developed. It includes the stability requirements imposed on the cyclic control processes connected with particular subsystems. The algorithm proposed is applied to the global multiperiodic optimization of some interconnected chemical production processes.

  14. Rapid presumptive identification of the Mycobacterium tuberculosis-bovis complex by radiometric determination of heat stable urease

    International Nuclear Information System (INIS)

    Gandy, J.H.; Pruden, E.L.; Cox, F.R.

    1983-01-01

    Simple and rapid Bactec methodologies for the determination of neat (unaltered) and heat stable urease activity of mycobacteria are presented. Clinical isolates (63) and stock cultures (32)--consisting of: M. tuberculosis (19), M. bovis (5), M. kansasii (15), M. marinum (4), M. simiae (3), M. scrofulaceum (16), M. gordonae (6), M. szulgai (6), M. flavescens (1), M. gastri (1), M. intracellulare (6), M. fortuitum-chelonei complex (12), and M. smegmatis (1)--were tested for neat urease activity by Bactec radiometry. Mycobacterial isolates (50-100 mg wet weight) were incubated at 35 degrees C for 30 minutes with microCi14C-urea. Urease-positive mycobacteria gave Bactec growth index (GI) values greater than 100 units, whereas urease-negative species gave values less than 10 GI units. Eighty-three isolates possessing neat urease activity were heated at 80 degrees C for 30 minutes followed by incubation at 35 degrees C for 30 minutes with 1 microCi14C-urea. Mycobacterium tuberculosis-bovis complex demonstrated heat-stable urease activity (GI more than 130 units) and could be distinguished from mycobacteria other than tuberculosis (MOTT), which gave GI values equal to or less than 40 units

  15. Experimental and numerical study of atmospheric turbulence and dispersion in stable conditions and in near field at a complex site

    International Nuclear Information System (INIS)

    Wei, Xiao

    2016-01-01

    An experimental program has been designed in order to study pollutants dispersion at a complex site with a focus on stable conditions, which are still challenging for numerical modelling. This experimental program is being conducted at the SIRTA site in a southern suburb of Paris and consists in measuring, in near field, the turbulence and the pollutants dispersion. The aim of this program is to characterize the fine structure of turbulence and associated dispersion through high temporal and spatial resolution measurements. Then, these measurements allow to validate and improve the performance of CFD simulation for turbulence and dispersion in a heterogeneous field. The instrumental set up includes 12 ultrasonic anemometers measuring continuously wind velocity and temperature at 10 Hz, and 6 photo-ionization detectors (PIDs) measuring gas concentration at 50 Hz during tracer tests. Intensive observations periods (IOPs) with gas releases have been performed since March 2012.First of all, a detailed study of flow on the site is made, because it must be characterised and properly simulated before attempting to simulate the pollutants dispersion. This study is based on two years of continuous measurements and on measurements performed during IOPs. Turbulence strong anisotropy in the surface layer is characterized by calculating variances, integral length scales and power spectra of the three wind velocity components. Propagation of turbulent structures between sensors has been characterized with velocity correlations. Energy spectra show several slopes in different frequency regions. Also, data analyses show impact of terrain heterogeneity on the measurements. The forest to the north of experimental field modifies wind velocity and direction for a large northerly sector. It induces a strong directional wind shear and a wind deceleration below the forest height. Numerical simulations are carried out using the CFD code Code-Saturne in RANS mode with a standard κ

  16. Experimental and numerical study of atmospheric turbulence and dispersion in stable conditions and in near field at a complex site

    International Nuclear Information System (INIS)

    Wei, Xiao

    2016-01-01

    An experimental program has been designed in order to study pollutants dispersion at a complex site with a focus on stable conditions, which are still challenging for numerical modelling. This experimental program is being conducted at the SIRTA site in a southern suburb of Paris and consists in measuring, in near field, the turbulence and the pollutants dispersion. The aim of this program is to characterize the fine structure of turbulence and associated dispersion through high temporal and spatial resolution measurements. Then, these measurements allow to validate and improve the performance of CFD simulation for turbulence and dispersion in a heterogeneous field. The instrumental set up includes 12 ultrasonic anemometers measuring continuously wind velocity and temperature at 10 Hz, and 6 photo-ionization detectors (PIDs) measuring gas concentration at 50 Hz during tracer tests. Intensive observations periods (IOPs) with gas releases have been performed since March 2012. First of all, a detailed study of flow on the site is made, because it must be characterised and properly simulated before attempting to simulate the pollutants dispersion. This study is based on two years of continuous measurements and on measurements performed during IOPs. Turbulence strong anisotropy in the surface layer is characterized by calculating variances, integral length scales and power spectra of the three wind velocity components. Propagation of turbulent structures between sensors has been characterized with velocity correlations. Energy spectra show several slopes in different frequency regions. Also, data analyses show impact of terrain heterogeneity on the measurements. The forest to the north of the experimental field modifies wind velocity and direction for a large northerly sector. It induces a strong directional wind shear and a wind deceleration below the forest height. Numerical simulations are carried out using the CFD code, Code-Saturne, in RANS mode with a standard k

  17. Integration as the basis of stable and dynamic development of enterprises in agroindustrial complex

    Directory of Open Access Journals (Sweden)

    Petr Ivanovich Ogorodnikov

    2011-12-01

    Full Text Available Formation of market relations in Russian economy generates an objective need to address a number of problems in the relationship between agroundustrial complex organizations in connection with privatization, liberalization of prices and imbalances in the existing inter-industry production and economic relations that negatively affect the results of their economic activities. Because of the flagrant violations of the replenishment process, a diverse range of connections and relationships between producers and processors was broken. The major direction of lifting agricultural economy in this situation is the development of cooperatives and agroindustrial integration. In addition, the formation of large integrated complexes demonstrates high efficiency and rapid development, which is the basis of agroindustrial sector in many developed countries. The increase of competition forces business entities to combine capabilities and mutually beneficial cooperation in the struggle for the strengthening of market positions. Thus, increasing the degree of integration in the agricultural sector helps to get out of the protracted crisis and move more quickly to the innovations.

  18. Identifying apparent local stable isotope equilibrium in a complex non-equilibrium system.

    Science.gov (United States)

    He, Yuyang; Cao, Xiaobin; Wang, Jianwei; Bao, Huiming

    2018-02-28

    Although being out of equilibrium, biomolecules in organisms have the potential to approach isotope equilibrium locally because enzymatic reactions are intrinsically reversible. A rigorous approach that can describe isotope distribution among biomolecules and their apparent deviation from equilibrium state is lacking, however. Applying the concept of distance matrix in graph theory, we propose that apparent local isotope equilibrium among a subset of biomolecules can be assessed using an apparent fractionation difference (|Δα|) matrix, in which the differences between the observed isotope composition (δ') and the calculated equilibrium fractionation factor (1000lnβ) can be more rigorously evaluated than by using a previous approach for multiple biomolecules. We tested our |Δα| matrix approach by re-analyzing published data of different amino acids (AAs) in potato and in green alga. Our re-analysis shows that biosynthesis pathways could be the reason for an apparently close-to-equilibrium relationship inside AA families in potato leaves. Different biosynthesis/degradation pathways in tubers may have led to the observed isotope distribution difference between potato leaves and tubers. The analysis of data from green algae does not support the conclusion that AAs are further from equilibrium in glucose-cultured green algae than in the autotrophic ones. Application of the |Δα| matrix can help us to locate potential reversible reactions or reaction networks in a complex system such as a metabolic system. The same approach can be broadly applied to all complex systems that have multiple components, e.g. geochemical or atmospheric systems of early Earth or other planets. Copyright © 2017 John Wiley & Sons, Ltd.

  19. COMPARISON BETAXOLOL AND METOPROLOL TARTRATE THERAPIES IN PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH STABLE ANGINA

    Directory of Open Access Journals (Sweden)

    A. A. Anderzhanova

    2016-01-01

    Full Text Available Aim. To compare antihypertensive, antianginal and antiischemic efficacy of β1-selective adrenoblockers (betaxolol and metoprolol tartrate in patients with arterial hypertension (HT of 1-2 degree associated with stable angina class II.Material and methods. 100 patients (aged 23-66 y.o. with HT associated with stable angina or without angina were involved in the study. Patients were randomized into 2 groups (G1 and G2. G1 patients were treated with betaxolol, and G2 patients – with metoprolol tartrate. Ambulatory BP and electrocardiogram monitoring, exercise stress-test, echocardiography, evaluating of respiratory function, blood analysis was performed initially and in 30 and 90 days of treatment.Results. Target BP level was reached in 44 (88% patients treated with betaxolol (average daily dose 10±4 mg. 34 patients of G1 took 10 mg daily. Target BP level was reached in 41 (82% patients treated with metoprolol tartrate (average daily dose 150±27 mg. 30 patients of G2 took 150 mg daily. Exercise tolerance increased and a number of ischemic ST segment depressions reduced significantly in both groups. There were no significant differences in antihypertensive, antianginal, and antiischemic efficacy between groups.Conclusion. Betaxolol advantage is an ability to maintain target BP level more than 24 hours. A possibility to take betaxolol once a day raises patient’s compliance with therapy.

  20. Stable isotopes reveal rail-associated behavior in a threatened carnivore.

    Science.gov (United States)

    Hopkins, John B; Whittington, Jesse; Clevenger, Anthony P; Sawaya, Michael A; St Clair, Colleen Cassady

    2014-01-01

    Human-wildlife conflict is a leading cause of adult mortality for large carnivores worldwide. Train collision is the primary cause of mortality for threatened grizzly bears (Ursus arctos) in Banff National Park. We investigated the use of stable isotope analysis as a tool for identifying bears that use the railway in Banff. Rail-associated bears had higher δ(15)N and δ(34)S values than bears sampled away from the rail, but similar δ(13)C values. Because elevated δ(15)N values are indicative of higher animal protein consumption, rail-associated bears likely preyed on ungulates that foraged along the rail or scavenged on train-killed animals. The higher δ(34)S values in bear hair could have resulted from bears consuming sulfur pellets spilled on the rail or through the uptake of sulfur in the plants bears or animals consumed. Similar δ(13)C values suggest that the two types of bears had generally similar plant-based diets. Results from this study suggest that stable isotopes analysis could be used as a non-invasive, affordable, and efficient technique to identify and monitor bears that forage on the railway in Banff and potentially other transportation corridors worldwide.

  1. Weak polyelectrolyte complexation driven by associative charging

    Science.gov (United States)

    Rathee, Vikramjit S.; Zervoudakis, Aristotle J.; Sidky, Hythem; Sikora, Benjamin J.; Whitmer, Jonathan K.

    2018-03-01

    Weak polyelectrolytes are relevant for a wide range of fields; in particular, they have been investigated as "smart" materials for chemical separations and drug delivery. The charges on weak polyelectrolytes are dynamic, causing polymer chains to adopt different equilibrium conformations even with relatively small changes to the surrounding environment. Currently, there exists no comprehensive picture of this behavior, particularly where polymer-polymer interactions have the potential to affect charging properties significantly. In this study, we elucidate the novel interplay between weak polyelectrolyte charging and complexation behavior through coupled molecular dynamics and Monte Carlo simulations. Specifically, we investigate a model of two equal-length and oppositely charging polymer chains in an implicit salt solution represented through Debye-Hückel interactions. The charging tendency of each chain, along with the salt concentration, is varied to determine the existence and extent of cooperativity in charging and complexation. Strong cooperation in the charging of these chains is observed at large Debye lengths, corresponding to low salt concentrations, while at lower Debye lengths (higher salt concentrations), the chains behave in apparent isolation. When the electrostatic coupling is long-ranged, we find that a highly charged chain strongly promotes the charging of its partner chain, even if the environment is unfavorable for an isolated version of that partner chain. Evidence of this phenomenon is supported by a drop in the potential energy of the system, which does not occur at the lower Debye lengths where both potential energies and charge fractions converge for all partner chain charging tendencies. The discovery of this cooperation will be helpful in developing "smart" drug delivery mechanisms by allowing for better predictions for the dissociation point of delivery complexes.

  2. The Enhanced Intramolecular Energy Transfer and Strengthened ff Luminescence of a Stable Helical Eu Complex in Ionic Liquids.

    Science.gov (United States)

    Hasegawa, Yuki; Ishii, Ayumi; Inazuka, Yudai; Yajima, Naho; Kawaguchi, Shogo; Sugimoto, Kunihisa; Hasegawa, Miki

    2018-01-24

    The luminescence of a Eu complex (EuL) is enhanced by stabilization of the coordination structure in highly viscous ionic liquids. The EuL was found to maintain a stable single helical structure both in organic solvents and in the ionic liquids [BMIM][PF₆] and [EMIM][PF₆]. A colorless solution of EuL dissolved in [BMIM][PF₆] exhibits bright red luminescence with a quantum yield of 32.3%, a value that is much higher than that in acetonitrile (12%). Estimated rate constants for the energy relaxation pathway indicate that the energy transfer efficiency is enhanced in [BMIM][PF₆] as a result of the suppression of molecular fluctuations in the ligands. Additionally, a highly luminescent helical structure is preserved in [EMIM][PF₆] up to 120 °C.

  3. The association between self-esteem and happiness differs in relationally mobile vs. stable contexts

    Directory of Open Access Journals (Sweden)

    Kosuke eSato

    2014-10-01

    Full Text Available Does a change in the nature of surrounding social context affect the strength of association between self-esteem and happiness? This paper aims to answer this question from a socio-ecological perspective, focusing on the role of relational mobility. Recent research has shown that this association is stronger in societies that are higher in relational mobility, where there is a greater freedom of choice in interpersonal relationships and group memberships. In this study, we tested if this hypothesis could be applied to situational differences within the same physical setting. Using a quasi-experimental design, we tested if the association between self-esteem and happiness was stronger for first-year students at a Japanese university who had just entered the college and thus were in a relatively higher mobility context, than the second year students at the same university whose relationships tended to be more stable and long-standing. The results showed, as predicted, that the association between self-esteem and happiness was stronger for the first-year students than for the second-year students. Implications for the theory and research on social change are discussed.

  4. The association between self-esteem and happiness differs in relationally mobile vs. stable interpersonal contexts.

    Science.gov (United States)

    Sato, Kosuke; Yuki, Masaki

    2014-01-01

    Does a change in the nature of surrounding social context affect the strength of association between self-esteem and happiness? This paper aims to answer this question from a socio-ecological perspective, focusing on the role of relational mobility. Recent research has shown that this association is stronger in societies that are higher in relational mobility, where there is a greater freedom of choice in interpersonal relationships and group memberships. In this study, we tested if this hypothesis could be applied to situational differences within the same physical setting. Using a quasi-experimental design, we tested if the association between self-esteem and happiness was stronger for first-year students at a Japanese university who had just entered the college and thus were in a relatively higher mobility context, than the second-year students at the same university whose relationships tended to be more stable and long-standing. The results showed, as predicted, that the association between self-esteem and happiness was stronger for the first-year students than for the second-year students. Implications for the theory and research on social change are discussed.

  5. Stable intergenerational associations of childhood overweight during the development of the obesity epidemic

    DEFF Research Database (Denmark)

    Ajslev, Teresa A; Ängquist, Lars; Silventoinen, Karri

    2015-01-01

    of children born to parents with and without childhood overweight. METHODS: The study population was from the Copenhagen School Health Records Register, which includes age- and sex-specific body mass index (BMI; kg/m(2) ) of children. This study used BMI values from 7-year-old children born 1952-1989 and from....... RESULTS: Stable levels in parent-child overweight associations were observed across child BMI groups born to parents with and without childhood overweight. A slight upward odds ratio trend was observed across time in children born to two overweight parents at age 13, but not at age 7 years. CONCLUSIONS......: Parent-child resemblance in childhood overweight showed small changes during the development of the obesity epidemic, suggesting that the obesogenic environment inducing the epidemic in Denmark influenced children irrespective of their familial predisposition....

  6. Carbon Stable Isotope Values in Plankton and Mussels Reflect Changes in Carbonate Chemistry Associated with Nutrient Enhanced Net Production

    Science.gov (United States)

    Coastal ecosystems are inherently complex and potentially adaptive as they respond to changes in nutrient loads and climate. We documented the role that carbon stable isotope (δ13C) measurements could play in understanding that adaptation with a series of three Ecostat (i.e...

  7. Exploratory study of the association between insight and Theory of Mind (ToM) in stable schizophrenia patients.

    Science.gov (United States)

    Pousa, Esther; Duñó, Rosó; Blas Navarro, J; Ruiz, Ada I; Obiols, Jordi E; David, Anthony S

    2008-05-01

    Poor insight and impairment in Theory of Mind (ToM) reasoning are common in schizophrenia, predicting poorer clinical and functional outcomes. The present study aimed to explore the relationship between these phenomena. 61 individuals with a DSM-IV diagnosis of schizophrenia during a stable phase were included. ToM was assessed using a picture sequencing task developed by Langdon and Coltheart (1999), and insight with the Scale to Assess Unawareness of Mental Disorder (SUMD; Amador et al., 1993). Multivariate linear regression analysis was carried out to estimate the predictive value of insight on ToM, taking into account several possible confounders and interaction variables. No direct significant associations were found between any of the insight dimensions and ToM using bivariate analysis. However, a significant linear regression model which explained 48% of the variance in ToM was revealed in the multivariate analysis. This included the 5 insight dimensions and 3 interaction variables. Misattribution of symptoms--in aware patients with age at onset >20 years--and unawareness of need for medication--in patients with GAF >60--were significantly predictive of better ToM. Insight and ToM are two complex and distinct phenomena in schizophrenia. Relationships between them are mediated by psychosocial, clinical, and neurocognitive variables. Intact ToM may be a prerequisite for aware patients to attribute their symptoms to causes other than mental illness, which could in turn be associated with denial of need for medication.

  8. Using stable isotopes to associate migratory shorebirds with their wintering locations in Argentina

    Science.gov (United States)

    Farmer, A.H.; Abril, M.; Fernandez, M.; Torres, J.; Kester, C.; Bern, C.

    2004-01-01

    We are evaluating the use of stable isotopes to identify the wintering areas of Neotropical migratory shorebirds in Argentina. Our goal is to associate individual birds, captured on the breeding grounds or in migration with specific winter sites, thereby helping to identify distinct areas used by different subpopulations. In January and February 2002 and 2003, we collected flight feathers from shorebirds at 23 wintering sites distributed across seven province s in Argentina (n = 170). Feathers samples were pre- pared and analyzed for δ13C, δ15N, δ34S, δ18O and δD by continuous flow methods. A discriminant function based on deuterium alone was not an accurate predictor of a shorebird’s province of origin, ranging from 8% correct (Santiago del Estero) to 80% correct (San ta Cruz). When other isotopes were included, the prediction accuracy increased substantially (from 56% in Buenos Aires to 100% in Tucumán). The improvement in accuracy was due to C/N, which separated D-depleted sites in the Andes from those in the south, and the inclusion of S separated sites with respect to their distance from the Atlantic. We also were able to correctly discriminate shorebirds from among two closely spaced sites within the province of Tierra del Fuego. These results suggest the feasibility of identifying the origin of a shorebird at a provincial level of accuracy, as well as uniquely identifying birds from some closely spaced sites. There is a high degree of intra- and inter-bird variability, especially in the Pampas region, where there is wide variety of wetland/water conditions. In that important shorebird region, the variability itself may in fact be the “signature.” Future addition of trace elements to the analyses may improve predictions based solely on stable isotopes.

  9. Tourette's disorder and associated complex behaviors: a case report.

    OpenAIRE

    McDougle, C. J.; Southwick, S. M.; Rohrbaugh, R. M.

    1990-01-01

    A case of a man with Tourette's disorder associated with obsessive-compulsive disorder, multiple sexual paraphilias, and aggressive behavior is described. Treatment with haloperidol led to improvement in the characteristic tics of Tourette's disorder as well as to improvement in these three complex-associated behaviors. After haloperidol was discontinued, an exacerbation of tics and the associated behaviors occurred.

  10. Partial Seizures Are Associated with Early Increases in Signal Complexity

    Science.gov (United States)

    Jouny, Christophe C; Bergey, Gregory K; Franaszczuk, Piotr J

    2009-01-01

    Objectives Partial seizures are often believed to be associated with EEG signals of low complexity because seizures are associated with increased neural network synchrony. The investigations reported here provide an assessment of the signal complexity of epileptic seizure onsets using newly developed quantitative measures. Methods Using the Gabor atom density (GAD) measure of signal complexity, 339 partial seizures in 45 patients with intracranial electrode arrays were analyzed. Segmentation procedures were applied to determine the timing and amplitude of GAD changes relative to the electrographic onset of the seizure. Results 330 out of 339 seizures have significant complexity level changes, with 319 (97%) having an increase in complexity. GAD increases occur within seconds of the onset of the partial seizure but are not observed in channels remote from the focus. The complexity increase is similar for seizures from mesial temporal origin, neocortical temporal and extra-temporal origin. Conclusions Partial onset seizures are associated with early increases in signal complexity as measured by GAD. This increase is independent of the location of the seizure focus. Significance Despite the often predominant rhythmic activity that characterizes onset and early evolution of epileptic seizures, partial seizure onset is associated with an early increase in complexity. These changes are common to partial seizures originating from different brain regions, indicating a similar seizure dynamic. PMID:19910249

  11. Understanding trophic interactions in host-parasite associations using stable isotopes of carbon and nitrogen.

    Science.gov (United States)

    Nachev, Milen; Jochmann, Maik A; Walter, Friederike; Wolbert, J Benjamin; Schulte, S Marcel; Schmidt, Torsten C; Sures, Bernd

    2017-02-17

    Stable isotope analysis of carbon and nitrogen can deliver insights into trophic interactions between organisms. While many studies on free-living organisms are available, the number of those focusing on trophic interactions between hosts and their associated parasites still remains scarce. In some cases information about taxa (e.g. acanthocephalans) is completely missing. Additionally, available data revealed different and occasionally contrasting patterns, depending on the parasite's taxonomic position and its degree of development, which is most probably determined by its feeding strategy (absorption of nutrients through the tegument versus active feeding) and its localization in the host. Using stable isotope analysis of carbon and nitrogen we provided first data on the trophic position of an acanthocephalan species with respect to its fish host. Barbels (Barbus barbus) infected only with adult acanthocephalans Pomphorhynchus laevis as well as fish co-infected with the larval (L4) nematodes Eustrongylides sp. from host body cavity were investigated in order to determine the factors shaping host-parasite trophic interactions. Fish were collected in different seasons, to study also potential isotopic shifts over time, whereas barbels with single infection were obtained in summer and co-infected ones in autumn. Acanthocephalans as absorptive feeders showed lower isotope discrimination values of δ 15 N than the fish host. Results obtained for the acanthocephalans were in line with other parasitic taxa (e.g. cestodes), which exhibit a similar feeding strategy. We assumed that they feed mainly on metabolites, which were reprocessed by the host and are therefore isotopically lighter. In contrast, the nematodes were enriched in the heavier isotope δ 15 N with respect to their host and the acanthocephalans, respectively. As active feeders they feed on tissues and blood in the body cavity of the host and thus showed isotope discrimination patterns resembling those of

  12. Stable Isotope Evidence for a Complex Fluid Evolution of the Northwestern British Columbia Coast Ranges Related to Terrane Accretion

    Science.gov (United States)

    Moertle, J.; Holk, G. J.

    2015-12-01

    Stable isotope geochemistry reveals a complex fluid evolution for the Western Metamorphic Belt (WMB), Coast Ranges Batholith (CRB), Central Gneiss Complex (CGC) and Coast Ranges Megalineament (CRM). These fluids are a product of a complex tectonic history related to terrane accretion that includes oblique convergence, metamorphism, magmatism, and orogenic collapse. From W-to-E, these fluid systems are as follows. High-pressure greenschist-to-amphibolite facies metasedimentary rocks of the WMB record variable mineral δD (-61 to -104‰) and δ18O (e.g., quartz +9.6 to +13.4‰) values with multiple minerals in apparent isotopic equilibrium (T ~ 450-550°C) suggest a low W/R system dominated by metamorphic fluids. Variable and non-equilibrium δD (-53 to -143‰) and δ18O (e.g., biotite +2.3 to +5.3‰) values from diorites of the Quottoon pluton affected by the ductile CRM suggest a complex evolution that involved both metamorphic and meteoric-hydrothermal fluids in this dextral shear zone; these results differ from those 300 km along strike to the north that documented only metamorphic fluids in the CRM (Goldfarb et al., 1988). Our data and those of Magaritz and Taylor (1976) from granulite facies metasediments of the CGC and plutons of the western CRB reveal homogeneous δD values (-62 to -78‰) and a restricted range of δ18O values (e.g., quartz +8.5 to +11.5‰) with all minerals in equilibrium at T > 570°C indicate a system dominated by magmatic fluids. Calculated whole-rock δ18O values (~ +7‰) for the Quottoon pluton and CRB intrusive rocks suggest a mantle origin for these magmas. Reinterpretation of very low δD (< -150‰) and quartz-feldspar δ18O pairs that display extreme disequilibrium (feldspar δ18O values as low as -5‰) from the Ponder pluton, eastern CRB, and Hazelton Group point reveals that the major meteoric-hydrothermal system that affected these rocks was related to Eocene detachment faulting along the Shames Lake fault system, a

  13. Stable intergenerational associations of childhood overweight during the development of the obesity epidemic.

    Science.gov (United States)

    Ajslev, Teresa A; Ängquist, Lars; Silventoinen, Karri; Baker, Jennifer L; Sørensen, Thorkild I A

    2015-06-01

    The obesity epidemic may have developed as a response to the obesogenic environment among the genetically predisposed. This investigation examined whether the intergenerational resemblances in childhood overweight changed across the development of the obesity epidemic in groups of children born to parents with and without childhood overweight. The study population was from the Copenhagen School Health Records Register, which includes age- and sex-specific body mass index (BMI; kg/m(2) ) of children. This study used BMI values from 7-year-old children born 1952-1989 and from their parents at ages 7 and 13 years. The available number of parent-child pairs ranged from 17,926 through 42,184. The odds ratios of childhood overweight (BMI z-score >90th percentile) were calculated using logistic regression by parental BMI groups (BMI > or ≤90th percentile) and child birth year intervals. Stable levels in parent-child overweight associations were observed across child BMI groups born to parents with and without childhood overweight. A slight upward odds ratio trend was observed across time in children born to two overweight parents at age 13, but not at age 7 years. Parent-child resemblance in childhood overweight showed small changes during the development of the obesity epidemic, suggesting that the obesogenic environment inducing the epidemic in Denmark influenced children irrespective of their familial predisposition. © 2015 The Obesity Society.

  14. Chronic stable angina is associated with lower health-related quality of life: evidence from Chinese patients.

    Directory of Open Access Journals (Sweden)

    Jing Wu

    Full Text Available OBJECTIVES: To compare health-related quality of life (HRQoL between patients with stable angina and the general population in China and to examine factors associated with HRQoL among patients with stable angina. METHODS: A cross-sectional HRQoL survey of stable angina patients recruited from 4 hospitals (n = 411 and the general population recruited from 3 Physical Examination Centers (n = 549 was conducted from July to December, 2011 in two large cities, Tianjin and Chengdu. HRQoL was assessed using the EQ-5D, EQ-VAS, and SF-6D instruments. The health status specific to patients with stable angina was assessed using the Seattle Angina Questionnaire (SAQ. Information on socio-demographic, clinical, and lifestyle factors were also collected. Nested regressions were performed to explore how these factors were associated with HRQoL in patients with stable angina. RESULTS: Compared with the general population (44.2 ± 10 years, 49.9% females, stable angina patients (68.1 ± 12 years, 50.4% females had significantly lower HRQoL scores in EQ-5D utility index (0.75 ± 0.19 vs. 0.90 ± 0.20, p<0.05, SF-6D utility index (0.68 ± 0.12 vs. 0.85 ± 0.11, p<0.05, and EQ-VAS (71.2 ± 12.3 vs. 83.9 ± 10.9, p<0.05. The differences remained (-0.05 for EQ-5D, -9.27 for EQ-VAS and -0.13 for SF-6D after controlling for socio-economic characteristics. SAQ scores showed that stable angina patients experienced impaired disease-specific health status, especially in angina stability (40.5 ± 34.6. Nested regressions indicated stable angina-specific health status explained most of the variation in HRQoL, among which disease perception, physical limitation, and angina stability were the strongest predictors. More physical exercise and better sleep were positively related with HRQoL. CONCLUSIONS: Compared to the general population, stable angina patients were associated with lower HRQoL and lower health utility scores, which were largely impacted by clinical symptoms

  15. Association of small dense LDL serum levels and circulating monocyte subsets in stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Konstantin A Krychtiuk

    Full Text Available Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-, intermediate monocytes (IM; CD14++CD16+ and non-classical monocytes (NCM; CD14+CD16++. Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3 showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01 when compared with patients in the middle (sdLDL=2-3mg/dL;T2 and lowest tertile (sdLDL=0-1mg/dL;T1. Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1. Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively. In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.

  16. Complex Partial Epilepsy Associated with Temporal Lobe Developmental Venous Anomaly.

    Science.gov (United States)

    Sohail, Amna; Xiong, Zhengming; Qureshi, Mushtaq H; Qureshi, Adnan I

    2015-05-01

    Developmental venous anomalies (DVA) are found incidentally but sometimes patients with these anomalies present with varying degrees of neurologic manifestations. We report a patient with early onset complex partial epilepsy and associated DVA and discuss the natural history, neuroimaging and clinical characteristics, and management. A 21-year-old man presented with a history of complex partial epilepsy with secondary generalization which started at the age of 4 years. An electroencephalogram (EEG) was performed which demonstrated spike and wave discharges predominantly in the left frontotemporal region. A magnetic resonance imaging (MRI) was performed which demonstrated a linear flow void suggestive of a DVA. The angiogram demonstrated DVA that connected with the left transverse venous sinus and an anastomotic vein between the straight sinus and the transverse venous sinus traversing the brain parenchyma. He was started on carbamezipine for the treatment of complex partial seizures. Temporal lobe DVA may be associated with complex partial seizures and can be diagnosed by MRI and angiographic findings.

  17. Identification and Validation of PTEN Complex, Associated Proteins

    Science.gov (United States)

    2005-11-01

    not engage in cell cycle arrest or apoptosis. If this approach will fail we will re-clone the ProteinA -CBP- PTEN fusion protein under a Tetracycline...1-0029 TITLE: Identification and Validation of PTEN Complex, Associated Proteins...TYPE Annual Summary 3. DATES COVERED (From - To) 1 Nov 2004 – 31 Oct 2005 4. TITLE AND SUBTITLE Identification and Validation of PTEN Complex

  18. Synergistic effect of signaling from receptors of soluble platelet agonists and outside-in signaling in formation of a stable fibrinogen-integrin αIIbβ3-actin cytoskeleton complex.

    Science.gov (United States)

    Budnik, Ivan; Shenkman, Boris; Savion, Naphtali

    2015-01-01

    Thrombus formation in the injured vessel wall is a highly complex process involving various blood-born components that go through specific temporal and spatial changes as observed by intravital videomicroscopy. Platelets bind transiently to the developing thrombus and may either become stably incorporated into or disengage from the thrombus. The aim of the present study was to reveal the processes involved in the formation of a stable thrombus. Platelet-rich plasma and washed platelets were studied by the aggregometer. The aggregate stability was challenged by eptifibatide. Platelet Triton-insoluble fraction was prepared and the actin and αIIb content in the cytoskeleton was analyzed by western blot. Maximal actin polymerization is achieved 1min after platelet activation while maximal αIIbβ3-actin cytoskeleton association requires 5 to 10min of activation and fibrinogen-mediated platelet-to-platelet bridging. Thus, actin polymerization is dependent on platelet activation and requires neither αIIbβ3 integrin occupation nor platelet aggregation. Formation of a stable aggregate requires platelet activation for more than 1min, complete increase in actin cytoskeleton fraction and partial association of αIIbβ3 with the actin cytoskeleton. However, direct αIIbβ3 activation is not sufficient for cytoskeleton complex formation. Thus, stable αIIbβ3-fibrinogen interaction, representing stable aggregate, is achieved after more than 1min agonist activation, involving inside-out and outside-in signaling but not after direct integrin activation, involving only outside-in signaling. Formation of a stable fibrinogen-αIIbβ3-actin cytoskeleton complex is the result of the combined effect of platelet stimulation by soluble agonists, activation of αIIbβ3, fibrinogen binding and platelet-to-platelet bridging. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

    Science.gov (United States)

    Barba, Carmen; Specchio, Nicola; Guerrini, Renzo; Tassi, Laura; De Masi, Salvatore; Cardinale, Francesco; Pellacani, Simona; De Palma, Luca; Battaglia, Domenica; Tamburrini, Gianpiero; Didato, Giuseppe; Freri, Elena; Consales, Alessandro; Nozza, Paolo; Zamponi, Nelia; Cesaroni, Elisabetta; Di Gennaro, Giancarlo; Esposito, Vincenzo; Giulioni, Marco; Tinuper, Paolo; Colicchio, Gabriella; Rocchi, Raffaele; Rubboli, Guido; Giordano, Flavio; Lo Russo, Giorgio; Marras, Carlo Efisio; Cossu, Massimo

    2017-10-01

    The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014. A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014. Retrospective data on 527 surgical procedures were collected. The most frequent surgical approaches were temporal lobe resections and disconnections (133, 25.2%) and extratemporal lesionectomies (128, 24.3%); the most frequent etiologies were FCD II (107, 20.3%) and glioneuronal tumors (105, 19.9%). Volumes of surgeries increased over time independently from the age at surgery and the epilepsy surgery center. Engel class I was achieved in 73.6% of patients (range: 54.8 to 91.7%), with no significant changes between 2008 and 2014. Univariate analyses showed a decrease in the proportion of temporal resections and tumors and an increase in the proportion of FCDII, while multivariate analyses revealed an increase in the proportion of extratemporal surgeries over time. A higher proportion of temporal surgeries and tumors and a lower proportion of extratemporal and multilobar surgeries and of FCD were observed in low (epilepsy surgery in Italy between 2008 and 2014, associated with a stable seizure outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Transient association of MCM complex proteins with the nuclear matrix during initiation of mammalian DNA replication.

    Science.gov (United States)

    Hesketh, Emma L; Knight, John R P; Wilson, Rosemary H C; Chong, James P J; Coverley, Dawn

    2015-01-01

    The minichromosome maintenance complex (MCM2-7) is the putative DNA helicase in eukaryotes, and essential for DNA replication. By applying serial extractions to mammalian cells synchronized by release from quiescence, we reveal dynamic changes to the sub-nuclear compartmentalization of MCM2 as cells pass through late G1 and early S phase, identifying a brief window when MCM2 becomes transiently attached to the nuclear-matrix. The data distinguish 3 states that correspond to loose association with chromatin prior to DNA replication, transient highly stable binding to the nuclear-matrix coincident with initiation, and a post-initiation phase when MCM2 remains tightly associated with chromatin but not the nuclear-matrix. The data suggests that functional MCM complex loading takes place at the nuclear-matrix.

  1. Contribution of Large Region Joint Associations to Complex Traits Genetics

    Science.gov (United States)

    Paré, Guillaume; Asma, Senay; Deng, Wei Q.

    2015-01-01

    A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

  2. Inert and stable erbium(III)-cored complexes based on metalloporphyrins bearing aryl-ether dendron for optical amplification: synthesis and emission enhancement

    International Nuclear Information System (INIS)

    Oh, Jae Buem; Kim, Yong Hee; Nah, Min Kook; Kim, Hwan Kyu

    2005-01-01

    We have developed novel inert and stable erbium (Er)(III)-cored complexes based on metalloporphyrins for optical amplification. The functionalized metalloporphyrin ligands have been designed and synthesized to provide enough coordination sites for the formation of inert and stable 9-coordinated Er(III)-cored complexes. Er 3+ ions were encapsulated by the metalloporphyrin ligands, such as Zn(II)- and Pt(II)-porphyrins. The near-infrared (IR) emission intensity of Er 3+ ion is much stronger in the Er(III)-cored complex based on Pt(II)-porphyrin than Er(III)-cored complex based on Zn(II)-porphyrin. Furthermore, we have incorporated a G2-aryl-ether functionalized dendron into the Er(III)-cored complex, yielding an Er(III)-cored dendrimer complex bearing the Pt(II)-porphyrin. The Er(III)-cored dendrimer complex shows the stronger near-IR emission intensity than the corresponding complex based on Pt(II)-porphyrin by seven times in solid state. The lifetimes of the emission band of Pt(II)-porphyrin ligands in the visible region were found to be 30 and 40 μs for the Er(III)-cored complex and the Er(III)-cored dendrimer complex based on Pt(II)-porphyrin in deoxygenated THF solution samples, respectively. Also, in both cases, the sensitized luminescence intensity is increased in deoxygenated solution. Therefore, it indicates that the energy transfer from the metalloporphyrins to Er 3+ ions takes places through the triplet state. In this paper, the synthesis and photophysical properties of novel Er(III)-cored complexes based on metalloporphyrins and Er(III)-cored dendrimer complex based on metalloporphyrin will be discussed

  3. Bark Beetle-Fungal Symbiosis: Context Dependency in Complex Associations

    Science.gov (United States)

    Kier D. Klepzig; D.L. Six

    2004-01-01

    Recent thinking in symbiosis research has emphasized a holistic consideration of these complex interactions. Bark beetles and their associated microbes are one group which has previously not been addressed in this manner. We review the study of symbiotic interactions among bark beetles and microbes in light of this thinking. We describe the considerable progress...

  4. [OEIS complex. Description of a case associated with cardiopathy].

    Science.gov (United States)

    Faranda, F; Zucchinetti, P; Pozzolo, S; Romagnoli, G; Camera, G

    1993-01-01

    We describe a newborn affected by OEIS complex (Omphalocele--Exstrophy of bladder--Imperforate anus--Spinal defect) associated with atrial septal defect. Terminal ileostomy, closure of the abdominal wall defect and suture of the cecal and vesical plates were performed. The patient died at 5 months and four days.

  5. Progresses in the stable isotope studies of microbial processes associated with wetland methane production

    International Nuclear Information System (INIS)

    Li Qing; Lin Guanghui

    2013-01-01

    Methane emissions from wetlands play a key role in regulating global atmospheric methane concentration, so better understanding of microbial processes for the methane emission in wetlands is critical for developing process models and reducing uncertainty in global methane emission inventory. In this review, we describe basic microbial processes for wetland methane production and then demonstrate how stable isotope fractionation and stable isotope probing can be used to investigate the mechanisms underlying different methanogenic pathways and to quantify microbial species involved in wetland methane production. When applying stable isotope technique to calculate contributions of different pathways to the total methane production in various wetlands, the technical challenge is how to determine isotopic fractionation factors for the acetate derived methane production and carbon dioxide derived methane production. Although the application of stable isotope probing techniques to study the actual functions of different microbial organisms to methane production process is significantly superior to the traditional molecular biology method, the combination of these two technologies will be crucial for direct linking of the microbial community and functional structure with the corresponding metabolic functions, and provide new ideas for future studies. (authors)

  6. Environmental parameters associated with stable fly (Diptera: Muscidae) development at hay feeding sites

    Science.gov (United States)

    Substrates composed of hay residues, dung, and urine accumulate around winter hay feeding sites in cattle pastures, providing developmental habitats for stable flies. The objective of this study was to relate physiochemical and microbial properties of these substrates to the presence or absence of s...

  7. Environmental parameters associated with stable fly development at hay feeding sites

    Science.gov (United States)

    Substrates composed of hay residues, dung, and urine accumulate around winter hay feeding sites in cattle pastures providing developmental habitat for stable flies. The objective of this study was to relate physiochemical and microbial properties of this substrate to the presence or absence of devel...

  8. Environmental Parameters Associated With Stable Fly (Diptera: Muscidae) Development at Hay Feeding Sites.

    Science.gov (United States)

    Friesen, Kristina; Berkebile, Dennis; Wienhold, Brian; Durso, Lisa; Zhu, Jerry; Taylor, David B

    2016-03-25

    Substrates composed of hay residues, dung, and urine accumulate around winter hay feeding sites in cattle pastures, providing developmental habitats for stable flies. The objective of this study was to relate physiochemical and microbial properties of these substrates to the presence or absence of stable fly larvae. Properties included pH, temperature, moisture, ammonium concentration, electrical conductivity, and numbers of coliform, fecal coliform,Escherichia coli, andEnterococcusbacteria. Each physiochemical sample was classified as a function of belonging to one of the three 2-m concentric zones radiating from the feeder as well as presence or absence of larvae. In total, 538 samples were collected from 13 sites during 2005-2011. Stable fly larvae were most likely to be found in moist, slightly alkaline substrates with high levels of ammonium and low temperature. The probability of larvae being present in a sample was the highest when the moisture content was 347% relative to dry weight and the average pH was 8.4. Larvae were recovered within all zones, with a nonsignificant, but slightly higher, percentage of samples containing larvae taken 2-4 m from the center. All methods used to enumerate bacteria, except total coliform, indicated decreasing concentrations in hay bale residue throughout the summer. In addition to the environmental parameters, cumulative degree day 10°C had a significant effect on the probability of observing stable fly larvae in a sample, indicating that unidentified seasonal effects also influenced immature stable fly populations. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the United States.

  9. Rapid Associative Learning and Stable Long-Term Memory in the Squid Euprymna scolopes.

    Science.gov (United States)

    Zepeda, Emily A; Veline, Robert J; Crook, Robyn J

    2017-06-01

    Learning and memory in cephalopod molluscs have received intensive study because of cephalopods' complex behavioral repertoire and relatively accessible nervous systems. While most of this research has been conducted using octopus and cuttlefish species, there has been relatively little work on squid. Euprymna scolopes Berry, 1913, a sepiolid squid, is a promising model for further exploration of cephalopod cognition. These small squid have been studied in detail for their symbiotic relationship with bioluminescent bacteria, and their short generation time and successful captive breeding through multiple generations make them appealing models for neurobiological research. However, little is known about their behavior or cognitive ability. Using the well-established "prawn-in-the-tube" assay of learning and memory, we show that within a single 10-min trial E. scolopes learns to inhibit its predatory behavior, and after three trials it can retain this memory for at least 12 d. Rapid learning and very long-term retention were apparent under two different training schedules. To our knowledge, this study is the first demonstration of learning and memory in this species as well as the first demonstration of associative learning in any squid.

  10. Regulation of the Chlamydomonas Cell Cycle by a Stable, Chromatin-Associated Retinoblastoma Tumor Suppressor Complex

    Czech Academy of Sciences Publication Activity Database

    Olson, B. J. S. C.; Oberholzer, M.; Li, Y.; Zones, J. M.; Kohli, H. S.; Bišová, Kateřina; Fang, S.; Ch.; Meisenhelder, J.; Hunter, T.; Umen, J. G.

    2010-01-01

    Roč. 22, č. 10 (2010), s. 3331-3347 ISSN 1040-4651 Institutional research plan: CEZ:AV0Z50200510 Keywords : GENOME-WIDE ANALYSIS * TRANSCRIPTION FACTOR * GENE-PRODUCT Subject RIV: EE - Microbiology, Virology Impact factor: 9.396, year: 2010

  11. Fear conditioning with film clips: a complex associative learning paradigm.

    Science.gov (United States)

    Kunze, Anna E; Arntz, Arnoud; Kindt, Merel

    2015-06-01

    We argue that the stimuli used in traditional fear conditioning paradigms are too simple to model the learning and unlearning of complex fear memories. We therefore developed and tested an adapted fear conditioning paradigm, specifically designed for the study of complex associative memories. Second, we explored whether manipulating the meaning and complexity of the CS-UCS association strengthened the learned fear association. In a two-day differential fear conditioning study, participants were randomly assigned to two experimental conditions. All participants were subjected to the same CSs (i.e., pictures) and UCS (i.e., 3 s film clip) during fear conditioning. However, in one of the conditions (negative-relevant context), the reinforced CS and UCS were meaningfully connected to each other by a 12 min aversive film clip presented prior to fear acquisition. Participants in the other condition (neutral context) were not able to make such meaningful connection between these stimuli, as they viewed a neutral film clip. Fear learning and unlearning were observed on fear-potentiated startle data and distress ratings within the adapted paradigm. Moreover, several group differences on these measures indicated increased UCS valence and enhanced associative memory strength in the negative-relevant context condition compared to the neutral context condition. Due to technical equipment failure, skin conductance data could not be interpreted. The fear conditioning paradigm as presented in the negative-relevant context condition holds considerable promise for the study of complex associative fear memories and therapeutic interventions for such memories. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model.

    Directory of Open Access Journals (Sweden)

    Tilman Jobst-Schwan

    Full Text Available Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest.

  13. Decomposition of overlapping protein complexes: A graph theoretical method for analyzing static and dynamic protein associations

    Directory of Open Access Journals (Sweden)

    Guimarães Katia S

    2006-04-01

    Full Text Available Abstract Background Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. Some proteins form stable complexes, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. Results We propose a new method for identifying and representing overlapping protein complexes (or larger units called functional groups within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. We illustrate the effectiveness of our method by applying it to TNFα/NF-κB and pheromone signaling pathways. Conclusion The proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. Our results show that the proposed method opens a new avenue for the analysis of protein interaction networks.

  14. Dentigerous cyst associated with multiple complex composite odontomas

    Directory of Open Access Journals (Sweden)

    Sangeeta P Wanjari

    2011-01-01

    Full Text Available Odontomas are considered to be hamartomatous malformations rather than true neoplasms. This most common odontogenic lesion results from the growth of completely differentiated epithelial and mesenchymal cells that give rise to ameloblasts and odontoblasts. Dentigerous cyst is an epithelium-lined sac enclosing the crown of an unerupted tooth. Apparently, the dentigerous cyst arises by the accumulation of fluid between reduced enamel epithelium and the tooth crown. Occasionally it is associated with supernumerary tooth or odontoma. We report a case of dentigerous cyst associated with complex composite odontoma and an impacted lateral incisor in a 30-year-old male patient.

  15. Metabolic syndrome is independently associated with increased 20-year mortality in patients with stable coronary artery disease.

    Science.gov (United States)

    Younis, Arwa; Younis, Anan; Tzur, Boaz; Peled, Yael; Shlomo, Nir; Goldenberg, Ilan; Fisman, Enrique Z; Tenenbaum, Alexander; Klempfner, Robert

    2016-10-28

    Data regarding long-term association of metabolic syndrome (MetS) with adverse outcomes are conflicting. We aim to determine the independent association of MetS (based on its different definitions) with 20 year all-cause mortality among patients with stable coronary artery disease (CAD). Our study comprised 15,524 patients who were enrolled in the Bezafibrate Infarction Prevention registry between February 1, 1990, and October 31, 1992, and subsequently followed-up for the long-term mortality through December 31, 2014. MetS was defined according to two definitions: The International Diabetes Federation (IDF); and the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP). According to the IDF criteria 2122 (14%) patients had MetS, whereas according to the NCEP definition 7446 (48%) patients had MetS. Kaplan-Meier survival analysis showed that all-cause mortality was significantly higher among patients with MetS defined by both the IDF (67 vs. 61%; log rank-p definition. Subgroup analysis demonstrated that long-term increased mortality risk associated with MetS was consistent among most clinical subgroups excepted patients with renal failure (p value for interaction Metabolic syndrome is independently associated with an increased 20-year all-cause mortality risk among patients with stable CAD. This association was consistent when either the IDF or NCEP definitions were used. Trial registration retrospective registered.

  16. Is going into stable symptomatic remission associated with a more positive development of life satisfaction?

    DEFF Research Database (Denmark)

    Gardsjord, Erlend Strand; Romm, Kristin Lie; Røssberg, Jan Ivar

    2017-01-01

    by the Remission in Schizophrenia Working Group. One-way ANOVA, mixed model analysis, bivariate correlations and multiple regression analyses were performed. RESULTS: Patients going into stable symptomatic remission showed a more positive S-QoL-development over the follow-up period and reported higher life...... satisfaction at 10-year follow-up compared to non-remission. At 10-year follow-up, depressive symptoms and alcohol abuse or dependence explained a significant amount of variance in S-QoL among patients in remission. Among patients in non-remission, PANSS excitative component explained a significant amount...... implications. While patients in remission might need treatment for depressive symptoms to increase S-QoL, in non-remission measures aiming to decrease hostility and uncooperativeness should be part of the treatment approach. Alcohol problems should be treated regardless of remission status....

  17. Carbon Stable Isotope Values in Plankton and Mussels Reflect Changes in Carbonate Chemistry Associated with Nutrient Enhanced Net Production

    Directory of Open Access Journals (Sweden)

    Autumn Oczkowski

    2018-02-01

    Full Text Available Coastal ecosystems are inherently complex and potentially adaptive as they respond to changes in nutrient loads and climate. We documented the role that carbon stable isotope (δ13C measurements could play in understanding that adaptation with a series of three Ecostat (i.e., continuous culture experiments. We quantified linkages among δ13C, nutrients, carbonate chemistry, primary, and secondary production in temperate estuarine waters. Experimental culture vessels (9.1 L containing 33% whole and 67% filtered (0.2 μm seawater were amended with dissolved inorganic nitrogen (N and phosphorous (P in low (3 vessels; 5 μM N, 0.3 μM P, moderate (3 vessels; 25 μM N, 1.6 μM P, and high amounts (3 vessels; 50 μM N, 3.1 μM P. The parameters necessary to calculate carbonate chemistry, chlorophyll-a concentrations, and particulate δ13C values were measured throughout the 14 day experiments. Outflow lines from the experimental vessels fed 250 ml containers seeded with juvenile blue mussels (Mytilus edulis. Mussel subsamples were harvested on days 0, 7, and 14 and their tissues were analyzed for δ13C values. We consistently observed that particulate δ13C values were positively correlated with chlorophyll-a, carbonate chemistry, and to changes in the ratio of bicarbonate to dissolved carbon dioxide (HCO3-:CO2. While the relative proportion of HCO3- to CO2 increased over the 14 days, concentrations of each declined, reflecting the drawdown of carbon associated with enhanced production. Plankton δ13C values, like chlorophyll-a concentrations, increased over the course of each experiment, with the greatest increases in the moderate and high treatments. Trends in δ13C over time were also observed in the mussel tissues. Despite ecological variability and different plankton abundances the experiments consistently demonstrated how δ13C values in primary producers and consumers reflected nutrient availability, via its impact on carbonate chemistry. We

  18. Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation in COPD at Stable State and Exacerbations

    Science.gov (United States)

    Barker, Bethan L.; Haldar, Koirobi; Patel, Hemu; Pavord, Ian D.; Barer, Michael R.; Brightling, Christopher E.

    2015-01-01

    BACKGROUND: Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear. Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations. METHODS: Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform. Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR. Symptoms were quantified using the visual analog scale. RESULTS: At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae. Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis. Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α. H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β. In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations. CONCLUSIONS: At stable state, H influenzae is associated with increased airway inflammation in COPD. The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. PMID:25103335

  19. A thermally stable and sterically unprotected terminal electrophilic phosphinidene complex of cobalt and its conversion to an eta(1)-phosphirene.

    Science.gov (United States)

    Sánchez-Nieves, Javier; Sterenberg, Brian T; Udachin, Konstantin A; Carty, Arthur J

    2003-03-05

    The terminal chloroaminophosphido complex [Co(CO)3(PPh3){P(Cl)NiPr2}] is formed via reaction of K[Co(CO)4] with iPr2NPCl2 in the presence of triphenylphosphine. Chloride abstraction by aluminum trichloride leads to the first terminal phosphinidene complex of cobalt, [Co(CO)3(PPh3)(PNiPr2)][AlCl4]. The electrophilicity of the phosphinidene was demonstrated by its reaction with diphenylacetylene to form the phosphirene complex [Co(CO)3(PPh3){P(NiPr2)C(Ph)C(Ph)}][AlCl4].

  20. Histopathological insight of complex odontoma associated with a dentigerous cyst.

    Science.gov (United States)

    Astekar, Madhusudan; Manjunatha, Bhari Sharanesha; Kaur, Prabhpreet; Singh, Jappreet

    2014-01-31

    Odontomas and dentigerous cysts are common findings for practicing dental professionals. However, simultaneous occurrence of pathologies like odontoma and dentigerous cyst are uncommon and their diagnosis based on the radiographic appearance alone is a challenge to overcome. They together are a potential for complications like attaining large size, root resorption, destruction of the jaw bones and sometimes neoplastic changes like ameloblastoma. This paper presents a case of complex odontoma associated with dentigerous cyst in relation to a retained deciduous tooth in the maxillary anterior region and confirming its diagnosis histopathologically.

  1. Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

    Science.gov (United States)

    Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

    2015-01-01

    Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

  2. The association between self-esteem and happiness differs in relationally mobile vs. stable interpersonal contexts

    OpenAIRE

    Sato, Kosuke; Yuki, Masaki

    2014-01-01

    Does a change in the nature of surrounding social context affect the strength of association between self-esteem and happiness? This paper aims to answer this question from a socio-ecological perspective, focusing on the role of relational mobility. Recent research has shown that this association is stronger in societies that are higher in relational mobility, where there is a greater freedom of choice in interpersonal relationships and group memberships. In this study, we tested if this hypo...

  3. Till death do us part: stable sponge-bacteria associations under thermal and food shortage stresses.

    Directory of Open Access Journals (Sweden)

    Lucía Pita

    Full Text Available Sporadic mass mortality events of Mediterranean sponges following periods of anomalously high temperatures or longer than usual stratification of the seawater column (i.e. low food availability suggest that these animals are sensitive to environmental stresses. The Mediterranean sponges Ircinia fasciculata and I. oros harbor distinct, species-specific bacterial communities that are highly stable over time and space but little is known about how anomalous environmental conditions affect the structure of the resident bacterial communities. Here, we monitored the bacterial communities in I. fasciculata (largely affected by mass mortalities and I. oros (overall unaffected maintained in aquaria during 3 weeks under 4 treatments that mimicked realistic stress pressures: control conditions (13°C, unfiltered seawater, low food availability (13°C, 0.1 µm-filtered seawater, elevated temperatures (25°C, unfiltered seawater, and a combination of the 2 stressors (25°C, 0.1 µm-filtered seawater. Bacterial community structure was assessed using terminal restriction fragment length polymorphism (T-RFLP analysis of 16S rRNA gene sequences and transmission electron microscopy (TEM. As I. fasciculata harbors cyanobacteria, we also measured chlorophyll a (chl a levels in this species. Multivariate analysis revealed no significant differences in bacterial T-RFLP profiles among treatments for either host sponge species, indicating no effect of high temperatures and food shortage on symbiont community structure. In I. fasciculata, chl a content did not significantly differ among treatments although TEM micrographs revealed some cyanobacteria cells undergoing degradation when exposed to both elevated temperature and food shortage conditions. Arguably, longer-term treatments (months could have eventually affected bacterial community structure. However, we evidenced no appreciable decay of the symbiotic community in response to medium-term (3 weeks environmental

  4. Complex Medial Meniscus Tears Are Associated With a Biconcave Medial Tibial Plateau.

    Science.gov (United States)

    Barber, F Alan; Getelman, Mark H; Berry, Kathy L

    2017-04-01

    To determine whether an association exists between a biconcave medial tibial plateau and complex medial meniscus tears. A consecutive series of stable knees undergoing arthroscopy were evaluated retrospectively with the use of preoperative magnetic resonance imaging (MRI), radiographs, and arthroscopy documented by intraoperative videos. Investigators independently performed blinded reviews of the MRI or videos. Based on the arthroscopy findings, medial tibial plateaus were classified as either biconcave or not biconcave. A transverse coronal plane ridge, separating the front of the tibial plateau from the back near the inner margin of the posterior body of the medial meniscus, was defined as biconcave. The medial plateau slope was calculated with MRI sagittal views. General demographic information, body mass index, and arthroscopically confirmed knee pathology were recorded. A total of 179 consecutive knees were studied from July 2014 through August 2015; 49 (27.2%) biconcave medial tibial plateaus and 130 (72.8%) controls were identified at arthroscopy. Complex medial meniscus tears were found in 103. Patients with a biconcave medial tibial plateau were found to have more complex medial meniscus tears (69.4%) than those without a biconcavity (53.1%) (P = .049) despite having lower body mass index (P = .020). No difference in medial tibial plateau slope was observed for biconcavities involving both cartilage and bone, bone only, or an indeterminate group (P = .47). Biconcave medial tibial plateaus were present in 27.4% of a consecutive series of patients undergoing knee arthroscopy. A biconcave medial tibial plateau was more frequently associated with a complex medial meniscus tear. Level III, case-control study. Copyright © 2016 Arthroscopy Association of North America. All rights reserved.

  5. Highly Chemo- and Stereoselective Transfer Semihydrogenation of Alkynes Catalyzed by a Stable, Well-defined Manganese(II) Complex

    KAUST Repository

    Brzozowska, Aleksandra

    2018-03-30

    The first example of manganese catalyzed semihydrogenation of internal alkynes to (Z)-alkenes using ammonia borane as a hydrogen donor is reported. The reaction is catalyzed by a pincer complex of the earth abundant manganese(II) salt in the absence of any additives, base or super hydride. The ammonia borane smoothly reduces the manganese pre-catalyst [Mn(II)-PNP][Cl]2 to the catalytically active species [Mn(I)-PNP]-hydride in the triplet spin state. This manganese hydride is highly stabilized by complexation with the alkyne substrate. Computational DFT analysis studies of the reaction mechanism rationalizes the origin of stereoselectivity towards formation of (Z)-alkenes.

  6. Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8.

    Science.gov (United States)

    Murakami, Takeshi; Takano, Ryuji; Takeo, Satoshi; Taniguchi, Rina; Ogawa, Kaori; Ohashi, Eiji; Tsurimoto, Toshiki

    2010-11-05

    One of the proliferating cell nuclear antigen loader complexes, Ctf18-replication factor C (RFC), is involved in sister chromatid cohesion. To examine its relationship with factors involved in DNA replication, we performed a proteomics analysis of Ctf18-interacting proteins. We found that Ctf18 interacts with a replicative DNA polymerase, DNA polymerase ε (pol ε). Co-immunoprecipitation with recombinant Ctf18-RFC and pol ε demonstrated that their binding is direct and mediated by two distinct interactions, one weak and one stable. Three subunits that are specifically required for cohesion in yeast, Ctf18, Dcc1, and Ctf8, formed a trimeric complex (18-1-8) and together enabled stable binding with pol ε. The C-terminal 23-amino acid stretch of Ctf18 was necessary for the trimeric association of 18-1-8 and was required for the stable interaction. The weak interaction was observed with alternative loader complexes including Ctf18-RFC(5), which lacks Dcc1 and Ctf8, suggesting that the common loader structures, including the RFC small subunits (RFC2-5), are responsible for the weak interaction. The two interaction modes, mediated through distinguishable structures of Ctf18-RFC, both occurred through the N-terminal half of pol ε, which includes the catalytic domain. The addition of Ctf18-RFC or Ctf18-RFC(5) to the DNA synthesis reaction caused partial inhibition and stimulation, respectively. Thus, Ctf18-RFC has multiple interactions with pol ε that promote polymorphic modulation of DNA synthesis. We propose that their interaction alters the DNA synthesis mode to enable the replication fork to cooperate with the establishment of cohesion.

  7. Encounter complexes and dimensionality reduction in protein–protein association

    Science.gov (United States)

    Kozakov, Dima; Li, Keyong; Hall, David R; Beglov, Dmitri; Zheng, Jiefu; Vakili, Pirooz; Schueler-Furman, Ora; Paschalidis, Ioannis Ch; Clore, G Marius; Vajda, Sandor

    2014-01-01

    An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition. DOI: http://dx.doi.org/10.7554/eLife.01370.001 PMID:24714491

  8. Encounter complexes and dimensionality reduction in protein-protein association.

    Science.gov (United States)

    Kozakov, Dima; Li, Keyong; Hall, David R; Beglov, Dmitri; Zheng, Jiefu; Vakili, Pirooz; Schueler-Furman, Ora; Paschalidis, Ioannis Ch; Clore, G Marius; Vajda, Sandor

    2014-04-08

    An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein-protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition. DOI: http://dx.doi.org/10.7554/eLife.01370.001.

  9. Comparison of association mapping methods in a complex pedigreed population

    DEFF Research Database (Denmark)

    Sahana, Goutam; Guldbrandtsen, Bernt; Janss, Luc

    2010-01-01

    Association mapping methods were compared using a simulation with a complex pedigree structure. The pedigree was simulated while keeping the present Danish Holstein population pedigree in view. A total of 15 quantitative trait loci (QTL) with varying effect sizes (10%, 5% and 2% of total genetic...... variance) were simulated. We compared the single-marker test, haplotype-based analysis, mixed model approach, and Bayesian analysis. The methods were compared for power, precision of location estimates, and type I error rates. Results found the best performance in a Bayesian method that included genetic...... background effects and simultaneously fitted all single-nucleotide polymorphisms (SNPs) with a variable selection method. A mixed model analysis that fitted genetic background effects and tested one SNP at a time performed nearly as well as the Bayesian method. For the Bayesian method, it proved necessary...

  10. Nitrogen acquisition, transport and metabolism in intact ectomycorrhizal associations studied by 15N stable isotope techniques

    International Nuclear Information System (INIS)

    Ek, H.

    1993-05-01

    The focus of this thesis is on the external mycelium and its role in nitrogen uptake, assimilation and translocation. Tree seedlings in association with ectomycorrhizal fungi were grown in observation chambers. The fungal mycelium were fed with 15-N ammonium or 15-N nitrate or a combination of both. The effects of Collembola on the ectomycorrhizal symbiosis were also studied. The results demonstrates an important role of the external mycelium of Paxillus involutus not only in the uptake but also in the assimilation of ammonium into a variety of different amino acids, primarily glutamine but also glutamic acid, aspartic acid, and alanine, immediately after uptake. The results indicate that ammonium is assimilated by GS and GOGAT or GDH in the mycelium at the uptake site. When nitrate was added to the mycelium as the sole nitrogen source nitrate was reduced in the mycelium and the product assimilated into amino acids. When ammonium nitrate was supplied to the fungal mycelium nitrate was taken up the fungus and transferred to the plant, however, apparently no assimilation of nitrate occurred in the external mycelium. Ammonium or an assimilation product, such as glutamine, probably represses nitrate reductase (NR) but not nitrate uptake and transfer in P. involutus. P. involutus nitrogen uptake and transfer to the associated mycorrhizal pine was up to 76% higher when low numbers of the Collembola Onychiurus armatus were present compared to when they were completely absent. This was probably an indirect effect as P. involutus hyphal growth rate and extramatrical biomass increased at a low Collembola density. At high Collembola densities P. involutus hyphal growth rate was retarded. (74 refs.)

  11. Smaller Fixation Target Size Is Associated with More Stable Fixation and Less Variance in Threshold Sensitivity.

    Directory of Open Access Journals (Sweden)

    Kazunori Hirasawa

    Full Text Available The aims of this randomized observational case control study were to quantify fixation behavior during standard automated perimetry (SAP with different fixation targets and to evaluate the relationship between fixation behavior and threshold variability at each test point in healthy young participants experienced with perimetry. SAP was performed on the right eyes of 29 participants using the Octopus 900 perimeter, program 32, dynamic strategy. The fixation targets of Point, Cross, and Ring were used for SAP. Fixation behavior was recorded using a wearable eye-tracking glass. All participants underwent SAP twice with each fixation target in a random fashion. Fixation behavior was quantified by calculating the bivariate contour ellipse area (BCEA and the frequency of deviation from the fixation target. The BCEAs (deg2 of Point, Cross, and Ring targets were 1.11, 1.46, and 2.02, respectively. In all cases, BCEA increased significantly with increasing fixation target size (p < 0.05. The logarithmic value of BCEA demonstrated the same tendency (p < 0.05. A positive correlation was identified between fixation behavior and threshold variability for the Point and Cross targets (ρ = 0.413-0.534, p < 0.05. Fixation behavior increased with increasing fixation target size. Moreover, a larger fixation behavior tended to be associated with a higher threshold variability. A small fixation target is recommended during the visual field test.

  12. Association between Depression, Pressure Pain Sensitivity, Stress and Autonomous Nervous System Function in Stable Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Ballegaard, Søren; Bergmann, Natasha; Karpatschof, Benny

    2016-01-01

    Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt...... table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction....... Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting...

  13. Expanding the Therapeutic Potential of the Iron Chelator Deferasirox in the Development of Aqueous Stable Ti(IV) Anticancer Complexes.

    Science.gov (United States)

    Loza-Rosas, Sergio A; Vázquez-Salgado, Alexandra M; Rivero, Kennett I; Negrón, Lenny J; Delgado, Yamixa; Benjamín-Rivera, Josué A; Vázquez-Maldonado, Angel L; Parks, Timothy B; Munet-Colón, Charlene; Tinoco, Arthur D

    2017-07-17

    The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV). This metal affinity preference drives deferasirox to facilitate the release of cytotoxic Ti(IV) intracellularly in exchange for Fe(III). An aqueous speciation study performed by potentiometric titration from pH 4 to 8 with micromolar levels of Ti(IV) deferasirox at a 1:2 ratio reveals exclusively Ti(deferasirox) 2 in solution. The predominant complex at pH 7.4, [Ti(deferasirox) 2 ] 2- , exhibits the one of the highest aqueous stabilities observed for a potent cytotoxic Ti(IV) species, demonstrating little dissociation even after 1 month in cell culture media. UV-vis and 1 H NMR studies show that the stability is unaffected by the presence of biomolecular Ti(IV) binders such as citrate, STf, and albumin, which have been shown to induce dissociation or regulate cellular uptake and can alter the activity of other antiproliferative Ti(IV) complexes. Kinetic studies on [Ti(deferasirox) 2 ] 2- transmetalation with Fe(III) show that a labile Fe(III) source is required to induce this process. The initial step of this process occurs on the time scale of minutes, and equilibrium for the complete transmetalation is reached on a time scale of hours to a day. This work reveals a mechanism to deliver Ti(IV) compounds into cells and trigger Ti(IV) release by a labile Fe(III) species. Cellular studies including other cTfm ligands confirm the Fe(III) depletion

  14. Evaluation of the contamination by stable and unstable isotopes in the coastal zones associated to hydrographic basins of Costa Rica

    International Nuclear Information System (INIS)

    Loria Meneses, Luis Guillermo; Lizano Rodriguez, Omar G.; Salazar Matarrita, Alfonso; Jimenez Dam, Ricardo

    2003-01-01

    The degree of contamination by the stable and unstable isotopes concentration in sediments of beaches of Costa Rica is evaluated. It establishes relations between the trace elements in sediments from beaches not associated to hydrographic basins and associated sediments to basins. The totality of sediments coming of beaches were analyzed by the technique of gamma spectroscopy and x-rays spectroscopy. It was determined that the beaches associated to bays and gulfs present greater concentrations as for the presence of radioactive isotopes. In addition, the existing concentrations for unstable isotopes present low values in the zones of open sea; whereas the values of radiation background in beaches and gulfs allow, to future, to detect if is presenting anthropogenic contamination of origin in that type of isotopes or could be a greater presence of these. The obtained results show that the values of radiation of background in beaches were unknown, as well as the unstable isotopes concentration. Also was found the presence of Cs 137, which comes normally from nuclear blasts. The work already includes two published documents [es

  15. Dynamic reorganization of chromatin structure and selective DNA demethylation prior to stable enhancer complex formation during differentiation of primary hematopoietic cells in vitro.

    Science.gov (United States)

    Tagoh, Hiromi; Melnik, Svitlana; Lefevre, Pascal; Chong, Suyinn; Riggs, Arthur D; Bonifer, Constanze

    2004-04-15

    In order to gain insights in the true molecular mechanisms involved in cell fate decisions, it is important to study the molecular details of gene activation where such decisions occur, which is at the level of the chromatin structure of individual genes. In the study presented here we addressed this issue and examined the dynamic development of an active chromatin structure at the chicken lysozyme locus during the differentiation of primary myeloid cells from transgenic mouse bone marrow. Using in vivo footprinting we found that stable enhancer complex assembly and high-level gene expression are late events in cell differentiation. However, even before the onset of gene expression and stable transcription factor binding, specific chromatin alterations are observed. This includes changes in DNA topology and the selective demethylation of CpG dinucleotides located in the cores of critical transcription factor binding sites, but not in flanking DNA. These results firmly support the idea that epigenetic programs guiding blood cell differentiation are engraved into the chromatin of lineage-specific genes and that such chromatin changes are implemented before cell lineage specification.

  16. Mechanism of HIV reverse transcriptase inhibition by zinc: formation of a highly stable enzyme-(primer-template) complex with profoundly diminished catalytic activity.

    Science.gov (United States)

    Fenstermacher, Katherine J; DeStefano, Jeffrey J

    2011-11-25

    Several physiologically relevant cations including Ca(2+), Mn(2+), and Zn(2+) have been shown to inhibit HIV reverse transcriptase (RT), presumably by competitively displacing one or more Mg(2+) ions bound to RT. We analyzed the effects of Zn(2+) on reverse transcription and compared them to Ca(2+) and Mn(2+). Using nucleotide extension efficiency as a readout, Zn(2+) showed significant inhibition of reactions with 2 mM Mg(2+), even when present at only ∼5 μM. Mn(2+) and Ca(2+) were also inhibitory but at higher concentrations. Both Mn(2+) and Zn(2+) (but not Ca(2+)) supported RT incorporation in the absence of Mg(2+) with Mn(2+) being much more efficient. The maximum extension rates with Zn(2+), Mn(2+), and Mg(2+) were ∼0.1, 1, and 3.5 nucleotides per second, respectively. Zinc supported optimal RNase H activity at ∼25 μM, similar to the optimal for nucleotide addition in the presence of low dNTP concentrations. Surprisingly, processivity (average number of nucleotides incorporated in a single binding event with enzyme) during reverse transcription was comparable with Zn(2+) and Mg(2+), and single RT molecules were able to continue extension in the presence of Zn(2+) for several hours on the same template. Consistent with this result, the half-life for RT-Zn(2+)-(primer-template) complexes was 220 ± 60 min and only 1.7 ± 1 min with Mg(2+), indicating ∼130-fold more stable binding with Zn(2+). Essentially, the presence of Zn(2+) promotes the formation of a highly stable slowly progressing RT-(primer-template) complex.

  17. Factors associated with health-related quality of life in stable ambulatory congestive heart failure patients: Systematic review.

    Science.gov (United States)

    Baert, Anneleen; De Smedt, Delphine; De Sutter, Johan; De Bacquer, Dirk; Puddu, Paolo Emilio; Clays, Els; Pardaens, Sofie

    2018-03-01

    Background Since improved treatment of congestive heart failure has resulted in decreased mortality and hospitalisation rates, increasing self-perceived health-related quality of life (HRQoL) has become a major goal of congestive heart failure treatment. However, an overview on predictieve factors of HRQoL is currently lacking in literature. Purpose The aim of this study was to identify key factors associated with HRQoL in stable ambulatory patients with congestive heart failure. Methods A systematic review was performed. MEDLINE, Web of Science and Embase were searched for the following combination of terms: heart failure, quality of life, health perception or functional status between the period 2000 and February 2017. Literature screening was done by two independent reviewers. Results Thirty-five studies out of 8374 titles were included for quality appraisal, of which 29 were selected for further data extraction. Four distinct categories grouping different types of variables were identified: socio-demographic characteristics, clinical characteristics, health and health behaviour, and care provider characteristics. Within the above-mentioned categories the presence of depressive symptoms was most consistently related to a worse HRQoL, followed by a higher New York Heart Association functional class, younger age and female gender. Conclusion Through a systematic literature search, factors associated with HRQoL among congestive heart failure patients were investigated. Age, gender, New York Heart Association functional class and depressive symptoms are the most consistent variables explaining the variance in HRQoL in patients with congestive heart failure. These findings are partly in line with previous research on predictors for hard endpoints in patients with congestive heart failure.

  18. Major histocompatibility complex class I peptide presentation after Salmonella enterica serovar typhimurium infection assessed via stable isotope tagging of the B27-presented peptide repertoire

    NARCIS (Netherlands)

    Ringrose, Jeffrey H.; Meiring, Hugo D.; Speijer, Dave; Feltkamp, Theodorus E. W.; van Els, Cecile A. C. M.; de Jong, Ad P. J. M.; Dankert, Jacob

    2004-01-01

    Reactive arthritis (ReA) induced by infection with several gram-negative bacteria is strongly associated with expression of the major histocompatibility complex class I molecule HLA-B27. It is thought that due to the intracellular lifestyle of ReA-inducing bacteria, bacterial fragments can be

  19. Can 13C stable isotope analysis uncover essential amino acid provisioning by termite-associated gut microbes?

    Directory of Open Access Journals (Sweden)

    Paul A. Ayayee

    2015-08-01

    Full Text Available Gut-associated microbes of insects are postulated to provide a variety of nutritional functions including provisioning essential amino acids (EAAs. Demonstrations of EAA provisioning in insect-gut microbial systems, nonetheless, are scant. In this study, we investigated whether the eastern subterranean termite Reticulitermes flavipes sourced EAAs from its gut-associated microbiota. δ13CEAA data from termite carcass, termite gut filtrate and dietary (wood samples were determined following 13C stable isotope analysis. Termite carcass samples (−27.0 ± 0.4‰, mean ± s.e. were significantly different from termite gut filtrate samples (−27.53 ± 0.5‰, but not the wood diet (−26.0 ± 0.5‰ (F(2,64 = 6, P < 0.0052. δ13CEAA-offsets between termite samples and diet suggested possible non-dietary EAA input. Predictive modeling identified gut-associated bacteria and fungi, respectively as potential major and minor sources of EAAs in both termite carcass and gut filtrate samples, based on δ13CEAA data of four and three EAAs from representative bacteria, fungi and plant data. The wood diet, however, was classified as fungal rather than plant in origin by the model. This is attributed to fungal infestation of the wood diet in the termite colony. This lowers the confidence with which gut microbes (bacteria and fungi can be attributed with being the source of EAA input to the termite host. Despite this limitation, this study provides tentative data in support of hypothesized EAA provisioning by gut microbes, and also a baseline/framework upon which further work can be carried out to definitively verify this function.

  20. Synthesis and X-ray Crystal Structure of a Stable cis-1,2-bis(diphenylphosphinoethene Monodentate Thiolate Platinum Complex and TGA Studies of its Precursors

    Directory of Open Access Journals (Sweden)

    Vaz Rodrigo H.

    2002-01-01

    Full Text Available The stable Pt(II complex [Pt(SPh2(dppen (4, (dppen, Ph2PCH=CHPPh2 was obtained from [PtCl(SPh2(SnPh3cod] (1 (cod = 1,5-cyclooctadiene by reductive elimination reaction of SnClPh3 and substitution of the cod ligand by the diphosphine, albeit in low yields. Yields of 80% were obtained when [Pt(SPh2cod] (3 was used as the starting material instead. The viability of these reactions was suggested by a TG study, performed on the starting materials. Complex 4 was characterized by multinuclear NMR (195Pt, 31P, ¹H and 13C and IR spectroscopies and elemental analysis. The molecular structure, solved by an X-ray diffraction study, exhibted a slightly distorted square-planar geometry and short C=C and Pt-P bond distances which were interpreted in terms of a p interaction between the double bond and the metal-ligand bond, as observed for other diphosphine compounds described previously.

  1. Water-soluble and photo-stable silver(I) dicarboxylate complexes containing 1,10-phenanthroline ligands: Antimicrobial and anticancer chemotherapeutic potential, DNA interactions and antioxidant activity.

    Science.gov (United States)

    Thornton, Laura; Dixit, Vidya; Assad, Letícia O N; Ribeiro, Thales P; Queiroz, Daniela D; Kellett, Andrew; Casey, Alan; Colleran, John; Pereira, Marcos D; Rochford, Garret; McCann, Malachy; O'Shea, Denis; Dempsey, Rita; McClean, Siobhán; Kia, Agnieszka Foltyn-Arfa; Walsh, Maureen; Creaven, Bernadette; Howe, Orla; Devereux, Michael

    2016-06-01

    The complexes [Ag2(OOC-(CH2)n-COO)] (n=1-10) (1-10) were synthesised and reacted with 1,10-phenanthroline (phen) to yield derivatives formulating as [Ag2(phen)x(OOC-(CH2)y-COO)]·zH2O (x=2 or 3; y=1-10; z=1-4) (11-20) which are highly water-soluble and photo-stable in aqueous solution. The phen derivatives 11-20 exhibit chemotherapeutic potential against Candida albicans, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and against cisplatin-sensitive breast (MCF-7) and resistant ovarian (SKOV-3) cancer cell lines. Cyclic voltammetric analysis and DNA binding and intercalation studies indicate that the mechanism of action of 11-20 is significantly different to that of their silver(I) dicarboxylate precursors and they do not induce DNA damage or ROS generation in mammalian cells. The representative complexes 9 and 19 (containing the undecanedioate ligand) were both found to significantly reduce superoxide and hydrogen peroxide induced oxidative stress in the yeast S. cerevisiae. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Interaction between Nbp35 and Cfd1 proteins of cytosolic Fe-S cluster assembly reveals a stable complex formation in Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Shadab Anwar

    Full Text Available Iron-Sulfur (Fe-S proteins are involved in many biological functions such as electron transport, photosynthesis, regulation of gene expression and enzymatic activities. Biosynthesis and transfer of Fe-S clusters depend on Fe-S clusters assembly processes such as ISC, SUF, NIF, and CIA systems. Unlike other eukaryotes which possess ISC and CIA systems, amitochondriate Entamoeba histolytica has retained NIF & CIA systems for Fe-S cluster assembly in the cytosol. In the present study, we have elucidated interaction between two proteins of E. histolytica CIA system, Cytosolic Fe-S cluster deficient 1 (Cfd1 protein and Nucleotide binding protein 35 (Nbp35. In-silico analysis showed that structural regions ranging from amino acid residues (P33-K35, G131-V135 and I147-E151 of Nbp35 and (G5-V6, M34-D39 and G46-A52 of Cfd1 are involved in the formation of protein-protein complex. Furthermore, Molecular dynamic (MD simulations study suggested that hydrophobic forces surpass over hydrophilic forces between Nbp35 and Cfd1 and Van-der-Waal interaction plays crucial role in the formation of stable complex. Both proteins were separately cloned, expressed as recombinant fusion proteins in E. coli and purified to homogeneity by affinity column chromatography. Physical interaction between Nbp35 and Cfd1 proteins was confirmed in vitro by co-purification of recombinant Nbp35 with thrombin digested Cfd1 and in vivo by pull down assay and immunoprecipitation. The insilico, in vitro as well as in vivo results prove a stable interaction between these two proteins, supporting the possibility of its involvement in Fe-S cluster transfer to target apo-proteins through CIA machinery in E. histolytica. Our study indicates that initial synthesis of a Fe-S precursor in mitochondria is not necessary for the formation of Cfd1-Nbp35 complex. Thus, Cfd1 and Nbp35 with the help of cytosolic NifS and NifU proteins can participate in the maturation of non-mitosomal Fe-S proteins

  3. Stable mucus-associated bacterial communities in bleached and healthy corals of Porites lobata from the Arabian Seas

    KAUST Repository

    Hadaidi, Ghaida Ali Hassan

    2017-03-31

    Coral reefs are subject to coral bleaching manifested by the loss of endosymbiotic algae from coral host tissue. Besides algae, corals associate with bacteria. In particular, bacteria residing in the surface mucus layer are thought to mediate coral health, but their role in coral bleaching is unknown. We collected mucus from bleached and healthy Porites lobata colonies in the Persian/Arabian Gulf (PAG) and the Red Sea (RS) to investigate bacterial microbiome composition using 16S rRNA gene amplicon sequencing. We found that bacterial community structure was notably similar in bleached and healthy corals, and the most abundant bacterial taxa were identical. However, fine-scale differences in bacterial community composition between the PAG and RS were present and aligned with predicted differences in sulfur- and nitrogen-cycling processes. Based on our data, we argue that bleached corals benefit from the stable composition of mucus bacteria that resemble their healthy coral counterparts and presumably provide a conserved suite of protective functions, but monitoring of post-bleaching survival is needed to further confirm this assumption. Conversely, fine-scale site-specific differences highlight flexibility of the bacterial microbiome that may underlie adjustment to local environmental conditions and contribute to the widespread success of Porites lobata.

  4. First observations of elevated ducts associated with intermittent turbulence in the stable boundary layer over Bosten Lake, China

    Science.gov (United States)

    Sun, Zheng; Ning, Hui; Song, Shihui; Yan, Dongmei

    2016-10-01

    Nocturnal radiative cooling is a main driver for atmospheric duct formation. Within this atmospheric process, the impacts of intermittent turbulence on ducting have seldom been studied. In this paper, we reported two confusing ducting events observed in the early morning in August 2014 over Bosten Lake, China, when a stable boundary layer (SBL) still survived, by using tethered high-resolution GPS radiosondes. Elevated ducts with strong humidity inversions were observed during the balloon ascents but were absent during observations made upon the balloon descents several minutes later. This phenomenon was initially hypothesized to be attributable to turbulence motions in the SBL, and the connection between the turbulence event and the radar duct was examined by the statistical Thorpe method. Turbulence patches were detected from the ascent profiles but not from the descent profiles. The possible reasons for the duct formation and elimination were discussed in detail. The turbulent transport of moisture in the SBL and the advection due to airflows coming from the lake are the most probable reasons for duct formation. In one case, the downward transport of moisture by turbulence mixing within a Kelvin-Helmholtz billow at the top of the low-level jet resulted in duct elimination. In another case, the passage of density currents originating from the lake may have caused the elimination of the duct. Few studies have attempted to associate intermittent turbulence with radar ducts; thus, this work represents a pioneering study into the connection between turbulent events and atmospheric ducts in a SBL.

  5. A Review of the Stable Isotope Bio-geochemistry of the Global Silicon Cycle and Its Associated Trace Elements

    Directory of Open Access Journals (Sweden)

    Jill N. Sutton

    2018-01-01

    Full Text Available Silicon (Si is the second most abundant element in the Earth's crust and is an important nutrient in the ocean. The global Si cycle plays a critical role in regulating primary productivity and carbon cycling on the continents and in the oceans. Development of the analytical tools used to study the sources, sinks, and fluxes of the global Si cycle (e.g., elemental and stable isotope ratio data for Ge, Si, Zn, etc. have recently led to major advances in our understanding of the mechanisms and processes that constrain the cycling of Si in the modern environment and in the past. Here, we provide background on the geochemical tools that are available for studying the Si cycle and highlight our current understanding of the marine, freshwater and terrestrial systems. We place emphasis on the geochemistry (e.g., Al/Si, Ge/Si, Zn/Si, δ13C, δ15N, δ18O, δ30Si of dissolved and biogenic Si, present case studies, such as the Silicic Acid Leakage Hypothesis, and discuss challenges associated with the development of these environmental proxies for the global Si cycle. We also discuss how each system within the global Si cycle might change over time (i.e., sources, sinks, and processes and the potential technical and conceptual limitations that need to be considered for future studies.

  6. Stable isotopes

    International Nuclear Information System (INIS)

    Evans, D.K.

    1986-01-01

    Seventy-five percent of the world's stable isotope supply comes from one producer, Oak Ridge Nuclear Laboratory (ORNL) in the US. Canadian concern is that foreign needs will be met only after domestic needs, thus creating a shortage of stable isotopes in Canada. This article describes the present situation in Canada (availability and cost) of stable isotopes, the isotope enrichment techniques, and related research programs at Chalk River Nuclear Laboratories (CRNL)

  7. Broadening the phenotype of DFNB28: Mutations in TRIOBP are associated with moderate, stable hereditary hearing impairment.

    Science.gov (United States)

    Wesdorp, Mieke; van de Kamp, Jiddeke M; Hensen, Erik F; Schraders, Margit; Oostrik, Jaap; Yntema, Helger G; Feenstra, Ilse; Admiraal, Ronald J C; Kunst, Henricus P M; Tekin, Mustafa; Kanaan, Moien; Kremer, Hannie; Pennings, Ronald J E

    2017-04-01

    DFNB28 is characterized by prelingual, severe to profound sensorineural hearing impairment (HI). It is associated with mutations in exon 6 and 7 of TRIOBP and has not been reported in the European population. Here, we describe two isolated cases of Dutch origin with congenital, moderate HI and compound heterozygous mutations in TRIOBP. Three of the mutations are novel, one nonsense mutation (c.5014G>T (p.Gly1672*)) and two frameshift mutations (c.2653del (p.Arg885Alafs*120) and c.3460_3461del (p.Leu1154Alafs*29)). The fourth mutation is the known c.3232dup (p.Arg1078Profs*6) mutation. Longitudinal audiometric analyses in one of the subjects revealed that HI was stable over a period of 15 years. Vestibular function was normal. Predicted effects of the mutations do not explain the relatively mild phenotype in the presented subjects, whereas location of the mutation might well contribute to the milder HI in one of the subjects. It is known that isoform classes TRIOBP-4 and TRIOBP-5 are important for stereocilia stability and rigidity. To our knowledge, p.Gly1672* is the first pathogenic variant identified in DFNB28 that does not affect isoform class TRIOBP-4. This suggests that a single TRIOBP copy to encode wildtype TRIOBP-4 is insufficient for normal hearing, and that at least one TRIOBP copy to encode TRIOBP-5 is indispensable for normal inner ear function. Furthermore, this study demonstrates that DFNB28 can be milder than reported so far and that mutations in TRIOBP are thus associated with a heterogeneous phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Complex Frontal Pneumosinus Dilatans Associated with Meningioma: A Report of Two Cases and Associated Literature Review

    Science.gov (United States)

    Timms, Sara; Lakhani, Raj; Connor, Steve; Hopkins, Claire

    2017-01-01

    Introduction  Pneumosinus dilatans (PSD) is a rare phenomenon involving the expansion of the paranasal sinuses, without bony destruction or a mass. Previously documented cases have demonstrated simple expansion of a solitary air cell. We present two unique cases of PSD in the presence of meningioma, in which complex new cells developed within the frontal sinus. One of the two patients developed associated sinus disease. Case 1  A 28-year-old man presented with facial pain. A computed tomography scan showed an abnormally enlarged, septated right frontal sinus, not present on childhood scans. He underwent a modified endoscopic Lothrop approach to divide the septations, and his symptoms resolved. Case 2  A 72-year-old woman presented with a 3-month history of headaches. Scans revealed a left frontal meningioma and multiple enlarged, dilated left frontal air cells. She had no clinical sinusitis and therefore was managed conservatively. Conclusions  PSD has been widely documented in association with fibrous dysplasia and meningioma. The most prevalent theory of the mechanism of PSD is of obstruction of the sinus ostium causing sinus expansion through a “ball-valve” effect. Our cases, which demonstrate septated PSD, suggest a more complex process involving local mediators and highlight the need to consider underlying meningioma in pneumosinus dilatans. PMID:28752019

  9. Binary Molecular Complexes and the Nature of Molecular Association

    African Journals Online (AJOL)

    Asurvey is presented of the results of some ab initio calculations of the properties of a variety of binary molecular complexes. The properties include the molecular structures, the interaction energies and the vibrational spectra. The interaction energies have been correlated with some physical properties of the interacting ...

  10. What's in a Name? AIDS Dementia Complex, HIV-associated ...

    African Journals Online (AJOL)

    language; abstraction- executive; complex motor; memory and sensory perceptual/motor skills). ... abstraction/executive functioning; memory; speed of information language, visuoconstructional-perceptual ability, .... symbol coding test, Hopkins auditory verbal learning test, grooved peg board and colour trails 1 and 2 ...

  11. Stable Breathing in Patients With Obstructive Sleep Apnea Is Associated With Increased Effort but Not Lowered Metabolic Rate.

    Science.gov (United States)

    de Melo, Camila M; Taranto-Montemurro, Luigi; Butler, James P; White, David P; Loring, Stephen H; Azarbarzin, Ali; Marques, Melania; Berger, Philip J; Wellman, Andrew; Sands, Scott A

    2017-10-01

    In principle, if metabolic rate were to fall during sleep in a patient with obstructive sleep apnea (OSA), ventilatory requirements could be met without increased respiratory effort thereby favoring stable breathing. Indeed, most patients achieve periods of stable flow-limited breathing without respiratory events for periods during the night for reasons that are unclear. Thus, we tested the hypothesis that in patients with OSA, periods of stable breathing occur when metabolic rate (VO2) declines. Twelve OSA patients (apnea-hypopnea index >15 events/h) completed overnight polysomnography including measurements of VO2 (using ventilation and intranasal PO2) and respiratory effort (esophageal pressure). Contrary to our hypothesis, VO2 did not differ between stable and unstable breathing periods in non-REM stage 2 (208 ± 20 vs. 213 ± 18 mL/min), despite elevated respiratory effort during stable breathing (26 ± 2 versus 23 ± 2 cmH2O, p = .03). However, VO2 was lowered during deeper sleep (244 to 179 mL/min from non-REM stages 1 to 3, p = .04) in conjunction with more stable breathing. Further analysis revealed that airflow obstruction curtailed metabolism in both stable and unstable periods, since CPAP increased VO2 by 14% in both cases (p = .02, .03, respectively). Patients whose VO2 fell most during sleep avoided an increase in PCO2 and respiratory effort. OSA patients typically convert from unstable to stable breathing without lowering metabolic rate. During sleep, OSA patients labor with increased respiratory effort but fail to satisfy metabolic demand even in the absence of overt respiratory events. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  12. The amygdala complex: multiple roles in associative learning and attention.

    OpenAIRE

    Gallagher, M; Holland, P C

    1994-01-01

    Although certain neurophysiological functions of the amygdala complex in learning seem well established, the purpose of this review is to propose that an additional conceptualization of amygdala function is now needed. The research we review provides evidence that a subsystem within the amygdala provides a coordinated regulation of attentional processes. An important aspect of this additional neuropsychology of the amygdala is that it may aid in understanding the importance of connections bet...

  13. On the wedding of certain dynamical processes in disordered complex materials to the theory of stable (Lévy) distribution functions

    Science.gov (United States)

    Montroll, Elliott W.; Shlesinger, Michael F.

    We review and comment on styles of applied mathematics before exhibiting our own in regard to relating the theory of Lévy's stable distributions to dynamic processes in complex disordered materials. Lévy's probability distributions have long tails, infinite moments and elegant scaling properties. Our first example connects intermittant currents in certain xerographic films to a Lévy distribution of waiting times for the jumping of charges out of a distribution of deep traps. We then extend our analysis from transport to electron-hole recombination reactions in amorphous materials. A Lévy distribution of first passage times appears both in this recombination problem as well as in the dielectric relaxation phenomena described by the Williams-Watts formula. Lastly, the most famous scaling problem, "1/f noise", is shown to be related to a log-normal distribution of relaxation times. We derive the log-normal distribution in a generic fashion and show it to be a limiting form of a Lévy distribution.

  14. Role of neurotoxin associated proteins in the low pH induced structural changes in the botulinum neurotoxin complex.

    Science.gov (United States)

    Chellappan, Gowri; Kumar, Raj; Cai, Shuowei; Singh, Bal Ram

    2014-12-01

    Botulinum Neurotoxin (BoNT) produced by the bacterium Clostridium botulinum as a complex with NAPs causes botulism. It has been known that the NAPs protect the toxin from both extremes of pHs and proteases of the GI tract. In an attempt to emulate the physiological conditions encountered by the toxin, we examined BoNT/A, BoNT/A complex, and NAPs under different pH conditions and monitored their structural characteristics by far-UV CD and thermal denaturation analysis. BoNT/A complex showed the maximum CD signal with a mean residue weight ellipticity of -1.8 × 10(5)° cm(2)/dmol at 222 nm at both acidic and neutral pHs. Thermal denaturation analysis revealed NAPs to be the most stable amongst the three protein samples examined. Interestingly and quite uniquely, at pH 2.5, there was an increase in CD signal for BoNT complex as a function of temperature, which correlated with the NAPs profile, indicating a shielding effect of NAPs on BoNT complex at low pH. Calculation of the weighted mean of the ellipticities at the Tm for thermal unfolding of toxin and NAPs at neutral and acidic pHs showed variation with that of BoNT complex, suggesting structural reorganization in BoNT complex upon the association of NAPs and BoNT. In conclusion, this study reveals the structural behavior of BoNT complex and NAPs with pH changes substantially, which could be quite relevant for BoNT survival under extreme pH conditions in vivo.

  15. Association of Photosystem I and Light-Harvesting Complex II during State Transitions

    NARCIS (Netherlands)

    Boekema, Egbert J.; Kouřil, Roman; Dekker, Jan P.; Jensen, Poul Erik; Golbeck, J.H.

    2006-01-01

    Green plant photosystem I (PS I) not only binds a chlorophyll a/b-binding, membrane-intrinsic antenna complex (LHCI) that is associated with the PS I core complex under almost all physiological conditions, but it can also transiently bind the major chlorophyll a/b-binding light-harvesting complex

  16. Complex Phenotype Associated with 17q21.31 Microdeletion

    Science.gov (United States)

    Dornelles-Wawruk, H.; Pic-Taylor, A.; Rosenberg, C.; Krepischi, A.C.V.; Safatle, H.P.N.; Ferrari, I.; Mazzeu, J.F.

    2013-01-01

    We report on a patient carrying a 17q21.31 microdeletion and exhibiting many common syndrome features, together with other clinical signs which have rarely or never been described to date. The detected 695-kb 17q21.31 deletion is larger than in most previously reported cases but is still probably the result of recombination between flanking low-copy repeats. Due to the complexity of the patient's clinical condition, together with the presence of 3 previously unreported symptoms, namely chronic anemia, cervical vertebrae arthrosis and vertebrae fusion, this case is an important addition to the existing knowledge about the 17q21.31 microdeletion syndrome. PMID:24167466

  17. Association between mutation spectra and stable and unstable DNA adduct profiles in Salmonella for benzo[a]pyrene and dibenzo[a,l]pyrene

    Energy Technology Data Exchange (ETDEWEB)

    DeMarini, David M., E-mail: demarini.david@epa.gov [Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hanley, Nancy M.; Warren, Sarah H.; Adams, Linda D.; King, Leon C. [Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2011-09-01

    Highlights: {yields} Benzo[a]pyrene (BP) induces stable DNA adducts and mutations primarily at guanine. {yields} Dibenzo[a,l]pyrene (DBP) induces them primarily at adenine. {yields} BP induces abasic sites, but DBP does not in the Salmonella mutagenicity assay. {yields} Stable DNA adducts alone appear to account for the mutation spectrum of DBP. {yields} Stable DNA adducts and possibly abasic sites account for the mutation spectrum of BP. - Abstract: Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative roles of these unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TA100 and TA104 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts ({sup 32}P-postlabeling/HPLC) induced by these PAHs in TA104. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TA100. The mutation spectra of DBP and BP were significantly different in TA98 and TA104, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TA104, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine

  18. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events

    DEFF Research Database (Denmark)

    Jespersen, L.; Hvelplund, A.; Abildstrom, S. Z.

    2012-01-01

    Aims Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no o...... with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.......Aims Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD...... (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P

  19. Pregnancy associated plasma protein-A as a marker for myocardial infarction and death in patients with stable coronary artery disease: A prognostic study within the CLARICOR Trial

    DEFF Research Database (Denmark)

    Iversen, Kasper K; Teisner, Børge; Winkel, Per

    2011-01-01

    OBJECTIVE: Pregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable...... outcomes were all-cause mortality and myocardial infarction. RESULTS: Patients (n=4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62-2.45, p...

  20. Substrate properties of stable fly (Diptera: Muscidae) developmental sites associated with round bale hay feeding sites in eastern Nebraska.

    Science.gov (United States)

    Wienhold, B J; Taylor, D B

    2012-04-01

    Residues at sites where stationary feeders were used to provide hay as supplemental forage for cattle during the winter are developmental substrates for immature stable flies, Stomoxys calcitrans (L.), in the central United States. Spatial patterns in physical (substrate depth, temperature, water content), chemical (pH, electrical conductivity [EC(lab)], total nitrogen [N] and carbon [C], ammoniacal nitrogen [NH(4)-N], extractable phosphorus [P]), and biological (microbial respiration rate) substrate properties for two feeding sites were estimated and the correlations between these properties and adult emergence were characterized. Hay feeding sites had a circular footprint with residues extending ≈7 m from the feeder. With the exception of extractable P and total N, all substrate properties exhibited spatial patterns centered on the feeder location. Adult stable fly emergence densities were significantly correlated with substrate microbial respiration rate, NH(4)-N concentration, EC(lab), total C concentration, pH, and moisture content. Logistic regression indicated that EC best predicted the probability of stable flies emerging from a substrate and that the other properties did not provide additional information. A better understanding of the physical, chemical, and biological conditions needed for stable fly larval development may help in identifying previously unrecognized developmental habitats and management of this pest. Targeted implementation of management practices such as sanitation and chemical treatments can be applied to smaller areas reducing labor and improving cost effectiveness.

  1. Cardiac rhabdomyoma associated with tuberosclerosis complex in a newborn

    Directory of Open Access Journals (Sweden)

    Birgin Torer

    2016-03-01

    Full Text Available Cardiac rhabdomyomas are the most comman cardiac tumors in children. They are hamartomatous benign tumors composed of myocytes. They often presents as multiple lesions involving the ventricular cavities. Rhabdomyomas are usually detected in utero by fetal echocardiography. Although patients with cardiac rhabdomyomas are generally asymptomatic these tumors may cause heart failure, severe arrhyhmias and sudden death. Cardiac rhabdomyomas are often associated with tuberosclerosis and they may be the earliest manifestation of tuberosclerosis. Here, we report a newborn infant with antenatally detected cardiac rhabdomyomas associated with tuberosclerosis and we want to emphasize that other diagnostic features of tuberosclerosis should be evaluated in patients with cardiac rhabdomyomas. [Cukurova Med J 2016; 41(0.100: 56-59

  2. Increased circulating follicular regulatory T cells are associated with lower auto-antibodies in stable remission rheumatoid arthritis patients.

    Science.gov (United States)

    Liu, Chen; Wang, Dongwei; Lu, Songsong; Xu, Qinzhu; Zhao, Lei; Zhao, Jingzhong; Song, Ying; Wang, Hui

    2018-01-30

    To examine expression and function changes of circulating CD4 + CXCR5 + FoxP3 + Follicular regulatory T (TFR) cells in active and stable remission rheumatoid arthritis (RA) patients and to clarify the role of TFR cells in the pathogenesis of RA. TFR and follicular helper T cells (TFH) levels in peripheral blood of 39 active RA patients, 39 stable remission RA patients and 33 healthy controls were detected by flow cytometry. The function of TFR cells was measured by co-culturing with TFH and B cells. The activated CD45RA - FoxP3 hi TFR cells were analyzed as well. Clinical indicators including serum levels of Ig and auto-antibodies were tested and correlations with TFR cells were systematically analyzed. DAS28 scores were further calculated and correlation analysis with TFR was conducted as well. The level of CD4 + CXCR5 + FOXP3 + TFR cells and the ratio of TFR/TFH in peripheral blood of stable remission RA patients were significantly increased compared with active RA patients and healthy controls. The function of TFR was enhanced and the activated CD45RA - FoxP3 hi TFR subset was increased in stable remission RA patients compared with healthy controls. Furthermore, TFR cells in RA patients were inversely correlated with Ig G, RF, anti-CCP, as well as DAS28 scores. Circulating TFR cells were increased as RA patients develop to a stable state and increased TFR cells could suppress autoimmunity of RA patients to stabilize their condition. Our results provide novel insight into the pathogenesis process of RA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Neurosurgical management of occult spinal dysraphism associated with OEIS complex.

    Science.gov (United States)

    Morioka, Takato; Hashiguchi, Kimiaki; Yoshida, Fumiaki; Matsumoto, Kenichi; Miyagi, Yasushi; Nagata, Shinji; Yoshiura, Takashi; Masumoto, Kouji; Taguchi, Tomoaki; Sasaki, Tomio

    2008-06-01

    OEIS complex has been described as a combination of defects consisting of omphalocele (O), exstrophy of the cloaca (E), imperforate anus (I), and spinal defects (S). As the first three defects are life-threatening and treated on a priority basis, neurosurgical intervention for spinal defects is deferred until recuperation from abdominogenital repair. However, the best timing for neurosurgical operation has not been precisely described. We reviewed our neurosurgical management of three cases (case 1: myelomeningocele; cases 2 and 3: terminal myelocystocele). At 2-6 (3.6 on average) months after birth, neurosurgical procedures, including reduction of the size of the lumbosacral cystic lesion and untethering of the spinal cord, were performed. During this period, the patients' weights increased from 1,911 to 3,368 g on average, and the lumbosacral cystic lesion was markedly enlarged. In all cases, no neurological deterioration was seen, and ventriculoperitoneal shunt was not indicated. Thus, neurosurgical procedures can be performed in patients weighing 3-4 kg and/or at an age of 3 months, after confirming recuperated conditions from abdominogenital repair. Careful observation should be made of the size of the lumbosacral cystic lesion and neurological deterioration.

  4. Unsupervised learning of complex associations in an animal model.

    Science.gov (United States)

    Castro, Leyre; Wasserman, Edward A; Lauffer, Marisol

    2018-04-01

    Supervised learning results from explicit corrective feedback, whereas unsupervised learning results from statistical co-occurrence. In an initial training phase, we gave pigeons an unsupervised learning task to see if mere pairing could establish associations between multiple pairs of visual images. To assess learning, we administered occasional testing trials in which pigeons were shown an object and had to choose between previously paired and unpaired tokens. Learning was evidenced by preferential choice of the previously unpaired token. In a subsequent supervised training phase, learning was facilitated if the object and token had previously been paired. These results document unsupervised learning in pigeons and resemble statistical learning in infants, suggesting an important parallel between human and animal cognition. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease

    DEFF Research Database (Denmark)

    Jensen, Gorm B; Hilden, Jørgen; Als-Nielsen, Bodil

    2010-01-01

    In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter...... CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard.......0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease...

  6. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1994-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets, with a few more additions - with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers - exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the foree of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc. (orig.)

  7. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

  8. Characterisation of the nascent polypeptide-associated complex in fission yeast

    DEFF Research Database (Denmark)

    Andersen, Katrine M; Semple, Colin A; Hartmann-Petersen, Rasmus

    2007-01-01

    The nascent polypeptide-associated complex (NAC) is an abundant and phylogenetically conserved protein complex. It is composed of two subunits and interacts with nascent polypeptide chains emerging from the ribosome. It has been proposed to protect the nascent chains from premature interaction...

  9. Association between gross-motor and executive function depends on age and motor task complexity

    DEFF Research Database (Denmark)

    Spedden, Meaghan Elizabeth; Malling, Anne Sofie B; Andersen, Ken Kjøller

    2017-01-01

    The objective was to examine associations between motor and executive function across the adult lifespan and to investigate the role of motor complexity in these associations. Young, middle-aged and older adults (n = 82; 19-83y) performed two gross-motor tasks with different levels of complexity...... and a Stroop-like computer task. Performance was decreased in older adults. The association between motor and cognitive performance was significant for older adults in the complex motor task (p = 0.03, rs = -0.41), whereas no significant associations were found for young or middle-aged groups, suggesting...... that the link between gross-motor and executive function emerges with age and depends on motor complexity....

  10. High relative abundance of the stable fly Stomoxys calcitrans is associated with lumpy skin disease outbreaks in Israeli dairy farms.

    Science.gov (United States)

    Kahana-Sutin, E; Klement, E; Lensky, I; Gottlieb, Y

    2017-06-01

    The vector of lumpy skin disease (LSD), a viral disease affecting Bovidae, is currently unknown. To evaluate the possible vector of LSD virus (LSDV) under field conditions, a yearlong trapping of dipterans was conducted in dairy farms that had been affected by LSD, 1-2 years previously. This was done in order to calculate monthly relative abundances of each dipteran in each farm throughout the year. The relative abundances of Stomoxys calcitrans (Diptera: Muscidae) in the months parallel to the outbreaks (December and April) were significantly higher than those of other dipterans. A stable fly population model based on weather parameters for the affected area was used to validate these findings. Its results were significantly correlated with S. calcitrans abundance. This model, based on weather parameters during the epidemic years showed that S. calcitrans populations peaked in the months of LSD onset in the studied farms. These observations and model predictions revealed a lower abundance of stable flies during October and November, when LSD affected adjacent grazing beef herds. These findings therefore suggest that S. calcitrans is a potential vector of LSD in dairy farms and that another vector is probably involved in LSDV transmission in grazing herds. These findings should be followed up with vector competence studies. © 2016 The Royal Entomological Society.

  11. Assessment of the effects of cage fish-farming on damselfish-associated food chains using stable-isotope analyses

    International Nuclear Information System (INIS)

    Jan, Rong-Quen; Kao, Shuh-Ji; Dai, Chang-Feng; Ho, Cheng-Tze

    2014-01-01

    Highlights: • Damselfishes living at sites near a cage farm bore lower δ 13 C and higher δ 15 N. • Similar trends occurred in zooplankton and detritus, major foods for damselfishes. • δ 15 N enrichment in fish may have arisen from the uptake of excess feed and prey. • Farm wastes were documented entering the ecosystem through the pelagic food chain. • No clear evidence of the effects of cage farming on stable isotopes in macroalgae. - Abstract: To assess the effect of cage fish-farming on the coral reef ecosystem off Xiaoliuchiu Island, southern Taiwan, geographical differences in the food chain of each of two damselfishes, Pomacentrus vaiuli and Chromis margaritifer, were examined using a stable-isotope approach. For each damselfish, individuals were found to consume similar foods at all sites. However, specimens collected at sites near the cage farm (as the experimental sites) exhibited lower δ 13 C and higher δ 15 N signatures compared to those from reference sites. Similar trends also occurred in the zooplankton and detritus, two major food sources for both damselfishes. This finding indicates that particulate organic matter released by the farm may have entered the coral reef ecosystem through the pelagic food chain. Artificial reef emplacement is recommended to provide extra habitats under cage farms to support additional pelagic-feeding fish populations, thereby reducing environmental impacts of cage farming on coral reefs

  12. In good company: association between fungal glycans generates molecular complexes with unique functions

    Directory of Open Access Journals (Sweden)

    Marcio eRodrigues

    2012-07-01

    Full Text Available The biological properties of fungal immunogens have historically utilized testing of isolated molecules. Recent findings, however, indicate that fungal glycans differing in structure and function can interact to form hybrid complexes with unique properties. In the pathogenic yeast Cryptococcus neoformans, chitin-like molecules associate with capsular glucuronoxylomannan to form functionally distinct glycan complexes. Such interactions between glycans that result in the formation of structures with different functions strongly suggest that additional molecular complexes with unknown properties may exist in fungal pathogens. Moreover, the identification of these novel complexes has stimulated the search of new immunogens with potential to protect human and animal hosts against systemic mycoses.

  13. Medication Regimen Complexity and Polypharmacy as Factors Associated With All-Cause Mortality in Older People

    Science.gov (United States)

    Wimmer, Barbara C.; Bell, J. Simon; Fastbom, Johan; Wiese, Michael D.; Johnell, Kristina

    2016-01-01

    Objectives: To investigate whether medication regimen complexity and/or polypharmacy are associated with all-cause mortality in older people. Methods: This was a population-based cohort study among community-dwelling and institutionalized people ≥60 years old (n = 3348). Medication regimen complexity was assessed using the 65-item Medication Regimen Complexity Index (MRCI) in 10-unit steps. Polypharmacy was assessed as a continuous variable (number of medications). Mortality data were obtained from the Swedish National Cause of Death Register. Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% CIs for the association between regimen complexity and polypharmacy with all-cause mortality over a 3-year period. Subanalyses were performed stratifying by age (≤80 and>80 years), sex, and cognition (Mini-Mental State Examination [MMSE] 80 years old or with MMSE 80 years old, or in those with MMSE<26. These different associations with mortality deserve further investigation. PMID:26681444

  14. Stable beams

    CERN Multimedia

    2015-01-01

    Stable beams: two simple words that carry so much meaning at CERN. When LHC page one switched from "squeeze" to "stable beams" at 10.40 a.m. on Wednesday, 3 June, it triggered scenes of jubilation in control rooms around the CERN sites, as the LHC experiments started to record physics data for the first time in 27 months. This is what CERN is here for, and it’s great to be back in business after such a long period of preparation for the next stage in the LHC adventure.   I’ve said it before, but I’ll say it again. This was a great achievement, and testimony to the hard and dedicated work of so many people in the global CERN community. I could start to list the teams that have contributed, but that would be a mistake. Instead, I’d simply like to say that an achievement as impressive as running the LHC – a machine of superlatives in every respect – takes the combined effort and enthusiasm of everyone ...

  15. Cemento-osseous dysplasia-like lesion and complex odontoma associated with an impacted third molar.

    Science.gov (United States)

    Prodromidis, Georgios I; Tosios, Konstantinos I; Koutlas, Ioannis G

    2011-12-01

    We present a case of a 36-year-old female with a benign fibro-osseous lesion consistent with cemento-osseous dysplasia (COD) that was located coronally to the crown of an impacted mandibular third molar tooth and was associated with a complex odontoma. The pathogenesis of this unusual association is discussed and the odontogenic origin of COD is suggested.

  16. Decreased Expression of Stable RNA Can Alleviate the Lethality Associated with RNase E Deficiency in Escherichia coli.

    Science.gov (United States)

    Himabindu, P; Anupama, K

    2017-04-15

    The endoribonuclease RNase E participates in mRNA degradation, rRNA processing, and tRNA maturation in Escherichia coli , but the precise reasons for its essentiality are unclear and much debated. The enzyme is most active on RNA substrates with a 5'-terminal monophosphate, which is sensed by a domain in the enzyme that includes residue R169; E. coli also possesses a 5'-pyrophosphohydrolase, RppH, that catalyzes conversion of 5'-terminal triphosphate to 5'-terminal monophosphate on RNAs. Although the C-terminal half (CTH), beyond residue approximately 500, of RNase E is dispensable for viability, deletion of the CTH is lethal when combined with an R169Q mutation or with deletion of rppH In this work, we show that both these lethalities can be rescued in derivatives in which four or five of the seven rrn operons in the genome have been deleted. We hypothesize that the reduced stable RNA levels under these conditions minimize the need of RNase E to process them, thereby allowing for its diversion for mRNA degradation. In support of this hypothesis, we have found that other conditions that are known to reduce stable RNA levels also suppress one or both lethalities: (i) alterations in relA and spoT , which are expected to lead to increased basal ppGpp levels; (ii) stringent rpoB mutations, which mimic high intracellular ppGpp levels; and (iii) overexpression of DksA. Lethality suppression by these perturbations was RNase R dependent. Our work therefore suggests that its actions on the various substrates (mRNA, rRNA, and tRNA) jointly contribute to the essentiality of RNase E in E. coli IMPORTANCE The endoribonuclease RNase E is essential for viability in many Gram-negative bacteria, including Escherichia coli Different explanations have been offered for its essentiality, including its roles in global mRNA degradation or in the processing of several tRNA and rRNA species. Our work suggests that, rather than its role in the processing of any one particular substrate, its

  17. Syndromes and disorders associated with omphalocele (II): OEIS complex and Pentalogy of Cantrell.

    Science.gov (United States)

    Chen, Chih-Ping

    2007-06-01

    Omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is characterized by a combination of omphalocele, exstrophy of the bladder, an imperforate anus, and spinal defects. Pentalogy of Cantrell is characterized by a combination of a midline supraumbilical abdominal wall defect, a defect of the lower sternum, a defect of the diaphragmatic pericardium, a deficiency of the anterior diaphragm, and congenital cardiac anomalies. This article provides a comprehensive review of OEIS complex and pentalogy of Cantrell, including the pathogenesis, prenatal diagnosis, differential diagnosis, and associated malformations. Omphalocele is an important sonographic marker for OEIS complex and pentalogy of Cantrell. Prenatal detection of an abdominal wall defect associated with multiple midline defects should alert one to the possibility of OEIS complex and pentalogy of Cantrell and prompt the genetic investigation and counseling of the disorders.

  18. Syndromes and Disorders Associated with Omphalocele (II: OEIS Complex and Pentalogy Of Cantrell

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-06-01

    Full Text Available Omphalocele-exstrophy-imperforate anus-spinal defects (OEIS complex is characterized by a combination of omphalocele, exstrophy of the bladder, an imperforate anus, and spinal defects. Pentalogy of Cantrell is characterized by a combination of a midline supraumbilical abdominal wall defect, a defect of the lower sternum, a defect of the diaphragmatic pericardium, a deficiency of the anterior diaphragm, and congenital cardiac anomalies. This article provides a comprehensive review of OEIS complex and pentalogy of Cantrell, including the pathogenesis, prenatal diagnosis, differential diagnosis, and associated malformations. Omphalocele is an important sonographic marker for OEIS complex and pentalogy of Cantrell. Prenatal detection of an abdominal wall defect associated with multiple midline defects should alert one to the possibility of OEIS complex and pentalogy of Cantrell and prompt the genetic investigation and counseling of the disorders.

  19. Structural and Functional Characterization of an Archaeal Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated Complex for Antiviral Defense (CASCADE)

    DEFF Research Database (Denmark)

    Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K

    2011-01-01

    In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA....... The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5......a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2...

  20. Stable cystatin C serum levels confirm normal renal function in patients with dronedarone-associated increase in serum creatinine.

    Science.gov (United States)

    Duncker, David; Oswald, Hanno; Gardiwal, Ajmal; Lüsebrink, Ulrich; König, Thorben; Schreyer, Hendrik; Klein, Gunnar

    2013-03-01

    Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubule with creatinine, serum creatinine and its derived estimated glomerular filtration rate might not reflect true renal function in patients on dronedarone. We therefore investigated alternative markers for renal function in these patients. We prospectively included 20 patients with nonpermanent AF in whom dronedarone 400 mg twice daily was started. Patients had normal renal function and serum creatinine; serum cystatin C and creatinine clearance were measured before treatment and 10 and 90 days after treatment started. Mean serum creatinine level for all 20 patients at baseline (day 0) was 84.55 ± 12.14 and 87.8 ± 17.59 µmol/L on day 10. This slight increase in all patients was not significant. Patients were now divided into the predefined groups of "increased creatinine" (increase in serum creatinine level > 1 standard deviation) and "not increased creatinine." Patients with increased creatinine levels (n = 5) showed a significant elevation of serum creatinine levels from day 0 to day 10 (82.4 ± 9.18 to 104.4 ± 12.74 µmol/L; P = .003), whereas change in serum creatinine levels in the not increased creatinine group (n = 15) was not significant. Serum cystatin C levels remained stable in both of these groups (increased creatinine group: 0.76 ± 0.08 to 0.78 ± 0.08 mg/L; P = .65; not increased creatinine group: 0.77 ± 0.108 to 0.77 ± 0.107 mg/L; P = .906). In conclusion, cystatin C represents an easily available and reliable biomarker for estimation of true renal function in patients on dronedarone treatment.

  1. In good company: association between fungal glycans generates molecular complexes with unique functions

    OpenAIRE

    Marcio eRodrigues; Marcio eRodrigues; Leonardo eNimrichter

    2012-01-01

    The biological properties of fungal immunogens have historically utilized testing of isolated molecules. Recent findings, however, indicate that fungal glycans differing in structure and function can interact to form hybrid complexes with unique properties. In the pathogenic yeast Cryptococcus neoformans, chitin-like molecules associate with capsular glucuronoxylomannan to form functionally distinct glycan complexes. Such interactions between glycans that result in the formation of structures...

  2. The stable subgroup graph

    Directory of Open Access Journals (Sweden)

    Behnaz Tolue

    2018-07-01

    Full Text Available In this paper we introduce stable subgroup graph associated to the group $G$. It is a graph with vertex set all subgroups of $G$ and two distinct subgroups $H_1$ and $H_2$ are adjacent if $St_{G}(H_1\\cap H_2\

  3. CmRBP50 protein phosphorylation is essential for assembly of a stable phloem-mobile high-affinity ribonucleoprotein complex.

    Science.gov (United States)

    Li, Pingfang; Ham, Byung-Kook; Lucas, William J

    2011-07-01

    RNA-binding proteins (RBPs) form ribonucleoprotein (RNP) complexes that play crucial roles in RNA processing for gene regulation. The angiosperm sieve tube system contains a unique population of transcripts, some of which function as long-distance signaling agents involved in regulating organ development. These phloem-mobile mRNAs are translocated as RNP complexes. One such complex is based on a phloem RBP named Cucurbita maxima RNA-binding protein 50 (CmRBP50), a member of the polypyrimidine track binding protein family. The core of this RNP complex contains six additional phloem proteins. Here, requirements for assembly of this CmRBP50 RNP complex are reported. Phosphorylation sites on CmRBP50 were mapped, and then coimmunoprecipitation and protein overlay studies established that the phosphoserine residues, located at the C terminus of CmRBP50, are critical for RNP complex assembly. In vitro pull-down experiments revealed that three phloem proteins, C. maxima phloem protein 16, C. maxima GTP-binding protein, and C. maxima phosphoinositide-specific phospholipase-like protein, bind directly with CmRBP50. This interaction required CmRBP50 phosphorylation. Gel mobility-shift assays demonstrated that assembly of the CmRBP50-based protein complex results in a system having enhanced binding affinity for phloem-mobile mRNAs carrying polypyrimidine track binding motifs. This property would be essential for effective long-distance translocation of bound mRNA to the target tissues.

  4. Stable nitrogen isotope ratios of macrophytes and associated periphyton along a nitrate gradient in two subtropical, spring-fed streams

    DEFF Research Database (Denmark)

    De Brabandere, Loreto; Frazer, Thomas K.; Montoya, Joseph P.

    2007-01-01

    1. An increase in human population and associated changes in land use have caused an increase in groundwater nitrate concentrations throughout central Florida. Within the region, this nitrate-laden groundwater returns to the surface via numerous large springs that serve as the origin of flow for ...

  5. Proterozoic microbial reef complexes and associated hydrothermal mineralizations in the Banfora Cliffs, Burkina Faso

    Science.gov (United States)

    Álvaro, J. Javier; Vizcaïno, Daniel

    2012-07-01

    The Proterozoic Guena-Souroukoundinga Formation of the Mopti arm (Gourma Aulacogen, southerm Taoudeni Basin) consists of a shale-dominated succession, up to 200 m thick, with scattered microbial reef complexes. Quarry exposures of the Tiara reef complex allow reconstruction of a transect across back-reef peritidal laminites, reef margin and peri-reef ooidal shoals, and fore-reef slope strata. Microbial carbonate productivity nucleated on isolated palaeohighs during transgression, whereas its end was controlled by two tectonically induced drowning pulses that led to the successive record of onlapping kerogenous limestones and pelagic shales. Reef carbonates are crosscut by fractures and fissures occluded by hydrothermal mineralizations, which are related to the rifting activity of the Gourma Aulacogen. The Tiara reef complex is similar to other Proterozoic reefs in being composed nearly entirely of stromatolites, although calcimicrobial (filamentous) and thromboid textures are locally abundant, which contrast with their scarcity or absence in coeval stable-platform microbial reefs of the northern Taoudeni Basin.

  6. Synthesis, Physical Properties and Reactivity of Stable Antiaromatic 1,4-DIHYDROPYRAZINES and Their Associated Radical Cations

    Science.gov (United States)

    Brook, David James Rawsthorne

    Self condensation of 3-(chloromethyl)-5,6-dihydro -5,5-dimethyl oxazin-2-one and 3-(chloromethyl)-5,6-dihydro -1,5, 5-trimethylpyrazin-2-one gave the 1,4-dihydropyrazines, 4a,8a-diaza-2,6-dioxa-3,4,7,8-tetrahydro- 4,4,8,8 -tetramethylanthracene-1,5,-dione (DDTTA), and 2,4,4,6,8,8-hexamethyl-2,4a,6,8a-tetraaza - 3,4,7,8-tetrahydroanthracene-1,5-dione (HTTA), respectively. Extension of this reaction to other systems resulted in failure. Thionation of DDTTA with phosphorus pentasulphide in pyridine gave mono and dithiono ester derivatives. The dihydropyrazine rings of these systems were planar and showed long wavelength pi-pi^* electronic absorption resulting in the compounds being coloured. The long wavelength band showed significant solvatochromism. NMR measurements indicated that the rings are also paratropic. DDTTA, HTTA and the thiones all showed reversible one electron oxidation to the radical cation which was characterised by electron spin resonance spectroscopy. HTTA and DDTTA also showed reversible oxidation of the radical cation to the dication. Hydrogenation of DDTTA resulted in a tetrahydropyrazine derivative, 4a,8a-diaza-2,6-dioxa -3,4,7,8,9,9a-hexahydro- 4,4,8,8-tetramethylanthracene -1,5-dione (4.5), which underwent atmospheric oxidation back to DDTTA and the alcohol 4a,8a-diaza-2,6-dioxa-3,4,7,8,9,9a -hexahydro-9a-hydroxy- 4,4,8,8-tetramethylanthracene -1,5-dione (4.6). The HTTA analogue 2,4,4,6,8,8-hexamethyl -3,4,7,8,9,9a-hexahydro- 2,4a,6,8a-tetraazaanthracene -1,5-dione (4.9) is stable under the same conditions. The difference in behaviour was explained as a result of the captodative effect. DDTTA was found to undergo rapid (2 + 2) cycloaddition to the dienophile, 4-phenyl-1,2,4-triazoline -3,5-dione (PTAD). Reaction of DDTTA with ^ {3}O_{2} was found to be solvent dependent. In acetic acid the dioxetane 4a,8a-diaza-2,6-dioxa-9,9a-epidioxy-3,4,7,8,9,9a -hexahydro- 4,4,8,8-tetramethylanthracene -1,5-dione was observed; whereas, in acetonitrile

  7. Molecular basis for DPY-30 association to COMPASS-like and NURF complexes.

    Science.gov (United States)

    Tremblay, Véronique; Zhang, Pamela; Chaturvedi, Chandra-Prakash; Thornton, Janet; Brunzelle, Joseph S; Skiniotis, Georgios; Shilatifard, Ali; Brand, Marjorie; Couture, Jean-François

    2014-12-02

    DPY-30 is a subunit of mammalian COMPASS-like complexes (complex of proteins associated with Set1) and regulates global histone H3 Lys-4 trimethylation. Here we report structural evidence showing that the incorporation of DPY-30 into COMPASS-like complexes is mediated by several hydrophobic interactions between an amphipathic α helix located on the C terminus of COMPASS subunit ASH2L and the inner surface of the DPY-30 dimerization/docking (D/D) module. Mutations impairing the interaction between ASH2L and DPY-30 result in a loss of histone H3K4me3 at the β locus control region and cause a delay in erythroid cell terminal differentiation. Using overlay assays, we defined a consensus sequence for DPY-30 binding proteins and found that DPY-30 interacts with BAP18, a subunit of the nucleosome remodeling factor complex. Overall, our results indicate that the ASH2L/DPY-30 complex is important for cell differentiation and provide insights into the ability of DPY-30 to associate with functionally divergent multisubunit complexes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Stable Host Gene Expression in the Gut of Adult Drosophila melanogaster with Different Bacterial Mono-Associations

    Science.gov (United States)

    Zhang, Vivian; Ludington, William B.; Eisen, Michael B.

    2016-01-01

    There is growing evidence that the microbes found in the digestive tracts of animals influence host biology, but we still do not understand how they accomplish this. Here, we evaluated how different microbial species commonly associated with laboratory-reared Drosophila melanogaster impact host biology at the level of gene expression in the dissected adult gut and in the entire adult organism. We observed that guts from animals associated from the embryonic stage with either zero, one or three bacterial species demonstrated indistinguishable transcriptional profiles. Additionally, we found that the gut transcriptional profiles of animals reared in the presence of the yeast Saccharomyces cerevisiae alone or in combination with bacteria could recapitulate those of conventionally-reared animals. In contrast, we found whole body transcriptional profiles of conventionally-reared animals were distinct from all of the treatments tested. Our data suggest that adult flies are insensitive to the ingestion of the bacteria found in their gut, but that prior to adulthood, different microbes impact the host in ways that lead to global transcriptional differences observable across the whole adult body. PMID:27898741

  9. Zygomaticomaxillary complex fracture in a zygomatic bone affected by monostotic fibrous dysplasia: a very rare association.

    Science.gov (United States)

    Pinto, Lara Carolina D'Araújo; Ribeiro, André Luis Ribeiro; Aquime, João Rafael Habib Souza; Carreira, Aline Semblano Dias; Alves-Junior, Sérgio M; Pinheiro, João J V

    2013-05-01

    The association between fibrous dysplasia (FD) and fractures is very rare. This paper reports the case of a zygomaticomaxillary complex fracture in a bone affected by FD, a 29-year-old man who was involved in a bicycle accident and who subsequently presented with a zygomaticomaxillary complex fracture. Computed tomography revealed multiple fractures of the left zygomaticomaxillary complex with dysplastic bone alterations. Fracture lines occurred near transitional areas between the lesion and healthy bone. The patient was treated through an intraoral approach by an open reduction and internal fixation procedure, using a titanium miniplate and screws. An incisional biopsy was performed through the maxillary sinus to confirm the diagnosis of FD. After 12 months of follow-up, there were no postoperative complications. This paper reports a rare association thought to be caused by irregular trabecular bone deposition, which increases bone thickness/resiliency and thus increases its clinical fracture resistance.

  10. The complex formation-partition and partition-association models of solvent extraction of ions

    International Nuclear Information System (INIS)

    Siekierski, S.

    1976-01-01

    Two models of the extraction process have been proposed. In the first model it is assumed that the partitioning neutral species is at first formed in the aqueous phase and then transferred into the organic phase. The second model is based on the assumption that equivalent amounts of cations are at first transferred from the aqueous into the organic phase and then associated to form a neutral molecule. The role of the solubility parameter in extraction and the relation between the solubility of liquid organic substances in water and the partition of complexes have been discussed. The extraction of simple complexes and complexes with organic ligands has been discussed using the first model. Partition coefficients have been calculated theoretically and compared with experimental values in some very simple cases. The extraction of ion pairs has been discussed using the partition-association model and the concept of single-ion partition coefficients. (author)

  11. Trans-sphenoidal encephalocele in association with Dandy-Walker complex and cardiovascular anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Joy, H.M.; Barker, C.S. [Wessex Neurological Centre, Southampton (United Kingdom); Small, J.H. [Dept. of Radiology, Royal Bournemouth Hospital (United Kingdom); Armitage, M. [Bournemouth Diabetes and Endocrine Centre, Royal Bournemouth Hospital (United Kingdom)

    2001-01-01

    We present a case of trans-sphenoidal encephalomeningocele in association with a posterior cranial fossa malformation which fulfils the criteria for the Dandy-Walker complex. Congenital cardiovascular defects were also present. An abnormality of neural crest development may be responsible for the combined occurrence of these anomalies. (orig.)

  12. Corrective Surgery for Congenital Scoliosis Associated with Split Cord Malformation: It May Be Safe to Leave Diastematomyelia Untreated in Patients with Intact or Stable Neurological Status.

    Science.gov (United States)

    Shen, Jianxiong; Zhang, Jianguo; Feng, Fan; Wang, Yipeng; Qiu, Guixing; Li, Zheng

    2016-06-01

    The treatment of congenital scoliosis associated with split cord malformation (SCM) raises the issue of how to best manage such patients to avoid neurological deficit while achieving a satisfactory correction. This prospective clinical study was performed at our center from March 2000 through June 2013. We enrolled a total of 214 patients (61 male and 153 female) with congenital scoliosis associated with SCM who were undergoing spinal correction surgery. The mean age at surgery was 14.1 years. The inclusion criteria were congenital scoliosis with confirmed SCM; status as neurologically intact or stable over the preceding 2 years; and no neurological deterioration as evidenced on traction, side-bending, or fulcrum-bending radiographs. Patients with unstable neurological status or for whom vertebral column resection surgery was planned were excluded. All patients underwent scoliosis surgery without prophylactic detethering. On the basis of the Pang classification, 73 patients were in the type-I SCM group, and 141 were in the type-II SCM group. The groups did not differ significantly with respect to preoperative characteristics, operative time, blood loss, or number of levels fused. The mean follow-up was 37 months (range, 24 to 108 months). The rate of scoliosis correction was lower in the type-I group than in the type-II group (p patients experienced transient neurological complications, with no significant difference between the groups (p = 0.415). No patient experienced permanent neurological deficit during surgery or follow-up. Patients with congenital scoliosis associated with SCM, regardless of type, can safely and effectively undergo spinal deformity correction and achieve spinal balance without neurological intervention. For such patients with intact or stable neurological status, prophylactic detethering prior to scoliosis surgery may not be necessary. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence

  13. Stable Isotope (δ13C, δ15N, δ34S) Analysis and Satellite Telemetry Depict the Complexity of Gray Wolf (Canis lupus) Diets in Southwest Alaska

    Science.gov (United States)

    Stanek, A.; Watts, D. E.; Cohn, B. R.; Spencer, P.; Mangipane, B.; Welker, J. M.

    2010-12-01

    Throughout Alaska, gray wolves (Canis lupus) are a top predator of large ungulates. While they primarily rely on ungulates such as moose (Alces alces) and caribou (Rangifer tarandus) as food, they are opportunistic and use alternative resources. The variation and supplemental protein sources in wolf diet has not been studied extensively on live animals currently using the landscape. With large seasonal influxes of Pacific salmon (Oncorhynchus sp.) into Alaska, terrestrial carnivore use of marine species is of particular interest. Using stable isotope (δ13C, δ15N, δ34S) analysis of wolf guard hair and blood, this study aims to determine the proportion of marine derived nutrients (MDN) in the diet of wolf packs within and surrounding Lake Clark National Park and Preserve and Alaska Peninsula and Becharof National Wildlife Refuges in Southwest Alaska. Satellite telemetry from the animals sampled facilitates quantification of landscape use patterns in correspondence with isotopic traits. Wolf pack territories within and surrounding the Lake Clark region appear to vary in spatial extent and in availability of MDN, such as salmon. Initial analysis shows that two packs with smaller home ranges, centrally located around areas with greater salmon availability, have enriched δ15N values compared to packs that have larger home ranges not centralized around salmon spawning waters. This pattern of isotopic enrichment is found in red blood cells, blood serum and hair, representing diets over different time scales. The enrichment in both blood and hair indicates a sustained use of MDN over the previous six to nine months. In the Lake Clark region, simple mixing model estimates suggest that up to 30% of wolf pack diets may be from marine sources. In contrast, packs with larger home ranges and less access to salmon have stable isotope values representative of a terrestrial diet.

  14. Depletion of the heaviest stable N isotope is associated with NH4+/NH3 toxicity in NH4+-fed plants

    Directory of Open Access Journals (Sweden)

    Martins-Loução Maria A

    2011-05-01

    transports N in the molecular form and is associated with fractionation and another that transports N in the ionic form and is not associated with fractionation.

  15. The role of multivalency in the association kinetics of patchy particle complexes.

    Science.gov (United States)

    Newton, Arthur C; Groenewold, Jan; Kegel, Willem K; Bolhuis, Peter G

    2017-06-21

    Association and dissociation of particles are elementary steps in many natural and technological relevant processes. For many such processes, the presence of multiple binding sites is essential. For instance, protein complexes and regular structures such as virus shells are formed from elementary building blocks with multiple binding sites. Here we address a fundamental question concerning the role of multivalency of binding sites in the association kinetics of such complexes. Using single replica transition interface sampling simulations, we investigate the influence of the multivalency on the binding kinetics and the association mechanism of patchy particles that form polyhedral clusters. When the individual bond strength is fixed, the kinetics naturally is very dependent on the multivalency, with dissociation rate constants exponentially decreasing with the number of bonds. In contrast, we find that when the total bond energy per particle is kept constant, association and dissociation rate constants turn out rather independent of multivalency, although of course still very dependent on the total energy. The association and dissociation mechanisms, however, depend on the presence and nature of the intermediate states. For instance, pathways that visit intermediate states are less prevalent for particles with five binding sites compared to the case of particles with only three bonds. The presence of intermediate states can lead to kinetic trapping and malformed aggregates. We discuss implications for natural forming complexes such as virus shells and for the design of artificial colloidal patchy particles.

  16. Initial characterization of the nascent polypeptide-associated complex in yeast.

    Science.gov (United States)

    Reimann, B; Bradsher, J; Franke, J; Hartmann, E; Wiedmann, M; Prehn, S; Wiedmann, B

    1999-03-30

    The three subunits of the nascent polypeptide-associated complex (alpha, beta1, beta3) in Saccharomyces cerevisiae are encoded by three genes (EGD2, EGD1, BTT1). We found the complex bound to ribosomes via the beta-subunits in a salt-sensitive manner, in close proximity to nascent polypeptides. Estimation of the molecular weight of the complex of wild-type cells and cells lacking one or two subunits revealed that the composition of the complex is variable and that as yet unknown proteins might be included. Regardless of the variability, a certain balance of the subunits has to be maintained: the deletion of one subunit causes downregulation of the remaining subunits at physiological growth temperature. Cells lacking both beta-subunits are unable to grow at 37 degrees C, most likely due to a toxic effect of the alpha-subunit. Based on in vitro experiments, it has been proposed that the function of mammalian nascent-polypeptide associated complexes (NAC) is to prevent inappropriate targeting of non-secretory nascent polypeptides. In vivo, however, the lack of NAC does not cause secretion of signal-less invertase in yeast. This result and the lack of a drastic phenotype of cells missing one, two or three subunits at optimal conditions (28 degrees C, YPD-medium) suggest either the existence of a substitute for NAC or that cells tolerate or 'repair' the damage caused by the absence of NAC.

  17. Stable association of a Drosophila-derived microbiota with its animal partner and the nutritional environment throughout a fly population's life cycle.

    Science.gov (United States)

    Téfit, Mélisandre A; Gillet, Benjamin; Joncour, Pauline; Hughes, Sandrine; Leulier, François

    2017-09-12

    In the past years, the fruit fly Drosophila melanogaster has been extensively used to study the relationship between animals and their associated microbes. Compared to the one of wild populations, the microbiota of laboratory-reared flies is less diverse, and comprises fewer bacterial taxa; nevertheless, the main commensal bacteria found in fly microbiota always belong to the Acetobacteraceae and Lactobacillaceae families. The bacterial communities associated with the fly are environmentally acquired, and the partners engage in a perpetual re-association process. Adult flies constantly ingest and excrete microbes from and onto their feeding substrate, which are then transmitted to the next generation developing within this shared habitat. We wanted to analyze the potential changes in the bacterial community during its reciprocal transfer between the two compartments of the niche (i.e. the fly and the diet). To address this question, we used a diverse, wild-derived microbial community and analyzed its relationship with the fly population and the nutritive substrate in a given habitat. Here we show that the community was overall well maintained upon transmission to a new niche, to a new fly population and to their progeny, illustrating the stable association of a Drosophila-derived microbiota with its fly partner and the nutritional environment. These results highlight the preponderant role of the nutritional substrate in the dynamics of Drosophila/microbiota interactions, and the need to fully integrate this variable when performing such studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility

    Science.gov (United States)

    Jin, Hui; Arase, Noriko; Hirayasu, Kouyuki; Kohyama, Masako; Suenaga, Tadahiro; Saito, Fumiji; Tanimura, Kenji; Matsuoka, Sumiko; Ebina, Kosuke; Shi, Kenrin; Toyama-Sorimachi, Noriko; Yasuda, Shinsuke; Horita, Tetsuya; Hiwa, Ryosuke; Takasugi, Kiyoshi; Ohmura, Koichiro; Yoshikawa, Hideki; Saito, Takashi; Atsumi, Tatsuya; Sasazuki, Takehiko; Katayama, Ichiro; Lanier, Lewis L.; Arase, Hisashi

    2014-01-01

    Specific HLA class II alleles are strongly associated with susceptibility to rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to RA has remained unclear. Recently, we found a unique function of HLA class II molecules: their ability to aberrantly transport cellular misfolded proteins to the cell surface without processing to peptides. Rheumatoid factor (RF) is an autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected in 70–80% of RA patients but also in patients with other diseases. Here, we report that intact IgG heavy chain (IgGH) is transported to the cell surface by HLA class II via association with the peptide-binding groove and that IgGH/HLA class II complexes are specifically recognized by autoantibodies in RF-positive sera from RA patients. In contrast, autoantibodies in RF-positive sera from non-RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for that allele’s association with RA was observed (r = 0.81; P = 4.6 × 10−5). Our findings suggest that IgGH complexed with certain HLA class II alleles is a target for autoantibodies in RA, which might explain why these HLA class II alleles confer susceptibility to RA. PMID:24567378

  19. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    is tested on matched employer-employee data from the entire Danish population. The analysis reveals that self-employed stay longer in their employment status compared to individuals in paid-employment. This effect is not explained by reduced attractiveness to the wage sector (lock-in effect). We interpret......Does entrepreneurship lower the losses associated with labor market mismatching by lowering employment turnover? This paper examines whether a transition to self-employment induces a shift into an individual’s stayer-mover tendency. Using a propensity score-matching technique, the hypothesis...

  20. Complex-based OCT angiography algorithm recovers microvascular information better than amplitude- or phase-based algorithms in phase-stable systems

    Science.gov (United States)

    Xu, Jingjiang; Song, Shaozhen; Li, Yuandong; Wang, Ruikang K.

    2018-01-01

    Optical coherence tomography angiography (OCTA) is increasingly becoming a popular inspection tool for biomedical imaging applications. By exploring the amplitude, phase and complex information available in OCT signals, numerous algorithms have been proposed that contrast functional vessel networks within microcirculatory tissue beds. However, it is not clear which algorithm delivers optimal imaging performance. Here, we investigate systematically how amplitude and phase information have an impact on the OCTA imaging performance, to establish the relationship of amplitude and phase stability with OCT signal-to-noise ratio (SNR), time interval and particle dynamics. With either repeated A-scan or repeated B-scan imaging protocols, the amplitude noise increases with the increase of OCT SNR; however, the phase noise does the opposite, i.e. it increases with the decrease of OCT SNR. Coupled with experimental measurements, we utilize a simple Monte Carlo (MC) model to simulate the performance of amplitude-, phase- and complex-based algorithms for OCTA imaging, the results of which suggest that complex-based algorithms deliver the best performance when the phase noise is  animal models and human retina to verify the findings from the MC model through assessing the OCTA performance metrics of vessel connectivity, image SNR and contrast-to-noise ratio. We show that for all the metrics assessed, the complex-based algorithm delivers better performance than either the amplitude- or phase-based algorithms for both the repeated A-scan and the B-scan imaging protocols, which agrees well with the conclusion drawn from the MC simulations.

  1. 3,4,3-LI(1,2-HOPO): In Vitro Formation of Highly Stable Lanthanide Complexes Translates into Efficacious In Vivo Europium Decorporation

    Energy Technology Data Exchange (ETDEWEB)

    Sturzbecher-Hoehne, Manuel; Ng Pak Leung, Clara; Daleo, Anthony; Kullgren, Birgitta; Prigent, Anne-Laure; Shuh, David K.; Raymond, Kenneth N.; Abergel, Rebecca J.

    2011-07-13

    The spermine-based hydroxypyridonate octadentate chelator 3,4,3-LI(1,2-HOPO) was investigated for its ability to act as an antennae that sensitizes the emission of Sm{sup III}, Eu{sup III}, and Tb{sup III} in the Visible range (Φ{sub tot} = 0.2 - 7%) and the emission of Pr{sup III}, Nd{sup III}, Sm{sup III}, and Yb{sup III} in the Near Infra-Red range, with decay times varying from 1.78 μs to 805 μs at room temperature. The particular luminescence spectroscopic properties of these lanthanide complexes formed with 3,4,3-LI(1,2-HOPO) were used to characterize their respective solution thermodynamic stabilities as well as those of the corresponding La{sup III}, Gd{sup III}, Dy{sup III}, Ho{sup III}, Er{sup III}, Tm{sup III}, and Lu{sup III} complexes. The remarkably high affinity of 3,4,3-LI(1,2-HOPO) for lanthanide metal ions and the resulting high complex stabilities (pM values ranging from 17.2 for La{sup III} to 23.1 for Yb{sup III}) constitute a necessary but not sufficient criteria to consider this octadentate ligand an optimal candidate for in vivo metal decorporation. The in vivo lanthanide complex stability and decorporation capacity of the ligand were assessed, using the radioactive isotope {sup 152}Eu as a tracer in a rodent model, which provided a direct comparison with the in vitro thermodynamic results and demonstrated the great potential of 3,4,3-LI(1,2-HOPO) as a therapeutic metal chelating agent.

  2. Redox Activity of Oxo-Bridged Iridium Dimers in an N,O-Donor Environment: Characterization of Remarkably Stable Ir(IV,V) Complexes.

    Science.gov (United States)

    Sinha, Shashi Bhushan; Shopov, Dimitar Y; Sharninghausen, Liam S; Stein, Christopher J; Mercado, Brandon Q; Balcells, David; Pedersen, Thomas Bondo; Reiher, Markus; Brudvig, Gary W; Crabtree, Robert H

    2017-07-19

    Chemical and electrochemical oxidation or reduction of our recently reported Ir(IV,IV) mono-μ-oxo dimers results in the formation of fully characterized Ir(IV,V) and Ir(III,III) complexes. The Ir(IV,V) dimers are unprecedented and exhibit remarkable stability under ambient conditions. This stability and modest reduction potential of 0.99 V vs NHE is in part attributed to complete charge delocalization across both Ir centers. Trends in crystallographic bond lengths and angles shed light on the structural changes accompanying oxidation and reduction. The similarity of these mono-μ-oxo dimers to our Ir "blue solution" water-oxidation catalyst gives insight into potential reactive intermediates of this structurally elusive catalyst. Additionally, a highly reactive material, proposed to be a Ir(V,V) μ-oxo species, is formed on electrochemical oxidation of the Ir(IV,V) complex in organic solvents at 1.9 V vs NHE. Spectroelectrochemistry shows reversible conversion between the Ir(IV,V) and proposed Ir(V,V) species without any degradation, highlighting the exceptional oxidation resistance of the 2-(2-pyridinyl)-2-propanolate (pyalk) ligand and robustness of these dimers. The Ir(III,III), Ir(IV,IV) and Ir(IV,V) redox states have been computationally studied both with DFT and multiconfigurational calculations. The calculations support the stability of these complexes and provide further insight into their electronic structures.

  3. Host-dependent differences in resource use associated with Anilocra spp. parasitism in two coral reef fishes, as revealed by stable carbon and nitrogen isotope analyses

    Science.gov (United States)

    Welicky, Rachel; Demopoulos, Amanda W. J.; Sikkel, Paul C.

    2017-01-01

    The role of parasites in trophic ecology is poorly understood in marine ecosystems. Stable isotope analyses (SIA) have been widely used in studies of trophic ecology, but have rarely been applied to study the role of parasites. Considering that some parasites are associated with altered host foraging patterns, SIA can help elucidate whether parasitism influences host trophic interactions. French grunt (Haemulon flavolineatum), an abundant Caribbean coral reef fish, contributes greatly to trophic connectivity. They typically depart the reef at dusk, feed overnight in seagrass beds, and return to the reef at dawn. The large parasitic isopod Anilocra haemuli commonly infects French grunt, and infected fish are less likely to complete their diel migration, and are in poorer condition than uninfected conspecifics. Brown chromis (Chromis multilineata) are diurnally feeding planktivores and infection by Anilocra chromis does not influence host condition. To determine if Anilocra infection influences host diet and foraging locality, we conducted stable carbon and nitrogen isotope analyses on scale, muscle, heart and gill tissues of infected and uninfected French grunt and brown chromis. We determined that all French grunt had δ13C values representative of seagrass habitats, but infected French grunt were significantly enriched in 13C and 15N compared to uninfected conspecifics. This suggests that compared to uninfected conspecifics, infected French grunt forage in seagrass, but on isotopically enriched prey, and/or are in poorer condition, which can elevate δ13C and δ15N values. For brown chromis, infection did not significantly influence any δ13C and δ15N values; hence they all foraged in the same environment and on similar prey. This is the first study to use SIA to examine differences in resource use by Caribbean coral reef fishes associated with parasitism and to evaluate how closely related parasites might have host-dependent effects on host trophic ecology.

  4. The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: A proof of principle study on stable and controlled RNA interference in human cell lines

    International Nuclear Information System (INIS)

    Loublier, Sandrine; Bayot, Aurelien; Rak, Malgorzata; El-Khoury, Riyad; Benit, Paule; Rustin, Pierre

    2011-01-01

    Highlights: → NDUFB6 is required for activity of mitochondrial complex I in human cell lines. → Lentivirus based RNA interference results in frequent off target insertions. → Flp-In recombinase mediated miRNA insertion allows gene-specific extinction. -- Abstract: Molecular bases of inherited deficiencies of mitochondrial respiratory chain complex I are still unknown in a high proportion of patients. Among 45 subunits making up this large complex, more than half has unknown function(s). Understanding the function of these subunits would contribute to our knowledge on mitochondrial physiology but might also reveal that some of these subunits are not required for the catalytic activity of the complex. A direct consequence of this finding would be the reduction of the number of candidate genes to be sequenced in patients with decreased complex I activity. In this study, we tested two different methods to stably extinct complex I subunits in cultured cells. We first found that lentivirus-mediated shRNA expression frequently resulted in the unpredicted extinction of additional gene(s) beside targeted ones. This can be ascribed to uncontrolled genetic material insertions in the genome of the host cell. This approach thus appeared inappropriate to study unknown functions of a gene. Next, we found it possible to specifically extinct a CI subunit gene by direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In cells). By using this strategy we unambiguously demonstrated that the NDUFB6 subunit is required for complex I activity, and defined conditions suitable to undertake a systematic and stable extinction of the different supernumerary subunits in human cells.

  5. The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: A proof of principle study on stable and controlled RNA interference in human cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Loublier, Sandrine; Bayot, Aurelien; Rak, Malgorzata; El-Khoury, Riyad; Benit, Paule [Inserm U676, Hopital Robert Debre, F-75019 Paris (France); Universite Paris 7, Faculte de medecine Denis Diderot, IFR02 Paris (France); Rustin, Pierre, E-mail: pierre.rustin@inserm.fr [Inserm U676, Hopital Robert Debre, F-75019 Paris (France); Universite Paris 7, Faculte de medecine Denis Diderot, IFR02 Paris (France)

    2011-10-22

    Highlights: {yields} NDUFB6 is required for activity of mitochondrial complex I in human cell lines. {yields} Lentivirus based RNA interference results in frequent off target insertions. {yields} Flp-In recombinase mediated miRNA insertion allows gene-specific extinction. -- Abstract: Molecular bases of inherited deficiencies of mitochondrial respiratory chain complex I are still unknown in a high proportion of patients. Among 45 subunits making up this large complex, more than half has unknown function(s). Understanding the function of these subunits would contribute to our knowledge on mitochondrial physiology but might also reveal that some of these subunits are not required for the catalytic activity of the complex. A direct consequence of this finding would be the reduction of the number of candidate genes to be sequenced in patients with decreased complex I activity. In this study, we tested two different methods to stably extinct complex I subunits in cultured cells. We first found that lentivirus-mediated shRNA expression frequently resulted in the unpredicted extinction of additional gene(s) beside targeted ones. This can be ascribed to uncontrolled genetic material insertions in the genome of the host cell. This approach thus appeared inappropriate to study unknown functions of a gene. Next, we found it possible to specifically extinct a CI subunit gene by direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In cells). By using this strategy we unambiguously demonstrated that the NDUFB6 subunit is required for complex I activity, and defined conditions suitable to undertake a systematic and stable extinction of the different supernumerary subunits in human cells.

  6. IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution.

    Science.gov (United States)

    Lin, Chien-Chin; Hou, Hsin-An; Chou, Wen-Chien; Kuo, Yuan-Yeh; Liu, Chieh-Yu; Chen, Chien-Yuan; Lai, Yan-Jun; Tseng, Mei-Hsuan; Huang, Chi-Fei; Chiang, Ying-Chieh; Lee, Fen-Yu; Liu, Ming-Chih; Liu, Chia-Wen; Tang, Jih-Luh; Yao, Ming; Huang, Shang-Yi; Ko, Bor-Sheng; Wu, Shang-Ju; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

    2014-02-01

    Current information about clinical significance of IDH mutations in myelodysplastic syndromes (MDS), their association with other genetic alterations and the stability during disease progression is limited. In this study, IDH mutations were identified in 4.6% of 477 patients with MDS based on the FAB classification and in 2.2 % of 368 patients based on the 2008 WHO classification. IDH mutations were closely associated with older age, higher platelet counts, and mutations of DNMT3A (36.4% vs. 8.7%, P IDH2 mutation was a poor prognostic factor for overall survival in patients with lower-risk MDS, based on international prognosis scoring system (IPSS), FAB classification, WHO classification, or revised IPSS (all P ≦ 0.001), but not in higher-risk groups. Sequential studies in 151 patients demonstrated that all IDH-mutated patients retained the same mutation during disease evolution while none of the IDH-wild patients acquired a novel mutation during follow-ups. In conclusion, IDH mutation is a useful biomarker for risk stratification of patients with lower-risk MDS. IDH mutations are stable during the clinical course. The mutation, in association with other genetic alterations, may play a role in the development, but not progression of MDS. Copyright © 2013 Wiley Periodicals, Inc.

  7. Induction of CD4+CD25+Foxp3+ regulatory T cells by mesenchymal stem cells is associated with RUNX complex factors.

    Science.gov (United States)

    Khosravi, Maryam; Bidmeshkipour, Ali; Moravej, Ali; Hojjat-Assari, Suzzan; Naserian, Sina; Karimi, Mohammad Hossein

    2018-02-01

    Among the particular immunomodulation properties of mesenchymal stem cells (MSCs), one relies on their capacity to regulatory T cell (Treg) induction from effector T cells. Stable expression of Foxp3 has a dominant role in suppressive phenotype and stability of induced regulatory T cells (iTregs). How MSCs induce stable Foxp3 expression in iTregs remains unknown. We previously showed MSCs could enhance demethylation of Treg-specific demethylated region (TSDR) in iTregs in cell-cell contact manner (unpublished data). Here, we evaluated the possible effect of MSCs on the mRNA expression of Runx complex genes (Runx1, Runx3, and CBFB) that perch on TSDR in iTregs and play the main role in suppressive properties of Tregs, a regulatory pathway that has not yet been explored by MSCs. Also, we investigated the mRNA expression of MBD2 that promotes TSDR demethylation in Tregs. We first showed that in vitro MSC-iTreg induction was associated with strong mRNA modifications of genes involved in Runx complex. We next injected high doses of MSCs in a murine model of C57BL/6 into Balb/C allogeneic skin transplantation to prolong allograft survival. When splenocytes of grafted mice were analyzed, we realized that the Foxp3 expression was increased at day 5 and 10 post-graft merely in MSC-treated mice. Furthermore, Foxp3 mRNA expression was associated with modified Runx complex mRNA expression comparable to what was shown in in vitro studies. Hence, our data identify a possible mechanism in which MSCs convert conventional T cells to iTreg through strong modifications of mRNA of genes that are involved in Runx complex of Foxp3.

  8. Early-life immune activation increases song complexity and alters phenotypic associations between sexual ornaments.

    Science.gov (United States)

    Merrill, Loren; Naylor, Madeleine F; Dalimonte, Merria; McLaughlin, Sean; Stewart, Tara E; Grindstaff, Jennifer L

    2017-12-01

    Early-life adversity can have long-lasting effects on physiological, behavioural, cognitive, and somatic processes. Consequently, these effects may alter an organism's life-history strategy and reproductive tactics.In response to early-life immune activation, we quantified levels of the acute phase protein haptoglobin (Hp) during development in male zebra finches ( Taeniopygia guttata ). Then, we examined the long-term impacts of early-life immune activation on an important static sexual signal, song complexity, as well as effects of early-life immune activation on the relationship between song complexity and a dynamic sexual signal, beak colouration. Finally, we performed mate-choice trials to determine if male early-life experience impacted female preference.Challenge with keyhole limpet hemocyanin (KLH) resulted in increased song complexity compared to lipopolysaccharide (LPS) treatment or the control. Hp levels were inversely correlated with song complexity. Moreover, KLH-treatment resulted in negative associations between the two sexual signals (beak colouration and song complexity). Females demonstrated some preference for KLH-treated males over controls and for control males over LPS-treated males in mate choice trials.Developmental immune activation has variable effects on the expression of secondary sexual traits in adulthood, including enhancing the expression of some traits. Because developmental levels of Hp and adult song complexity were correlated, future studies should explore a potential role for exposure to inflammation during development on song learning.Early-life adversity may differentially impact static versus dynamic signals. The use of phenotypic correlations can be a powerful tool for examining the impact of early-life experience on the associations among different traits, including sexual signals.

  9. Method for data compression by associating complex numbers with files of data values

    Science.gov (United States)

    Feo, John Thomas; Hanks, David Carlton; Kraay, Thomas Arthur

    1998-02-10

    A method for compressing data for storage or transmission. Given a complex polynomial and a value assigned to each root, a root generated data file (RGDF) is created, one entry at a time. Each entry is mapped to a point in a complex plane. An iterative root finding technique is used to map the coordinates of the point to the coordinates of one of the roots of the polynomial. The value associated with that root is assigned to the entry. An equational data compression (EDC) method reverses this procedure. Given a target data file, the EDC method uses a search algorithm to calculate a set of m complex numbers and a value map that will generate the target data file. The error between a simple target data file and generated data file is typically less than 10%. Data files can be transmitted or stored without loss by transmitting the m complex numbers, their associated values, and an error file whose size is at most one-tenth of the size of the input data file.

  10. OEIS complex associated with chromosome 1p36 deletion: a case report and review.

    Science.gov (United States)

    El-Hattab, Ayman W; Skorupski, Josh C; Hsieh, Michael H; Breman, Amy M; Patel, Ankita; Cheung, Sau Wai; Craigen, William J

    2010-02-01

    OEIS complex (Omphalocele, Exstrophy of the cloaca, Imperforate anus, and Spine abnormalities) is a rare defect with estimated incidence of 1 in 200,000 live births. Most cases are sporadic, with no obvious cause. However, it has been rarely reported in patients with family members having similar malformations or with chromosomal anomalies. In addition, OEIS complex has been observed in association with environmental exposures, twinning, and in vitro fertilization. Monosomy 1p36 is the most common terminal deletion syndrome, with a prevalence of 1 in 5,000 newborns. It is characterized by specific facial features, developmental delay, and heart, skeletal, genitourinary, and neurological defects. We describe an infant with OEIS complex and 1p36 deletion who had features of both disorders, including omphalocele, cloacal exstrophy, imperforate anus, sacral multiple segmentation, renal malposition and malrotation, genital anomalies, diastasis of the symphysis pubis, microbrachycephaly, large anterior fontanel, cardiac septal defects, rib fusion, a limb deformity, developmental delay, and typical facial features. Chromosomal microarray analysis detected a 2.4 Mb terminal deletion of chromosome 1p. This is the first reported case with OEIS complex in association with a chromosome 1p36 deletion. Copyright 2010 Wiley-Liss, Inc.

  11. Ring chromosome in myeloid neoplasms is associated with complex karyotype and disease progression.

    Science.gov (United States)

    Rosenbaum, Matthew W; Pozdnyakova, Olga; Geyer, Julia T; Dal Cin, Paola; Hasserjian, Robert P

    2017-10-01

    Ring chromosome (RC) is a poorly understood genetic anomaly seen in myeloid neoplasms. This study aims to shed light on the clinical significance of this finding. We identified 96 cases of myeloid neoplasms with RC from 3 academic hospitals. Clinicopathologic features and overall (OS) and leukemia-free survival were reviewed and compared to cases of myeloid neoplasms lacking RC. We identified 59 acute myeloid leukemias (AML-RC) and 37 myelodysplastic syndromes (MDS-RC) with RC identified on routine karyotyping. Seventy-five percent of AML-RC and 97% of MDS-RC had complex (>3 independent cytogenetic abnormalities) karyotypes. The median OS of AML-RC with complex karyotype was significantly shorter than AML-RC patients with a non-complex (≤3 independent cytogenetic abnormalities) karyotype (P=.001), but similar to AML patients with complex karyotype lacking RC (P=not significant). Compared to complex-karyotype MDS lacking RC, MDS-RC patients had shorter leukemia-free survival (P=.016) and a trend for shorter OS (P=.10). RCs were sometimes lost after therapy or appeared during disease relapse, suggesting that they may be associated with genetic instability. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. New insight from noble gas and stable isotopes of geothermal/hydrothermal fluids at Caviahue-Copahue Volcanic Complex: Boiling steam separation and water-rock interaction at shallow depth

    Science.gov (United States)

    Roulleau, Emilie; Tardani, Daniele; Sano, Yuji; Takahata, Naoto; Vinet, Nicolas; Bravo, Francisco; Muñoz, Carlos; Sanchez, Juan

    2016-12-01

    We measured noble gas and stable isotopes of the geothermal and hydrothermal fluids of the Caviahue-Copahue Volcanic Complex (CCVC), one of the most important geothermal systems in Argentina/Chile, in order to provide new insights into fluid circulation and origin. With the exception of Anfiteatro and Chancho-co geothermal systems, mantle-derived helium dominates in the CCVC fluids, with measured 3He/4He ratios up to 7.86Ra in 2015. Their positive δ15N is an evidence for subducted sediment-derived nitrogen, which is commonly observed in subduction settings. Both He-N2-Ar composition and positive correlation between δD-H2O and δ18O-H2O suggest that the fluids from Anfiteatro and Chancho-co (and partly from Pucon-Mahuida as well, on the southern flank of Copahue volcano) represent a meteoric water composition with a minor magmatic contribution. The Ne, Kr and Xe isotopic compositions are entirely of atmospheric origin, but processes of boiling and steam separation have led to fractionation of their elemental abundances. We modeled the CCVC fluid evolution using Rayleigh distillation curves, considering an initial air saturated geothermal water (ASGW) end-member at 250 and 300 °C, followed by boiling and steam separation at lower temperatures (from 200 °C to 150 °C). Between 2014 and 2015, the CCVC hydrogen and oxygen isotopes shifted from local meteoric water-dominated to andesitic water-dominated signature. This shift is associated with an increase of δ13C values and Stotal, HCl and He contents. These characteristics are consistent with a change in the gas ascent pathway between 2014 and 2015, which in turn induced higher magmatic-hydrothermal contribution in the fluid signature. The composition of the magmatic source of the CCVC fluids is: 3He/4He = 7.7Ra, δ15N = + 6‰, and δ13C = - 6.5‰. Mixing models between air-corrected He and N suggest the involvement of 0.5% to 5% of subducted sediments in the magmatic source. The magmatic sulfur isotopic

  13. Transient association of MCM complex proteins with the nuclear matrix during initiation of mammalian DNA replication

    OpenAIRE

    Hesketh, Emma L; Knight, John RP; Wilson, Rosemary HC; Chong, James PJ; Coverley, Dawn

    2015-01-01

    The minichromosome maintenance complex (MCM2-7) is the putative DNA helicase in eukaryotes, and essential for DNA replication. By applying serial extractions to mammalian cells synchronized by release from quiescence, we reveal dynamic changes to the sub-nuclear compartmentalization of MCM2 as cells pass through late G1 and early S phase, identifying a brief window when MCM2 becomes transiently attached to the nuclear-matrix. The data distinguish 3 states that correspond to loose association ...

  14. Evolutionary scenarios associated with the Pteronotus parnellii cryptic species-complex (Chiroptera: Mormoopidae).

    OpenAIRE

    López-Wilchis, Ricardo; Flores-Romero, Mayela; Guevara-Chumacero, Luis M.; Serrato-Díaz, Alejandra; Díaz-Larrea, Jhoana; Salgado-Mejía, Fernando; Ibáñez, Carlos; Salles, Leandro O.; Juste, Javier

    2016-01-01

    One of the major challenges to understanding the evolution of Neotropical bats concerns our capacity to successfully scrutinize phylogenetic patterns associated with cases of cryptic species complexes. In this study Pteronotus parnellii is examined as a selected example of a known lineage of mormoopid bat that potentially contains several cryptic species. A samples of 452 individuals from 83 different localities, essentially covering its entire mainland distribution, was evaluated using two g...

  15. Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases.

    Science.gov (United States)

    da Silva-Boghossian, Carina Maciel; do Souto, Renata Martins; Luiz, Ronir R; Colombo, Ana Paula Vieira

    2011-09-01

    Pathogens related to systemic infections have been detected in the periodontal microbiota. The relationship amongst these pathogens, periodontal bacteria and periodontal clinical status is poorly understood. This study evaluated the association amongst red complex, A. actinomycetemcomitans (A.a) and non-oral pathogenic bacteria in subjects with good periodontal health (PH), gingivitis (G), chronic (CP) and aggressive (AP) periodontitis. Subgingival biofilm samples were obtained from 51 PH, 42 G, 219 CP and 90 AP subjects. The presence and levels of A.a, red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola), Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by DNA probes and DNA-DNA hybridization technique. CP and AP subjects presented significantly higher prevalence and levels of A.a, red complex and A. baumannii than G and PH individuals (pperiodontal disease (pperiodontal pathogens and non-oral bacteria alone or in association were strongly associated with periodontitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Complex chromosomal aberrations in chronic lymphocytic leukemia are associated with cellular drug and irradiation resistance.

    Science.gov (United States)

    Koski, T; Karhu, R; Visakorpi, T; Vilpo, L; Knuutila, S; Vilpo, J

    2000-07-01

    Drug resistance is a major problem in chemotherapy of chronic lymphocytic leukemia (CLL). The genetic basis and molecular pathogenesis of drug resistance in CLL remain poorly understood. Here, we have investigated the association between chromosomal aberrations and cellular resistance of CLL cells against seven drugs, gamma and ultraviolet irradiation. Samples were obtained from 35 patients having a classical form of B-CLL. Chromosomal aberrations were first analyzed by traditional karyotyping improved by using optimized mitogen combinations. DNA sequence copy number changes throughout the genome were next screened by comparative genomic hybridization. Finally, fluorescence in situ hybridization was used to detect trisomy 12 and loss of Rb and deletions at chromosome 11. The cellular sensitivity in vitro was assessed by the reduction of macromolecular protein synthesis measured as incorporation of radioactive L-leucine as an endpoint. The overall analysis disclosed a statistically highly significant difference in cellular drug resistance between patients having at least three aberrations compared with patients with fewer or no aberrations. This strongly indicates that complex rather than simple molecular mechanisms are responsible for the drug and irradiation resistance in CLL. According to published results, complex aberrations are constantly associated with poor prognosis in CLL. We demonstrated here that complex chromosomal aberrations were associated with cellular irradiation and drug resistance, which, on the other hand, may be responsible for the poor clinical outcome in CLL.

  17. Turnip mosaic virus Moves Systemically through Both Phloem and Xylem as Membrane-Associated Complexes1

    Science.gov (United States)

    Zheng, Huanquan

    2015-01-01

    Plant viruses move systemically in plants through the phloem. They move as virions or as ribonucleic protein complexes, although it is not clear what these complexes are made of. The approximately 10-kb RNA genome of Turnip mosaic virus (TuMV) encodes a membrane protein, known as 6K2, that induces endomembrane rearrangements for the formation of viral replication factories. These factories take the form of vesicles that contain viral RNA (vRNA) and viral replication proteins. In this study, we report the presence of 6K2-tagged vesicles containing vRNA and the vRNA-dependent RNA polymerase in phloem sieve elements and in xylem vessels. Transmission electron microscopy observations showed the presence in the xylem vessels of vRNA-containing vesicles that were associated with viral particles. Stem-girdling experiments, which leave xylem vessels intact but destroy the surrounding tissues, confirmed that TuMV could establish a systemic infection of the plant by going through xylem vessels. Phloem sieve elements and xylem vessels from Potato virus X-infected plants also contained lipid-associated nonencapsidated vRNA, indicating that the presence of membrane-associated ribonucleic protein complexes in the phloem and xylem may not be limited to TuMV. Collectively, these studies indicate that viral replication factories could end up in the phloem and the xylem. PMID:25717035

  18. Heat Shock Protein member A2 forms a stable complex with angiotensin converting enzyme and protein disulfide isomerase A6 in human spermatozoa.

    Science.gov (United States)

    Bromfield, Elizabeth G; McLaughlin, Eileen A; Aitken, Robert John; Nixon, Brett

    2016-02-01

    Given the importance of the chaperone Heat Shock Protein A2 (HSPA2) in the regulation of male fertility, this study aimed to identify and characterize additional proteins that may rely on the activity of this chaperone in human spermatozoa. In view of the findings in this study we propose that angiotensin converting enzyme (ACE) and protein disulfide isomerase A6 (PDIA6) are novel interacting proteins of HSPA2 and that this multimeric complex may participate in key elements of the fertilization cascade. The molecular chaperone HSPA2 plays a pivotal role in the remodelling of the sperm surface during capacitation. Indeed, human spermatozoa that are deficient in HSPA2 protein expression lack the ability to recognize human oocytes, resulting in repeated IVF failure in a clinical setting. Moreover, our recent work has shown that defective HSPA2 function induced by oxidative stress leads to the aberrant surface expression of one of its interacting proteins, arylsulfatase A, and thus contributes to a loss of sperm-zona pellucida adhesion. Human spermatozoa were collected from fertile donors, capacitated and prepared for Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE) analysis. Protein complexes resolved via BN-PAGE were excised and their constituents were identified using mass spectrometry. The interactions between ACE, PDIA6 and HSPA2 were then confirmed using immunoprecipitation and proximity ligation assays and the localization of these proteins was assessed in isolated spermatozoa and commercially available human testis tissue sections. Finally, pharmacological inhibition of ACE was performed to assess the role of ACE in human sperm capacitation. Herein we have identified ACE and PDIA6 as potential HSPA2-interacting proteins and shown that this assemblage resides in membrane raft microdomains located in the peri-acrosomal region of the sperm head. Additionally, the surface expression of PDIA6, but not ACE, was shown to be dynamically regulated during sperm

  19. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase

    DEFF Research Database (Denmark)

    Hernández-Muñoz, Inmaculada; Lund, Anders H; van der Stoop, Petra

    2005-01-01

    protein BMI1 and the variant histone MACROH2A. We find that in addition to MACROH2A, PRC1 is recruited to the inactivated X chromosome in somatic cells in a highly dynamic, cell cycle-regulated manner. Importantly, RNAi-mediated knock-down of CULLIN3 or SPOP results in loss of MACROH2A1 from...... the inactivated X chromosome (Xi), leading to reactivation of the Xi in the presence of inhibitors of DNA methylation and histone deacetylation. Likewise, Xi reactivation is also seen on MacroH2A1 RNAi under these conditions. Hence, we propose that the PRC1 complex is involved in the maintenance of X chromosome...

  20. Integrating genome-wide association study summaries and element-gene interaction datasets identified multiple associations between elements and complex diseases.

    Science.gov (United States)

    He, Awen; Wang, Wenyu; Prakash, N Tejo; Tinkov, Alexey A; Skalny, Anatoly V; Wen, Yan; Hao, Jingcan; Guo, Xiong; Zhang, Feng

    2018-03-01

    Chemical elements are closely related to human health. Extensive genomic profile data of complex diseases offer us a good opportunity to systemically investigate the relationships between elements and complex diseases/traits. In this study, we applied gene set enrichment analysis (GSEA) approach to detect the associations between elements and complex diseases/traits though integrating element-gene interaction datasets and genome-wide association study (GWAS) data of complex diseases/traits. To illustrate the performance of GSEA, the element-gene interaction datasets of 24 elements were extracted from the comparative toxicogenomics database (CTD). GWAS summary datasets of 24 complex diseases or traits were downloaded from the dbGaP or GEFOS websites. We observed significant associations between 7 elements and 13 complex diseases or traits (all false discovery rate (FDR) elements and complex diseases. © 2017 WILEY PERIODICALS, INC.

  1. Stable isotope views on ecosystem function: challenging or challenged?

    Science.gov (United States)

    Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

    2010-01-01

    Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

  2. Association of DNA with poly(N-vinylpyrrolidone)-C sub 6 sub 0 complex in D sub 2 O

    CERN Document Server

    Toeroek, G; Lebedev, V T; Orlova, D N; Kaboev, O K; Sibilev, A I; Sibileva, M A; Zgonnik, V N; Melenevskaya, E Y; Vinogradova, L V

    2002-01-01

    The interaction of DNA with a poly(N-vinylpyrrolidone)-C sub 6 sub 0 complex in D sub 2 O has been studied by SANS at physiological temperatures T=20 C and 40 C. On increasing the concentration of the complex (C=0.1-1.0 wt. %) at a constant DNA content (C sup * =0.1 wt. %), we observed a progressive complex association with DNA, while the PVP revealed the opposite behaviour (maximum association at C=0.5 wt. %). Complexes clustering with DNA (gyration radius of the associates R sub G propor to 15-30 nm) are more pronounced at 40 C. (orig.)

  3. Identification and characterization of toxigenic fusaria associated with sorghum grain mold complex in India.

    Science.gov (United States)

    Sharma, Rajan; Thakur, Ram P; Senthilvel, Senapathy; Nayak, Spurthi; Reddy, S Veera; Rao, Veeranki Panduranga; Varshney, Rajeev K

    2011-03-01

    Fusarium species are dominant within the sorghum grain mold complex. Some species of Fusarium involved in grain mold complex produce mycotoxins, such as fumonisins. An attempt was made to identify Fusarium spp. associated with grain mold complex in major sorghum-growing areas in India through AFLP-based grouping of the isolates and to further confirm the species by sequencing part of α-Elongation factor gene and comparing the sequences with that available in the NCBI database. The dendrogram generated from the AFLP data clustered the isolates into 5 groups. Five species of Fusarium--F. proliferatum, F. thapsinum, F. equiseti, F. andiyazi and F. sacchari were identified based on sequence similarity of α-Elongation factor gene of the test isolates with those in the NCBI database. Fusarium thapsinum was identified as predominant species in Fusarium--grain mold complex in India and F. proliferatum as highly toxigenic for fumonisins production. Analysis of molecular variance (AMOVA) revealed 54% of the variation in the AFLP patterns of 63 isolates was due to the differences between Fusarium species, and 46% was due to differences between the strains within a species.

  4. Native tandem and ion mobility mass spectrometry highlight structural and modular similarities in clustered-regularly-interspaced shot-palindromic-repeats (CRISPR)-associated protein complexes from Escherichia coli and Pseudomonas aeruginosa.

    Science.gov (United States)

    van Duijn, Esther; Barbu, Ioana M; Barendregt, Arjan; Jore, Matthijs M; Wiedenheft, Blake; Lundgren, Magnus; Westra, Edze R; Brouns, Stan J J; Doudna, Jennifer A; van der Oost, John; Heck, Albert J R

    2012-11-01

    The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) immune system of bacteria and archaea provides acquired resistance against viruses and plasmids, by a strategy analogous to RNA-interference. Key components of the defense system are ribonucleoprotein complexes, the composition of which appears highly variable in different CRISPR/Cas subtypes. Previous studies combined mass spectrometry, electron microscopy, and small angle x-ray scattering to demonstrate that the E. coli Cascade complex (405 kDa) and the P. aeruginosa Csy-complex (350 kDa) are similar in that they share a central spiral-shaped hexameric structure, flanked by associating proteins and one CRISPR RNA. Recently, a cryo-electron microscopy structure of Cascade revealed that the CRISPR RNA molecule resides in a groove of the hexameric backbone. For both complexes we here describe the use of native mass spectrometry in combination with ion mobility mass spectrometry to assign a stable core surrounded by more loosely associated modules. Via computational modeling subcomplex structures were proposed that relate to the experimental IMMS data. Despite the absence of obvious sequence homology between several subunits, detailed analysis of sub-complexes strongly suggests analogy between subunits of the two complexes. Probing the specific association of E. coli Cascade/crRNA to its complementary DNA target reveals a conformational change. All together these findings provide relevant new information about the potential assembly process of the two CRISPR-associated complexes.

  5. Phenotypic characteristics associated with virulence of clinical isolates from the Sporothrix complex.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; de Oliveira, Luã Cardoso; Oliveira, Manoel Marques Evangelista; Gutierrez-Galhardo, Maria Clara; Nosanchuk, Joshua Daniel; Zancopé-Oliveira, Rosely Maria

    2015-01-01

    The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with a wide spectrum of clinical manifestations. Several specific phenotypic characteristics are associated with virulence in many fungi, but studies in this field involving the Sporothrix complex species are scarce. Melanization, thermotolerance, and production of proteases, catalase, and urease were investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains. The S. brasiliensis strains showed a higher expression of melanin and urease compared with S. schenckii. These two species, however, presented similar thermotolerances. Our S. globosa strain had low expression of all studied virulence factors. The relationship between these phenotypes and clinical aspects of sporotrichosis was also evaluated. Strains isolated from patients with spontaneous regression of infection were heavily melanized and produced high urease levels. Melanin was also related to dissemination of internal organs and protease production was associated with HIV-coinfection. A murine sporotrichosis model showed that a S. brasiliensis strain with high expression of virulence factors was able to disseminate and yield a high fungal burden in comparison with a control S. schenckii strain. Our results show that virulence-related phenotypes are variably expressed within the Sporothrix complex species and might be involved in clinical aspects of sporotrichosis.

  6. Subpopulations of Staphylococcus aureus clonal complex 121 are associated with distinct clinical entities.

    Directory of Open Access Journals (Sweden)

    Kevin Kurt

    Full Text Available We investigated the population structure of Staphylococcus aureus clonal complex CC121 by mutation discovery at 115 genetic housekeeping loci from each of 154 isolates, sampled on five continents between 1953 and 2009. In addition, we pyro-sequenced the genomes from ten representative isolates. The genome-wide SNPs that were ascertained revealed the evolutionary history of CC121, indicating at least six major clades (A to F within the clonal complex and dating its most recent common ancestor to the pre-antibiotic era. The toxin gene complement of CC121 isolates was correlated with their SNP-based phylogeny. Moreover, we found a highly significant association of clinical phenotypes with phylogenetic affiliations, which is unusual for S. aureus. All isolates evidently sampled from superficial infections (including staphylococcal scalded skin syndrome, bullous impetigo, exfoliative dermatitis, conjunctivitis clustered in clade F, which included the European epidemic fusidic-acid resistant impetigo clone (EEFIC. In comparison, isolates from deep-seated infections (abscess, furuncle, pyomyositis, necrotizing pneumonia were disseminated in several clades, but not in clade F. Our results demonstrate that phylogenetic lineages with distinct clinical properties exist within an S. aureus clonal complex, and that SNPs serve as powerful discriminatory markers, able to identify these lineages. All CC121 genomes harboured a 41-kilobase prophage that was dissimilar to S. aureus phages sequenced previously. Community-associated MRSA and MSSA from Cambodia were extremely closely related, suggesting this MRSA arose in the region.

  7. OPPORTUNITIES OF PROBIOTIC TREATMENT IN COMPLEX THERAPY OF ANTIBIOTIC-ASSOCIATED DIARRHEA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.N. Surkov

    2011-01-01

    Full Text Available Disorder of normal intestinal flora is widespread state in children with different types of somatic pathology. Intestinal disbiosis disturbs homeostasis, leads to significant disorders in function of other organs and systems. Thus the correction of intestinal disbacteriosis is an actual problem of clinical pediatrics, and different specialists meet this problem. One of common causes of intestinal disbiosis is antibacterial treatment. Almost all antimicrobial drugs influence gastrointestinal tract and their administration lead to dyspepsia and antibiotic-associated diarrhea. Normalization of intestinal microflora is significant stage of complex treatment of these pathological states in children. The choice of probiotic drug should be well grounded. The article presents main data on epidemiology, pathogenesis, clinical symptoms, diagnostics and treatment of antibiotic-associated diarrhea in children, efficacy of probiotic drugs is demonstrated.Key words: children, indigenous intestinal microflora, antibiotic-associated diarrhea, probiotics, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 132–136

  8. Phenome-wide association study maps new diseases to the human major histocompatibility complex region.

    Science.gov (United States)

    Liu, Jixia; Ye, Zhan; Mayer, John G; Hoch, Brian A; Green, Clayton; Rolak, Loren; Cold, Christopher; Khor, Seik-Soon; Zheng, Xiuwen; Miyagawa, Taku; Tokunaga, Katsushi; Brilliant, Murray H; Hebbring, Scott J

    2016-10-01

    Over 160 disease phenotypes have been mapped to the major histocompatibility complex (MHC) region on chromosome 6 by genome-wide association study (GWAS), suggesting that the MHC region as a whole may be involved in the aetiology of many phenotypes, including unstudied diseases. The phenome-wide association study (PheWAS), a powerful and complementary approach to GWAS, has demonstrated its ability to discover and rediscover genetic associations. The objective of this study is to comprehensively investigate the MHC region by PheWAS to identify new phenotypes mapped to this genetically important region. In the current study, we systematically explored the MHC region using PheWAS to associate 2692 MHC-linked variants (minor allele frequency ≥0.01) with 6221 phenotypes in a cohort of 7481 subjects from the Marshfield Clinic Personalized Medicine Research Project. Findings showed that expected associations previously identified by GWAS could be identified by PheWAS (eg, psoriasis, ankylosing spondylitis, type I diabetes and coeliac disease) with some having strong cross-phenotype associations potentially driven by pleiotropic effects. Importantly, novel associations with eight diseases not previously assessed by GWAS (eg, lichen planus) were also identified and replicated in an independent population. Many of these associated diseases appear to be immune-related disorders. Further assessment of these diseases in 16 484 Marshfield Clinic twins suggests that some of these diseases, including lichen planus, may have genetic aetiologies. These results demonstrate that the PheWAS approach is a powerful and novel method to discover SNP-disease associations, and is ideal when characterising cross-phenotype associations, and further emphasise the importance of the MHC region in human health and disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Hospitals with greater diversities of physiologically complex procedures do not achieve greater surgical growth in a market with stable numbers of such procedures.

    Science.gov (United States)

    Dexter, Franklin; Epstein, Richard H; Lubarsky, David A

    2018-01-30

    Although having a large diversity of types of procedures has a substantial operational impact on the surgical suites of hospitals, the strategic importance is unknown. In the current study, we used longitudinal data for all hospitals and patient ages in the State of Florida to evaluate whether hospitals with greater diversity of types of physiologically complex major therapeutic procedures (PCMTP) also had greater rates of surgical growth. Observational cohort study. 1479 combinations of hospitals in the State of Florida and fiscal years, 2008-2015. The types of International Classification of Diseases, Ninth revision, Clinical Modification (ICD-9-CM) procedures studied were PCMT, defined as: a) major therapeutic procedure; b) >7 American Society of Anesthesiologists base units; and c) performed during a hospitalization with a Diagnosis Related Group with a mean length of stay ≥4.0days. The number of procedures of each type of PCMTP commonly performed at each hospital was calculated by taking 1/Herfindahl index (i.e., sum of the squares of the proportions of all procedures of each type of PCMTP). Over the 8 successive years studied, there was no change in the number of PCMTP being performed (Kendall's τ b =-0.014±0.017 [standard error], P=0.44; N=1479 hospital×years). Busier and larger hospitals commonly performed more types of PCMTP, respectively categorized based on performed PCMTP (τ=0.606±0.017, Pmarket, the unique contributions of each large teaching hospital performing many different types of PCMTP needs to be considered relative to the combined capabilities of other hospitals in its region. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Synthesization of high-capacity auto-associative memories using complex-valued neural networks

    Science.gov (United States)

    Huang, Yu-Jiao; Wang, Xiao-Yan; Long, Hai-Xia; Yang, Xu-Hua

    2016-12-01

    In this paper, a novel design procedure is proposed for synthesizing high-capacity auto-associative memories based on complex-valued neural networks with real-imaginary-type activation functions and constant delays. Stability criteria dependent on external inputs of neural networks are derived. The designed networks can retrieve the stored patterns by external inputs rather than initial conditions. The derivation can memorize the desired patterns with lower-dimensional neural networks than real-valued neural networks, and eliminate spurious equilibria of complex-valued neural networks. One numerical example is provided to show the effectiveness and superiority of the presented results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61503338, 61573316, 61374152, and 11302195) and the Natural Science Foundation of Zhejiang Province, China (Grant No. LQ15F030005).

  11. Stable Isotope Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tissue samples (skin, bone, blood, muscle) are analyzed for stable carbon, stable nitrogen, and stable sulfur analysis. Many samples are used in their entirety for...

  12. Major histocompatibility complex loci are associated with susceptibility of Atlantic salmon to infectious hematopoietic necrosis virus

    Science.gov (United States)

    Miller, Kristina M.; Winton, James R.; Schulze, Angela D.; Purcell, Maureen K.; Ming, Tobi J.

    2004-01-01

    Infectious hematopoietic necrosis virus (IHNV) is one of the most significant viral pathogens of salmonids and is a leading cause of death among cultured juvenile fish. Although several vaccine strategies have been developed, some of which are highly protective, the delivery systems are still too costly for general use by the aquaculture industry. More cost effective methods could come from the identification of genes associated with IHNV resistance for use in selective breeding. Further, identification of susceptibility genes may lead to an improved understanding of viral pathogenesis and may therefore aid in the development of preventive and therapeutic measures. Genes of the major histocompatibility complex (MHC), involved in the primary recognition of foreign pathogens in the acquired immune response, are associated with resistance to a variety of diseases in vertebrate organisms. We conducted a preliminary analysis of MHC disease association in which an aquaculture strain of Atlantic salmon was challenged with IHNV at three different doses and individual fish were genotyped at three MHC loci using denaturing gradient gel electrophoresis (PCR-DGGE), followed by sequencing of all differentiated alleles. Nine to fourteen alleles per exon-locus were resolved, and alleles potentially associated with resistance or susceptibility were identified. One allele (Sasa-B-04) from a potentially non-classical class I locus was highly associated with resistance to infectious hematopoietic necrosis (p < 0.01). This information can be used to design crosses of specific haplotypes for family analysis of disease associations.

  13. Respiratory Chain Supercomplexes associate with the Cysteine Desulfurase Complex of the Iron-Sulfur Cluster Assembly Machinery.

    Science.gov (United States)

    Böttinger, Lena; Mårtensson, Christoph U; Song, Jiyao; Zufall, Nicole; Wiedemann, Nils; Becker, Thomas

    2018-01-31

    Mitochondria are the powerhouses of eukaryotic cells. The activity of the respiratory chain complexes generates a proton gradient across the inner membrane, which is used by the F 1 F O -ATP synthase to produce ATP for cellular metabolism. In baker's yeast Saccharomyces cerevisiae the cytochrome bc1 complex (complex III) and cytochrome c oxidase (complex IV) associate in respiratory chain supercomplexes. Iron-sulfur clusters (ISC) form reactive centers of respiratory chain complexes. The assembly of ISC occurs in the mitochondrial matrix and is essential for cell viability. The cysteine desulfurase Nfs1 provides sulfur for ISC assembly and forms with partner proteins the ISC-biogenesis desulfurase complex (ISD complex). Here, we report an unexpected interaction of the active ISD complex with the cytochrome bc1 complex and cytochrome c oxidase. The individual deletion of complex III or complex IV blocks the association of the ISD complex with respiratory chain components. We conclude that the ISD complex binds selectively to respiratory chain supercomplexes. We propose that this molecular link contributes to coordination of iron-sulfur cluster formation with respiratory activity. © 2018 by The American Society for Cell Biology.

  14. Structural and functional characterization of an archaeal clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for antiviral defense (CASCADE).

    Science.gov (United States)

    Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K; Graham, Shirley; Liu, Huanting; Naismith, James H; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J; White, Malcolm F; Lawrence, C Martin

    2011-06-17

    In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea.

  15. Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study.

    Science.gov (United States)

    Beatty, Alexis L; Zhang, Mary H; Ku, Ivy A; Na, Beeya; Schiller, Nelson B; Whooley, Mary A

    2012-02-01

    Serum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD. We measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded. During an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04-2.56, p=0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24-2.26, pheart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31-2.21, pheart failure and mortality among patients with existing IHD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Risk of Venous Thromboembolism After Receiving Prothrombin Complex Concentrate for Warfarin-associated Intracranial Hemorrhage.

    Science.gov (United States)

    Felton, Diana; Foley, Elizabeth M; Traub, Stephen J; Vodonos, Alina; Ganetsky, Michael

    2016-01-01

    Prothrombin complex concentrates (PCCs) are commonly used to rapidly reverse warfarin-associated coagulopathy; however, venous thromboembolism (VTE) is an established adverse event. To determine risk factors for VTE AFTER administration of a three-factor prothrombin complex concentrate (3F-PCC) for warfarin-associated intracranial hemorrhage (ICH). Retrospective chart review of all patients with a warfarin-associated ICH who received a 3F-PCC at a single tertiary care hospital between 2008 and 2013. Outcomes were VTE events (defined as deep vein thrombosis [DVT], pulmonary embolism [PE], limb ischemia, transient ischemic attack, cerebrovascular accident, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction, and unexplained sudden death) occurring within 30 days of 3F-PCC administration. Risk factors in subjects with and without VTE complications were compared via Fisher's exact test, Student's t-test, Mann-Whitney U test, and univariate logistic regression as appropriate. Two hundred nine subjects received 3F-PCC for warfarin-associated ICH. There were 22 VTE events in 19 subjects (9.1%). Baseline characteristics of subjects with and without VTE were similar. There was a significant increase in VTE events in 29 subjects who were taking warfarin for a previous PE or DVT (36.8% vs. 11.6%, p = 0.007; logistic regression odds ratio 4.455, p = 0.005). Patients with a prior history of PE or DVT who were given 3F-PCC for warfarin-associated ICH were 4.5 times more likely to sustain a VTE within 30 days. A careful analysis of risks and benefits of rapidly reversing anticoagulation must be made prior to the administration of 3F-PCC in this patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Low paraoxonase 1 arylesterase activity and high von Willebrand factor levels are associated with severe coronary atherosclerosis in patients with non-diabetic stable coronary artery disease.

    Science.gov (United States)

    Ding, Jieying; Chen, Qizhi; Zhuang, Xing; Feng, Zhilei; Xu, Lili; Chen, Fuxiang

    2014-11-25

    Paraoxonase 1 (PON1) activity and von Willebrand factor (VWF) release are associated with lesion initiation in atherosclerosis. Diabetes can complicate coronary artery disease (CAD) due to the production of advanced glycation end products. This study evaluated PON1 activity and VWF levels in non-post-acute coronary syndrome, stable CAD (SCAD) patients without diabetes. Non-diabetic SCAD patients and patients experiencing acute stress periods were selected (n=130). Forty-seven cases with normal coronary angiography and 50 healthy individuals served as controls. The non-diabetic SCAD group was then stratified into single-vessel lesions, multiple-vessel lesions, and mild or severe luminal stenosis according to the number and the degree of luminal stenoses. Serum PON1 paraoxonase and arylesterase activities, and plasma VWF levels were measured, as well as serum total cholesterol, total triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A1. PON1 arylesterase activity was detected with an ordinary chemistry system using a novel phenylacetate derivative. Both PON1 paraoxonase and arylesterase were lower in the non-diabetic SCAD group, but VWF levels were higher (versus controls, all Pparaoxonase activity (OR=0.991), PON1 arylesterase activity (OR=0.981), and VWF (OR 2.854) influenced SCAD in multiple logistic regression. Decreased PON1 arylesterase activity and increased VWF levels were associated with severe atherosclerosis in non-diabetic SCAD patients. We also observed a slight negative correlation between VWF and PON1 paraoxonase/arylesterase. PON1 and VWF are detectable markers that may predict the severity of stenoses, ideally facilitating a non-diabetic SCAD diagnosis before the sudden onset of life-threatening symptoms.

  18. Neural associations of the early retinotopic cortex with the lateral occipital complex during visual perception.

    Directory of Open Access Journals (Sweden)

    Delong Zhang

    Full Text Available Previous studies have demonstrated that the early retinotopic cortex (ERC, i.e., V1/V2/V3 is highly associated with the lateral occipital complex (LOC during visual perception. However, it remains largely unclear how to evaluate their associations in quantitative way. The present study tried to apply a multivariate pattern analysis (MVPA to quantify the neural activity in ERC and its association with that of the LOC when participants saw visual images. To this end, we assessed whether low-level visual features (Gabor features could predict the neural activity in the ERC and LOC according to a voxel-based encoding model (VBEM, and then quantified the association of the neural activity between these regions by using an analogical VBEM. We found that the Gabor features remarkably predicted the activity of the ERC (e.g., the predicted accuracy was 52.5% for a participant instead of that of the LOC (4.2%. Moreover, the MVPA approach can also be used to establish corresponding relationships between the activity patterns in the LOC and those in the ERC (64.2%. In particular, we found that the integration of the Gabor features and LOC visual information could dramatically improve the 'prediction' of ERC activity (88.3%. Overall, the present study provides new evidences for the possibility of quantifying the association of the neural activity between the regions of ERC and LOC. This approach will help to provide further insights into the neural substrates of the visual processing.

  19. Protein kinase that phosphorylates light-harvesting complex is autophosphorylated and is associated with photosystem II

    International Nuclear Information System (INIS)

    Coughlan, S.J.; Hind, G.

    1987-01-01

    Thylakoid membranes were phosphorylated with [γ- 32 P]ATP and extracted with octyl glucoside and cholate. Among the radiolabeled phosphoproteins in the extract was a previously characterized protein kinase of 64-kDa apparent mass. The ability of this enzyme to undergo autophosphorylation in situ was used to monitor its distribution in the membrane. Fractionation studies showed that the kinase is confined to granal regions of the thylakoid, where it appears to be associated with the light-harvesting chlorophyll-protein complex of photosystem II. The kinetics of kinase autophosphorylation were investigated both in situ and in extracted, purified enzyme. In the membrane, autophosphorylation saturated within 20-30 min and was reversed with a half-time of 7-8 min upon removal of ATP or oxidative inactivation of the kinase; the accompanying dephosphorylation of light-harvesting complex was slower and kinetically complex. Fluoride (10 mM) inhibited these dephosphorylations. Autophosphorylation of the isolated kinase was independent of enzyme concentration, indicative of an intramolecular mechanism. A maximum of one serine residue per mole of kinase was esterified. Autophosphorylation was more rapid in the presence of histone IIIs, an exogenous substrate. Dephosphorylation of the isolated enzyme was not observed

  20. [Complex febrile seizures: study of the associated pathology and practical use of complementary tests].

    Science.gov (United States)

    Berzosa López, R; Ramos Fernández, J M; Martínez Antón, J; Espinosa Fernández, M G; Urda Cardona, A

    2014-06-01

    Although one third of febrile seizures are complex, a consensus has still not been reached on how to manage them, as is the case with simple febrile seizures. The objective of this study is to estimate the usefulness of complementary examinations and the risk of associated serious intracranial pathology. A retrospective review was conducted from 2003 until 2011 on patients from 6 months to 6 years presenting with a complex febrile seizure admitted to a tertiary care hospital, excluding the cases with previous neurological disease. Epidemiological and clinic variables were collected, as well as complementary tests and complications. We found 65 patients (31 females and 34 males), of whom 44 had repeated seizures in the first 24 hours, with 15 having focal seizures. The vast majority (90%) of the recurrences occurred before 15 hours. The mean age was 20.7 months and temperature was 39.1 ± 0.12°C. None of the patients had severe intracranial pathology. The electroencephalogram gave no helpful information for the diagnosis. Neuroimaging was normal in all studied cases. The incidence of complications in complex febrile seizure in our series did not justify the systematic admission or the systematic study with complementary tests when the neurological examination was normal. The routine electroencephalogram does not appear to be justified. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  1. Neurofibromatosis Type 1: A Novel NF1 Mutation Associated with Mitochondrial Complex I Deficiency

    Directory of Open Access Journals (Sweden)

    Sara Domingues

    2014-01-01

    Full Text Available Background. Neurofibromatosis type 1 is a multisystemic, progressive disease, with an estimated incidence of 1/3500-2500. Mitochondrial diseases are generally multisystemic and may be present at any age, and the global prevalence is 1/8500. The diagnosis of these disorders is complex because of its clinical and genetic heterogeneity. Case Report. We present a rare case of the association of these two different genetic diseases, in which a heterozygous missense mutation in the NF1 gene was identified which had not yet been described (p.M1149 V. Additionally, the patient is suspected of carrying an unspecified mutation causing respiratory chain complex I deficiency. Clinical presentation included hypotonia, global development delay, reduced growth rate, progressive microcephaly, and numerous café-au-lait spots. Discussion. To the best of our knowledge this is the first report of complex I deficiency in a patient with neurofibromatosis type 1. It is very important to maintain a high index of suspicion for the diagnosis of mitochondrial disorders. In this patient, both the laboratory screening and muscle histology were normal and only the biochemical study of muscle allowed us to confirm the diagnosis.

  2. Associations of Volatile Compounds with Sensory Aroma and Flavor: The Complex Nature of Flavor

    Directory of Open Access Journals (Sweden)

    Edgar Chambers IV

    2013-04-01

    Full Text Available Attempts to relate sensory analysis data to specific chemicals such as volatile compounds have been frequent. Often these associations are difficult to interpret or are weak in nature. Although some difficulties may relate to the methods used, the difficulties also result from the complex nature of flavor. For example, there are multiple volatiles responsible for a flavor sensation, combinations of volatiles yield different flavors than those expected from individual compounds, and the differences in perception of volatiles in different matrices. This review identifies some of the reasons sensory analysis and instrumental measurements result in poor associations and suggests issues that need to be addressed in future research for better understanding of the relationships of flavor/aroma phenomena and chemical composition.

  3. Double lumbosacral lipomas of the dorsal and filar types associated with OEIS complex: case report.

    Science.gov (United States)

    Tokunaga, So; Morioka, Takato; Hashiguchi, Kimiaki; Samura, Kazuhiro; Yoshida, Fumiaki; Miyagi, Yasushi; Yoshiura, Takashi; Yamanouchi, Takeshi; Sasaki, Tomio

    2009-10-01

    A female baby was born at 37 weeks and 6 days gestation by vaginal delivery with omphalocele, exstrophy of the cloaca, and imperforate anus, indicating the presence of OEIS complex, a rare combination of defects consisting of omphalocele (O), exstrophy of the cloaca (E), imperforate anus (I), and spinal deformity (S), associated with lumbosacral lipoma. The most common associated spinal deformity is terminal myelocystocele, and spinal lipoma is rare. Constructive interference in steady-state magnetic resonance imaging clearly revealed double lipomas, a dorsal-type lipoma, located dorsal to the low-lying conus medullaris, and a filar-type lipoma, revealed by a thickened and fatty filum terminale. After recovery from abdominogenital repairs, debulking of the dorsal-type lipoma and untethering of the spinal cord by sectioning of the filar-type lipoma were performed at the age of 14 months. Neurosurgical treatment for occult spinal dysraphism should be undertaken after recovery from the initial series of major abdominogenital procedures.

  4. [Analysis of factors associated with multiple pregnancies in assisted reproduction treatment complex].

    Science.gov (United States)

    Hernández-Nieto, C A; Méndez-Lozano, D H; Fraustro-Ávila, M E; García-Martínez, M R; Soto-Cossio, L E; Basurto-Díaz, D; Flores-Mendoza, H

    2016-01-01

    Today, advances in technology provide the best success rates in the reproductive medicine field. One of the biggest concerns about it, is the high risk of achieving multiple pregnancies, which may carry greater health risks for both; the mother and fetuses. Besides that, multiple pregnancies are considered a complication or an adverse effect of assisted reproduction treatments. To compare the factors associated with multiple pregnancy in patients who underwent complex assisted reproduction techniques. A retrospective and transversal case control study was rolled to compare the factors associated with multiple pregnancy rates, these results were correlated using a logistic regression model. a total of 1063 cases were reviewed, we obtained a pregnancy rate of 35.9%, and a multiple pregnancy rate of 31.5%. We found positive statistical association between patient age, total number of oocytes obtained, total embryos transferred, total vitrified embryos per cycle, total serum cuantitative B-GCH level, endometrial thickness in milimeters, and the Honest of a multiple pregnancy. In the logistic regression model, we found statistical association between the number of embryos transferred, number of embryos obtained, embryo quality, total vitrified embryos and the risk for multiple pregnancies. The total number of embryos transferred in a cycle of a complex assisted reproduction, is the most important factor for the onset of multiple pregnancies. The age of patients, the number of oocytes, total number of embryos obtained, the number of embryos transferred, the quality of embryos transferred and the number of frozen embryos per cycle, correlate significantly with more risk for multiple pregnancies.

  5. Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance.

    Directory of Open Access Journals (Sweden)

    Courtney M Yuen

    Full Text Available BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14 adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90 adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83. CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management.

  6. A detailed, hierarchical study of Giardia lamblia's ventral disc reveals novel microtubule-associated protein complexes.

    Directory of Open Access Journals (Sweden)

    Cindi L Schwartz

    Full Text Available Giardia lamblia is a flagellated, unicellular parasite of mammals infecting over one billion people worldwide. Giardia's two-stage life cycle includes a motile trophozoite stage that colonizes the host small intestine and an infectious cyst form that can persist in the environment. Similar to many eukaryotic cells, Giardia contains several complex microtubule arrays that are involved in motility, chromosome segregation, organelle transport, maintenance of cell shape and transformation between the two life cycle stages. Giardia trophozoites also possess a unique spiral microtubule array, the ventral disc, made of approximately 50 parallel microtubules and associated microribbons, as well as a variety of associated proteins. The ventral disc maintains trophozoite attachment to the host intestinal epithelium. With the help of a combined SEM/microtome based slice and view method called 3View® (Gatan Inc., Pleasanton, CA, we present an entire trophozoite cell reconstruction and describe the arrangement of the major cytoskeletal elements. To aid in future analyses of disc-mediated attachment, we used electron-tomography of freeze-substituted, plastic-embedded trophozoites to explore the detailed architecture of ventral disc microtubules and their associated components. Lastly, we examined the disc microtubule array in three dimensions in unprecedented detail using cryo-electron tomography combined with internal sub-tomogram volume averaging of repetitive domains. We discovered details of protein complexes stabilizing microtubules by attachment to their inner and outer wall. A unique tri-laminar microribbon structure is attached vertically to the disc microtubules and is connected to neighboring microribbons via crossbridges. This work provides novel insight into the structure of the ventral disc microtubules, microribbons and associated proteins. Knowledge of the components comprising these structures and their three-dimensional organization is

  7. Differential association of protein subunits with the human RNase MRP and RNase P complexes.

    Science.gov (United States)

    Welting, Tim J M; Kikkert, Bastiaan J; van Venrooij, Walther J; Pruijn, Ger J M

    2006-07-01

    RNase MRP is a eukaryotic endoribonuclease involved in nucleolar and mitochondrial RNA processing events. RNase MRP is a ribonucleoprotein particle, which is structurally related to RNase P, an endoribonuclease involved in pre-tRNA processing. Most of the protein components of RNase MRP have been reported to be associated with RNase P as well. In this study we determined the association of these protein subunits with the human RNase MRP and RNase P particles by glycerol gradient sedimentation and coimmunoprecipitation. In agreement with previous studies, RNase MRP sedimented at 12S and 60-80S. In contrast, only a single major peak was observed for RNase P at 12S. The analysis of individual protein subunits revealed that hPop4 (also known as Rpp29), Rpp21, Rpp20, and Rpp25 only sedimented in 12S fractions, whereas hPop1, Rpp40, Rpp38, and Rpp30 were also found in 60-80S fractions. In agreement with their cosedimentation with RNase P RNA in the 12S peak, coimmunoprecipitation with VSV-epitope-tagged protein subunits revealed that hPop4, Rpp21, and in addition Rpp14 preferentially associate with RNase P. These data show that hPop4, Rpp21, and Rpp14 may not be associated with RNase MRP. Furthermore, Rpp20 and Rpp25 appear to be associated with only a subset of RNase MRP particles, in contrast to hPop1, Rpp40, Rpp38, and Rpp30 (and possibly also hPop5), which are probably associated with all RNase MRP complexes. Our data are consistent with a transient association of Rpp20 and Rpp25 with RNase MRP, which may be inversely correlated to its involvement in pre-rRNA processing.

  8. Logistic Bayesian LASSO for genetic association analysis of data from complex sampling designs.

    Science.gov (United States)

    Zhang, Yuan; Hofmann, Jonathan N; Purdue, Mark P; Lin, Shili; Biswas, Swati

    2017-09-01

    Detecting gene-environment interactions with rare variants is critical in dissecting the etiology of common diseases. Interactions with rare haplotype variants (rHTVs) are of particular interest. At the same time, complex sampling designs, such as stratified random sampling, are becoming increasingly popular for designing case-control studies, especially for recruiting controls. The US Kidney Cancer Study (KCS) is an example, wherein all available cases were included while the controls at each site were randomly selected from the population by frequency matching with cases based on age, sex and race. There is currently no rHTV association method that can account for such a complex sampling design. To fill this gap, we consider logistic Bayesian LASSO (LBL), an existing rHTV approach for case-control data, and show that its model can easily accommodate the complex sampling design. We study two extensions that include stratifying variables either as main effects only or with additional modeling of their interactions with haplotypes. We conduct extensive simulation studies to compare the complex sampling methods with the original LBL methods. We find that, when there is no interaction between haplotype and stratifying variables, both extensions perform well while the original LBL methods lead to inflated type I error rates. However, when such an interaction exists, it is necessary to include the interaction effect in the model to control the type I error rate. Finally, we analyze the KCS data and find a significant interaction between (current) smoking and a specific rHTV in the N-acetyltransferase 2 gene.

  9. Multiple supernumerary teeth not associated with complex syndromes: a retrospective study.

    Science.gov (United States)

    Yagüe-García, José; Berini-Aytés, Leonardo; Gay-Escoda, Cosme

    2009-07-01

    To determine the epidemiology and describe the clinical and radiographic characteristics, the type of treatment, and the possible delayed appearance of new supernumerary teeth in patients with non-syndromic multiple hyperdontia. We conducted a small retrospective observational study of 8 patients diagnosed with non-syndromic multiple hyperodontia. Multiple hyperdontia not associated to complex syndromes was defined as apparently generally healthy patients with one or more supernumerary teeth in two or more areas. The average patient age was 16.23 years; males predominated (3:1). Multiple hyperodontia with a minimum of 2 and a maximum of 9 supernumerary teeth was found (total: 34 mean: 4.25). The most frequent location was the upper jaw (76.47%). Eumorphic teeth were seen at lower premolar level, while the rest were all heteromorphic. There was altered eruption of the contiguous teeth of 4 of the impacted supernumerary teeth all the rest being asymptomatic. Extraction was the treatment in all patients, and in one of them the delayed appearance of 4 supernumerary teeth was detected. Multiple hyperodontia rarely occurs without being associated with complex syndromes. Prophylactic surgical removal of the supernumerary teeth is generally the treatment of choice.

  10. PITX2 associates with PTIP-containing histone H3 lysine 4 methyltransferase complex.

    Science.gov (United States)

    Liu, Yan; Huang, Yue; Fan, Jun; Zhu, Guo-Zhang

    2014-02-21

    Pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of Wnt/β-catenin signaling, plays substantial roles in embryonic development and human disorders. The mechanism of its functions, however, is not fully understood. In this study, we demonstrated that PITX2 associated with histone H3 lysine 4 (H3K4) methyltransferase (HKMT) mixed-lineage leukemia 4 (MLL4/KMT2D), Pax transactivation domain-interacting protein (PTIP), and other H3K4·HKMT core subunits. This association of PITX2 with H3K4·HKMT complex was dependent on PITX2's homeodomain. Consistently, the PITX2 protein complex was shown to possess H3K4·HKMT activity. Furthermore, the chromatin immunoprecipitation result revealed co-occupancy of PITX2 and PTIP on the promoter of the PITX2's transcriptional target. Taken together, our data provide new mechanistic perspectives on PITX2's functions and its related biological processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska complex to kinetochores

    Directory of Open Access Journals (Sweden)

    Sushama Sivakumar

    2017-11-01

    Full Text Available Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The spindle- and kinetochore-associated (Ska complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1 to kinetochores. Here we show that PP1 and protein phosphatase 2A (PP2A both promote accumulation of Ska at kinetochores. Depletion of PP1 or PP2A by siRNA reduces Ska binding at kinetochores, impairs alignment of chromosomes to the spindle midplane, and causes metaphase delay or arrest, phenotypes that are also seen after depletion of Ska. Artificial tethering of PP1 to the outer kinetochore protein Nuf2 promotes Ska recruitment to kinetochores, and it reduces but does not fully rescue chromosome alignment and metaphase arrest defects seen after Ska depletion. We propose that Ska has multiple functions in promoting mitotic progression and that kinetochore-associated phosphatases function in a positive feedback cycle to reinforce Ska complex accumulation at kinetochores.

  12. Tuna and dolphin associations in the North-east Atlantic: Evidence of different ecological niches from stable isotope and heavy metal measurements

    Energy Technology Data Exchange (ETDEWEB)

    Das, K.; Lepoint, G.; Loizeau, V.; Debacker, V.; Dauby, P.; Bouquegneau, J.M

    2000-02-01

    Associations of tunas and dolphins in the wild are quite frequent events and the question arises how predators requiring similar diet in the same habitat share their environmental resources. As isotopic composition of an animal is related to that of its preys, stable isotope ({sup 13}C/{sup 12}C and {sup 15}N/{sup 14}N) analyses were performed in three predator species from the North-east Atlantic: the striped dolphin, Stenella coeruleoalba, the common dolphin Delphinus delphis and the albacore tuna, Thunnus alalunga, and compared to their previously described stomach content. Heavy metals (Cd, Zn, Cu and Fe) are mainly transferred through the diet and so, have been determined in the tissues of the animals. Tuna muscles display higher {delta}{sup 15}N than in common and striped dolphins (mean: 11.4 vs. 10.3%o and 10.4%o, respectively) which reflects their higher trophic level nutrition. Higher {delta}{sup 13}C are found in common (-18.4%o) and striped dolphin (-18.1%o) muscles than in albacore tuna (-19.3%o) probably in relation with its migratory pattern. The most striking feature is the presence of two levels of cadmium concentrations in the livers of the tunas (32 mg kg{sup -1} dry weight (DW) vs. 5 mg kg{sup -1} DW). These two groups also differ by their iron concentrations and their {delta}{sup 15}N and {delta}{sup 13}C liver values. These results suggest that in the Biscay Bay, tunas occupy two different ecological niches probably based on different squid inputs in their diet.

  13. Tuna and dolphin associations in the North-east Atlantic: Evidence of different ecological niches from stable isotope and heavy metal measurements

    International Nuclear Information System (INIS)

    Das, K.; Lepoint, G.; Loizeau, V.; Debacker, V.; Dauby, P.; Bouquegneau, J.M.

    2000-01-01

    Associations of tunas and dolphins in the wild are quite frequent events and the question arises how predators requiring similar diet in the same habitat share their environmental resources. As isotopic composition of an animal is related to that of its preys, stable isotope ( 13 C/ 12 C and 15 N/ 14 N) analyses were performed in three predator species from the North-east Atlantic: the striped dolphin, Stenella coeruleoalba, the common dolphin Delphinus delphis and the albacore tuna, Thunnus alalunga, and compared to their previously described stomach content. Heavy metals (Cd, Zn, Cu and Fe) are mainly transferred through the diet and so, have been determined in the tissues of the animals. Tuna muscles display higher δ 15 N than in common and striped dolphins (mean: 11.4 vs. 10.3%o and 10.4%o, respectively) which reflects their higher trophic level nutrition. Higher δ 13 C are found in common (-18.4%o) and striped dolphin (-18.1%o) muscles than in albacore tuna (-19.3%o) probably in relation with its migratory pattern. The most striking feature is the presence of two levels of cadmium concentrations in the livers of the tunas (32 mg kg -1 dry weight (DW) vs. 5 mg kg -1 DW). These two groups also differ by their iron concentrations and their δ 15 N and δ 13 C liver values. These results suggest that in the Biscay Bay, tunas occupy two different ecological niches probably based on different squid inputs in their diet

  14. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    Directory of Open Access Journals (Sweden)

    Brasch-Andersen Charlotte

    2007-10-01

    Full Text Available Abstract Background The etiology of multifactorial human diseases involves complex interactions between numerous environmental factors and alleles of many genes. Efficient statistical tools are demanded in identifying the genetic and environmental variants that affect the risk of disease development. This paper introduces a retrospective polytomous logistic regression model to measure both the main and interaction effects in genetic association studies of human discrete and continuous complex traits. In this model, combinations of genotypes at two interacting loci or of environmental exposure and genotypes at one locus are treated as nominal outcomes of which the proportions are modeled as a function of the disease trait assigning both main and interaction effects and with no assumption of normality in the trait distribution. Performance of our method in detecting interaction effect is compared with that of the case-only model. Results Results from our simulation study indicate that our retrospective model exhibits high power in capturing even relatively small effect with reasonable sample sizes. Application of our method to data from an association study on the catalase -262C/T promoter polymorphism and aging phenotypes detected significant main and interaction effects for age-group and allele T on individual's cognitive functioning and produced consistent results in estimating the interaction effect as compared with the popular case-only model. Conclusion The retrospective polytomous logistic regression model can be used as a convenient tool for assessing both main and interaction effects in genetic association studies of human multifactorial diseases involving genetic and non-genetic factors as well as categorical or continuous traits.

  15. Occurrence and Genesis of Palygorskite and Associated Clay Minerals in a Pleistocene Calcrete Complex, Sde Boqer, Negev Desert, Israel

    OpenAIRE

    Verrecchia, Eric P.; Le Coustumer, M.-N.

    2017-01-01

    Palygorskite and associated clay minerals have been studied in a Pleistocene calcrete complex from the Negev desert (Sde Boqer, Israel). This complex is divided into five main parts: the chalky and marly bedrock overlain by its weathered product, a brecciated calcrete hardpan; the laminar crust; loess pockets trapped in the calcrete; and the overlying soft surficial soil. The distribution of clay minerals is directly dependent on the position of the sample in the calcrete complex. Smectite is...

  16. Stable convergence and stable limit theorems

    CERN Document Server

    Häusler, Erich

    2015-01-01

    The authors present a concise but complete exposition of the mathematical theory of stable convergence and give various applications in different areas of probability theory and mathematical statistics to illustrate the usefulness of this concept. Stable convergence holds in many limit theorems of probability theory and statistics – such as the classical central limit theorem – which are usually formulated in terms of convergence in distribution. Originated by Alfred Rényi, the notion of stable convergence is stronger than the classical weak convergence of probability measures. A variety of methods is described which can be used to establish this stronger stable convergence in many limit theorems which were originally formulated only in terms of weak convergence. Naturally, these stronger limit theorems have new and stronger consequences which should not be missed by neglecting the notion of stable convergence. The presentation will be accessible to researchers and advanced students at the master's level...

  17. Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis

    International Nuclear Information System (INIS)

    Urbach, H.; Mader, I.; Rauer, S.; Baumgartner, A.; Paus, S.; Wagner, J.; Malter, M.P.; Pruess, H.; Lewerenz, J.; Kassubek, J.; Hegen, H.; Auer, M.; Deisenhammer, F.; Ufer, F.; Bien, C.G.

    2015-01-01

    Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE. (orig.)

  18. Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Mader, I. [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Rauer, S.; Baumgartner, A. [University Medical Center Freiburg, Department of Neurology, Freiburg (Germany); Paus, S. [University Medical Center, Department of Neurology, Bonn (Germany); Wagner, J. [University Medical Center, Department of Epileptology, Bonn (Germany); Malter, M.P. [University of Cologne, Department of Neurology, Cologne (Germany); Pruess, H. [Charite - Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Lewerenz, J.; Kassubek, J. [Ulm University, Department of Neurology, Ulm (Germany); Hegen, H.; Auer, M.; Deisenhammer, F. [University Innsbruck, Department of Neurology, Innsbruck (Austria); Ufer, F. [University Medical Center, Department of Neurology, Hamburg (Germany); Bien, C.G. [Epilepsy Centre Bethel, Bielefeld-Bethel (Germany)

    2015-12-15

    Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE. (orig.)

  19. Substrate-induced stable enzyme-inhibitor complex formation allows tight binding of novel 2-aminopyrimidin-4(3H)-ones to drug-resistant HIV-1 reverse transcriptase mutants.

    Science.gov (United States)

    Samuele, Alberta; Facchini, Marcella; Rotili, Dante; Mai, Antonello; Artico, Marino; Armand-Ugón, Mercedes; Esté, José A; Maga, Giovanni

    2008-09-01

    We recently reported the synthesis and biological evaluation of a novel series of 5-alkyl-2-(N,N-disubstituted)amino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones (F(2)-N,N-DABOs). These compounds are highly active against both wild-type HIV-1 and the K103N, Y181C, and Y188L mutant strains. Herein we present novel 6-(2-chloro-6-fluorophenylalkyl)-N,N-DABO (2-Cl-6-F-N,N-DABO) derivatives and investigate the molecular basis for their high-affinity binding to HIV-1 reverse transcriptase (RT). Our results show that the new compounds display higher association rates than the difluoro derivatives toward wild-type HIV-1 RT or drug-resistant RT mutant forms. We also show that they preferentially associate to either the free enzyme or the enzyme-nucleic acid binary complex, and that this binding is stabilized upon formation of the ternary complex between HIV-1 RT and both the nucleic acid and nucleotide substrates. Interestingly, one compound showed dissociation rates from the ternary complex with RT mutants K103N and Y181I 10-20-fold slower than from the corresponding complex with wild-type RT.

  20. Responsive Hydrogels from Associative Block Copolymers: Physical Gelling through Polyion Complexation

    Directory of Open Access Journals (Sweden)

    Christine M. Papadakis

    2017-01-01

    Full Text Available The present review article highlights a specific class of responsive polymer-based hydrogels which are formed through association of oppositely charged polyion segments. The underpinning temporary three-dimensional network is constituted of hydrophilic chains (either ionic or neutral physically crosslinked by ion pair formation arising from intermolecular polyionic complexation of oppositely charged repeating units (polyacid/polybase ionic interactions. Two types of hydrogels are presented: (i hydrogels formed by triblock copolymers bearing oppositely charged blocks (block copolyampholytes, forming self-assembled networks; and (ii hydrogels formed by co-assembly of oppositely charged polyelectrolyte segments belonging to different macromolecules (either block copolymers or homopolyelectrolytes. Due to the weak nature of the involved polyions, these hydrogels respond to pH and are sensitive to the presence of salts. Discussing and evaluating their solution, rheological and structural properties in dependence on pH and ionic strength, it comes out that the hydrogel properties are tunable towards potential applications.

  1. DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons.

    Science.gov (United States)

    Zhong, Xuehua; Hale, Christopher J; Law, Julie A; Johnson, Lianna M; Feng, Suhua; Tu, Andy; Jacobsen, Steven E

    2012-09-01

    The plant-specific DNA-dependent RNA polymerase V (Pol V) evolved from Pol II to function in an RNA-directed DNA methylation pathway. Here, we have identified targets of Pol V in Arabidopsis thaliana on a genome-wide scale using ChIP-seq of NRPE1, the largest catalytic subunit of Pol V. We found that Pol V is enriched at promoters and evolutionarily recent transposons. This localization pattern is highly correlated with Pol V-dependent DNA methylation and small RNA accumulation. We also show that genome-wide chromatin association of Pol V is dependent on all members of a putative chromatin-remodeling complex termed DDR. Our study presents a genome-wide view of Pol V occupancy and sheds light on the mechanistic basis of Pol V localization. Furthermore, these findings suggest a role for Pol V and RNA-directed DNA methylation in genome surveillance and in responding to genome evolution.

  2. Discovery of rare variants via sequencing: implications for the design of complex trait association studies.

    Directory of Open Access Journals (Sweden)

    Bingshan Li

    2009-05-01

    Full Text Available There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates.

  3. Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Caroline Perronnet

    2010-01-01

    Full Text Available Two decades of molecular, cellular, and functional studies considerably increased our understanding of dystrophins function and unveiled the complex etiology of the cognitive deficits in Duchenne muscular dystrophy (DMD, which involves altered expression of several dystrophin-gene products in brain. Dystrophins are normally part of critical cytoskeleton-associated membrane-bound molecular scaffolds involved in the clustering of receptors, ion channels, and signaling proteins that contribute to synapse physiology and blood-brain barrier function. The utrophin gene also drives brain expression of several paralogs proteins, which cellular expression and biological roles remain to be elucidated. Here we review the structural and functional properties of dystrophins and utrophins in brain, the consequences of dystrophins loss-of-function as revealed by numerous studies in mouse models of DMD, and we discuss future challenges and putative therapeutic strategies that may compensate for the cognitive impairment in DMD based on experimental manipulation of dystrophins and/or utrophins brain expression.

  4. Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome.

    Science.gov (United States)

    Vasileiou, Georgia; Vergarajauregui, Silvia; Endele, Sabine; Popp, Bernt; Büttner, Christian; Ekici, Arif B; Gerard, Marion; Bramswig, Nuria C; Albrecht, Beate; Clayton-Smith, Jill; Morton, Jenny; Tomkins, Susan; Low, Karen; Weber, Astrid; Wenzel, Maren; Altmüller, Janine; Li, Yun; Wollnik, Bernd; Hoganson, George; Plona, Maria-Renée; Cho, Megan T; Thiel, Christian T; Lüdecke, Hermann-Josef; Strom, Tim M; Calpena, Eduardo; Wilkie, Andrew O M; Wieczorek, Dagmar; Engel, Felix B; Reis, André

    2018-03-01

    Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome. Furthermore, variants in proteins containing PHD fingers, motifs recognizing specific histone tail modifications, have been associated with several neurological and developmental-delay disorders. Here, we report eight heterozygous de novo variants (one frameshift, two splice site, and five missense) in the gene encoding the BAF complex subunit double plant homeodomain finger 2 (DPF2). Affected individuals share common clinical features described in individuals with Coffin-Siris syndrome, including coarse facial features, global developmental delay, intellectual disability, speech impairment, and hypoplasia of fingernails and toenails. All variants occur within the highly conserved PHD1 and PHD2 motifs. Moreover, missense variants are situated close to zinc binding sites and are predicted to disrupt these sites. Pull-down assays of recombinant proteins and histone peptides revealed that a subset of the identified missense variants abolish or impaire DPF2 binding to unmodified and modified H3 histone tails. These results suggest an impairment of PHD finger structural integrity and cohesion and most likely an aberrant recognition of histone modifications. Furthermore, the overexpression of these variants in HEK293 and COS7 cell lines was associated with the formation of nuclear aggregates and the recruitment of both wild-type DPF2 and BRG1 to these aggregates. Expression analysis of truncating variants found in the affected individuals indicated that the aberrant transcripts escape nonsense-mediated decay. Altogether, we provide compelling evidence that de novo variants in DPF2 cause Coffin-Siris syndrome and propose a dominant-negative mechanism of pathogenicity. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options

    Directory of Open Access Journals (Sweden)

    Wang S

    2014-10-01

    Full Text Available Shelly Wang,1 Aria Fallah2,3 1Department of Neurosurgery, University of Toronto, Toronto, ON, Canada; 2Department of Neurosurgery, Miami Children’s Hospital, Miami, FL, USA; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Abstract: Seizures are clinically significant manifestations associated with 79%–90% of patients with tuberous sclerosis complex. Often occurring within the first year of life in the form of infantile spasms, seizures interfere with neuropsychiatric, social, and cognitive development and carry significant individual and societal consequences. Prompt identification and treatment of seizures is an important focus in the overall management of tuberous sclerosis complex patients. Medical management, either after seizure onset or prophylactically in infants with electroencephalographic abnormalities, is considered first-line therapy. Vigabatrin and adrenocorticotropic hormone have emerged over the past few decades as mainstay pharmacologic modalities. Furthermore, emerging research on mammalian target of rapamycin inhibitors demonstrated promise for the management of seizures and subependymal giant cell astrocytoma. For appropriate surgical candidates with an epileptogenic zone associated with one or more glioneuronal hamartomas, ideally in noneloquent cortex, resective surgery can be considered, which provides a cure in 56% of patients. For medically refractory patients who do not meet criteria for curative surgery, palliative surgical approaches focused on reducing seizure burden, in the form of corpus callosotomy and vagus nerve stimulation, are alternative management options. Lastly, the ketogenic diet, a reemerging therapy based on the anticonvulsant effects of ketone bodies, can be utilized independently or in conjunction with other treatment modalities for the management of difficult-to-treat seizures. Keywords: epilepsy, adrenocorticotropic hormone, vigabatrin, mammalian

  6. Colorimetric determination of sildenafil citrate (Viagra) through ion-associate complex formation.

    Science.gov (United States)

    Amin, Alaa S; Moustafa, Moustafa E; El-Dosoky, Reham

    2009-01-01

    A simple, quick, accurate, and sensitive colorimetric method is described for the determination of sildenafil citrate (SLD). The method is based on the reaction of SLD with Congo Red, Sudan II, and Gentian Violet in buffered aqueous solutions at pH 2.5, 6.5, and 11.0, respectively, to give highly colored soluble ion-associate complex species; the colored products are quantitated colorimetrically at 523, 554, and 569 nm, respectively. The various experimental conditions were optimized. The stoichiometric ratio was found to be 1:1 for all ion associates; the calculated logarithmic stability constants were 8.51, 7.79, and 5.58, respectively. Beer's law was obeyed over the concentration range of 0.2-7.0 microg/mL, whereas the Ringbom optimum concentration range was 0.4-6.5 microg/mL. Values for molar absorptivity, Sandell sensitivity, and detection and quantification limits were also calculated. The proposed method was successfully applied to the determination of SLD in Viagra tablets and in serum samples by using the technique of standard additions with mean accuracy values of 100.06 +/- 1.14, 99.87 +/- 0.70, and 99.86 +/- 0.97% for Viagra tablets and 99.88 +/- 0.60, 99.90 +/- 0.90, and 100.24 +/- 0.80% for serum samples, respectively.

  7. THE COMPLEX ANALYSIS METHOD OF SEMANTIC ASSOCIATIONS IN STUDYING THE STUDENTS’ CREATIVE ETHOS

    Directory of Open Access Journals (Sweden)

    P. A. Starikov

    2013-01-01

    Full Text Available The paper demonstrates the sociological research findings concerning the students’ ideas of creativity based on the questionnaires and testing of the students of the natural science, humanities and technical profiles at Siberian Federal University over the period of 2007-2011.The author suggests a new method of semantic association analysis in order to identify the latent groups of notions related to the concept of creativity. The range of students’ common opinions demonstrate the obvious trend for humanizing the idea of creativity, considering  it as the perfect mode of human existence, which coincide with the ideas of K. Rogers, A. Maslow and other scholars. Today’s students associate creativity primarily with pleasure, self-development, self-expression, inspiration, improvisation, spontaneity; and the resulting semantic complex incorporates such characteristics of creative work as goodness, abundance of energy, integrity, health, freedom and independence, self-development and spirituality.The obtained data prove the importance of the inspiration experience in creative pedagogy; the research outcomes along with the continuing monitoring of students attitude to creativity development can optimize the learning process. The author emphasizes the necessity of introducing some special courses, based on the integral approach (including social, philosophical, psychological, psycho-social and technical aspects, and aimed at developing students’ creative competence. 

  8. Osteomeatal complex obstruction is not associated with adjacent sinus disease in chronic rhinosinusitis with polyps.

    Science.gov (United States)

    Leung, Randy M; Kern, Robert C; Conley, David B; Tan, Bruce K; Chandra, Rakesh K

    2011-01-01

    It is universally accepted that osteomeatal complex (OMC) disease is linked to the subsequent development of chronic rhinosinusitis without nasal polyps (CRSsNPs) via postobstructive mechanisms. The role of OMC obstruction in the pathogenesis of CRSwNPs is less clear. This study was designed to identify if there is an association between OMC obstruction and inflammation of the adjacent sinuses, when patients are stratified by polyp status. This is a follow-up and expanded series of a previous pilot study from our group. CT scans of 144 patients with CRSsNPs and 123 patients with CRS with nasal polyps (CRSwNPs) were evaluated for each sinus and OMC. Patients had no previous surgeries for NPs. CT scans were obtained after a trial of maximal medical therapy. Increasing OMC involvement was associated with increasing Lund-Mackay score for both CRSsNPs and CRSwNPs. In CRSsNP patients, OMC status significantly correlated with adjacent sinus status (p OMC status does not correlate with adjacent sinus status (p = 0.328). OMC obstruction in the setting of CRSwNP may be a barometer of the overall disease process, but in this scenario, paranasal sinus inflammation can not be classified as a postobstructive phenomenon. These findings question the role of minimally invasive procedures in the management of CRSwNPs.

  9. Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Olya Grove

    Full Text Available Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity and intratumor density variation (feature 2: entropy ratio in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47 of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92. Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04 in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8. In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma.

  10. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  11. Skin autofluorescence is elevated in patients with stable coronary artery disease and is associated with serum levels of neopterin and the soluble receptor for advanced glycation end products

    NARCIS (Netherlands)

    Mulder, Douwe J.; van Haelst, Paul L.; Gross, Sascha; de Leeuw, Karina; Bijzet, Johannes; Graaff, Reindert; Gans, Rijk O.; Zijlstra, Felix; Smit, Andries J.

    Aims: To investigate whether skin autofluorescence (AF), a non-invasive marker for advanced glycation end products (AGEs), is elevated in stable coronary artery disease (sCAD) and to investigate its relationship with serum levels of the soluble receptor for AGEs (sRAGE), neopterin and C-reactive

  12. Comparative analysis of the heat stable proteome of radicles of Medicago truncatula seeds during germination identifies late embryogenesis abundant proteins associated with desiccation tolerance

    NARCIS (Netherlands)

    Boudet, J.; Buitink, J.; Hoekstra, F.A.; Rogniaux, H.; Larré, C.; Satour, P.; Leprince, O.

    2006-01-01

    A proteomic analysis was performed on the heat stable protein fraction of imbibed radicles of Medicago truncatula seeds to investigate whether proteins can be identified that are specifically linked to desiccation tolerance (DT). Radicles were compared before and after emergence (2.8 mm long) in

  13. The rationale and design of the PERindopril GENEtic association study (PERGENE): a pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease

    NARCIS (Netherlands)

    Brugts, J. J.; de Maat, M. P. M.; Boersma, E.; Witteman, J. C. M.; van Duijn, C.; Uitterlinden, A. G.; Bertrand, M.; Remme, W.; Fox, K.; Ferrari, R.; Danser, A. H. J.; Simoons, M. L.; Remme, W. J.; Aldershville, J.; Hildebrandt, P.; Bassand, J. P.; Cokkinos, D.; Toutouzas, P.; Eha, J.; Erhardt, L.; Erikssen, J.; Grybauskas, R.; Kalnins, U.; Karsch, K.; Sechtem, U.; Keltai, M.; Klein, W.; Luescher, T.; Mulcahy, D.; Nieminen, M.; Oto, A.; Ozsaruhan, O.; Paulus, W.; Providencia, L.; Riecansky, I.; Ruzyllo, W.; Santini, U.; Tavazzi, L.; Soler-Soler, J.; Widimsky, P.; Julian, D.; Dargie, H.; Kobler, W.; Duprez, D.; Steg, G.; Thygesen, K.; Drexel, H.; Gombotz, G.; Stoeckl, G.; Heyndrickx, G. H.; Legrand, V.; Materne, P.; van Mieghem, W.; Bocek, P.; Branny, M.; Cech, M.; Charouzek, J.; Drazka, J.; Fabik, L.; Florian, J.; Francek, L.; Groch, L.; Havranek, P.; Herman, A.; Hradec, J.; Jansky, P.; Jirmar, R.; Jokl, I.; Krejcova, H.; Kvasnak, M.; Maratka, T.; Marcinek, G.; Moravcova, J.; Nedbal, P.; Peterka, K.; Povolny, J.; Rosolova, H.; Semrad, B.; Sochor, K.; Spacek, R.; Spinar, J.; Stipal, R.; Stuchlik, K.; Sulda, M.; Ulman, J.; Vaclavicek, A.; Vojtisek, P.; Bjerregard Andersen, H.; Dorff, B.; Kristensen, K.; Madsen, J. K.; Markenvard, J.; Meibom, J.; Norgaard, A.; Scheibel, M.; Leht, A.; Teesalu, R.; Vahulaa, V.; Itkonen, A.; Juvonen, J.; Karmakoski, J.; Kilkki, E.; Koskela, E.; Kotila, M. J.; Melin, J.; Nieminen, M. S.; Savola, R.; Terho, T.; Voipio Pulkki, L. M.; Apffel, F.; Attali, P.; Baron, B.; Berthier, Y.; Dambrine, P.; Danchin, N.; Decoulx, E.; Deshayes, P.; Fouche, R.; Genest, M.; Godard, S.; Guillot, J. P.; Hanania, G.; Lelguen, C.; Leroy, F.; Mansourati, J.; Mery, D.; Michel, A. N.; Quiret, J. C.; Raynaud, P.; Rondepierre, D.; Roynard, J. L.; van Belle, E.; Veyrat, A.; Gaudron, P.; Karsch, K. R.; Lauer, B.; Rettig Stsrmer, G.; Riessen, R.; Rutsch, W.; Sigel, H. A.; Simon, R.; Stork, S.; von Schacky, C.; Winkelmann, B. R.; Christakos, S.; Feggos, S.; Geleris, P.; Georgiadis, S.; Gialafos, J.; Goudevenos, I.; Kardara, D.; Kardaras, F.; Karidis, C.; Kelesides, C.; Kyriakidis, M.; Koliopoulos, N.; Kremastinos, D.; Liberi, S.; Manolis, A. N.; Pyrgakis, V.; Papasteriadis, E.; Papazoglou, N.; Skoufas, P.; Stamatelopoulos, S.; Stambola, S.; Stavridis, A.; Syribeis, S.; Vardas, P.; Vassiliadis, I.; Voudris, V.; Zacharoulis, A.; Zobolos, S.; Zouras, C.; Berenyi, I.; Bocsa, Z.; Csendes, E.; Edes, I.; Gelesz, E.; Janosi, A.; Kalo, E.; Karpati, P.; Kornel, S.; Pap, I.; Pinter, I.; Polak, G.; Reiber, I.; Rusznak, M.; Simon, A.; Tarjan, J.; Tihanyi, L.; Timar, S.; Toth, K.; Veress, G.; Barton, J.; Crean, P.; Daly, K.; Kearney, P.; Meany, T. B.; Quigley, P.; Azzolini, P.; Barone, G.; Barsotti, A.; Bellone, E.; Borghetti, A.; Branzi, A.; Brunelli, C.; Capponi, E.; Capucci, A.; Casaccia, M.; Casali, G.; Cecchetti, E.; Ceci, V.; Celegon, L.; Chimini, C.; Colombo, A.; Corsini, G.; Cucchini, F.; Dalla Volta, S.; de Luca, I.; de Servi, S.; Delise, P.; Di Donato, M.; Di Giacomo, U.; Di Pasquale, G.; Fiorentini, C.; Gaddi, O.; Giannetto, M.; Giannuzzi, P.; Giordano, A.; Giovannini, E.; Iacono, A.; Inama, G.; Ippoliti, G.; Leghissa, R.; Lorusso, R.; Marzilli, M.; Minutiello, L.; Moretti, G.; Mosele, G. M.; Pasotti, C.; Pettinati, G.; Pezzano, A.; Polimeni, M. R.; Portaluppi, F.; Proto, C.; Riva, S.; Sanguinetti, M.; Santini, M.; Severi, S.; Sinagra, G.; Tantalo, L.; Vajola, S. F.; Vincenzi, M.; Volterrani, M.; Zavatteri, G.; Zogno, M.; Gailiss, E.; Gersamija, A.; Ozolina, M. A.; Skards, J.; Baubiniene, A.; Berukstis, E.; Grigoniene, L.; Grybauskas, A. N.; Kibarskis, A.; Kirkutis, A.; Marcinkus, R.; Milvidaite, I.; Vasiliauskas, D.; Aalders, J. C. A.; Bruggeling, W. A. J.; Bucx, J. J. J.; de Feyter, P. J.; de Leeuw, M. J.; de Waard, D. E. P.; de Weerd, G. J.; de Zwaan, C.; Dijkgraaf, R.; Droste, H. T.; Freericks, M. P.; Hagoort Kok, A. W.; Jap, W. T. J.; Jochemsen, G. M.; Kiemeney, K.; Kuijer, P. J. P.; Mannaerts, H. F. J.; Piek, J. J.; Saelman, J. P. M.; Slob, F. D.; Smits, W. C. G.; Spierenburg, H. A. M.; Suttorp, M. J.; Tan, T. B.; van Beek, G. J.; van Daele, M. E. R. M.; van den Merkhof, L. F. M.; van den Toren, E. W.; van Hessen, M. W. J.; van Langeveld, R. A. M.; van Loo, L. W. H.; van Nierop, P. R.; van Rey, F. J. W.; van Straalen, M. J.; Vos, J.; Werner, H. A.; Westendorp, J. J. C.; Zwiers, G.; Achremczyk, P.; Adamus, J.; Baska, J.; Bolinska Soltysiak, H.; Bubinski, R.; Ceremuzynski, L.; Cieslinski, A.; Dariusz, D.; Deptulski, T.; Drewla, P.; Drozdowski, P.; Dubiel, J. S.; Dudek, D.; Galewicz, M.; Ghlebus, K.; Halawa, B.; Jakubowska Majnigier, M.; Janion, M.; Jaworska, K.; Kaszewska, I.; Kleinrok, A.; Kornacewicz Jach, Z.; Krawczyk, W.; Krynicki, R.; Krzciuk, M.; Krzeminska Pakula, M.

    2009-01-01

    BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided

  14. There's More than Meets the Eye: Complex Associations of Daily Pain, Physical Symptoms, and Self-Efficacy with Activity in Middle and Older Adulthood.

    Science.gov (United States)

    Curtis, Rachel G; Windsor, Tim D; Mogle, Jacqueline A; Bielak, Allison A M

    2017-01-01

    . Within-person physical symptoms were positively related to social and mental activity. Stable individual differences as well as short-term within-person variation in physical and psychological functioning are associated with day-to-day variation in activity. Between-person associations did not always reflect within-person associations (e.g., for pain). These complex associations may be influenced by a range of factors including the type of activity and how it is defined (e.g., specific activities and their difficulty), the type of physical symptoms experienced, and age. © 2016 S. Karger AG, Basel.

  15. The Reactivity of Stable Metallacyclobutenes and Vinylcarbenes

    OpenAIRE

    Holland, Ryan Lynn

    2016-01-01

    Chapter 1. Historical Development of Stable Metallacyclobutenes Fred Tebbe and co-workers synthesized the first stable metallacyclobutene complexes in the late 1970’s by treatment of an intermediate titanium methylene species – later popularized as the “Tebbe reagent” – with acetylenes. Robert Grubbs at Caltech further studied this system, using it to detail a degenerate metathesis reaction and to isolate a metallacyclobutane complex – which was implicated in the emerging field of alkene meta...

  16. [The Stigma-discrimination Complex Associated With Mental Disorder as a Risk Factor for Suicide].

    Science.gov (United States)

    Campo-Arias, Adalberto; Herazo, Edwin

    2015-01-01

    The concept stigma-discrimination complex associated with mental disorder (SDCAMD) is proposed to encompass the terms used in the attribution theory: stigma, stereotype, prejudice and discrimination. SDCAMD is one of the most frequent disorders worldwide. Internalized and perceived SDCAMD may explain a number of suicide cases. To update the factors that may explain the association between SDCAMD and suicide, and postulate possible underlying mechanisms. Articles were identified in MEDLINE using the descriptors for "stigma", "mental disorders" and "suicide" or "suicide rate". Articles published between January 2000 and June 2014 were included. Reviews and case studies were not considered. The two included studies showed that stigma increased the risk of suicidal behaviors. It was evident that people who meet criteria for mental disorder and reported high self-stigma made a greater number of suicide attempts, and countries with high stigma in the general population have a higher suicide rate. It was considered that the relationship between SDCAMD and suicide is established by a set of interrelated mechanisms. A "direct" mechanism involving perceived stigma and is configured as a barrier to access mental health services, and an "indirect" mechanism involving the self-stigma, which increases the vulnerability to depressive episodes and repeated self-injurious behaviors that ultimately end in suicide. The SDCAMD impacts negatively on the quality of life of people who meet criteria for mental disorders, and accounts for a significant number of suicides. One way is related to the perceived stigma that is configured as a barrier to access mental health services and, the second one includes repeated self-injurious behaviors that reduce self-esteem and increases perceived stress. Further research is required to increase the knowledge of this association. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  17. Fine Mapping Major Histocompatibility Complex Associations in Psoriasis and Its Clinical Subtypes

    Science.gov (United States)

    Okada, Yukinori; Han, Buhm; Tsoi, Lam C.; Stuart, Philip E.; Ellinghaus, Eva; Tejasvi, Trilokraj; Chandran, Vinod; Pellett, Fawnda; Pollock, Remy; Bowcock, Anne M.; Krueger, Gerald G.; Weichenthal, Michael; Voorhees, John J.; Rahman, Proton; Gregersen, Peter K.; Franke, Andre; Nair, Rajan P.; Abecasis, Gonçalo R.; Gladman, Dafna D.; Elder, James T.; de Bakker, Paul I.W.; Raychaudhuri, Soumya

    2014-01-01

    Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C∗06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10−364). Stepwise analysis revealed multiple HLA-C∗06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C∗12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (pomnibus = 2.2 × 10−11), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC. PMID:25087609

  18. Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex.

    Science.gov (United States)

    Radovits, Tamás; Gerö, Domokos; Lin, Li-ni; Loganathan, Sivakkanan; Hoppe-Tichy, Torsten; Szabó, Csaba; Karck, Matthias; Sakurai, Hiromu; Szabó, Gábor

    2008-10-01

    Aging-associated nitro-oxidative stress causes tissue injury and activates proinflammatory pathways that play an important role in the pathogenesis of aging-associated cardiovascular dysfunction. It has been recently reported, that the copper(II)-aspirinate complex (CuAsp) exerts not only the well-known anti-inflammatory and platelet antiaggregating effects of aspirin, but, due to its superoxide dismutase mimetic activity, it acts as a potent antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated myocardial and endothelial dysfunction. Aging and young rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg per day per os). Left ventricular pressure-volume relations were measured by using a microtip pressure-volume conductance catheter, and indexes of contractility (e.g., slope of end-systolic pressure-volume relationships [ESPVR] [E(es)], and dP/dt(max) - end-diastolic volume [EDV]) were calculated. In organ bath experiments for isometric tension with isolated aortic rings, endothelium-dependent and -independent vasorelaxation were investigated by using acetylcholine and sodium nitroprusside. When compared to the young controls, aging rats showed impaired left ventricular contractility (E(es), 0.51 +/- 0.04 vs. 2.16 +/- 0.28 mmHg/microL; dP/dt(max) - EDV, 10.71 +/- 2.02 vs. 37.23 +/- 4.18 mmHg/sec per microL; p aging animals (94.83 +/- 0.73 vs. 66.66 +/- 1.30%; p cardiovascular functions of young rats. Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp.

  19. Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes.

    Science.gov (United States)

    Okada, Yukinori; Han, Buhm; Tsoi, Lam C; Stuart, Philip E; Ellinghaus, Eva; Tejasvi, Trilokraj; Chandran, Vinod; Pellett, Fawnda; Pollock, Remy; Bowcock, Anne M; Krueger, Gerald G; Weichenthal, Michael; Voorhees, John J; Rahman, Proton; Gregersen, Peter K; Franke, Andre; Nair, Rajan P; Abecasis, Gonçalo R; Gladman, Dafna D; Elder, James T; de Bakker, Paul I W; Raychaudhuri, Soumya

    2014-08-07

    Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C(∗)06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10(-364)). Stepwise analysis revealed multiple HLA-C(∗)06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C(∗)12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (Pomnibus = 2.2 × 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  20. The RecJ2 protein in the thermophilic archaeon Thermoplasma acidophilum is a 3'-5' exonuclease that associates with a DNA replication complex.

    Science.gov (United States)

    Ogino, Hiromi; Ishino, Sonoko; Kohda, Daisuke; Ishino, Yoshizumi

    2017-05-12

    RecJ/cell division cycle 45 (Cdc45) proteins are widely conserved in the three domains of life, i.e. in bacteria, Eukarya, and Archaea. Bacterial RecJ is a 5'-3' exonuclease and functions in DNA repair pathways by using its 5'-3' exonuclease activity. Eukaryotic Cdc45 has no identified enzymatic activity but participates in the CMG complex, so named because it is composed of Cdc45, minichromosome maintenance protein complex (MCM) proteins 2-7, and GINS complex proteins (Sld5, Psf11-3). Eukaryotic Cdc45 and bacterial/archaeal RecJ share similar amino acid sequences and are considered functional counterparts. In Archaea, a RecJ homolog in Thermococcus kodakarensis was shown to associate with GINS and accelerate its nuclease activity and was, therefore, designated GAN ( G INS- a ssociated n uclease); however, to date, no archaeal RecJ·MCM·GINS complex has been isolated. The thermophilic archaeon Thermoplasma acidophilum has two RecJ-like proteins, designated TaRecJ1 and TaRecJ2. TaRecJ1 exhibited DNA-specific 5'-3' exonuclease activity, whereas TaRecJ2 had 3'-5' exonuclease activity and preferred RNA over DNA. TaRecJ2, but not TaRecJ1, formed a stable complex with TaGINS in a 2:1 molar ratio. Furthermore, the TaRecJ2·TaGINS complex stimulated activity of TaMCM ( T. acidophilum MCM) helicase in vitro , and the TaRecJ2·TaMCM·TaGINS complex was also observed in vivo However, TaRecJ2 did not interact with TaMCM directly and was not required for the helicase activation in vitro These findings suggest that the function of archaeal RecJ in DNA replication evolved divergently from Cdc45 despite conservation of the CMG-like complex formation between Archaea and Eukarya. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

    DEFF Research Database (Denmark)

    Viken, M.K.; Blomhoff, A.; Olsson, M.

    2009-01-01

    The high-risk human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 alleles cannot explain the entire type 1 diabetes (T1D) association observed within the extended major histocompatibility complex. We have earlier identified an association with D6S2223, located 2.3 Mb telomeric of HLA-A, on the DRB1...

  2. Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin.

    Science.gov (United States)

    Park, Soo-Young; Ludwig, Michael Z; Tamarina, Natalia A; He, Bin Z; Carl, Sarah H; Dickerson, Desiree A; Barse, Levi; Arun, Bharath; Williams, Calvin L; Miles, Cecelia M; Philipson, Louis H; Steiner, Donald F; Bell, Graeme I; Kreitman, Martin

    2014-02-01

    Drosophila melanogaster has been widely used as a model of human Mendelian disease, but its value in modeling complex disease has received little attention. Fly models of complex disease would enable high-resolution mapping of disease-modifying loci and the identification of novel targets for therapeutic intervention. Here, we describe a fly model of permanent neonatal diabetes mellitus and explore the complexity of this model. The approach involves the transgenic expression of a misfolded mutant of human preproinsulin, hINS(C96Y), which is a cause of permanent neonatal diabetes. When expressed in fly imaginal discs, hINS(C96Y) causes a reduction of adult structures, including the eye, wing, and notum. Eye imaginal discs exhibit defects in both the structure and the arrangement of ommatidia. In the wing, expression of hINS(C96Y) leads to ectopic expression of veins and mechano-sensory organs, indicating disruption of wild-type signaling processes regulating cell fates. These readily measurable "disease" phenotypes are sensitive to temperature, gene dose, and sex. Mutant (but not wild-type) proinsulin expression in the eye imaginal disc induces IRE1-mediated XBP1 alternative splicing, a signal for endoplasmic reticulum stress response activation, and produces global change in gene expression. Mutant hINS transgene tester strains, when crossed to stocks from the Drosophila Genetic Reference Panel, produce F1 adults with a continuous range of disease phenotypes and large broad-sense heritability. Surprisingly, the severity of mutant hINS-induced disease in the eye is not correlated with that in the notum in these crosses, nor with eye reduction phenotypes caused by the expression of two dominant eye mutants acting in two different eye development pathways, Drop (Dr) or Lobe (L), when crossed into the same genetic backgrounds. The tissue specificity of genetic variability for mutant hINS-induced disease has, therefore, its own distinct signature. The genetic dominance

  3. A model-based approach to associate complexity and robustness in engineering systems

    DEFF Research Database (Denmark)

    Göhler, Simon Moritz; D. Frey, Daniel; Howard, Thomas J.

    2017-01-01

    Ever increasing functionality and complexity of products and systems challenge development companies in achieving high and consistent quality. A model-based approach is used to investigate the relationship between system complexity and system robustness. The measure for complexity is based...

  4. Association of Hospital Market Concentration With Costs of Complex Hepatopancreaticobiliary Surgery.

    Science.gov (United States)

    Cerullo, Marcelo; Chen, Sophia Y; Dillhoff, Mary; Schmidt, Carl; Canner, Joseph K; Pawlik, Timothy M

    2017-09-20

    associated with lower overall charges and lower costs of pancreatic and hepatic surgery. For complex, highly specialized procedures, hospital market consolidation may represent the best value proposition: better quality of care with lower costs.

  5. Hand lesion after arthroscopic rotator cuff repair: Association with complex regional pain syndrome.

    Science.gov (United States)

    Tanesue, Ryo; Gotoh, Masafumi; Mitsui, Yasuhiro; Nakamura, Hidehiro; Honda, Hirokazu; Ohzono, Hiroki; Shimokobe, Hisao; Tokunaga, Tsuyoshi; Imai, Takaki; Okawa, Takahiro; Shiba, Naoto

    2018-01-01

    It is known that complex regional pain syndrome (CRPS) occurs after arthroscopic rotator cuff repair (ARCR); however, few studies have investigated this complication. Therefore, the purpose of the present study was to evaluate CRPS after ARCR. A total of 182 patients who underwent ARCR were enrolled in this study. The average age of patients was 62.8 ± 10.0 years, with an average follow-up period of 21.5 ± 38.1 months. CRPS criteria outlined by the Ministry of Health, Labor, and Welfare study team for CRPS in Japan (MHLWJ) and International Association for the Study of Pain (IASP 2005) were utilized for diagnosis. There are two rating systems for the "clinical purpose" and "research purpose" in both criteria, respectively. Clinical outcomes, including Japanese Orthopedic Association (JOA) and University of California, Los Angeles scores, were evaluated using univariate and multivariate analysis. CRPS exclusively occurred in the hand of the operated limb, developing within 3 months of surgery. Two or more of the following symptoms were noted in patients with the hand lesion associated with CRPS: edema (93.4%), restricted range of motion (83.4%), hyperalgesia (30.1%), paridrosis (20.4%), and atrophic change (12.2%). Under these conditions, the incidences of CRPS were 24.2% (44/182) when evaluated by the MHLWJ rating system for the "clinical purpose;" 11% (22/182) by the MHLWJ rating system for the "research purpose;" 6% (11/182) by the IASP 2005 for the "clinical purpose;" and 0.5% (1/182) by the IASP 2005 for the "research purpose." Results of multivariate analysis demonstrated that "Function" in the JOA score was a risk factor for the development of CRPS after ARCR, when evaluated by a system for the "clinical purpose" of the MHLWJ. Following ARCR, CRPS-induced hand lesions occur more frequently than is generally believed, thereby suggesting that its impact on surgical outcomes should be clarified in the future. Copyright © 2017 The Japanese Orthopaedic

  6. Two stable steady states in the Hodgkin-Huxley axons

    OpenAIRE

    Aihara, K.; Matsumoto, G.

    1983-01-01

    Two stable steady states were found in the numerical solution of the Hodgkin-Huxley equations for the intact squid axon bathed in potassium-rich sea water with an externally applied inward current. Under the conditions the two stable steady-states exist, the Hodgkin-Huxley equations have a complex bifurcation structure including, in addition to the two stable steady-states, a stable limit cycle, two unstable equilibrium points, and one asymptotically stable equilibrium point. It was also conc...

  7. Head Position Change Is Not Associated with Acute Changes in Bilateral Cerebral Oxygenation in Stable Preterm Infants during the First 3 Days of Life.

    Science.gov (United States)

    Liao, Steve Ming-Che; Rao, Rakesh; Mathur, Amit M

    2015-06-01

    Several recent intraventricular hemorrhage prevention bundles include midline head positioning to prevent potential disturbances in cerebral hemodynamics. We aimed to study the impact of head position change on regional cerebral saturations (SctO2) in preterm infants (position change were compared using paired t-test. In relatively stable preterm infants (gestational age 26.5 ± 1.7 weeks, birth weight 930 ± 220 g; n = 20), bilateral SctO2 remained within normal range (71.1-75.3%) when the head was turned from midline position to either side. Stable preterm infants tolerated brief changes in head position from midline without significant alternation in bilateral SctO2; the impact on critically ill infants needs further evaluation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Association of non-traumatic complex regional pain syndrome with adenocarcinoma lung on 99mTc-MDP bone scan

    Science.gov (United States)

    Damle, Nishikant A; Tripathi, Madhavi; Singhal, Abhinav; Bal, Chandrasekhar; Kumar, Praveen; Kandasamy, Devasenathipathi; Jana, Manisha

    2012-01-01

    Complex regional pain syndrome (CRPS) is usually associated with trauma. Rarely, it may be seen in association with malignancies. We present here the bone scan and X-ray findings in the case of a 56-year-male-patient with adenocarcinoma lung who also had non-traumatic CRPS without involvement of the stellate ganglion. The case highlights the fact that spontaneous development of reflex sympathetic dystrophy may be associated with a neoplastic etiology. PMID:24019656

  9. Association of non-traumatic complex regional pain syndrome with adenocarcinoma lung on 99mTc-MDP bone scan

    International Nuclear Information System (INIS)

    Damle, Nishikant A.; Tripathi, Madhavi; Singhal, Abhinav; Bal, Chandrasekhar; Praveen Kumar; Kandasamy, Devasenathipathi; Jana, Manisha

    2012-01-01

    Complex regional pain syndrome (CRPS) is usually associated with trauma. Rarely, it may be seen in association with malignancies. We present here the bone scan and X-ray findings in the case of a 56-year-male-patient with adenocarcinoma lung who also had non-traumatic CRPS without involvement of the stellate ganglion. The case highlights the fact that spontaneous development of reflex sympathetic dystrophy may be associated with a neoplastic etiology. (author)

  10. Integral and peripheral association of proteins and protein complexes with Yersinia pestis inner and outer membranes

    Directory of Open Access Journals (Sweden)

    Bunai Christine L

    2009-02-01

    Full Text Available Abstract Yersinia pestis proteins were sequentially extracted from crude membranes with a high salt buffer (2.5 M NaBr, an alkaline solution (180 mM Na2CO3, pH 11.3 and membrane denaturants (8 M urea, 2 M thiourea and 1% amidosulfobetaine-14. Separation of proteins by 2D gel electrophoresis was followed by identification of more than 600 gene products by MS. Data from differential 2D gel display experiments, comparing protein abundances in cytoplasmic, periplasmic and all three membrane fractions, were used to assign proteins found in the membrane fractions to three protein categories: (i integral membrane proteins and peripheral membrane proteins with low solubility in aqueous solutions (220 entries; (ii peripheral membrane proteins with moderate to high solubility in aqueous solutions (127 entries; (iii cytoplasmic or ribosomal membrane-contaminating proteins (80 entries. Thirty-one proteins were experimentally associated with the outer membrane (OM. Circa 50 proteins thought to be part of membrane-localized, multi-subunit complexes were identified in high Mr fractions of membrane extracts via size exclusion chromatography. This data supported biologically meaningful assignments of many proteins to the membrane periphery. Since only 32 inner membrane (IM proteins with two or more predicted transmembrane domains (TMDs were profiled in 2D gels, we resorted to a proteomic analysis by 2D-LC-MS/MS. Ninety-four additional IM proteins with two or more TMDs were identified. The total number of proteins associated with Y. pestis membranes increased to 456 and included representatives of all six β-barrel OM protein families and 25 distinct IM transporter families.

  11. Major histocompatibility complex alleles associated with parasite susceptibility in wild giant pandas.

    Science.gov (United States)

    Zhang, L; Wu, Q; Hu, Y; Wu, H; Wei, F

    2015-01-01

    Major histocompatibility complex (MHC) polymorphism is thought to be driven by antagonistic coevolution between pathogens and hosts, mediated through either overdominance or frequency-dependent selection. However, investigations under natural conditions are still rare for endangered mammals which often exhibit depleted variation, and the mechanism of selection underlying the maintenance of characteristics remains a considerable debate. In this study, 87 wild giant pandas were used to investigate MHC variation associated with parasite load. With the knowledge of the MHC profile provided by the genomic data of the giant panda, seven DRB1, seven DQA1 and eight DQA2 alleles were identified at each single locus. Positive selection evidenced by a significantly higher number of non-synonymous substitutions per non-synonymous codon site relative to synonymous substitutions per synonymous codon site could only be detected at the DRB1 locus, which leads to the speculation that DRB1 may have a more important role in dealing with parasite infection for pandas. Coprological analyses revealed that 55.17% of individuals exhibited infection with 1-2 helminthes and 95.3% of infected pandas carried Baylisascaris shroederi. Using a generalized linear model, we found that Aime-DRB1*10 was significantly associated with parasite infection, but no resistant alleles could be detected. MHC heterozygosity of the pandas was found to be uncorrelated with the infection status or the infection intensity. These results suggested that the possible selection mechanisms in extant wild pandas may be frequency dependent rather than being determined by overdominance selection. Our findings could guide the candidate selection for the ongoing reintroduction or translocation of pandas.

  12. Identification of a mutation associated with permethrin resistance in the para-type sodium channel of the stable fly (Diptera: Muscidae).

    Science.gov (United States)

    Olafson, Pia U; Pitzer, Jimmy B; Kaufman, Phillip E

    2011-02-01

    The insect sodium channel is of particular interest for evaluating resistance to pyrethroids because it is the target molecule for this major class of neurotoxic insecticides. The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), sodium channel coding sequence representing domains IS6 through IVS6 was isolated, and the sequence encoding domain II was compared among individuals of a laboratory strain selected for resistance to permethrin and the unselected, parental generation. A point mutation resulting in a leucine-to-histidine amino acid change was identified (Leul014His), and its location corresponded with that observed for knockdown resistance (kdr) mutations in other insects. As a result, the allele was designated kdr-his. A molecular assay was developed to assess the frequency of this mutation in genomic DNA of individual stable flies from the laboratory selections, which provided further evidence that the kdr-his allele accounts for the observed level ofpermethrin resistance in the selected strain. The assay was then used to evaluate the frequency of the mutation from five field-collected populations originating from three horse farms near Ocala, FL; one horse farm near Gainesville, FL; and one dairy farm near Hague, FL. Frequency of the kdr-his allele ranged from 0.46 to 0.78, supporting further investigation of allele prevalence throughout the stable fly season and in response to field insecticide application.

  13. HPNS seizure risk: a role for the Golgi-associated retrograde protein complex?

    Science.gov (United States)

    McCall, R D

    2011-01-01

    Previous attempts to characterize the genetic contribution to differential risk of developing the HPNS seizure in a mouse model system are extended to additional data and an analytical mode that incorporates the set of linked resources for systems genetics in the GeneNetwork project. A quantitative trait locus (QTL) affecting HPNS seizure phenotype was mapped to a approximately 6 megabase (Mb) gene-rich region of Chr 17 based on the degree of expression covariation among genes in the region of the QTL and genes in the brains of BXD recombinant inbred mice in the same chromosomal region. Use of GeneNetwork's WebQTL analytical modules revealed that among > 220 positional candidate genes, vacuolar protein sorting gene 52 (Vps52) has highest priority. It appears that a single nearly null mutation in a distal region of Vps52 3'UTR (untranslated region) defined by a DNA probe set is associated with > 60% of the seizure risk difference between the high- and low-risk strains DBA/2 and C57BL/6, respectively. Based on the known contribution of the elements of the GARP complex--Vps52, -53 and -54--to motoneuron abnormalities, mutation-depleted Vps52 may be implicated in HPNS seizure risk variation in the mouse and, by gene homology, also with human VPS52.

  14. Mycobacterium avium complex-associated cholecystitis in AIDS patient: a case description and review of literature.

    Science.gov (United States)

    El Chaer, Firas; Harris, Nadine; El Sahly, Hana; Hemmige, Vagish; Martinez Blanco, Elvia; Woc-Colburn, Laila

    2016-11-01

    AIDS-related cholangiopathy was common in patients with AIDS prior to the advent of highly active antiretroviral therapy. Mycobacterium avium complex (MAC) is the most common opportunistic bacterial infection seen in AIDS patients and one of many opportunistic pathogens implicated in AIDS cholangiopathy. We describe a case of acute cholecystitis secondary to MAC in a patient with likely AIDS cholangiopathy. The patient, a 37-year-old Hispanic woman with CD4 + cell count of 10 cells/mm 3 who was previously diagnosed with disseminated MAC, presented with a eight days of diffuse abdominal pain and anorexia. Radiologic imaging suggested acute cholecystitis, so the patient underwent open cholecystectomy. Pathology staining of the gall bladder wall revealed acid-fast bacilli consistent with MAC. The patient had been receiving appropriate therapy as an outpatient for MAC with presumed reliable adherence, but we suggest her burden of disease was high due to her severe immunosuppressive state. A thorough review of the literature showed that there are many infectious and non-infectious aetiologies for AIDS-associated cholangiopathy. Acute cholecystitis can develop in the setting of AIDS cholangiopathy, potentially secondary to the opportunistic infection that initially caused the cholangiopathy. MAC-related gallbladder disease needs to be considered in patients with advanced AIDS who present with evidence of acute cholecystitis. © The Author(s) 2015.

  15. Human Herpesvirus 7 U21 Tetramerizes To Associate with Class I Major Histocompatibility Complex Molecules

    Science.gov (United States)

    May, Nathan A.; Wang, Qiuhong; Balbo, Andrea; Konrad, Sheryl L.; Buchli, Rico; Hildebrand, William H.; Schuck, Peter

    2014-01-01

    ABSTRACT The U21 gene product from human herpesvirus 7 binds to and redirects class I major histocompatibility complex (MHC) molecules to a lysosomal compartment. The molecular mechanism by which U21 reroutes class I MHC molecules to lysosomes is not known. Here, we have reconstituted the interaction between purified soluble U21 and class I MHC molecules, suggesting that U21 does not require additional cellular proteins to interact with class I MHC molecules. Our results demonstrate that U21, itself predicted to contain an MHC class I-like protein fold, interacts tightly with class I MHC molecules as a tetramer, in a 4:2 stoichiometry. These observations have helped to elucidate a refined model describing the mechanism by which U21 escorts class I MHC molecules to the lysosomal compartment. IMPORTANCE In this report, we show that the human herpesvirus 7 (HHV-7) immunoevasin U21, itself a class I MHC-like protein, binds with high affinity to class I MHC molecules as a tetramer and escorts them to lysosomes, where they are degraded. While many class I MHC-like molecules have been described in detail, this unusual viral class I-like protein functions as a tetramer, associating with class I MHC molecules in a 4:2 ratio, illuminating a functional significance of homooligomerization of a class I MHC-like protein. PMID:24390327

  16. Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears.

    Science.gov (United States)

    Bechshøft, T Ø; Sonne, C; Dietz, R; Born, E W; Muir, D C G; Letcher, R J; Novak, M A; Henchey, E; Meyer, J S; Jenssen, B M; Villanger, G D

    2012-07-01

    The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p'-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Mitochondrial Encephalomyopathy and Complex III Deficiency Associated with a Stop-Codon Mutation in the Cytochrome b Gene

    OpenAIRE

    Keightley, J. Andrew; Anitori, Roberto; Burton, Miriam D.; Quan, Franklin; Buist, Neil R. M.; Kennaway, Nancy G.

    2000-01-01

    We have reinvestigated a young woman, originally reported by us in 1983, who presented with exercise intolerance and lactic acidosis associated with severe deficiency of complex III and who responded to therapy with menadione and ascorbate. Gradually, she developed symptoms of a mitochondrial encephalomyopathy. Immunocytochemistry of serial sections of muscle showed a mosaic of fibers that reacted poorly with antibodies to subunits of complex III but reacted normally with antibodies to subuni...

  18. Spindle and kinetochore associated complex subunit 1 regulates the proliferation of oral adenosquamous carcinoma CAL-27 cells in vitro

    OpenAIRE

    Zhang, Bin; Li, Ke Yi; Chen, Hai Ying; Pan, Shao Dong; Jiang, Li Cheng; Wu, Ya Ping; Liu, Shu Wei

    2013-01-01

    Background The prognosis of oral squamous cell carcinoma is very poor due to local recurrence and metastasis. This study explores the molecular events involved in oral carcinoma with the goal of developing novel therapeutic strategies. The mitotic spindle is a complex mechanical apparatus required for the accurate segregation of sister chromosomes during mitosis. Spindle and kinetochore associated complex subunit 1 (SKA1) is a microtubule-binding subcomplex of the outer kinetochore that is es...

  19. Biological properties of aerococci and bacilli as a component of new associate-probiotic complex

    Directory of Open Access Journals (Sweden)

    S. I. Valchuk

    2015-03-01

    Full Text Available Dysbioses of the gastrointestinal tract are common among people of all ages and genders. Development of this pathology is associated with a number of complications, from indigestion to occurrence of malignant disease. Therefore, there is a need in development of measures of their prevention and correction. Probiotics are used as drugs against dysbiosis. Most of the presently known probiotics contain bacterial cells of one species, although combination preparations feature higher efficiency. At the same time, there are difficulties in construction of these drugs, primarily due to incompatibility of physiological properties of microorganisms and mutually antagonistic action of their components. The aim was to examine the compatibility of Bacillus subtilis and Aerococcus viridans in a single preparation, their antagonistic activity against different strains of test-cultures and general antagonism directed on different groups of bacteria for subsequent formation of associative probiotic complex. Properties of aerococci strains were studied and A. viridans 167 strain was selected for inclusion into the probiotic preparation. The tested strain showed the highest indicators of production of hydrogen peroxide, which is one of the mechanisms of antagonistic effect against opportunistic pathogens. General study of biological properties of aerococci strains showed that producing of hydrogen peroxide and superoxide radical in them was conditioned by functioning of NAD-independent lactatoxidase. It has been determined that antioxidant defense of aerococci from the action of endogenous and active excretable forms of oxygen was provided by activity of superoxide-dismutase and GSH-peroxidase. The method of deferred antagonism found no depressing mutual action between probiotic strains of B. subtilis 3 and A. viridans 167 at their joint cultivation. Inhibition of growth at the joint application of A. viridans 167 and B. subtilis 3 strains was recorded for both

  20. Kinetic stable Cr isotopic fractionation between aqueous Cr(III)-Cl-H2O complexes at 25 °C: Implications for Cr(III) mobility and isotopic variations in modern and ancient natural systems

    Science.gov (United States)

    Babechuk, Michael G.; Kleinhanns, Ilka C.; Reitter, Elmar; Schoenberg, Ronny

    2018-02-01

    dissolution of two Cr(III)-Cl solids (dried NIST SRM979 standard and commercial CrCl3·6H2O salt) in 0.01 M HCl (pH ≈ 2). The ε53/52Cr(CrCl2+/CrCl2+) for the CrCl2+ to CrCl2+ reaction is -0.19‰ (SRM979) and -0.38‰ (salt) and the ε53/52Cr(Cr3+/CrCl2+) for the CrCl2+ to Cr3+ reaction is consistent for both experiments at -0.49‰ (SRM979) and -0.51‰ (salt). Experiments where SRM979 is dissolved in 0.1 and 1 M HCl for a longer aging period provide preliminary evidence that the Cr3+/CrCl2+ Cr(III) isotopic fractionation scales with HCl concentration (transformation rate). Chromium(III) dissolved in 6 M HCl and aged 5 months still yields an inter-species Cr isotope distribution that is apparently inherited from kinetic effects (light Cr isotopes in Cr3+), attesting to the slow development of inter-species isotopic equilibrium, which instead predicts progressively heavier Cr isotopes from CrCl2+ to CrCl2+ to Cr3+. The kinetic Cr(III) isotopic fractionation documented herein is proposed to be relevant to understanding systems where aqueous Cr(III)-Cl species may be temporarily stable (e.g., metamorphic and hydrothermal systems or lateritic weathering). Further, the complexation of Cr(III) with other ligands (e.g., CO32-, organics), combined with additional kinetic effects of Cr(III) potentially occurring in soils or sediment, must be explored prior to establishing the significance of empirical stable Cr isotope signatures in marine and continental environments. Further understanding of non-redox effects may lead to stable Cr isotopes developing as a proxy for system pH or ligand chemistry.

  1. Rybp, a polycomb complex-associated protein, is required for mouse eye development

    Directory of Open Access Journals (Sweden)

    Schreiber-Agus Nicole

    2007-04-01

    Full Text Available Abstract Background Rybp (Ring1 and YY1 binding protein is a zinc finger protein which interacts with the members of the mammalian polycomb complexes. Previously we have shown that Rybp is critical for early embryogenesis and that haploinsufficiency of Rybp in a subset of embryos causes failure of neural tube closure. Here we investigated the requirement for Rybp in ocular development using four in vivo mouse models which resulted in either the ablation or overexpression of Rybp. Results Our results demonstrate that loss of a single Rybp allele in conventional knockout mice often resulted in retinal coloboma, an incomplete closure of the optic fissure, characterized by perturbed localization of Pax6 but not of Pax2. In addition, about one half of Rybp-/- Rybp+/+ chimeric embryos also developed retinal colobomas and malformed lenses. Tissue-specific transgenic overexpression of Rybp in the lens resulted in abnormal fiber cell differentiation and severe lens opacification with increased levels of AP-2α and Sox2, and reduced levels of βA4-crystallin gene expression. Ubiquitous transgenic overexpression of Rybp in the entire eye caused abnormal retinal folds, corneal neovascularization, and lens opacification. Additional changes included defects in anterior eye development. Conclusion These studies establish Rybp as a novel gene that has been associated with coloboma. Other genes linked to coloboma encode various classes of transcription factors such as BCOR, CBP, Chx10, Pax2, Pax6, Six3, Ski, Vax1 and Vax2. We propose that the multiple functions for Rybp in regulating mouse retinal and lens development are mediated by genetic, epigenetic and physical interactions between these genes and proteins.

  2. Benchmarking in pathology: development of a benchmarking complexity unit and associated key performance indicators.

    Science.gov (United States)

    Neil, Amanda; Pfeffer, Sally; Burnett, Leslie

    2013-01-01

    This paper details the development of a new type of pathology laboratory productivity unit, the benchmarking complexity unit (BCU). The BCU provides a comparative index of laboratory efficiency, regardless of test mix. It also enables estimation of a measure of how much complex pathology a laboratory performs, and the identification of peer organisations for the purposes of comparison and benchmarking. The BCU is based on the theory that wage rates reflect productivity at the margin. A weighting factor for the ratio of medical to technical staff time was dynamically calculated based on actual participant site data. Given this weighting, a complexity value for each test, at each site, was calculated. The median complexity value (number of BCUs) for that test across all participating sites was taken as its complexity value for the Benchmarking in Pathology Program. The BCU allowed implementation of an unbiased comparison unit and test listing that was found to be a robust indicator of the relative complexity for each test. Employing the BCU data, a number of Key Performance Indicators (KPIs) were developed, including three that address comparative organisational complexity, analytical depth and performance efficiency, respectively. Peer groups were also established using the BCU combined with simple organisational and environmental metrics. The BCU has enabled productivity statistics to be compared between organisations. The BCU corrects for differences in test mix and workload complexity of different organisations and also allows for objective stratification into peer groups.

  3. Reactions associated with arene replacement in bis-(arene) iron complexes

    Czech Academy of Sciences Publication Activity Database

    Štíbr, Bohumil

    2012-01-01

    Roč. 716, OCTOBER (2012), s. 1-5 ISSN 0022-328X R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : arene replacement reactions * ferracarboranes * iron-iron arene complexes * iron cyclohexadienyl complexes * metallacarboranes Subject RIV: CA - Inorganic Chemistry Impact factor: 2.000, year: 2012

  4. Health of white sucker within the St. Louis River area of concern associated with habitat usage as assessed using stable isotopes

    Science.gov (United States)

    Blazer, V.S.; Hoffman, J.; Walsh, H.L.; Braham, R.P.; Hahn, C.; Collins, P.; Jorgenson, Z.; Ledder, T.

    2014-01-01

    In Spring 2011, 200 adult white sucker were collected in four areas of the St. Louis River area of concern (AOC), located in Minnesota and Wisconsin, USA. The areas included the upper AOC as a reference area, the upper estuary, St. Louis Bay and Superior Bay. Grossly visible abnormalities were documented and preserved for microscopic analyses, as were five to eight representative pieces of liver tissue. A piece of dorsal muscle was preserved for stable isotope analyses and otoliths removed for age determination. The incidence of raised skin lesions (mucoid plaques) was high (31 %), however, microscopically only 4.5 % of the white suckers had neoplasia (papillomas). The remaining lesions were epidermal hyperplasia. Superior Bay had the lowest percentage of skin/lip lesions (10 %), while St. Louis Bay had the highest (44 %). St. Louis Bay also had the highest incidence of skin neoplasms (12 %). No hepatocellular neoplasms were documented, however bile duct tumors were observed in 4.5 % of the suckers. Foci of cellular alteration were observed in fish from all sites except the upper AOC. Stable isotope data indicated that most of the suckers relied on the St. Louis River AOC for the majority (>75 %) of their diet, indicating they were resident within the AOC and not in Lake Superior. The amount of diet obtained from the upper estuary was a significant predictor of skin lesion incidence. Hence, habitat use within the AOC appears to be an important risk factor for skin and possibly, liver lesions.

  5. Shame, Dissociation, and Complex PTSD Symptoms in Traumatized Psychiatric and Control Groups: Direct and Indirect Associations With Relationship Distress.

    Science.gov (United States)

    Dorahy, Martin J; Corry, Mary; Black, Rebecca; Matheson, Laura; Coles, Holly; Curran, David; Seager, Lenaire; Middleton, Warwick; Dyer, Kevin F W

    2017-04-01

    Elevated shame and dissociation are common in dissociative identity disorder (DID) and chronic posttraumatic stress disorder (PTSD) and are part of the constellation of symptoms defined as complex PTSD. Previous work examined the relationship between shame, dissociation, and complex PTSD and whether they are associated with intimate relationship anxiety, relationship depression, and fear of relationships. This study investigated these variables in traumatized clinical samples and a nonclinical community group. Participants were drawn from the DID (n = 20), conflict-related chronic PTSD (n = 65), and nonclinical (n = 125) populations and completed questionnaires assessing the variables of interest. A model examining the direct impact of shame and dissociation on relationship functioning, and their indirect effect via complex PTSD symptoms, was tested through path analysis. The DID sample reported significantly higher dissociation, shame, complex PTSD symptom severity, relationship anxiety, relationship depression, and fear of relationships than the other two samples. Support was found for the proposed model, with shame directly affecting relationship anxiety and fear of relationships, and pathological dissociation directly affecting relationship anxiety and relationship depression. The indirect effect of shame and dissociation via complex PTSD symptom severity was evident on all relationship variables. Shame and pathological dissociation are important for not only the effect they have on the development of other complex PTSD symptoms, but also their direct and indirect effects on distress associated with relationships. © 2016 Wiley Periodicals, Inc.

  6. The PAM domain, a multi-protein complex-associated module with an all-alpha-helix fold

    Directory of Open Access Journals (Sweden)

    Izaurralde Elisa

    2003-12-01

    Full Text Available Abstract Background Multimeric protein complexes have a role in many cellular pathways and are highly interconnected with various other proteins. The characterization of their domain composition and organization provides useful information on the specific role of each region of their sequence. Results We identified a new module, the PAM domain (PCI/PINT associated module, present in single subunits of well characterized multiprotein complexes, like the regulatory lid of the 26S proteasome, the COP-9 signalosome and the Sac3-Thp1 complex. This module is an around 200 residue long domain with a predicted TPR-like all-alpha-helical fold. Conclusions The occurrence of the PAM domain in specific subunits of multimeric protein complexes, together with the role of other all-alpha-helical folds in protein-protein interactions, suggest a function for this domain in mediating transient binding to diverse target proteins.

  7. Liquid-liquid extraction of ion-association complexes of cobalt(II-4-(2-pyridylazoresorcinol with ditetrazolium salts

    Directory of Open Access Journals (Sweden)

    Divarova Vidka V.

    2015-01-01

    Full Text Available The formation and liquid-liquid extraction of ion-association complexes between Co(II-4-(2-Pyridylazoresorcinol (PAR anionic chelates and cations of three ditetrazolium chlorides were studied: Blue Tetrazolium chloride (BTC, Neotetrazolium chloride (NTC and Nitro Blue Tetrazolium chloride (NBT. The optimum conditions for the formation and solvent extraction of the ion-association comlpex chelates were determined. It has been found that in the systems of Co(II-PAR-DTS, the reactants are reacted in molar ratios 1:2:1 and the general formula of complexes was suggested. The extraction equilibria were investigated and quantitatively characterized by the equilibrium constants and the recovery factors. The analytical characteristics of the complexes were calculated.

  8. Complex associative memory processing and sleep: a systematic review and meta-analysis of behavioural evidence and underlying EEG mechanisms.

    Science.gov (United States)

    Chatburn, Alex; Lushington, Kurt; Kohler, Mark J

    2014-11-01

    The beneficial influence of sleep on memory consolidation is well established; however, the mechanisms by which sleep can dynamically consolidate new memories into existing networks for the continued environmental adaptation of the individual are unclear. The role of sleep in complex associative memory is an emerging field and the literature has not yet been systematically reviewed. Here, we systematically review the published literature on the role of sleep in complex associative memory processing to determine (i) if there is reasonable published evidence to support an active role for sleep facilitating complex associative processes such rule and gist extraction and false memory; (ii) to determine which sleep physiological events and states impact these processes, and to quantify the strength of these relationships through meta-analysis. Twenty-seven studies in healthy adults were identified which combined indicate a moderate effect of sleep in facilitating associative memory as tested behaviourally. Studies which have measured sleep physiology have reported mixed findings. Significant associations between sleep electrophysiology and outcome appear to be based largely on mode of acquisition. We interpret these findings as supporting reactivation based models of associative processing.

  9. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  10. Stable Boundary Layer Issues

    NARCIS (Netherlands)

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The

  11. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    IAS Admin

    After Maynard-Smith and Price [1] mathematically derived why a given behaviour or strategy was adopted by a certain proportion of the population at a given time, it was shown that a strategy which is currently stable in a population need not be stable in evolutionary time (across generations). Additionally it was sug-.

  12. Anatomic complexity quantitated by nephrometry score is associated with prolonged warm ischemia time during robotic partial nephrectomy

    Science.gov (United States)

    Tomaszewski, Jeffrey J.; Smaldone, Marc C.; Mehrazin, Reza; Kocher, Neil; Ito, Timothy; Abbosh, Philip; Baber, Jacob; Kutikov, Alexander; Viterbo, Rosalia; Chen, David Y. T.; Canter, Daniel J.; Uzzo, Robert G.

    2014-01-01

    Objective To assess the association between Nephrometry Score (NS) and prolonged warm ischemia time (WIT) in patients undergoing robotic partial nephrectomy (RPN) for clinically localized renal masses. Methods We queried our prospectively maintained kidney cancer database to identify all patients undergoing RPN for localized tumors from 2007–2012. Patient and tumor characteristics were compared between complexity groups using ANOVA and Chi square tests. Multivariable logistic regression models were used to examine the relationship between NS complexity and warm ischemia >30 minutes. Results 375 patients (mean age 59±11 years, mean CCI 1.0 ±1.3) undergoing RPN under warm ischemia for clinically localized renal tumors (mean tumor size 3.1±1.5 cm, mean NS 6.8±1.8) met inclusion criteria and had NS available. Stratified by complexity, groups differed with respect to age at surgery, tumor size, proximity to the hilum, collecting system entry, EBL, and operative time (all p values ≤ 0.05). Significant differences in mean warm ischemia time were observed when comparing low (19.4±12.1 min), intermediate (28.6±12.8 min) and high (36.1±13.7 min) NS complexity groups (p<0.0001). Adjusting for confounders, patients with intermediate (OR 2.1 [CI 1.2–3.9]) and high (OR 3.7 [CI 1.1–11.8]) NS complexity were more likely to require prolonged warm ischemia time when compared to patients with low complexity tumors. Conclusions In our large institutional cohort, quantification of anatomic complexity using the NS is associated with WIT greater than 30 minutes in patients undergoing RPN for localized renal tumors. This provides further evidence that standardized reporting of tumor anatomic complexity affords meaningful outcome comparisons. PMID:24925833

  13. Characterization of the population structure, drug resistance mechanisms and plasmids of the community-associated Enterobacter cloacae complex in China

    NARCIS (Netherlands)

    Zhou, Kai; Yu, Wei; Cao, Xiaoli; Shen, Ping; Lu, Haifeng; Luo, Qixia; Rossen, John W. A.; Xiao, Yonghong

    Objectives: To investigate the population structure, drug resistance mechanisms and plasmids of community-associated Enterobacter cloacae complex (CA-ECC) isolates in China. Methods: Sixty-two CA-ECC isolates collected from 31 hospitals across China were typed by hsp60 typing and MLST. ESBL and

  14. Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet

    NARCIS (Netherlands)

    Wijburg, F. A.; Barth, P. G.; Bindoff, L. A.; Birch-Machin, M. A.; van der Blij, J. F.; Ruitenbeek, W.; TURNBULL, D. M.; Schutgens, R. B.

    1992-01-01

    A one-year-old boy suffering from intermittent lactic acidosis, muscular hypotonia, horizontal gaze paralysis and spasticity in both legs had low activity of the pyruvate dehydrogenase complex associated with low amounts of immunoreactive E 1 alpha and E 1 beta. Leigh syndrome was diagnosed on the

  15. Functional Analysis of γ-Tubulin Complex Proteins Indicates Specific Lateral Association via Their N-terminal Domains.

    Science.gov (United States)

    Farache, Dorian; Jauneau, Alain; Chemin, Cécile; Chartrain, Marine; Rémy, Marie-Hélène; Merdes, Andreas; Haren, Laurence

    2016-10-28

    Microtubules are nucleated from multiprotein complexes containing γ-tubulin and associated γ-tubulin complex proteins (GCPs). Small complexes (γTuSCs) comprise two molecules of γ-tubulin bound to the C-terminal domains of GCP2 and GCP3. γTuSCs associate laterally into helical structures, providing a structural template for microtubule nucleation. In most eukaryotes γTuSCs associate with additional GCPs (4, 5, and 6) to form the core of the so-called γ-tubulin ring complex (γTuRC). GCPs 2-6 constitute a family of homologous proteins. Previous structural analysis and modeling of GCPs suggest that all family members can potentially integrate into the helical structure. Here we provide experimental evidence for this model. Using chimeric proteins in which the N- and C-terminal domains of different GCPs are swapped, we show that the N-terminal domains define the functional identity of GCPs, whereas the C-terminal domains are exchangeable. FLIM-FRET experiments indicate that GCP4 and GCP5 associate laterally within the complex, and their interaction is mediated by their N-terminal domains as previously shown for γTuSCs. Our results suggest that all GCPs are incorporated into the helix via lateral interactions between their N-terminal domains, whereas the C-terminal domains mediate longitudinal interactions with γ-tubulin. Moreover, we show that binding to γ-tubulin is not essential for integrating into the helical complex. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. The association of complex liver disorders with HBV genotypes prevalent in Pakistan

    Directory of Open Access Journals (Sweden)

    Qureshi Huma

    2007-11-01

    Full Text Available Abstract Background Genotyping of HBV is generally used for determining the epidemiological relationship between various virus strains and origin of infection mostly in research studies. The utility of genotyping for clinical applications is only beginning to gain importance. Whether HBV genotyping will constitute part of the clinical evaluation of Hepatitis B patients depends largely on the availability of the relevance of the evidence based information. Since Pakistan has a HBV genotype distribution which has been considered less virulent as investigated by earlier studies from south East Asian countries, a study on correlation between HBV genotypes and risk of progression to further complex hepatic infection was much needed Methods A total of 295 patients with HBsAg positive were selected from the Pakistan Medical Research Council's (PMRC out patient clinics. Two hundred and twenty six (77% were males, sixty nine (23% were females (M to F ratio 3.3:1. Results Out of 295 patients, 156 (53.2% had Acute(CAH, 71 (24.2% were HBV Carriers, 54 (18.4% had Chronic liver disease (CLD Hepatitis. 14 (4.7% were Cirrhosis and HCC patients. Genotype D was the most prevalent genotype in all categories of HBV patients, Acute (108, Chronic (39, and Carrier (53. Cirrhosis/HCC (7 were HBV/D positive. Genotype A was the second most prevalent with 28 (13% in acute cases, 12 (22.2% in chronics, 14 (19.7% in carriers and 5 (41.7 in Cirrhosis/HCC patients. Mixed genotype (A/D was found in 20 (12.8% of Acute patients, 3 (5.6% of Chronic and 4 (5.6% of carriers, none in case of severe liver conditions. Conclusion Mixed HBV genotypes A, D and A/D combination were present in all categories of patients except that no A/D combination was detected in severe conditions. Genotype D was the dominant genotype. However, genotype A was found to be more strongly associated with severe liver disease. Mixed genotype (A/D did not significantly appear to influence the clinical outcome.

  17. Recurrent evolution of host and vector association in bacteria of the Borrelia burgdorferi sensu lato species complex.

    Science.gov (United States)

    Becker, Noémie S; Margos, Gabriele; Blum, Helmut; Krebs, Stefan; Graf, Alexander; Lane, Robert S; Castillo-Ramírez, Santiago; Sing, Andreas; Fingerle, Volker

    2016-09-15

    The Borrelia burgdorferi sensu lato (s.l.) species complex consists of tick-transmitted bacteria and currently comprises approximately 20 named and proposed genospecies some of which are known to cause Lyme Borreliosis. Species have been defined via genetic distances and ecological niches they occupy. Understanding the evolutionary relationship of species of the complex is fundamental to explaining patterns of speciation. This in turn forms a crucial basis to frame testable hypotheses concerning the underlying processes including host and vector adaptations. Illumina Technology was used to obtain genome-wide sequence data for 93 strains of 14 named genospecies of the B. burgdorferi species complex and genomic data already published for 18 additional strain (including one new species) was added. Phylogenetic reconstruction based on 114 orthologous single copy genes shows that the genospecies represent clearly distinguishable taxa with recent and still ongoing speciation events apparent in Europe and Asia. The position of Borrelia species in the phylogeny is consistent with host associations constituting a major driver for speciation. Interestingly, the data also demonstrate that vector associations are an additional driver for diversification in this tick-borne species complex. This is particularly obvious in B. bavariensis, a rodent adapted species that has diverged from the bird-associated B. garinii most likely in Asia. It now consists of two populations one of which most probably invaded Europe following adaptation to a new vector (Ixodes ricinus) and currently expands its distribution range. The results imply that genotypes/species with novel properties regarding host or vector associations have evolved recurrently during the history of the species complex and may emerge at any time. We suggest that the finding of vector associations as a driver for diversification may be a general pattern for tick-borne pathogens. The core genome analysis presented here

  18. Neuronal complex I deficiency occurs throughout the Parkinson's disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage.

    Science.gov (United States)

    Flønes, Irene H; Fernandez-Vizarra, Erika; Lykouri, Maria; Brakedal, Brage; Skeie, Geir Olve; Miletic, Hrvoje; Lilleng, Peer K; Alves, Guido; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Dölle, Christian; Zeviani, Massimo; Tzoulis, Charalampos

    2018-03-01

    Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson's disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson's disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, Western blot and activity measurements, to assess complex I quantity and function in multiple brain regions from an extensively characterized population-based cohort of idiopathic Parkinson's disease (n = 18) and gender and age matched healthy controls (n = 11). Mitochondrial DNA was assessed in single neurons from the same areas by real-time PCR. Immunohistochemistry showed that neuronal complex I deficiency occurs throughout the Parkinson's disease brain, including areas spared by the neurodegenerative process such as the cerebellum. Activity measurements in brain homogenate confirmed a moderate decrease of complex I function, whereas Western blot was less sensitive, detecting only a mild reduction, which did not reach statistical significance at the group level. With the exception of the substantia nigra, neuronal complex I loss showed no correlation with the load of somatic mitochondrial DNA damage. Interestingly, α-synuclein aggregation was less common in complex I deficient neurons in the substantia nigra. We show that neuronal complex I deficiency is a widespread phenomenon in the Parkinson's disease brain which, contrary to mainstream theory, does not follow the anatomical distribution of neurodegeneration and is not associated with the neuronal load of mitochondrial DNA mutation. Our findings suggest that complex I deficiency in Parkinson's disease can

  19. Using a combination of radiogenic and stable isotopes coupled with hydrogeochemistry, limnometrics and meteorological data in hydrological research of complex underground mine-pit lake systems: The case of Cueva de la Mora

    Science.gov (United States)

    Sánchez-España, J.; Diez Ercilla, M.; Pérez Cerdán, F.; Yusta, I.

    2012-04-01

    This study presents a combination of radiogenic and stable isotopes (3H, 2H and 18O on pit lake water, and 34S on dissolved sulfate) coupled with bathymetric, meteorological and limnometric investigations, and detailed hydrogeochemical studies to decipher the flooding history and hydrological dynamics of a meromictic and deeply stratified pit lake in SW Spain. The application of these combined techniques has been specially succesful considering the complexity of the studied system, which includes a substantial number of horizontal galleries, shafts and large rooms physically connected to the pit lake. Specific conductance and temperature profiles have depicted a physical structure of the water body which includes four monimolimnetic layers of increasing density with depth. This internal configuration includes m-scale layers separated by sharp transional zones and is rarely observed in natural, fresh water bodies and most other pit lakes. The tritium abundance of the different layers indicate that the deepest water consists in strongly acidified and metal-laden meteoric water infiltrated in the mine system soon after the mine closure in 1971-72. Oxygen and hydrogen isotope ratios of the different layers reflect a sharp stratification with increasing evaporative influence towards the lake surface. The combination of tritium data with the oxygen and hydrogen isotope composition of the different layers suggests a model of pit lake formation with an initial stage of flooding (with entrance of highly metal- and sulfate-loaded mine drainage from the underlying mine galleries) that deeply determined the physical structure and meromictic nature of the lake. After reaching the present water level and morphology, the stagnant, anoxic part of pit lake seems to have remained chemically and isotopically unmodified during its 40 year-old history. Although the pit lake receives significant water input during autumn and winter (which in turn provoke significant volumetric increases

  20. Colony geometry and structural complexity of the endangered species Acropora cervicornis partly explains the structure of their associated fish assemblage

    Directory of Open Access Journals (Sweden)

    Esteban A. Agudo-Adriani

    2016-04-01

    Full Text Available In the past decade, significant efforts have been made to describe fish-habitat associations. However, most studies have oversimplified actual connections between fish assemblages and their habitats by using univariate correlations. The purpose of this study was to identify the features of habitat forming corals that facilitate and influences assemblages of associated species such as fishes. For this we developed three-dimensional models of colonies of Acropora cervicornis to estimate geometry (length and height, structural complexity (i.e., volume, density of branches, etc. and biological features of the colonies (i.e., live coral tissue, algae. We then correlated these colony characteristics with the associated fish assemblage using multivariate analyses. We found that geometry and complexity were better predictors of the structure of fish community, compared to other variables such as percentage of live coral tissue or algae. Combined, the geometry of each colony explained 40% of the variability of the fish assemblage structure associated with this coral species; 61% of the abundance and 69% of fish richness, respectively. Our study shows that three-dimensional reconstructions of discrete colonies of Acropora cervicornis provides a useful description of the colonial structural complexity and may explain a great deal of the variance in the structure of the associated coral reef fish community. This demonstration of the strongly trait-dependent ecosystem role of this threatened species has important implications for restoration and conservation efforts.

  1. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...... Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process...

  2. Applications of stable isotopes

    International Nuclear Information System (INIS)

    Letolle, R.; Mariotti, A.; Bariac, T.

    1991-06-01

    This report reviews the historical background and the properties of stable isotopes, the methods used for their measurement (mass spectrometry and others), the present technics for isotope enrichment and separation, and at last the various present and foreseeable application (in nuclear energy, physical and chemical research, materials industry and research; tracing in industrial, medical and agronomical tests; the use of natural isotope variations for environmental studies, agronomy, natural resources appraising: water, minerals, energy). Some new possibilities in the use of stable isotope are offered. A last chapter gives the present state and forecast development of stable isotope uses in France and Europe

  3. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

    Science.gov (United States)

    Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

    2015-05-01

    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

  4. Development of hypomelanotic macules is associated with constitutive activated mTORC1 in tuberous sclerosis complex

    DEFF Research Database (Denmark)

    Møller, Lisbeth Birk; Schönewolf-Greulich, Bitten; Rosengren, Thomas

    2017-01-01

    of TSC1/2 form a complex which at energy limiting states, down-regulates the activity of the regulator of protein synthesis, the mammalian target of rapamycin complex1 (mTORC1). As expected, in contrast to cultured control fibroblasts, starvation of cultured patient fibroblasts obtained from...... a hypomelanotic macule did not lead to repression of mTORC1, whereas partial repression was observed in patient fibroblasts obtained from non-lesional skin. The findings indicate that the development of hypomelanotic macules is associated with constitutive activated mTORC1, whereas mild deregulation of mTORC1...

  5. Chromosomes A07 and A05 associated with stable and major QTLs for pod weight and size in cultivated peanut (Arachis hypogaea L.).

    Science.gov (United States)

    Luo, Huaiyong; Guo, Jianbin; Ren, Xiaoping; Chen, Weigang; Huang, Li; Zhou, Xiaojing; Chen, Yuning; Liu, Nian; Xiong, Fei; Lei, Yong; Liao, Boshou; Jiang, Huifang

    2018-02-01

    Co-localized intervals and candidate genes were identified for major and stable QTLs controlling pod weight and size on chromosomes A07 and A05 in an RIL population across four environments. Cultivated peanut (Arachis hypogaea L.) is an important legume crops grown in > 100 countries. Hundred-pod weight (HPW) is an important yield trait in peanut, but its underlying genetic mechanism was not well studied. In this study, a mapping population (Xuhua 13 × Zhonghua 6) with 187 recombinant inbred lines (RILs) was developed to map quantitative trait loci (QTLs) for HPW together with pod length (PL) and pod width (PW) by both unconditional and conditional QTL analyses. A genetic map covering 1756.48 cM was constructed with 817 markers. Additive effects, epistatic interactions, and genotype-by-environment interactions were analyzed using the phenotyping data generated across four environments. Twelve additive QTLs were identified on chromosomes A05, A07, and A08 by unconditional analysis, and five of them (qPLA07, qPLA05.1, qPWA07, qHPWA07.1, and qHPWA05.2) showed major and stable expressions in all environments. Conditional QTL mapping found that PL had stronger influences on HPW than PW. Notably, qHPWA07.1, qPLA07, and qPWA07 that explained 17.93-43.63% of the phenotypic variations of the three traits were co-localized in a 5 cM interval (1.48 Mb in physical map) on chromosome A07 with 147 candidate genes related to catalytic activity and metabolic process. In addition, qHPWA05.2 and qPLA05.1 were co-localized with minor QTL qPWA05.2 to a 1.3 cM genetic interval (280 kb in physical map) on chromosome A05 with 12 candidate genes. This study provides a comprehensive characterization of the genetic components controlling pod weight and size as well as candidate QTLs and genes for improving pod yield in future peanut breeding.

  6. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Groothuis, D.R.; Mikhael, M.A.

    1986-06-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

  7. A complex odontoma of the anterior maxilla associated with an erupting canine.

    Science.gov (United States)

    Pillai, Ajay; Moghe, Swapnil; Gupta, Mithilesh K; Pathak, Abhishek

    2013-11-12

    Many developmental anomalies of the jaw are accidentally diagnosed during radiographic investigations for other symptoms. Complex odontomas are odontogenic tumours, relatively rare in the anterior maxilla and generally asymptomatic. Frequently the odontoma may interfere with the eruption of teeth. This paper describes a case of complex odontoma in an 8-year-old girl, which resulted in the palatal displacement of the lateral incisor and an erupting permanent canine. A calcified mass was seen on the radiograph and was provisionally diagnosed as an odontoma which was surgically enucleated. Routine follow-up was carried out for more than 1 year and no recurrence was seen.

  8. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    International Nuclear Information System (INIS)

    Groothuis, D.R.; Mikhael, M.A.

    1986-01-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system

  9. Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015–2016

    Science.gov (United States)

    Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E.; Williams, James A.; Arno, Janet N.; Tai, Albert; Batteiger, Teresa A.

    2017-01-01

    At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae–negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade. PMID:28098538

  10. Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015-2016.

    Science.gov (United States)

    Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E; Williams, James A; Arno, Janet N; Tai, Albert; Batteiger, Teresa A; Nelson, David E

    2017-02-01

    At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae-negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade.

  11. Species of the Colletotrichum acutatum complex associated with anthracnose diseases of fruit in Brazil

    NARCIS (Netherlands)

    Bragança, Carlos A.D.; Damm, Ulrike; Baroncelli, Riccardo; Massola Júnior, Nelson S.; Crous, Pedro W.

    Abstract Although Colletotrichum acutatum was recently investigated and shown to be a species complex comprising about 30 species, the name is still used in its broad sense for anthracnose pathogens of fruits in Brazil. In this study, a multilocus molecular analysis was carried out based on a

  12. Left atrial isomerism associated with asplenia: prenatal echocardiographic detection of complex congenital cardiac malformations

    NARCIS (Netherlands)

    Stewart, P. A.; Becker, A. E.; Wladimiroff, J. W.; Essed, C. E.

    1984-01-01

    Complex congenital heart disease with suspected isomerism of the atria was diagnosed in two fetuses of 20 and 29 weeks' gestation using two-dimensional and M-mode scanning techniques. The first pregnancy was terminated at 21 weeks' gestation and stillbirth occurred at 31 weeks' gestation in the

  13. Analysing Stable Time Series

    National Research Council Canada - National Science Library

    Adler, Robert

    1997-01-01

    We describe how to take a stable, ARMA, time series through the various stages of model identification, parameter estimation, and diagnostic checking, and accompany the discussion with a goodly number...

  14. Molecular and physiological properties associated with zebra complex disease in potatoes and its relation with Candidatus Liberibacter contents in psyllid vectors.

    Science.gov (United States)

    Alvarado, Veria Y; Odokonyero, Denis; Duncan, Olivia; Mirkov, T Erik; Scholthof, Herman B

    2012-01-01

    Zebra complex (ZC) disease on potatoes is associated with Candidatus Liberibacter solanacearum (CLs), an α-proteobacterium that resides in the plant phloem and is transmitted by the potato psyllid Bactericera cockerelli (Šulc). The name ZC originates from the brown striping in fried chips of infected tubers, but the whole plants also exhibit a variety of morphological features and symptoms for which the physiological or molecular basis are not understood. We determined that compared to healthy plants, stems of ZC-plants accumulate starch and more than three-fold total protein, including gene expression regulatory factors (e.g. cyclophilin) and tuber storage proteins (e.g., patatins), indicating that ZC-affected stems are reprogrammed to exhibit tuber-like physiological properties. Furthermore, the total phenolic content in ZC potato stems was elevated two-fold, and amounts of polyphenol oxidase enzyme were also high, both serving to explain the ZC-hallmark rapid brown discoloration of air-exposed damaged tissue. Newly developed quantitative and/or conventional PCR demonstrated that the percentage of psyllids in laboratory colonies containing detectable levels of CLs and its titer could fluctuate over time with effects on colony prolificacy, but presumed reproduction-associated primary endosymbiont levels remained stable. Potato plants exposed in the laboratory to psyllid populations with relatively low-CLs content survived while exposure of plants to high-CLs psyllids rapidly culminated in a lethal collapse. In conclusion, we identified plant physiological biomarkers associated with the presence of ZC and/or CLs in the vegetative potato plant tissue and determined that the titer of CLs in the psyllid population directly affects the rate of disease development in plants.

  15. The Structure of the Neurotoxin- Associated Protein HA33/A from Clostridium botulinum Suggests a Reoccurring Beta-Trefoil Fold in the Progenitor Toxin Complex

    National Research Council Canada - National Science Library

    Arndt, Joseph W; Gu, Jenny; Jaroszewski, Lukasz; Schwarzenbacher, Robert; Hanson, Michael A; Lebeda, Frank L; Stevens, Raymond C

    2004-01-01

    The hemagglutinating protein HA33 from Clostridium botulinum is associated with the large botulinum neurotoxin secreted complexes and is critical in toxin protection, internalization, and possibly activation...

  16. Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

    Science.gov (United States)

    Ramos, Caroline L.; Fonseca, Fernanda L.; Rodrigues, Jessica; Guimarães, Allan J.; Cinelli, Leonardo P.; Miranda, Kildare; Nimrichter, Leonardo; Casadevall, Arturo; Travassos, Luiz R.

    2012-01-01

    In prior studies, we demonstrated that glucuronoxylomannan (GXM), the major capsular polysaccharide of the fungal pathogen Cryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. The structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. In this study, we demonstrate that glycan complexes composed of chitooligomers and GXM are formed during fungal growth and macrophage infection by C. neoformans. To investigate the required determinants for the assembly of chitin-GXM complexes, we developed a quantitative scanning electron microscopy-based method using different polysaccharide samples as inhibitors of the interaction of chitin with GXM. This assay revealed that chitin-GXM association involves noncovalent bonds and large GXM fibers and depends on the N-acetyl amino group of chitin. Carboxyl and O-acetyl groups of GXM are not required for polysaccharide-polysaccharide interactions. Glycan complex structures composed of cryptococcal GXM and chitin-derived oligomers were tested for their ability to induce pulmonary cytokines in mice. They were significantly more efficient than either GXM or chitin oligomers alone in inducing the production of lung interleukin 10 (IL-10), IL-17, and tumor necrosis factor alpha (TNF-α). These results indicate that association of chitin-derived structures with GXM through their N-acetyl amino groups generates glycan complexes with previously unknown properties. PMID:22562469

  17. Omphalocele-Exstrophy-Imperforate Anus-Spinal Defects Complex: Associated Malformations in 12 New Cases.

    Science.gov (United States)

    Mallmann, Michael Rudolf; Reutter, Heiko; Müller, Annette Margarete; Geipel, Annegret; Berg, Christoph; Gembruch, Ulrich

    2017-01-01

    The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is a rare variant of the bladder exstrophy epispadias complex with in most cases unknown etiology. Due to the rarity of the disease, no large series exist that describe the prenatal spectrum of disease or additional malformations. In this study, we present the prenatal findings in a series of 12 cases. All fetuses showed exstrophy of the bladder, 9/12 omphalocele, 9/12 anal atresia, 10/12 neural tube defects, 4/12 vertebral defects, 5/12 lower extremity defects including clubfeet, and 4/12 a single umbilical artery. Additional malformations included hydrocephalus, hypertelorism, aplasia of the gall bladder, heart defects and kidney malformations. All karyotyped fetuses (11/11) showed a normal karyotype. These findings illustrate the spectrum of disease in prenatal diagnosis. © 2016 S. Karger AG, Basel.

  18. Defibrillation success is not associated with near field electrogram complexity or shock timing.

    Science.gov (United States)

    Vigmond, Edward J; Kimber, Shane; Suzuki, Go; Faris, Peter; Leon, L Joshua

    2013-09-01

    It has been suggested that more-complex fibrillation requires higher energy shocks to terminate. Furthermore, animal studies have demonstrated that shock timing also plays a role. The objective of this study was to test these assertions in a clinical context. Near- and far-field electrograms were collected during defibrillation threshold testing. Fibrillation complexity was measured by quantifying the organization in the signals with wavelet-based methods, scaling exponent, and cross-correlation analysis. Receiver operator characteristic curves were used to determine predictive value. The effect of the phase at which defibrillation shocks were applied was also determined. No measure was able to classify whether a particular shock would be successful. All performed very poorly. Shock timing played no role in defibrillation outcome. Signal organization of a local electrogram and phase of shock delivery do not relate to minimum defibrillation shock energy immediately after ventricular fibrillation onset. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  19. Syndromes and Disorders Associated with Omphalocele (II): OEIS Complex and Pentalogy Of Cantrell

    OpenAIRE

    Chen, Chih-Ping

    2007-01-01

    Omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is characterized by a combination of omphalocele, exstrophy of the bladder, an imperforate anus, and spinal defects. Pentalogy of Cantrell is characterized by a combination of a midline supraumbilical abdominal wall defect, a defect of the lower sternum, a defect of the diaphragmatic pericardium, a deficiency of the anterior diaphragm, and congenital cardiac anomalies. This article provides a comprehensive review of OEIS com...

  20. Complex Mixture-Associated Hormesis and Toxicity: The Case of Leather Tanning Industry

    OpenAIRE

    Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

    2008-01-01

    A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capr...

  1. The Rooiwater complex and associated rocks, Murchison granitoid-greenstone terrane, Kaapvaal Craton

    International Nuclear Information System (INIS)

    Vearncombe, J.R.; Walsh, K.L.

    1987-01-01

    The greater than 2625 Ma Rooiwater Complex is a thick, on-end differentiated basic igneous body exposed along the northern margin of the Murchison schist belt. It is metamorphosed to amphibolite facies and regionally retrograded and hydrothermally altered. Metamorphosed anorthosite, gabbro, pyroxenite, sulphide-bearing gabbros, thick magnetite layers, and granites are compatible with the hypothesis that the Complex is a layered intrusion, tectonically rotated and intruded by younger, genetically unrelated granites. Increasing TiO 2 and decreasing V 2 O 3 contents southwards in the magnetites layers combined with a general southern disposition of differentiated hornblende granite suggest that the Rooiwater Complex faces south. Although the Rubbervale Formation is pervasively deformed and metamorphosed at the greenschist facies, field relations and isotopic and rare earth element data tentatively suggest that a genetic relationship exists, the Rubbervale Formation being a possible roof to the Rooiwater intrusion, being derived from the same or a similar undepleted magmatic source. A paucity of ultramafic cumulates and up to 1,5 km of hornblende granites may relate to a source magma more felsic than that of other layered intrusions. In order to determine model ages for the Eden pluton, the Free State hornblende granite, the Quagga quartz amphibolite, the Rubbervale formation, and the Novengilla gabbro-anorthosite series. Rb-Sr and Pb isotopic analyses were undertaken

  2. AMACO is a novel component of the basement membrane associated Fraser complex

    Science.gov (United States)

    Richardson, Rebecca J.; Gebauer, Jan M.; Zhang, Jin-Li; Kobbe, Birgit; Keene, Douglas R.; Karlsen, Kristina Røkenes; Richetti, Stefânia; Wohl, Alexander P.; Sengle, Gerhard; Neiss, Wolfram F.; Paulsson, Mats; Hammerschmidt, Matthias; Wagener, Raimund

    2015-01-01

    Fraser syndrome (FS) is a phenotypically variable, autosomal recessive disorder characterized by cryptophthalmus, cutaneous syndactyly and other malformations resulting from mutations in FRAS1, FREM2 and GRIP1. Transient embryonic epidermal blistering causes the characteristic defects of the disorder. Fras1, Frem1 and Frem2 form the extracellular Fraser complex, which is believed to stabilize the basement membrane (BM). However, several cases of FS could not be attributed to mutations in FRAS1, FREM2 or GRIP1, while Fraser syndrome displays high clinical variability, suggesting there is an additional genetic, possibly modifying contribution to this disorder. AMACO, encoded by the VWA2 gene, has a very similar tissue distribution to the Fraser complex proteins in both mouse and zebrafish. Here, we show that AMACO deposition is lost in Fras1 deficient zebrafish and mice and that Fras1 and AMACO interact directly via their CSPG and P2 domains. Knockdown of vwa2, which alone causes no phenotype, enhances the phenotype of hypomorphic Fras1 mutant zebrafish. Together, our data suggest that AMACO represents a novel member of the Fraser complex. PMID:24232570

  3. AMACO is a component of the basement membrane-associated Fraser complex.

    Science.gov (United States)

    Richardson, Rebecca J; Gebauer, Jan M; Zhang, Jin-Li; Kobbe, Birgit; Keene, Douglas R; Karlsen, Kristina Røkenes; Richetti, Stefânia; Wohl, Alexander P; Sengle, Gerhard; Neiss, Wolfram F; Paulsson, Mats; Hammerschmidt, Matthias; Wagener, Raimund

    2014-05-01

    Fraser syndrome (FS) is a phenotypically variable, autosomal recessive disorder characterized by cryptophthalmus, cutaneous syndactyly, and other malformations resulting from mutations in FRAS1, FREM2, and GRIP1. Transient embryonic epidermal blistering causes the characteristic defects of the disorder. Fras1, Frem1, and Frem2 form the extracellular Fraser complex, which is believed to stabilize the basement membrane. However, several cases of FS could not be attributed to mutations in FRAS1, FREM2, or GRIP1, and FS displays high clinical variability, suggesting that there is an additional genetic, possibly modifying contribution to this disorder. An extracellular matrix protein containing VWA-like domains related to those in matrilins and collagens (AMACO), encoded by the VWA2 gene, has a very similar tissue distribution to the Fraser complex proteins in both mouse and zebrafish. Here, we show that AMACO deposition is lost in Fras1-deficient zebrafish and mice and that Fras1 and AMACO interact directly via their chondroitin sulfate proteoglycan (CSPG) and P2 domains. Knockdown of vwa2, which alone causes no phenotype, enhances the phenotype of hypomorphic Fras1 mutant zebrafish. Together, our data suggest that AMACO represents a member of the Fraser complex.

  4. Downregulation of Major Histocompatibility Complex Class I Molecules by Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 Proteins

    OpenAIRE

    Ishido, Satoshi; Wang, Chunyang; Lee, Bok-Soo; Cohen, George B.; Jung, J. U.

    2000-01-01

    The T-cell-mediated immune response plays a central role in the defense against intracellular pathogens. To avoid this immune response, viruses have evolved elaborate mechanisms that target and modulate many different aspects of the host's immune system. A target common to many of these viruses is the major histocompatibility complex (MHC) class I molecules. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes K3 and K5 zinc finger membrane proteins which remove MHC class I molecules from t...

  5. Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome.

    Science.gov (United States)

    Pech, Markus; Spreter, Thomas; Beckmann, Roland; Beatrix, Birgitta

    2010-06-18

    Nascent polypeptide-associated complex (NAC) was identified in eukaryotes as the first cytosolic factor that contacts the nascent polypeptide chain emerging from the ribosome. NAC is present as a homodimer in archaea and as a highly conserved heterodimer in eukaryotes. Mutations in NAC cause severe embryonically lethal phenotypes in mice, Drosophila melanogaster, and Caenorhabditis elegans. In the yeast Saccharomyces cerevisiae NAC is quantitatively associated with ribosomes. Here we show that NAC contacts several ribosomal proteins. The N terminus of betaNAC, however, specifically contacts near the tunnel exit ribosomal protein Rpl31, which is unique to eukaryotes and archaea. Moreover, the first 23 amino acids of betaNAC are sufficient to direct an otherwise non-associated protein to the ribosome. In contrast, alphaNAC (Egd2p) contacts Rpl17, the direct neighbor of Rpl31 at the ribosomal tunnel exit site. Rpl31 was also recently identified as a contact site for the SRP receptor and the ribosome-associated complex. Furthermore, in Escherichia coli peptide deformylase (PDF) interacts with the corresponding surface area on the eubacterial ribosome. In addition to the previously identified universal adapter site represented by Rpl25/Rpl35, we therefore refer to Rpl31/Rpl17 as a novel universal docking site for ribosome-associated factors on the eukaryotic ribosome.

  6. Large-Scale Association Study Confirms Genetic Complexity Underlying Type 2 Diabetes

    OpenAIRE

    Barroso, Inês; Luan, Jian'an; Middelberg, Rita P. S; Harding, Anne-Helen; Franks, Paul W; Jakes, Rupert W; Clayton, David; Schafer, Alan J; O'Rahilly, Stephen; Wareham, Nicholas J

    2003-01-01

    Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenoty...

  7. Strategies for haplotype-based association mapping in complex pedigreed populations

    DEFF Research Database (Denmark)

    Boleckova, J; Christensen, Ole Fredslund; Sørensen, Peter

    2012-01-01

    increases the number of parameters in the model, resulting in low accuracy of the estimates especially for the low-frequency haplotypes. Modeling of haplotype effects can be improved if they are assumed to be random effects, as only one parameter i.e. haplotype variance needs to be estimated compared......, 4, 6, 10 and 20. The simulated data resembled the Danish Holstein cattle pedigree representing a complex relationship structure and QTL effects of different sizes were simulated. We observed that the random haplotype models had high power and very low type I error rates (after Bonferroni correction...

  8. Henoch-Schönlein purpura associated with pulmonary Mycobacterium avium-intracellulare complex.

    Science.gov (United States)

    Yano, Shuichi

    2004-09-01

    A 57-year-old woman presented with bloody sputum and high grade fever. She had been treated for Mycobacterium avium-intracellulare complex (MAC). High grade fever slightly decreased and bloody sputum disappeared after two weeks, but low grade fever persisted. After 3 days of recurrence of bloody sputum, she suddenly complained of palpable pururitic lesions on the bilateral lower extremities with bilateral gonalgia. Although there are some reports of direct skin lesions due to MAC, there are no reports of hypersensitivity vasculitis, Henoch-Schönlein purpura, in MAC. It is necessary to consider MAC infection as a potential cause of Henoch-Schönlein purpura.

  9. Calcium stable isotope geochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gausonne, Nikolaus [Muenster Univ. (Germany). Inst. fuer Mineralogie; Schmitt, Anne-Desiree [Strasbourg Univ. (France). LHyGeS/EOST; Heuser, Alexander [Bonn Univ. (Germany). Steinmann-Inst. fuer Geologie, Mineralogie und Palaeontologie; Wombacher, Frank [Koeln Univ. (Germany). Inst. fuer Geologie und Mineralogie; Dietzel, Martin [Technische Univ. Graz (Austria). Inst. fuer Angewandte Geowissenschaften; Tipper, Edward [Cambridge Univ. (United Kingdom). Dept. of Earth Sciences; Schiller, Martin [Copenhagen Univ. (Denmark). Natural History Museum of Denmark

    2016-08-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  10. Association studies to transporting proteins of fac-ReI(CO)3(pterin)(H2O) complex.

    Science.gov (United States)

    Ragone, Fabricio; Saavedra, Héctor H Martínez; García, Pablo F; Wolcan, Ezequiel; Argüello, Gerardo A; Ruiz, Gustavo T

    2017-01-01

    A new synthetic route to acquire the water soluble complex fac-Re I (CO) 3 (pterin)(H 2 O) was carried out in aqueous solution. The complex has been obtained with success via the fac-[Re I (CO) 3 (H 2 O) 3 ]Cl precursor complex. Re I (CO) 3 (pterin)(H 2 O) has been found to bind strongly with bovine and human serum albumins (BSA and HSA) with intrinsic-binding constants, K b , of 6.5 × 10 5 M -1 and 5.6 × 10 5 M -1 at 310 K, respectively. The interactions of serum albumins with Re I (CO) 3 (pterin)(H 2 O) were evaluated employing UV-vis fluorescence and absorption spectroscopy and circular dichroism. The results suggest that the serum albumins-Re I (CO) 3 (pterin)(H 2 O) interactions occurred in the domain IIA-binding pocket without loss of helical stability of the proteins. The comparison of the fluorescence quenching of BSA and HSA due to the binding to the Re(I) complex suggested that local interaction around the Trp 214 residue had taken place. The analysis of the thermodynamic parameters ΔG 0 , ΔH 0 , and ΔS 0 indicated that the hydrophobic interactions played a major role in both HSA-Re(I) and BSA-Re(I) association processes. All these experimental results suggest that these proteins can be considered as good carriers for transportation of Re I (CO) 3 (pterin)(H 2 O) complex. This is of significant importance in relation to the use of this Re(I) complex in several biomedical fields, such as photodynamic therapy and radiopharmacy.

  11. A computational interactome for prioritizing genes associated with complex agronomic traits in rice (Oryza sativa).

    Science.gov (United States)

    Liu, Shiwei; Liu, Yihui; Zhao, Jiawei; Cai, Shitao; Qian, Hongmei; Zuo, Kaijing; Zhao, Lingxia; Zhang, Lida

    2017-04-01

    Rice (Oryza sativa) is one of the most important staple foods for more than half of the global population. Many rice traits are quantitative, complex and controlled by multiple interacting genes. Thus, a full understanding of genetic relationships will be critical to systematically identify genes controlling agronomic traits. We developed a genome-wide rice protein-protein interaction network (RicePPINet, http://netbio.sjtu.edu.cn/riceppinet) using machine learning with structural relationship and functional information. RicePPINet contained 708 819 predicted interactions for 16 895 non-transposable element related proteins. The power of the network for discovering novel protein interactions was demonstrated through comparison with other publicly available protein-protein interaction (PPI) prediction methods, and by experimentally determined PPI data sets. Furthermore, global analysis of domain-mediated interactions revealed RicePPINet accurately reflects PPIs at the domain level. Our studies showed the efficiency of the RicePPINet-based method in prioritizing candidate genes involved in complex agronomic traits, such as disease resistance and drought tolerance, was approximately 2-11 times better than random prediction. RicePPINet provides an expanded landscape of computational interactome for the genetic dissection of agronomically important traits in rice. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  12. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  13. Evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis

    International Nuclear Information System (INIS)

    McDonald, Terence P.; Pitt, Andrew R.; Brown, Gaie; Rixon, Helen W. McL.; Sugrue, Richard J.

    2004-01-01

    The interaction between the respiratory syncytial virus (RSV) polymerase complex and lipid rafts was examined in HEp2 cells. Lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by Western blotting and mass spectrometry. This analysis revealed the presence of the N, P, L, M2-1 and M proteins. However, these proteins appeared to differ from one another in their association with these structures, with the M2-1 protein showing a greater partitioning into raft membranes compared to that of the N, P or M proteins. Determination of the polymerase activity profile of the gradient fractions revealed that 95% of the detectable viral enzyme activity was associated with lipid-raft membranes. Furthermore, analysis of virus-infected cells by confocal microscopy suggested an association between these proteins and the raft-lipid, GM1. Together, these results provide evidence that the RSV polymerase complex is able to associate with lipid rafts in virus-infected cells

  14. Genetic variation in a tropical tree species influences the associated epiphytic plant and invertebrate communities in a complex forest ecosystem

    Science.gov (United States)

    Zytynska, Sharon E.; Fay, Michael F.; Penney, David; Preziosi, Richard F.

    2011-01-01

    Genetic differences among tree species, their hybrids and within tree species are known to influence associated ecological communities and ecosystem processes in areas of limited species diversity. The extent to which this same phenomenon occurs based on genetic variation within a single tree species, in a diverse complex ecosystem such as a tropical forest, is unknown. The level of biodiversity and complexity of the ecosystem may reduce the impact of a single tree species on associated communities. We assessed the influence of within-species genetic variation in the tree Brosimum alicastrum (Moraceae) on associated epiphytic and invertebrate communities in a neotropical rainforest. We found a significant positive association between genetic distance of trees and community difference of the epiphytic plants growing on the tree, the invertebrates living among the leaf litter around the base of the tree, and the invertebrates found on the tree trunk. This means that the more genetically similar trees are host to more similar epiphyte and invertebrate communities. Our work has implications for whole ecosystem conservation management, since maintaining sufficient genetic diversity at the primary producer level will enhance species diversity of other plants and animals. PMID:21444307

  15. Complex Copy Number Variation of AMY1 does not Associate with Obesity in two East Asian Cohorts.

    Science.gov (United States)

    Yong, Rita Y Y; Mustaffa, Su'Aidah B; Wasan, Pavandip S; Sheng, Liang; Marshall, Christian R; Scherer, Stephen W; Teo, Yik-Ying; Yap, Eric P H

    2016-07-01

    The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch-rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non-normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3-4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case-control cohorts (n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies. © 2016 WILEY PERIODICALS, INC.

  16. Stable Fly, (L., Dispersal and Governing Factors

    Directory of Open Access Journals (Sweden)

    Allan T. Showler

    2015-01-01

    Full Text Available Although the movement of stable fly, Stomoxys calcitrans (L., has been studied, its extent and significance has been uncertain. On a local scale (13 km is mainly wind-driven by weather fronts that carry stable flies from inland farm areas for up to 225 km to beaches of northwestern Florida and Lake Superior. Stable flies can reproduce for a short time each year in washed-up sea grass, but the beaches are not conducive to establishment. Such movement is passive and does not appear to be advantageous to stable fly's survival. On a regional scale, stable flies exhibit little genetic differentiation, and on the global scale, while there might be more than one “lineage”, the species is nevertheless considered to be panmictic. Population expansion across much of the globe likely occurred from the late Pleistocene to the early Holocene in association with the spread of domesticated nomad livestock and particularly with more sedentary, penned livestock.

  17. Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex.

    Science.gov (United States)

    Thakker, Suhani; Purushothaman, Pravinkumar; Gupta, Namrata; Challa, Shanthan; Cai, Qiliang; Verma, Subhash C

    2015-05-01

    Major histocompatibility complex class II (MHC-II) molecules play a central role in adaptive antiviral immunity by presenting viral peptides to CD4(+) T cells. Due to their key role in adaptive immunity, many viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), have evolved multiple strategies to inhibit the MHC-II antigen presentation pathway. The expression of MHC-II, which is controlled mainly at the level of transcription, is strictly dependent upon the binding of the class II transactivator (CIITA) to the highly conserved promoters of all MHC-II genes. The recruitment of CIITA to MHC-II promoters requires its direct interactions with a preassembled MHC-II enhanceosome consisting of cyclic AMP response element-binding protein (CREB) and nuclear factor Y (NF-Y) complex and regulatory factor X (RFX) complex proteins. Here, we show that KSHV-encoded latency-associated nuclear antigen (LANA) disrupts the association of CIITA with the MHC-II enhanceosome by binding to the components of the RFX complex. Our data show that LANA is capable of binding to all three components of the RFX complex, RFX-associated protein (RFXAP), RFX5, and RFX-associated ankyrin-containing protein (RFXANK), in vivo but binds more strongly with the RFXAP component in in vitro binding assays. Levels of MHC-II proteins were significantly reduced in KSHV-infected as well as LANA-expressing B cells. Additionally, the expression of LANA in a luciferase promoter reporter assay showed reduced HLA-DRA promoter activity in a dose-dependent manner. Chromatin immunoprecipitation assays showed that LANA binds to the MHC-II promoter along with RFX proteins and that the overexpression of LANA disrupts the association of CIITA with the MHC-II promoter. These assays led to the conclusion that the interaction of LANA with RFX proteins interferes with the recruitment of CIITA to MHC-II promoters, resulting in an inhibition of MHC-II gene expression. Thus, the data presented here identify a novel

  18. Thermally Stable, Latent Olefin Metathesis Catalysts

    OpenAIRE

    Thomas, Renee M.; Fedorov, Alexey; Keitz, Benjamin K.; Grubbs, Robert H.

    2011-01-01

    Highly thermally stable N-aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium catalysts were designed and synthesized for latent olefin metathesis. These catalysts showed excellent latent behavior toward metathesis reactions, whereby the complexes were inactive at ambient temperature and initiated at elevated temperatures, a challenging property to achieve with second generation catalysts. A sterically hindered N-tert-butyl substituent on the NHC ligand of the ruthenium complex was found to i...

  19. Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Takahiro Tsujikawa

    2017-04-01

    Full Text Available Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.

  20. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Brasch-Andersen, Charlotte

    2007-01-01

    with that of the case-only model. RESULTS: Results from our simulation study indicate that our retrospective model exhibits high power in capturing even relatively small effect with reasonable sample sizes. Application of our method to data from an association study on the catalase -262C/T promoter polymorphism...

  1. Fungal pathogen complexes associated with rambutan, longan and mango diseases in Puerto Rico

    Science.gov (United States)

    Different fungi have been associated with diseased inflorescences, leaves, and fruits of mango, rambutan and longan. During a fungal disease survey conducted between 2008 and 2013 at six orchards of rambutan and longan, and one orchard of mango in Puerto Rico, symptoms such as fruit rot, infloresc...

  2. Comparison of genome-wide association methods in analyses of admixed populations with complex familial relationships.

    Directory of Open Access Journals (Sweden)

    Naveen K Kadri

    Full Text Available Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P and family (K levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic markers. Linear models that ignored K were also tested. Correction for P was performed using principal component or structured association analysis. In analyses of simulated and real data, linear mixed models that corrected for K were able to control for type-I error, regardless of whether they also corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree and genomic relationships. In summary, in association studies using samples with both P and K, ancestries estimated using principal components or structured assignment were not sufficient to correct type-I errors. In such cases type-I errors may be controlled by use of linear mixed models with relationships derived from either pedigree or from genetic markers.

  3. Ecological speciation in anemone-associated snapping shrimps (Alpheus armatus species complex).

    Science.gov (United States)

    Hurt, C; Silliman, K; Anker, A; Knowlton, N

    2013-09-01

    Divergent natural selection driven by competition for limited resources can promote speciation, even in the presence of gene flow. Reproductive isolation is more likely to result from divergent selection when the partitioned resource is closely linked to mating. Obligate symbiosis and host fidelity (mating on or near the host) can provide this link, creating ideal conditions for speciation in the absence of physical barriers to dispersal. Symbiotic organisms often experience competition for hosts, and host fidelity ensures that divergent selection for a specific host or host habitat can lead to speciation and strengthen pre-existing reproductive barriers. Here, we present evidence that diversification of a sympatric species complex occurred despite the potential for gene flow and that partitioning of host resources (both by species and by host habitat) has contributed to this diversification. Four species of snapping shrimps (Alpheus armatus, A. immaculatus, A. polystictus and A. roquensis) are distributed mainly sympatrically in the Caribbean, while the fifth species (A. rudolphi) is restricted to Brazil. All five species are obligate commensals of sea anemones with a high degree of fidelity and ecological specificity for host species and habitat. We analysed sequence data from 10 nuclear genes and the mitochondrial COI gene in 11-16 individuals from each of the Caribbean taxa and from the only available specimen of the Brazilian taxon. Phylogenetic analyses support morphology-based species assignments and a well-supported Caribbean clade. The Brazilian A. rudolphi is recovered as an outgroup to the Caribbean taxa. Isolation-migration coalescent analysis provides evidence for historical gene flow among sympatric sister species. Our data suggest that both selection for a novel host and selection for host microhabitat may have promoted diversification of this complex despite gene flow. © 2013 John Wiley & Sons Ltd.

  4. Performance of predictive models in phase equilibria of complex associating systems: PC-SAFT and CEOS/GE

    Directory of Open Access Journals (Sweden)

    N. Bender

    2013-03-01

    Full Text Available Cubic equations of state combined with excess Gibbs energy predictive models (like UNIFAC and equations of state based on applied statistical mechanics are among the main alternatives for phase equilibria prediction involving polar substances in wide temperature and pressure ranges. In this work, the predictive performances of the PC-SAFT with association contribution and Peng-Robinson (PR combined with UNIFAC (Do through mixing rules are compared. Binary and multi-component systems involving polar and non-polar substances were analyzed. Results were also compared to experimental data available in the literature. Results show a similar predictive performance for PC-SAFT with association and cubic equations combined with UNIFAC (Do through mixing rules. Although PC-SAFT with association requires less parameters, it is more complex and requires more computation time.

  5. Mechanical Dyssynchrony by Tissue Doppler Cross-Correlation is Associated with Risk for Complex Ventricular Arrhythmias after Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Tayal, Bhupendar; Gorcsan, John; Delgado-Montero, Antonia

    2015-01-01

    BACKGROUND: Tissue Doppler cross-correlation analysis has been shown to be associated with long-term survival after cardiac resynchronization defibrillator therapy (CRT-D). Its association with ventricular arrhythmia (VA) is unknown. METHODS: From two centers 151 CRT-D patients (New York Heart...... with a substantially increased risk for VA (hazard ratio [HR], 4.4; 95% CI, 1.2-16.3; P = .03) and VA or death (HR, 4.0; 95% CI, 1.7-9.6; P = .002) after adjusting for other covariates. Similarly, patients with new dyssynchrony had increased risk for VA (HR, 10.6; 95% CI, 2.8-40.4; P = .001) and VA or death (HR, 5.......0; 95% CI, 1.8-13.5; P = .002). CONCLUSIONS: Persistent and new mechanical dyssynchrony after CRT-D was associated with subsequent complex VA. Dyssynchrony after CRT-D is a marker of poor prognosis....

  6. Investigating the Complex Association Between Viral Ecology, Environment, and Northeast Pacific Sea Star Wasting

    Directory of Open Access Journals (Sweden)

    Ian Hewson

    2018-03-01

    Full Text Available Sea Star Wasting Disease (SSWD describes a suite of disease signs that affected >20 species of asteroid since 2013 along a broad geographic range from the Alaska Peninsula to Baja California. Previous work identified the Sea Star associated Densovirus (SSaDV as the best candidate pathogen for SSWD in three species of common asteroid (Pycnopodia helianthoides, Pisaster ochraceus, and Evasterias troscheli, and virus-sized material (<0.22 μm elicited SSWD signs in P. helianthoides. However, the ability of virus-sized material to elicit SSWD in other species of asteroids was not known. Discordance between detection of SSaDV by qPCR and by viral metagenomics inspired the redesign of qPCR primers to encompass SSaDV and two densoviral genotypes detected in wasting asteroids. Analysis of asteroid samples collected during SSWD emergence in 2013–2014 showed an association between wasting asteroid-associated densoviruses (WAaDs and SSWD in only one species (P. helianthoides. WAaDs were found in association with asymptomatic asteroids in contemporary (2016 and later populations, suggesting that they may form subclinical infections at the times they were sampled. WAaDs were found in SSWD-affected P. helianthoides after being absent in asymptomatic individuals a year earlier at one location (Kodiak. Direct challenge of P. ochraceus, Pisaster brevispinus, and E. troscheli with virus-sized material from SSWD-affected individuals did not elicit SSWD in any trial. RNA viral genomes discovered in viral metagenomes and host transcriptomes had viral loads and metagenome fragment recruitment patterns that were inconsistent with SSWD. Analysis of water temperature and precipitation patterns on a regional scale suggests that SSWD occurred following dry conditions at several locations, but mostly was inconsistently associated with either parameter. Semi-continuous monitoring of SSWD subtidally at two sites in the Salish Sea from 2013 to 2017 indicated that SSWD in E

  7. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General ... Using some examples of classical games, we show how evolutionary game theory can help understand behavioural decisions of animals.

  8. The Stable Concordance Genus

    OpenAIRE

    Kearney, M. Kate

    2013-01-01

    The concordance genus of a knot is the least genus of any knot in its concordance class. Although difficult to compute, it is a useful invariant that highlights the distinction between the three-genus and four-genus. In this paper we define and discuss the stable concordance genus of a knot, which describes the behavior of the concordance genus under connected sum.

  9. Manifolds admitting stable forms

    Czech Academy of Sciences Publication Activity Database

    Le, Hong-Van; Panák, Martin; Vanžura, Jiří

    2008-01-01

    Roč. 49, č. 1 (2008), s. 101-11 ISSN 0010-2628 R&D Projects: GA ČR(CZ) GP201/05/P088 Institutional research plan: CEZ:AV0Z10190503 Keywords : stable forms * automorphism groups Subject RIV: BA - General Mathematics

  10. Stable isotope studies

    International Nuclear Information System (INIS)

    Ishida, T.

    1992-01-01

    The research has been in four general areas: (1) correlation of isotope effects with molecular forces and molecular structures, (2) correlation of zero-point energy and its isotope effects with molecular structure and molecular forces, (3) vapor pressure isotope effects, and (4) fractionation of stable isotopes. 73 refs, 38 figs, 29 tabs

  11. Interactive Stable Ray Tracing

    DEFF Research Database (Denmark)

    Dal Corso, Alessandro; Salvi, Marco; Kolb, Craig

    2017-01-01

    Interactive ray tracing applications running on commodity hardware can suffer from objectionable temporal artifacts due to a low sample count. We introduce stable ray tracing, a technique that improves temporal stability without the over-blurring and ghosting artifacts typical of temporal post-pr...

  12. Buildings 104 and 142 Complex Physical Protection and Material Control and Accounting Upgrades at the Mayak Production Association

    International Nuclear Information System (INIS)

    Aichele, Walter T.; Dwyer, Gregory M.; Larsen, R.; Malone, Tim

    2004-01-01

    The Federal State Unitary Enterprise Mayak Production Association (Mayak) and the U.S. Material Protection, Control and Accounting (MPC and A) United States Project Team (USPT) have worked together for a number of years as part of the U.S. national Nuclear Security Administration's (NNSA) MPC and A program to implement both Physical Protection (PP) and Material Control and Accounting (MC and A) upgrades within the Buildings 104 and 142 Complex, a long-term storage area for uranium and plutonium oxide located within Mayak's RT-1 Spent Fuel Reprocessing Plant. This paper focuses on the successes and areas for improvement in the analysis, planning, construction, implementation, and completion of a complex and labor-intensive project aimed at the refurbishment of two existing, in service, long-term special nuclear material (SNM) storage buildings within a Russian SNM production facility

  13. The association of posttraumatic stress disorder, complex posttraumatic stress disorder, and borderline personality disorder from a network analytical perspective.

    Science.gov (United States)

    Knefel, Matthias; Tran, Ulrich S; Lueger-Schuster, Brigitte

    2016-10-01

    Posttraumatic Stress Disorder (PTSD), Complex PTSD, and Borderline Personality Disorder (BPD) share etiological risk factors and an overlapping set of associated symptoms. Since the ICD-11 proposal for trauma-related disorders, the relationship of these disorders has to be clarified. A novel approach to psychopathology, network analysis, allows for a detailed analysis of comorbidity on symptom level. Symptoms were assessed in adult survivors of childhood abuse (N=219) using the newly developed ICD-11 Trauma-Questionnaire and the SCID-II. The psychopathological network was analyzed using the network approach. PTSD and Complex PTSD symptoms were strongly connected within disorders and to a lesser degree between disorders. Symptoms of BPD were weakly connected to others. Re-experiencing and dissociation were the most central symptoms. Mental disorders are no discrete entities, clear boundaries are unlikely to be found. The psychopathological network revealed central symptoms that might be important targets for specific first interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Metagenomic analysis of the complex microbial consortium associated with cultures of the oil-rich alga Botryococcus braunii.

    Science.gov (United States)

    Sambles, Christine; Moore, Karen; Lux, Thomas M; Jones, Katy; Littlejohn, George R; Gouveia, João D; Aves, Stephen J; Studholme, David J; Lee, Rob; Love, John

    2017-08-01

    Microalgae are widely viewed as a promising and sustainable source of renewable chemicals and biofuels. Botryococcus braunii synthesizes and secretes significant amounts of long-chain (C 30 -C 40 ) hydrocarbons that can be subsequently converted into gasoline, diesel, and aviation fuel. B. braunii cultures are not axenic and the effects of co-cultured microorganisms on B. braunii growth and hydrocarbon yield are important, but sometimes contradictory. To understand the composition of the B. braunii microbial consortium, we used high throughput Illumina sequencing of metagenomic DNA to profile the microbiota within a well established, stable B. braunii culture and characterized the demographic changes in the microcosm following modification to the culture conditions. DNA sequences attributed to B. braunii were present in equal quantities in all treatments, whereas sequences assigned to the associated microbial community were dramatically altered. Bacterial species least affected by treatments, and more robustly associated with the algal cells, included members of Rhizobiales, comprising Bradyrhizobium and Methylobacterium, and representatives of Dyadobacter, Achromobacter and Asticcacaulis. The presence of bacterial species identified by metagenomics was confirmed by additional 16S rDNA analysis of bacterial isolates. Our study demonstrates the advantages of high throughput sequencing and robust metagenomic analyses to define microcosms and further our understanding of microbial ecology. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  15. Critical Limb Ischemia in Association with Charcot Neuroarthropathy: Complex Endovascular Therapy for Limb Salvage

    Energy Technology Data Exchange (ETDEWEB)

    Palena, Luis Mariano, E-mail: marianopalena@hotmail.com [Policlinico Abano Terme, Interventional Radiology Unit (Italy); Brocco, Enrico [Policlinico Abano Terme, Diabetic Foot Department, Foot and Ankle Clinic (Italy); Manzi, Marco [Policlinico Abano Terme, Interventional Radiology Unit (Italy)

    2013-05-09

    Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical and orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.

  16. Comparison of Genome-Wide Association Methods in Analyses of Admixed Populations with Complex Familial Relationships

    DEFF Research Database (Denmark)

    Kadri, Naveen; Guldbrandtsen, Bernt; Sørensen, Peter

    2014-01-01

    Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P) and family (K......) levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic...... corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree...

  17. A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH.

    Science.gov (United States)

    Sun, Ye; Wang, Cheng; Hao, Zheng; Dai, Jin; Chen, Dongyang; Xu, Zhihong; Shi, Dongquan; Mao, Ping; Teng, Huajian; Gao, Xiang; Hu, Zhibin; Shen, Hongbing; Jiang, Qing

    2015-01-01

    Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH. We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B). In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A. Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.

  18. A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH.

    Directory of Open Access Journals (Sweden)

    Ye Sun

    Full Text Available Genetic basis of Developmental dysplasia of the hip (DDH remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS for DDH.We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A to conduct a genome-wide association study (GWAS. Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B.In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7. In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338 with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19-1.53 for allele A.Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.

  19. Cor triatriatum dexter associated with atrial septal defect: Management in a complex clinical case.

    Science.gov (United States)

    Sozzi, Fabiola B; Montanaro, Claudia; Bacà, Laura; Viani, Giacomo M; Zilocchi, Massimo; Canetta, Ciro; Meazza, Roberto; Pavone, Laura; Lombardi, Federico

    2017-11-01

    The coexistence of an atrial septal defect and a prominent eustachian valve is a rare congenital anomaly, rarely reported in literature. Differentiation between a giant eustachian valve and cor triatriatum dexter can be difficult. A case of a large atrial septal defect associated with cor triatriatum dexter diagnosed by echocardiography in an asymptomatic woman is reported. A watchful waiting strategy was adopted. © 2017, Wiley Periodicals, Inc.

  20. Nef enhances HIV-1 infectivity via association with the virus assembly complex

    International Nuclear Information System (INIS)

    Qi Mingli; Aiken, Christopher

    2008-01-01

    The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle

  1. Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97.

    Science.gov (United States)

    Milbradt, Jens; Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Sticht, Heinrich; Britt, William J; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

    2018-01-13

    The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction.

  2. Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits.

    Science.gov (United States)

    Smith, Andrew J P; Deloukas, Panos; Munroe, Patricia B

    2018-04-13

    Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, type 2 diabetes, cancer, obesity and autoimmune disease. We focus on analysis of variants occurring within non-coding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants, and how these may relate to the pathology of the trait, and look towards future directions for these technologies in post-GWAS analysis, such as base-editing.

  3. Complex mixture-associated hormesis and toxicity: the case of leather tanning industry.

    Science.gov (United States)

    Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

    2008-01-01

    A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels > or =1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels > or =1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process.

  4. Femoral facial syndrome associated with a de novo complex chromosome 2q37 rearrangement.

    Science.gov (United States)

    Spielmann, Malte; Marx, Sylvie; Barbi, Gotthold; Flöttmann, Ricarda; Kehrer-Sawatzki, Hildegard; König, Rainer; Horn, Denise; Mundlos, Stefan; Nader, Sean; Borck, Guntram

    2016-05-01

    The femoral facial syndrome (FFS) is a rare congenital anomaly syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism. The etiology of FFS is currently unknown but maternal/gestational diabetes has been proposed as a strong risk factor for syndromic femoral hypoplasia. In affected children born to non-diabetic mothers, a genetic contribution to FFS is suspected; however, no chromosomal anomalies or gene mutations have been identified so far. Here, we report on a girl with FFS and a de novo complex chromosome rearrangement of terminal chromosome 2q37.2. Radiographs of the pelvis and lower limbs showed bilateral shortening and bowing of the femur and radiographs of hands and feet revealed a brachydactyly type E (BDE). Using high resolution array-CGH, qPCR, and FISH, we detected a ~1.9 Mb duplication in the chromosomal region 2q37.2 and a ~5.4 Mb deletion on chromosome 2q37.3 that were absent in the parents. The duplication contains six genes and the deletion encompasses 68 genes; the latter has previously been shown to cause BDE (through haploinsufficiency for HDAC4) but not femoral hypoplasia. Therefore, we propose that the duplication 2q37.2 could be causative for the femur phenotype. To the best of our knowledge, our report is the first to propose a genetic cause in a case of FFS. © 2016 Wiley Periodicals, Inc.

  5. Helicobacter pylori-associated gastritis and dyspepsia. The influence on migrating motor complexes

    DEFF Research Database (Denmark)

    Qvist, N; Rasmussen, L; Axelsson, C K

    1994-01-01

    patients with a median age of 42 (range, 32-56) years H. pylori-negative gastritis was found. After an overnight fast the patients underwent an ambulatory duodenal motility study for 6-8 h. Twenty-five young healthy men served as the control group. In patients with H. pylori-positive gastritis the duration...... of phase I of the migrating motor complex (MMC) was significantly shorter than in the control group. The median value was 33 min (quartiles, 24-49), and in controls 56 min (40-136 min). Phase II was of significantly longer duration, with a median value of 88 min (51-121 min) in the patient group and 39 min......Twenty-five patients with dyspepsia were included. In 19 patients with a median age of 48 (range, 20-72) years endoscopy and histologic examination of biopsy specimens from the antrum and corpus of the stomach showed Helicobacter pylori-positive gastritis as the only pathologic finding. In six...

  6. The risk of stable partnerships: associations between partnership characteristics and unprotected anal intercourse among men who have sex with men and transgender women recently diagnosed with HIV and/or STI in Lima, Peru.

    Directory of Open Access Journals (Sweden)

    Mary C Cambou

    Full Text Available Partnership type is an important factor associated with unprotected anal intercourse (UAI and subsequent risk for HIV and sexually transmitted infections (STI. We examined the association of partnership type with UAI among men who have sex with men (MSM and male-to-female transgender women (TGW in Lima, Peru, recently diagnosed with HIV and/or STI.We report data from a cross-sectional analysis of MSM and TGW recently diagnosed with HIV and/or STI in Lima, Peru between 2011 and 2012. We surveyed participants regarding UAI with up to their three most recent sexual partners according to partner type. Multivariable Generalized Estimate Equating (GEE models with Poisson distribution were used to estimate prevalence ratios (PR for UAI according to partner type.Among 339 MSM and TGW recently diagnosed with HIV and/or STI (mean age: 30.6 years, SD 9.0, 65.5% self-identified as homosexual/gay, 16.0% as bisexual, 15.2% as male-to-female transgender, and 3.3% as heterosexual. Participants provided information on 893 recent male or TGW partners with whom they had engaged in insertive or receptive anal intercourse: 28.9% stable partners, 56.4% non-stable/non-transactional partners (i.e. casual or anonymous, and 14.7% transactional partners (i.e. transactional sex client or sex worker. Unprotected anal intercourse was reported with 41.3% of all partners. In multivariable analysis, factors associated with UAI included partnership type (non-stable/non-transactional partner APR 0.73, [95% CI 0.59-0.91], transactional partner APR 0.53 [0.36-0.78], p10 encounters APR 1.43 [1.06-1.92], p10 sexual encounters, suggesting UAI is more prevalent in partnerships with a greater degree of interpersonal commitment. Further research assessing partner-level factors and behavior is critical for improving HIV and/or STI prevention efforts among Peruvian MSM and TGW.

  7. The risk of stable partnerships: associations between partnership characteristics and unprotected anal intercourse among men who have sex with men and transgender women recently diagnosed with HIV and/or STI in Lima, Peru.

    Science.gov (United States)

    Cambou, Mary C; Perez-Brumer, Amaya G; Segura, Eddy R; Salvatierra, H Javier; Lama, Javier R; Sanchez, Jorge; Clark, Jesse L

    2014-01-01

    Partnership type is an important factor associated with unprotected anal intercourse (UAI) and subsequent risk for HIV and sexually transmitted infections (STI). We examined the association of partnership type with UAI among men who have sex with men (MSM) and male-to-female transgender women (TGW) in Lima, Peru, recently diagnosed with HIV and/or STI. We report data from a cross-sectional analysis of MSM and TGW recently diagnosed with HIV and/or STI in Lima, Peru between 2011 and 2012. We surveyed participants regarding UAI with up to their three most recent sexual partners according to partner type. Multivariable Generalized Estimate Equating (GEE) models with Poisson distribution were used to estimate prevalence ratios (PR) for UAI according to partner type. Among 339 MSM and TGW recently diagnosed with HIV and/or STI (mean age: 30.6 years, SD 9.0), 65.5% self-identified as homosexual/gay, 16.0% as bisexual, 15.2% as male-to-female transgender, and 3.3% as heterosexual. Participants provided information on 893 recent male or TGW partners with whom they had engaged in insertive or receptive anal intercourse: 28.9% stable partners, 56.4% non-stable/non-transactional partners (i.e. casual or anonymous), and 14.7% transactional partners (i.e. transactional sex client or sex worker). Unprotected anal intercourse was reported with 41.3% of all partners. In multivariable analysis, factors associated with UAI included partnership type (non-stable/non-transactional partner APR 0.73, [95% CI 0.59-0.91], transactional partner APR 0.53 [0.36-0.78], p10 encounters APR 1.43 [1.06-1.92], p10 sexual encounters, suggesting UAI is more prevalent in partnerships with a greater degree of interpersonal commitment. Further research assessing partner-level factors and behavior is critical for improving HIV and/or STI prevention efforts among Peruvian MSM and TGW.

  8. Quantitative Analysis of Dynamic Protein Interactions during Transcription Reveals a Role for Casein Kinase II in Polymerase-associated Factor (PAF) Complex Phosphorylation and Regulation of Histone H2B Monoubiquitylation.

    Science.gov (United States)

    Bedard, Lynn Glowczewski; Dronamraju, Raghuvar; Kerschner, Jenny L; Hunter, Gerald O; Axley, Elizabeth DeVlieger; Boyd, Asha K; Strahl, Brian D; Mosley, Amber L

    2016-06-24

    Using affinity purification MS approaches, we have identified a novel role for casein kinase II (CKII) in the modification of the polymerase associated factor complex (PAF-C). Our data indicate that the facilitates chromatin transcription complex (FACT) interacts with CKII and may facilitate PAF complex phosphorylation. Posttranslational modification analysis of affinity-isolated PAF-C shows extensive CKII phosphorylation of all five subunits of PAF-C, although CKII subunits were not detected as interacting partners. Consistent with this, recombinant CKII or FACT-associated CKII isolated from cells can phosphorylate PAF-C in vitro, whereas no intrinsic kinase activity was detected in PAF-C samples. Significantly, PAF-C purifications combined with stable isotope labeling in cells (SILAC) quantitation for PAF-C phosphorylation from wild-type and CKII temperature-sensitive strains (cka1Δ cka2-8) showed that PAF-C phosphorylation at consensus CKII sites is significantly reduced in cka1Δ cka2-8 strains. Consistent with a role of CKII in FACT and PAF-C function, we show that decreased CKII function in vivo results in decreased levels of histone H2B lysine 123 monoubiquitylation, a modification dependent on FACT and PAF-C. Taken together, our results define a coordinated role of CKII and FACT in the regulation of RNA polymerase II transcription through chromatin via phosphorylation of PAF-C. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Kaposi's sarcoma-associated herpesvirus ORF45 interacts with kinesin-2 transporting viral capsid-tegument complexes along microtubules.

    Directory of Open Access Journals (Sweden)

    Narayanan Sathish

    2009-03-01

    Full Text Available Open reading frame (ORF 45 of Kaposi's sarcoma-associated herpesvirus (KSHV is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A-ORF45 interaction either by the use of a headless dominant negative (DN mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles.

  10. Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

    Directory of Open Access Journals (Sweden)

    Greenblatt Jack F

    2007-09-01

    Full Text Available Abstract Background Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4. Results Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC. While mutational inactivation of the histone acetyltransferase (HAT gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2 exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork. Conclusion We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p. The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

  11. TWENTY-FIVE-GAUGE PARS PLANA VITRECTOMY IN COMPLEX RETINAL DETACHMENTS ASSOCIATED WITH GIANT RETINAL TEAR.

    Science.gov (United States)

    Kumar, Vinod; Kumawat, Devesh; Bhari, Anju; Chandra, Parijat

    2018-04-01

    To study the structural and functional outcomes of 25-gauge pars plana vitrectomy in giant retinal tear-associated retinal detachments. Seventeen eyes of 17 patients with giant retinal tear, who underwent 25-gauge pars plana vitrectomy over a period of 15 months at a tertiary eye care center by a single surgeon, were recruited in this retrospective interventional study. Giant retinal tears were mostly traumatic (35.3%) or associated with myopia (35.3%) and occurred in young (mean age 25.7 years) males (94.1%). Most eyes had best-corrected visual acuity ≤20/1,200 (in 82.3%), foveal detachment (in 88.2%), and proliferative vitreoretinopathy ≤Grade B (in 82.3%). The giant retinal tear extent was more than 180° in 29.4% and the fellow eye was involved in 35.2% of eyes. All eyes underwent 25-gauge pars plana vitrectomy with encircling band in 41.1%, perfluorocarbon liquid use in 82.3%, and endotamponade with sulphur hexafluoride (23.6%) or silicone oil (76.4%). At mean follow-up of 10.2 months, reattachment rate was 88.2%. Only 35.2% of eyes achieved final visual acuity ≥20/80 with a cause of poor vision being cataract, secondary glaucoma, macular pucker, and corneal edema. Twenty-five-gauge pars plana vitrectomy can achieve excellent attachment rates in eyes with giant retinal tear-associated retinal detachment. It can be as efficient as larger-gauge vitrectomy, at the same time retaining all advantages of smaller-gauge surgery.

  12. A High Molar Extinction Coefficient Ru(II Complex Functionalized with cis-Dithiocyanato-bis-(9-anthracenyl-10-(2-methyl-2-butenoic acid-1,10-phenanthroline: Potential Sensitizer for Stable Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Adewale O. Adeloye

    2014-01-01

    Full Text Available New heteroleptic ruthenium(II complex was formulated as [Ru(L12(NCS2], where L1 = 9-anthracenyl-10-(2-methyl-2-butenoic acid-1,10-phenanthroline was synthesized and its photophysical properties were studied and compared to previously reported analogue complex containing no anthracene moiety [Ru(L22(NCS2], L2 = (2-methyl-2-butenoic acid-1,10-phenanthroline. The two complexes though exhibit very strong molar extinction coefficient values; however, [Ru(L12(NCS2] shows better characteristic broad and intense metal-to-ligand charge transfer (MLCT absorption band and higher molar absorptivity coefficient at (λmax=522 nm, ε=6.60×104 M−1 cm−1 than that of [Ru(L22(NCS2] complex, (λmax=446 nm, ε=4.82×104 M−1 cm−1. At room temperature, long wavelength emissions with strong intensity ratio centered at 660 nm were recorded for [Ru(L12(NCS2] complex with a bathochromic shift (λem=700 nm for [Ru(L22(NCS2] complex. It was shown that the luminescence wavelength characteristic of the complexes may be a function relating to the increasing length of π-conjugation and/or molecular weight. A preliminary cyclic voltammetry of [Ru(L12(NCS2] complex also exhibits good electroredox activity with oxidation potential of about 1.04 V, significantly better than other Ru(II polypyridine complexes containing bidentate ligands.

  13. Xylophage complex associated with the decline of the Atlas cedar Belezma

    International Nuclear Information System (INIS)

    Yamina, T.; Taril, B.R.

    2015-01-01

    The study of insects associated with the decline of Atlas cedar (Cedrus atlantica Manetti) in the massif of Belezma (Algeria), resulted in the determination of18 species of xylophagous beetles. Their majority (85%) are represented by the subfamily of Scolytinae. The most dominant were Scolytus amygdali Guerin, 1847 andCryphalus numidicus Eichhoff, 1878.The Buprestidae occupy second place with 14.24% from the total of inventoried xylophagouswith 6 species, whereas the most common was Melanophila marmottani (Fairmaire, 1868). The knowledge of bioecology and outbreaks mechanisms of these species is necessary in order to develop efficient protection strategy against them. (author)

  14. Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Sablitzky Fred

    2004-01-01

    Full Text Available Abstract Background Inactivating genes in vivo is an important technique for establishing their function in the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and the compensatory regulation of other genes. One approach to producing conditional activation or inactivation of genes involves the use of Cre recombinase to remove loxP-flanked segments of DNA. We have studied the effects of delivering Cre to the hippocampus and neocortex of adult mice by injecting replication-deficient adeno-associated virus (AAV and lentiviral (LV vectors into discrete regions of the forebrain. Results Recombinant AAV-Cre, AAV-GFP (green fluorescent protein and LV-Cre-EGFP (enhanced GFP were made with the transgene controlled by the cytomegalovirus promoter. Infecting 293T cells in vitro with AAV-Cre and LV-Cre-EGFP resulted in transduction of most cells as shown by GFP fluorescence and Cre immunoreactivity. Injections of submicrolitre quantities of LV-Cre-EGFP and mixtures of AAV-Cre with AAV-GFP into the neocortex and hippocampus of adult Rosa26 reporter mice resulted in strong Cre and GFP expression in the dentate gyrus and moderate to strong labelling in specific regions of the hippocampus and in the neocortex, mainly in neurons. The pattern of expression of Cre and GFP obtained with AAV and LV vectors was very similar. X-gal staining showed that Cre-mediated recombination had occurred in neurons in the same regions of the brain, starting at 3 days post-injection. No obvious toxic effects of Cre expression were detected even after four weeks post-injection. Conclusion AAV and LV vectors are capable of delivering Cre to neurons in discrete regions of the adult mouse brain and producing recombination.

  15. A High Molar Extinction Coefficient Ru(II) Complex Functionalized with cis-Dithiocyanato-bis-(9-anthracenyl-10-(2-methyl-2-butenoic acid)-1,10-phenanthroline): Potential Sensitizer for Stable Dye-Sensitized Solar Cells

    OpenAIRE

    Adeloye, Adewale O.; Ajibade, Peter A.

    2014-01-01

    New heteroleptic ruthenium(II) complex was formulated as [Ru(L1)2(NCS)2], where L1 = 9-anthracenyl-10-(2-methyl-2-butenoic acid)-1,10-phenanthroline was synthesized and its photophysical properties were studied and compared to previously reported analogue complex containing no anthracene moiety [Ru(L2)2(NCS)2], L2 = (2-methyl-2-butenoic acid)-1,10-phenanthroline. The two complexes though exhibit very strong molar extinction coefficient values; however, [Ru(L1)2(NCS)2] shows better characteris...

  16. Mental stress and ischemic heart disease: evolving awareness of a complex association.

    Science.gov (United States)

    Proietti, Riccardo; Mapelli, Daniela; Volpe, Biancarosa; Bartoletti, Stefano; Sagone, Antonio; Dal Bianco, Lucia; Daliento, Luciano

    2011-05-01

    The connection between cardiovascular disease and psychosocial risk factors has been the subject of an ever-growing body of literature over the last 50 years. Studies on the role of negative emotions, personality traits, chronic stress and social determinants have brought to light their possible role in triggering acute coronary syndromes, although further studies are required to clarify controversial results regarding the association between cardiovascular risk and important psychological problems such as depression and anxiety. The recognition of the role of emotional events in acute coronary syndromes paved the way for provocation experiments, aimed at inducing mental stress in a controlled setting and then documenting reversible impairment of myocardial perfusion, depolarization anomalies and arrhythmias. This ultimately led to the formalization of the concept of mental stress-induced myocardial ischemia. Accumulating evidence on the mechanistic bases of such phenomena outline a wide range of central and peripheral physiological changes associated with emotions and behaviors, whose effects are exerted on the cardiovascular system, sympathetic nervous system and the hypothalamus-hypophysis neuroendocrine axis. This article outlines the main steps in the identification of psychological aspects as cardiovascular risk factors and emphasizes the relevance of emotional stress as a trigger of acute cardiovascular events. Finally, a description is provided of the pathophysiological mechanisms behind mental stress-induced myocardial ischemia and pathways connecting the heart and brain.

  17. The adeno-associated virus major regulatory protein Rep78-c-Jun-DNA motif complex modulates AP-1 activity

    International Nuclear Information System (INIS)

    Prasad, C. Krishna; Meyers, Craig; Zhan Dejin; You Hong; Chiriva-Internati, Maurizio; Mehta, Jawahar L.; Liu Yong; Hermonat, Paul L.

    2003-01-01

    Multiple epidemiologic studies show that adeno-associated virus (AAV) is negatively associated with cervical cancer (CX CA), a cancer which is positively associated with human papillomavirus (HPV) infection. Mechanisms for this correlation may be by Rep78's (AAV's major regulatory protein) ability to bind the HPV-16 p97 promoter DNA and inhibit transcription, to bind and interfere with the functions of the E7 oncoprotein of HPV-16, and to bind a variety of HPV-important cellular transcription factors such as Sp1 and TBP. c-Jun is another important cellular factor intimately linked to the HPV life cycle, as well as keratinocyte differentiation and skin development. Skin is the natural host tissue for both HPV and AAV. In this article it is demonstrated that Rep78 directly interacts with c-Jun, both in vitro and in vivo, as analyzed by Western blot, yeast two-hybrid cDNA, and electrophoretic mobility shift-supershift assay (EMSA supershift). Addition of anti-Rep78 antibodies inhibited the EMSA supershift. Investigating the biological implications of this interaction, Rep78 inhibited the c-Jun-dependent c-jun promoter in transient and stable chloramphenicol acetyl-transferase (CAT) assays. Rep78 also inhibited c-Jun-augmented c-jun promoter as well as the HPV-16 p97 promoter activity (also c-Jun regulated) in in vitro transcription assays in T47D nuclear extracts. Finally, the Rep78-c-Jun interaction mapped to the amino-half of Rep78. The ability of Rep78 to interact with c-Jun and down-regulate AP-1-dependent transcription suggests one more mechanism by which AAV may modulate the HPV life cycle and the carcinogenesis process

  18. The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery.

    LENUS (Irish Health Repository)

    Iohom, Gabriella

    2012-02-03

    In this study, we compared the effects of two analgesic regimens on perioperative nitric oxide index (NOx) and the likelihood of subsequent development of chronic postsurgical pain (CPSP) after breast surgery and sought to determine the association among early postoperative pain, NOx, and the likelihood of subsequent development of CPSP. Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were randomly allocated to one of two groups. Patients in group S (n = 15) received a standard intraoperative and postoperative analgesic regimen (morphine sulfate, diclofenac, dextropropoxyphene hydrochloride + acetaminophen prn). Patients in group N (n = 14) received a continuous paravertebral block (for 48 h) and acetaminophen and parecoxib (followed by celecoxib up to 5 days). Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day. A telephone interview was conducted 10 wk postoperatively. The McGill Pain Questionnaire was used to characterize pain. NOx was estimated preoperatively, at the end of surgery, 30 min and 2, 4, 12, 24, 48 h postoperatively. Twelve (80%) patients in group S and no patient in group N developed CPSP (P = 0.009). Compared with patients with a pain rating index > or =1 (n = 18) 10 wk postoperatively, patients with a pain rating index = 0 (n = 11) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively (P < 0.005) and at rest 30 min (0.6 +\\/- 1.5 versus 30.2 +\\/- 26.8; P = 0.004), 4 h (2.3 +\\/- 7.5 versus 19.0 +\\/- 25.8; P = 0.013), 8 h (4.4 +\\/- 10.2 versus 21.4 +\\/- 27.0; P = 0.03) and 12 h (0.7 +\\/- 1.2 versus 15.4 +\\/- 27.0; P = 0.035) postoperatively. NOx values were greater in group N compared with group S 48 h postoperatively (40.6 +\\/- 20.1 versus 26.4 +\\/- 13.5; P = 0.04).

  19. Ecological Inferences from a deep screening of the Complex Bacterial Consortia associated with the coral, Porites astreoides.

    Science.gov (United States)

    Rodriguez-Lanetty, Mauricio; Granados-Cifuentes, Camila; Barberan, Albert; Bellantuono, Anthony J; Bastidas, Carolina

    2013-08-01

    The functional role of the bacterial organisms in the reef ecosystem and their contribution to the coral well-being remain largely unclear. The first step in addressing this gap of knowledge relies on in-depth characterization of the coral microbial community and its changes in diversity across coral species, space and time. In this study, we focused on the exploration of microbial community assemblages associated with an ecologically important Caribbean scleractinian coral, Porites astreoides, using Illumina high-throughput sequencing of the V5 fragment of 16S rRNA gene. We collected data from a large set of biological replicates, allowing us to detect patterns of geographical structure and resolve co-occurrence patterns using network analyses. The taxonomic analysis of the resolved diversity showed consistent and dominant presence of two OTUs affiliated with the order Oceanospirillales, which corroborates a specific pattern of bacterial association emerging for this coral species and for many other corals within the genus Porites. We argue that this specific association might indicate a symbiotic association with the adult coral partner. Furthermore, we identified a highly diverse rare bacterial 'biosphere' (725 OTUs) also living along with the dominant bacterial symbionts, but the assemblage of this biosphere is significantly structured along the geographical scale. We further discuss that some of these rare bacterial members show significant association with other members of the community reflecting the complexity of the networked consortia within the coral holobiont. © 2013 John Wiley & Sons Ltd.

  20. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Satoko Arai

    2013-04-01

    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  1. Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia† †Electronic supplementary information (ESI) available. CCDC 1001632–1001634. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5dt02537k Click here for additional data file. Click here for additional data file.

    Science.gov (United States)

    Alam, Israt S.; Arrowsmith, Rory L.; Cortezon-Tamarit, Fernando; Twyman, Frazer; Kociok-Köhn, Gabriele; Botchway, Stanley W.; Dilworth, Jonathan R.

    2016-01-01

    We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under ‘cold’ and ‘hot’ biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. 68Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration. PMID:26583314

  2. Association of satellites with a mastrevirus in natural infection: complexity of Wheat dwarf India virus disease.

    Science.gov (United States)

    Kumar, Jitendra; Kumar, Jitesh; Singh, Sudhir P; Tuli, Rakesh

    2014-06-01

    In contrast to begomoviruses, mastreviruses have not previously been shown to interact with satellites. This study reports the first identification of the association of satellites with a mastrevirus in field-grown plants. Two alphasatellite species were detected in different field samples of wheat infected with Wheat Dwarf India Virus (WDIV), a Cotton leaf curl Multan alphasatellite (CLCuMA) and a Guar leaf curl alphasatellite (GLCuA). In addition to the alphasatellites, a betasatellite, Ageratum yellow leaf curl betasatellite (AYLCB), was also identified in the wheat samples. No begomovirus was detected in the wheat samples, thus establishing association of the above-named satellites with WDIV. Agrobacterium-mediated inoculation of WDIV in wheat, in the presence of either of the alphasatellites or the betasatellite, resulted in infections inducing more severe symptoms. WDIV efficiently maintained each of the alphasatellites and the betasatellite in wheat. The satellites enhanced the level of WDIV DNA in wheat. Inoculation of the satellites isolated from wheat with various begomoviruses into Nicotiana tabacum demonstrated that these remain capable of interacting with the viruses with which they were first identified. Virus-specific small RNAs accumulated in wheat upon infection with WDIV but were lower in abundance in plants coinfected with the satellites, suggesting that both the alphasatellites and the betasatellite suppress RNA silencing. These results suggest that the selective advantage for the maintenance of the alphasatellites and the betasatellite by WDIV in the field is in overcoming RNA silencing-mediated host defense. Wheat is the most widely cultivated cereal crop in the world. A number of viruses are important pathogens of wheat, including the viruses of the genus Mastrevirus, family Geminiviridae. This study reports the association of subgenomic components, called satellites (alpha- and betasatellites), with a mastrevirus, Wheat Dwarf India Virus

  3. Complex Association of Sex Hormones on Left Ventricular Systolic Function: Insight into Sexual Dimorphism.

    Science.gov (United States)

    Salem, Joe-Elie; Nguyen, Lee S; Hammoudi, Nadjib; Preud'homme, Gisèle; Hulot, Jean-Sebastien; Leban, Monique; Funck-Brentano, Christian; Touraine, Philippe; Isnard, Richard; Bachelot, Anne

    2018-02-01

    Normal values of left ventricular ejection fraction (LVEF) and absolute values of global longitudinal strain (GLS) are lower in men than in women. Data concerning the association of sex hormone levels on these left ventricular systolic function surrogates are scarce. The aim of this study was to determine the association of sex hormones with systolic left ventricular function in healthy subjects and patients with congenital adrenal hyperplasia (CAH) as a model of testosterone dysregulation. Eighty-four adult patients with CAH (58 women; median age, 27 years; interquartile range, 23-36 years) and 84 healthy subjects matched for sex and age were prospectively included. Circulating concentrations of sex hormones were measured within 48 hours of echocardiography with assessment of LVEF and left ventricular longitudinal, radial, and circumferential strain. LVEF and GLS were higher in healthy women than in healthy men (63.9 ± 4.2% vs 60.9 ± 5.1% [P interquartile range, 0.04-0.14 ng/mL] vs 0.16 ng/mL [interquartile range, 0.04-0.3 ng/mL], P interquartile range, 1.3-3 ng/mL] vs 2.9 ng/mL [interquartile range, 2.5-3.4 ng/mL], P < .05). In men, LVEF and GLS were negatively correlated with bioavailable testosterone levels (r = -0.3, P ≤ .05, and r = -0.45, P < .01, respectively), while midventricular radial strain was positively correlated with bioavailable testosterone level (r = 0.38, P < .05). The absolute value of circumferential strain was positively correlated with follicle-stimulating hormone (r = 0.65, P < .0001). These data support that the existence of sex dimorphism concerning left ventricular systolic cardiac function is significantly associated with testosterone levels. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  4. Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways.

    Directory of Open Access Journals (Sweden)

    Srinivas B Narayan

    Full Text Available Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD and glutamate dehydrogenase (GDH explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1 from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein.

  5. Nucleoporin Nup98 associates with Trx/MLL and NSL histone-modifying complexes and regulates Hox gene expression.

    Science.gov (United States)

    Pascual-Garcia, Pau; Jeong, Jieun; Capelson, Maya

    2014-10-23

    The nuclear pore complex is a transport channel embedded in the nuclear envelope and made up of 30 different components termed nucleoporins (Nups). In addition to their classical role in transport, a subset of Nups has a conserved role in the regulation of transcription via direct binding to chromatin. The molecular details of this function remain obscure, and it is unknown how metazoan Nups are recruited to their chromatin locations or what transcription steps they regulate. Here, we demonstrate genome-wide and physical association between Nup98 and histone-modifying complexes MBD-R2/NSL [corrected] and Trx/MLL. Importantly, we identify a requirement for MBD-R2 in recruitment of Nup98 to many of its genomic target sites. Consistent with its interaction with the Trx/MLL complex, Nup98 is shown to be necessary for Hox gene expression in developing fly tissues. These findings introduce roles of Nup98 in epigenetic regulation that may underlie the basis of oncogenicity of Nup98 fusions in leukemia.

  6. Nucleoporin Nup98 Associates with Trx/MLL and NSL Histone-Modifying Complexes and Regulates Hox Gene Expression

    Directory of Open Access Journals (Sweden)

    Pau Pascual-Garcia

    2014-10-01

    Full Text Available The nuclear pore complex is a transport channel embedded in the nuclear envelope and made up of 30 different components termed nucleoporins (Nups. In addition to their classical role in transport, a subset of Nups has a conserved role in the regulation of transcription via direct binding to chromatin. The molecular details of this function remain obscure, and it is unknown how metazoan Nups are recruited to their chromatin locations or what transcription steps they regulate. Here, we demonstrate genome-wide and physical association between Nup98 and histone-modifying complexes MBR-R2/NSL and Trx/MLL. Importantly, we identify a requirement for MBD-R2 in recruitment of Nup98 to many of its genomic target sites. Consistent with its interaction with the Trx/MLL complex, Nup98 is shown to be necessary for Hox gene expression in developing fly tissues. These findings introduce roles of Nup98 in epigenetic regulation that may underlie the basis of oncogenicity of Nup98 fusions in leukemia.

  7. Stable isotope analysis

    International Nuclear Information System (INIS)

    Tibari, Elghali; Taous, Fouad; Marah, Hamid

    2014-01-01

    This report presents results related to stable isotopes analysis carried out at the CNESTEN DASTE in Rabat (Morocco), on behalf of Senegal. These analyzes cover 127 samples. These results demonstrate that Oxygen-18 and Deuterium in water analysis were performed by infrared Laser spectroscopy using a LGR / DLT-100 with Autosampler. Also, the results are expressed in δ values (‰) relative to V-SMOW to ± 0.3 ‰ for oxygen-18 and ± 1 ‰ for deuterium.

  8. Factors associated with development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics.

    Science.gov (United States)

    Joffe, Daniel J; Lelewski, Roxana; Weese, J Scott; Mcgill-Worsley, Jamie; Shankel, Catharine; Mendonca, Sonia; Sager, Tara; Smith, Michael; Poljak, Zvonimir

    2016-01-01

    This study investigated the association between presence of respiratory pathogens and development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics. In total, 86 dogs were tested using a commercial PCR respiratory panel; 64 dogs were considered as cases and 22 were control dogs matched by veterinary clinic. No control animals (0/22) were positive for canine parainfluenza virus (CPIV), whereas 27/64 (42%) CIRDC cases were positive. Furthermore, 81% of case dogs tested positive for Mycoplasma cynos, compared with 73% of control dogs. Canine respiratory corona virus (CRCoV) was detected in no control dogs compared with 9.4% of clinical dogs. No animals were positive for any influenza virus type A present in the diagnostic panel. Presence of CPIV was associated (P < 0.01) with the occurrence of CIRDC after adjustment for demographic factors and presence of CRCoV (P = 0.09).

  9. Forensic Stable Isotope Biogeochemistry

    Science.gov (United States)

    Cerling, Thure E.; Barnette, Janet E.; Bowen, Gabriel J.; Chesson, Lesley A.; Ehleringer, James R.; Remien, Christopher H.; Shea, Patrick; Tipple, Brett J.; West, Jason B.

    2016-06-01

    Stable isotopes are being used for forensic science studies, with applications to both natural and manufactured products. In this review we discuss how scientific evidence can be used in the legal context and where the scientific progress of hypothesis revisions can be in tension with the legal expectations of widely used methods for measurements. Although this review is written in the context of US law, many of the considerations of scientific reproducibility and acceptance of relevant scientific data span other legal systems that might apply different legal principles and therefore reach different conclusions. Stable isotopes are used in legal situations for comparing samples for authenticity or evidentiary considerations, in understanding trade patterns of illegal materials, and in understanding the origins of unknown decedents. Isotope evidence is particularly useful when considered in the broad framework of physiochemical processes and in recognizing regional to global patterns found in many materials, including foods and food products, drugs, and humans. Stable isotopes considered in the larger spatial context add an important dimension to forensic science.

  10. Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

    Directory of Open Access Journals (Sweden)

    Konstantina Fragaki

    Full Text Available BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %, thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

  11. Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology.

    Science.gov (United States)

    Betz, Charles; Stracka, Daniele; Prescianotto-Baschong, Cristina; Frieden, Maud; Demaurex, Nicolas; Hall, Michael N

    2013-07-30

    The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of growth. Mammalian TOR complex 2 (mTORC2) regulates AGC kinase family members and is implicated in various disorders, including cancer and diabetes. Here we report that mTORC2 is localized to the endoplasmic reticulum (ER) subcompartment termed mitochondria-associated ER membrane (MAM). mTORC2 localization to MAM was growth factor-stimulated, and mTORC2 at MAM interacted with the IP3 receptor (IP3R)-Grp75-voltage-dependent anion-selective channel 1 ER-mitochondrial tethering complex. mTORC2 deficiency disrupted MAM, causing mitochondrial defects including increases in mitochondrial membrane potential, ATP production, and calcium uptake. mTORC2 controlled MAM integrity and mitochondrial function via Akt mediated phosphorylation of the MAM associated proteins IP3R, Hexokinase 2, and phosphofurin acidic cluster sorting protein 2. Thus, mTORC2 is at the core of a MAM signaling hub that controls growth and metabolism.

  12. mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology

    Science.gov (United States)

    Betz, Charles; Stracka, Daniele; Prescianotto-Baschong, Cristina; Frieden, Maud; Demaurex, Nicolas; Hall, Michael N.

    2013-01-01

    The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of growth. Mammalian TOR complex 2 (mTORC2) regulates AGC kinase family members and is implicated in various disorders, including cancer and diabetes. Here we report that mTORC2 is localized to the endoplasmic reticulum (ER) subcompartment termed mitochondria-associated ER membrane (MAM). mTORC2 localization to MAM was growth factor-stimulated, and mTORC2 at MAM interacted with the IP3 receptor (IP3R)-Grp75–voltage-dependent anion-selective channel 1 ER-mitochondrial tethering complex. mTORC2 deficiency disrupted MAM, causing mitochondrial defects including increases in mitochondrial membrane potential, ATP production, and calcium uptake. mTORC2 controlled MAM integrity and mitochondrial function via Akt mediated phosphorylation of the MAM associated proteins IP3R, Hexokinase 2, and phosphofurin acidic cluster sorting protein 2. Thus, mTORC2 is at the core of a MAM signaling hub that controls growth and metabolism. PMID:23852728

  13. Role for ribosome-associated complex and stress-seventy subfamily B (RAC-Ssb) in integral membrane protein translation.

    Science.gov (United States)

    Acosta-Sampson, Ligia; Döring, Kristina; Lin, Yuping; Yu, Vivian Y; Bukau, Bernd; Kramer, Günter; Cate, Jamie H D

    2017-12-01

    Targeting of most integral membrane proteins to the endoplasmic reticulum is controlled by the signal recognition particle, which recognizes a hydrophobic signal sequence near the protein N terminus. Proper folding of these proteins is monitored by the unfolded protein response and involves protein degradation pathways to ensure quality control. Here, we identify a new pathway for quality control of major facilitator superfamily transporters that occurs before the first transmembrane helix, the signal sequence recognized by the signal recognition particle, is made by the ribosome. Increased rates of translation elongation of the N-terminal sequence of these integral membrane proteins can divert the nascent protein chains to the ribosome-associated complex and stress-seventy subfamily B chaperones. We also show that quality control of integral membrane proteins by ribosome-associated complex-stress-seventy subfamily B couples translation rate to the unfolded protein response, which has implications for understanding mechanisms underlying human disease and protein production in biotechnology. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. cis-Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture

    Directory of Open Access Journals (Sweden)

    Jennifer Yihong Tan

    2017-02-01

    Full Text Available Intergenic long noncoding RNAs (lincRNAs are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits.

  15. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex

    Directory of Open Access Journals (Sweden)

    Franz DN

    2013-10-01

    Full Text Available David Neal Franz Department of Pediatrics, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Abstract: Tuberous sclerosis complex (TSC is an autosomal dominant genetic disorder caused by inactivating mutations in either the TSC1 or TSC2 genes. It is characterized by the development of multiple, benign tumors in several organs throughout the body. Lesions occur in the brain, kidneys, heart, liver, lungs, and skin and result in seizures and epilepsy, mental retardation, autism, and renal and pulmonary organ system dysfunction, as well as other complications. Elucidation of the molecular pathways and etiological factors responsible for causing TSC has led to a paradigm shift in the management and treatment of the disease. TSC1 or TSC2 mutations lead to constitutive upregulation of the mammalian target of rapamycin pathway, which affects many cellular processes involved in tumor growth. By targeting mammalian target of rapamycin with everolimus, an orally active rapamycin derivative, clinically meaningful and statistically significant reductions in tumor burden have been achieved for the main brain (subependymal giant cell astrocytoma and renal manifestations (angiomyolipoma associated with TSC. This review provides an overview of TSC, everolimus, and the clinical trials that led to its approval for the treatment of TSC-associated subependymal giant cell astrocytoma and renal angiomyolipoma. Keywords: everolimus, subependymal giant cell astrocytoma, angiomyolipomas, lymphangioleiomyomatosis, facial angiofibromas, tuberous sclerosis complex

  16. Hydrophobically associating terpolymer and its complex with a stabilizer in brine for enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Dong Lijian; Wang Biao [Scientific Research Inst. of Petroleum Exploration and Development, Beijing (China)

    1995-11-01

    This paper relates to tertiary recovery employing a polymer thickened aqueous drive fluid or mobility control fluid, more particularly, this paper relates to a novel type of thickening agent named AST agent for drive fluid composed of a hydrophobically associating terpolymer (PAAE) and a stabilizer (AN). AST thickening agent exhibits good thermal stability (at 100 C, thermal aging in 33,000 mg/l brine) and electrolytic tolerance (salinity ranging from 16,500 mg/l to 66,000 mg/l) and good resistance to shear relative to the conventional water-soluble polymers such as polyacrylamide, acrylamide/acrylic acid copolymer etc., and furthermore, AST agent has some surface activity. Many laboratory experiments have been shown that AST thickening agent could be considered as an advanced one in comparison with the conventional water-soluble polymers. Especially AST thickening agent is more suitable for a mobility control fluid in the hostile environment in subterranean formations such as in high salinity and high temperature formations.

  17. Genomic and phenotypic diversity of Listeria monocytogenes clonal complexes associated with human listeriosis.

    Science.gov (United States)

    Bergholz, Teresa M; Shah, Manoj K; Burall, Laurel S; Rakic-Martinez, Mira; Datta, Atin R

    2018-04-01

    Listeria monocytogenes is a pathogen of significant concern in many ready to eat foods due to its ability to survive and multiply even under significant environmental stresses. Listeriosis in humans is a concern, especially to high-risk populations such as those who are immunocompromised or pregnant, due to the high rates of morbidity and mortality. Whole genome sequencing has become a routine part of assessing L. monocytogenes isolated from patients, and the frequency of different genetic subtypes associated with listeriosis is now being reported. The recent abundance of genome sequences for L. monocytogenes has provided a wealth of information regarding the variation in core and accessory genomic elements. Newly described accessory genomic regions have been linked to greater virulence capabilities as well as greater resistance to environmental stressors such as sanitizers commonly used in food processing facilities. This review will provide a summary of our current understanding of stress response and virulence phenotypes of L. monocytogenes, within the context of the genetic diversity of the pathogen.

  18. Modelling of atmospheric dispersion in a complex medium and associated uncertainties

    International Nuclear Information System (INIS)

    Demael, Emmanuel

    2007-01-01

    This research thesis addresses the study of the digital modelling of atmospheric dispersions. It aimed at validating the Mercure-Saturne tool used with a RANS (Reynolds Averaged Navier-Stokes) approach within the frame of an impact study or of an accidental scenario on a nuclear site while taking buildings and ground relief into account, at comparing the Mercure-Saturne model with a more simple and less costly (in terms of computation time) Gaussian tool (the ADMS software, Atmospheric Dispersion Modelling System), and at quantifying uncertainties related to the use of the Mercure-Saturne model. The first part introduces theoretical elements of atmosphere physics and of the atmospheric dispersion in a boundary layer, presents the Gaussian model and the Mercure-Saturne tool and its associated RANS approach. The second part reports the comparison of the Mercure-Saturne model with conventional Gaussian plume models. The third part reports the study of the atmospheric flow and dispersion about the Bugey nuclear site, based on a study performed in a wind tunnel. The fourth part reports the same kind of study for the Flamanville site. The fifth part reports the use of different approaches for the study of uncertainties in the case of the Bugey site: application of the Morris method (a screening method), and of the Monte Carlo method (quantification of the uncertainty and of the sensitivity of each uncertainty source) [fr

  19. Biology of cancer and aging: a complex association with cellular senescence.

    Science.gov (United States)

    Falandry, Claire; Bonnefoy, Marc; Freyer, Gilles; Gilson, Eric

    2014-08-20

    Over the last 50 years, major improvements have been made in our understanding of the driving forces, both parallel and opposing, that lead to aging and cancer. Many theories on aging first proposed in the 1950s, including those associated with telomere biology, senescence, and adult stem-cell regulation, have since gained support from cumulative experimental evidence. These views suggest that the accumulation of mutations might be a common driver of both aging and cancer. Moreover, some tumor suppressor pathways lead to aging in line with the theory of antagonist pleiotropy. According to the evolutionary-selected disposable soma theory, aging should affect primarily somatic cells. At the cellular level, both intrinsic and extrinsic pathways regulate aging and senescence. However, increasing lines of evidence support the hypothesis that these driving forces might be regulated by evolutionary-conserved pathways that modulate energy balance. According to the hyperfunction theory, aging is a quasi-program favoring both age-related diseases and cancer that could be inhibited by the regulation of longevity pathways. This review summarizes these hypotheses, as well as the experimental data that have accumulated over the last 60 years linking aging and cancer.

  20. Soft-bottom macrobenthic faunal associations in the southern Chilean glacial fjord complex

    Directory of Open Access Journals (Sweden)

    Carlos Ríos

    2005-12-01

    Full Text Available Macrobenthic associations were investigated at 29 sampling stations with a semi-quantitative Agassiz trawl, ranging from the South Patagonian Icefield to the Straits of Magellan in the South Chilean fjord system. A total of 1,895 individuals belonging to 131 species were collected. 19 species belong to colonial organisms, mainly Bryozoa (17 species and Octocorallia (2 species. The phylum Echinodermata was the most diverse in species number (47 species, with asteroids (25 species and ophiuroids (13 species being the best represented within this taxon. Polychaeta was the second dominant group in terms of species richness (46 species. Multidimensional scaling ordination (MDS separated two station groups, one related to fjords and channels off the South Patagonian Icefield and the second one to stations surrounding the Straits of Magellan. 45 species account for 90% of the dissimilarity between these two groups. These differences can mainly be explained by the influence of local environmental conditions determined by processes closely related to the presence/absence of glaciers. Abiotic parameters such as water depth, type of sediment and chemical features of the superficial sediment were not correlated with the numbers of individuals caught by the Agassiz trawl in each group of sampling stations.

  1. Effects of habitat complexity on the structure of macrobenthic association in a Spartina altemiflora marsh

    Directory of Open Access Journals (Sweden)

    Maurea Nicoletti Flynn

    1996-01-01

    Full Text Available The structure and seasonal variability of macrobenthic associations in four different patches on a Sportillo alterniflora bed at Arrozal Point, Cananéia, São Paulo State are described and compared. In the local intertidal marsh, densities of S. oltemifloro plants appear in sparsely or denscly arranged patches, both in tall and short forms. The infaunal polychaetes Copitella copitata, Isolda pulchella, Laconereis acuta accounted for 44.0% of the total individuals while epifaunal forms such as Helcobia australis, Littorina ollngulifera, Tholozidium rhombofrotalis and Sphoeromopsis mourei were the second most abundant components with 39.5%. Classilication analyses of sampling time in the same sampling patch indicated that species groups were formed basically by spatial similarity and peak densities of macrofauna and secondarily by temporal patterns. Temporal variations were evident with higher number of species in eolder months (winter and spring. Species diversity and evenness did not show clear seasonal pattcrns, although they were sigmlicantly different in sampling patchcs and time. Heleobia australis, Littorina agulifera and Anomalocardia brasilienses were dominant in tall sparse S. alterniflora with density pcaks occurring in winter/spring pcriods. Tholozodium rhombofrontalis and Sphoeromopsis mourei; were dominant in short sparse S. olterniflora with density peaks in summer. In tall, densely distributed S. altemiflora plants the higher densities occurred in winter and the dominant spccies were Nereis oligohoalina, Isolda pulchella and Copitella capitata. The species H. australis, L ongulifera and A. brasiliensis predominated in the short S. alterniflora plants denscly distributed, with faunistic peaks recorded in spring. The results suggcst that differenccs in form and aggregation of S. alternifloraimpart changes in the structure of macrobenthic fauna associated to this vegetation.A estrutura e variação temporal de associações macrobent

  2. The medical-industrial complex, professional medical associations, and continuing medical education.

    Science.gov (United States)

    Schofferman, Jerome

    2011-12-01

    Financial relationships among the biomedical industries, physicians, and professional medical associations (PMAs) can be professional, ethical, mutually beneficial, and, most importantly, can lead to improved medical care. However, such relationships, by their very nature, present conflicts of interest (COIs). One of the greatest concerns regarding COI is continuing medical education (CME), especially because currently industry funds 40-60% of CME. COIs have the potential to bias physicians in practice, educators, and those in leadership positions of PMAs and well as the staff of a PMA. These conflicts lead to the potential to bias the content and type of CME presentations and thereby influence physicians' practice patterns and patient care. Physicians are generally aware of the potential for bias when industry contributes funding for CME, but they are most often unable to detect the bias. This may because it is very subtle and/or the educators themselves may not realize that they have been influenced by their relationships with industry. Following Accreditation Council for Continuing Medical Education guidelines and mandating disclosure that is transparent and complete have become the fallback positions to manage COIs, but such disclosure does not really mitigate the conflict. The eventual and best solutions to ensure evidence-based education are complete divestment by educators and leaders of PMAs, minimal and highly controlled industry funding of PMAs, blind pooling of any industry contributions to PMAs and CME, strict verification of disclosures, clear separation of marketing from education at CME events, and strict oversight of presentations for the presence of bias. Wiley Periodicals, Inc.

  3. Modelling stable water isotopes: Status and perspectives

    Directory of Open Access Journals (Sweden)

    Werner M.

    2010-12-01

    Full Text Available Modelling of stable water isotopes H2 18O and HDO within various parts of the Earth’s hydrological cycle has clearly improved our understanding of the interplay between climatic variations and related isotope fractionation processes. In this article key principles and major research results of stable water isotope modelling studies are described. Emphasis is put on research work using explicit isotope diagnostics within general circulation models as this highly complex model setup bears many resemblances with studies using simpler isotope modelling approaches.

  4. A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder.

    Science.gov (United States)

    Xie, Zengyan; Yang, Xianyan; Deng, Xiaoya; Ma, Mingyue; Shu, Kunxian

    2017-12-19

    Bipolar disorder is a common and severe mental illness with unsolved pathophysiology. A genome-wide association study (GWAS) has been used to find a number of risk genes, but it is difficult for a GWAS to find genes indirectly associated with a disease. To find core hub genes, we introduce a network analysis after the GWAS was conducted. Six thousand four hundred fifty eight single nucleotide polymorphisms (SNPs) with p sifted out from Wellcome Trust Case Control Consortium (WTCCC) dataset and mapped to 2045 genes, which are then compared with the protein-protein network. One hundred twelve genes with a degree >17 were chosen as hub genes from which five significant modules and four core hub genes ( FBXL13 , WDFY2 , bFGF , and MTHFD1L ) were found. These core hub genes have not been reported to be directly associated with BD but may function by interacting with genes directly related to BD. Our method engenders new thoughts on finding genes indirectly associated with, but important for, complex diseases.

  5. A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Zengyan Xie

    2017-12-01

    Full Text Available Bipolar disorder is a common and severe mental illness with unsolved pathophysiology. A genome-wide association study (GWAS has been used to find a number of risk genes, but it is difficult for a GWAS to find genes indirectly associated with a disease. To find core hub genes, we introduce a network analysis after the GWAS was conducted. Six thousand four hundred fifty eight single nucleotide polymorphisms (SNPs with p < 0.01 were sifted out from Wellcome Trust Case Control Consortium (WTCCC dataset and mapped to 2045 genes, which are then compared with the protein–protein network. One hundred twelve genes with a degree >17 were chosen as hub genes from which five significant modules and four core hub genes (FBXL13, WDFY2, bFGF, and MTHFD1L were found. These core hub genes have not been reported to be directly associated with BD but may function by interacting with genes directly related to BD. Our method engenders new thoughts on finding genes indirectly associated with, but important for, complex diseases.

  6. The potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex via alpha-syntrophin in glia.

    Science.gov (United States)

    Connors, Nathan C; Adams, Marvin E; Froehner, Stanley C; Kofuji, Paulo

    2004-07-02

    One of the major physiological roles of potassium channels in glial cells is to promote "potassium spatial buffering" in the central nervous system, a process necessary to maintain an optimal potassium concentration in the extracellular environment. This process requires the precise distribution of potassium channels accumulated at high density in discrete subdomains of glial cell membranes. To obtain a better understanding of how glial cells selectively target potassium channels to discrete membrane subdomains, we addressed the question of whether the glial inwardly rectifying potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex (DGC). Immunoprecipitation experiments revealed that Kir4.1 is associated with the DGC in mouse brain and cultured cortical astrocytes. In vitro immunoprecipitation and pull-down assays demonstrated that Kir4.1 can bind directly to alpha-syntrophin, requiring the presence of the last three amino acids of the channel (SNV), a consensus PDZ domain-binding motif. Furthermore, Kir4.1 failed to associate with the DGC in brains from alpha-syntrophin knockout mice. These results suggest that Kir4.1 is localized in glial cells by its association with the DGC through a PDZ domain-mediated interaction with alpha-syntrophin and suggest an important role for the DGC in central nervous system physiology.

  7. Oligomerization of ethylene catalysed by nickel complexes associated with nitrogen ligands in ionic liquids; Oligomerisation de l'ethylene catalysee par des complexes du nickel associes a des ligands azotes dans les liquides ioniques

    Energy Technology Data Exchange (ETDEWEB)

    Lecocq, V.

    2003-09-01

    We report here the use of a new class of catalytic systems based on a nickel active center associated with nitrogen ligands, such as di-imines, or imino-pyridines, for the oligomerization of ethylene in a biphasic medium using ionic liquids as the catalyst solvent. The nickel catalyst is immobilized in the ionic liquid phase in which the olefinic reaction products are poorly miscible. This biphasic system makes possible an easy separation and recycle of the catalyst. Numerous di-imine and imino-pyridine ligands with different steric and electronic properties have been synthesized and their corresponding nickel complexes isolated and characterized. Different ionic liquids, based on chloro-aluminates or non-chloro-aluminates anions, have also been prepared and characterized. The effect of the nature of the ligand, the ionic liquid, the nickel precursor and its mode of activation have been studied and correlated with the selectivity and activity of the transformation of ethylene. (author)

  8. Multistep Redox Sequences of Azopyridyl (L) Bridged Reaction Centres in Stable Radical Complex Ions {(.mu.-L)[MCl(.eta.5-C5Me5)]2}.+, M = Rh or Ir: Spectroelectrochemistry and High-frequency EPR Spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Frantz, S.; Reinhardt, R.; Greulich, S.; Wanner, M.; Fiedler, Jan; Duboc-Toia, C.; Kaim, W.

    č. 18 (2003), s. 3370-3375 ISSN 1477-9226 R&D Projects: GA ČR GA203/03/0821; GA MŠk OC D15.10 Institutional research plan: CEZ:AV0Z4040901 Keywords : EPR spectroscopy * radical complex ions Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.908, year: 2003

  9. The prevalence at birth of congenital malformations in the city of Ozyorsk located near the nuclear complex Mayak production association

    International Nuclear Information System (INIS)

    Petrushkina, N. P.; Koshurnikova, N. A.; Okatenko, P. V.

    2004-01-01

    For many years possible genetic effects of exposure to ionizing radiation have been a subject of interest and concern, but data from studies of the risk of radiation-induced hereditary effects in humans are limited. the most extensive human studies of genetic effects were those conducted on the Japanese. A-bomb survivors. In These studies in investigators examined the association of various levels of radiation exposure and several different endpoints, including major congenital defects, stillbirth, death during the first week of life, survivals, and sex ratio and Down's syndrome (8, (14-16). Although associations of these outcomes with radiation exposure were in the positive direction, none were close to statistical significance. Only teratogenic effects of in utero exposure at Hiroshima and Nagasaki, microcephaly and mental retardation, have been observed (8, (10, 16)). Of most interest is possible association of congenital malformations (CMs) with parental occupational radiation exposure. Determination of the role of parental occupational exposure in induction of CMs in children is necessary to evaluate reliability of radiation protection standards Epidemiological studies conducted on the basis of Registries of children who were born in regions located near a nuclear complex may be useful for such evaluation. It is preferable to carry out such studies on the basis of population registries, since long follow-up in large populations allows to reveal increased frequency of even very rare forms of congenital abnormalities. In a case-control study of association of parental occupational exposure due to Hanford Nuclear Site and risk of CMs in their offspring there was no evidence of such an association (12, 13). Our investigation is conducted on the basis of the basis of the Registry of children of Ozyorsk. The whole Registry includes all children with 1948-1988 birth years show were born or-came to town at the age of 0-14 years, and were residents of these towns one

  10. Formulation of stable protein powders by supercritical fluid drying

    NARCIS (Netherlands)

    Jovanović, N.

    2007-01-01

    Protein pharmaceuticals are potent drugs for the treatment of several chronic and life-threatening diseases. However, the complex and sensitive nature of protein molecules requires special attention in the development of stable dosage forms. Developing stable aqueous protein formulations is often a

  11. First-trimester prenatal sonographic findings associated with OEIS (omphalocele-exstrophy-imperforate anus-spinal defects) complex: a case and review of the literature.

    Science.gov (United States)

    Girz, B A; Sherer, D M; Atkin, J; Venanzi, M; Ahlborn, L; Cestone, L

    1998-01-01

    First-trimester sonographic findings associated with omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex and review of the literature regarding this rare congenital anomaly are presented.

  12. Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

    Science.gov (United States)

    Rutten, Bert; Tersteeg, Claudia; Vrijenhoek, Joyce E P; van Holten, Thijs C; Elsenberg, Ellen H A M; Mak-Nienhuis, Elske M; de Borst, Gert Jan; Jukema, J Wouter; Pijls, Nico H J; Waltenberger, Johannes; van Zonneveld, Anton Jan; Moll, Frans L; McClellan, Elizabeth; Stubbs, Andrew; Pasterkamp, Gerard; Hoefer, Imo; de Groot, Philip G; Roest, Mark

    2014-01-01

    Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation. Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

  13. Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

    Directory of Open Access Journals (Sweden)

    Bert Rutten

    Full Text Available Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs and macrophages in human atherosclerotic carotid plaques.Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP, in two independent cohorts: the Circulating Cells cohort (n = 244 and the Athero-Express cohort (n = 91. Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort. Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort.We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range: 4153 (1585-11267 area under the curve (AUC vs. 9633 (3580-21565 AUC, P<0.001. Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02. All associations remained significant after adjustment for age, sex and use of drugs against platelet activation.Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

  14. IASP diagnostic criteria for complex regional pain syndrome: a preliminary empirical validation study. International Association for the Study of Pain.

    Science.gov (United States)

    Galer, B S; Bruehl, S; Harden, R N

    1998-03-01

    To assess the ability of the International Association for the Study of Pain Complex Regional Pain Syndrome (CRPS) diagnostic criteria and associated features to discriminate between CRPS patients and patients with painful diabetic neuropathy. Prospective assessment of signs and symptoms in a series of CRPS and diabetic neuropathy patients. University of Washington Multidisciplinary Pain Center. A consecutive series of 18 CRPS patients and 30 diabetic neuropathy patients. Patients completed a 10-item patient history questionnaire assessing symptoms of CRPS prior to medical evaluation. The evaluating physician completed a 10-item patient examination questionnaire assessing objective signs of CRPS. The analyses conducted were designed to test the ability of CRPS signs and symptoms and associated features to discriminate between CRPS patients and diabetic neuropathy patients. Data analysis suggested that CRPS decision rules may lead to overdiagnosis of the disorder. Diagnosis based on self-reported symptoms can be diagnostically useful in some circumstances. The addition of trophic tissue changes, range of motion changes, and "burning" quality of pain did not improve diagnostic accuracy, but the addition of motor neglect signs did. Test of a CRPS scoring system resulted in improved accuracy relative to current criteria and decision rules. Poorly understood disorders lacking prototypical signs/symptoms and diagnostic laboratory testing must rely on the development of reliable diagnostic guidelines. The results of this study should assist in the further refinement of the CRPS diagnostic criteria.

  15. Association of early onset myasthenia gravis in Newfoundland dogs with the canine major histocompatibility complex class I.

    Science.gov (United States)

    Wolf, Zena; Vernau, Karen; Safra, Noa; Shelton, G Diane; King, Jason; Owen, Joseph; Weich, Kalie; Bannasch, Danika

    2017-05-01

    Acquired Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder whose development in humans has been associated with the Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA). There is a form of early onset MG (EOMG) in Newfoundland dogs that mimics the clinical presentation in humans and appears to have familial inheritance. Genotyping of three classical Dog Leukocyte Antigen (DLA) class II genes, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in 16 Newfoundlands with EOMG and 46 unaffected Newfoundlands, identified DLA-DQB1 *00301 (p-value = 0.0051 OR: 7.41) as a risk locus for the development of EOMG in this breed. In order to further investigate the extent of the association to the entire MHC region, 208 additional SNPs were genotyped in two phases. Both a risk locus for EOMG to the DLA class I (chr12: 458483-506460) and a protective locus for EOMG susceptibility that extends outside of the DLA class I (chr12: 89701-475348) were identified. Four additional dog breeds with an elevated risk for the development of MG were SNP genotyped, but no shared or significant associations were found. MHC involvement in canine MG disease manifestation overlaps with loci identified in human studies and highlights the value of dogs as a model for genetic studies of naturally occurring diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Regression-based approach for testing the association between multi-region haplotype configuration and complex trait

    Directory of Open Access Journals (Sweden)

    Zhao Hongbo

    2009-09-01

    Full Text Available Abstract Background It is quite common that the genetic architecture of complex traits involves many genes and their interactions. Therefore, dealing with multiple unlinked genomic regions simultaneously is desirable. Results In this paper we develop a regression-based approach to assess the interactions of haplotypes that belong to different unlinked regions, and we use score statistics to test the null hypothesis of non-genetic association. Additionally, multiple marker combinations at each unlinked region are considered. The multiple tests are settled via the minP approach. The P value of the "best" multi-region multi-marker configuration is corrected via Monte-Carlo simulations. Through simulation studies, we assess the performance of the proposed approach and demonstrate its validity and power in testing for haplotype interaction association. Conclusion Our simulations showed that, for binary trait without covariates, our proposed methods prove to be equal and even more powerful than htr and hapcc which are part of the FAMHAP program. Additionally, our model can be applied to a wider variety of traits and allow adjustment for other covariates. To test the validity, our methods are applied to analyze the association between four unlinked candidate genes and pig meat quality.

  17. Molecular Gas toward the Gemini OB1 Molecular Cloud Complex. II. CO Outflow Candidates with Possible WISE Associations

    Science.gov (United States)

    Li, Yingjie; Li, Fa-Cheng; Xu, Ye; Wang, Chen; Du, Xin-Yu; Yang, Wenjin; Yang, Ji

    2018-03-01

    We present a large-scale survey of CO outflows in the Gem OB1 molecular cloud complex and its surroundings, using the Purple Mountain Observatory Delingha 13.7 m telescope. A total of 198 outflow candidates were identified over a large area (∼58.5 square degrees), of which 193 are newly detected. Approximately 68% (134/198) are associated with the Gem OB1 molecular cloud complex, including clouds GGMC 1, GGMC 2, BFS 52, GGMC 3, and GGMC 4. Other regions studied are: the Local arm (Local Lynds, West Front), Swallow, Horn, and Remote cloud. Outflow candidates in GGMC 1, BFS 52, and Swallow are mainly located at ring-like or filamentary structures. To avoid excessive uncertainty in distant regions (≳3.8 kpc), we only estimated the physical parameters for clouds in the Gem OB1 molecular cloud complex and in the Local arm. In those clouds, the total kinetic energy and the energy injection rate of the identified outflow candidates are ≲1% and ≲3% of the turbulent energy and the turbulent dissipation rate of each cloud, indicating that the identified outflow candidates cannot provide enough energy to balance turbulence of their host cloud at the scale of the entire cloud (several to dozens of parsecs). The gravitational binding energy of each cloud is ≳135 times the total kinetic energy of the identified outflow candidates within the corresponding cloud, indicating that the identified outflow candidates cannot cause major disruptions to the integrity of their host cloud at the scale of the entire cloud.

  18. Late extensional shear zones and associated recumbent folds in the Alpujarride subduction complex, Betic Cordillera, southern Spain

    International Nuclear Information System (INIS)

    Orozco, M.; Alonso-Chaves, F.; Platt, J.

    2017-01-01

    The existence in the Alpujarride Complex (Betic Cordillera, southern Spain) of a relatively continuous extensional event (following crustal thickening) is based on detailed structural studies and is consistent with the P-T paths and geochronological data established for the Alpujarride rocks. According to our research, the Alpujarride Complex contains two large-scale shear zones accommodating early Miocene extension. The shear zones contain km-scale recumbent folds, some with sheath fold geometry, and megaboudinage structures, and are closely associated with detachment faults. Large-scale folds and boudins cause dome-like undulations in the detachments, which are inferred to overlap in time with the deformation in the shear zones. One shear zone in the eastern part of the orogen is top-N; the other, in the western part, is top-E. The change in the shear direction may represent a temporal evolution in the direction of shear, possibly related to a change in the subduction direction in space and time.

  19. Membrane association of the PTEN tumor suppressor: neutron scattering and MD simulations reveal the structure of protein-membrane complexes.

    Science.gov (United States)

    Nanda, Hirsh; Heinrich, Frank; Lösche, Mathias

    2015-05-01

    Neutron reflection (NR) from planar interfaces is an emerging technology that provides unique and otherwise inaccessible structural information on disordered molecular systems such as membrane proteins associated with fluid bilayers, thus addressing one of the remaining challenges of structural biology. Although intrinsically a low-resolution technique, using structural information from crystallography or NMR allows the construction of NR models that describe the architecture of protein-membrane complexes at high resolution. In addition, a combination of these methods with molecular dynamics (MD) simulations has the potential to reveal the dynamics of protein interactions with the bilayer in atomistic detail. We review recent advances in this area by discussing the application of these techniques to the complex formed by the PTEN phosphatase with the plasma membrane. These studies provide insights in the cellular regulation of PTEN, its interaction with PI(4,5)P2 in the inner plasma membrane and the pathway by which its substrate, PI(3,4,5)P3, accesses the PTEN catalytic site. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Late extensional shear zones and associated recumbent folds in the Alpujarride subduction complex, Betic Cordillera, southern Spain

    Energy Technology Data Exchange (ETDEWEB)

    Orozco, M.; Alonso-Chaves, F.; Platt, J.

    2017-11-01

    The existence in the Alpujarride Complex (Betic Cordillera, southern Spain) of a relatively continuous extensional event (following crustal thickening) is based on detailed structural studies and is consistent with the P-T paths and geochronological data established for the Alpujarride rocks. According to our research, the Alpujarride Complex contains two large-scale shear zones accommodating early Miocene extension. The shear zones contain km-scale recumbent folds, some with sheath fold geometry, and megaboudinage structures, and are closely associated with detachment faults. Large-scale folds and boudins cause dome-like undulations in the detachments, which are inferred to overlap in time with the deformation in the shear zones. One shear zone in the eastern part of the orogen is top-N; the other, in the western part, is top-E. The change in the shear direction may represent a temporal evolution in the direction of shear, possibly related to a change in the subduction direction in space and time.

  1. Study of the Formulation and Preparation of Chewable Tablets With a Calcium Complex Association and Vitamin D3

    Directory of Open Access Journals (Sweden)

    Emma Creţu

    2010-06-01

    Full Text Available The experimental study objective was the development of
    chewable tablets with the calcium complex association, the minerals and vitamin D3 for children, subject to the rules as stipulated by the Romanian Pharmacopoeia Xth edition. Generating sources of calcium, used as raw materials in the preparation of these tablets are natural products represented by complex mineral rich in calcium - Lactoval (R HiCal (ratio of calcium and phosphorus is 2,2:1, report the same as breast milk and 30% bovine colostrums [1, 3], making the absorption of calcium should be increased. Also, in order to
    fix and better absorb calcium in the body was added to make the preparation of these chewable tablets and vitamin D3.
    Was chosen as a method of preparing direct compression. Excipients for direct compression are diluents-binder-disaggregated. They are unitary excipients or co-processed products, multi-processed excipients together to meet those properties: microcrystalline cellulose (Vivapur 102 Ludipress, lactose (Tablettose 80, Kollidon CL Isomalt DC 100. Was also added to a lubricant (magnesium stearate and sweetener and flavoring to carry out the preparation of tablets and after 30 days as provided Romanian Pharmacopoeia Xth and its 2001 supplement, which comprises: organoleptic control, uniformity of weight, strength, disintegration and their friability. Working method chosen and make the appropriate choice leads to tablets in terms of quality standards officinal.

  2. Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave-T complex).

    Science.gov (United States)

    Bruneau, N; Roux, S; Adrien, J L; Barthélémy, C

    1999-11-01

    Auditory processing at the cortical level was investigated with late auditory evoked potentials (N1 wave-T complex) in 4-8-year-old autistic children with mental retardation and compared to both age-matched normal and mentally retarded children (16 children in each group). Two negative peaks which occurred in the 80-200 ms latency range were analyzed according to stimulus intensity level (50 to 80 dB SPL): the first culminated at fronto-central sites (N1b) and the second at bitemporal sites (N1c, equivalent to Tb of the T complex). The latter wave was the most prominent and reliable response in normal children at this age. Our results in autistic children indicated abnormalities of this wave with markedly smaller amplitude at bitemporal sites and pronounced peak latency delay (around 20 ms). Moreover, in both reference groups the intensity effect was found on both sides whereas in autistic children it was absent on the left side but present on the right. These findings in autistic children showing very disturbed verbal communication argue for dysfunction in brain areas involved in N1c generation i.e., the auditory associative cortex in the lateral part of the superior temporal gyrus, with more specific left side defects when auditory stimulus have to be processed.

  3. Variations in the radiation sensitivity of foodborne pathogens associated with complex ready-to-eat food products

    International Nuclear Information System (INIS)

    Sommers, Christopher H.; Boyd, Glenn

    2006-01-01

    Foodborne illness outbreaks and product recalls are occasionally associated with ready-to-eat (RTE) sandwiches and other 'heat and eat' multi-component RTE products. Ionizing radiation can inactivate foodborne pathogens on meat and poultry, fruits and vegetables, seafood, and RTE meat products. However, less data are available on the ability of low-dose ionizing radiation, doses under 5 kGy typically used for pasteurization purposes, to inactivate pathogenic bacteria on complex multi-component food products. In this study, the efficacy of ionizing radiation to inactivate Salmonella spp., Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, and Yersinia enterocolitica on RTE foods including a 'frankfurter on a roll', a 'beef cheeseburger on a bun' and a 'vegetarian cheeseburger on a bun' was investigated. The average D-10 values, the radiation dose needed to inactivate 1 log 1 of pathogen, by bacterium species, were 0.61, 0.54, 0.47, 0.36 and 0.15 kGy for Salmonella spp., S. aureus, L. monocytogenes, E. coli O157:H7, and Y. enterocolitica, respectively when inoculated onto the three product types. These results indicate that irradiation may be an effective means for inactivating common foodborne pathogens including Salmonella spp, S. aureus, L. monocytogenes, E. coli O157:H7 and Y. enterocolitica in complex RTE food products such as 'heat and eat' sandwich products

  4. The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences.

    Science.gov (United States)

    Smith, R H; Spano, A J; Kotin, R M

    1997-06-01

    The Rep78 and Rep68 proteins of adeno-associated virus (AAV) are replication initiator proteins that bind the viral replicative-form origin of replication, nick the origin in a site- and strand-specific fashion, and mediate vectorial unwinding of the DNA duplex via an ATP-dependent helicase activity, thus initiating a strand displacement mechanism of viral DNA replication. Genetic and biochemical studies have identified Rep mutants that demonstrate a trans-dominant negative phenotype in vitro and in vivo, suggesting the possibility that multimerization of Rep is essential for certain replicative functions. In this study, we have investigated the ability of the largest of the Rep proteins, Rep78, to self-associate in vitro and in vivo. Self-association of Rep78 in vivo was demonstrated through the use of a mammalian two-hybrid system. Rep-Rep protein interaction was confirmed in vitro through coimmunoprecipitation experiments with a bacterially expressed maltose-binding protein-Rep78 fusion protein in combination with [35S]methionine-labeled Rep78 synthesized in a coupled in vitro transcription-translation system. Mapping studies with N- and C-terminal truncation mutant forms of Rep indicate that amino acid sequences required for maximal self-association occur between residues 164 and 484. Site-directed mutagenesis identified two essential motifs within this 321-amino-acid region: (i) a putative alpha-helix bearing a 3,4-hydrophobic heptad repeat reminiscent of those found in coiled-coil domains and (ii) a previously recognized nucleoside triphosphate-binding motif. Deletion of either of these regions from the full-length polypeptide resulted in severe impairment of Rep-Rep interaction. In addition, gel filtration chromatography and protein cross-linking experiments indicated that Rep78 forms a hexameric complex in the presence of AAV ori sequences.

  5. MDM2 Associates with Polycomb Repressor Complex 2 and Enhances Stemness-Promoting Chromatin Modifications Independent of p53

    DEFF Research Database (Denmark)

    Wienken, Magdalena; Dickmanns, Antje; Nemajerova, Alice

    2016-01-01

    in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the MDM2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. MDM2 physically...... associated with EZH2 on chromatin, enhancing the trimethylation of histone 3 at lysine 27 and the ubiquitination of histone 2A at lysine 119 (H2AK119) at its target genes. Removing MDM2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell...... proliferation. In conclusion, MDM2 supports the Polycomb-mediated repression of lineage-specific genes, independent of p53....

  6. Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis

    Directory of Open Access Journals (Sweden)

    Ming-Fa Liu

    2015-01-01

    Full Text Available Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT and preoperative urine samples (Preop-1d urine. Activity was reduced by seven days after surgery (Postop-1w urine and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients.

  7. The Stable Diiron (2.5) Complex Ion [(NC).sub.5./sub.Fe(ć-tz)Fe(CN).sub.5./sub.].sup.5-./sup., tz=1,2,4,5-Tetrazine, and Its Neighboring Oxidation States

    Czech Academy of Sciences Publication Activity Database

    Glöckle, M.; Kaim, W.; Klein, A.; Roduner, E.; Hübner, G.; Záliš, Stanislav; Slageren van, J.; Renz, F.; Gütlich, P.

    2001-01-01

    Roč. 40, č. 10 (2001), s. 2256-2262 ISSN 0020-1669 R&D Projects: GA MŠk OC D14.20; GA MŠk OC D15.10 Institutional research plan: CEZ:AV0Z4040901 Keywords : mixed valent compound * diiron tetrazine complex * spectroelectrochemistry Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.946, year: 2001

  8. Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen.

    Science.gov (United States)

    Moriwaki, Hiroki; Resch, Daniel; Li, Hengguang; Ojima, Iwao; Takeda, Ryosuke; Aceña, José Luis; Soloshonok, Vadim A

    2014-01-01

    A family of chiral ligands derived from α-phenylethylamine and 2-aminobenzophenone were prepared by alkylation of the nitrogen atom. Upon reaction with glycine and a Ni(II) salt, these ligands were transformed into diastereomeric complexes, as a result of the configurational stability of the stereogenic nitrogen atom. Different diastereomeric ratios were observed depending on the substituent R introduced in the starting ligand, and stereochemical assignments were based on X-ray analysis, along with NMR studies and optical rotation measurements.

  9. The GIP gamma-tubulin complex-associated proteins are involved in nuclear architecture in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Morgane eBatzenschlager

    2013-11-01

    Full Text Available During interphase, the microtubular cytoskeleton of cycling plant cells is organized in both cortical and perinuclear arrays. Perinuclear microtubules (MTs are nucleated from γ-Tubulin Complexes (γ-TuCs located at the surface of the nucleus. The molecular mechanisms of γ-TuC association to the nuclear envelope are currently unknown. The γ-TuC Protein 3 (GCP3-Interacting Protein 1 (GIP1 is the smallest γ-TuC component identified so far. AtGIP1 and its homologous protein AtGIP2 participate in the localization of active γ-TuCs at interphasic and mitotic MT nucleation sites. Arabidopsis gip1gip2 mutants are impaired in establishing a fully functional mitotic spindle and exhibit severe developmental defects.In this study, gip1gip2 knock down mutants were further characterized at the cellular level. In addition to defects in both the localization of γ-TuC core proteins and MT fibre robustness, gip1gip2 mutants exhibited a severe alteration of the nuclear shape associated with an abnormal distribution of the nuclear pore complexes. Simultaneously, they showed a misorganization of the inner nuclear membrane protein AtSUN1. Furthermore, AtGIP1 was identified as an interacting partner of AtTSA1 which was detected, like the AtGIP proteins, at the nuclear envelope.These results provide the first evidence for the involvement of a γ-TuC component in both nuclear shaping and nuclear envelope organization. Functional hypotheses are discussed in order to propose a model for a GIP-dependent nucleo-cytoplasmic continuum.

  10. Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

    Science.gov (United States)

    Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza

    2016-11-01

    We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Marginally Stable Nuclear Burning

    Science.gov (United States)

    Strohmayer, Tod E.; Altamirano, D.

    2012-01-01

    Thermonuclear X-ray bursts result from unstable nuclear burning of the material accreted on neutron stars in some low mass X-ray binaries (LMXBs). Theory predicts that close to the boundary of stability oscillatory burning can occur. This marginally stable regime has so far been identified in only a small number of sources. We present Rossi X-ray Timing Explorer (RXTE) observations of the bursting, high- inclination LMXB 4U 1323-619 that reveal for the first time in this source the signature of marginally stable burning. The source was observed during two successive RXTE orbits for approximately 5 ksec beginning at 10:14:01 UTC on March 28, 2011. Significant mHz quasi- periodic oscillations (QPO) at a frequency of 8.1 mHz are detected for approximately 1600 s from the beginning of the observation until the occurrence of a thermonuclear X-ray burst at 10:42:22 UTC. The mHz oscillations are not detected following the X-ray burst. The average fractional rms amplitude of the mHz QPOs is 6.4% (3 - 20 keV), and the amplitude increases to about 8% below 10 keV.This phenomenology is strikingly similar to that seen in the LMXB 4U 1636-53. Indeed, the frequency of the mHz QPOs in 4U 1323-619 prior to the X-ray burst is very similar to the transition frequency between mHz QPO and bursts found in 4U 1636-53 by Altamirano et al. (2008). These results strongly suggest that the observed QPOs in 4U 1323-619 are, like those in 4U 1636-53, due to marginally stable nuclear burning. We also explore the dependence of the energy spectrum on the oscillation phase, and we place the present observations within the context of the spectral evolution of the accretion-powered flux from the source.

  12. Synthesis and stereochemical assignments of diastereomeric Ni(II complexes of glycine Schiff base with (R-2-(N-{2-[N-alkyl-N-(1-phenylethylamino]acetyl}aminobenzophenone; a case of configurationally stable stereogenic nitrogen

    Directory of Open Access Journals (Sweden)

    Hiroki Moriwaki

    2014-02-01

    Full Text Available A family of chiral ligands derived from α-phenylethylamine and 2-aminobenzophenone were prepared by alkylation of the nitrogen atom. Upon reaction with glycine and a Ni(II salt, these ligands were transformed into diastereomeric complexes, as a result of the configurational stability of the stereogenic nitrogen atom. Different diastereomeric ratios were observed depending on the substituent R introduced in the starting ligand, and stereochemical assignments were based on X-ray analysis, along with NMR studies and optical rotation measurements.

  13. Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits

    Directory of Open Access Journals (Sweden)

    Michael F. Wangler

    2017-02-01

    Full Text Available Human genome-wide association studies (GWAS have successfully identified thousands of susceptibility loci for common diseases with complex genetic etiologies. Although the susceptibility variants identified by GWAS usually have only modest effects on individual disease risk, they contribute to a substantial burden of trait variation in the overall population. GWAS also offer valuable clues to disease mechanisms that have long proven to be elusive. These insights could lead the way to breakthrough treatments; however, several challenges hinder progress, making innovative approaches to accelerate the follow-up of results from GWAS an urgent priority. Here, we discuss the largely untapped potential of the fruit fly, Drosophila melanogaster, for functional investigation of findings from human GWAS. We highlight selected examples where strong genomic conservation with humans along with the rapid and powerful genetic tools available for flies have already facilitated fine mapping of association signals, elucidated gene mechanisms, and revealed novel disease-relevant biology. We emphasize current research opportunities in this rapidly advancing field, and present bioinformatic analyses that systematically explore the applicability of Drosophila for interrogation of susceptibility signals implicated in more than 1000 human traits, based on all GWAS completed to date. Thus, our discussion is targeted at both human geneticists seeking innovative strategies for experimental validation of findings from GWAS, as well as the Drosophila research community, by whom ongoing investigations of the implicated genes will powerfully inform our understanding of human disease.

  14. A Complex Network of MicroRNAs Expressed in Brain and Genes Associated with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Santosh Shinde

    2013-01-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a rare neurological disease affecting mainly motor neurons and often leads to paralysis and death in extreme cases. For exploring the role of microRNAs in genes regulation in ALS disease, miRanda was employed for prediction of target sites of miRNAs expressed in various parts of brain and CNS on 35 genes associated with ALS. Similar search was conducted using TargetScan and PicTar for prediction of target sites in 3′ UTR only. 1456 target sites were predicted using miRanda and more target sites were found in 5′ UTR and CDS region as compared to 3′ UTR. 11 target sites were predicted to be common by all the algorithms and, thus, these represent the most significant sites. Target site hotspots were identified and were recognized as hotspots for multiple miRNAs action, thus, acting as favoured sites of action for the repression of gene expression. The complex interplay of genes and miRNAs brought about by multiplicity and cooperativity was explored. This investigation will aid in elucidating the mechanism of action of miRNAs for the considered genes. The intrinsic network of miRNAs expressed in nervous system and genes associated with ALS may provide rapid and effective outcome for therapeutic applications and diagnosis.

  15. A geographic distribution database of the Neotropical cassava whitefly complex (Hemiptera, Aleyrodidae) and their associated parasitoids and hyperparasitoids (Hymenoptera).

    Science.gov (United States)

    Vásquez-Ordóñez, Aymer Andrés; Hazzi, Nicolas A; Escobar-Prieto, David; Paz-Jojoa, Dario; Parsa, Soroush

    2015-01-01

    Whiteflies (Hemiptera, Aleyrodidae) are represented by more than 1,500 herbivorous species around the world. Some of them are notorious pests of cassava (Manihot esculenta), a primary food crop in the tropics. Particularly destructive is a complex of Neotropical cassava whiteflies whose distribution remains restricted to their native range. Despite their importance, neither their distribution, nor that of their associated parasitoids, is well documented. This paper therefore reports observational and specimen-based occurrence records of Neotropical cassava whiteflies and their associated parasitoids and hyperparasitoids. The dataset consists of 1,311 distribution records documented by the International Center for Tropical Agriculture (CIAT) between 1975 and 2012. The specimens are held at CIAT's Arthropod Reference Collection (CIATARC, Cali, Colombia). Eleven species of whiteflies, 14 species of parasitoids and one species of hyperparasitoids are reported. Approximately 66% of the whitefly records belong to Aleurotrachelus socialis and 16% to Bemisia tuberculata. The parasitoids with most records are Encarsia hispida, Amitus macgowni and Encarsia bellottii for Aleurotrachelus socialis; and Encarsia sophia for Bemisia tuberculata. The complete dataset is available in Darwin Core Archive format via the Global Biodiversity Information Facility (GBIF).

  16. Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits

    Science.gov (United States)

    Wangler, Michael F.; Hu, Yanhui

    2017-01-01

    ABSTRACT Human genome-wide association studies (GWAS) have successfully identified thousands of susceptibility loci for common diseases with complex genetic etiologies. Although the susceptibility variants identified by GWAS usually have only modest effects on individual disease risk, they contribute to a substantial burden of trait variation in the overall population. GWAS also offer valuable clues to disease mechanisms that have long proven to be elusive. These insights could lead the way to breakthrough treatments; however, several challenges hinder progress, making innovative approaches to accelerate the follow-up of results from GWAS an urgent priority. Here, we discuss the largely untapped potential of the fruit fly, Drosophila melanogaster, for functional investigation of findings from human GWAS. We highlight selected examples where strong genomic conservation with humans along with the rapid and powerful genetic tools available for flies have already facilitated fine mapping of association signals, elucidated gene mechanisms, and revealed novel disease-relevant biology. We emphasize current research opportunities in this rapidly advancing field, and present bioinformatic analyses that systematically explore the applicability of Drosophila for interrogation of susceptibility signals implicated in more than 1000 human traits, based on all GWAS completed to date. Thus, our discussion is targeted at both human geneticists seeking innovative strategies for experimental validation of findings from GWAS, as well as the Drosophila research community, by whom ongoing investigations of the implicated genes will powerfully inform our understanding of human disease. PMID:28151408

  17. Association Between Major Histocompatibility Complex Class I Chain-Related Gene Polymorphisms and Susceptibility of Systemic Lupus Erythematosus.

    Science.gov (United States)

    Yu, Ping; Zhu, Quan; Chen, Chunjing; Fu, Xiaoling; Li, Yu; Liu, Limin; Luo, Qizhi; Wang, Fuyan; Wang, Yong

    2017-10-01

    Major histocompatibility complex class I chain-related gene (MIC) polymorphisms have been associated with many autoimmune diseases. To explore the correlation between MIC polymorphisms and systemic lupus erythematosus (SLE), we compared the sequence of the MIC gene in Han Chinese patients with SLE from Hainan Island, China, with healthy individuals. In this study, the MIC polymorphisms in 296 subjects (159 patients with SLE and 137 healthy volunteers) of Han ethnicity from Hainan Island were characterized. A chi-square test was performed to evaluate the differences in the allelic frequency of the MIC genes between patients with SLE and the control subjects. The genotyping results indicated that the frequencies of the MICA*010, MICB*014, and MICB*002 alleles were significantly higher in the control subjects than the patients with SLE. Additionally, the results also indicated that the frequency of the MICB*009N in the SLE group was significantly increased compared to that in the matched control subjects. The results of this study suggested that the MICB*009N allele might be a risk factor for SLE, whereas the MICB*014, MICA*010 and MICB*002 alleles were associated with reduced incidence of SLE in the study population. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  18. Association between premature ventricular complexes during exercise, long-term occurrence of life-threatening arrhythmia and mortality.

    Science.gov (United States)

    Aviles-Rosales, Jorge; Ilarraza-Lomeli, Hermes; Garcia-Saldivia, Marianna; Rojano-Castillo, Jessica; Rius-Suarez, Maria-Dolores; Nunez-Urquiza, Juan-Pablo; Iturralde, Pedro

    2017-08-14

    Exercise-induced premature ventricular complexes (EiPVCs) are often considered as benign arrhythmias, although they are associated with a high risk of all-cause death in the general healthy population. However, an intermediate pathophysiological process remains unclear, particularly in patients with known cardiovascular disease. The aim of this study was to find an association between EiPVCs, the occurrence of life-threatening ventricular arrhythmias (LACO), and all-cause mortality in patients with cardiovascular disease. This was an observational study of a cohort of patients with coronary artery disease (CAD) or idiopathic cardiomyopathy (ICM). Stress testing was performed as a part of the routine cardiovascular evaluation. The occurrence of EiPVCs was evaluated during exercise testing (ET). At follow-up, long-term occurrence of LACO was evaluated. A bivariate and multivariate analysis was performed. Out of the total of 1442 patients analysed, 700 (49%) had EiPVCs. During 14 years of following-up after ET, 106 LACO outcomes were observed. Long-term all-cause mortality was 4% (n=61). A bivariate analysis showed that patients with EiPVCs had an increased risk for LACO (RR=2.81, 95% CI; 1.9-4.3, P<.001), and for mortality (RR=2.1, CI 95% 1.2-3.4, P<.01). Occurrence of LACO was also associated with a higher mortality risk (RR=5.7, 95% CI; 3.4-9.4, P<.001). After a post hoc analysis, LACO remained as a highly predictive variable for mortality. Patients with EiPVCs have a high risk of LACO and all-cause mortality. The presence of LACO could be an intermediate stage between EiPVCs and mortality in subjects with cardiovascular disease. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  19. Structure of stable degeneration of K3 surfaces into pairs of rational elliptic surfaces

    OpenAIRE

    Kimura, Yusuke

    2018-01-01

    F-theory/heterotic duality is formulated in the stable degeneration limit of a K3 fibration on the F-theory side. In this note, we analyze the structure of the stable degeneration limit. We discuss whether stable degeneration exists for pairs of rational elliptic surfaces. We demonstrate that, when two rational elliptic surfaces have an identical complex structure, stable degeneration always exists. We provide an equation that systematically describes the stable degeneration of a K3 surface i...

  20. Unraveling the Alteration History of Serpentinites and Associated Ultramafic Rocks from the Kampos HPLT Subduction Complex, Syros, Greece

    Science.gov (United States)

    Cooperdock, E. H. G.; Stockli, D. F.

    2016-12-01

    Serpentinization, hydration of peridotite, has a profound effect on fundamental tectonic and petrologic processes such as deformation of the lithosphere, bulk rheology, fluid-mobile element cycling and deep earth carbon cycling. Though numerous studies have investigated the petrology, structure and geochemistry of serpentinites, the absolute chronology of serpentinization remains elusive due to a lack of accessory minerals that can be dated using established geochronological techniques. Magnetite forms as a common secondary mineral in serpentinites from the fluid-induced breakdown reaction of primary peridotite minerals. Magnetite (U-Th)/He chronometry provides the potential to directly date the cooling of exhumed ultramafic bodies and the low-temperature fluid alteration of serpentinites. We present the first application of magnetite (U-Th)/He chronometry to date stages of alteration in ultramafic rocks from the Kampos mélange belt, a high-pressure low-temperature (HP-LT) subduction complex that experienced exhumation in the Miocene on the island of Syros, Greece. Two generations of magnetite are distinguishable by grain size, magnetite trace element geochemistry and (U-Th)/He age. Large magnetite grains (mm) from a chlorite schist and a serpentinite schist have distinct geochemical signatures indicative of formation during blackwall-related fluid alteration and record Mid-Miocene exhumation-related cooling ages, similar to zircon (U-Th)/He ages from northern Syros. Smaller grains (µm) from the serpentinite schist lack blackwall-related fluid signatures and record post-exhumation mineral formation associated with widespread high-angle Pliocene normal faulting. These results reveal evidence for multiple episodes of fluid-rock alteration, which has implications for the cooling history and local geochemical exchanges of this HP-LT terrane. Given the fundamental impact of serpentinizaton on a vast array of tectonic, petrological, and geochemical processes, the

  1. Variations in the radiation sensitivity of foodborne pathogens associated with complex ready-to-eat food products

    Energy Technology Data Exchange (ETDEWEB)

    Sommers, Christopher H. [Food Safety Intervention Technologies Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, 600 East Mermaid Lane, Wyndmoor, PA 19038 (United States)]. E-mail: csommers@errc.ars.usda.gov; Boyd, Glenn [Food Safety Intervention Technologies Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, 600 East Mermaid Lane, Wyndmoor, PA 19038 (United States)

    2006-07-15

    Foodborne illness outbreaks and product recalls are occasionally associated with ready-to-eat (RTE) sandwiches and other 'heat and eat' multi-component RTE products. Ionizing radiation can inactivate foodborne pathogens on meat and poultry, fruits and vegetables, seafood, and RTE meat products. However, less data are available on the ability of low-dose ionizing radiation, doses under 5 kGy typically used for pasteurization purposes, to inactivate pathogenic bacteria on complex multi-component food products. In this study, the efficacy of ionizing radiation to inactivate Salmonella spp., Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, and Yersinia enterocolitica on RTE foods including a 'frankfurter on a roll', a 'beef cheeseburger on a bun' and a 'vegetarian cheeseburger on a bun' was investigated. The average D-10 values, the radiation dose needed to inactivate 1 log{sub 1} of pathogen, by bacterium species, were 0.61, 0.54, 0.47, 0.36 and 0.15 kGy for Salmonella spp., S. aureus, L. monocytogenes, E. coli O157:H7, and Y. enterocolitica, respectively when inoculated onto the three product types. These results indicate that irradiation may be an effective means for inactivating common foodborne pathogens including Salmonella spp, S. aureus, L. monocytogenes, E. coli O157:H7 and Y. enterocolitica in complex RTE food products such as 'heat and eat' sandwich products.

  2. Comparison of gene-based rare variant association mapping methods for quantitative traits in a bovine population with complex familial relationships

    NARCIS (Netherlands)

    Zhang, Qianqian; Guldbrandtsen, Bernt; Calus, Mario P.L.; Lund, Mogens Sandø; Sahana, Goutam

    2016-01-01

    Background: There is growing interest in the role of rare variants in the variation of complex traits due to increasing evidence that rare variants are associated with quantitative traits. However, association methods that are commonly used for mapping common variants are not effective to map

  3. Evolution of reproductive mode variation and host associations in a sexual-asexual complex of aphid parasitoids

    Directory of Open Access Journals (Sweden)

    Sandrock Christoph

    2011-12-01

    Full Text Available Abstract Background The Lysiphlebus fabarum group is a taxonomically poorly resolved complex of aphid parasitoids, presently split into three described species that comprise sexual (arrhenotokous and asexual (thelytokous lineages of unknown relationship. Specifically, it is unclear how asexuals evolved from sexuals in this system, to what extent reproductive modes are still connected by genetic exchange, how much the complex is structured by geography or by host-associated differentiation, and whether species designations are valid. Using a combination of population genetic and phylogenetic approaches, we addressed these issues in a comprehensive sample of parasitoid wasps from across Europe. Results Asexual reproduction predominated in parasitoids of the L. fabarum group, with asexual populations exhibiting high genotypic diversity. Sexual populations were only common in southern France; elsewhere sexual reproduction was restricted to specific aphid hosts. Although reproductive modes were aggregated on the mitochondrial genealogy and significantly differentiated at nuclear microsatellite loci, there was clear evidence for genetic exchange, especially on hosts attacked by sexual and asexual parasitoids. The microsatellite data further revealed that parasitoids collected from certain host aphids were significantly differentiated, yet the mitochondrial sequence variation across the entire L. fabarum group did not exceed 1.32% and exhibited a very shallow topology. Morphological characters used for delineation of described species were found to be phylogenetically non-conservative. Conclusions Our results suggest that the sexual-asexual L. fabarum group represents a young complex of lineages with incomplete isolation between reproductive modes. We propose three mechanisms of genetic exchange that may jointly explain the high genotypic diversity observed in asexual parasitoids: (i the formation of new asexual lineages via 'contagious parthenogenesis

  4. Perinatal features of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS complex) associated with large meningomyeloceles and severe limb defects.

    Science.gov (United States)

    Chen, C P; Shih, S L; Liu, F F; Jan, S W; Jeng, C J; Lan, C C

    1997-05-01

    Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS complex), a combination of omphalocele, exstrophy of the bladder, an imperforate anus and spinal defects, arises from a single localized defect in the early development of the mesoderm that will later contribute to infraumbilical mesenchyme, cloacal septum, and caudal vertebrae. In this report, we document the perinatal features of two cases of OEIS complex associated with meningomyeloceles and severe lower limb defects, and discuss the prenatal diagnosis, inheritance, and differential diagnosis of this association of malformations. Although long-term survival can be achieved by successful corrective surgery, the associated structural defects such as large meningomyelocele and severe limb aplasia or hypoplasia, as seen in our patient, can influence the patient's quality of life. We would like to emphasize that an accurate prenatal diagnosis of OEIS complex and associated malformations is important for the detailed counseling of the family as well as appropriate perinatal management by the obstetricians, pediatric surgeons, urologists, neurosurgeons, and neonatologists.

  5. Elevation of Non-Classical (CD14+/lowCD16++) Monocytes Is Associated with Increased Albuminuria and Urine TGF-β1 in HIV-Infected Individuals on Stable Antiretroviral Therapy.

    Science.gov (United States)

    Mitchell, Brooks I; Byron, Mary Margaret; Ng, Roland C; Chow, Dominic C; Ndhlovu, Lishomwa C; Shikuma, Cecilia M

    2016-01-01

    High rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART). Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants. Cross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC) using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR). Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology. Among 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL), 18 patients (19%) had albuminuria. Non-classical (CD14low/+CD16++) monocytes were significantly elevated in subjects with albuminuria (p = 0.034) and were correlated to UACR (r = 0.238, p = 0.019). Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007). Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042). Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017). Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.

  6. Spectrofluorimetric determination of stoichiometry and association constants of the complexes of harmane and harmine with beta-cyclodextrin and chemically modified beta-cyclodextrins.

    Science.gov (United States)

    Martín, L; León, A; Olives, A I; Del Castillo, B; Martín, M A

    2003-06-13

    The association characteristics of the inclusion complexes of the beta-carboline alkaloids harmane and harmine with beta-cyclodextrin (beta-CD) and chemically modified beta-cyclodextrins such as hydroxypropyl-beta-cyclodextrin (HPbeta-CD), 2,3-di-O-methyl-beta-cyclodextrin (DMbeta-CD) and 2,3,6-tri-O-methyl-beta-cyclodextrin (TMbeta-CD) are described. The association constants vary from 112 for harmine/DMbeta-CD to 418 for harmane/HPbeta-CD. The magnitude of the interactions between the host and the guest molecules depends on the chemical and geometrical characteristics of the guest molecules and therefore the association constants vary for the different cyclodextrin complexes. The steric hindrance is higher in the case of harmine due to the presence of methoxy group on the beta-carboline ring. The association obtained for the harmane complexes is stronger than the one observed for harmine complexes except in the case of harmine/TMbeta-CD. Important differences in the association constants were observed depending on the experimental variable used in the calculations (absolute value of fluorescence intensity or the ratio between the fluorescence intensities corresponding to the neutral and cationic forms). When fluorescence intensity values were considered, the association constants were higher than when the ratio of the emission intensity for the cationic and neutral species was used. These differences are a consequence of the co-existence of acid-base equilibria in the ground and in excited states together with the complexation equilibria. The existence of a proton transfer reaction in the excited states of harmane or harmine implies the need for the experimental dialysis procedure for separation of the complexes from free harmane or harmine. Such methodology allows quantitative results for stoichiometry determinations to be obtained, which show the existence of both 1:1 and 1:2 beta-carboline alkaloid:CD complexes with different solubility properties.

  7. Digital surgical templates for managing high-energy zygomaticomaxillary complex injuries associated with orbital volume change: a quantitative assessment.

    Science.gov (United States)

    Liu, Xiang-Zhen; Shu, Da-Long; Ran, Wei; Guo, Bing; Liao, Xin

    2013-10-01

    This study sought to introduce 3-dimensional (3D) virtual surgical planning and digital rapid-prototyping templates for zygomaticomaxillary complex (ZMC) injuries associated with orbital volume change and to evaluate the surgical outcomes quantitatively. Eight patients who underwent open reduction and fixation for a ZMC injury with orbital volume change were studied. Computed tomographic (CT) scan of the zygomaticomaxillary area was performed before the operation in each case. Scanned data were converted into 3D models using Mimics software (Materialise, Brussels, Belgium) for surgical designs. Virtual surgical reductions and correlated guiding templates were designed using Mimics and Magics software (Materialise). The operations were performed with the help of prefabricated templates to reduce the fractures. A postoperative CT scan of each patient was obtained within 2 weeks after surgery, and quantitative measurements were made to assess the surgical outcomes. Preoperative volumes of the bilateral orbits were compared, and concordance with postoperative volumes of the bilateral orbits was assessed. Twenty-one pairs of distances from 7 marker points to 3 reference planes were measured to assess postoperative facial symmetry. Volumes of the injured orbits were significantly different from volumes of the uninjured orbits preoperatively (P .05). In addition, 19 of the 21 pairs of bilateral distances showed no significant difference postoperatively (P > .05). Quantitative assessment showed that digitally designed, rapid-prototyping templates for ZMC fractures have a positive impact on restoring facial symmetry and concordance of bilateral orbital volumes. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Model cortical association fields account for the time course and dependence on target complexity of human contour perception.

    Directory of Open Access Journals (Sweden)

    Vadas Gintautas

    2011-10-01

    Full Text Available Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas distributed among groups of randomly rotated fragments (clutter. The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms, followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.

  9. Measurement issues associated with quantitative molecular biology analysis of complex food matrices for the detection of food fraud.

    Science.gov (United States)

    Burns, Malcolm; Wiseman, Gordon; Knight, Angus; Bramley, Peter; Foster, Lucy; Rollinson, Sophie; Damant, Andrew; Primrose, Sandy

    2016-01-07

    Following a report on a significant amount of horse DNA being detected in a beef burger product on sale to the public at a UK supermarket in early 2013, the Elliott report was published in 2014 and contained a list of recommendations for helping ensure food integrity. One of the recommendations included improving laboratory testing capacity and capability to ensure a harmonised approach for testing for food authenticity. Molecular biologists have developed exquisitely sensitive methods based on the polymerase chain reaction (PCR) or mass spectrometry for detecting the presence of particular nucleic acid or peptide/protein sequences. These methods have been shown to be specific and sensitive in terms of lower limits of applicability, but they are largely qualitative in nature. Historically, the conversion of these qualitative techniques into reliable quantitative methods has been beset with problems even when used on relatively simple sample matrices. When the methods are applied to complex sample matrices, as found in many foods, the problems are magnified resulting in a high measurement uncertainty associated with the result which may mean that the assay is not fit for purpose. However, recent advances in the technology and the understanding of molecular biology approaches have further given rise to the re-assessment of these methods for their quantitative potential. This review focuses on important issues for consideration when validating a molecular biology assay and the various factors that can impact on the measurement uncertainty of a result associated with molecular biology approaches used in detection of food fraud, with a particular focus on quantitative PCR-based and proteomics assays.

  10. Age and source of water in springs associated with the Jacksonville Thrust Fault Complex, Calhoun County, Alabama

    Science.gov (United States)

    Robinson, James L.

    2004-01-01

    Water from wells and springs accounts for more than 90 percent of the public water supply in Calhoun County, Alabama. Springs associated with the Jacksonville Thrust Fault Complex are used for public water supply for the cities of Anniston and Jacksonville. The largest ground-water supply is Coldwater Spring, the primary source of water for Anniston, Alabama. The average discharge of Coldwater Spring is about 32 million gallons per day, and the variability of discharge is about 75 percent. Water-quality samples were collected from 6 springs and 15 wells in Calhoun County from November 2001 to January 2003. The pH of the ground water typically was greater than 6.0, and specific conductance was less than 300 microsiemens per centimeter. The water chemistry was dominated by calcium, carbonate, and bicarbonate ions. The hydrogen and oxygen isotopic composition of the water samples indicates the occurrence of a low-temperature, water-rock weathering reaction known as silicate hydrolysis. The residence time of the ground water, or ground-water age, was estimated by using analysis of chlorofluorocarbon, sulfur hexafluoride, and regression modeling. Estimated ground-water ages ranged from less than 10 to approximately 40 years, with a median age of about 18 years. The Spearman rho test was used to identify statistically significant covariance among selected physical properties and constituents in the ground water. The alkalinity, specific conductance, and dissolved solids increased as age increased; these correlations reflect common changes in ground-water quality that occur with increasing residence time and support the accuracy of the age estimates. The concentration of sodium and chloride increased as age increased; the correlation of these constituents is interpreted to indicate natural sources for chloride and sodium. The concentration of silica increased as the concentration of potassium increased; this correlation, in addition to the isotopic data, is evidence that

  11. ER-associated complexes (ERACs) containing aggregated cystic fibrosis transmembrane conductance regulator (CFTR) are degraded by autophagy.

    Science.gov (United States)

    Fu, Lianwu; Sztul, Elizabeth

    2009-04-01

    The ubiquitin-proteasome pathway and autophagy are the two major mechanisms responsible for the clearance of cellular proteins. We have used the yeast Saccharomyces cerevisiae as a model system and the cystic fibrosis transmembrane conductance regulator (CFTR) as a model substrate to study the interactive function of these two pathways in the degradation of misfolded proteins. EGFP-tagged human CFTR was introduced into yeast and expressed under a copper-inducible promoter. The localization and degradation of EGFP-CFTR in live cells were monitored by time-lapse imaging following its de novo synthesis. EGFP-CFTR first appears within the perinuclear and sub-cortical ER and is mobile within the plane of the membrane as assessed by fluorescence recovery after photobleaching (FRAP). This pool of EGFP-CFTR is subsequently degraded through a proteasome-dependent pathway that is inhibited in the pre1-1 yeast strain defective in proteasomal degradation. Prolonged expression of EGFP-CFTR leads to the sequestration of EGFP-CFTR molecules into ER structures called ER-associated complexes (ERACs). The sequestration of EGFP-CFTR into ERACs appears to be driven by aggregation since EGFP-CFTR molecules present within ERACs are immobile as measured by FRAP. Individual ERACs are cleared from cells through the autophagic pathway that is blocked in the atg6Delta and atg1Delta yeast strains defective in autophagy. Our results suggest that the proteasomal and the autophagic pathways function together to clear misfolded proteins from the ER.

  12. Post-transplant immune complex nephritis in a patient with systemic lupus erythematosus associated with ANCA vasculitis.

    Science.gov (United States)

    Sanchez, Carlos; Rebolledo, Alejandra; Gahona, Junior; Rojas, Mauricio; Jiménez, Raquel; Bojórquez, Aurora

    2017-05-01

    Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA-associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys. A 17-year-old female with crescentic glomerulonephritis, p-ANCA-positive antibodies with pauci-immune pattern in kidney biopsy develops end-stage renal disease requiring hemodialysis. Deceased donor kidney transplant was performed receiving triple immunosuppression thereafter. Thirteen months later serum creatinine rises without evidence of infection, urinary obstruction, or clinical and serologic disease relapse. Allograft biopsy reports mesangial proliferation and "full-house" immunofluorescence. The role of ANCA in SLE physiopathology is controversial, and its relation with lupus nephritis is also discordant. ANCA could represent an important factor in the heterogeneity of systemic lupus erythematosus and lupus nephritis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex.

    Science.gov (United States)

    Kishimoto, Mai; Tsuchiaka, Shinobu; Rahpaya, Sayed Samim; Hasebe, Ayako; Otsu, Keiko; Sugimura, Satoshi; Kobayashi, Suguru; Komatsu, Natsumi; Nagai, Makoto; Omatsu, Tsutomu; Naoi, Yuki; Sano, Kaori; Okazaki-Terashima, Sachiko; Oba, Mami; Katayama, Yukie; Sato, Reiichiro; Asai, Tetsuo; Mizutani, Tetsuya

    2017-03-18

    Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.

  14. Adeno-associated virus-2 and its primary cellular receptor-Cryo-EM structure of a heparin complex

    International Nuclear Information System (INIS)

    O'Donnell, Jason; Taylor, Kenneth A.; Chapman, Michael S.

    2009-01-01

    Adeno-associated virus serotype 2 (AAV-2) is a leading candidate vector for gene therapy. Cell entry starts with attachment to a primary receptor, Heparan Sulfate Proteoglycan (HSPG) before binding to a co-receptor. Here, cryo-electron microscopy provides direct visualization of the virus-HSPG interactions. Single particle analysis was performed on AAV-2 complexed with a 17 kDa heparin fragment at 8.3 A resolution. Heparin density covers the shoulder of spikes surrounding viral 3-fold symmetry axes. Previously implicated, positively charged residues R 448/585 , R 451/588 and R 350/487 from another subunit cluster at the center of the heparin footprint. The footprint is much more extensive than apparent through mutagenesis, including R 347/484 , K 395/532 and K 390/527 that are more conserved, but whose roles have been controversial. It also includes much of a region proposed as a co-receptor site, because prior studies had not revealed heparin interactions. Heparin density bridges over the viral 3-fold axes, indicating multi-valent attachment to symmetry-related binding sites

  15. SWI/SNF chromatin remodeling complex is critical for the expression of microphthalmia-associated transcription factor in melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Vachtenheim, Jiri, E-mail: jivach@upn.anet.cz [Laboratory of Molecular Biology, University Hospital, Charles University, Prague (Czech Republic); Ondrusova, Lubica [Laboratory of Molecular Biology, University Hospital, Charles University, Prague (Czech Republic); Borovansky, Jan [Institute of Biochemistry and Experimental Oncology, 1st Faculty of Medicine, Charles University, Prague (Czech Republic)

    2010-02-12

    The microphthalmia-associated transcription factor (MITF) is required for melanocyte development, maintenance of the melanocyte-specific transcription, and survival of melanoma cells. MITF positively regulates expression of more than 25 genes in pigment cells. Recently, it has been demonstrated that expression of several MITF downstream targets requires the SWI/SNF chromatin remodeling complex, which contains one of the two catalytic subunits, Brm or Brg1. Here we show that the expression of MITF itself critically requires active SWI/SNF. In several Brm/Brg1-expressing melanoma cell lines, knockdown of Brg1 severely compromised MITF expression with a concomitant dowregulation of MITF targets and decreased cell proliferation. Although Brm was able to substitute for Brg1 in maintaining MITF expression and melanoma cell proliferation, sequential knockdown of both Brm and Brg1 in 501mel cells abolished proliferation. In Brg1-null SK-MEL-5 melanoma cells, depletion of Brm alone was sufficient to abrogate MITF expression and cell proliferation. Chromatin immunoprecipitation confirmed the binding of Brg1 or Brm to the promoter of MITF. Together these results demonstrate the essential role of SWI/SNF for expression of MITF and suggest that SWI/SNF may be a promissing target in melanoma therapy.

  16. RNase MRP RNA and RNase P activity in plants are associated with a Pop1p containing complex.

    Science.gov (United States)

    Krehan, Mario; Heubeck, Christian; Menzel, Nicolas; Seibel, Peter; Schön, Astrid

    2012-09-01

    RNase P processes the 5'-end of tRNAs. An essential catalytic RNA has been demonstrated in Bacteria, Archaea and the nuclei of most eukaryotes; an organism-specific number of proteins complement the holoenzyme. Nuclear RNase P from yeast and humans is well understood and contains an RNA, similar to the sister enzyme RNase MRP. In contrast, no protein subunits have yet been identified in the plant enzymes, and the presence of a nucleic acid in RNase P is still enigmatic. We have thus set out to identify and characterize the subunits of these enzymes in two plant model systems. Expression of the two known Arabidopsis MRP RNA genes in vivo was verified. The first wheat MRP RNA sequences are presented, leading to improved structure models for plant MRP RNAs. A novel mRNA encoding the central RNase P/MRP protein Pop1p was identified in Arabidopsis, suggesting the expression of distinct protein variants from this gene in vivo. Pop1p-specific antibodies precipitate RNase P activity and MRP RNAs from wheat extracts. Our results provide evidence that in plants, Pop1p is associated with MRP RNAs and with the catalytic subunit of RNase P, either separately or in a single large complex.

  17. Serum amyloid P component-DNA complexes are decreased in systemic lupus erythematosus. inverse association with anti-dsDNA antibodies

    DEFF Research Database (Denmark)

    Voss, Anne; Nielsen, Ellen Holm; Svehag, Sven Erik

    2008-01-01

    OBJECTIVE: To study serum levels of serum amyloid P component (SAP) and SAP-DNA complexes in a population-based cohort of patients with systemic lupus erythematosus (SLE). METHODS: The study population comprised 82 unselected patients of predominantly Scandinavian ancestry with SLE according...... to current classification criteria. Serum samples were collected at baseline and serially for up to 2 years. SAP component and SAP-DNA complexes were measured by ELISA. Associations between SAP-DNA and clinical manifestations or serological findings were analyzed. Ninety healthy, age-matched blood donors...... served as controls. RESULTS: SLE patients had normal serum concentrations of SAP, whereas SAP-DNA complexes were decreased. Two-thirds of the SLE patients tested persistently SAP-DNA complex-negative. There was no relationship between the occurrence of SAP-DNA complexes and clinical manifestations. SAP...

  18. X-ray studies on crystalline complexes involving amino acids and peptides. XLII. Adipic acid complexes of L- and DL-arginine and supramolecular association in arginine-dicarboxylic acid complexes.

    Science.gov (United States)

    Roy, Siddhartha; Singh, Desh Deepak; Vijayan, M

    2005-02-01

    The adipic acid complexes of DL-arginine and L-arginine are made up of zwitterionic, singularly positively charged arginium ions and doubly negatively charged adipate ions, with a 2:1 stoichiometry. One of the two crystallographically independent arginium ions in the L-arginine complex has a conformation hitherto unobserved in crystal structures containing the amino acid. In the present study the structural data on arginine complexes of saturated dicarboxylic acids with 0-5 C atoms separating the two carboxyl functions are given. In terms of molecular aggregation, formic and acetic acid complexes behave in a similar way to those involving fairly long carboxylic acids such as adipic acid. By and large, the supramolecular assembly in complexes involving dicarboxylic acids with 3 or more C atoms separating the carboxyl groups (glutaric, adipic and pimelic acids), and those involving formic and acetic acids, have common features. The aggregation patterns in complexes involving oxalic, malonic and maleic acids do not share striking features among themselves (except for the mode of hydrogen-bonded dimerization of arginium ions) or with those involving larger dicarboxylic acids. Complexes of succinic acid, the shortest linear dicarboxylic acid, share features with those involving shorter as well as longer dicarboxylic acids. The difference in the behaviour of long and short dicarboxylic acids and the ambiguous behaviour of succinic acid can be broadly related to their lengths.

  19. Stable chaos in fluctuation driven neural circuits

    International Nuclear Information System (INIS)

    Angulo-Garcia, David; Torcini, Alessandro

    2014-01-01

    Highlights: • Nonlinear instabilities in fluctuation driven (balanced) neural circuits are studied. • Balanced networks display chaos and stable phases at different post-synaptic widths. • Linear instabilities coexists with nonlinear ones in the chaotic regime. • Erratic motion appears also in linearly stable phase due to stable chaos. - Abstract: We study the dynamical stability of pulse coupled networks of leaky integrate-and-fire neurons against infinitesimal and finite perturbations. In particular, we compare mean versus fluctuations driven networks, the former (latter) is realized by considering purely excitatory (inhibitory) sparse neural circuits. In the excitatory case the instabilities of the system can be completely captured by an usual linear stability (Lyapunov) analysis, whereas the inhibitory networks can display the coexistence of linear and nonlinear instabilities. The nonlinear effects are associated to finite amplitude instabilities, which have been characterized in terms of suitable indicators. For inhibitory coupling one observes a transition from chaotic to non chaotic dynamics by decreasing the pulse-width. For sufficiently fast synapses the system, despite showing an erratic evolution, is linearly stable, thus representing a prototypical example of stable chaos

  20. Radioisotope trithiol complexes

    Science.gov (United States)

    Jurisson, Silvia S.; Cutler, Cathy S.; Degraffenreid, Anthony J.

    2016-08-30

    The present invention is directed to a series of stable radioisotope trithiol complexes that provide a simplified route for the direct complexation of radioisotopes present in low concentrations. In certain embodiments, the complex contains a linking domain configured to conjugate the radioisotope trithiol complex to a targeting vector. The invention is also directed to a novel method of linking the radioisotope to a trithiol compound to form the radioisotope trithiol complex. The inventive radioisotope trithiol complexes may be utilized for a variety of applications, including diagnostics and/or treatment in nuclear medicine.

  1. Dynamical attraction to stable processes

    OpenAIRE

    Fisher, Albert M.; Talet, Marina

    2012-01-01

    We apply dynamical ideas within probability theory, proving an almost-sure invariance principle in log density for stable processes. The familiar scaling property (self-similarity) of the stable process has a stronger expression, that the scaling flow on Skorokhod path space is a Bernoulli flow. We prove that typical paths of a random walk with i.i.d. increments in the domain of attraction of a stable law can be paired with paths of a stable process so that, after applying a non-random regula...

  2. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  3. Synthesis and characterization of thermally stable oligomer-metal ...

    African Journals Online (AJOL)

    Synthesis and characterization of thermally stable oligomer-metal complexes of copper(II), nickel(II), zinc(II) and cobalt(II) derived from oligo- p - nitrophenylazomethinephenol. ... Based on half degradation temperature parameters Cu(II) and Zn(II) complexes were more resistant than the others. KEY WORDS: Oligomer metal ...

  4. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  5. Factors associated with the healing of complex surgical wounds in the breast and abdomen: retrospective cohort study.

    Science.gov (United States)

    Borges, Eline Lima; Pires, José Ferreira; Abreu, Mery Natali Silva; Lima, Vera Lúcia de Araújo; Silva, Patrícia Aparecida Barbosa; Soares, Sônia Maria

    2016-10-10

    to estimate the healing rate of complex surgical wounds and its associated factors. retrospective cohort study from 2003 to 2014 with 160 outpatients of a Brazilian university hospital. Data were obtained through consultation of the medical records. Survival function was estimated using the Kaplan-Meier method and Cox regression model to estimate the likelihood of the occurrence of healing. the complex surgical wound healing rate was 67.8% (95% CI: 60.8-74.9). Factors associated with a higher likelihood of wound healing were segmentectomy/quadrantectomy surgery, consumption of more than 20 grams/day of alcohol, wound extent of less that 17.3 cm2 and the length of existence of the wound prior to outpatient treatment of less than 15 days, while the use of hydrocolloid covering and Marlex mesh were associated with a lower likelihood of healing. the wound healing rate was considered high and was associated with the type of surgical intervention, alcohol consumption, type of covering, extent and length of wound existence. Preventive measures can be implemented during the monitoring of the evolution of the complex surgical wound closure, with possibilities of intervention in the modifiable risk factors. estimar a taxa de cicatrização de ferida cirúrgica complexa e seus fatores associados. coorte retrospectiva de 2003 a 2014 com 160 pacientes ambulatoriais de um hospital universitário brasileiro. Os dados foram obtidos por meio de consulta aos prontuários médicos. Função de sobrevida foi estimada pelo método de Kaplan-Meier e modelo de regressão de Cox para estimação do risco de ocorrência da cicatrização. a taxa de cicatrização da ferida cirúrgica complexa foi 67,8% (IC 95%: 60,8-74,9). Os fatores associados a um maior risco de cicatrização da ferida foram cirurgia de setorectomia / quadrantectomia, consumo de mais de 20 gramas/dia de etanol, extensão da ferida menor que 17,3 cm2 e tempo de existência da ferida pré-tratamento ambulatorial inferior

  6. The 3D structure of the apical complex and association with the flagellar apparatus revealed by serial TEM tomography in Psammosa pacifica, a distant relative of the Apicomplexa.

    Science.gov (United States)

    Okamoto, Noriko; Keeling, Patrick J

    2014-01-01

    The apical complex is one of the defining features of apicomplexan parasites, including the malaria parasite Plasmodium, where it mediates host penetration and invasion. The apical complex is also known in a few related lineages, including several non-parasitic heterotrophs, where it mediates feeding behaviour. The origin of the apical complex is unclear, and one reason for this is that in apicomplexans it exists in only part of the life cycle, and never simultaneously with other major cytoskeletal structures like flagella and basal bodies. Here, we used conventional TEM and serial TEM tomography to reconstruct the three dimensional structure of the apical complex in Psammosa pacifica, a predatory relative of apicomplexans and dinoflagellates that retains the archetype apical complex and the flagellar apparatus simultaneously. The P. pacifica apical complex is associated with the gullet and consists of the pseudoconoid, micronemes, and electron dense vesicles. The pseudoconoid is a convex sheet consisting of eight short microtubules, plus a band made up of microtubules that originate from the flagellar apparatus. The flagellar apparatus consists of three microtubular roots. One of the microtubular roots attached to the posterior basal body is connected to bypassing microtubular strands, which are themselves connected to the extension of the pseudoconoid. These complex connections where the apical complex is an extension of the flagellar apparatus, reflect the ancestral state of both, dating back to the common ancestor of apicaomplexans and dinoflagellates.

  7. Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

    Science.gov (United States)

    Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna S; Rao, Sunil; Weintraub, William; Henry, Timothy D; Farhan, Serdar; Vogel, Birgit; Sorrentino, Sabato; Ge, Zhen; Kapadia, Samir; Muhlestein, Joseph B; Weiss, Sandra; Strauss, Craig; Toma, Catalin; DeFranco, Anthony; Effron, Mark B; Keller, Stuart; Baker, Brian A; Pocock, Stuart; Dangas, George; Mehran, Roxana

    2018-03-01

    Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. Copyright © 2018. Published by Elsevier Inc.

  8. Influence of horse stable environment on human airways

    Directory of Open Access Journals (Sweden)

    Pringle John

    2009-05-01

    Full Text Available Abstract Background Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. Methods The horse stable environment and stable-workers (n = 13 in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function. Results Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-β-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated. Conclusion Biomarkers involved in the development of airway diseases have been studied in relation to

  9. Using Convolutional Neural Networks for Enhanced Capture of Breast Parenchymal Complexity Patterns Associated with Breast Cancer Risk.

    Science.gov (United States)

    Gastounioti, Aimilia; Oustimov, Andrew; Hsieh, Meng-Kang; Pantalone, Lauren; Conant, Emily F; Kontos, Despina

    2018-01-30

    We evaluate utilizing convolutional neural networks (CNNs) to optimally fuse parenchymal complexity measurements generated by texture analysis into discriminative meta-features relevant for breast cancer risk prediction. With Institutional Review Board approval and Health Insurance Portability and Accountability Act compliance, we retrospectively analyzed "For Processing" contralateral digital mammograms (GE Healthcare 2000D/DS) from 106 women with unilateral invasive breast cancer and 318 age-matched controls. We coupled established texture features (histogram, co-occurrence, run-length, structural), extracted using a previously validated lattice-based strategy, with a multichannel CNN into a hybrid framework in which a multitude of texture feature maps are reduced to meta-features predicting the case or control status. We evaluated the framework in a randomized split-sample setting, using the area under the curve (AUC) of the receiver operating characteristic (ROC) to assess case-control discriminatory capacity. We also compared the framework to CNNs directly fed with mammographic images, as well as to conventional texture analysis, where texture feature maps are summarized via simple statistical measures that are then used as inputs to a logistic regression model. Strong case-control discriminatory capacity was demonstrated on the basis of the meta-features generated by the hybrid framework (AUC = 0.90), outperforming both CNNs applied directly to raw image data (AUC = 0.63, P images, which can be extracted and summarized via a multichannel CNN architecture toward leveraging the associations of textural measurements to breast cancer risk. Copyright © 2018. Published by Elsevier Inc.

  10. Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum.

    Science.gov (United States)

    Alahmadi, Adnan A S; Samson, Rebecca S; Gasston, David; Pardini, Matteo; Friston, Karl J; D'Angelo, Egidio; Toosy, Ahmed T; Wheeler-Kingshott, Claudia A M

    2016-06-01

    Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

  11. Major histocompatibility complex diversity is positively associated with stream water temperatures in proximate populations of sockeye salmon.

    Science.gov (United States)

    Larson, W A; Lisi, P J; Seeb, J E; Seeb, L W; Schindler, D E

    2016-09-01

    Local adaptation to heterogeneous environments generates population diversity within species, significantly increasing ecosystem stability and flows of ecosystem services. However, few studies have isolated the specific mechanisms that create and maintain this diversity. Here, we examined the relationship between water temperature in streams used for spawning and genetic diversity at a gene involved in immune function [the major histocompatibility complex (MHC)] in 14 populations of sockeye salmon (Oncorhynchus nerka) sampled across the Wood River basin in south-western Alaska. The largest influence on MHC diversity was lake basin, but we also found a significant positive correlation between average water temperature and MHC diversity. This positive relationship between temperature and MHC diversity appears to have been produced by natural selection at very local scales rather than neutral processes, as no correlation was observed between temperature and genetic diversity at 90 neutral markers. Additionally, no significant relationship was observed between temperature variability and MHC diversity. Although lake basin was the largest driver of differences in MHC diversity, our results also demonstrate that fine-scale differences in water temperature may generate variable selection regimes in populations that spawn in habitats separated by as little as 1 km. Additionally, our results indicated that some populations may be reaching a maximum level of MHC diversity. We postulate that salmon from populations in warm streams may delay spawning until late summer to avoid thermal stress as well as the elevated levels of pathogen prevalence and virulence associated with warm temperatures earlier in the summer. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  12. EXTRACTION AND SPECIATION OF CHROMIUM(VI AND CHROMIUM(III AS ION-ASSOCIATION COMPLEXES OF TETRAMETHYLAMMONIUM-CHROMATE

    Directory of Open Access Journals (Sweden)

    Valencia Widiyaningrum Wandoyo

    2010-06-01

    Full Text Available A specific, selective and simple method for speciation of chromium(VI and chromium(III has been developed. This method is based on the quantitative extraction of chromium(VI and chromium(III as an ion association of tetramethylammonium-chromate in methyl isobutyl ketone (MIBK, followed by back extraction and preconcentration with an acidic diphenylcarbazide (DPC solution. Back extraction was applied to achieve further preconcentration by a final factor of 20. The chromium(VI-DPC complex was determined by a UV-Visible spectrophotometer. The optimum conditions of this method are as follows, optimum wavelength at 545 nm, MIBK as organic solvent, 7.5 mL of nitric acid (65% for each 100 mL sample, mole ratio of TMAC to Cr(VI of 2x104:1, 5 min shaking time, mole ratio of DPC to chromium(VI of 8:1, and immediate UV-Vis measurement after obtaining of back-extract. The calibration curve was linear in the concentration range 0.00-0.40 µg.mL-1 of chromium(VI with a regression equation of Abs=0.0038+1.7427x, in which x was the chromium species concentration ( µg.mL-1. The correlation coefficient (r for the curve was 0.9991 and the detection limit was found to be 0.946 µg.mL-1. The result of analysis and speciation of chromium in water samples from a river near a leather processing plant in Yogyakarta area showed that the total content of chromium was in the range of 0.04 - 0.05 µg.mL-1 consisting of 0.03 - 0.04 µg.mL-1 of chromium(VI and 0.002 - 0.01 µg.mL-1 of chromium(III. This result indicates that the concentration of chromium in the river is still below the safety limit.   Keywords: extraction, speciation, chromium, preconcentration, ion-association, tetramethylammonium

  13. Elevation of Non-Classical (CD14+/lowCD16++ Monocytes Is Associated with Increased Albuminuria and Urine TGF-β1 in HIV-Infected Individuals on Stable Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Brooks I Mitchell

    Full Text Available High rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART. Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants.Cross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR. Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology.Among 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL, 18 patients (19% had albuminuria. Non-classical (CD14low/+CD16++ monocytes were significantly elevated in subjects with albuminuria (p = 0.034 and were correlated to UACR (r = 0.238, p = 0.019. Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007. Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042. Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017.Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.

  14. Stable transfection of Acanthamoeba.

    Science.gov (United States)

    Yin, J; Henney, H R

    1997-03-01

    The promoter activity of an Acanthamoeba polyubiquitin gene was analyzed in its homologous system. A modified calcium phosphate transfection method using a neomycin marker vector was developed to achieve highly efficient transfection of the Acanthamoeba polyubiquitin gene into Acanthamoeba cells. In this transfection procedure, the calcium phosphate-DNA complex was formed gradually in the medium during incubation with cells and precipitated on the cells. The crucial factors for obtaining efficient transfection were the pH (6.95) of the transfection buffer used for the calcium phosphate precipitation and the amount (25 micrograms/96-well tissue culture plate) and form (circular) of transfecting DNA. Under these conditions, Acanthamoeba isolate 1B6 was transfected at an efficiency of about 40% with the constructed vector pOPSBU, a pOP13CAT-based polyubiquitin gene incorporated neomycin resistance vector. Acanthamoeba polyphaga was transfected at an efficiency of about 10% with this vector. Transfection of both Acanthamoeba strains appeared to result in low copy plasmid integration (about two copies per cell are suggested). The chloramphenicol acetyltransferase (CAT) assays showed that the promoter of the Acanthamoeba polyubiquitin gene in the constructed vector was especially strong in A. polyphaga, thus the pOPSBU-Acanthamoeba system may be useful for the construction of cDNA expression libraries, as well as for the expression of cloned genes.

  15. Production of yeastolates for uniform stable isotope labelling in eukaryotic cell culture.

    NARCIS (Netherlands)

    Egorova-Zachernyuk, T.A.; Bosman, G.J.C.G.M.; Pistorius, A.M.A.; Grip, W.J. de

    2009-01-01

    Preparation of stable isotope-labelled yeastolates opens up ways to establish more cost-effective stable isotope labelling of biomolecules in insect and mammalian cell lines and hence to employ higher eukaryotic cell lines for stable isotope labelling of complex recombinant proteins. Therefore, we

  16. Significant elevation and correlation of plasma neutrophil gelatinase associated lipocalin and its complex with matrix metalloproteinase-9 in patients with pelvic inflammatory disease.

    Science.gov (United States)

    Tsai, Hsiu-Ting; Su, Pen-Hua; Lee, Tsung-Hsien; Tee, Yi-Torng; Lin, Long-Yau; Yang, Shun-Fa; Wang, Po-Hui

    2011-06-11

    To detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID). Enzyme-linked immunosorbent assay was used to measure the levels of plasma NGAL and NGAL/MMP-9 complex. The levels of plasma NGAL or NGAL/MMP-9 complex were increased in patients with PID compared with those in normal controls and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In patients with PID, plasma level of NGAL/MMP-9 complex was correlated with plasma level of NGAL or MMP-9 significantly. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%; the negative predictive values, 72.7% and 74.5%. Plasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. In patients with PID, about 80% have plasma levels of NGAL or NGAL/MMP-9 complex level >10.04 ng/ml or 2.33 ng/ml, respectively. Copyright © 2011. Published by Elsevier B.V.

  17. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA

    NARCIS (Netherlands)

    Fehrmann, Rudolf S N; Jansen, Ritsert C; Veldink, Jan H; Westra, Harm Jan; Arends, Danny; Bonder, Marc Jan; Fu, Jingyuan; Deelen, Patrick; Groen, Hendricus; Smolonska, Joanna; Weersma, Rinse K; Hofstra, Robert M W; Buurman, Wim A; Rensen, Sander; Wolfs, Marcel G M; Platteel, Mathieu; Zhernakova, Alexandra; Elbers, Clara C; Festen, Noortje; Trynka, Gosia; Hofker, Marten H; Saris, Christiaan G J; Ophoff, Roel A; van den Berg, Leonard H; van Heel, David A; Wijmenga, Cisca; te Meerman, Gerhardus; Franke, Lude

    2011-01-01

    For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these variants cause these phenotypes. Knowledge of these intermediate steps is crucial to understand pathogenesis, while also providing leads for potential

  18. Characterization of carotenoid-protein complexes and gene expression analysis associated with carotenoid sequestration in pigmented cassava (Manihot esculenta Crantz) storage root

    Science.gov (United States)

    Carotenoid-protein complex separation by size exclusion chromatography, protein fractionation by SDS-PAGE, and shotgun PROTEOMICS technology were used to identify and characterize carotenoid associated proteins (CAPs) of chromoplast-enriched suspensions from cassava intense yellow storage root. A no...

  19. Complex regional pain syndrome type I : Use of the International Association for the Study of Pain diagnostic criteria defined in 1994

    NARCIS (Netherlands)

    Reinders, M.F.; Geertzen, J.H.B.; Dijkstra, P.U.

    2002-01-01

    Objectives: The objective was to assess the reported use in recent publications of the diagnostic criteria for complex regional pain syndrome type I (CRPS 1) proposed by the International Association for the Study of Pain (IASP) in 1994. Methods: A literature search of MEDLINE (January 1996 to July

  20. Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study

    DEFF Research Database (Denmark)

    Celicanin, M; Blaabjerg, Morten; Maersk-Moller, C

    2017-01-01

    BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2...

  1. The Immunogenicity of a Proline-Substituted Altered Peptide Ligand toward the Cancer-Associated TEIPP Neoepitope Trh4 Is Unrelated to Complex Stability.

    Science.gov (United States)

    Hafstrand, Ida; Doorduijn, Elien M; Sun, Renhua; Talyzina, Anna; Sluijter, Marjolein; Pellegrino, Sara; Sandalova, Tatyana; Duru, Adil Doganay; van Hall, Thorbald; Achour, Adnane

    2018-03-05

    Human cancers frequently display defects in Ag processing and presentation allowing for immune evasion, and they therefore constitute a significant challenge for T cell-based immunotherapy. We have previously demonstrated that the antigenicity of tumor-associated Ags can be significantly enhanced through unconventional residue modifications as a novel tool for MHC class I (MHC-I)-based immunotherapy approaches. We have also previously identified a novel category of cancer neo-epitopes, that is, T cell epitopes associated with impaired peptide processing (TEIPP), that are selectively presented by MHC-I on cells lacking the peptide transporter TAP. In this study, we demonstrate that substitution of the nonanchoring position 3 into a proline residue of the first identified TEIPP peptide, the murine Trh4, results in significantly enhanced recognition by antitumor CTLs toward the wild-type epitope. Although higher immunogenicity has in most cases been associated with increased MHC/peptide complex stability, our results demonstrate that the overall stability of H-2D b in complex with the highly immunogenic altered peptide ligand Trh4-p3P is significantly reduced compared with wild-type H-2D b /Trh4. Comparison of the crystal structures of the H-2D b /Trh4-p3P and H-2D b /Trh4 complexes revealed that the conformation of the nonconventional methionine anchor residue p5M is altered, deleting its capacity to form adequate sulfur-π interactions with H-2D b residues, thus reducing the overall longevity of the complex. Collectively, our results indicate that vaccination with Thr4-p3P significantly enhances T cell recognition of targets presenting the wild-type TEIPP epitope and that higher immunogenicity is not necessarily directly related to MHC/peptide complex stability, opening for the possibility to design novel peptide vaccines with reduced MHC/peptide complex stability. Copyright © 2018 by The American Association of Immunologists, Inc.

  2. Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies.

    NARCIS (Netherlands)

    Vissers, L.E.L.M.; Stankiewicz, P.; Yatsenko, S.A.; Crawford, E.; Creswick, H.; Proud, V.K.; Vries, B. de; Pfundt, R.; Marcelis, C.L.M.; Zackowski, J.; Bi, W.; Geurts van Kessel, A.H.M.; Lupski, J.R.; Veltman, J.A.

    2007-01-01

    Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved.

  3. Tempered stable distributions stochastic models for multiscale processes

    CERN Document Server

    Grabchak, Michael

    2015-01-01

    This brief is concerned with tempered stable distributions and their associated Levy processes. It is a good text for researchers interested in learning about tempered stable distributions.  A tempered stable distribution is one which takes a stable distribution and modifies its tails to make them lighter. The motivation for this class comes from the fact that infinite variance stable distributions appear to provide a good fit to data in a variety of situations, but the extremely heavy tails of these models are not realistic for most real world applications. The idea of using distributions that modify the tails of stable models to make them lighter seems to have originated in the influential paper of Mantegna and Stanley (1994). Since then, these distributions have been extended and generalized in a variety of ways. They have been applied to a wide variety of areas including mathematical finance, biostatistics,computer science, and physics.

  4. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dutch...... and into French. The complexity of the undertaking proved to be a central element in the students' learning, as the collaboration closely resembles the complexity of international documentation workplaces of language service providers. © Association of Teachers of Technical Writing....

  5. Stable isotopes in Lithuanian bioarcheological material

    Science.gov (United States)

    Skipityte, Raminta; Jankauskas, Rimantas; Remeikis, Vidmantas

    2015-04-01

    Investigation of bioarcheological material of ancient human populations allows us to understand the subsistence behavior associated with various adaptations to the environment. Feeding habits are essential to the survival and growth of ancient populations. Stable isotope analysis is accepted tool in paleodiet (Schutkowski et al, 1999) and paleoenvironmental (Zernitskaya et al, 2014) studies. However, stable isotopes can be useful not only in investigating human feeding habits but also in describing social and cultural structure of the past populations (Le Huray and Schutkowski, 2005). Only few stable isotope investigations have been performed before in Lithuanian region suggesting a quite uniform diet between males and females and protein intake from freshwater fish and animal protein. Previously, stable isotope analysis has only been used to study a Stone Age population however, more recently studies have been conducted on Iron Age and Late medieval samples (Jacobs et al, 2009). Anyway, there was a need for more precise examination. Stable isotope analysis were performed on human bone collagen and apatite samples in this study. Data represented various ages (from 5-7th cent. to 18th cent.). Stable carbon and nitrogen isotope analysis on medieval populations indicated that individuals in studied sites in Lithuania were almost exclusively consuming C3 plants, C3 fed terrestrial animals, and some freshwater resources. Current investigation demonstrated social differences between elites and country people and is promising in paleodietary and daily life reconstruction. Acknowledgement I thank prof. dr. G. Grupe, Director of the Anthropological and Palaeoanatomical State Collection in Munich for providing the opportunity to work in her laboratory. The part of this work was funded by DAAD. Antanaitis-Jacobs, Indre, et al. "Diet in early Lithuanian prehistory and the new stable isotope evidence." Archaeologia Baltica 12 (2009): 12-30. Le Huray, Jonathan D., and Holger

  6. What can Fe stable isotopes tell us about magmas?

    DEFF Research Database (Denmark)

    Stausberg, Niklas

    The majority of the Earth’s crust is formed by magmas, and understanding their production and differentiation is important to interpret the geologic rock record. A powerful tool to investigate magmatic processes is the distribution of the stable isotopes of the major redox-sensitive element...... the differentiation of magmas from the perspective of Fe stable isotopes, integrated with petrology, by studying igneous rocks and their constituent phases (minerals and glasses) from the Bushveld Complex, South Africa, Thingmuli, Iceland, Pantelleria, Italy, and the Bishop Tuff, USA. The findings are interpreted...... and for more quantitative model of the magmatic processes producing enigmatic stable isotope compositions of rhyolitic and granite magmas....

  7. Shelf-Stable Food Safety